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Introduction Cerebral palsy (CP) is a heterogeneous group of permanent, non-progressive motor disorders of movement and posture caused by chronic brain injuries that originate in the prenatal, perinatal, or postnatal period. It is the most common cause of physical disability in childhood.[12] The four major subtypes of CP are spastic, athetoid, ataxic, and mixed cerebral palsy, with spastic forms being the most common (65%).[3] CP prevalence is increasingly encountered in neonatal clinics since more number of premature infants survives because of better neonatal care made available these days. Besides motor deficits in cerebral palsy, the other causes of handicap are the associated disabilities, in particular intellectual impairment, epilepsy, speech defects, disorders of vision and hearing, and specific educational and behavioral abnormalities, with the result that the majority of sufferers cannot take their place in normal society[4–6] (Crothers and Paine, 1959; Henderson, 1961; Ingram, 1964a). In recent years, the neurophysiologic examination of children with CP has been of increasing interest to both pediatricians and vision researchers because it provides new insights into mechanisms of brain damage and repair in CP. However, there are only very few reports on electrophysiological investigations on children having cerebral palsy[7–10] and on Visual Evoked Potentials (VEPs) along with Brainstem Auditory Evoked Potentials (BAEPs) in children with CP in this part of the world.

insights into mechanisms of brain damage and repair in CP. However, there are only very few reports on electrophysiological investigations on children having cerebral palsy[7–10] and on Visual Evoked Potentials (VEPs) along with Brainstem Auditory Evoked Potentials (BAEPs) in children with CP in this part of the world. Hence the present study was undertaken to investigate children with spastic cerebral palsy using VEPs and BAEPs and correlate the electrophysiological findings with clinical features. Materials and Methods The study was conducted in the Neurophysiology Unit of the Department of Physiology. A total of 50 subjects were investigated for the evaluation of VEPs and BAEPs after obtaining ethics committee approval for the present study. Fifteen children with spastic CP in the ages ranging from 4 months to 10 years participated as patient group in this study. A control group of 35 children with the same age range and with no significant birth history or visual anomaly was also tested. The number of controls was two times greater than the study group to increase statistical power of this study. Data of spastic CP children were collected retrospectively regarding patient’s age, pre-, peri- and postnatal events, and history of epilepsy. Clinical eye examinations included observation of fixation, following objects, pupillary reflexes, refraction, and fundus examination.

increase statistical power of this study. Data of spastic CP children were collected retrospectively regarding patient’s age, pre-, peri- and postnatal events, and history of epilepsy. Clinical eye examinations included observation of fixation, following objects, pupillary reflexes, refraction, and fundus examination. Recording procedure for VEP and BAEP The recording was done using RMS EMG. EP MARK II machine manufactured by RMS Recorders and Medicare System, Chandigarh. The stimulus for VEP recording was a monocular flash from light-emitting diode goggles that were held lightly over the infants’ eyes. Flashes were presented at 0.5 per second. Silver cup electrodes were attached with paste and tape, with impedances below 5 kilo-ohms. As per 10-20 International System of EEG placements, the reference electrode (Fz) was placed 12cm above the nasion, the ground electrode (Cz) at the vertex and the active electrode (Oz) at approximately 2 cm above the inion. A band pass of 1 to 100 Hz was employed, the gain was 10,000, the sweep was 1 sec, and automatic artifact reject routine was employed. For BAEP recording, same surface electrodes were used and placed at the vertex (Cz), both ear lobes (Ai and Ac) and forehead (ground). Monoaural auditory stimulus consisting of rarefaction clicks were delivered through an electrically shielded earphone at a rate of 11.1/sec. contra-lateral ear was masked with pure white noise 40 dB below that of BAEP stimulus. A band pass of 150-3000 Hz was used to filter out undesirable frequencies in the surrounding. Responses to 2000 click presentations were averaged for 10 msec.

delivered through an electrically shielded earphone at a rate of 11.1/sec. contra-lateral ear was masked with pure white noise 40 dB below that of BAEP stimulus. A band pass of 150-3000 Hz was used to filter out undesirable frequencies in the surrounding. Responses to 2000 click presentations were averaged for 10 msec. The testing procedures were explained to a parent of each subject who volunteered to participate and a consent form was signed. Parameters studied The absolute latencies of the peaks of positive wave P2 and the negative waves N1 and N2 were recorded. The amplitude of P2 is measured from the peak of N2 to the trough of P2 (N2 – P2). The absolute difference in the components evoked by the right eye and left eye stimulation (inter ocular differences) are also determined. BAEP threshold for each ear with absolute latencies of I, III, V waves, interpeak latencies of I-III, III-V, I-V and ratio of V to I amplitude (V:I) were considered from recordings for comparison among the two groups. Results VEPs and BAEPs were recorded in the children with CP and compared with healthy controls. The VEP parameters of all the 15 children with CP are given in Table 1. The lowest latency obtained was 111.9 msec and highest value was 146.9 msec with maximum amplitude of the most prominent positivity as 13.24 µv. The range of variation in interocular difference for latency was 1.2 to 16.6 msec and for amplitude was 0.14 to 8.1 µv. Table 1 Visual evoked potentials parameters of the children with cerebral palsy

Results VEPs and BAEPs were recorded in the children with CP and compared with healthy controls. The VEP parameters of all the 15 children with CP are given in Table 1. The lowest latency obtained was 111.9 msec and highest value was 146.9 msec with maximum amplitude of the most prominent positivity as 13.24 µv. The range of variation in interocular difference for latency was 1.2 to 16.6 msec and for amplitude was 0.14 to 8.1 µv. Table 1 Visual evoked potentials parameters of the children with cerebral palsy Case no. Name of the subject Sex RE P2 latency (msec) RE P2 amp. (µV) LE P2 latency (msec) LE P2 amp. (µV) Inter-ocular diff. in P2 latency Inter-ocular diff. in P2 amp (µV) 1. KVM F 116.3 6.13 114.4 6.31 1.9 0.18 2. CAK M 145.6 5.15 132.5 1.4 13.1 3.75 3. KVD M 131.3 4.28 139.4 9.73 8.1 5.45 4. ARG M 143.1 7.54 131.3 6.74 11.8 0.8 5 JRK M 133.5 5.35 118.8 1.20 14.7 4.15 6 ASK M 138.1 10.84 120.8 2.74 17.3 8.1 7. BDC M 139.3 1.34 137.5 1.15 1.8 0.19 8. RGT M 120.6 2.37 122.5 3.28 1.9 0.91 9. ONM M 130.0 10.20 143.8 7.16 13.8 3.04 10. SBK M 121.9 5.45 128.1 4.20 6.2 1.25 11. MVP M 111.9 7.48 117.5 8.00 5.6 0.52 12. TVS M 130.6 12.61 123.8 13.24 6.8 0.63 13 ASN F 130.3 0.55 146.9 0.41 16.6 0.14 14 NNM F 139.4 5.81 130.6 6.13 8.8 0.32 15 NDT M 120.6 8.26 119.4 8.63 1.2 0.37 The mean latencies and amplitude of Flash VEP records in the patient group and control group have been tabulated in Table 2. It is quite evident from the observations on VEP that there is a peculiar characteristic which is outstandingly seen in the patient group i.e. a marked delay in the latency as well as a reduction in the amplitude when compared with the controls. The means for all VEP parameters of patient group were statistically different from the control group (P<0.05).

ions on VEP that there is a peculiar characteristic which is outstandingly seen in the patient group i.e. a marked delay in the latency as well as a reduction in the amplitude when compared with the controls. The means for all VEP parameters of patient group were statistically different from the control group (P<0.05). Table 2 Mean latencies and amplitudes of VEP recordings Groups RE P2 latency (msec) LE P2 latency (msec) Inter-ocular diff. in P2 latency RE P2 amplitude (µV) LE P2 amplitude (µV) Inter-ocular diff. in P2 amplitude (µV) Patient group (mean± SD) No. = 15 130.17±10.10 128.49±10.05 8.64±5.63 6.29±3.30 5.42 ± 3.63 1.99±2.4 Control group (mean± SD) No. = 35 97.7±5.61 97.67±4.51 2.02±2.31 13.01±3.5 13.18±3.29 1.13±1.44 Unpaired t test P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 Apart from this, the variations in VEPs records in our study were seen as: Unusual and improper waveform as obtained in Case No.2 having CP with microcephaly, mental retardation with seizure disorder. Monocular delayed latency and reduced amplitude as in Case No.8 having CP with typical febrile seizure and mental retardation. Abnormally delayed latencies and missing components as in: Case no.5 with CP with microcephaly, seizure disorder, mental retardation with global developmental delay with corpus callosal agenesis. Case no.7 with CP with microcephaly, mental retardation with global developmental delay with B/L primary optic atrophy. “W” Pattern or bifid P wave morphology as in: Case no.1 with CP with microcephaly, seizure disorder, delayed milestones, mental retardation and partial corpus callosal agenesis

Abnormally delayed latencies and missing components as in: Case no.5 with CP with microcephaly, seizure disorder, mental retardation with global developmental delay with corpus callosal agenesis. Case no.7 with CP with microcephaly, mental retardation with global developmental delay with B/L primary optic atrophy. “W” Pattern or bifid P wave morphology as in: Case no.1 with CP with microcephaly, seizure disorder, delayed milestones, mental retardation and partial corpus callosal agenesis Case no.4 with CP with microcephaly, global developmental delay with seizure disorder Broadened “P wave” was obtained in case no.14 having CP with frontal lobe atrophy. Absent waveform was observed in Case no. 13 with CP with sensorineural hearing loss (SNHL). Its MRI revealed cerebral atrophy in B/L hemispheres. Out of the total 15 cases, the presenting features of 10 children with spastic CP along with some associated abnormalities such as microcephaly, mental retardation, delayed development and others are elucidated in Table 3. Table 3 Presenting features of children with spastic CP and associated abnormalities

Absent waveform was observed in Case no. 13 with CP with sensorineural hearing loss (SNHL). Its MRI revealed cerebral atrophy in B/L hemispheres. Out of the total 15 cases, the presenting features of 10 children with spastic CP along with some associated abnormalities such as microcephaly, mental retardation, delayed development and others are elucidated in Table 3. Table 3 Presenting features of children with spastic CP and associated abnormalities Case no. Name Sex Micro-cephaly Associated abnormality with cerebral palsy Other abnormalities Mental retardation Developmental milestones 1 KVM F + − Not attained any Partial corpus callosal agenesis 2 CAK M + + Attained Seizure disorder, B/L SNHL 3 KVD M − − Delayed Birth asphyxia, hyperbilirubinemia 4 ARG M + − Global delay Seizure disorder 5 JRK M − + Global delay Corpus callosal agenesis, SNHL 7 BDC M + + Global delay Seizure disorder, primary Optic atrophy 8 RGT M − + Attained Typical febrile seizure 10 SBK M + + Attained No seizure disorder 13 ASN F − − Attained Cerebral atrophy, SNHL 14 NNM F − − Delayed Frontal lobe atrophy SNHL implies sensorineural hearing loss “+” implies present “−” implies absent The above mentioned associated disorders found along with spastic CP are supported by CT and MRI investigations and the diagnosis was confirmed with the help of pediatrician’s opinion. The peculiar neurophysiological findings in these 10 cases have been represented in Table 4.

Case no. Name Sex Micro-cephaly Associated abnormality with cerebral palsy Other abnormalities Mental retardation Developmental milestones 1 KVM F + − Not attained any Partial corpus callosal agenesis 2 CAK M + + Attained Seizure disorder, B/L SNHL 3 KVD M − − Delayed Birth asphyxia, hyperbilirubinemia 4 ARG M + − Global delay Seizure disorder 5 JRK M − + Global delay Corpus callosal agenesis, SNHL 7 BDC M + + Global delay Seizure disorder, primary Optic atrophy 8 RGT M − + Attained Typical febrile seizure 10 SBK M + + Attained No seizure disorder 13 ASN F − − Attained Cerebral atrophy, SNHL 14 NNM F − − Delayed Frontal lobe atrophy SNHL implies sensorineural hearing loss “+” implies present “−” implies absent The above mentioned associated disorders found along with spastic CP are supported by CT and MRI investigations and the diagnosis was confirmed with the help of pediatrician’s opinion. The peculiar neurophysiological findings in these 10 cases have been represented in Table 4. As far as the BAEP recordings are concerned, it is observed that average BAEP threshold for control group was 32.00 ±4.06 dB for left ear and 34.29 ± 5.02 dB for right ear whereas in patient group it was estimated as 44.67 ± 24.75 dB for left ear and 53.33 ± 28.45 dB for right ear. Table 4 Peculiarities in neurophysiological findings of the above 10 cases of CP

As far as the BAEP recordings are concerned, it is observed that average BAEP threshold for control group was 32.00 ±4.06 dB for left ear and 34.29 ± 5.02 dB for right ear whereas in patient group it was estimated as 44.67 ± 24.75 dB for left ear and 53.33 ± 28.45 dB for right ear. Table 4 Peculiarities in neurophysiological findings of the above 10 cases of CP Case no. Name of subject VEP abnormality BAEP threshold Left ear Right ear 1 KVM ↓ P2 amplitude in LE ↑ Latency in RE 30 dB 40 dB 2 CAK ↓ P2 amplitude in LE ↑ Latency in RE 40 dB 60 dB 3 KVD ↓ P2 amplitude in LE ↑ Latency B/L 30 dB 40 dB 4 ARG ↓ P2 amplitude B/L ↑ Latency in RE 30 dB 80 dB 5 JRK Markedly↓ amp. B/L ↑ Latency in RE 50 dB 40 dB 7 BDC Markedly↓ P2 amplitude ↑ Latency B/L 30 dB 40 dB 8 RGT Markedly ↓ P2 amplitude B/L ↑ Latency in RE 30 dB 30 dB 10 SBK P2 amplitude WNL B/L ↑ Latency B/L 30 dB 30 dB 13 ASN Markedly ↓ P2 amplitude B/L ↑ Latency in RE 50 dB 100 dB 14 NNM ↓ P2 amplitude in LE ↑ Latency in RE 30 dB 30 dB The BAEP parameters of all the 15 children with CP are shown in Table 5. and mean latencies and amplitudes of BAEP waveforms are depicted in Table 6. Striking BAEP abnormalities in CP patients include prolongation of absolute latency of wave V, interpeak latencies of III–V and lowered V–I ratio as compared to the controls. The difference of means of all the BAEP parameters was statistically significant between the two groups (P<0.05). Abnormal VEPs and BAEPs in children with spastic cerebral palsy demonstrated a significant correlation with the presence of global developmental delay.

I–V and lowered V–I ratio as compared to the controls. The difference of means of all the BAEP parameters was statistically significant between the two groups (P<0.05). Abnormal VEPs and BAEPs in children with spastic cerebral palsy demonstrated a significant correlation with the presence of global developmental delay. Table 5 BAEP parameters of the children with CP

I–V and lowered V–I ratio as compared to the controls. The difference of means of all the BAEP parameters was statistically significant between the two groups (P<0.05). Abnormal VEPs and BAEPs in children with spastic cerebral palsy demonstrated a significant correlation with the presence of global developmental delay. Table 5 BAEP parameters of the children with CP Case no. Absolute latencies left ear Interpeak latencies left ear V: I ratio LE Absolute latencies right ear Interpeak latencies right ear V: I ratio RE I III V I-III III-V I-V I III V I-III III-V I-V 1. 3.77 5.85 7.23 2.08 1.38 3.46 1.27 4.21 5.48 7.63 1.27 2.15 3.42 3.55 2. 3.1 5.4 6.98 2.3 1.58 3.88 2.11 3.67 5.08 7.27 1.41 2.19 3.6 2.12 3. 3.65 5.96 7.65 2.31 1.69 4 6.17 3.52 5.69 7.42 2.17 1.73 3.9 2.57 4. 3.1 5.08 7.13 1.98 2.05 4.03 1.02 2.38 4.85 6.88 2.47 2.03 4.5 11.7 5 2.19 3.9 6.1 1.71 2.2 3.91 1.1 2.71 4.54 6.21 1.83 1.67 3.5 2.48 6 2.63 5 6.79 2.37 1.79 4.16 0.97 3.73 5.4 7.63 1.67 2.23 3.9 1.84 7. 3.13 5.31 7.4 2.18 2.09 4.27 2.93 3.13 5.13 7.15 2 2.02 4.02 5.26 8. 3.02 4.71 6.58 1.69 1.87 3.56 2.49 3.19 5.73 7.71 2.54 1.98 4.52 3.81 9. 1.8 3.54 5.87 1.74 2.33 4.07 1.5 1.65 3.96 5.98 2.31 2.02 4.33 1.25 10 3.63 5.77 7.79 2.14 2.02 4.16 5.68 3.35 5.52 7.21 2.17 1.69 3.86 2.25 11 1.73 4.29 6.15 2.56 1.86 4.42 1.69 3.35 4.69 6.04 1.34 1.35 2.69 4.13 12 3.42 5.4 7.04 1.98 1.64 3.62 3.3 2.54 5.17 6.92 2.63 1.75 4.38 1.03 13 2.29 5.04 6.02 2.75 0.98 3.73 1.28 1.48 3.81 5.65 2.33 1.84 4.17 0.97 14 2.92 4.54 5.96 1.62 1.42 3.04 2.15 2.5 4.96 6.92 2.46 1.96 4.42 2.93 15 3.08 5.88 7.77 2.8 1.89 4.69 6.89 2.94 5.96 7.92 3.02 1.96 4.98 7.25 Table 6 Mean Latencies and Amplitudes of BAEP Recordings

64 3.62 3.3 2.54 5.17 6.92 2.63 1.75 4.38 1.03 13 2.29 5.04 6.02 2.75 0.98 3.73 1.28 1.48 3.81 5.65 2.33 1.84 4.17 0.97 14 2.92 4.54 5.96 1.62 1.42 3.04 2.15 2.5 4.96 6.92 2.46 1.96 4.42 2.93 15 3.08 5.88 7.77 2.8 1.89 4.69 6.89 2.94 5.96 7.92 3.02 1.96 4.98 7.25 Table 6 Mean Latencies and Amplitudes of BAEP Recordings Groups Absolute latencies left ear Interpeak latencies left ear V: I Ratio Lt Ear Absolute latencies right ear Interpeak latencies right ear V: I ratio RE I III V I-III III-V I-V I III V I-III III-V I-V Patient group (mean±SD) No. = 15 2.90 ± 0.65 5.04 ± 0.73 6.83 ± 0.68 2.15±0.37 1.79 ± 0.35 3.93 ± 0.41 2.70 ± 1.97 2.96±0.76 5.06±0.62 6.97±0.70 2.11±0.51 1.90±0.23 4.01±0.56 3.54±2.81 Control group (mean±SD) No. = 35 3.03±0.50 5.32±0.51 6.07±0.48 2.55±1.67 1.75±0.27 4.04±0.45 5.50±4.75 3.21±0.65 5.53±0.55 7.42±0.54 2.32±0.58 1.90±0.37 4.21±0.66 6.14±6.19 Unpaired t test P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 P<0.05 Discussion This article describes neurophysiological study using flash VEPs and BAEPs in children with CP. It was observed that those children who had other neurological symptoms associated with CP showed extensive deviation from the regular pattern of waveforms obtained in VEP investigations some of which are depicted in the Figure 1. This is in consonance with the notion put forward by previous workers that children with CP have abnormalities of the visual sensory and motor pathways at rates exceeding those detected in neurologically normal children.[11–17]

tern of waveforms obtained in VEP investigations some of which are depicted in the Figure 1. This is in consonance with the notion put forward by previous workers that children with CP have abnormalities of the visual sensory and motor pathways at rates exceeding those detected in neurologically normal children.[11–17] Figure 1 Variations in VEP Waveforms of children with CP In a recent neurophysiologic study[9] on CP patients, increased latencies of VEPs were reported to occur more frequently with alterations in the optic radiation supported by MRI findings. Similar results are obtained in our study in those patients where their MRI findings reveal cerebral disorders such as corpus callosal agenesis, frontal lobe atrophy, cerebral atrophic changes etc. It has been documented in the past[18] that microcephaly leads to more than 40% reduction in VEP amplitude. The small head size might be a possible cause of reduced VEP amplitudes found in microcephalic children of the present study. The abnormal flash VEP findings of our study in cases of CP with developmental delay are in agreement with a most recent study[10] in children with bilateral spastic CP in which they have demonstrated significant correlation of VEP with moderate to severe developmental delay.

It has been documented in the past[18] that microcephaly leads to more than 40% reduction in VEP amplitude. The small head size might be a possible cause of reduced VEP amplitudes found in microcephalic children of the present study. The abnormal flash VEP findings of our study in cases of CP with developmental delay are in agreement with a most recent study[10] in children with bilateral spastic CP in which they have demonstrated significant correlation of VEP with moderate to severe developmental delay. Nowadays the neurophysiologic techniques especially VEPs are able to demonstrate the brain plasticity in children with cerebral palsy. The mechanisms of plasticity have been postulated as a change in the balance of excitation and inhibition; a long-term potentiation or long-term depression; a change in neuronal membrane excitability; the anatomical changes-formation of new axon terminals and new synapses.[2] It has been suggested that children with CP have a remarkable ability to recover from early brain injures. The utility of the neurophysiologic investigations like VEPs in the determination of brain reorganization and repair in patients with cerebral palsy (CP) has been described in a study.[9] According to this, VEP can be a useful tool in the determination of brain plasticity in children with CP as it has been suggested that VEP latencies are valuable estimators of neuronal injury and even predictors of later intellectual performance.[19]

n patients with cerebral palsy (CP) has been described in a study.[9] According to this, VEP can be a useful tool in the determination of brain plasticity in children with CP as it has been suggested that VEP latencies are valuable estimators of neuronal injury and even predictors of later intellectual performance.[19] High frequency of abnormal BAEP has been reported in children with spastic cerebral palsy. The BAEP abnormality has been significantly related by previous researchers to term delivery, perinatal etiology of cerebral palsy, visual abnormality, inability to walk independently and many more aspects. In a retrospective study on 75 children with spastic cerebral palsy, 22.7% had abnormal BAEP.[20] In our study profound sensorineural hearing loss (SNHL) was observed in case no.13 with CP along with cerebral atrophy. Bilateral mild to moderate SNHL was evident in a case no. 2 with CP along with MR, microcephaly and seizure disorder [Figure 2]. Moderate SNHL was also seen in right ear of case no.4 who had Eustachian tube defect in the same ear and in case no.5 who had raised threshold in left ear. Figure 2 BAEP Threshold in waveforms of children with CP

High frequency of abnormal BAEP has been reported in children with spastic cerebral palsy. The BAEP abnormality has been significantly related by previous researchers to term delivery, perinatal etiology of cerebral palsy, visual abnormality, inability to walk independently and many more aspects. In a retrospective study on 75 children with spastic cerebral palsy, 22.7% had abnormal BAEP.[20] In our study profound sensorineural hearing loss (SNHL) was observed in case no.13 with CP along with cerebral atrophy. Bilateral mild to moderate SNHL was evident in a case no. 2 with CP along with MR, microcephaly and seizure disorder [Figure 2]. Moderate SNHL was also seen in right ear of case no.4 who had Eustachian tube defect in the same ear and in case no.5 who had raised threshold in left ear. Figure 2 BAEP Threshold in waveforms of children with CP Conclusion The differences in VEPs and BAEPs were determined between CP children and healthy children. It is concluded that VEPs of the patient group revealed a marked delay in the latency as well as a reduction in the amplitude apart from certain variations in the waveforms. BAEP abnormalities in CP patients include prolongation of absolute latency of wave V, interpeak latencies of III–V and lowered V–I ratio as compared to the controls. The average threshold for hearing also greatly increased in the patient group as compared to controls. The abnormalities found are probably linked to the neurological deficits present in cases of cerebral palsy although the exact etiology remains to be unleashed. Further to conclude, since VEPs and BAEPs are non-invasive neurophysiological investigations; they can serve as important tools in the diagnostic work up of spastic cerebral palsy.

nd are probably linked to the neurological deficits present in cases of cerebral palsy although the exact etiology remains to be unleashed. Further to conclude, since VEPs and BAEPs are non-invasive neurophysiological investigations; they can serve as important tools in the diagnostic work up of spastic cerebral palsy. We gratefully acknowledge the support rendered by the Dean, MGIMS & Secretary, KHS. Special thanks to our statistician Dr. Bharambe for his valuable help. Source of Support: Nil. Conflict of Interest: None declared.

Introduction The appropriate timing as well as type of surgical intervention in patients with persistent post-traumatic CSF leaks remains unclear. Many surgical approaches – both intracranial and extracranial – may be successful, depending on patient factors and the anatomy of the fistula. The goal of neurosurgical management of CSF rhinorrhea is to prevent external deformity of the skull, seal the CSF leak, and to avoid chronic sinusitis. The best method of closing frontobasal defects is still a matter of debate, especially if there is a need for reconstructive surgery.[1–5] We report a case of post traumatic CSF rhinorrhea resulting from extensive dural tears and anterior cranial fossa floor fractures and its subsequent repair using titanium mesh and pedicled pericranial flap.

g frontobasal defects is still a matter of debate, especially if there is a need for reconstructive surgery.[1–5] We report a case of post traumatic CSF rhinorrhea resulting from extensive dural tears and anterior cranial fossa floor fractures and its subsequent repair using titanium mesh and pedicled pericranial flap. Case Report A 9-year-old boy presented to us with complaints of watery nasal discharge from right nostril after seven months following fall from 20 feet. He had suffered four episodes of high grade fever in the intervening period. On presentation, he was fully conscious without any neurological deficits. An MRI cisternography was done which showed extensive bilateral cribriform plate defects with a doubtful defect from the sellar floor into the sphenoid sinus [Figure 1]. The patient was taken for surgery and a bicoronal flap was raised. A bipedicled pericranial flap was raised for use as an onlay graft. Multiple dural defects were noted in bilateral basifrontal region with large bilateral cribriform plate defects through which the frontal lobe was herniating. The herniating brain tissue was released from these outpouchings with sharp dissection. Dural defects were repaired primarily. In view of large bilateral bony defects, it was decided to reinforce the anterior cranial fossa floor with titanium mesh which was contoured and placed over the anterior skull base. The mesh was fixed to the floor [Figure 2] with the help of 4 mm screws. An onlay graft of the pedicled pericranium flap was interposed between the mesh and the dura using fibrin glue.

s decided to reinforce the anterior cranial fossa floor with titanium mesh which was contoured and placed over the anterior skull base. The mesh was fixed to the floor [Figure 2] with the help of 4 mm screws. An onlay graft of the pedicled pericranium flap was interposed between the mesh and the dura using fibrin glue. Figure 1 MRI cisternography coronal (A) and sagittal (B) views showing the bilateral cribriform plate defects Figure 2 Postoperative CT head with 3D reconstruction showing reconstruction of anterior cranial floor with the titanium mesh A lumbar drain was placed prophylactically and CSF drainage was continued till third post operative day. The remainder of the hospital course was uneventful and the patient could be discharged on the sixth post operative day and remains asymptomatic at last follow up. Discussion The use of titanium mesh in skull base surgery has previously been reported in craniofacial and cranial vault procedures.[1–4] Its use in skull base applications may prove useful in certain situations. There are a variety of options for techniques to repair the defect of the anterior skull base, but the principle concept is to have a ‘water-tight’ closure.

surgery has previously been reported in craniofacial and cranial vault procedures.[1–4] Its use in skull base applications may prove useful in certain situations. There are a variety of options for techniques to repair the defect of the anterior skull base, but the principle concept is to have a ‘water-tight’ closure. Badie[5] evaluated the usefulness of titanium mesh along with two layered pericranium flap in reconstruction of anterior cranial fossa floor in 13 patients and found that none of the patients had complications like infections or meningocele formation at a mean follow-up of 22 months. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. We, however, placed the titanium mesh inferior to the two layers of continuous vascularized pericranium to prevent injury to the pericranium by the mesh. Conclusion Our case shows that the use of titanium mesh is a safe and feasible method for reconstructing large anterior skull base. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Neurological conditions associated with polycythemia may warrant an emergency non contrast CT scan of the head. The unique findings associated with polycythemia have not been well characterized in literature. We present two cases of polycythemia both associated with hyperdense dural venous sinuses and cerebral vasculature, hence simulating the appearance of a contrast enhanced CT on plain CT films. Case Reports Case 1 A 27-year-old male patient presented to our emergency department with history of fever and headache for the past four days with altered sensorium for 2 days and a brief episode of loss of consciousness two days back. Patient had a history of breathlessness on and off since three years of age. He was diagnosed as a case of heart disease but financial constraints prevented timely treatment. Examination revealed central cyanosis, Rt- hemiparesis and a pansystolic murmur over the epicardium. NCCT findings were suggestive of left temporoparietal cerebral abscess associated with hyperdensity of all cerebral venous sinuses and cerebral vasculature(patient had not been given any intravenous contrast agents). Findings were suggestive of left temporoparietal cerebral abscess with hyper-attenuating cerebral vasculature, left transverse sinus, straight sinus and parts of superior sagittal and sigmoid sinus (appearance simulating CECT on an NCCT head)

NCCT findings were suggestive of left temporoparietal cerebral abscess associated with hyperdensity of all cerebral venous sinuses and cerebral vasculature(patient had not been given any intravenous contrast agents). Findings were suggestive of left temporoparietal cerebral abscess with hyper-attenuating cerebral vasculature, left transverse sinus, straight sinus and parts of superior sagittal and sigmoid sinus (appearance simulating CECT on an NCCT head) Chest X ray revealed cardiomegaly with pulmonary plethora [Figure 1]. Echocardiography was suggestive of complex cyanotic heart disease with transposition of great arteries with pulmonary stenosis and bidirectional shunt associated with a large VSD and ASD. Figure 1 Chest X-ray - Cardiomegaly with pulmonary plethora with a narrow pedicle (case 1) Case 2 A 6-year-old male child presented to our emergency department with history of high grade fever and semi comatose state for past one day. He had been diagnosed with Tetrology of Fallot at the age of two years in a peripheral secondary care centre. He had history of recurrent cyanotic spells since two years of age. Patient was brought to our hospital one month back and was scheduled for a cardiac surgery. Surgery was deferred in view of the current clinical status. On NCCT hyperdense cerebral vasculature was observed and all venous sinuses were found to be hyperdense with attenuation values above 60 HU. A left parietal lobe hypodense lesion with surrounding rim hyperdensity was seen [Figures 2 and 3].

Case 2 A 6-year-old male child presented to our emergency department with history of high grade fever and semi comatose state for past one day. He had been diagnosed with Tetrology of Fallot at the age of two years in a peripheral secondary care centre. He had history of recurrent cyanotic spells since two years of age. Patient was brought to our hospital one month back and was scheduled for a cardiac surgery. Surgery was deferred in view of the current clinical status. On NCCT hyperdense cerebral vasculature was observed and all venous sinuses were found to be hyperdense with attenuation values above 60 HU. A left parietal lobe hypodense lesion with surrounding rim hyperdensity was seen [Figures 2 and 3]. Figure 2 NCCT shows well defined hypodense lesion in left parietal lobe with edema and a hyperdensity of straight and sagittal sinuses Figure 3 Hyperdensity in cerebral vasculature on non contrast CT scan of head simulating a CECT (case 2) On contrast enhancement (CECT), there was rim enhancement of the parietal lobe lesion, suggesting an abscess in view of the toxic symptomatology and the cerebral vasculature and venous sinuses were further seen to enhance with contrast [Figure 4]. Figure 4 CECT of case #2 with enhancing rim of cerebral abscess and further enhancement of vasculature Catheter angiocardiography done previously had revealed dextrocardia, Rt aortic arch, sub aortic VSD, ASD, tiny pulmonary artery filling retrogradely from collaterals with normal LV function and no evidence of coarctation of aorta.

Figure 4 CECT of case #2 with enhancing rim of cerebral abscess and further enhancement of vasculature Catheter angiocardiography done previously had revealed dextrocardia, Rt aortic arch, sub aortic VSD, ASD, tiny pulmonary artery filling retrogradely from collaterals with normal LV function and no evidence of coarctation of aorta. Discussion Features of polycythemia on NCCT head are not well characterised in literature; however, it includes Increased attenuation of cerebral vessels and subtle increase in radiographic attenuation of venous sinuses. Increased radiographic attenuation is primarily a reflection of hemoconcentration and attenuation of the hemoglobin protein (with minimal contribution from increased iron content.[1] However, increased attenuation of venous sinuses is typically seen in cerebral venous sinus thrombosis. Cerebral venous thrombosis is a known complication of polycythemia and hypercoagulable states and hence may coexist. MR venography, CT venography[2] or catheter venography may be required to differentiate between cerebral venous thrombosis in a patient of polycythemia with hyper dense venous sinuses. Hematocrit levels help in the diagnosis of a patient with hyperdense venous sinuses on a non contrast CT scan. Hematocrit in our first case was 76.3% and Hb level was 25.8 gm%. Hematocrit in our second case was 66% and Hb level was 22.2gm%. Polycythemia may mimic cerebral venous thrombosis and polycythemia may cause cerebral venous thrombosis.

Hematocrit levels help in the diagnosis of a patient with hyperdense venous sinuses on a non contrast CT scan. Hematocrit in our first case was 76.3% and Hb level was 25.8 gm%. Hematocrit in our second case was 66% and Hb level was 22.2gm%. Polycythemia may mimic cerebral venous thrombosis and polycythemia may cause cerebral venous thrombosis. Conclusion We hence conclude that hyperdensity of cerebral vessels and venous sinuses may be associated with polycythemia and cerebral venous thrombosis must be meticulously ruled out in such cases as the two may coexist. Source of Support: Nil. Conflict of Interest: None declared.

Sacrococcygeal teratomas (SCT) are neoplasms composed of diverse tissues foreign to the anatomical site of origin (incidence: 1–2 per 40,000 deliveries). They originate from totipotent cells from Hansen’s node or primitive germ cells.[1] A 6-day-old female child, following normal delivery, was born with a sacrococcygeal lump with no apparent neurological deficit. A sacrococcygeal swelling (sized 8 cm X 9 cm) was present with a variable solid to cystic consistency, transilluminant in certain areas [Figure 1]. Magnetic resonance imaging revealed a multiloculated swelling between the sacrococcygeal spine and the rectum [Figure 2]. Figure 1 A sacrococcygeal swelling (sized 8 cm × 9 cm) was present with a variable solid to cystic consistency, transilluminant in certain areas Figure 2 Sagittal T1 (A), T2 (B) and axial (C–E) magnetic resonance imaging revealed a multiloculated dumbell (both internal and external type) swelling between the sacrococcygeal spine and anorectal canal SCT are derived from all three germinal layers and contain neural elements, squamous and intestinal epithelium, skin appendages, teeth and, at times, calcium. Their inheritance may be sporadic but, occasionally, autosomal dominant.[12] They are more common in girls (4:1) but are more often malignant in boys. Fifteen percent have associated congenital anomalies like imperforate anus, sacral bone defects, duplication of uterus or vagina, spina bifida and meningomyelocele (scimitar sacrum, anorectal malformation and presacral mass forming Currarino’s triad).[1–3]

ore common in girls (4:1) but are more often malignant in boys. Fifteen percent have associated congenital anomalies like imperforate anus, sacral bone defects, duplication of uterus or vagina, spina bifida and meningomyelocele (scimitar sacrum, anorectal malformation and presacral mass forming Currarino’s triad).[1–3] The American Association of Pediatric Surgery has classified them into four types: (1) 47%, exophytic and external; (2) 34%, dumbbell shaped, with equal internal/external components (present patient); (3) 9%, primarily located within the abdomen/pelvis; (4) 10%, entirely internal, no external components. In a viable foetus, caesarean section delivery is recommended if SCT measures >5 cm to prevent dystocia or rupture of SCT. Early excision of the tumor in continuity with the coccyx should be achieved as failure to remove the coccyx results in 30–40% risk of local recurrence. Excess or damaged skin should be removed to allow a cosmetic reconstruction. The perianal sphincteric muscles are sutured to the presacral space.[12] In type 2/3 SCT, a combined abdominoperineal approach may be required. Malignant tumors require surgical excision, chemotherapy and radiation. Intrauterine surgery by interrupting the feeding vessel has been suggested when the fetus develops hydrops prior to viability. The role of open intrauterine surgery, however, is limited because it carries high morbidity to the mother and the fetus. Radiofrequency ablation has shown promising results in the treatment of fetal SCT.[1]

urgery by interrupting the feeding vessel has been suggested when the fetus develops hydrops prior to viability. The role of open intrauterine surgery, however, is limited because it carries high morbidity to the mother and the fetus. Radiofrequency ablation has shown promising results in the treatment of fetal SCT.[1] Risk of malignancy depends on the time of diagnosis (7–10% at <2 months, 37% at 1 year and 50% at 2 years). In benign tumors, disease-free survival is >90%, whereas malignant tumors have significant mortality. Hence, frequent follow-up with serum α-fetoprotein level measurement and surveillance by imaging is recommended. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Cerebral sinovenous thrombosis (CSVT) is a rare disorder in children. Its incidence is declining as some of the conditions historically associated with CSVT (such as mastoiditis) are now treatable.[1] However, CSVT is being increasingly diagnosed now because of greater awareness among clinicians, availability of advanced neuroimaging techniques, and the survivalof children with previously lethal diseases that confer a predispositionto sinovenous thrombosis.[1] One such predisposing condition is intensive induction treatment of leukemia. The treatment of patients with childhood Acute Lymphoblastic Leukemia (ALL) has extended the 5-year event-free survival rates and, consequently, the morbidities secondary to treatment for ALL have assumed increasing importance.[2] Thromboembolic events, including CSVT, are among the more frequent and serious complications of ALL and its treatment.[23] The timing of thrombosis in children with ALL is very consistent in the literature, occurring either during or immediately after chemotherapy with L-asparaginase.[23]

umed increasing importance.[2] Thromboembolic events, including CSVT, are among the more frequent and serious complications of ALL and its treatment.[23] The timing of thrombosis in children with ALL is very consistent in the literature, occurring either during or immediately after chemotherapy with L-asparaginase.[23] Case Reports Case 1 A 10-year-old boy with newly diagnosed ALL, receiving intravenous vincristine and doxorubicin as well as oral prednisolone and intrathecal methotrexate, was now on treatment with intravenous l-asparaginase. He reported headache while on treatment with L-asparaginase. On examination, Kernig’s sign was absent and there was no papilledema. The initial plain CT did not reveal any definite focal lesion in the brain. Two days later, his headache worsened and he developed vomiting followed by seizures and loss of conciousness. He was resuscitated and anticonvulsant medication was given intravenously. Noncontrast CT now showed hemorrhagic infarcts in the bilateral high parietal regions [Figure 1]; the infarcts were larger on the left side, with a mass effect and midline shift toward the right [Figure 2]. Contrast-enhanced CT showed hypodense attenuation of the superior sagittal sinus posteriorly with peripheral enhancement (called the empty delta sign), Which was suggestive of sinus thrombosis [Figure 2]. The patient’s coagulogram was significantly altered, with antithrombin level of 50% and fibrinogen level of 0.9 g/l; the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were abnormal. L-asparaginase was stopped and fresh frozen plasma was infused in an attempt to reverse L-asparaginase-induced antithrombin deficiency. Phenytoin injections were continued for control of seizures. However, the patient continued to deteriorate and the coagulogram abnormalities could not be reversed; he expired 2 days after diagnosis of superior sagittal sinus thrombosis complicated by venous infarction.

se L-asparaginase-induced antithrombin deficiency. Phenytoin injections were continued for control of seizures. However, the patient continued to deteriorate and the coagulogram abnormalities could not be reversed; he expired 2 days after diagnosis of superior sagittal sinus thrombosis complicated by venous infarction. Figure 1 Noncontrast transverse CT image of the brain showing venous infarcts with hemorrhage in the bilateral parietal regions of the cerebral hemispheres Figure 2 Contrast-enhanced transverse CT image showing the empty delta sign in the superior sagittal sinus posteriorly, with a large infarct in the lefthemisphere causing a midline shift to the right

Figure 1 Noncontrast transverse CT image of the brain showing venous infarcts with hemorrhage in the bilateral parietal regions of the cerebral hemispheres Figure 2 Contrast-enhanced transverse CT image showing the empty delta sign in the superior sagittal sinus posteriorly, with a large infarct in the lefthemisphere causing a midline shift to the right Case 2 A 13-year-old girl being treated for acute mixed phenotypic leukemia developed headache and an episode of focal seizure. She was being given induction therapy for leukemia, with L-asparaginase 10000 units, vincristine 2 mg, and daunorubicin 40 mg. The coagulogram was significantly deranged at the time of presentation: the PT was 57% of normal, APTT was 62 sec, and INR was 1.38. Brain imaging was performed with plain and contrast-enhanced MRI to look for possible intracranial complications of leukemia as the cause of the neurological manifestations. Initial noncontrast T2-weighted MR image revealed a small hyperintense lesion in the left high parietal region of the brain, predominantly involving the white matter [Figure 3]. Coronal plane contrast-enhanced T1-weighted image demonstrated a nonenhancing superior sagittal sinus with the empty delta sign [Figure 4]. On MR venography there was nonvisualization of the anterior portion of the superior sagittal sinus due to absent flow, confirming the presence of thrombosis [Figure 5]. The clinical history, coagulogram readings, and imaging findings were diagnostic of asparaginase-induced coagulopathy manifesting as dural sinus thrombosis. Anticoagulation was started with low molecular weight heparin and continued with oral warfarin. Coagulogram parameters normalized over 5 days of treatment and the patient made a gradual but full clinical recovery. Repeat MRI showed normal signal intensity and enhancement of the previously thrombosed superior sagittal sinus.

oagulation was started with low molecular weight heparin and continued with oral warfarin. Coagulogram parameters normalized over 5 days of treatment and the patient made a gradual but full clinical recovery. Repeat MRI showed normal signal intensity and enhancement of the previously thrombosed superior sagittal sinus. Figure 3 T2-weighted axial MR image showing a small area of subcortical white matter edema in the left high parietal parasagittal region due to a venous infarct Figure 4 Coronal T1-weighted postcontrast MR image showing empty delta sign due to superior sagittal sinus thrombosis Figure 5 Maximum-intensity projection (MIP) MR venography image shows nonvizualization of the anterior portion of the superior sagittal sinus due to thrombosis

Figure 3 T2-weighted axial MR image showing a small area of subcortical white matter edema in the left high parietal parasagittal region due to a venous infarct Figure 4 Coronal T1-weighted postcontrast MR image showing empty delta sign due to superior sagittal sinus thrombosis Figure 5 Maximum-intensity projection (MIP) MR venography image shows nonvizualization of the anterior portion of the superior sagittal sinus due to thrombosis Discussion Cerebral events in leukemia may be due to ischemia, hemorrhage, infection, or spread of the primary disease to brain.[4] Venous thrombosis may cause as many as 30% of the acute central nervous system events in acute leukemias. The estimated risk of thrombosis during the treatment of ALL in children is about 5%. Thrombotic events mainly occur in the central nervous system and upper limbs. Most of the thrombotic events occur during the induction phase of leukemia treatment. This is because of more intense treatment during this initial phase and, more importantly, the disease being active at this stage, there is a large lymphoblast population undergoing cytolysis. Patients receiving postinduction treatment have more stable disease and less thrombotic risk.[5] Drugs that enhance the risk of thrombosis include, most importantly, L-asparaginase and steroids.

and, more importantly, the disease being active at this stage, there is a large lymphoblast population undergoing cytolysis. Patients receiving postinduction treatment have more stable disease and less thrombotic risk.[5] Drugs that enhance the risk of thrombosis include, most importantly, L-asparaginase and steroids. L-asparaginase is established as an important treatment component during remission induction therapy of children with ALL.[6] L-asparaginase hydrolyses asparagine to aspartic acid and ammonia, and this may affect important proteins in the body. The changes affecting the proteins of the blood coagulation system have considerable clinical impact as they may induce bleeding as well as thromboembolic events.[5–7] Life-threatening complications may result when the central nervous system is involved. L-asparaginase may impair the hemostatic system by reducing the synthesis of coagulation factors (including fibrinogen, factor II, IX, and X) and inhibitors of coagulation (such as antithrombin, protein C, and protein S) as a consequence of asparagine depletion.[5–7] Despite a reduction of both procoagulant and anticoagulant activity, the hemostatic balance appears to be shifted towards a hypercoagulable state.[7] Asparaginase-induced deficiency of antithrombin III, the most important endogenous anticoagulant, significantly increases the risk of sinovenous thrombosis in the brain.[6] About 2% of children treated with L-asparaginase develop hemorrhagic or nonhemorrhagic infarcts consequent to CSVT.

rds a hypercoagulable state.[7] Asparaginase-induced deficiency of antithrombin III, the most important endogenous anticoagulant, significantly increases the risk of sinovenous thrombosis in the brain.[6] About 2% of children treated with L-asparaginase develop hemorrhagic or nonhemorrhagic infarcts consequent to CSVT. The clinical manifestations of CSVT are variable and include headache, vomiting, altered mental status, focal deficits, and seizures.[17] The underlying pathology responsible for these symptoms is the spectrum of unilateral and bilateral venous infarcts and hemorrhages. Infarction and tissue damage result from decreased blood flow as a result of elevated retrograde venous pressure.[48] The evaluation of children with suspected CSVT has been made considerably easier by the modern neuroimaging techniques of CT and MRI. If emergency imaging ofthe venous sinuses is not undertaken the diagnosis is verylikely to be missed in affected children.[8]

flow as a result of elevated retrograde venous pressure.[48] The evaluation of children with suspected CSVT has been made considerably easier by the modern neuroimaging techniques of CT and MRI. If emergency imaging ofthe venous sinuses is not undertaken the diagnosis is verylikely to be missed in affected children.[8] Thrombosed sinus may appear hyperdense on noncontrast CT. Contrast-enhanced CT reveals enhancement around the thrombosed sinus in the form of the empty delta sign. Parenchymal infarcts in the distribution of the thrombosed draining vein/sinus, with or without hemorrhage, are additional findings on CT.[48] However, CT scan with contrast missesthe diagnosis of CSVT in up to 40% of patients. Early CT in case 1 of our series missed dural sinus thrombosis; when it was subsequently identified on the repeat CT, the damage had already been done. MRI is more sensitive for detection of early infarction.[9] Case 2 exemplifies this, with postcontrast MRI and MR venography identifying dural sinus thrombus when only subtle infarction was visible on plain CT. CT venography or MRI with venous MR(MRV) are now the methods of choice for investigation of CSVT.[10] The diagnosis is established by demonstratinga lack of flow in the dural sinuses and cerebral veins, with or without typicalimages of brain infarcts. Parenchymal MR and MRV are importantin the demonstration of both the infarct and the thrombus withinthe sinuses.[910] On MRI, the thrombus is readily recognizable inthe subacute phase, when it is of high signal intensity on T1-weightedimages; MRV is then often not required. In the acute phase, thethrombus shows isointense signal intensity on T1-weighted and low signalon T2-weighted imaging. This can be mistaken for flowing bloodbut MRV will demonstrate an absence of flow in the thrombosedsinus.[910]

when it is of high signal intensity on T1-weightedimages; MRV is then often not required. In the acute phase, thethrombus shows isointense signal intensity on T1-weighted and low signalon T2-weighted imaging. This can be mistaken for flowing bloodbut MRV will demonstrate an absence of flow in the thrombosedsinus.[910] Treatment of CSVT resulting from L-asparaginase-induced antithrombin deficiency includes general supportive measures, anticonvulsants for seizures, and anticoagulation.[157] L-asparaginase may be stopped for some time.[6] However, the key to management is early diagnosis by imaging as delayed institution of anticoagulation may be futile as in case 1. Rapid replenishment of coagulation factors may be achieved with fresh frozen plasma; antithrombin concentrates are preferred for this.[6] For therapeutic anticoagulation, low molecular weight heparin is given initially and this may be continued or it may be substituted by oral anticoagulants for 3–6 months.[1578] We conclude that, diagnosis of CSVT in leukemic patients being treated with L-asparaginase requires a high index of clinical suspicion in the presence of seizures, a focal neurological deficit, and features of raised intracranial tension. Early diagnosis demands a low threshold for imaging, and MRI should be preferred over CT. Identification of relevant findings such as venous infarcts, the empty delta sign, and absent flow in the dural sinuses on CT and MR venography enables proper diagnosis and management. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Generalized seizure after laminectomy is very rare and, to our knowledge, has not been reported after lipomyelomeningocele surgery so far. Here, two cases of seizure following laminectomy for lumbar and lumbosacral lipomyelomeningocele are reported, and different aspects regarding the potential etiology of the event have been discussed. Case Report Among all 107 cases of lipomyelomeningocele who underwent surgery in our center between 2000 and 2008, two patients developed generalized seizure postoperatively. One of them was a 7-month-old boy with lumbosacral transitional-type lipomyelomeningocele and the other was a 9-month-old boy with dorsal-type lipomyelomeningocele in the lumbar area. On admission, both patients had normal motor function but decreased anal sphincter tone and neurogenic bladder confirmed by urodynamic study. None of the children had a previous history of seizure. The patients had neither siblings with the same problem nor history of seizure in their families. Preoperative laboratory tests were in the normal range. Standard surgical and anesthetic approach was performed in both patients. The patients were premedicated with fentanyl (1 μg/kg). Anesthesia was induced with inhalation of halothane and intravenous thiopental (5 mg/kg) and maintained with halothane at 1.5 minimum alveolar anesthetic concentration and N2O 50%. The patients then turned prone and standard surgery for lipomyelomeningocele was performed, including lipoma resection, releasing nerve roots, cord untethering, placode pial suturing and repairing dural and facial defects.

g/kg) and maintained with halothane at 1.5 minimum alveolar anesthetic concentration and N2O 50%. The patients then turned prone and standard surgery for lipomyelomeningocele was performed, including lipoma resection, releasing nerve roots, cord untethering, placode pial suturing and repairing dural and facial defects. During surgery, no exogenous material entered the field and there was no antibiotic in the water for irrigation. Both patients were extubated in the operation room and transferred to the ward after uneventful recovery. The first patient developed generalized tonic clonic (GTC) seizure 2 hours after surgery, which was controlled with diazepam. The other had one episode of GTC seizure 12 hours after surgery, which was repeated on the next morning. Both attacks were controlled with phenytoin. Laboratory tests and serum electrolytes were normal in both patients. A brain computed tomography (CT) scan was performed in both, which was normal in the first case but revealed a small pneumocephalus of <1 cm thickness in the right frontal area in the second patient. There was no midline shift, edema or hematoma [Figure 1]. Electroencephalography was performed in both patients, which was normal. Figure 1 Brain computed tomography scan of the second patient shows a small rim of pneumocephalus Both patients were discharged from the hospital 7 days later and no episodes of seizure occurred afterwards.

During surgery, no exogenous material entered the field and there was no antibiotic in the water for irrigation. Both patients were extubated in the operation room and transferred to the ward after uneventful recovery. The first patient developed generalized tonic clonic (GTC) seizure 2 hours after surgery, which was controlled with diazepam. The other had one episode of GTC seizure 12 hours after surgery, which was repeated on the next morning. Both attacks were controlled with phenytoin. Laboratory tests and serum electrolytes were normal in both patients. A brain computed tomography (CT) scan was performed in both, which was normal in the first case but revealed a small pneumocephalus of <1 cm thickness in the right frontal area in the second patient. There was no midline shift, edema or hematoma [Figure 1]. Electroencephalography was performed in both patients, which was normal. Figure 1 Brain computed tomography scan of the second patient shows a small rim of pneumocephalus Both patients were discharged from the hospital 7 days later and no episodes of seizure occurred afterwards. Discussions The occurrence of seizure after laminectomy for the spinal procedure is very rare. Two cases of such complications have been reported after cervical and thoracic laminectomy,[12] although seizure after laminectomy for lipomyelomeningocele has not been reported beforehand.

Both patients were discharged from the hospital 7 days later and no episodes of seizure occurred afterwards. Discussions The occurrence of seizure after laminectomy for the spinal procedure is very rare. Two cases of such complications have been reported after cervical and thoracic laminectomy,[12] although seizure after laminectomy for lipomyelomeningocele has not been reported beforehand. In myelomeningocele, which is a distinct entity, the range of seizure incidence varies from 14.7% to 29%.[3] Seizure in these patients is mainly related to the hydrocephalus, in particular, to the ventriculoperitoneal shunt and its complications.[34] Considering the fact that these patients had lipomyelomeningocele, which never associated with hydrocephalus, the seizure cannot be attributed to this issue. Different aspects related to the anesthetic course may cause postoperative seizure. However, anesthesia was managed without any hypotensive or hypoxic problems in these patients, with none of the agents being known to be epileptogenic.

In myelomeningocele, which is a distinct entity, the range of seizure incidence varies from 14.7% to 29%.[3] Seizure in these patients is mainly related to the hydrocephalus, in particular, to the ventriculoperitoneal shunt and its complications.[34] Considering the fact that these patients had lipomyelomeningocele, which never associated with hydrocephalus, the seizure cannot be attributed to this issue. Different aspects related to the anesthetic course may cause postoperative seizure. However, anesthesia was managed without any hypotensive or hypoxic problems in these patients, with none of the agents being known to be epileptogenic. Some cerebral and spinal mechanisms can be considered for a justification of the seizure after lipomyelomeningocele surgery. Pneumocephalus has been reported as a reason for generalized convulsion after cervical laminectomy,[2] as can be considered in one of these cases. Postoperative seizure after laminectomy may occur as a result of unrecognized dural tear, resulting in acute cerebrospinal fluid (CSF) loss and the drastic decrease in the CSF pressure.[1] Brain CT in such intracranial hypotension may show dural enhancement or meningeal reaction as decreased distance between the brain and the dura.[1] Different kinds of intracranial hemorrhage, particularly subdural, subsequent to CSF leakage after spinal procedures have been associated with seizure.[15]

CSF pressure.[1] Brain CT in such intracranial hypotension may show dural enhancement or meningeal reaction as decreased distance between the brain and the dura.[1] Different kinds of intracranial hemorrhage, particularly subdural, subsequent to CSF leakage after spinal procedures have been associated with seizure.[15] Some spinal basis can be supposed for this postoperative seizure. The issue of spinal-induced seizure is well documented in the literature and commonly used for experimental purposes.[67] The investigations on vagus nerve stimulation on induced spinal cord seizure confirm the seizure with a merely spinal origin.[8] Neurons of the spinal cord, just as in the cerebral cortex, are known to become hyperactive and cause spinal cord “seizures.”[9] Transection of the spinal cord of the cat at a thoracic or lumbar level results in an altered excitability that repeated natural stimulation of the dermatome just caudal to the transection site will induce seizure discharges.[7] Spinal seizure has been reported in humans with transverse myelopathy as well.[10] Although our patients had no paresis before surgery and no cord injury happened during the procedure, it is possible that minor surgical manipulation had stimulated the neural pathways to act as a trigger zone for spinal seizure.

ges.[7] Spinal seizure has been reported in humans with transverse myelopathy as well.[10] Although our patients had no paresis before surgery and no cord injury happened during the procedure, it is possible that minor surgical manipulation had stimulated the neural pathways to act as a trigger zone for spinal seizure. Spinal cord seizure can be induced with stimulation via numerous drugs and chemicals. Strychnine or tranexamic acid was shown to have such influences.[9] Topical or systemic administration of a toxic amount of penicillin can induce convulsive activity.[6] A case of postlaminectomy convulsion due to a large amount of iodophendylate used for preoperative myelogram has been reported as well.[11] Regarding the fact that chemical spinal stimulation can trigger seizure and that no exogenous substance entered to our field during surgery, it can be considered that the fat molecules inside the lipoma may act as the source of stimulation. It is possible that these molecules were released from the fat tissue in their original form or even in the form of free radicals as a result of resection or thermal coagulation, and had a contact with exposed placode and cerebral neural structures and induced a trigger zone in the cord or brain. Conclusion Although it cannot be determined by certainty, postsurgical seizure after lipomyelomeningocele operation in these cases can be attributed to either pneumocephalus or direct spinal stimulation through surgical manipulation or the potential toxic effect of fat molecules. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Desmoplastic infantile ganglioglioma (DIG) was first described by Vanderberg in 1987.[1] Before his introduction, similar tumors were labeled as composite cerebral neuroblastoma and astrocytoma.[2] Now, this tumor is recognized as a distinct entity and is included in the World Health Organization (WHO) classification under the category of neural and mixed glio-neuronal tumors, and is in the grade I of the WHO classification.[3] Until now, <60 cases of DIG have been described.[4] We present a case in a 3-month-old male infant presenting with intractable seizure and a large mass in the right temporal lobe, which showed classic histological features of DIG. Hence, the current case extends the reported spectrum of this rare tumor and helps pathologists in considering the diagnosis especially in young patients. Case Report A 3-month-old infant was admitted with the chief complaint of seizure. He was the first child of the family, born during an uncomplicated full-term pregnancy and a normal vaginal delivery. The family history was unremarkable. Physical examination revealed no abnormality, with a normal neurological examination. Magnetic resonance imaging (MRI) scan showed a hypodense area in the right temporal region, with marked enhancement in the medial parts and severe surrounding brain edema [Figure 1]. Figure 1 Brain MRI scan shows a large superficial and temporal mass A right temporal craniotomy accompanied by peripheral temporal lobectomy was performed and more than 90% of the tumor was excised. The postoperative period was uneventful, with no seizure after surgery.

Case Report A 3-month-old infant was admitted with the chief complaint of seizure. He was the first child of the family, born during an uncomplicated full-term pregnancy and a normal vaginal delivery. The family history was unremarkable. Physical examination revealed no abnormality, with a normal neurological examination. Magnetic resonance imaging (MRI) scan showed a hypodense area in the right temporal region, with marked enhancement in the medial parts and severe surrounding brain edema [Figure 1]. Figure 1 Brain MRI scan shows a large superficial and temporal mass A right temporal craniotomy accompanied by peripheral temporal lobectomy was performed and more than 90% of the tumor was excised. The postoperative period was uneventful, with no seizure after surgery. The specimen, which was received in the pathology department, showed multiple fragments of grayish and firm tissue, altogether measuring about 3 cm × 3 cm × 2 cm. The hematoxylin and eosin (H and E) stain revealed a markedly desmoplastic tumor, showing deposition of dense collagen fibers. The neoplastic cell population was heterogenous, composed of spindle-shaped astrocytes with a fascicular arrangement in the abundant collagenous reticulin-rich stroma [Figure 2]. Scattered ganglion cells were also observed, indicating neuronal differentiation [Figure 3]. No mitosis or necrosis was present. A preliminary diagnosis of desmoplastic infantile ganglioglioma was made.

spindle-shaped astrocytes with a fascicular arrangement in the abundant collagenous reticulin-rich stroma [Figure 2]. Scattered ganglion cells were also observed, indicating neuronal differentiation [Figure 3]. No mitosis or necrosis was present. A preliminary diagnosis of desmoplastic infantile ganglioglioma was made. Immunohistochemistry (IHC) was performed to confirm the diagnosis. There was diffuse reactivity with glial fibrillary acidic protein (GFAP) in addition to focal isolated ganglion cells being positive with synaptophysin [Figure 4A and B] Figure 2 Low power view of the sections from brain tumor shows severe desmoplasia and fascicular pattern of the arrangement of tumor cells (H&E, ×100) Figure 3 High power view shows isolated ganglion-like cells. (H&E, ×250) Figure 4A Diffusely GFAP reactive tumor cells along with focal isolated ganglion cells being positive with synaptophysin Figure 4B Isolated synaptophysin positive ganglion cells (arrow) Follow-up of the patient after 6 months is unremarkable, with no seizure or any evidence of recurrence. Discussion DIGs are rare intracranial tumors, most likely diagnosed in the first 24 months of life.[3] Boys are affected more commonly than girls.[4] Symptoms of DIG are intracranial hypertension, sunset eye, enlarging head circumference, bulging fontanels, variable localizing signs, including seizures, or paresis.[5]

Follow-up of the patient after 6 months is unremarkable, with no seizure or any evidence of recurrence. Discussion DIGs are rare intracranial tumors, most likely diagnosed in the first 24 months of life.[3] Boys are affected more commonly than girls.[4] Symptoms of DIG are intracranial hypertension, sunset eye, enlarging head circumference, bulging fontanels, variable localizing signs, including seizures, or paresis.[5] They are massive, firmly attached to the dura, extensively infiltrate the subarachnoid space but do not involve the ventricular system.[6] Most commonly, CT scan and magnetic resonance imaging show a large superficial large cerebral mass with solid and cystic areas.[4] The solid component of the tumor frequently shows contrast enhancement. Calcification has not been reported in imaging studies.[3] Pathologic features of the tumor have been clearly described in several previous reports. Histologically, the most prominent feature of DIG is desmoplasia and spindle cells with a storiform pattern of arrangement.[5] There is also a ganglion cell component, which is present as single cells or clusters.[7] The first component can be shown to be GFAP positive, but the latter component is of neuroepithelial origin and reactive with markers such as synaptophysin.[7]

Pathologic features of the tumor have been clearly described in several previous reports. Histologically, the most prominent feature of DIG is desmoplasia and spindle cells with a storiform pattern of arrangement.[5] There is also a ganglion cell component, which is present as single cells or clusters.[7] The first component can be shown to be GFAP positive, but the latter component is of neuroepithelial origin and reactive with markers such as synaptophysin.[7] The main histologic differential diagnoses are reticulin-rich desmoplastic tumors such as pleomorphic xanthoastrocytoma, which can be differentiated by age of the patient, prominent lipidization of the cells and absence of neural component.[6] Another tumor in this category is gliofibroma, which is infratentorial and lacks the neural component.[9] Age of the patient and lack of desmoplasia in the ganglioglioma can differentiate this tumor from DIG.[6] Our case was a 3-month-old baby with intractable seizure of undetermined cause. CT showed a large superficial tumor in the temporal lobe, which is the third most common site of brain involvement. Pathology of the tumor revealed typical histologic and IHC features. Complete resection is usually curative with no further additional therapy.[8] Our case is also well after tumor resection and now, after 6 months, has no evidence of tumor progression or recurrence. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Neurofibromatosis type 1 (NF-1), previously known as Von Recklinghausen disease, is a phakomatosis or neurocutaneous syndrome with autosomal-dominant inheritance, primarily affecting the development and growth of nerve cell tissues, with a frequency of approximately 1 in 3,000 births.[1] Pathologically, neurofibromas in NF-1 can be divided into three types, the most common being localized neurofibroma, the least common being diffuse neurofibroma and the most characteristic lesion of the disease being plexiform neurofibroma.[2] Plexiform neurofibromatosis, pathognomonic of NF-1, exhibits a characteristic “bag of worms” appearance on gross examination and cross-sectional imaging because of the involvement of the long segment of a major nerve trunk and its branches.[3] This lesion, in its most extreme form, may involve an entire extremity, with gigantic hypertrophy of the skin, soft tissues and the underlying skeleton.[4] They may become very large and deformed, and is therefore named as “elephantiasis neuromatosa” by Virchow.[1]

ng segment of a major nerve trunk and its branches.[3] This lesion, in its most extreme form, may involve an entire extremity, with gigantic hypertrophy of the skin, soft tissues and the underlying skeleton.[4] They may become very large and deformed, and is therefore named as “elephantiasis neuromatosa” by Virchow.[1] Case Report A 15-year-old male child with known NF-1 was referred to our radiology department for detailed assessment of a large disabling right leg plexiform neurofibroma that had recently undergone skin ulceration and had affected the patient’s gait. This slow-growing plexiform neurofibroma since childhood had resulted in gross limb enlargement and disfigurement [Figure 1], necessitating debulking surgery. Local examination revealed marked soft tissue hypertrophy of the right leg extending from the knee to the ankle. Clinically, the patient had no neurological or visual symptoms. However, physical examination revealed numerous “café au lait” spots (>5 mm in greatest diameter) randomly distributed all over the body [Figure 2], with axillary freckling. Slit lamp examination of both eyes revealed multiple pigmented iris hamartomas (Lisch nodules); five in the right eye [Figure 3] and three in the left eye. Blood and urine tests, including the vanillylmandelic acid test, were all within normal ranges. There was no family history of NF-1 in first-degree relatives. Figure 1 Photograph of bilateral lower extremities showing gross right limb enlargement, hypertrophy, disfigurement and skin ulceration

Case Report A 15-year-old male child with known NF-1 was referred to our radiology department for detailed assessment of a large disabling right leg plexiform neurofibroma that had recently undergone skin ulceration and had affected the patient’s gait. This slow-growing plexiform neurofibroma since childhood had resulted in gross limb enlargement and disfigurement [Figure 1], necessitating debulking surgery. Local examination revealed marked soft tissue hypertrophy of the right leg extending from the knee to the ankle. Clinically, the patient had no neurological or visual symptoms. However, physical examination revealed numerous “café au lait” spots (>5 mm in greatest diameter) randomly distributed all over the body [Figure 2], with axillary freckling. Slit lamp examination of both eyes revealed multiple pigmented iris hamartomas (Lisch nodules); five in the right eye [Figure 3] and three in the left eye. Blood and urine tests, including the vanillylmandelic acid test, were all within normal ranges. There was no family history of NF-1 in first-degree relatives. Figure 1 Photograph of bilateral lower extremities showing gross right limb enlargement, hypertrophy, disfigurement and skin ulceration Figure 2 Photograph of the back of the trunk showing multiple “café au lait” spots of variable sizes Figure 3 Slit lamp examination of the right eye showing multiple (five) pigmented iris hamartomas (Lisch nodules)

Figure 1 Photograph of bilateral lower extremities showing gross right limb enlargement, hypertrophy, disfigurement and skin ulceration Figure 2 Photograph of the back of the trunk showing multiple “café au lait” spots of variable sizes Figure 3 Slit lamp examination of the right eye showing multiple (five) pigmented iris hamartomas (Lisch nodules) Conventional radiograph showed relative lengthening and marked soft tissue hypertrophy of the right leg. Osseous abnormalities included thinning of bones, erosion of distal articular surfaces and periosteal dysplasia [Figure 4]. Gray scale evaluation revealed a diffuse infiltrative, interdigitating network of tumors oriented along the long axis of the nerve. The lesions were heterogeneous in nature and had characteristic “target sign” appearances. However, due to the diffuse infiltrative nature of the lesion, the entering/exiting nerve points could not be detected [Figure 5]. Plain computed tomography (CT) (bone and soft tissue window) confirmed the plain X-ray findings of periosteal dysplasia and cortical erosions. In addition, it also demonstrated an infiltrating network of low attenuated masses traversing the soft tissue and invading the periosteum through a large periosteal defect [Figures 6 and 7]. All magnetic resonance imaging (MRI) sequences demonstrated extensive, conglomerate soft tissue masses infiltrating the subcutaneous fat and multiple muscular compartments of the right leg, causing marked atrophy and poor differentiation of individual muscles. The masses had a variegated appearance, ranging from nodular to thick irregular cords, few showing a branching pattern. The lesion exhibited mixed signal intensity similar to, and slightly higher than, that of muscle on T1W sequence [Figure 8] and heterogeneously high signal intensity on T2W/STIR sequences giving a “bag of worms” appearance – the characteristic of plexiform neurofibromatosis [Figure 9]. Marked, but inhomogenous, enhancement of both the soft tissue and the subperiosteal component of the mass was evident on intravenous injection of gadolinium [Figure 10]. The dynamic contrast-enhanced 3D CT angiography revealed hypertrophy of the right lower limb vessels; all main arteries were enlarged but patent. There were multiple tortuous collateral branches that infiltrated the soft tissues of the calf [Figure 11]. The venous phase also revealed several enlarged draining veins (not shown).

ic contrast-enhanced 3D CT angiography revealed hypertrophy of the right lower limb vessels; all main arteries were enlarged but patent. There were multiple tortuous collateral branches that infiltrated the soft tissues of the calf [Figure 11]. The venous phase also revealed several enlarged draining veins (not shown). Figure 4 Conventional radiograph of the bilateral lower limbs shows disparity in limb length. The right limb appears relatively longer and shows soft tissue hypertrophy, periosteal and endosteal thickening (involving middle 1/3rd shaft of the tibia), scalloping of planter surface of right calcaneum and erosion of articular surfaces of the right talocalcaneal joint Figure 5 Gray scale ultrasonography of the right lower limb shows multilobulated tortuous entanglement of tumors, oriented along the long axis of the nerve on longitudinal section, and “target sign” on transverse scan, evident as echogenic center and hypoechoic periphery Figure 6 Plain computed tomography (bone window) demonstrates a large periosteal defect giving way to the infiltrating mass lesion, periosteal/ endosteal thickening (axial and coronal image-arrows) and cortical erosions at talocalcaneal joint (sagittal image-arrows) Figure 7 Plain computed tomography (soft tissue window) shows thick wavy cords of low attenuated masses traversing the soft tissue and giving a reticular-network appearance to the right leg

Figure 6 Plain computed tomography (bone window) demonstrates a large periosteal defect giving way to the infiltrating mass lesion, periosteal/ endosteal thickening (axial and coronal image-arrows) and cortical erosions at talocalcaneal joint (sagittal image-arrows) Figure 7 Plain computed tomography (soft tissue window) shows thick wavy cords of low attenuated masses traversing the soft tissue and giving a reticular-network appearance to the right leg Figure 8 T1W sagittal and coronal sequences show marked atrophy and poor differentiation of individual muscles and variegated appearance of masses, ranging from nodular to thick irregular cords, few of them showing a branching pattern. The lesion shows signal intensity similar to as well as slightly higher than that of muscle Figure 9 On T2W/STIR (sagittal and coronal) sequences, the lesion demonstrates a characteristic “bag of worms” appearance of plexiform neurofibromatosis Figure 10 Postcontrast T1W fat saturation image reveals marked but slight inhomogenous enhancement of the soft tissue (asterisk) and subperiosteal component (arrow) of the mass. The subperiosteal component also shows a central area of cystic necrosis Figure 11 Dynamic 3D postcontrast computed tomography angiography (arterial phase) reveals hypertrophy of the right lower limb main arteries, which otherwise appear to be patent. Multiple tortuous collateral branches infiltrating soft tissues of the calf are also seen

Figure 10 Postcontrast T1W fat saturation image reveals marked but slight inhomogenous enhancement of the soft tissue (asterisk) and subperiosteal component (arrow) of the mass. The subperiosteal component also shows a central area of cystic necrosis Figure 11 Dynamic 3D postcontrast computed tomography angiography (arterial phase) reveals hypertrophy of the right lower limb main arteries, which otherwise appear to be patent. Multiple tortuous collateral branches infiltrating soft tissues of the calf are also seen Screening MRI of the brain showed a well-defined lesion in the left basal ganglia, particularly involving the internal capsule, adjoining part of the globus pallidus and the thalamus. The lesion demonstrated mixed hypo- and hypersignal intensity on T1WI, high signal intensity on T2W/FLAIR sequences and no enhancement after contrast administration. The lesion typically did not exhibit mass effect, edema or contrast enhancement, suggesting non-neoplastic hamartoma [Figure 12]. Figure 12 Screening magnetic resonance imaging of the brain shows a nonneoplastic hamartomatous lesion in the left basal ganglia The patient underwent partial tumor resection and cosmetic repair of the right leg. He was also advised follow-up MRI of the brain for hamartomatous lesion, which normally shows spontaneous regression with time.

Figure 12 Screening magnetic resonance imaging of the brain shows a nonneoplastic hamartomatous lesion in the left basal ganglia The patient underwent partial tumor resection and cosmetic repair of the right leg. He was also advised follow-up MRI of the brain for hamartomatous lesion, which normally shows spontaneous regression with time. The histopathologic evaluation of the resected mass revealed a non-capsulated lesion comprising a large number of irregular infiltrative spindle cells and several nerve segments of varying length embedded in subcutaneous fat. The nerves were surrounded by a myxoid stroma that extended into the papillary dermis. Many mast cells were also seen within the diffuse component of the tumor. However, no mitosis was detected. The findings were suggestive of diffuse plexiform neurofibromatosis [Figure 13]. Figure 13 Histopathology of the resected mass reveals a large number of irregular infiltrative spindle cells, several nerve segments of varying length embedded in subcutaneous fat, many mast cells and myxoid stroma – finding consistent with diffuse plexiform neurofibromatosis

The histopathologic evaluation of the resected mass revealed a non-capsulated lesion comprising a large number of irregular infiltrative spindle cells and several nerve segments of varying length embedded in subcutaneous fat. The nerves were surrounded by a myxoid stroma that extended into the papillary dermis. Many mast cells were also seen within the diffuse component of the tumor. However, no mitosis was detected. The findings were suggestive of diffuse plexiform neurofibromatosis [Figure 13]. Figure 13 Histopathology of the resected mass reveals a large number of irregular infiltrative spindle cells, several nerve segments of varying length embedded in subcutaneous fat, many mast cells and myxoid stroma – finding consistent with diffuse plexiform neurofibromatosis Discussion NF-1 is a hamartomatous disorder, with the genetic defect localized to the long arm of chromosome 17q11.2.[1] It is characterized by various skin lesions and peripheral or central nervous system neoplasm. The National Institutes of Health (NIH) in 1987 established diagnostic criteria of patients with NF-1. These well-recognized diagnostic criteria are neurofibromas (two or more simple, or one plexiform neurofibroma), café-au-lait spots (six or more, >5 mm in greatest diameter in children and >15 mm in adults), Lish hamartomas in iris (two or more), axillary or inguinal freckling, skeletal abnormalities (sphenoid dysplasias or cortical thinning, with or without pseudoarthrosis), optic glioma and first-degree relative with NF-1. Presence of two or more of these seven criteria establishes the diagnosis of NF-1. In our patient, five of the seven above-mentioned diagnostic features were present.[5]

skeletal abnormalities (sphenoid dysplasias or cortical thinning, with or without pseudoarthrosis), optic glioma and first-degree relative with NF-1. Presence of two or more of these seven criteria establishes the diagnosis of NF-1. In our patient, five of the seven above-mentioned diagnostic features were present.[5] Plexiform neurofibroma, found in up to 26% of patients with NF-1 is considered an uncommon skin tumor, usually presenting at birth or during the first several years of life. They are unencapsulated, poorly circumscribed tumors that diffusely infiltrate the nerve and the adjacent fat and muscle. As a result, neurofibromas are usually unresectable tumors, where tumor resection is impossible without sacrificing the nerve tissue. Fusiform enlargement of multiple nerve fascicles and branches is characteristic. Plexiform neurofibromas contain a mixture of Schwann cells, fibroblasts, reticulin and collagen fibers and a loose mucoid matrix interspersed between the axons of the parent nerve. They typically affect the trunk and extremities, but may also involve the head-neck and bladder. Associated bone dysplasia is often encountered secondary to chronic hyperemia or as part of the mesodermal dysplasia. Such tumors give rise to a variety of problems, including disfigurement and functional impairment.[6]

ve. They typically affect the trunk and extremities, but may also involve the head-neck and bladder. Associated bone dysplasia is often encountered secondary to chronic hyperemia or as part of the mesodermal dysplasia. Such tumors give rise to a variety of problems, including disfigurement and functional impairment.[6] On ultrasound, these masses are usually hypoechoic, well defined and elliptical, oriented along the long axis of the nerve. Posterior acoustic enhancement is very common (70%). Color Doppler reveals variable vascular patterns, ranging from moderate, irregular central to predominantly peripheral vascularity. Some may not have any demonstrable vascularity.[7] MRI reveals large conglomerate masses consisting of innumerable neurofibromas, diffusely thickening the involved nerve and often extending into the nerve branches. This tumor has a locally aggressive behavior, but the infiltrative pattern is not indicative of malignancy and has no histologic evidence of anaplastic or mitotic features.[8] The typical pattern on MRI is relatively low signal intensity or signal intensity similar to that of muscle with T1-weighting and signal intensity greater than that of fat with T2-weighting. The hyperintense pattern on T2WI reflects the high water content of the myxoid matrix.[2] Three signs have been noted as diagnostic aids on MRI,[9] but they are also seen on ultrasound.[3] The “target sign” is characteristic of benign neurofibroma. The target appearance represents a geographic difference between the histologic zones of the neurofibroma. The high signal intensity seen in the peripheral zone is likely related to the high water content of the myxomatous tissue and the central low signal intensity is probably related to T2 shortening caused by the dense fibrocollageneous tissue. The fascicular sign refers to fascicular bundles in neurogenic tumors showing speckled appearance due to the presence of both high and low signal intensity. The split-fat sign is the presence of fine rind of fat at the periphery of the masses, and it represents the slow-growing nature of the tumor.

collageneous tissue. The fascicular sign refers to fascicular bundles in neurogenic tumors showing speckled appearance due to the presence of both high and low signal intensity. The split-fat sign is the presence of fine rind of fat at the periphery of the masses, and it represents the slow-growing nature of the tumor. The tumor usually exhibits avid contrast uptake but has a heterogeneous appearance on ultrasonography and MRI, owing to the presence of cysts, hemorrhage or necrosis.[3910] CT of plexiform neurofibromas shows large multilobulated low-attenuation masses, usually within a major nerve distribution.[4] MR or CT angiography is mainly used to assess the vascular supply of the tumor and abnormal tumor vessels and to locate vessels suitable for preoperative intra-arterial embolization.[45] Large and diffuse masses may cause venous obstruction and hypertrophy of the feeding vessels. Postcontrast images may also show the extensive capillary pooling of contrast throughout the soft tissue mass corresponding to the plethora of abnormal vessels in “the hemangio-neurofibroma” and the large ectatic veins, which is a pathognomonic finding of a hypervascularised plexiform neurofibroma.[4]

feeding vessels. Postcontrast images may also show the extensive capillary pooling of contrast throughout the soft tissue mass corresponding to the plethora of abnormal vessels in “the hemangio-neurofibroma” and the large ectatic veins, which is a pathognomonic finding of a hypervascularised plexiform neurofibroma.[4] The radiological modalities most often used in analyzing neurofibroma include CT and MRI. Ultrasound and color Doppler has a very limited role in the evaluation of a large mass, extending outside the range of the probe. Although CT is rarely helpful in making a specific diagnosis, it can provide a precise evaluation of the bone lesion and the extent of the soft tissue lesion; however, it is by far inferior to MRI in soft tissue contrast resolution and the visualization of tissue planes. Dynamic contrast-enhanced 3D MR or CT angiography represents a recent advance in imaging with rapid acquisition of high-quality angiographic images that permit a free choice of imaging planes and phases delineating the arterial and venous supplies, visualization of the abnormal changes of the vasculature in the affected limb, important landmarks in surgical planning. It should be emphasized that MRI and MR angiography may assist not only in the correct diagnosis of neurofibroma but also in imaging the vasculature of a plexiform neurofibroma, which is essential for proper surgical planning.

al changes of the vasculature in the affected limb, important landmarks in surgical planning. It should be emphasized that MRI and MR angiography may assist not only in the correct diagnosis of neurofibroma but also in imaging the vasculature of a plexiform neurofibroma, which is essential for proper surgical planning. Treatment of diffuse and progressive plexiform neurofibroma is primarily surgery. However, complete resection of the tumor is not possible because of marked entanglement of the tumor with the nerves. Improved understanding of the molecular and cellular biology of the cells involved in the formation and growth of neurofibromas has lead to development of other forms of treatments, including drug therapies, whose role is yet to be defined.[10] The common differential diagnosis in this case is other soft tissue tumors causing elephantiasis, such as filariasis, macrodystrophia lipomatosa, lymphangiomatosis, vascular malformation such as hemangioma and massive subperiosteal hematoma. Conclusion There are many imaging modalities available today to study the peripheral nerves. It should be emphasized that MRI and angiography (MR or CT angiography) may assist not only in the correct diagnosis of neurofibroma but also in imaging the vasculature of a plexiform neurofibroma, which is essential for proper surgical planning. Source of Support: Nil. Conflict of Interest: None declared.

Introduction In humans, the incidence of balanced chromosome translocations is approximately one in 500.[1] In cytogenetic evaluation, balanced chromosome translocations are defined as those rearrangements where no loss or gain of genetic material is observed. Most of the balanced chromosome rearrangements (BCRs) are not considered to be associated with the clinical (phenotype) abnormalities. But, they are of concern, as the carriers of BCRs offer a greater risk to their descendents with congenital anomalies or recurrent miscarriages. On the basis of a few evaluation procedures, it is estimated that 6.7% of the carriers of de novo BCRs have the risk of phenotypic abnormalities.[2] Most of the hypotheses that have been proposed to explain the association of BCRs with phenotypic abnormalities[3] include monogenic disorder, such as sickle cell anemia caused by modification or disruption of genes, unbalanced rearrangement at the molecular level, mosaic or varied chromosomal complement for unbalanced rearrangement in another tissue, uniparental disomy of one of the chromosomes involved in the rearrangement and position effect variegation phenomenon.

ickle cell anemia caused by modification or disruption of genes, unbalanced rearrangement at the molecular level, mosaic or varied chromosomal complement for unbalanced rearrangement in another tissue, uniparental disomy of one of the chromosomes involved in the rearrangement and position effect variegation phenomenon. Almost all the carriers of the balanced reciprocal translocations are believed to be normal by phenotype. Moreover, it is known that the modification or inactivation of specific disease genes at chromosomal breakpoints have been very phenomenal in identifying genes that are associated with a variety of disorders, mostly early-onset disorders.[4] In the present paper, we describe paternally inherited autosomal-balanced reciprocal translocation involving chromosomes 8 and 18 in the progeny associated with delayed milestone development. Case Report The proband is a 3-year-old girl, the first female child of a healthy, young, nonconsanguineous couple. Pregnancy and delivery at 38 weeks were normal. Birth weight was 2,800 grams. The proband was referred for cytogenetic evaluation with a history of delayed milestone development. Her height was 60 cm, weight 7 kg and head circumference 35 cm. The second female child was born normal. Written informed consent was taken from the individuals of the family for this study.

irth weight was 2,800 grams. The proband was referred for cytogenetic evaluation with a history of delayed milestone development. Her height was 60 cm, weight 7 kg and head circumference 35 cm. The second female child was born normal. Written informed consent was taken from the individuals of the family for this study. Cytogenetic analysis About 2 ml of peripheral blood was collected from the family members for the cytogenetic evaluation with their informed written consent. All the samples were subjected to lymphocyte culture according to standard cytogenetic protocols.[5] About 50 Giemsa–Trypsin–Giemsa (GTG)-banded[6] metaphase chromosomes were analyzed for all the individuals of the family. In individuals with abnormalities, a total of 100 metaphases were analyzed.

rmed written consent. All the samples were subjected to lymphocyte culture according to standard cytogenetic protocols.[5] About 50 Giemsa–Trypsin–Giemsa (GTG)-banded[6] metaphase chromosomes were analyzed for all the individuals of the family. In individuals with abnormalities, a total of 100 metaphases were analyzed. Fluorescence in situ hybridization (FISH) and microscopy FISH was performed on metaphase spreads derived from the patient’s lymphocytes. Hybridizations were performed using a chromosome 8-specific DNA probe (WCP 8) Spectrum Green (Vysis, Naperville, IL, USA) and a chromosome 18-specific DNA probe (WCP 18) Spectrum Red according to the Vysis manufacturer’s protocol. Targeted metaphase slides were counterstained with 20 μl of 4-6-diamino-2-phenylinodole (DAPI) (10 g/ml). Bright light and fluorescence microscopy was performed using a Zeiss Axioscope microscope (Zeiss, Jena, Germany). A triple filter set (Vysis) was used for simultaneous detection of DAPI, Spectrum Green and Spectrum Red signals. Several images were analyzed using a Cytovision-automated karyotyping system (Applied Imaging, Santa Barbara, CA, USA). Every slide was scored by a minimum of three cytogeneticists.

(Zeiss, Jena, Germany). A triple filter set (Vysis) was used for simultaneous detection of DAPI, Spectrum Green and Spectrum Red signals. Several images were analyzed using a Cytovision-automated karyotyping system (Applied Imaging, Santa Barbara, CA, USA). Every slide was scored by a minimum of three cytogeneticists. Results Cytogenetic evaluation of the GTG-banded metaphases from a lymphocyte culture showed a balanced reciprocal translocation involving chromosomes 8 and 18 in the proband with a karyotype of 46,XX,t(8;18)(q22.1;q22) [Figure 1A]. To trace the origin of the translocation, cytogenetic analysis from peripheral blood of all the family members was performed, which revealed that the mother and sister of the proband showed a normal female karyotype, whereas the father of the proband was found to be a carrier of the balanced reciprocal translocation with 46,XY,t(8;18)(q22.1;q22) karyotype. Further confirmation of this balanced reciprocal translocation was performed by FISH using WCPs for chromosomes 8 and 18 [Figure 1B]. Figure 1 (A) Giemsa-Trypsin-Giemsa banding and ideogram results show autosomal-balanced reciprocal translocation involving chromosomal regions 8q and 18q. The arrows indicate the breakpoints on derivative chromosomes 8 and 18. (B) Fluorescence in situ hybridization of metaphase spread with the Vysis WCP DNA probes, which hybridize chromosome 8 (Spectrum Green) and chromosome 18 (Spectrum Red). The arrows indicate the derivative chromosomes 8 and 18. (C) Pedigree demonstrates characteristics of autosomal-recessive inheritance

osomes 8 and 18. (B) Fluorescence in situ hybridization of metaphase spread with the Vysis WCP DNA probes, which hybridize chromosome 8 (Spectrum Green) and chromosome 18 (Spectrum Red). The arrows indicate the derivative chromosomes 8 and 18. (C) Pedigree demonstrates characteristics of autosomal-recessive inheritance Discussion The sequencing of the entire human genome has revealed the location of an estimated 50,000 genes approximately, although very little is known about their role in human morbidity. Physical mapping of genes involves chromosome abnormalities and variations as two important factors. Hence, to establish genotype–phenotype relationships, a large-scale strategic approach will be of greater importance. Linking up the association of disease consistently with chromosome abnormalities such as deletions, duplications and translocations would be the simple way of mapping disease genes. Mapping of von Recklinghausen neurofibromatosis (NF1) to chromosome 17[7] and the rare congenital disorder campomelic dysplasia (CMPD1), also mapped to chromosome 17[8–11], are good examples of this strategy. Molecular characterization of chromosomal breakpoints in carriers of balanced translocation would be one of the vital strategies to be implemented. Thus, disease-associated chromosome rearrangements[12] that truncate, delete or otherwise inactivate specific genes have been instrumental in the positional cloning of many disease genes.[4] In this paper, we report an interesting case with apparently inherited reciprocal-balanced translocation that has resulted in delayed development of milestones. Delayed milestones or developmental delays are defined as a lag in the child’s development compared to the established standard normal ranges for his or her age. From birth to 6 years of age, 8% of all children show delays in one or more areas of development. The present report indicates that the proband had developmental lags in the first year of her life. She could not crawl by 8 months of age and walk by the middle of the second year; thus, 5 or 6 months behind the normal standard schedule in reaching these milestones, indicating developmental delay regarding mobility. The proband was not speaking words or sentences by her third birthday, while almost all normal children begin to speak their first words before or at the age of 18 months, and by age 3, the majority of children speak short sentences.

edule in reaching these milestones, indicating developmental delay regarding mobility. The proband was not speaking words or sentences by her third birthday, while almost all normal children begin to speak their first words before or at the age of 18 months, and by age 3, the majority of children speak short sentences. At toddlerhood, the proband was found to be reserved and less adventuresome as compared to a normal kid who begins to explore the environment with avid curiosity and immense energy to strike out independently and master new skills. Parents had no history of delayed milestones in their childhood. Balanced chromosomal translocations may cause damage or alteration of the functional genes at the breakpoints of the defective chromosomes resulting in the disease phenotype.[13] It was described previously that children who inherit reciprocal balanced translocation from one of the parents show association with congenital malformation.[14–16] The present case report, however, is the first report of paternal inheritance of balanced reciprocal translocation involving chromosomes 8 and 18 at their respective breakpoint, which shows an association with delayed milestones and which has not been reported previously.

ssociation with congenital malformation.[14–16] The present case report, however, is the first report of paternal inheritance of balanced reciprocal translocation involving chromosomes 8 and 18 at their respective breakpoint, which shows an association with delayed milestones and which has not been reported previously. Couples with balanced reciprocal translocations could have a 50% risk of having spontaneous abortions and a 20% risk of having children with unbalanced karyotype.[17] On the basis of the chromosomes involved and on the location of breakpoints, the production of normal, balanced or unbalanced gametes is decided.[1819] The configuration of the hexavalent at the pachytene stage of meiosis was predominantly used to consider the pattern of segregation; only two configurations result in a normal or balanced gamete karyotype.

ved and on the location of breakpoints, the production of normal, balanced or unbalanced gametes is decided.[1819] The configuration of the hexavalent at the pachytene stage of meiosis was predominantly used to consider the pattern of segregation; only two configurations result in a normal or balanced gamete karyotype. In carriers of balanced translocation, the possible reason for the association of congenital malformations could be gene inactivation or disruption at the breakpoint or a position effect.[20] However, in the case of inherited reciprocal translocation seen in the proband, the breakpoint could inactivate genes, subsequently unmasking a recessive allele inherited from the other parent.[21] The other possible reason could be the occurrence of unequal crossing-over during meiosis that may have resulted in submicroscopic duplications or deletions, as proposed by Jacobs.[20] The present case report shows the inheritance of autosomal balanced reciprocal translocation by the proband from her carrier father who is phenotypically normal. This could be explained as an autosomal-recessive inheritance where, unlike the normal child, there is inheritance of the dominant alleles from both the parents and the recessive alleles along with defective alleles inherited to the proband [Figure 1C].

the proband from her carrier father who is phenotypically normal. This could be explained as an autosomal-recessive inheritance where, unlike the normal child, there is inheritance of the dominant alleles from both the parents and the recessive alleles along with defective alleles inherited to the proband [Figure 1C]. The gene COH1 that maps at 8q22.2 encodes a potential transmembrane protein that functions in vesicle-mediated transport and sorting of proteins within the cell. This protein plays an important role in the development and the function of the eye, hematological system and central nervous system.[22] Mutations in this gene have been associated with Cohen syndrome.[23] Another important gene NEDD4L mapped to 18q21 is the candidate gene for autosomal-dominant orthostatic hypotensive disorder. Also, NEDD4L showed linkage evidence for a susceptibility locus for bipolar affective disorder.[24] Hence, disruption of the gene or group of genes at this breakpoint suggests a cause for delayed developmental milestones. The possible reason leading to delayed milestones may be due to the consequence of the abnormality described in the patient. Hence, further analysis of the breakpoints and molecular characterization of these genes might help in understanding the basis of delayed development of milestones. In view of an increased risk of having congenitally abnormal children, carriers of balanced reciprocal translocation should, therefore, be advised to seek genetic counseling. The genetic counseling for a balanced translocation carrier is often difficult and may require some caution, especially when the fetal karyotype is balanced.[16] Bonthron et al.[24] raised this warning in their report of de novo submicroscopic deletion of an inherited Robertsonian translocation. Hence, carriers of balanced translocation should be counseled for increased risk of birth defects in their offspring due to de novo submicroscopic rearrangements, and reproductive management is performed accordingly.

warning in their report of de novo submicroscopic deletion of an inherited Robertsonian translocation. Hence, carriers of balanced translocation should be counseled for increased risk of birth defects in their offspring due to de novo submicroscopic rearrangements, and reproductive management is performed accordingly. This study was supported by a core grant from the Centre for Scientific and Industrial Research, New Delhi, Government of India. Source of Support: Grant from the Centre for Scientific and Industrial Research, New Delhi, Government of India. Conflict of Interest: None declared.

Introduction In Acute Myeloid Leukemia (AML), malignant clones of immature myeloid cells (primarily blasts) proliferate and eventually replace the bone marrow, circulate in blood and invade other tissues of the body. The usual manifestations are due to the suppression of normal hematopoiesis by leukemia. In this report, the unique presentation of bilateral proptosis resulting from orbital infiltration as well as bilateral temporal swelling by AML is being reported.

ne marrow, circulate in blood and invade other tissues of the body. The usual manifestations are due to the suppression of normal hematopoiesis by leukemia. In this report, the unique presentation of bilateral proptosis resulting from orbital infiltration as well as bilateral temporal swelling by AML is being reported. Case Report A 6-year-old girl presented with low-grade fever for 1 month, with progressive increasing bitemporal swelling and bilateral proptosis (right greater than left) [Figure 1]. On examination, she was markedly cachexic and had significant loss of appetite and weight. She had bilateral proptosis with normal visual acuity and extraocular movements. There was an ill-defined, nontender, firm swelling in the bilateral temporal region with the skin over the swelling being normal. Her neurological examination was normal. There was no palpable abdominal organomegaly and no lymphadenopathy. The contrast-enhanced axial Computed Tomographic (CT) images showed an enhancing infiltrate occupying the lateral wall of the orbit pushing the globe outwards and manifesting as proptosis. The infiltrate extended toward the bilateral temporal fossae beneath the temporalis muscle. There were extradural infiltrates extending bilaterally beneath the frontal and temporal bones. On both sides, small lobules were extending into the cortex of the frontal lobes and causing perifocal edema [Figures 2 and 3]. The coronal CT showed that the left maxilla was also filled by the lesion [Figure 4]. Her hemoglobin was 9 gm% and the total leucocyte count was 34,800/mm3. Her differential leucocytic count showed 5% neutrophils, 14% lymphocytes and 1% reticulocytes. The rest of the cells were immature and deformed cells. The FNAC from the bitemporal swelling showed clusters of atypical cells with a high nuclear–cytoplasmic ratio. The cells contained an irregularly shaped nuclei, with two to three nucleoli and scanty cytoplasm. The cytology was suggestive of a leukemic infiltrate. The bone marrow aspirate and biopsy showed hypercellular marrow smears with proliferation of blasts (approximately 25–30%). The blasts were positive for myeloperoxidase; erythroid cells and megakaryocytes were reduced. The findings were suggestive of AML [Figures 5–8].

cytology was suggestive of a leukemic infiltrate. The bone marrow aspirate and biopsy showed hypercellular marrow smears with proliferation of blasts (approximately 25–30%). The blasts were positive for myeloperoxidase; erythroid cells and megakaryocytes were reduced. The findings were suggestive of AML [Figures 5–8]. Figure 1 A 6-year-old female child showing bilateral proptosis and bitemporal swelling Figure 2 Axial CECT showing enhancing infiltrates occupying the lateral orbital wall and causing proptosis. The infiltrate extended toward the bilateral temporal fossae beneath the temporalis muscle. There were extradural infiltrates extending bilaterally extradurally beneath the temporal bones Figure 3 Axial CECT showing extradural infiltrates extending bilaterally beneath the frontal and temporal bones. On both sides, small lobules were extending into the cortex of the frontal lobes and causing perifocal edema Figure 4 Coronal CT showed the left maxilla also infiltrated by the lesion Figure 5 Bone marrow biopsy showing hypercellular marrow with sheets of blast cells (H & E, 40×) Figure 6 FNAC from temporal swelling with hemorrhagic background showing blast cells (May Grunwald Geimsa stain, 20×) Figure 7 FNAC from temporal swelling showing clumped blast cells with an occasional signal blast cell (May Grunwald Geimsa stain, 20×) Figure 8 Peripheral blood smear showing blast cells (Giemsa stain, 40×)

Figure 5 Bone marrow biopsy showing hypercellular marrow with sheets of blast cells (H & E, 40×) Figure 6 FNAC from temporal swelling with hemorrhagic background showing blast cells (May Grunwald Geimsa stain, 20×) Figure 7 FNAC from temporal swelling showing clumped blast cells with an occasional signal blast cell (May Grunwald Geimsa stain, 20×) Figure 8 Peripheral blood smear showing blast cells (Giemsa stain, 40×) Following diagnosis, she undertook two cycles of intensive chemotherapy, including cytosine arabinoside (100 mg/m2) and doxorubicin (30 mg/m2) in a 7-day cycle at her local hospital, with consequent remission of the disease. She did not report for a subsequent follow-up at our center. Discussion AML accounts for approximately 15% of all leukemias in children.[1] Leukemic cells may infiltrate any extramedullary site. Their accumulation in soft tissue or bone is termed as granulocytic sarcoma, an uncommon presentation, occurring in approximately 3% of patients with AML.[2] This is also termed as chloroma,[3] because leukemic cells containing myeloperoxidase turn green when exposed to ultraviolet light. AML most commonly affects children and young adults, the median age at presentation being 7 years.[4]

coma, an uncommon presentation, occurring in approximately 3% of patients with AML.[2] This is also termed as chloroma,[3] because leukemic cells containing myeloperoxidase turn green when exposed to ultraviolet light. AML most commonly affects children and young adults, the median age at presentation being 7 years.[4] Leukemic cells originate in the bone marrow.[1] In the head and neck, they involve the skull, orbits and paranasal sinuses.[1] Our patient had the unique presentation of bilateral proptosis with bitemporal swelling. The tumor had also infiltrated the frontotemporal extra- and intradural compartments and the paranasal sinuses. The presence of unilateral and bilateral proptosis has been reported with AML.[4–6] The proptosis in these cases is mainly due to leukemic infiltrates, retrobulbar hemorrhage, orbital muscle infiltration or venous blockage. In a study, AML was associated with 9.3% orbital masses.[5] Other presentations due to orbital involvement include ptosis, lacrimal gland involvement, conjuctival masses, iridic and diffuse uveal involvement.[26] Most of the reported cases have decreased visual acuity and restricted extra-ocular movements. Our patient was different in having normal visual acuity and eyeball movements perhaps due to an early detection of the leukemia as well as extension of the leukemic infiltration toward the bilateral temporal fossae rather than within the orbit.

cases have decreased visual acuity and restricted extra-ocular movements. Our patient was different in having normal visual acuity and eyeball movements perhaps due to an early detection of the leukemia as well as extension of the leukemic infiltration toward the bilateral temporal fossae rather than within the orbit. She also had bitemporal swelling that was firm, not tender and had molded into the inner and outer surfaces of bilateral orbital walls without causing any destruction. Although unilateral temporal swelling with AML has also been described in the literature,[7] to the best of our knowledge, the simultaneous presence of both bilateral proptosis and bitemporal swellings have not been previously reported in AML. Other infiltrative lesions like non-Hodgkin lymphoma[8] or eosinophilic granuloma[9] or other temporal bone tumors, developmental lesions like arachnoid cyst,[10] fibrous dysplasia[11] and neurofibromatosis with sphenoid wing dysplasia[12] are often unilateral and usually not associated with bilateral proptosis.

n AML. Other infiltrative lesions like non-Hodgkin lymphoma[8] or eosinophilic granuloma[9] or other temporal bone tumors, developmental lesions like arachnoid cyst,[10] fibrous dysplasia[11] and neurofibromatosis with sphenoid wing dysplasia[12] are often unilateral and usually not associated with bilateral proptosis. Peripheral smear is an invaluable tool in diagnosing the systemic form of AML showing immature blast cells with a high total leukocyte count and relative neutropenia. Leukemic proptosis, however, may not always be associated with leukocytosis or immature cells in the peripheral smear. Doing a peripheral smear along with bone marrow aspirate and biopsy in all patients of AML manifesting with proptosis in the pediatric age is, therefore, justified. Immunohistochemistry and immunocytochemistry are used to detect the antibody against myeloperoxidase. On CT scan, the extramedullary leukemia within the orbits may appear as a well defined lesion, isodense to muscles[1] and enhancing on contrast, usually confined to the orbits but occasionally also extending to the extradural temporal fossae, temporal and frontal regions and rarely also to the paranasal sinuses, as seen in our patient. On magnetic resonance imaging, the lesion is isointense on T1-weighted and hyperintense on T2-weighted image, with intense enhancement on contrast.[136] The prognosis depends on the course of underlying systemic malignancy. The presence of extramedullary leukemia does not alter the survival of patients with AML.[6]

nt. On magnetic resonance imaging, the lesion is isointense on T1-weighted and hyperintense on T2-weighted image, with intense enhancement on contrast.[136] The prognosis depends on the course of underlying systemic malignancy. The presence of extramedullary leukemia does not alter the survival of patients with AML.[6] Chemotherapy is the mainstay of treatment.[16] Chemotherapy includes both an intensive and consolidation phase. In the intensive phase, the drugs doxorubicin and cytosine arabinocide are used. Bone marrow suppression is strictly monitored with the patients being kept in isolation and being administered proper supportive treatment. Growth factor helps in stimulating marrow following the intensive phase of chemotherapy. At the end of 4 weeks, bone marrow aspirate and biopsy should be repeated to assess for remission. If remission has not been achieved, the same cycle of chemotherapy is repeated. In case remission has been achieved, the consolidation phase starts in the form of cytosine arabinoside (over a period of 4–8 months).[13] Despite the advances in chemotherapeutic schedules, an allogenic bone marrow transplantation from a matched family donor still remains the best long-term option that provides remission-free survival for most patients.[13]

consolidation phase starts in the form of cytosine arabinoside (over a period of 4–8 months).[13] Despite the advances in chemotherapeutic schedules, an allogenic bone marrow transplantation from a matched family donor still remains the best long-term option that provides remission-free survival for most patients.[13] Conclusion AML should be kept in the differential diagnosis of a child presenting with proptosis or orbital mass with or without skull lesions. A peripheral blood smear should be performed in all cases along with bone marrow aspirate and biopsy for an early detection of AML. Institution of early intervention in this potentially fatal disease is often associated with gratifying 5-year survival rates. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Postoperative intracranial hemorrhage is a serious complication of intracranial procedures. Hyatai reported that the incidence of postoperative hematoma formation following brain surgery was 2.1%.[1] Of these, 64% were intracerebral, 18% subdural, 14% epidural, and 4% cerebellar.[1] Postoperative intracranial hemorrhage mostly occurs within the operative site. Remote, sequential, multiple epidural hematomas (EDHs) following shunting has only been reported once before.[2] Here we report the formation of multiple EDHs remote from the site of craniotomy following pineal tumor resection. The patient underwent successful reoperation for EDH at four different sites. We discuss the mechanism of development and suggest techniques for avoidance of such complications. Case Report A 9-year-old boy presented with progressive gait disturbance and right-sided weakness of 1 year’s duration. His past medical history was significant for hydrocephaly, and he had experienced several episodes of tonic-type seizures prior to the age of 3 years. He had demonstrated clinical improvement without specific antiepileptic therapy.

esented with progressive gait disturbance and right-sided weakness of 1 year’s duration. His past medical history was significant for hydrocephaly, and he had experienced several episodes of tonic-type seizures prior to the age of 3 years. He had demonstrated clinical improvement without specific antiepileptic therapy. Upon admission, he was diagnosed with a pineal gland tumor on the basis of the physical examination and radiologic findings [Figure 1]. The tumor was resected by the supracerebellar infratentorial approach, with the patient in the Concord position. A preoperative extraventricular drainage to the right side of Kocher’s point was performed and cerebrospinal fluid (CSF) was noted to drain slowly. The dura was opened, the cisterna magna was dissected, the bridging veins draining to the transverse sinus were removed, and the cerebellum was allowed to move inferiorly. The mass was then completely resected without complication. Pathology confirmed the presence of a mature teratoma. Figure 1A Preoperative brain computed tomography (CT) image showing a calcified cystic mass in the pineal gland (A) Figure 1B T1-weighted gadolinium-enhanced axial magnetic resonance (MR) images (B) showing an inhomogenous enhancing mass in the pineal gland

Upon admission, he was diagnosed with a pineal gland tumor on the basis of the physical examination and radiologic findings [Figure 1]. The tumor was resected by the supracerebellar infratentorial approach, with the patient in the Concord position. A preoperative extraventricular drainage to the right side of Kocher’s point was performed and cerebrospinal fluid (CSF) was noted to drain slowly. The dura was opened, the cisterna magna was dissected, the bridging veins draining to the transverse sinus were removed, and the cerebellum was allowed to move inferiorly. The mass was then completely resected without complication. Pathology confirmed the presence of a mature teratoma. Figure 1A Preoperative brain computed tomography (CT) image showing a calcified cystic mass in the pineal gland (A) Figure 1B T1-weighted gadolinium-enhanced axial magnetic resonance (MR) images (B) showing an inhomogenous enhancing mass in the pineal gland The patient was noted to be lethargic postoperatively and, when a subsequent brain CT scan showed bilateral parietal EDHs, emergency craniotomy was performed for their removal [Figure 2]. Follow-up brain CT after reoperation demonstrated the presence of small bifrontal EDHs [Figure 3]. The mentality was recovered but the patient complained of continuously headache and gait disturbance and, therefore bilateral frontal twist trephination and hematoma removal was performed 2 weeks later. The headache, gait disturbance, and right hemiparesis improved following this and there has been no evidence of tumor recurrence during the 3-year follow-up period [Figure 4].

continuously headache and gait disturbance and, therefore bilateral frontal twist trephination and hematoma removal was performed 2 weeks later. The headache, gait disturbance, and right hemiparesis improved following this and there has been no evidence of tumor recurrence during the 3-year follow-up period [Figure 4]. Figure 2 Immediate postoperative brain CT showing acute EDHs in bilateral frontoparietal regions Figure 3 Brain CT showing acute EDHs following reoperation in the bifrontal areas and pneumoventricle in bilateral frontal horns Figure 4 Magnetic resonance (MR) image 3 years following tumor resection showing no evidence of recurrence

Figure 2 Immediate postoperative brain CT showing acute EDHs in bilateral frontoparietal regions Figure 3 Brain CT showing acute EDHs following reoperation in the bifrontal areas and pneumoventricle in bilateral frontal horns Figure 4 Magnetic resonance (MR) image 3 years following tumor resection showing no evidence of recurrence Discussion Postoperative intracranial hematoma is one of the most serious complications of intracranial operations. Palmar et al. reported that the most common procedure leading to the formation of postoperative hematoma was meningioma resection, with a rate of 6.2%; this was followed by craniotomy for trauma (at 3.7%), aneurysm surgery (at 2.6%), and intrinsic supratentorial tumors (at 2.2%).[3] Postoperative hematomas were noted to be intraparenchymal in 43% of cases, subdural in 5%, extradural in 33%, mixed in 8%, and confined to the superficial wound in 11%.[3] The rate of postoperative EDHs has been reported to be approximately 1% at the site of craniotomy; however, multiple remote EDHs are quite rare.[4] Postoperative EDHs may produce serious complications, given that the neurologic symptoms may be seemingly unrelated to the original operative site. Postoperative remote EDHs following ventriculoperitoneal shunting and cranial operation have been reported earlier in the literature.[5–10]

e remote EDHs are quite rare.[4] Postoperative EDHs may produce serious complications, given that the neurologic symptoms may be seemingly unrelated to the original operative site. Postoperative remote EDHs following ventriculoperitoneal shunting and cranial operation have been reported earlier in the literature.[5–10] The pathophysiology of remote intracranial hemorrhage following craniotomy suggests that sudden decreased intracranial pressure, unequal distribution of intracranial pressure between compartments with a consequent shifting of brain parenchyma, massive drainage of CSF, or a bleeding tendency may all serve as potential triggers.[5781011] In cases of remote EDH following ventriculoperitoneal shunting, the massive drainage of CSF is an important causative factor.[28] Unclear sentence was changed to : Young age is another contributory factor, the adhesion between the dura and the cranium could become weak with age. A prone position and severe adhesion between the arachnoid and pia mater are also important pathophysiologic factors.[28] Yacubian et al. reported that remote EDH is influenced by multiple factors, including brain shifting, dural detachment due to improvement of blood flow in the contralateral compressed dural vessel, and massive drainage of CSF.[10] Many pineal gland masses are associated with hydrocephalus secondary to compression of the aqueduct of Sylvius. If the pineal gland mass results in a noncommunicating hydrocephalus early in life, craniocephalic disproportion ensues. The ratio of brain parenchyma to intracranial volume is relatively small in this form of hydrocephalus, and the greater the craniocephalic disproportion the larger the potential EDH. Park reported that distant EDH following ventriculoperitoneal shunting commonly occurs in the frontal area due to the weak adhesion between the dura and calvarium in this location.[2]

volume is relatively small in this form of hydrocephalus, and the greater the craniocephalic disproportion the larger the potential EDH. Park reported that distant EDH following ventriculoperitoneal shunting commonly occurs in the frontal area due to the weak adhesion between the dura and calvarium in this location.[2] There are many potential contributing factors for the formation of remote, multiple, EDHs in the present case. First, massive removal of CSF by preoperative extraventricular drainage and opening of the cistern during the arachnoid dissection resulted in a symmetric decrease in intracranial pressure. Second, removal of the centrally located mass with the patient in the prone position caused brain shifting. Finally, the weak attachment between the dura and the cranium, as well as the high compliance of the dura, resulted in easy detachment. Bae et al.[5] suggested that sudden perioperative lowering of intracranial pressure by massive CSF drainage should be avoided and that the head should be lowered when the patient is in the prone position during the operation to avoid such complications.[5] Preoperative ventriculoperitoneal shunting should then be performed 1 or 2 weeks prior to tumor resection. Brain CT is mandatory in the presence of postoperative lethargy, a new neurologic deficit, prolonged decreased mentation, or neurologic deficits unrelated to the operative field.

on to avoid such complications.[5] Preoperative ventriculoperitoneal shunting should then be performed 1 or 2 weeks prior to tumor resection. Brain CT is mandatory in the presence of postoperative lethargy, a new neurologic deficit, prolonged decreased mentation, or neurologic deficits unrelated to the operative field. Conservative management may be the choice of treatment in cases of small EDH or mild symptoms; however, large EDHs, as were present in this case, require urgent surgical intervention. As rapid hematoma removal may induce contralateral hemorrhage, subsequent brain CT should be performed. Conclusion Here, we report a case of pineal tumor combined with hydrocephalus, complicated by multiple postoperative EDHs. The mature teratoma of the pineal gland is considered curable by surgical resection. In cases combined with severe hydrocephalus, preoperative ventriculostomy may be performed. A gradual reduction of intracranial pressure may prevent sudden ventricular collapse. Postoperative intracranial hemorrhage must be evacuated immediately in symptomatic patients. Source of Support: Nil. Conflict of Interest: None declared.

Sir, Biotinidase deficiency is a rare metabolic disorder with an estimated incidence of 1:61,067 population, although severe or profound disease is much rarer (1:1,37,401 population).[1] Clinical manifestations include neurological, dermatological, immunological and ophthalmological abnormalities.[2] Biochemically, the disease is characterized by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia and mental retardation.[3]

emically, the disease is characterized by metabolic acidosis and organic aciduria. Treatment with biotin results in pronounced, rapid, clinical and biochemical improvement, but some patients have residual neurological damage comprising neurosensory hearing loss, visual pathway defects, ataxia and mental retardation.[3] A 6-month-old male child born of nonconsanguineous marriage presented with a history of seizures from 3 months of age and was being treated with sodium valproate, but seizure control was not observed. Antenatal and natal history was uneventful. There was no family history of seizure disorders. According to the mother, the child developed normally for the first 3 months and after that was not growing normally. On examination, the child had normal neurological findings, except for hypotonia, irritability and alopecia [Figure 1]. The child also had a mild developmental delay. Laboratory investigations revealed normal hemogram, liver functions, serum ammonia and serum electrolytes. Blood gas analysis showed metabolic acidosis and the baby also had persistent ketonuria, while cerebrospinal fluid examination was normal. Ophthalmological and brainstem-evoked audiometry examination was normal and magnetic resonance imaging revealed diffuse cortical atrophy. A specific enzyme assay showed deficient biotinidase activity of 0.6 nmol/min/mL (normal >5 nmol/min/mL). The child was given biotin (20 mg/day) orally. This treatment produced a pronounced, rapid, clinical and biochemical improvement and good control over seizures, resulting in discontinuation of antiepileptic drugs.

A specific enzyme assay showed deficient biotinidase activity of 0.6 nmol/min/mL (normal >5 nmol/min/mL). The child was given biotin (20 mg/day) orally. This treatment produced a pronounced, rapid, clinical and biochemical improvement and good control over seizures, resulting in discontinuation of antiepileptic drugs. Figure 1 Alopecia in biotinidase deficiency Biotin is a cofactor required by acetyl CoA carboxylase, pyruvate carboxylase, propionyl CoA carboxylase and 3 methylcrotonyl CoA carboxylase. It is covalently attached to the apocarboxylases by the epsilon amino group of a lysine residue, where it functions at the active site as a carbon dioxide carrier in the carboxylation reactions. Biotinylation of the apocarboxylases is catalyzed by holocarboxylase synthetase in an adenosine triphosphate-dependent reaction, with the intermediate formation of biotinyl adenosine monophosphate. The turnover of carboxylases yields biotinyllysine (biocytin) from which biotin is regenerated by the action of a specific amidolyase, biotinidase. This enzyme is also required for the release of dietary protein-bound biotin.[3] Individual inherited disorders of all four biotin-dependent carboxylases have been reported in addition to reports of patients with simultaneous defects of all four enzymes (combined carboxylase deficiency). In a majority of patients with late-onset combined carboxylase deficiency, the underlying defect is biotinidase deficiency.[4] The early-onset form, on the other hand, is due to holocarboxylase synthetase deficiency.[5]

reports of patients with simultaneous defects of all four enzymes (combined carboxylase deficiency). In a majority of patients with late-onset combined carboxylase deficiency, the underlying defect is biotinidase deficiency.[4] The early-onset form, on the other hand, is due to holocarboxylase synthetase deficiency.[5] Biotinidase deficiency can be profound (<10% enzyme level) or partial (10-30% enzyme level). Clinical presentation depends on the severity of enzymatic defect. Profound defects usually manifest between 3 and 6 months of age, with neurological manifestations (seizures, hypotonia and developmental delay), skin manifestations (eczematous skin rash, seborrheic dermatitis, alopecia) and (c) respiratory problems (hyperventilation, laryngeal stridor and apnea). Older children and adolescents may exhibit limb weakness, neurosensory hearing loss and eye problems, e.g. optic atrophy and scotomas. The present case had only seizures and alopecia. Many symptomatic children with biotinidase deficiency exhibit various neuroimaging abnormalities, e.g. cerebral edema, attenuated white matter signal, cerebral atrophy and compensatory ventricular enlargement. Neuroimaging features may improve or become normal after biotin treatment.[6] Laboratory findings include metabolic acidosis and abnormal organic acids in the urine, and diagnosis can be established by estimating biotidinase in the serum. Biotinidase deficiency may be detected on screening of the newborn.[7]

Biotinidase deficiency can be profound (<10% enzyme level) or partial (10-30% enzyme level). Clinical presentation depends on the severity of enzymatic defect. Profound defects usually manifest between 3 and 6 months of age, with neurological manifestations (seizures, hypotonia and developmental delay), skin manifestations (eczematous skin rash, seborrheic dermatitis, alopecia) and (c) respiratory problems (hyperventilation, laryngeal stridor and apnea). Older children and adolescents may exhibit limb weakness, neurosensory hearing loss and eye problems, e.g. optic atrophy and scotomas. The present case had only seizures and alopecia. Many symptomatic children with biotinidase deficiency exhibit various neuroimaging abnormalities, e.g. cerebral edema, attenuated white matter signal, cerebral atrophy and compensatory ventricular enlargement. Neuroimaging features may improve or become normal after biotin treatment.[6] Laboratory findings include metabolic acidosis and abnormal organic acids in the urine, and diagnosis can be established by estimating biotidinase in the serum. Biotinidase deficiency may be detected on screening of the newborn.[7] Biotinidase deficiency may be confused with holocarboxylase deficiency, previously called early-onset or infantile multiple or combined carboxylase deficiency, which presents early and the biotidinase level is normal. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.

Sir, The corpus callosum is a white matter structure connecting the cerebral hemispheres and is important in coordinating information and bilateral exchange of sensory stimuli. It is derived from the lamina terminalis in the portion of the neural tube cephalic to the rostral neuropore. Until the fourth month of gestation, only the most rostral part of the corpus callosum is formed; the caudal portion develops only after the fifth month.[12] Insults responsible for agenesis of the corpus callosum or varying degrees of hypoplasia of the corpus callosum are not identified. An early failure may lead to complete agenesis, whereas a later one will lead to hypoplasia.[3] There is a discrepancy in the reported incidence between autopsy series and those based on pneumoencephalographic studies. The incidence ranges from 0.7% to 5.3%.[45] Lacey[6] stated that the incidence of agenesis of the corpus callosum was only 0.0005% in an unselected random autopsy population; this seems to be lower than one would expect for a malformation which is so well known in the dysmorphology literature and community of specialists.

incidence ranges from 0.7% to 5.3%.[45] Lacey[6] stated that the incidence of agenesis of the corpus callosum was only 0.0005% in an unselected random autopsy population; this seems to be lower than one would expect for a malformation which is so well known in the dysmorphology literature and community of specialists. A 23-year-old primigravida was seen for ultrasonographic fetal examination, at her visit to the antenatal clinic. Antenatal USG was performed, which showed features suggestive of hydrocephalus. At 38 weeks, elective cesarean section produced a female infant weighing 2.6 kg, with Apgar scores of 7 at 1 min and 10 at 5 min. The baby looked normal at general inspection. Ultrasonic examination confirmed dilatation of the occipital horns of the lateral ventricles and again the features were told to be suggestive of mild mydrocephalus. On clinical examination, the head circumference was normal, thus suspecting some other diagnosis and she was referred for an MRI scan. There was difficulty in visualizing the corpus callosum; MRI of the head confirmed agenesis of the corpus callosum. The films showed presence of calpocephaly and rabbits horn appearance or the devils horn appearence [Figure 1]. This child illustrates the difficulty in identifying agenesis of the corpus callosum antenatally, though it was suspected by us because of the finding of an isolated dilatation of occipital horns of the lateral ventricles without any other structural anomalies being identified. Figure 1 MRI showing calpocephaly and a ”rabbit ear appearance” or “devils horn appearance”

A 23-year-old primigravida was seen for ultrasonographic fetal examination, at her visit to the antenatal clinic. Antenatal USG was performed, which showed features suggestive of hydrocephalus. At 38 weeks, elective cesarean section produced a female infant weighing 2.6 kg, with Apgar scores of 7 at 1 min and 10 at 5 min. The baby looked normal at general inspection. Ultrasonic examination confirmed dilatation of the occipital horns of the lateral ventricles and again the features were told to be suggestive of mild mydrocephalus. On clinical examination, the head circumference was normal, thus suspecting some other diagnosis and she was referred for an MRI scan. There was difficulty in visualizing the corpus callosum; MRI of the head confirmed agenesis of the corpus callosum. The films showed presence of calpocephaly and rabbits horn appearance or the devils horn appearence [Figure 1]. This child illustrates the difficulty in identifying agenesis of the corpus callosum antenatally, though it was suspected by us because of the finding of an isolated dilatation of occipital horns of the lateral ventricles without any other structural anomalies being identified. Figure 1 MRI showing calpocephaly and a ”rabbit ear appearance” or “devils horn appearance” Agenesis of the corpus callosum is an uncommon cerebral malformation that has been reported in 1 in 19,000 unselected autopsies and 2.3% of children with mental retardation.[47] The defect may be complete or partial, depending on the stage at which callosal development is arrested.

Figure 1 MRI showing calpocephaly and a ”rabbit ear appearance” or “devils horn appearance” Agenesis of the corpus callosum is an uncommon cerebral malformation that has been reported in 1 in 19,000 unselected autopsies and 2.3% of children with mental retardation.[47] The defect may be complete or partial, depending on the stage at which callosal development is arrested. Agenesis of the corpus callosum produces characteristic pathologic changes of the cerebral hemispheres and the ventricular system. On sagittal cuts of the MRI, the corpus callosum, cingulate gyrus, and sulcus are absent or malformed. In addition, there is a high-riding third ventricle that is open superiorly to the interhemispheric fissure. The sulci and gyri on the medial hemispheric surface have a radial or “spoke-like” configuration around the third ventricle. There is occasionally a dorsal cyst present in this space.

us are absent or malformed. In addition, there is a high-riding third ventricle that is open superiorly to the interhemispheric fissure. The sulci and gyri on the medial hemispheric surface have a radial or “spoke-like” configuration around the third ventricle. There is occasionally a dorsal cyst present in this space. The lateral cerebral ventricles are displaced laterally and superiorly. In most cases, on transverse cuts of the brain, colpocephaly, or dilated occipital horns, are commonly appreciated. There is a stable, non-progressive dilatation. The reason for this enlargement is not known.[8–10] There is no evidence of obstruction along the CSF pathways. There is neither increased intraventricular pressure nor progressive ventriculomegaly. Probst bundles are longitudinal white matter tracts that indent and invaginate into the superior medial aspect of the lateral ventricles.[8–10] There are demonstrable Probst”s bundles in children with true agenesis, on a sagittal MR midline scan, which is the definitive radiological modality for evaluating agenesis of the corpus callosum. Byrd et al.[11] reported that MR is the best technique to evaluate the child or newborn with suspected agenesis of the corpus callosum and associated brain anomalies. He also found that ultrasound is a good screening modality of the neonatal head and can be used to demonstrate agenesis of the corpus callosum. When the findings are subtle on the ultrasound, or when agenesis of the corpus callosum is demonstrated on the ultrasonic examination, a CT or preferably an MR should be obtained to evaluate the brain for a complete outline of the corpus callosum and associated structures.

o demonstrate agenesis of the corpus callosum. When the findings are subtle on the ultrasound, or when agenesis of the corpus callosum is demonstrated on the ultrasonic examination, a CT or preferably an MR should be obtained to evaluate the brain for a complete outline of the corpus callosum and associated structures. Differential diagnosis: Arachnoid cyst, porencephaly, hydrocephaly, and prominent septum cavum pellucidum. The corpus callosum is phylogenetically a recent structure, and its absence is not lethal. Isolated agenesis of the corpus callosum may be either a completely asymptomatic event (found incidentally) or revealed during the course of a neurological examination by subtle deficits, such as inability to match stimuli using both hands or to discriminate differences in temperature, shape, and weight in objects placed in both hands.[12]

the corpus callosum may be either a completely asymptomatic event (found incidentally) or revealed during the course of a neurological examination by subtle deficits, such as inability to match stimuli using both hands or to discriminate differences in temperature, shape, and weight in objects placed in both hands.[12] Persons with agenesis of the corpus callosum may have neurological problems, such as seizures (60%), intellectual impairment (70%), and psychosis.[1–3] However, these conditions are believed to be caused by abnormalities in associated cerebral anomalies rather than in the corpus callosum per se. Byrd et al.[11] studied a group of 105 children with a diagnosis of agenesis of the corpus callosum and reported that 26 (25%) had isolated agenesis of the corpus callosum with no associated brain anomalies. Eight of these presented with seizures which were controlled medically. Of the 105 children, 85% had symptoms and/or abnormal signs. The most common signs were macrocephaly with hydrocephalus and seizures. Postnatally, they found MR was the best radiological imaging modality for evaluating children with agenesis of the corpus callosum and associated brain anomalies. The most common associated brain anomalies (in decreasing frequency) were interhemispheric cyst with hydrocephalus, Dandy-Walker malformation, migrational disorder, absence of the inferior vermis, cephalocele, and lipoma of the interhemispheric fissure. The children who had the best prognosis without any significant neurologic sequelae were those with isolated agenesis of the corpus callosum.

nterhemispheric cyst with hydrocephalus, Dandy-Walker malformation, migrational disorder, absence of the inferior vermis, cephalocele, and lipoma of the interhemispheric fissure. The children who had the best prognosis without any significant neurologic sequelae were those with isolated agenesis of the corpus callosum. The children with the worst prognosis and neurological sequelae were those with agenesis of the corpus callosum and migrational disorder with or without Dandy-Walker malformations.[11] Hence, prognosis is determined primarily by the underlying or associated malformation(s).[13] In utero, the presence of hydrocephalus is usually assessed from the V/H ratio. This is the ratio of the ventricular width, as measured from the midline to the lateral wall of the lateral ventricle, to the width of the cerebral hemisphere. In agenesis of the corpus callosum, the lateral ventricles are widely separated, giving a falsely high value for the V/H ratio. The prominent posterior horns reinforce the impression of hydrocephalus as the posterior horn. V/H ratio is high and both medial and lateral borders are clearly visualized. Comstock et al, suggested that coronal view should be obtained if possible as this would show the characteristic concavity of the medial walls of the lateral ventricles and also possibly the absence of the corpus callosum.[14] According to Romero et al, upward displacement of the third ventricle is very specific.[15]

. Comstock et al, suggested that coronal view should be obtained if possible as this would show the characteristic concavity of the medial walls of the lateral ventricles and also possibly the absence of the corpus callosum.[14] According to Romero et al, upward displacement of the third ventricle is very specific.[15] It is important to be aware of the features of agenesis of the corpus callosum. First, to distinguish it from hydrocephalus and second to instigate a search for further, more serious, anomalies with which it may be associated.

Sir, Epilepsy is characterized by recurrent unprovoked seizures and is one of the most prevalent neurologic diseases. As a result of the limitations of older drugs and improvements in our understanding of epilepsy and the mechanisms of action of the drugs used to treat it, several new agents have been approved in the past decade. Oxcarbazepine (OXC) is a new anti-epileptic drug that has been registered in several countries worldwide since 1990.[1] It is a keto analog of carbamazepine and has a more favorable pharmacokinetic profile. The results of clinical trials suggest that it is better tolerated than carbamazepine.[1–3] The most common adverse events are usually related to the central nervous (dizziness, diplopia, ataxia, headache, weakness, nystagmus, slurred speech) or gastrointestinal systems (nausea, vomiting, epigastric distress, diarrhea). The other adverse events are allergic rashes and hyponatremia. We now report a child who experienced tardive dyskinesia soon after OXC therapy. An 8-year-old girl was admitted to the hospital with two complex partial seizures in the last month. She was born from nonconsanguineous marriage with uncomplicated delivery. Her mental and motor development were normal. Her physical and neurological examinations were also normal. In history, she was diagnosed as attention-deficit hyperactivity disorder (ADHD) 1 year ago at the pediatric psychiatry outpatient clinic, without medical treatment.

nguineous marriage with uncomplicated delivery. Her mental and motor development were normal. Her physical and neurological examinations were also normal. In history, she was diagnosed as attention-deficit hyperactivity disorder (ADHD) 1 year ago at the pediatric psychiatry outpatient clinic, without medical treatment. Magnetic resonance imaging revealed no abnormality. Interictal electroencephalogram showed rolandic spikes in the left hemisphere with normal background activity. OXC therapy was begun at 15 mg/kg daily for 1 week and then 30 mg/kg/d. Three days after full-dose treatment, she was admitted to the emergency service with abnormal movements. In her examination, she had trismus, tongue protrusion, deviation of the eyes and lateral flexion of the trunk. She was diagnosed as tardive dyskinesia. OXC was stopped. Single-dose intravenous diazepam was administered and then oral difenhydramine treatment was given for 2 weeks. Her symptoms ceased in 3 days. Acute dystonic reactions occur after exposure to dopamine (DA) receptor blocking agents, a class that includes neuroleptic agents and antiemetic agents. It is well recognized that some anticonvulsant therapy may also be associated with various dyskinesias, including chorea, choreoathetosis, dystonia and asterixis. Phenitoin, primidone, phenobabitone, phenobarbital, ethosuximide and carbamazepine have been implicated as offending agents.[45] Dyskinesias due to anticonvulsants usually result from toxicity and initial exposure of drug or, more commonly, during chronic usage.

ncluding chorea, choreoathetosis, dystonia and asterixis. Phenitoin, primidone, phenobabitone, phenobarbital, ethosuximide and carbamazepine have been implicated as offending agents.[45] Dyskinesias due to anticonvulsants usually result from toxicity and initial exposure of drug or, more commonly, during chronic usage. Tardive dyskinesia is not a common adverse reaction after OXC treatment. In the literature, there are rare reports about carbamazepine-induced tic disorders and tardive dyskinesia-like syndrome.[67] It was thought that the presence of striatal DA receptor supersensitivity serves as the prevailing hypothesis regarding the underlying neurobiological mechanism for tics.[6] This is based on the following observations: DA receptor antagonists are the most effective drugs for suppressing tics and that tics may be worsened by drugs that enhance dopaminergic neurotransmission, such as amphetamins. This dopaminergic effect of carbamazepine may be responsible for the induction of tics, but the drug has a multiplicity of other central neurochemical effects that may be involved as well. The possible mechanism of OXC-induced dyskinesia may be similar to that of carbamazepine. Although there are conflicting results in the literature, carbamazepine has been reported to be useful in the treatment of tardive dyskinesia related to chronic neuroleptic use.[89] But, it is not clear, whether it is the result of a state-dependent condition rather than the action of carbamazepine.

Tardive dyskinesia is not a common adverse reaction after OXC treatment. In the literature, there are rare reports about carbamazepine-induced tic disorders and tardive dyskinesia-like syndrome.[67] It was thought that the presence of striatal DA receptor supersensitivity serves as the prevailing hypothesis regarding the underlying neurobiological mechanism for tics.[6] This is based on the following observations: DA receptor antagonists are the most effective drugs for suppressing tics and that tics may be worsened by drugs that enhance dopaminergic neurotransmission, such as amphetamins. This dopaminergic effect of carbamazepine may be responsible for the induction of tics, but the drug has a multiplicity of other central neurochemical effects that may be involved as well. The possible mechanism of OXC-induced dyskinesia may be similar to that of carbamazepine. Although there are conflicting results in the literature, carbamazepine has been reported to be useful in the treatment of tardive dyskinesia related to chronic neuroleptic use.[89] But, it is not clear, whether it is the result of a state-dependent condition rather than the action of carbamazepine. ADHD is a neurobehavioral syndrome, both defined and diagnosed by the presence of a certain number and intensity of behaviors classified into three symptom groups: inattention, impulsivity and hyperactivity. In ADHD pathogenesis, besides various endogen and exogen factors, some abnormalities in the central dopaminergic system have been reported. In these patients, the level of homovalinic acid that is the principal metabolite of DA has been found to be abnormal.[10] Because of this, it is important to be careful when using agents that induced the dopaminergic system in these patients.

s, some abnormalities in the central dopaminergic system have been reported. In these patients, the level of homovalinic acid that is the principal metabolite of DA has been found to be abnormal.[10] Because of this, it is important to be careful when using agents that induced the dopaminergic system in these patients. In conclusion, tardive dyskinesia is a rare adverse reaction during OXC therapy, also seen in the early phase of therapy. Use of the Naranjo ADR Probability Scale indicated a probable (the score was 6) relationship between tardive dyskinesia and OXC therapy in this patient.[11] Such agents that affect the central dopaminergic systems should be administered with caution in patients having dopaminergic abnormalities.

Sir, A 7-year-old boy, a known case of GTCS (generalized tonic–clonic seizures) since 8 months of age whose seizures were poorly controlled with antiepileptic medications, was admitted with increased jerky movements of the body for the past few days. He had a history of birth asphyxia and delayed developmental milestones as well as cognitive impairment. On admission, the patient was conscious and hemodynamically stable. Cognitive impairment was present. He was moving all four limbs. He had an ataxic gait. He was able to hear and apparently had no vision problems. The plantars were bilaterally flexor.

nd delayed developmental milestones as well as cognitive impairment. On admission, the patient was conscious and hemodynamically stable. Cognitive impairment was present. He was moving all four limbs. He had an ataxic gait. He was able to hear and apparently had no vision problems. The plantars were bilaterally flexor. MRI showed no focal lesion and a normal hippocampus bilaterally. A 24-hour prolonged digital video EEG [Figures 1–4] recorded three events of clinical head drop accompanied by electroencephalgraphic (EEG) magnification of pseudonormalization, each lasting for 3–4 seconds. The interictal EEG record was suggestive of multifocal spike-and-wave discharges in both hemispheres, particularly in the left frontocentral, right parieto-temporo-occipital region, and left parieto-occipital region, with intermittent independent generalized polyspike wave discharge and intermittent <3-Hz generalized spike-and-wave discharges lasting 1–8 seconds. The VEP (visual evoked potential) [Figure 5, 6] report showed bilateral prolonged P100 latency and decreased amplitude. The BAER (brainstem audiometry-evoked response) study was normal bilaterally. The tandem mass spectroscopy report was negative. All routine blood investigations were normal. The patient was managed with syrup valproate, with tablet lamotrigine added later. Satisfactory control of seizures was achieved.

eased amplitude. The BAER (brainstem audiometry-evoked response) study was normal bilaterally. The tandem mass spectroscopy report was negative. All routine blood investigations were normal. The patient was managed with syrup valproate, with tablet lamotrigine added later. Satisfactory control of seizures was achieved. Figure 1 The 24 hour prolonged digital video EEG recorded from 02/02/2010 to 03/02/2010 recorded three events showing clinically head drop with EEG magnification of Pseudo-normalization lasting for 3-4 seconds. Interictal EEG record is suggestive of multifocal discharges Figure 2 The 24 hour prolonged digital video EEG recorded from 02/02/2010 to 03/02/2010 recorded three events showing clinically head drop with EEG magnification of Pseudo-normalization lasting for 3-4 seconds. Interictal EEG record is suggestive of multifocal discharges Figure 3 The 24 hour prolonged digital video EEG Figure 4 The 24 hour prolonged digital video EEG recorded from 02/02/2010 to 03/02/2010 recorded three events showing clinically head drop with EEG magnification of Pseudo-normalization lasting for 3-4 seconds. Interictal EEG record is suggestive of multifocal discharges Figure 5 VEP showed bilateral prolonged P100 latency Figure 6 VEP showed bilateral prolonged P100 latency

Figure 4 The 24 hour prolonged digital video EEG recorded from 02/02/2010 to 03/02/2010 recorded three events showing clinically head drop with EEG magnification of Pseudo-normalization lasting for 3-4 seconds. Interictal EEG record is suggestive of multifocal discharges Figure 5 VEP showed bilateral prolonged P100 latency Figure 6 VEP showed bilateral prolonged P100 latency The Lennox-Gastaut syndrome (LGS) is classified as an epileptic syndrome characterized by the presence of various types of generalized seizures (tonic, atonic, and atypical absences) that appear at a certain age (1–8 years), with an interictal EEG showing an abnormally slow basic rhythm interrupted by slow spike-and-wave complexes (<3 Hz) and progressive mental deterioration.[1] It accounts for only 2%–5% of childhood epilepsies. LGS is a severe form of childhood epilepsy, characterized by multiple seizures and cognitive impairment.

ears), with an interictal EEG showing an abnormally slow basic rhythm interrupted by slow spike-and-wave complexes (<3 Hz) and progressive mental deterioration.[1] It accounts for only 2%–5% of childhood epilepsies. LGS is a severe form of childhood epilepsy, characterized by multiple seizures and cognitive impairment. To date, there are no known laboratory investigations to aid in the diagnosis of LGS. Neuroimaging has an important role to play in the search for the underlying etiology of LGS. Abnormalities associated with LGS that have been revealed by neuroimaging include tuberous sclerosis, brain malformations (e.g., cortical dysplasias), hypoxia-ischemia injury and frontal lobe lesions. The diagnosis depends on the presence of the specific EEG findings. Prolonged video EEG should be performed to record both awake and sleep EEG to assist in confirming a suspected diagnosis and to capture and classify each of the patient’s multiple seizure types. The hallmark of the awake interictal EEG in patients with LGS is the diffuse slow spike wave. This pattern consists of bursts of irregular and generalized spikes or sharp waves followed by a sinusoidal 35- to 400-millisecond slow wave with an amplitude of 200–800 μV, which can be symmetric or asymmetric. The frequency of the slow spike wave activity is commonly 1.5–2.5 Hz. The optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious. Rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy.[2] Valproate, used alone, produces a decrease in seizures (of greater than 50%) in 25%–30% of patients. In late 2008, the Food and Drug Administration approved rufinamide for adjunctive use in the treatment of seizures associated with LGS, which makes it the first new antiepileptic drug to be approved for use in the pediatric age-group prior to approval for use in adults.[3] Co-administration of valproate decreases rufinamide clearance, thus requiring dose adjustment. The simulations support the proposal for a lower maximum daily rufinamide dose for patients under 30 kg receiving both drugs: a dose of 600 mg/day is proposed as a maximum daily dose in children who are also receiving valproate concomitantly whereas, in the absence of valproate, the maximum daily dose is 1000 mg/day.[4] Lastly, resective epilepsy surgery should be considered for children with LGS, even though there may be abundant generalized and multiregional EEG abnormalities.[5]

Sir, I read the current publication of Sankhla and Khan with great interest.[1] I agree that their new criteria are successful in the reduction of cerebrospinal fluid (CSF) shunt placement. However, there are some points to be addressed. First, the clarification on the additional cost according to the protocol of new criteria should be compared to the reducing cost of reducing CSF shunt. Second, the quality of life comparing between two alternatives must be clarified. These can be useful judging the use of a new technique for reduction of CSF shunt placement

Sir, Ventriculoperitoneal (VP) shunt involves diversion of cerebrospinal fluid (CSF) from the ventricular system to the peritoneal cavity at a rate determined by the characteristics of the valve device. When the rate at which the CSF enters the cavity is higher than its capacity to absorb it is overwhelmed, ascitis can occur, with abdominal distension and increase in intraperitoneal pressure. A number of abdominal complications have been reported following the VP shunt placement.[1–5] Burst abdomen is however rare. Our review of the literature on abdominal complications following shunt insertion did not reveal any reported case of burst abdomen following the procedure. In this paper, we report a case of burst abdomen following shunt insertion in a 14-week-old baby. We believe that one major reason for the complication in this patient was the level of malnutrition in the face of other already existing risk factors. Our patient is a 12-week-old baby who was admitted with progressive increase in head size, weight loss and vomiting. He had previously been admitted for a febrile illness and jaundice. The mother confirmed having had fever at 24 weeks of gestation.

A number of abdominal complications have been reported following the VP shunt placement.[1–5] Burst abdomen is however rare. Our review of the literature on abdominal complications following shunt insertion did not reveal any reported case of burst abdomen following the procedure. In this paper, we report a case of burst abdomen following shunt insertion in a 14-week-old baby. We believe that one major reason for the complication in this patient was the level of malnutrition in the face of other already existing risk factors. Our patient is a 12-week-old baby who was admitted with progressive increase in head size, weight loss and vomiting. He had previously been admitted for a febrile illness and jaundice. The mother confirmed having had fever at 24 weeks of gestation. Examination revealed an irritable, ill-looking and severely malnourished infant with edema of both hands and feet. His head circumference was 53.5 cm. The anterior fontanel was bulging and tense and his scalp was thin and shiny with engorged veins. There was global hypertonia and sunset phenomenon was evident. Investigations performed include skull X-ray, transfontanel ultrasound scan, full blood count, serum proteins, urea and electrolytes. The main positive findings were anemia, hypoproteinemia and electrolyte imbalance. Because he was not fit for immediate surgical intervention, the patient was built up over the next 2 weeks. Treatment during this period included blood transfusion, intravenous fluids, correction of his electrolytes, vitamin supplements and increased breast feeding.

Examination revealed an irritable, ill-looking and severely malnourished infant with edema of both hands and feet. His head circumference was 53.5 cm. The anterior fontanel was bulging and tense and his scalp was thin and shiny with engorged veins. There was global hypertonia and sunset phenomenon was evident. Investigations performed include skull X-ray, transfontanel ultrasound scan, full blood count, serum proteins, urea and electrolytes. The main positive findings were anemia, hypoproteinemia and electrolyte imbalance. Because he was not fit for immediate surgical intervention, the patient was built up over the next 2 weeks. Treatment during this period included blood transfusion, intravenous fluids, correction of his electrolytes, vitamin supplements and increased breast feeding. At the end of 2 weeks, with the normalization of his serum proteins, electrolytes and hematocrit, it was determined that he was relatively fit for surgery. VP shunt was performed by standard methods using a medium pressure valve device. The first few days after surgery were marked by increased bowel movements. By the sixth day after operation, the abdomen was observed to be distended and the abdominal wound dressing showed a slight bulge. On wound exposure, a loop of small bowel was seen protruding through the incision. The child was immediately transferred to our pediatric surgery unit and scheduled for emergency laparotomy.

y the sixth day after operation, the abdomen was observed to be distended and the abdominal wound dressing showed a slight bulge. On wound exposure, a loop of small bowel was seen protruding through the incision. The child was immediately transferred to our pediatric surgery unit and scheduled for emergency laparotomy. At this operation, it was discovered that there was no evidence of commencement of wound healing and all the sutures applied to the abdominal wound at the time of the VP shunt had given way. Most of the distal small bowel was gangrenous. The affected segment, together with the ileo-cecal valve, was resected and jejuno-colic anastomosis was performed. Examination of the scalp wound also showed no evidence of healing. All the sutures had eroded through the tissues and had fallen off with exposure of the shunt device. The postoperative course was turbulent. The patient remained hypertonic and had persistent electrolyte imbalance, anemia and sepsis. Attempts were made to correct these, but the patient continued to deteriorate and finally died 1 week later.

At this operation, it was discovered that there was no evidence of commencement of wound healing and all the sutures applied to the abdominal wound at the time of the VP shunt had given way. Most of the distal small bowel was gangrenous. The affected segment, together with the ileo-cecal valve, was resected and jejuno-colic anastomosis was performed. Examination of the scalp wound also showed no evidence of healing. All the sutures had eroded through the tissues and had fallen off with exposure of the shunt device. The postoperative course was turbulent. The patient remained hypertonic and had persistent electrolyte imbalance, anemia and sepsis. Attempts were made to correct these, but the patient continued to deteriorate and finally died 1 week later. Burst abdomen is characterized by surgical wound disruption following abdominal operations, with herniation of the abdominal contents. Major predisposing causes include raised intra-abdominal pressure (as occurs in chronic obstructive uropathy, constipation, global hypertonia and chronic cough) and abdominal distension. Others include infections, hypoproteinemia and anemia. The latter causes delayed or poor wound healing. Abdominal complications following shunt surgery are not uncommon.[12] Well-known ones include peritonitis, volvulus, intestinal obstruction, ascitis, paralytic ileus, spontaneous extrusion of the silicone tube, abdominal cysts,[45] etc. Failure to thrive, occurring as a result of prolonged malnutrition, is a well-know feature of advanced hydrocephalus.[6] Essentially, it is the outcome of a combination of repeated vomiting and poor feeding found in many of these patients.

tic ileus, spontaneous extrusion of the silicone tube, abdominal cysts,[45] etc. Failure to thrive, occurring as a result of prolonged malnutrition, is a well-know feature of advanced hydrocephalus.[6] Essentially, it is the outcome of a combination of repeated vomiting and poor feeding found in many of these patients. Our patient was markedly malnourished before surgery, and even though this was intensively treated as part of the preoperative preparation, it was obviously not enough to ensure adequate wound healing in the interval of 2 weeks. In addition, the gross abdominal distension that occurred following diversion of fluid to the peritoneal cavity on the one hand and the global hypertonia with sustained raised intra-abdominal pressure on the other resulted in the sutures giving away easily. In malnourished patients with advanced hydrocephalus scheduled for shunting procedures, prevention of this complication must include measures aimed at ensuring that the nutritional status is adequate so as to facilitate wound healing. The operation might need to be delayed for as long as feasible. In the interim, other measures to control the intracranial pressure, such as external ventricular drainage, might be helpful. Furthermore, the peritoneal perforation should be as tiny as possible and should be closed with nonabsorbable purse-string sutures. Where the stab wound is bigger, however, meticulous repair with narrow interval between stitches is recommended.

Sir, Cysticercosis, the infection caused by the larval stage of the tapeworm Taenia solium, is the most common parasitic infestation of the central nervous system (CNS). Seizure is the most common presentation and is the single most common cause of acquired epileptic seizure in the developing world.[1] However, the clinical presentations can be pleomorphic depending on the stage and the location of the cysts in the nervous system. Neurocysticercosis (NCC) must therefore be considered in the differential diagnosis of a wide variety of neurologic disorders, particularly in endemic areas.[2] We report a case of multiple NCC with hydrocephalus with bilateral optic atrophy because of the rarity of the presentation. The relevant literature and possible pathogenesis has been reviewed. An 8-year-old child presented with a history of diminished vision for the last 3 years. There was a history of generalized tonic–clonic seizure for the same duration. There was no history suggestive of raised intracranial pressure (ICP). On examination, visual acuity showed perception of hand movement close to the face. Fundus examination showed bilateral optic nerve atrophy. Higher mental functions and cranial nerves were intact. Tone was increased in all four limbs and there were exaggerated knee jerks. Planter showed withdrawal response on both sides. Examinations of the other systems were normal.

f hand movement close to the face. Fundus examination showed bilateral optic nerve atrophy. Higher mental functions and cranial nerves were intact. Tone was increased in all four limbs and there were exaggerated knee jerks. Planter showed withdrawal response on both sides. Examinations of the other systems were normal. Magnetic resonance imaging (MRI) of the brain showed multiple NCC in vesicular stages in the bilateral cerebral parenchyma and cerebellum with no perilesional edema and mass effect. There was significant hydrocephalus due to a lesion obstructing the out flow of the fourth ventricle at the foramen of Magendi. Hemogram showed normal values and Mantoux test was negative. The child was put on phenytoin, acetazolamide and prednisolone. A right ventriculoperitoneal shunt was performed. Postoperatively, the child was stable and regained a visual acuity of finger counting at 1½ feet distance. The child was discharged at 1 week on oral prednisolone and phenytoin. Taenia solium, the pork tape worm, is a two-host zoonotic cestode. Man harbors the adult tape worm in the small intestine and is the only known definitive host. As in all cestodes, the gravid proglottids at the terminal end of the worm are full of eggs, which are the source of infection with the larval stage, or cysticercosis. The pig is the natural intermediate host, which harbors larval cysts anywhere in its body. Humans become infected with cysts by accidental ingestion of T. solium-infective eggs by feco-oral contamination. In such a case, it preferentially infests the CNS.[1–3]

ource of infection with the larval stage, or cysticercosis. The pig is the natural intermediate host, which harbors larval cysts anywhere in its body. Humans become infected with cysts by accidental ingestion of T. solium-infective eggs by feco-oral contamination. In such a case, it preferentially infests the CNS.[1–3] Symptomatic disease occurs almost exclusively from invasion of the CNS and the eye. NCC can be divided as parenchymal and extra-parenchymal. Seizure is the most common presentation of the parenchymal form, which accounts for 70–90% of the overall presenting features.[3] Reports of uncommon presentations of NCC are few but depict the pleomorphic nature of the disease and hence NCC should be suspected in a wide variety of neurological diseases in an endemic area.[34]

is the most common presentation of the parenchymal form, which accounts for 70–90% of the overall presenting features.[3] Reports of uncommon presentations of NCC are few but depict the pleomorphic nature of the disease and hence NCC should be suspected in a wide variety of neurological diseases in an endemic area.[34] Visual loss in NCC is a serious consequence and can result either from direct ocular involvement or secondary to CNS involvement. It can affect any part of the visual pathway from the eye ball, optic nerve to the visual cortex. Optic nerve affection in NCC can be secondary to compression of the optic nerve in the optic canal and optic chiasma or due to a variable duration of raised ICT. Papilliedema, unilateral optic atrophy and bilateral optic atrophy have all been described. In the series of 23 cases with visual impairment reported by Chang et al., 13 cases were found to be due to optic neuropathy secondary to papilledema.[5] Proaño et al., in their series of giant neurocyticercosis, encountered a case of bilateral optic atrophy due to nerve entrapment secondary to basal arachnoididtis.[6] Similarly, Pansey et al. reported a 5-year-old child presenting with headache and blindness, and bilateral optic atrophy who recovered completely after antiparasitic treatment.[7] In our case, the child presented with diminished vision due to bilateral optic atrophy resulting from hydrocephalus caused by NCC. The cases reported have demonstrated a good visual recovery after VP shunt and antiparasitic treatment in their respective case reports. Our case also showed a trend toward adequate recovery following surgical management.

with diminished vision due to bilateral optic atrophy resulting from hydrocephalus caused by NCC. The cases reported have demonstrated a good visual recovery after VP shunt and antiparasitic treatment in their respective case reports. Our case also showed a trend toward adequate recovery following surgical management. Hydrocephalus is a recognized presentation of extraparenchymal lesions, which occurs consequent to mechanical obstruction of the ventricles or the basal cisterns, either by the cysts themselves or by an inflammatory reaction (ependymitis and/or arachnoiditis). Because the cyst membrane is thin and the fluid is isodense with the cerebrospinal fluid, uninflamed extraparenchymal cysticerci are usually not visible on computed tomography scanning and may only reveal subtle, indirect findings on MRI. Therefore, neuroimaging may reveal hydrocephalus without noticeable cysts.[2] The association of hydrocephalus and bilateral optic atrophy is not unique to NCC. Pojda-Wilczek studied 15 severely visually impaired children with hydrocephalus and associated diseases. They concluded that optic atrophy is the main cause of low vision in children with hydrocephalus.[8] The pathogenesis of optic atrophy associated with hydrocephalus in children could be either secondary to a long-standing unaddressed papilledema or due to stretching of the optic nerve resultant to the expanding skull.[4] The former mechanism is more likely in older children as in our case.

ldren with hydrocephalus.[8] The pathogenesis of optic atrophy associated with hydrocephalus in children could be either secondary to a long-standing unaddressed papilledema or due to stretching of the optic nerve resultant to the expanding skull.[4] The former mechanism is more likely in older children as in our case. We report this case as a rare presentation of NCC. In our case, there were multiple intraparenchymal NCC and diagnosis was relatively easy following MR study. However, as discussed above, extraparenchymal NCC may be missed in neuroimaging. Therefore, in a child with unexplained hydrocephalus with or without bilateral optic atrophy, NCC should be considered in the differential diagnosis.

Introduction Perinatal asphyxia is one of the major causes of neonatal mortality and long-term morbidity. Neurobiology research has extended our understanding of the mechanisms that culminate in neuronal loss after hypoxic–ischemic insult. Asphyxia leads to two types of cerebral insults: the primary neuronal injury that occurs at the time of the hypoxic–ischemic insult and the secondary neuronal injury that occurs over hours to even days following the accumulation of excessive intraneuronal calcium as a result of excitatory amino acid stimulation of the N-methyl–D-aspartate (NMDA) cell receptors. It has been shown that NMDA receptor antagonists block calcium ion entry and preserve neuronal function and structure. MK 801, a NMDA receptor antagonist, has been shown to be neuroprotective in immature animals with asphyxia, but is too toxic to be evaluated in the human neonate.[1] Magnesium ion gates the NMDA channels in a voltage-dependent manner and may protect the brain from NMDA receptor-mediated injury.[2] In an earlier study, we have reported that a dose of 250 mg/kg and 125 mg/kg of magnesium sulfate given as an infusion is safe and well tolerated by asphyxiated neonates.[3] The present study was planned to evaluate the neuroprotective role of this dose of magnesium in birth asphyxia.

NMDA receptor-mediated injury.[2] In an earlier study, we have reported that a dose of 250 mg/kg and 125 mg/kg of magnesium sulfate given as an infusion is safe and well tolerated by asphyxiated neonates.[3] The present study was planned to evaluate the neuroprotective role of this dose of magnesium in birth asphyxia. Material and Methods The study was performed in the Neonatal Services Division of the Department of Pediatrics, Pt. B.D. Sharma PGIMS, Rohtak. Forty term, appropriate for gestational age neonates, born in the hospital with an Apgar score of 3 or less at 1 min and 6 or less at 5 min, formed the subjects for the study. These babies were randomized to either the study group or the control group using a random number table. A preinformed consent was obtained from the parents and the study was cleared by the hospital ethics committee. Babies with congenital malformations and those whose mothers had received magnesium sulfate, pethidine, phenobarbitone or other drugs likely to depress the baby were excluded from the study.

dom number table. A preinformed consent was obtained from the parents and the study was cleared by the hospital ethics committee. Babies with congenital malformations and those whose mothers had received magnesium sulfate, pethidine, phenobarbitone or other drugs likely to depress the baby were excluded from the study. Neonates in the study group received magnesium sulfate at a dose of 250 mg/kg initially within half an hour of birth followed by 125 mg/kg at 24 and 48 h of birth. This was given as an intravenous infusion in 5% dextrose over half an hour. Cranial computed tomography (CT) scan and electroencephalography (EEG) were performed for all the babies. The CT scan and the EEG were evaluated by examiners who were blinded to the groups to which the babies belonged. A detailed neurological examination of the neonates was carried out at the time of discharge and the babies were followed-up for neurodevelopmental assessment till the age of 6 months, when Denver II[4] was used to assess the outcome. The Unpaired “t” test and chi-square test were used for data analysis.

bies belonged. A detailed neurological examination of the neonates was carried out at the time of discharge and the babies were followed-up for neurodevelopmental assessment till the age of 6 months, when Denver II[4] was used to assess the outcome. The Unpaired “t” test and chi-square test were used for data analysis. Results The mean gestational age (38.9 ± 0.4 weeks versus 38.7 ± 0.5 weeks), birth weight (2.78 ± 0.26 kg versus 2.8 ± 0.33 kg), mean cord pH (6.98 ± 0.03 versus 6.97 ± 0.02) and mean Apgar score at 1 and 5 min (1.75 ± 0.44 and 4.85 ± 1.08 versus 1.65 ± 0.5and 4.8 ± 1.19) were comparable in the control and the study groups (P > 0.05). Magnesium infusion was well tolerated and there were no significant alterations in heart rate, oxygen saturation, respiratory rate or mean arterial pressure following magnesium infusion either with the 250 mg/kg or the 125 mg/kg doses.

± 0.5and 4.8 ± 1.19) were comparable in the control and the study groups (P > 0.05). Magnesium infusion was well tolerated and there were no significant alterations in heart rate, oxygen saturation, respiratory rate or mean arterial pressure following magnesium infusion either with the 250 mg/kg or the 125 mg/kg doses. Two babies died with severe hypoxic ischemic encephalopathy in each group. An additional two babies in each group died of nosocomial sepsis. Therefore, there were 16 babies in each group that were available for follow-up assessment till the age of 6 months. Seizures occurred in 50% of the neonates in the control group compared with 35% in the study group. However, this difference was not statistically significant (P > 0.05). Two babies in the control group compared with one in the study group had refractory seizures. EEG abnormalities (slowing of electrical seizure activity and discontinuous pattern) occurred in 43.75% of the cases in the control group compared with 31.25% in the study group (P > 0.05). CT scan abnormalities (focal, multifocal or diffuse hypodensities) occurred in 62.5% of the control compared with 37.5% of the cases in the study group (P > 0.05) [Table 1]. Table 1 CT scan abnormalities

Two babies died with severe hypoxic ischemic encephalopathy in each group. An additional two babies in each group died of nosocomial sepsis. Therefore, there were 16 babies in each group that were available for follow-up assessment till the age of 6 months. Seizures occurred in 50% of the neonates in the control group compared with 35% in the study group. However, this difference was not statistically significant (P > 0.05). Two babies in the control group compared with one in the study group had refractory seizures. EEG abnormalities (slowing of electrical seizure activity and discontinuous pattern) occurred in 43.75% of the cases in the control group compared with 31.25% in the study group (P > 0.05). CT scan abnormalities (focal, multifocal or diffuse hypodensities) occurred in 62.5% of the control compared with 37.5% of the cases in the study group (P > 0.05) [Table 1]. Table 1 CT scan abnormalities CT scan abnormality Control group (n = 16) Study group (n = 16) P-value Diffuse hypodensities 6 (37.5) 2 (12.5) >0.05 Multifocal areas of hypodensity 1 (6.25) 2 (12.5) >0.05 Focal area of hypodensity 3 (18.75) 2 (12.5) >0.05 Total 10 (62.5) 6 (37.5) >0.05 The mean occipitofrontal circumference at 6 months in the control group (43.11 ± 1.41 cm) was comparable to that in the study group (43.09 ± 0.86 cm). The developmental outcome using Denver II at the age of 6 months revealed that there were two babies that were abnormal in the control group versus one in the study group and there were three babies that were suspect in the control group compared with two in the study group. However, these differences between the two groups did not reach statistical significance [Table 2].

6 months revealed that there were two babies that were abnormal in the control group versus one in the study group and there were three babies that were suspect in the control group compared with two in the study group. However, these differences between the two groups did not reach statistical significance [Table 2]. Table 2 Developmental outcome at 6 months: Denver II Outcome Control (n = 16) Study (n = 16) P-value Normal 11 (68.7) 13 (81.2) >0.05 Suspect 3 (18.07) 2 (12.5) >0.05 Abnormal 2 (12.5) 1 (6.25) >0.5 Figures in parenthesis are in percentage. Discussion The study and control groups were comparable for gestational age, birth weight, Apgar scores and cord pH. Two babies in both groups expired in the initial neonatal period as a result of asphyxia and its complications. This shows that magnesium therapy failed to prevent initial mortality due to asphyxia. However, the mortality was similar in the two groups, and no increase in mortality was seen in the group that received magnesium.

es in both groups expired in the initial neonatal period as a result of asphyxia and its complications. This shows that magnesium therapy failed to prevent initial mortality due to asphyxia. However, the mortality was similar in the two groups, and no increase in mortality was seen in the group that received magnesium. Both EEG and CT scan abnormalities occurred more frequently in the control group compared with the study group. Even though these differences did not reach statistical significance, magnesium did appear to have some beneficial effects. The follow-up assessment also revealed that more babies were either abnormal or suspect in the control group compared with the study group. Even though babies receiving magnesium appeared to have a better long-term outcome, a longer follow-up would have possibly helped to bring out the difference between the two groups better. On a 6-month follow-up, it may be possible to pick up motor abnormalities, but cognitive abnormalities that may occur as a consequence of asphyxia may be difficult to pick up at this age. A longer follow-up would have helped to pickup these cognitive abnormalities and possibly other sequelae better.

two groups better. On a 6-month follow-up, it may be possible to pick up motor abnormalities, but cognitive abnormalities that may occur as a consequence of asphyxia may be difficult to pick up at this age. A longer follow-up would have helped to pickup these cognitive abnormalities and possibly other sequelae better. In a recently reported randomized controlled trial, magnesium sulfate was used antenatally as a neuroprotective agent in women with fetuses younger than 30 weeks and threatened preterm labor. There was reduction in the outcome of substantial gross motor dysfunction or combined outcome of death and gross motor dysfunction in the magnesium group.[5] In the index study, mortality in the magnesium group was similar to the control group, but at the 6-month follow-up, more babies were neurologically abnormal in the control group compared with the magnesium group. In a double-blind, randomized, controlled pilot study of 22 asphyxiated full-term neonates where eight babies received magnesium sulfate, magnesium was reported to have no positive effect on the EEG patterns.[6] In the index study, EEG abnormalities occurred more frequently in the control group (44.75%) compared with the study group (31.25%). But, this difference did not reach statistical significance.

nates where eight babies received magnesium sulfate, magnesium was reported to have no positive effect on the EEG patterns.[6] In the index study, EEG abnormalities occurred more frequently in the control group (44.75%) compared with the study group (31.25%). But, this difference did not reach statistical significance. Ichibia et al. conducted a multicenter, randomized, controlled trial to determine whether postnatal magnesium sulfate infusion (250 mg/kg/day) for 3 days resulted in an improved outcome in babies with severe birth asphyxia.[7] Enrollment criteria included a 5-min Apgar score of 7 or less and either failure to initiate spontaneous respiration at 10 min after birth or occurrence of clinically apparent seizures within 24 h of birth. Survival with normal results on cranial CT, EEG and establishment of oral feeding by day 14 of age occurred significantly more often in the magnesium group than in the control group (12/17 versus 5/16, P = 0.04). In the present study too, CT scan abnormalities occurred more frequently in the control group compared with the magnesium group. In a recent report, three doses of magnesium sulfate infusion at the 250 mg/kg per dose given daily for the first 3 days of life was shown to improve neurologic outcomes at discharge for term neonates with severe perinatal asphyxia.[8]

Ichibia et al. conducted a multicenter, randomized, controlled trial to determine whether postnatal magnesium sulfate infusion (250 mg/kg/day) for 3 days resulted in an improved outcome in babies with severe birth asphyxia.[7] Enrollment criteria included a 5-min Apgar score of 7 or less and either failure to initiate spontaneous respiration at 10 min after birth or occurrence of clinically apparent seizures within 24 h of birth. Survival with normal results on cranial CT, EEG and establishment of oral feeding by day 14 of age occurred significantly more often in the magnesium group than in the control group (12/17 versus 5/16, P = 0.04). In the present study too, CT scan abnormalities occurred more frequently in the control group compared with the magnesium group. In a recent report, three doses of magnesium sulfate infusion at the 250 mg/kg per dose given daily for the first 3 days of life was shown to improve neurologic outcomes at discharge for term neonates with severe perinatal asphyxia.[8] Experimental work supports the potential value of magnesium by several mechanisms, i.e. antiexcitotoxic (blocks the NMDA receptor), antioxidant (essential for glutathione biosyntheses), anticytokine (decreases levels of inflammatory cytokines) and antiplatelet (decreases platelet aggregation) effects.[9–15] The systemic administration of magnesium after a simulated hypoxic ischemic insult limits neurological damage in several animal models.[16–18] The limited data regarding the potential value of magnesium in the prevention of brain injury secondary to asphyxia in the human neonate are promising. More data will be of tremendous interest as prevention of mortality and morbidity associated with asphyxia will have a definite impact on neonatal survival. A larger multicenter trial could possibly better define the neuroprotective role of magnesium in asphyxia.

econdary to asphyxia in the human neonate are promising. More data will be of tremendous interest as prevention of mortality and morbidity associated with asphyxia will have a definite impact on neonatal survival. A larger multicenter trial could possibly better define the neuroprotective role of magnesium in asphyxia. Source of Support: Nil Conflict of Interest: None declared

Introduction Minor physical anomalies (MPA) are defined as the unusual morphological features that are found in less than 4% of the general population.[1] The relationship between physical characteristics and behavior has intrigued man for centuries. Galen, a Roman physician and major medical authority during the Middle Ages, began the physiognomy era and advocated the view that physical features could reflect inner characteristics of behavior.[2] The concept of physiognomy suggest that deviant behavior could be predicted from certain physical characteristics of the head and hands. The specific physical deviations, such as jaw size and facial asymmetries can be related with the tendency to turn to criminal behavior.[3] The MPA do not directly cause behavioral deviances rather serve as markers for some fetal disturbance of development in the first and early second trimester.[4] The children with oral disruptions can have difficulty with socializing and may have neurological deficits from feeding difficulties during the first few months of life.[5] It is, therefore, hypothesized that disruptions during a critical stage of development of a physical feature can cause MPA that can lead to a change in brain development that can cause other behavioral problems. The relationship between MPA and behaviors is considerably consistent in males than in females. Furthermore, there is also a relationship between MPA and obstetrical complication.[6]

development of a physical feature can cause MPA that can lead to a change in brain development that can cause other behavioral problems. The relationship between MPA and behaviors is considerably consistent in males than in females. Furthermore, there is also a relationship between MPA and obstetrical complication.[6] In the absence of an identifiable syndrome, an increase in MPA have been reported in several groups including newborns,[78] school-aged children,[9] schizophrenic and autistic youngsters,[10] intellectually disabled children,[1112] psychoneurotic children, learning-disabled children,[1314] speech and language-impaired children,[1] hyperactive children[114] and inhibited children.[8] MPA have major informational value for diagnostic, prognostic and epidemiological purposes. They provide an important clue to specific malformation diagnosis, brain pathology and timing of pathology.[1516] A study by Steg and Rapoport reported a mean Waldrop scale score of 4.25 in a population of autistic children.[14] Trixler’s group focused on 56 informative variants in schizophrenic and alcohol-dependent patients and made a distinction between minor malformations and phenotypic variants. They found that schizophrenic patients had higher rates of both some minor malformations (furrowed tongue, multiple buccal frenula and hemangioma) as well as phenotypic variants (protruding auricle and large tongue).[17]

ohol-dependent patients and made a distinction between minor malformations and phenotypic variants. They found that schizophrenic patients had higher rates of both some minor malformations (furrowed tongue, multiple buccal frenula and hemangioma) as well as phenotypic variants (protruding auricle and large tongue).[17] Thyroid dysfunctions are more common in children with Down syndrome than in normal children. From 15 to 20% of children with Down syndrome have hypothyroidism. While investigating children with global developmental delay, it is also vital not to miss conditions which may be exacerbating it or those conditions which are treatable e.g., hypothyroidism.[18] Stavrakaki recorded that 27% of individuals with intellectual disability had anxiety disorder.[19] The comorbidity with other psychiatric illness e.g., depression is common. In more severe cases the behavioral symptoms associated with anxiety can be reliably assessed.[20] Vitielli et al, and Bodfish et al, reported that compulsions were significantly associated with stereotypies and self-injurious behavior (SIB).[2122] There are arguments for SIB, compulsions and stereotypies to be considered as atypical presentation of Obsessive Compulsive Disorder.[23] Gravestock suggested that 1-19% of adults with disabilities living in the community and 3-42% of those living in institutions have a diagnosable eating disorder.[24]

ior (SIB).[2122] There are arguments for SIB, compulsions and stereotypies to be considered as atypical presentation of Obsessive Compulsive Disorder.[23] Gravestock suggested that 1-19% of adults with disabilities living in the community and 3-42% of those living in institutions have a diagnosable eating disorder.[24] Individuals with Down syndrome have frequently been described as having charming personalities in accordance with a positive Down syndrome personality stereotype.[25] Older children and young adults with Down syndrome are described as primarily positive mood and predictable in their behavior but less active and persistent and more distractible than older children as well.[26] In separate studies Waldrop and Halverson et al, found evidence of possible congenital contributes to individual differences in impulse control. This evidence is based on finding that relatively uncontrolled, fast moving, hyperactive behavior is related to presence of certain MPA in young children.[5] Waldrop and Halverson have argued that stability in the number of MPA and not the specific category of MPA as a predictor for behavioral problems.[8] However, this is not true for all cases. For example, a higher incidence of anomalies of the mouth have been linked to psychosis in several studies as well as in schizophrenic patients.[26]

Correlation Global head Eyes Ears Mouth Hands Feet Waldrop total Global head 1.000 0.642 0.743 0.771 0.655 0.655 0.878 Eyes 0.642 1.000 0.623 0.482 0.447 0.424 0.707 Ears 0.743 0.623 1.000 0.644 0.618 0.728 0.826 Mouth 0.771 0.482 0.644 1.000 0.577 0.562 0.836 Hands 0.655 0.447 0.618 0.577 1.000 0.698 0.754 Feet 0.655 0.424 0.728 0.562 0.698 1.000 0.777 In all cases P - value is <0.001 Table 5 Correlation between Ismail score and DASH-II score Global Head Eyes Ears Mouth Hands Feet Waldrop Total ANX Pearson Correlation 0.170 -0.112 0.155 0.176 0.096 0.097 0.127 Sig (2-tailed) 0.160 0.356 0.200 0.145 0.430 0.423 0.293 N 70 70 70 70 70 70 70 DEPR Pearson Correlation 0.168 0.141 0.181 0.133 0.381** 0.252* 0.273* Sig (2-tailed) 0.165 0.246 0.133 0.271 0.001 0.035 0.022 N 70 70 70 70 70 70 70 MANIA Pearson Correlation 0.253* 0.329** 0.231 0.275* 0.020 0.082 0.257* Sig (2-tailed) 0.034 0.005 0.055 0.021 0.869 0.501 0.032 N 70 70 70 70 70 70 70 PDD Pearson Correlation -0.159 -0.063 -0.115 -0.214 -0.179 -0.062 -0.206 Sig (2-tailed) 0.187 0.606 0.341 0.075 0.139 0.610 0.087 N 70 70 70 70 70 70 70 SCHZ Pearson Correlation 0.025 -0.071 0.021 0.131 -0.105 -0.133 0.000 Sig (2-tailed) 0.837 0.558 0.862 0.279 0.385 0.271 1.000 N 70 70 70 70 70 70 70 STEREO Pearson Correlation 0.102 0.126 -0.040 0.092 -0.030 -0.023 0.041 Sig (2-tailed) 0.401 0.299 0.740 0.450 0.803 0.850 0.733 N 70 70 70 70 70 70 70 SIB Pearson Correlation 0.285* -0.203 -0.248* -0.219 -0.228 -0.210 -0.291* Sig (2-tailed) 0.017 0.092 0.038 0.068 0.058 0.080 0.015 N 70 70 70 70 70 70 70 ELIMIN Pearson Correlation 0.030 -0.058 0.088 0.130 -0.066 -0.032 0.047 Sig (2-tailed) 0.806 0.636 0.467 0.283 0.585 0.795 0.698 N 70 70 70 70 70 70 70 EATING Pearson Correlation 0.147 0.277* 0.264* 0.192 0.234 0.145 0.202 Sig (2-tailed) 0.225 0.020 0.027 0.111 0.051 0.230 0.093 N 70 70 70 70 70 70 70 SLEEP Pearson Correlation 0.118 0.301* 0.002 0.140 0.000 -0.074 0.088 Sig (2-tailed) 0.332 0.011 0.985 0.249 0.997 0.541 0.469 N 70 70 70 70 70 70 70 SEXUAL Pearson Correlation -0.075 -0.051 -0.141 -0.007 -0.115 -0.072 -0.121 Sig (2-tailed) 0.538 0.673 0.245 0.953 0.341 0.552 0.319 N 70 70 70 70 70 70 70 ORG Pearson Correlation -0.150 -0.067 -0.180 -0.174 -0.150 -0.004 -0.160 Sig (2-tailed) 0.210 0.584 0.135 0.150 0.216 0.972 0.186 N 70 70 70 70 70 70 70 IMP Pearson Correlation 0.012 0.125 0.066 0.037 0.070 0.067 0.084 Sig (2-tailed) 0.918 0.304 0.587 0.763 0.565 0.584 0.487 N 70 70 70 70 70 70 70 * Correlation is significant at the 0.05 level (2- tailed);

on have argued that stability in the number of MPA and not the specific category of MPA as a predictor for behavioral problems.[8] However, this is not true for all cases. For example, a higher incidence of anomalies of the mouth have been linked to psychosis in several studies as well as in schizophrenic patients.[26] The increased prevalence of MPA in the hand region of patients merit further interest since some groups of schizophrenic patients have shown aberrant dermatoglyphical patterns, which are also presumptive markers of prenatal neurodevelopmental disturbances.[14] About 60% of patients with schizophrenia have increased level of MPA (>6) in comparison to 5% of normal population.[16] The emotional problems in intellectually disabled persons are very severe and more pronounced than problems observed in general population. Over 500 recognized syndromes involving a genetic disorder have now been isolated and many have behavioral epiphenomena.[10] In two samples of 2-1/2-year children, the presence of multiple MPA was found to be associated with hyperkinetic, aggressive, impatient and intractable behaviors. Out of nearly 100 reliable behavioral variables, 18 in 1 sample and 16 in the other correlated with anomalies in the male subjects.[8]

oral epiphenomena.[10] In two samples of 2-1/2-year children, the presence of multiple MPA was found to be associated with hyperkinetic, aggressive, impatient and intractable behaviors. Out of nearly 100 reliable behavioral variables, 18 in 1 sample and 16 in the other correlated with anomalies in the male subjects.[8] Materials and Methods A careful dysmorphology exam is essential for the detection of MPA and because 71% of anomalies are present in the craniofacial area and the hands, careful attention to these areas can be helpful in diagnosing occult major anomalies.[11] The orofacial structures that do not form properly can result in problems with communication, emotional expression, mastication and deglutition. Anomalies that occur in the mouth can also lead to sucking problems and feeding irregularities during the first years of life that could also affect the mother-child relationship.[27] The behavioral phenotype is relatively a new concept. In a broad sense it seems to be a constellation of specific behaviors and specific disorder of genetic etiology.[9] An estimate that mental health problem is five times higher in intellectually disabled person is a conservative one.[28] Both in Western literature and in Indian context many studies have been done about the chromosomal abnormality of Down syndrome that is found by karyotyping, but most of them did not provide adequate information about its direct causal relationship with different phenotypic and behavioral variants. The aims and objectives of present study are:

e and in Indian context many studies have been done about the chromosomal abnormality of Down syndrome that is found by karyotyping, but most of them did not provide adequate information about its direct causal relationship with different phenotypic and behavioral variants. The aims and objectives of present study are: To assess clinico-demographic profile of patients and subjects. To find out MPAs and its incidence. To study the behavioral profile among the people with intellectual disability. The search for correlation between minor anomalies and behavioral profile. To get additional information about type of chromosomal anomaly and correlation with intelligent quotient (IQ).

To assess clinico-demographic profile of patients and subjects. To find out MPAs and its incidence. To study the behavioral profile among the people with intellectual disability. The search for correlation between minor anomalies and behavioral profile. To get additional information about type of chromosomal anomaly and correlation with intelligent quotient (IQ). The study design is a cross-sectional survey done independently by the three researchers. The study was conducted during the period from February 2007 to January 2009 [Figure 1]. The total sample size was 210 divided equally in three groups-cases (karyotype-confirmed Down syndrome group), control (other causes of intellectual disability) and normal (age-matched healthy population group). The MPA were assessed by using Modified Waldrop scale consisting of 18 plus 23 additional items.[8] The assessment of MPA takes only 15 minutes with very minimal removal of clothing (shoes and stockings). For practical reasons, visible surfaces like head, eyes, mouth, ears, hands and feet regions are studied. The items of diagnostic assessment scale for severely handicapped (DASH-II) scale comprises of a total of 83 items representing 13 disorder groups derived from subscales and individual items DSM-III R (American Psychiatric Association, 1987) as well as previously published studies of the population.[25] Three separate dimensions of behavior were used for rating namely frequency, severity and duration - for administrative convenience only frequency dimension had been analyzed. Each dimension provided for rating on one of three levels, scored 0, 1 or 2. The usual time required to apply this scale averages 60-90 minutes and less as the rater gets accustomed to use this scale.[20]

amely frequency, severity and duration - for administrative convenience only frequency dimension had been analyzed. Each dimension provided for rating on one of three levels, scored 0, 1 or 2. The usual time required to apply this scale averages 60-90 minutes and less as the rater gets accustomed to use this scale.[20] Figure 1 Algorithm of study design The inter-rater reliability of DASH-II mood subscale was found to be 0.88.[20] The depression subscale of the DASH-II displayed convergent validity of 0.75 with the Aberrant Behavior Checklist.[29]

-0.180 -0.174 -0.150 -0.004 -0.160 Sig (2-tailed) 0.210 0.584 0.135 0.150 0.216 0.972 0.186 N 70 70 70 70 70 70 70 IMP Pearson Correlation 0.012 0.125 0.066 0.037 0.070 0.067 0.084 Sig (2-tailed) 0.918 0.304 0.587 0.763 0.565 0.584 0.487 N 70 70 70 70 70 70 70 * Correlation is significant at the 0.05 level (2- tailed); ** Correlation is significant at the 0.01 level (2- tailed); ANX indicates anxiety; DEPR, depression; PDD, pervasive developmental disorder; SIB, self-injurious behavior, SCHZ, schizophrenia; STEREO, stereotypy; ELIMIN, elimination; ORG, organic; IMP, impulse.

amely frequency, severity and duration - for administrative convenience only frequency dimension had been analyzed. Each dimension provided for rating on one of three levels, scored 0, 1 or 2. The usual time required to apply this scale averages 60-90 minutes and less as the rater gets accustomed to use this scale.[20] Figure 1 Algorithm of study design The inter-rater reliability of DASH-II mood subscale was found to be 0.88.[20] The depression subscale of the DASH-II displayed convergent validity of 0.75 with the Aberrant Behavior Checklist.[29] Results and Discussion The three groups are represented uniformly as far as the population distribution is concerned. While age of Down syndrome cases ranged from 3 to 37 years that of comparison group 3 to 39 years and that of normal control group, 3 to 31 years. The sex difference in between the groups was not found to be statistically significant (χ2 = 5.833, df = 2, P = 0.054). The average paternal and maternal age at the time of childbirth in Down syndrome are 35.76 and 31.16 years, respectively, which corroborates the earlier findings that the incidence of Down syndrome increases with both increase in paternal and maternal age [Table 1]. The maternal age of marriage and income are other significant demographic variables (P<0.001). The only mosaic variety of Down syndrome in this study had total IQ of 64, with lower maternal age of childbirth (25 years) and less behavioral abnormalities. About 22.84% patients with Down syndrome also had hypothyroidism, and the only translocation variety case also had relatively higher total IQ (62) and borne by relatively younger mother (26 years). As the study areas are situated in the urban region most of the cases had come from the nuclear family with middle-class background with higher average parental age in comparison to the standard population. The Down syndrome group had significantly more MPA than other two groups and most of the MPA is situated in the global head region.

are situated in the urban region most of the cases had come from the nuclear family with middle-class background with higher average parental age in comparison to the standard population. The Down syndrome group had significantly more MPA than other two groups and most of the MPA is situated in the global head region. Table 1 Descriptive and ANOVA summary of demographical profile Demographical variables Group N Mean SD F Significance (P-value) Age DS 70 16.30 10.288 1.771 0.173 OTH 70 14.93 8.030 NOR 70 13.61 6.579 Paternal age at childbirth DS 70 35.76 7.264 11.731 < 0.001** OTH 70 32.51 4.886 NOR 70 31.50 3.446 Maternal age at childbirth DS 70 31.16 5.067 22.066 < 0.001** OTH 70 26.59 4.356 NOR 70 27.14 3.816 Income DS 70 3.06 1.020 3.724 0.026* OTH 70 2.90 0.837 NOR 70 3.29 0.617 Maternal age of marriage DS 70 28.60 4.308 74.373 < 0.001** OTH 70 22.64 3.750 NOR 70 22.09 2.048 Birth order DS 70 2.11 2.004 3.010 0.051 OTH 70 1.57 0.894 NOR 70 1.66 1.062 * P < 0.05 ** P < 0.01; DS indicates, Down syndrome; OTH, other causes of intellectual disability; NOR, normal.

Demographical variables Group N Mean SD F Significance (P-value) Age DS 70 16.30 10.288 1.771 0.173 OTH 70 14.93 8.030 NOR 70 13.61 6.579 Paternal age at childbirth DS 70 35.76 7.264 11.731 < 0.001** OTH 70 32.51 4.886 NOR 70 31.50 3.446 Maternal age at childbirth DS 70 31.16 5.067 22.066 < 0.001** OTH 70 26.59 4.356 NOR 70 27.14 3.816 Income DS 70 3.06 1.020 3.724 0.026* OTH 70 2.90 0.837 NOR 70 3.29 0.617 Maternal age of marriage DS 70 28.60 4.308 74.373 < 0.001** OTH 70 22.64 3.750 NOR 70 22.09 2.048 Birth order DS 70 2.11 2.004 3.010 0.051 OTH 70 1.57 0.894 NOR 70 1.66 1.062 * P < 0.05 ** P < 0.01; DS indicates, Down syndrome; OTH, other causes of intellectual disability; NOR, normal. The total score of Modified Waldrop scale (Ismail et al,) shows [Table 2] significantly higher values in the Down syndrome group (mean=17.04; SD= 5.462) than in the other intellectual disability group (mean=5.93; SD=2.628) and intellectually average age-matched group (mean=1.59; SD=1.378). Among the 13 major subscales in DASH II scale, the stereotypy (n=44, 62.9%), impulse control (n=36, 51.4%) and mania subscales (n=31, 44.3%) are present in significantly higher frequencies in the Down syndrome group, whereas organic subscale (n=48, 68.6%) and impulse control disorder subscales (n=42, 60.0%) more commonly present in the control group. [Table 3] The least frequent anomalies are schizophrenia and anxiety disorders in the Down syndrome group. Overall the behavioral abnormalities as evident from the scoring in the DASH II scale are more common in other non-Down syndrome cases of intellectual disability group than in Down syndrome group. The correlation matrix shows strong association (P<0.001) between the various grouped items of Modified Waldrop scale (including the anomalies in feet region) in cases of Down syndrome [Table 4] The correlation matrix between MPA and behavioral problems shows that not only anomalies around the mouth but also MPA distribution in other areas are also associated with behavioral abnormalities. Depression subscale is correlated with anomalies in the hands (P<0.001), feet and Waldrop total items (P<0.005). Mania item of DASH II scale is related with anomalies around the eyes (P<0.001), global head, mouth and Waldrop total score (P<0.005). SIB and total Waldrop score is negatively correlated with global head but positively related with anomalies around the ears. The eating disorder subscale is positively correlated to anomalies around the eyes and ears and the same correlation is seen between the sleeping disorder anomalies around the eyes (P<0.005). The items of DASH II scale that are not related to Waldrop scale are pervasive developmental disorder, schizophrenia, stereotypy, elimination, sexual, organic and impulse control disorder subscales [Table 5].

es and ears and the same correlation is seen between the sleeping disorder anomalies around the eyes (P<0.005). The items of DASH II scale that are not related to Waldrop scale are pervasive developmental disorder, schizophrenia, stereotypy, elimination, sexual, organic and impulse control disorder subscales [Table 5]. Table 2 Descriptive summary of modified Waldrop score in three groups Group N Mean Med Min Max Sd DS 70 17.04 18.0 6.0 30.0 5.462 Other ID 70 5.93 6.0 1.0 13.0 2.628 Normal 70 1.59 1.5 0.0 5.0 1.378 DS indicates, Down syndrome; NOR, normal. Table 3 Frequencies of DASH II subscales in the three groups studied Item DS Control Normal N % N % N % Anxiety 9 12.9 2 2.9 0 0.0 Depression 17 24.3 8 11.4 3 4.3 Mania 31 44.3* 7 10.0 2 2.9 PDD 28 40.0 23 32.9 0 0.0 Schizophrenia 5 7.1 3 4.3 0 0.0 Stereotypy 44 62.9* 41 58.6 1 1.4 Sib 6 8.6 28 40.0 0 0.0 Elimination 15 21.4 16 22.9 1 1.4 Eating 18 25.7 16 22.9 2 2.9 Sleep 20 28.6 18 25.7 3 4.3 Sexual 15 25.7 18 25.7 0 0.0 Organic 26 37.1 48 68.6* 0 0.0 Impulse 36 51.4* 42 60.0* 7 10.0 * Highest frequencies observed in the group; DS indicates Down syndrome cases; PDD, pervasive developmental disorder; SIB, self-injurious behavior. Table 4 Correlation matrix of grouped regions in Ismail 41 scale

Item DS Control Normal N % N % N % Anxiety 9 12.9 2 2.9 0 0.0 Depression 17 24.3 8 11.4 3 4.3 Mania 31 44.3* 7 10.0 2 2.9 PDD 28 40.0 23 32.9 0 0.0 Schizophrenia 5 7.1 3 4.3 0 0.0 Stereotypy 44 62.9* 41 58.6 1 1.4 Sib 6 8.6 28 40.0 0 0.0 Elimination 15 21.4 16 22.9 1 1.4 Eating 18 25.7 16 22.9 2 2.9 Sleep 20 28.6 18 25.7 3 4.3 Sexual 15 25.7 18 25.7 0 0.0 Organic 26 37.1 48 68.6* 0 0.0 Impulse 36 51.4* 42 60.0* 7 10.0 * Highest frequencies observed in the group; DS indicates Down syndrome cases; PDD, pervasive developmental disorder; SIB, self-injurious behavior. Table 4 Correlation matrix of grouped regions in Ismail 41 scale Correlation Global head Eyes Ears Mouth Hands Feet Waldrop total Global head 1.000 0.642 0.743 0.771 0.655 0.655 0.878 Eyes 0.642 1.000 0.623 0.482 0.447 0.424 0.707 Ears 0.743 0.623 1.000 0.644 0.618 0.728 0.826 Mouth 0.771 0.482 0.644 1.000 0.577 0.562 0.836 Hands 0.655 0.447 0.618 0.577 1.000 0.698 0.754 Feet 0.655 0.424 0.728 0.562 0.698 1.000 0.777 In all cases P - value is <0.001 Table 5 Correlation between Ismail score and DASH-II score

-0.180 -0.174 -0.150 -0.004 -0.160 Sig (2-tailed) 0.210 0.584 0.135 0.150 0.216 0.972 0.186 N 70 70 70 70 70 70 70 IMP Pearson Correlation 0.012 0.125 0.066 0.037 0.070 0.067 0.084 Sig (2-tailed) 0.918 0.304 0.587 0.763 0.565 0.584 0.487 N 70 70 70 70 70 70 70 * Correlation is significant at the 0.05 level (2- tailed); ** Correlation is significant at the 0.01 level (2- tailed); ANX indicates anxiety; DEPR, depression; PDD, pervasive developmental disorder; SIB, self-injurious behavior, SCHZ, schizophrenia; STEREO, stereotypy; ELIMIN, elimination; ORG, organic; IMP, impulse. Conclusion The sample size is only modest (70 in each group). The increased sample size could have increased the power of tests. No follow-up studies have been done. The study design is the single observation cross-sectional survey, but behavioral features can vary with time. Some of the physical features are very rare especially in Asian countries. A better scale with wider applicability, reliability and validity is required to detect MPA in different ethnic background. There was always the possibility that some of the informants (the legal guardians) would provide inaccurate information especially while assessing the behavioral abnormalities of the subjects and the interpretation may be erroneous. To minimize this error, appropriate consultation has been taken with the senior faculties of the department as well as liaison services have been sought for from the Department of Pediatrics and retrospective patient record sheet has also been reviewed. The metabolic screening has not been done due to administrative inconvenience. Therefore, associated disorders of Inborn Error of Metabolism if present can not be excluded. The congenital CNS structural anomaly can not be screened out as the routine structural imaging has not been performed due to cost constraints.

ed. The metabolic screening has not been done due to administrative inconvenience. Therefore, associated disorders of Inborn Error of Metabolism if present can not be excluded. The congenital CNS structural anomaly can not be screened out as the routine structural imaging has not been performed due to cost constraints. Despite the limitations as mentioned above, the study generated valuable information as discussed and the authors believe that the results of this study will help further research work regarding the incidence of MPA and correlation of MPA with behavioral abnormalities in the Down syndrome population group. Not only the Down syndrome group, but also other causes of intellectual disability group needs to be worked out. The large scale study is required to see whether MPA can be a predictor of future behavioral characteristics which can have preventive, therapeutic, rehabilitative and prognostic implications. Researchers believe that when a high number of MPAs as determined by the Waldrop scale are present, there are implications for behavioral variations. Recently, the literature is focused on the schizophrenic population. Although this study did not confirm the usefulness of screening the general population for MPAs as a predictor for behavior, the results demonstrate that the Down syndrome group has significantly more MPAs and a pattern of correlation between MPA and behavioral abnormalities in a large sample can be really worthwhile. Source of Support: Nil Conflict of Interest: None declared.

Introduction Moyamoya, meaning a “hazy puff of smoke” in Japanese, was first described by Takeuchi and Shimizu in 1957.[1] It is a chronic, occlusive cerebrovascular disease involving bilateral stenosis or occlusion of the terminal portion of the internal carotid arteries (ICAs) and/or the proximal portions of the anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and also the posterior circulation, with an abnormal vascular network at the base of the brain.[2] It is the most common pediatric cerebrovascular disease in Eastern Asia. The clinical presentation of moyamoya disease (MMD) in children usually includes episodes of transient ischemic attacks (TIAs), whereas in adults it is intracranial hemorrhage.[34] Very little is known about the pathogenesis of MMD, and thus curative treatment is still elusive. However, the benefits of revascularization surgery for the ischemic type of MMD are well-established.[5] Several surgical techniques have been described, in which revascularization of the ischemic regions of the brain is attempted. Direct revascularization by superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and indirect methods such as encephalomyosynangiosis (EMS), encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis (EDAMS), omental graft have been performed with varying results[6–11] and a combination of direct and indirect revascularization techniques have also been attempted.[12–14] Most surgical procedures have aimed at increasing the blood supply primarily to the MCA territory and do not directly benefit the ACA territory.[4121516]

), omental graft have been performed with varying results[6–11] and a combination of direct and indirect revascularization techniques have also been attempted.[12–14] Most surgical procedures have aimed at increasing the blood supply primarily to the MCA territory and do not directly benefit the ACA territory.[4121516] Clinical presentation History and presentation: This 10-year-old male child presented with complaints of chronic episodic headache of 5-years duration. Initially, at the peak of his headache he had only weakness of the left upper limb, but as his symptoms progressed he also developed weakness of the left lower limb, with speech and visual disturbances, lasting for a few minutes, followed by complete recovery. Six months prior to his admission he experienced four such episodes per day, with each attack of ischemia lasting for half an hour, followed by complete recovery. There was no history of loss of consciousness, or tonic clonic movements suggestive of a seizure. He was started on anticonvulsants elsewhere. There was no contributory family history. Examination On examination, the child was conscious, oriented with normal higher intellectual functions, with an intelligent quotient corresponding to his age. His fundi and cranial nerves functions were normal and he had no spinomotor or sensory deficits. His other systemic examination was normal.

Clinical presentation History and presentation: This 10-year-old male child presented with complaints of chronic episodic headache of 5-years duration. Initially, at the peak of his headache he had only weakness of the left upper limb, but as his symptoms progressed he also developed weakness of the left lower limb, with speech and visual disturbances, lasting for a few minutes, followed by complete recovery. Six months prior to his admission he experienced four such episodes per day, with each attack of ischemia lasting for half an hour, followed by complete recovery. There was no history of loss of consciousness, or tonic clonic movements suggestive of a seizure. He was started on anticonvulsants elsewhere. There was no contributory family history. Examination On examination, the child was conscious, oriented with normal higher intellectual functions, with an intelligent quotient corresponding to his age. His fundi and cranial nerves functions were normal and he had no spinomotor or sensory deficits. His other systemic examination was normal. Radiological investigations MRI and CT scan of the brain plain and contrast study showed multiple lacunar infarcts bilaterally [Figure 1]. MR angiogram of the brain showed bilateral stenosis of the ICA distal to the supraclinoid segment and in the posterior circulation [Figure 2]. Digital subtraction four-vessel angiography confirmed bilateral multiple stenosis of the supraclinoid portion of the ICA as well as stems of the ACA and MCAs and the posterior circulation with multiple collaterals arising proximal to the occluded vessels and from the external carotid artery [Figure 3]. Single photon emission computerized tomography (SPECT) images of the brain showed hypoperfusion in the right temporo-occipital area suggestive of an old infarct, with other areas in the brain parenchyma showing normal perfusion [Figure 4]. Adenosine brain SPECT study for evaluation of cerebrovascular reserve in stress and at rest showed a matched perfusion defect in the right temporo-occipital area, with no evidence of a new perfusion defect.

area suggestive of an old infarct, with other areas in the brain parenchyma showing normal perfusion [Figure 4]. Adenosine brain SPECT study for evaluation of cerebrovascular reserve in stress and at rest showed a matched perfusion defect in the right temporo-occipital area, with no evidence of a new perfusion defect. Figure 1 CT and MRI of the brain showing multiple lacunar infarcts bilaterally. Figure 2 MR angiogram of the brain showing bilateral stenosis of the supraclinoid segment of the internal carotid artery and posterior circulation with multiple collaterals. Figure 3 Digital subtraction four-vessel angiography showing bilateral multiple areas of stenosis of the supraclinoid portion of the internal carotid artery and the anterior cerebral, middle cerebral arteries and the posterior circulation with multiple collaterals arising proximal to the occluded vessels and from the external carotid artery Figure 4 SPECT images of the brain showing hypoperfusion in the right temporo-occipital area suggestive of an old infarct, with other areas in brain parenchyma showing normal perfusion.

Figure 3 Digital subtraction four-vessel angiography showing bilateral multiple areas of stenosis of the supraclinoid portion of the internal carotid artery and the anterior cerebral, middle cerebral arteries and the posterior circulation with multiple collaterals arising proximal to the occluded vessels and from the external carotid artery Figure 4 SPECT images of the brain showing hypoperfusion in the right temporo-occipital area suggestive of an old infarct, with other areas in brain parenchyma showing normal perfusion. Surgical technique Under general anesthesia, with the patient in supine position, head kept neutral and flexed so that there is good exposure of the calvaria, a bicoronal skin flap was marked. The skin was infiltrated with saline solution in the subgaleal plane as this makes the dissection easier. The skip flap was turned taking care to preserve the galea aponeurotica and scalp blood supply. The periosteum was left attached to the bone, preserving the vessels as this will form the collateral network. Multiple triangular-shaped incisions were made in the periosteum and elevated as small flaps to expose the bone. Five burr holes were made on each side over the frontal, temporal and parietal region. The burr holes are made at each exposed area, using a high-speed drill, about 3 cm apart and 3 cm off the midline to prevent injury to the sagittal sinus. The surgical microscope is then used and the dura was opened through the burr holes, preserving the meningeal arteries. The arachnoid and the pia are then opened just enough to ensure a true opening without causing significant bleeding. Cautery was avoided to preserve the potential anastomotic vessels. The elevated periosteal flaps were laid over the exposed brain through the corresponding burr holes [Figure 5]. The galea was carefully replaced and the scalp was closed in two layers. A compressive head dressing was applied for 5 days. Postoperatively there was no cerebrospinal fluid (CSF) leak. The child is doing well and on 6-months follow-up had one episode of TIA. The postoperative effectiveness of the neovascularization was demonstrated 6 months later by four-vessel angiogram showing excellent cerebral revascularization around the burr hole sites [Figure 6] and SPECT imaging [Figure 7] showed hypoperfusion in the right temporo-occipital area suggestive of an old infarct. There were no other perfusion defects in the rest of the brain parenchyma.

trated 6 months later by four-vessel angiogram showing excellent cerebral revascularization around the burr hole sites [Figure 6] and SPECT imaging [Figure 7] showed hypoperfusion in the right temporo-occipital area suggestive of an old infarct. There were no other perfusion defects in the rest of the brain parenchyma. Figure 5 Intraop pictures showing multiple burr holes drilled over the exposed areas of bone, through small incisions in the perisoteum a) scalp elevation, b) periosteal elevation, c) burr holes and dural opening and d) periosteal flap placed in direct contact with the brain. Figure 6 Postoperative four-vessel angiogram done after 6 months showing excellent cerebral revascularization around the burr hole sites. Figure 7 Postoperative SPECT imaging showing hypoperfusion in the right temporo-occipital area suggestive of an old infarct. There is evidence of no other perfusion defects seen in the rest of the brain parenchyma. Discussion Endo et al., in 1989 demonstrated marked neovascularization across a frontal burr hole, which was used for external drainage of an intraventricular hemorrhage in a child with MMD.[12] On the basis of this, they used additional frontal burr holes with EMS for treating children with MMD, and found better revascularization of the frontal area when compared to EMS alone. Kawaguchi et al,[17] performed the burr hole procedure alone in 1 adult and Sainte-Rose et al,[18] used the similar procedure of indirect revascularization in 14 children. They both demonstrated excellent revascularization without the necessity of a supplementary procedure.

the frontal area when compared to EMS alone. Kawaguchi et al,[17] performed the burr hole procedure alone in 1 adult and Sainte-Rose et al,[18] used the similar procedure of indirect revascularization in 14 children. They both demonstrated excellent revascularization without the necessity of a supplementary procedure. Even though the pathogenesis of MMD remains unclear, there are prominent pathological features noted; proliferation and migration of smooth muscle cells in the intima, leading to intimal thickening with morphological and biochemical alteration of extracellular matrix components such as elastin, collagen and proteoglycans[219] without signs of any inflammation or atheromatous plaque.[120] Junichi et al,[21] found MMD to have a bimodal peak of distribution with the first peak at 10 years and the second in the fourth decade. Clinically our patient had a history of multiple episodes of TIA, with radiological evidence of an area of chronic infarction which categorized him to be in stage IV Matsushima clinical grading of MMD.[9] Based on the angiographical findings, the patient was in Suzuki and Takaku stage IV; he had progressive narrowing of all the main cerebral arteries with almost complete disappearance of the posterior cerebral artery with minimal residual patency of basal vessels and the development of extracranial collateral vessels.[222] SPECT scan is the most commonly used test for evaluation of the hemodynamic changes in MMD and the finding of hypoperfusion generally correlates well with the clinical symptoms.[23] Preoperatively we did an adenosine brain SPECT study for evaluation of cerebrovascular reserve in stress and at rest. Adenosine infusion causes vasodilatation of cerebralarteries and can be used for the investigation of cerebrovascularperfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide isthe possibility of interrupting the test with reversal of clinicalsymptoms or patient discomfort within a few minutes.[24]

of cerebralarteries and can be used for the investigation of cerebrovascularperfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide isthe possibility of interrupting the test with reversal of clinicalsymptoms or patient discomfort within a few minutes.[24] The surgical procedures performed for ischaemic type of MMD can be classified into three categories: direct bypass, indirect bypass and combined revascularization techniques. The results obtained have been reported to be excellent, but it is still not clear which technique is the safest and most effective. Direct procedure includes STA-MCA anastomosis. This procedure was first adopted by Yasargil and repeated by Karyenbuhl.[25] The early improvement of cerebral hemodynamics is considered to be one of the major advantages of this procedure.[2627] However, the clinical outcome is not different from that achieved by an indirect procedure, thus making its benefit questionable. Also this procedure has limitations in the treatment of pediatric MMD, due to the small size of the donor and recipient vessels and the need for temporary occlusion of blood flow in the cortical artery during anastomosis.[1516] The indirect methods described are EMS, EDAS, EDAMS, omental flaps and pial synangiosis[6–9] and combinations of direct and indirect revascularization surgeries have also been done.[12–14] The principle of indirect revascularization in patients with MMD is based on the natural ability of collateral vessels to develop in these patients and, that revascularization of the ischemic brain areas can be achieved from an extracranial blood supply. Indirect procedures bring in circulation to the intracranial regions by introducing newly developed vasculature from newly approximated tissues.[28] Although not a specific marker for moyamoya, elevated basic fibroblast growth factor (bFGF) in CSF may serve as a weak predictor of the extent of angiogenesis to be expected in indirect revascularization procedures.[29] Yoshimoto et al, analyzed CSF samples obtained in patients with MMD and found changes in the CSF cytokines that act in an angiogenic manner.[30]

elevated basic fibroblast growth factor (bFGF) in CSF may serve as a weak predictor of the extent of angiogenesis to be expected in indirect revascularization procedures.[29] Yoshimoto et al, analyzed CSF samples obtained in patients with MMD and found changes in the CSF cytokines that act in an angiogenic manner.[30] Based on the child’s clinical and radiological findings we decided to do an indirect revascularization surgery, by making multiple burr holes and arachnoid openings over both cerebral hemispheres. Five burr holes were made in the frontotemporoparietal area of each hemisphere, as the child had symptoms of TIA, causing leg and hand weakness, with visual disturbances. The number of burr holes made depends on the site and extent of the disease. Sainte-Rose et al,[18] from their study have demonstrated an early improvement in cerebral perfusion following placement of multiple burr holes and use this technique in all patients with MMD.

g leg and hand weakness, with visual disturbances. The number of burr holes made depends on the site and extent of the disease. Sainte-Rose et al,[18] from their study have demonstrated an early improvement in cerebral perfusion following placement of multiple burr holes and use this technique in all patients with MMD. In children with MMD undergoing indirect revascularization techniques, or combined procedures, the extent of revascularization is dependent on the area and size of contact between the extracranial tissue and the brain, and Houkin et al, conclude that as much brain as possible be exposed and the external tissues be applied as widely as possible.[13] STA-MCA and EMS procedures improve symptoms mostly related to the MCA territory. They did not improve symptoms of TIA with leg weakness, abnormal cognition, and visual field defects due to ischemia in the areas supplied mainly by the ACA and posterior cerebral artery.[63132] Also, it is well known that MMD in children is dynamic and progressive,[3] thus deterioration of blood flow in the ACA territory can progress despite good collateral formation in the MCA territory. Conclusion This technique described can be performed in a single stage, on both sides by using a bicoronal flap, where multiple burr holes can be placed over the whole hemisphere where necessary. The procedure is short and safe, with excellent revascularization of most of the cortex underlying the burr holes, and additional revascularization surgeries are not required. The duration is short-making it an option in high-risk cases. Source of Support: Nil

Conclusion This technique described can be performed in a single stage, on both sides by using a bicoronal flap, where multiple burr holes can be placed over the whole hemisphere where necessary. The procedure is short and safe, with excellent revascularization of most of the cortex underlying the burr holes, and additional revascularization surgeries are not required. The duration is short-making it an option in high-risk cases. Source of Support: Nil Conflict of Interest: None declared.

Neuronal migration disorders refer to a wide spectrum of developmental malformations of the cortex caused by disruption to its normal process of formation, which includes proliferation, migration and organization. We illustrate case of a 2 year old male child who presented to us with complaints of delayed milestones of development since birth with multiple episodes of generalized tonic clonic seizures. Physical examination revealed a depressed anterior fontanelle. Computed tomography scan showed the presence of lissencephaly, colpocephaly and septal agenesis. This constellation of findings makes the ventricular system appear in shape of a crown of a king on the un-enhanced CT scan. Hence, we refer to this as “CROWN SIGN”, not previously described in neurosurgical literature. The child was started on anti-epileptics and cerebro-active agents. He showed gradual improvement on follow up with neck holding coming up as the first positive sign. Isolated defects are common but sometimes they occur in varying degrees of combination, giving a unique appearance on the imaging studies, as has been exemplified in our case.

on anti-epileptics and cerebro-active agents. He showed gradual improvement on follow up with neck holding coming up as the first positive sign. Isolated defects are common but sometimes they occur in varying degrees of combination, giving a unique appearance on the imaging studies, as has been exemplified in our case. A 2-year-old male child presented to us with complaints of delayed motor, language, and psychosocial milestones of development since birth. At the time of examination, there was no neck holding. For the last six months, the child also had multiple episodes of generalized tonic-clonic seizures. The perinatal period was insignificant. There was no positive family history. Physical examination revealed a depressed anterior fontanelle. Computed tomography (CT) scan was done, which showed the presence of lissencephaly (pachygyria-agyria complex) [Figure 1] with predominant enlargement of occipital horns (colpocephaly) [Figure 2]. Septal agenesis was also present, although the interhemispheric fissure was well developed. Dandy-Walker variant was present as an additional finding [Figure 3]. This triad of lissencephaly, colpocephaly, and absence of septum pellucidum gives a unique appearance to the ventricular system in form of a crown of a king on the unenhanced CT scan. Therefore, we refer to this as ‘CROWN SIGN,’ first described in neurosurgical literature [Figure 4]. This terminology has been used to provide a quick insight about the pathology that is being dealt with. The presence of ‘CROWN SIGN’ indicates that we are dealing with syndromic triad of lissencephaly, colpocephaly, and septal agenesis. The child was started on antiepileptics and cerebroactive agents. He showed gradual improvement on follow-up, with neck holding coming up as the first positive sign.

is being dealt with. The presence of ‘CROWN SIGN’ indicates that we are dealing with syndromic triad of lissencephaly, colpocephaly, and septal agenesis. The child was started on antiepileptics and cerebroactive agents. He showed gradual improvement on follow-up, with neck holding coming up as the first positive sign. Figure 1 Noncontrast axial CT scan showing the presence of lissencephaly with pachygyria-agyria complex Figure 2 Noncontrast axial CT scan showing the presence of colpocephaly with septal agenesis Figure 3 Dandy-Walker variant presenting as the ‘key sign’ Figure 4 Ventricular system presenting as the ‘Crown Sign’

is being dealt with. The presence of ‘CROWN SIGN’ indicates that we are dealing with syndromic triad of lissencephaly, colpocephaly, and septal agenesis. The child was started on antiepileptics and cerebroactive agents. He showed gradual improvement on follow-up, with neck holding coming up as the first positive sign. Figure 1 Noncontrast axial CT scan showing the presence of lissencephaly with pachygyria-agyria complex Figure 2 Noncontrast axial CT scan showing the presence of colpocephaly with septal agenesis Figure 3 Dandy-Walker variant presenting as the ‘key sign’ Figure 4 Ventricular system presenting as the ‘Crown Sign’ Discussion Neuronal migration disorders (also, and better, called cortical developmental anomaly) are caused by abnormal proliferation, migration, and organization (lamination, gyration, and sulcation). Proliferation of young neurons occurs in the germinal matrix, located in the subependymal layer of the walls of the lateral ventricles, during the seventh week of gestation. Starting from the eighth week of gestation, most of these neurons migrate from the germinal zone to their final destination in the cortex along specialized radial glial fibers, 10% migrate orthogonally to the radial glial cells. Migration follows an ‘inside-out’ sequence so that neurons of the deepest cortical layer migrate early, followed by those destined for layers 5, 4, 3, and 2, with the exception of neurons destined for layer 1 that are the first to reach the cortex. Once in the cortex, neurons organize into the normal six layers and develop synaptic contacts with the other neurons. Any event that interferes with the various steps of cortical formation can cause a developmental anomaly. This includes infections (cytomegalovirus, toxoplasmosis), ischemic insults, both exogenous and endogenous toxins from metabolic disorders and radiation exposure.[1]

evelop synaptic contacts with the other neurons. Any event that interferes with the various steps of cortical formation can cause a developmental anomaly. This includes infections (cytomegalovirus, toxoplasmosis), ischemic insults, both exogenous and endogenous toxins from metabolic disorders and radiation exposure.[1] Cortical malformations manifest clinically by producing seizures, mental retardation, and focal neurological deficits. Most frequently, patients experience medically refractory epilepsy, whose degree of severity and time of onset is variable. Other features include feeding and swallowing problems, muscle tone anomalies (early hypotonia and subsequently limb hypertonia), and severe psychomotor retardation.[23] CT changes of lissencephaly include lack of cortical sulci and gyri; calcification in the region of paraphysis; wide, shallow sylvian fissures; colpocephaly; poor development of white matter; and persistent cavum septum pellucidum and cavum vergae.[4] Isolated defects are common but sometimes they occur in varying degrees of combination,[5] giving a unique appearance on the imaging studies, as has been exemplified in our case. Source of Support: Nil Conflict of Interest: None declared

A 15-year-old female presented with seizures, cognitive impairment and right-sided hemiparesis since early childhood. On examination, she had hemiatrophy of the right side of the body with spastic hemiparesis and incomplete achievement of mental milestones. Magnetic resonance imaging (MRI) brain revealed atrophy of left cerebral hemisphere, cerebral peduncle, basal ganglia and thalamus. There was ipsilateral midline shift and ventricular dilatation along with skull vault thickening and prominent frontal sinus, suggestive of congenital type of cerebral hemiatrophy (CH) or Dyke–Davidoff–Masson syndrome (DDMS) [Figures 1A–C]. Figure 1A Axial T2-weighted image: Left cerebral hemiatrophy, ipsilateral occipital horn dilatation, ipsilateral midline shift, hypoplasia of thalamus, caudate nucleus, and lentiform nucleus are demonstrated. In addition, ipsilateral pneumosinus dilatans (frontal) is seen Figure 1B Axial T2-weighted image: Hypoplasia of left cerebral peduncle Figure 1C Axial T1-weighted image: Left cerebral hemiatrophy with calvarial thickening. Hypointensity in white matter represents gliosis

Figure 1A Axial T2-weighted image: Left cerebral hemiatrophy, ipsilateral occipital horn dilatation, ipsilateral midline shift, hypoplasia of thalamus, caudate nucleus, and lentiform nucleus are demonstrated. In addition, ipsilateral pneumosinus dilatans (frontal) is seen Figure 1B Axial T2-weighted image: Hypoplasia of left cerebral peduncle Figure 1C Axial T1-weighted image: Left cerebral hemiatrophy with calvarial thickening. Hypointensity in white matter represents gliosis Clinically, patients present with seizures, facial asymmetry, contralateral hemiparesis and mental retardation. The underlying etiology is cerebral insult that may occur in utero or early in life. Prenatal causes include congenital anomalies, cerebral infarction, vascular malformations and infections. Perinatal causes are birth trauma, hypoxia and intracranial bleed. Postnatal hemiatrophy can develop secondary to cerebral trauma, tumors, infections and febrile seizures. Infantile (congenital) type of DDMS, in contrast to adult (acquired) DDMS, shows enlargement of calvarium, diploic space and paranasal sinuses. These compensatory cranial changes occur to take up the relative vacuum created by the atrophied cerebral hemisphere.[12] Shen et al.[3] depicted three MR imaging patterns of cerebral hemiatrophy: MR imaging pattern I corresponds to diffuse cortical and subcortical atrophy; pattern II corresponds to diffuse cortical atrophy coupled with porencephalic cysts; and pattern III corresponds to previous infarction with gliosis in the middle cerebral artery (MCA) territory. In our case, pattern III was present. The atrophied cerebral hemisphere will have prominent sulcal spaces if the vascular insult occurs after birth or after end of sulcation. However, if ischemia occurs during embryogenesis when the formation of gyri and sulci is deficient, prominent sulcal spaces will be absent.[4]

y. In our case, pattern III was present. The atrophied cerebral hemisphere will have prominent sulcal spaces if the vascular insult occurs after birth or after end of sulcation. However, if ischemia occurs during embryogenesis when the formation of gyri and sulci is deficient, prominent sulcal spaces will be absent.[4] Children with medically refractive epilepsy and hemiplegia may be candidates for hemispherectomy, which is helpful in eradicating or significantly reducing seizures in 85% of patients.[5] MRI is a valuable method of examination in the analysis of cerebral hemiatrophy as it has the ability to bring to light changes in the cerebral hemispheres as well as highlighting bony structural changes and thus differentiating between congenital and acquired types of DDMS. Source of Support: Nil Conflict of Interest: None declared.

Introduction The normal pathway of catabolism of methionine produces cystine, with homocysteine as a pivotal intermediate. Most homocysteine is normally remethylated to methionine. This methionine-sparing reaction is catalyzed by the enzyme methione synthase, which requires a metabolite of folic acid (5-methyltetrahydrofolate) as a methyl donor and a metabolite of vitamin B12 (methylcobalamin) as a cofactor. Further conversion of homocysteine to cystathionine requires a pyridoxal phosphate-dependent enzyme, cystathionine ß synthase, deficiency of which results in accumulation of homocysteine and reconversion of homocysteine to methionine.[1] Homocystinuria type-1, due to the deficiency of cystathionine ß synthase, is the most common inborn error of methionine metabolism. It is characterized by developmental delay, ectopia lentis, progressive mental retardation, skeleton abnormalities resembling Marfan syndrome and thromboembolic episodes. Diagnosis is usually made after 3 years of age, when most of the patients present with subluxation of the lens. Homocystinuria can also occur due to defect in methylcobalamin formation, i.e. homocystinuria type-II, characterized by the triad of megaloblastic anemia, homocystinuria and hypomethionemia. Deficiency of the enzyme methyltetrahydrofolate reductase results in homocystinuria type-III, characterized by homocystinemia, homocystinuria and low-low normal levels of methionine.[12] We encountered a patient who presented to us with stroke, had megaloblastic anemia and ectopia lentis. We made the diagnosis of homocystinuria type-I and instituted specific treatment.

uctase results in homocystinuria type-III, characterized by homocystinemia, homocystinuria and low-low normal levels of methionine.[12] We encountered a patient who presented to us with stroke, had megaloblastic anemia and ectopia lentis. We made the diagnosis of homocystinuria type-I and instituted specific treatment. Case Report A 4 year old female child presented to us with complains of weakness of the right half of the body. According to the mother of the child, 5 days back, the child had passed urine and stools in the bed and was crying excessively. When the mother tried to make the child stand up, she noticed that the child was not moving her right upper and right lower limbs. There were no H/O fever, rash, abnormal body movements, altered sensorium and pus discharge from the ear, no H/O bluish discoloration, breathlessness, syncopal attacks and palpitation, no H/O joint pains, petechial/purpuric/ecchymotic spots over the body and no H/O head/neck/oral trauma, no family H/O bleeding diathesis or cerebrovascular accidents. The child was immunized for age and her developmental and dietary histories were normal. The child was born to a nonconsangunious marriage and there was no history suggestive of homocystinuria in the family. On examination, the child had fair complexion with light brown and woolly hair. Pallor was present. Rest of the general physical examination was normal. No marfanoid features, no neurocutaneous stigmata and no sternal tenderness were observed. Anthropometry was normal. There were no signs of any vitamin deficiency. Her vitals were stable.

child had fair complexion with light brown and woolly hair. Pallor was present. Rest of the general physical examination was normal. No marfanoid features, no neurocutaneous stigmata and no sternal tenderness were observed. Anthropometry was normal. There were no signs of any vitamin deficiency. Her vitals were stable. Central nervous system-wise, the child was conscious, cooperative and well oriented. No cranial nerve palsy was present. There were no meningeal signs and no abnormal movements of the limbs. Muscle bulk was normal bilaterally. Tone was increased in the right upper and right lower limbs. Deep tendon reflexes were brisk in the right upper and right lower limbs. Power was 2/5 in the right upper and 3/5 in the right lower limb. Plantars were downgoing bilaterally. No cerebellar signs were present. The skull and spine were normal. Chest, cardiovascular system, abdomen and musculoskeletal system were normal. Eye examination showed bilateral inferonasal ectopia lentis. Investigations revealed a haemoglobin of 8 gm% and a normal total and differential leucocyte count. The platelet count was 140 × 103/cmm. The reticulocyte count was 2.6% and Erythrocte sedimentation rate was 22mm in the 1st hour. Renal function test, Liver function test, serum electrolytes and blood sugar were normal.

Investigations revealed a haemoglobin of 8 gm% and a normal total and differential leucocyte count. The platelet count was 140 × 103/cmm. The reticulocyte count was 2.6% and Erythrocte sedimentation rate was 22mm in the 1st hour. Renal function test, Liver function test, serum electrolytes and blood sugar were normal. The peripheral smear showed anisopoikilocytosis, macroovalocytes, macrocytes, tear drop cells and polychromatic cells with coarse basophilic stippling. The mean corpuscular volume was 136 fL, the mean corpuscular hemoglobin was 36 pg, the mean corpuscular hemoglobin concentration was 30 g/dl and the bone marrow was suggestive of megaloblastic changes. Magnetic resonance imaging of the brain showed moderate-sized hyperintensities in the left centrum semiovale and subtle hyperintensities in the bilateral caudate nuclei.

The peripheral smear showed anisopoikilocytosis, macroovalocytes, macrocytes, tear drop cells and polychromatic cells with coarse basophilic stippling. The mean corpuscular volume was 136 fL, the mean corpuscular hemoglobin was 36 pg, the mean corpuscular hemoglobin concentration was 30 g/dl and the bone marrow was suggestive of megaloblastic changes. Magnetic resonance imaging of the brain showed moderate-sized hyperintensities in the left centrum semiovale and subtle hyperintensities in the bilateral caudate nuclei. Sodium nitroprusside test in the urine was positive. The serum homocysteine level was 256.91 μmol/L (normal range, 4.60–12.44). The serum vitamin B12 level was 310 pg/ml (normal range, 200–800 pg/ml). The fasting plasma methionine level was increased to 134.34 μmol/L (normal range, 0–90 μmol/L). Based on these investigations, we made the diagnosis of homocystinuria type-I and the patient was started on oral pyridoxine (400 mg/day) and oral folic acid (5 mg/day). Physiotherapy was also started. The child was also put on a low-protein, low-methionine diet. The child responded to treatment and started walking on day 5 of the treatment. The power was still 4/5 in the right upper limb at the time of discharge. Genetic counselling of the family was carried out. On follow-up after 3 months of treatment, the power was normal in the limbs, hemoglobin was 14 gm%, mean corpuscular volume decreased to 88.7 fL, mean corpuscular haemoglobin was 28.6 pg and mean corpuscular haemoglobin concentration was 33.68 g/dL. The platelet count increased to 180 × 103/μL. The serum homocysteine level was 52 μmol/L (normal range, 4.60–12.44).

power was normal in the limbs, hemoglobin was 14 gm%, mean corpuscular volume decreased to 88.7 fL, mean corpuscular haemoglobin was 28.6 pg and mean corpuscular haemoglobin concentration was 33.68 g/dL. The platelet count increased to 180 × 103/μL. The serum homocysteine level was 52 μmol/L (normal range, 4.60–12.44). Discussion Homocystinuria is an autosomal recessively inherited defect in the transsulfuration pathway (type-I) or methylation pathway (types II and III). The internationally reported incidence of homocystinuria varies between 1 in 50,000 and 1 in 200,000.[3] Normally, homocysteine is an intracellular intermediate and is not detectable in plasma or urine. However, when the reconversion of homocysteine to methionine or cysteine is blocked, it accumulates extracellularly and results in homocystinuria.[4] Infants with this disorder are normal at birth. Clinical manifestations during infancy are nonspecific, and may include failure to thrive and developmental delay. The diagnosis is usually made when subluxation of the ocular lens occurs. This causes severe myopia and iridiodonesis. Progressive mental retardation is common. Affected individuals with homocystinuria manifest skeletal abnormalities resembling those of Marfan syndrome. Children usually have fair complexions, blue eyes and a peculiar malar flush. Thromboembolic episodes involving both large and small vessels, especially those of the brain, are common and may occur at any age.

Affected individuals with homocystinuria manifest skeletal abnormalities resembling those of Marfan syndrome. Children usually have fair complexions, blue eyes and a peculiar malar flush. Thromboembolic episodes involving both large and small vessels, especially those of the brain, are common and may occur at any age. Classically, megaloblastic anemia has been known to be associated with homocystinuria type-II.[1] Not many cases of megaloblastic anemia have been seen with homocystinuria type-I. The mechanism of megaloblastic anemia seen in homocystinuria type-I is the development of folate deficiency due to excessive consumption of methyltetrahydrofolate in the methylation of homocysteine to form methionine.[4–6] Thrombocytopenia seen in our patient can be attributed to folate deficiency, which improved subsequently on treatment with folic acid.[7] The megaloblastic anemia seen in homocystinuria type-II responds to treatment with vitamin B12. However, treatment in type-I requires pyridoxine, which acts as a coenzyme for the enzyme cystathionine synthase and its administration results in greater binding of the enzyme with the substrate by a simple mass action.[2] Treatment with high doses of pyridoxine causes dramatic improvement in patients who are responsive to therapy (40%), as seen in our patient. The need for dietary restriction and its extent is controversial in patients with vitamin B6-responsive form. Treatment with Betaine has produced clinical improvement in patients who are unresponsive to pyridoxine therapy.[1] Ectopia lentis is specifically seen with type-I homocystinuria only.[8] Thromboembolic episodes involving both large and small vessels, especially those of the brain, are common in type-I homocystinuria and can occur at any age.[1] The risk for vascular disease is graded with respect to the level of homocysteine. However, no threshold abnormal value is accepted widely. Several factors have been suggested as the possible cause of accelerated vascular disease. These include - endothelial cell damage, smooth muscle cell proliferation, lipid abnormalities, upregulation of pro-thrombotic factors and downregulation of antithrombotic factors or endothelial-derived nitric oxide.[3]

d widely. Several factors have been suggested as the possible cause of accelerated vascular disease. These include - endothelial cell damage, smooth muscle cell proliferation, lipid abnormalities, upregulation of pro-thrombotic factors and downregulation of antithrombotic factors or endothelial-derived nitric oxide.[3] Thus, we conclude that homocystinuria must be kept in mind in the differential diagnosis of pediatric stroke, looking for other clinical manifestations like ectopia lentis and fair complexion, light hair and presence of megaloblastic anemia. All patients with homocystinuria treated with pyridoxine should receive folate supplementation. The treatment of homocystinuria assumes greater significance because institution of specific treatment can prevent progression of this disease and associated complications. Source of Support: Nil Conflict of Interest: None declared

Introduction Sturge–Weber syndrome occurs sporadically with a frequency of 1 in 50,000. It is characterized by meningofacial angiomatosis with cerebral calcification.[1] Klippel-Trenaunay syndrome is characterized by a triad of cutaneous vascular malformation along with bony or soft tissue hypertrophy and venous varicosities. Phakomatosis pigmentovascularis is a distinctive association of cutaneous hemangiomas and melanocytic nevi. Case Report A ten-month-old male child presented with developmental delay, reduced vision and right-sided focal seizures. A similar episode of seizure was reported one month back. He was the first born child of nonconsanguineous marriage. There was no significant family or birth history. The developmental milestones were delayed.

A ten-month-old male child presented with developmental delay, reduced vision and right-sided focal seizures. A similar episode of seizure was reported one month back. He was the first born child of nonconsanguineous marriage. There was no significant family or birth history. The developmental milestones were delayed. On examination, his weight was 9.3 kg (25th percentile), height was 72 cm (25th percentile) and head circumference was 52 cm. (>95th percentile, macrocephaly). Developmental assessment revealed a global developmental delay as he could not sit without support, had an absent palmar grasp, monosyllabic speech, would not smile at mirror image, or play with ball. There was a port-wine stain on his face and hyperpigmented lesions over trunk, abdomen and right leg as seen in Figure 1 suggestive of dermal melanocytosis. Hyperpigmentation on the left cornea and facial skin were suggestive of oculocutaneous melanosis (nevus of Ota). He had megalocornea and bilateral buphthalmos. His right lower limb was hypertrophied. Calf circumferences of right and left lower limb were 20.6 cm and 18.5 cm, respectively, thigh circumference of right and left lower limb were 26.5 cm and 25.3 cm, respectively, foot length of right and left lower limb were 137.91 cm and 124.21 cm, respectively. Figure 1 Showing hyperpigmented lesion on right leg and trunk.

circumferences of right and left lower limb were 20.6 cm and 18.5 cm, respectively, thigh circumference of right and left lower limb were 26.5 cm and 25.3 cm, respectively, foot length of right and left lower limb were 137.91 cm and 124.21 cm, respectively. Figure 1 Showing hyperpigmented lesion on right leg and trunk. The computerized tomography (CT) scan of brain of the patient as seen in Figure 2 showed generalized atrophy of brain along with generalized hyper dense area in white matter mainly in frontal lobe and left parietal lobe. Dystrophic calcification suggestive of chronic congenital ischemic change due to venous malformation was also noted. There was mild post contrast enhancement in the left parietal-occipital region. Ultrasound of abdomen did not show any vascular and renal anomaly. As the child had both the features of Sturge–Weber syndrome and Klippel–Trenaunay syndrome, a diagnosis of an overlap syndrome was made. Figure 2 CT of head showing atrophy of brain and calcification of left parietal region.

t parietal-occipital region. Ultrasound of abdomen did not show any vascular and renal anomaly. As the child had both the features of Sturge–Weber syndrome and Klippel–Trenaunay syndrome, a diagnosis of an overlap syndrome was made. Figure 2 CT of head showing atrophy of brain and calcification of left parietal region. Discussion Sturge–Weber syndrome is a mesodermal phakomatosis characterized by port-wine naevus covering face and cranium supplied by first division of trigeminal nerve along with atrophy and calcification of cerebral hemisphere homolateral to the skin lesion.[1] This syndrome occurs sporadically with a frequency of approximately 1 in 50,000.[2] Sturge–Weber syndrome is associated with glaucoma, seizures, paresis, and neurodevelopmental delay. About 70% of patients with epilepsy have their first seizure within the first year of their life. Neuroradiological findings in these patients show leptomeningeal enhancement along with signs of cortical atrophy and calcifications in the subjacent area.[3] In our patient, the central nervous system abnormalities on CT scan along with the port-wine stain, glaucoma, seizures, and developmental delay pointed to Sturge–Weber syndrome. But the right leg hypertrophy, extensive cutaneous vascular lesions and macrocephaly could not be explained by Sturge-Weber syndrome alone. Klippel–Trenaunay syndrome is a rare entity characterized by the combination of capillary nevus, early onset of varicosities and hypertrophy of tissues and bones of the affected limb.[4] Cutaneous lesions can occur in any area, but are more commonly located on the legs, buttocks, abdomen and lower trunk. The varicosities in Klippel–Trenaunay syndrome appear in most patients by the age of 12 years.[3] Central nervous system abnormalities associated with Klippel–Trenaunay syndrome include microcephaly, macrocephaly, cerebral arteriovenous malformations, spinal arteriovenous malformations, and orbito-frontal varices.[1] Our patient had leg hypertrophy associated with ipsilateral cutaneous vascular malformations and macrocephaly, which are features of this syndrome[Figure 3]. Figure 3 Showing leg hypertrophy

rocephaly, macrocephaly, cerebral arteriovenous malformations, spinal arteriovenous malformations, and orbito-frontal varices.[1] Our patient had leg hypertrophy associated with ipsilateral cutaneous vascular malformations and macrocephaly, which are features of this syndrome[Figure 3]. Figure 3 Showing leg hypertrophy Phakomatosis pigmentovascularis is characterized by the association of extensive nevus flammeus and pigmentary nevi in the form of widespread, aberrant and persistent Mongolian spots.[5] There are four types of phakomatosis pigmentovascularis all having nevus flammeus as a component. Along with nevus flammeus, type I has an epidermal nevus, type II has blue spots with or without nevus anemicus, type III has nevus spilus, with or without nevus anemicus, type IV has blue spots and nevus spilus with or without nevus anemicus.[6] The findings in our patient are in accordance with type IIa, according to the classification of phakomatosis pigmentovascularis.

s, type II has blue spots with or without nevus anemicus, type III has nevus spilus, with or without nevus anemicus, type IV has blue spots and nevus spilus with or without nevus anemicus.[6] The findings in our patient are in accordance with type IIa, according to the classification of phakomatosis pigmentovascularis. Over 40 reports of patients with overlap of Klippel–Trenaunay syndrome and Sturge–Weber syndrome have been published.[3] Neuroradiological studies have been performed only in few such studies.[2378] The CT scan abnormalities of central nervous system noted in them were malformation of the circle of Willis, cerebral hemihypertrophy, aplasia of the cervical internal carotid artery, cerebral atrophy, prominent choroid plexus, cerebral calcifications, leptomeningeal enhancement. Only in few patients, typical intracranial findings as seen in Sturge-Weber syndrome were seen. There is no specific curative treatment for this combined disorder. The management is directed towards underlying systemic and local anomalies. Our case represented an overlap syndrome between Klippel-Trenaunay syndrome and Sturge-Weber syndrome in association with phakomatosis pigmentovascularis, which to the best of our knowledge has been reported in very few earlier studies[679] and has not been reported from India. Source of Support: Nil Conflict of Interest: None declared

Introduction Meningiomas occurring in the first two decades of life are uncommon, accounting for only about 1-2% of all brain tumors.[12] Clear cell meningioma (CCM) is a rare phenotype, with a potentially aggressive clinical course and risk of recurrence.[3–5] The occurrence of this tumor in the supratentorial space is rare and adds to the uncertainty about its clinical course and prognosis. We report a case of such tumor at this unusual location and discuss about the dilemmas associated with the management and long-term prognosis.

linical course and risk of recurrence.[3–5] The occurrence of this tumor in the supratentorial space is rare and adds to the uncertainty about its clinical course and prognosis. We report a case of such tumor at this unusual location and discuss about the dilemmas associated with the management and long-term prognosis. Case Report A 15-year-old male child presented with history of worsening right-sided weakness of 2 years duration. He had progressive vision loss in the left eye for the past 1 year. He had multiple episodes of focal-onset generalized tonic clonic seizures with poor drug compliance. Headache with projectile vomitings had started lately. On clinical examination, the patient was blind in the left eye, with a normal right eye. There was mild right-sided seventh nerve weakness and hemiparesis. A magnetic resonance imaging scan of the brain revealed a left-sided large supratentorial tumor extending from the brain surface in the frontal and parietal cortex to the atrium and frontal horn of the lateral ventricle, causing significant compression [Figure 1]. There was brain edema with evidence of tentorial herniation. The tumor had both solid and cystic components [Figure 2]. The tumor showed heterogenous contrast enhancement after gadolinium injection [Figure 3]. Taking into consideration the radiological findings, a possibility of primitive neuroectodermal tumor was made. At surgery, after the bone flap was elevated, the cystic component of the tumor was found to be infiltrating the duramater near the lateral parietal region, causing an impression over the inner surface of the bone. The cystic component of the tumor contained xanthochromic fluid. The solid component was firm, moderately vascular and poorly suckable. A gross total resection of the tumor was performed along with resection of the infiltrated duramater overlying the parietal lobe. The patient had complete relief of headache and vomiting in the postoperative period and was free of seizures on phenytoin. A postoperative computed tomography (contrast) scan of the brain [Figure 4] revealed total excision of the tumor. Histopathology of the tumor revealed a diagnosis of CCM WHO grade II. The tumor was composed of lobules of loosely arranged cells set in a very loose myxoid stroma. The cells had scanty cytoplasm with indistinct cell margins and slender ovoid nuclei, some with intranuclear cytoplasmic inclusions [Figure 5].

the tumor. Histopathology of the tumor revealed a diagnosis of CCM WHO grade II. The tumor was composed of lobules of loosely arranged cells set in a very loose myxoid stroma. The cells had scanty cytoplasm with indistinct cell margins and slender ovoid nuclei, some with intranuclear cytoplasmic inclusions [Figure 5]. The tumor cells were positive for Epithelial membrane antigen (EMA) [Figure 6] and vimentin and negative for S-100, synaptophysin, Glial fibrillary acidic protien (GFAP), cytokeratin and desmin. The MIB -1 index of the tumor was 8%. The patient is doing well at 18 months of follow-up. Figure 1 Axial section of the T1-weighted magnetic resonance imaging image of the brain showing the tumor with a midline shift Figure 2 Axial section of the T2-weighted magnetic resonance imaging image of the brain showing solid and cystic components and peritumoral edema Figure 3 Coronal section of the contrast-enhanced magnetic resonance imaging image showing heterogenous enhancement of the tumor Figure 4 Postoperative contrast-enhanced computed tomography scan image showing no residual tumor Figure 5 Clear cell meningioma composed of loosely arranged cells in a myxoid stroma. A typical intranuclear inclusion is seen on the upper left Figure 6 Clear cell meningioma with strong EMA immunoreactivity in the tumor cells

Figure 4 Postoperative contrast-enhanced computed tomography scan image showing no residual tumor Figure 5 Clear cell meningioma composed of loosely arranged cells in a myxoid stroma. A typical intranuclear inclusion is seen on the upper left Figure 6 Clear cell meningioma with strong EMA immunoreactivity in the tumor cells Discussion CCM is a recently described histological subtype of meningioma and is reported to occur more frequently in the pediatric age group.[35–8] The most common site of occurrences are the spinal canal (intradural, 48%), the cerebellopontine angle, tentorium, skull base and foramen magnum.[145] Supratentorial location of pediatric CCM is rare. In a review of 35 cases of intracranial CCM, Ma et al. reported only two pediatric patients as having supratentorial intraparenchymal CCM.[56] They treated the patients with intracranial and spinal radiation after surgical removal.[8]

Discussion CCM is a recently described histological subtype of meningioma and is reported to occur more frequently in the pediatric age group.[35–8] The most common site of occurrences are the spinal canal (intradural, 48%), the cerebellopontine angle, tentorium, skull base and foramen magnum.[145] Supratentorial location of pediatric CCM is rare. In a review of 35 cases of intracranial CCM, Ma et al. reported only two pediatric patients as having supratentorial intraparenchymal CCM.[56] They treated the patients with intracranial and spinal radiation after surgical removal.[8] Radiologically, the lesions show strong and homogenous enhancement following contrast injection.[5] The histopathological differential diagnoses include microcystic meningioma, hemangioblastoma and clear cell ependymoma.[6] The characteristic histology and immunohistochemistry leads to the confirmation of diagnosis.[9–11] The clinical behavior of these tumors has been shown to be aggressive, with a high incidence of local recurrence, cerebrospinal fluid (CSF) spread or metastases.[35–7] However, the rate of increase of dimension of such a tumor is not known. There is no definitive method to identify the potential of recurrence of this tumor. In a study comparing the levels of proliferating cell nuclear antigen (pCNA) and MIB-1 index in nonrecurring and recurring CCM, it was reported that the mean values were 10.4% and 11% for nonrecurring and recurring tumors, respectively, for pCNA.[9] The mean values for the MIB-1 index were 7.4% and 13.3% for the nonrecurring and recurring tumors, respectively. Furthermore, no close association was noted between the recurrence of tumor and factors such as mitotic activity, pCNA proliferation indices, percent S-phase determination or DNA ploidy status.[11] The long-term outcome of CCM is unknown, with only few cases free of recurrence at 5 years or more in the follow-up period.[11] Local recurrence of the tumor has been reported even with low levels of MIB-1 index. The treatment strategies have been mainly reported for spinal CCMs. Gross total resection has been considered to be the treatment of choice and radiosurgery and chemotherapy have been considered treatment options in recurring cases.[14]

ocal recurrence of the tumor has been reported even with low levels of MIB-1 index. The treatment strategies have been mainly reported for spinal CCMs. Gross total resection has been considered to be the treatment of choice and radiosurgery and chemotherapy have been considered treatment options in recurring cases.[14] This child presented with a lesion in the left frontoparietal region. Such a location of the tumor with absence of any subarachnoid or CSF seedling is extremely rare. The radiological study revealed the tumor to be heterogenous in consistency with solid and cystic components and had a nonuniform enhancement after gadolinium injection. At surgery of this child, it was revealed that the cyst had caused an impression on the inner surface of the parietal bone, which may be suggestive of the gradual progression of the tumor. With reference to the literature review, CCM may have benign histological characteristics, but, clinically, it shows a high risk of progression and recurrence. Given the large dimension of the tumor (6-7 cm), local impression on the bone and long duration of symptoms, the rate of growth of the tumor seems to be slow in this case. The MIB-1 index in the patient was 8%, making the course of illness unpredictable. The recurrence rate for these tumors has mainly been reported with reference to spinal CCM and the guidelines for therapy are based there upon. Given the behavior of the tumor in the present case, we can safely recommend a close follow-up in the postoperative period, with radiotherapy reserved for cases with recurrence. Source of Support: Nil

This child presented with a lesion in the left frontoparietal region. Such a location of the tumor with absence of any subarachnoid or CSF seedling is extremely rare. The radiological study revealed the tumor to be heterogenous in consistency with solid and cystic components and had a nonuniform enhancement after gadolinium injection. At surgery of this child, it was revealed that the cyst had caused an impression on the inner surface of the parietal bone, which may be suggestive of the gradual progression of the tumor. With reference to the literature review, CCM may have benign histological characteristics, but, clinically, it shows a high risk of progression and recurrence. Given the large dimension of the tumor (6-7 cm), local impression on the bone and long duration of symptoms, the rate of growth of the tumor seems to be slow in this case. The MIB-1 index in the patient was 8%, making the course of illness unpredictable. The recurrence rate for these tumors has mainly been reported with reference to spinal CCM and the guidelines for therapy are based there upon. Given the behavior of the tumor in the present case, we can safely recommend a close follow-up in the postoperative period, with radiotherapy reserved for cases with recurrence. Source of Support: Nil Conflict of Interest: None declared

Introduction Brucellosis is a chronic granulomatous infection. Brucella, the bacteria causing brucellosis, spreads from animals to people, directly or indirectly, often via consumption of unpasteurized milk, cheese, and other dairy products made from infected animal products. This zoonotic disease may involve almost the entire organ systems of the human body. Primarily, it affects the reticuloendothelial system (RES) and the osteoarticular system. The condition may lead to clinic morbidity, as it becomes significant in the rural parts of developing countries where uncontrolled dairy products are widely consumed. The condition has a high prevalence particularly in countries at the Mediterranean basin and Middle East.[1] In brucellosis, the central nervous system (CNS) involvement is a rare event, and it may affect 5-7% of patients.[23] CNS involvement usually includes miscellaneous conditions such as meningitis, encephalitis, meningoencephalitis, meningovascular disease, brain abscess, and demyelination problems.[1] The diagnostic criteria in neurobrucellosis include unexplained neurological symptoms, the Wright agglutination test positivity over 1/160 for Brucella, increased protein and lymphocyte count, and a positive Wright agglutination test in cerebrospinal fluid (CSF) even with very low titers, and a dramatic response to antibiotic therapy.[4]

eria in neurobrucellosis include unexplained neurological symptoms, the Wright agglutination test positivity over 1/160 for Brucella, increased protein and lymphocyte count, and a positive Wright agglutination test in cerebrospinal fluid (CSF) even with very low titers, and a dramatic response to antibiotic therapy.[4] Clinical categorization of adult neurobrucellosis cannot be applied to children because neurobrucellosis usually affects the CNS and presents itself in an acute form in children. The period of symptoms may vary between 0.5 and 8 weeks.[25] In this report, neurobrucellosis with hydrocephalus has been discussed in a 10-year-old girl.

gorization of adult neurobrucellosis cannot be applied to children because neurobrucellosis usually affects the CNS and presents itself in an acute form in children. The period of symptoms may vary between 0.5 and 8 weeks.[25] In this report, neurobrucellosis with hydrocephalus has been discussed in a 10-year-old girl. Case Report A 10-year old girl was referred to our clinic for complaints of fever, headache, nausea, vomiting, lethargy, and urinary incontinence. No specific feature was present in her medical history. The patient experienced a normal psychomotor development. Clinical examination revealed a temperature of 38.5°C. Lethargy, nuchal rigidity (++), positive Kernig’s and Brudzinski’s signs, isochoric pupils, direct and indirect light reflexes (+) were detected during neurological examination. Posture and walking were found unstable during the examination of the motor system. Romberg (++) and cerebellar tests were competent. No loss of strength in bilateral upper and lower extremities was determined. Deep tendon reflexes were hypoactive, and pathological reflexes were absent. Grade I papilloedema was observed on ophthalmological examination. Cranial computed tomography (CT) demonstrated a significant temporal horn enlargement and a communicating hydrocephalus causing dilation of the 3rd and lateral ventricles [Figure 1].

endon reflexes were hypoactive, and pathological reflexes were absent. Grade I papilloedema was observed on ophthalmological examination. Cranial computed tomography (CT) demonstrated a significant temporal horn enlargement and a communicating hydrocephalus causing dilation of the 3rd and lateral ventricles [Figure 1]. Figure 1 (a) T1W (flair) and (b) T2W brain magnetic resonance imaging (MRI) shows communicating hydrocephalus and periventricular edema. (c) Axial CT demonstrates the catheter for external ventricular drainage in the frontal horn of the right lateral ventricle, decreased ventricular size, and disappearance of periventricular edema Hemoglobin was 9.8 mg/dl, erythrocyte sedimentation rate was 40 mm/hour, C-reactive protein was 24 mg/l (0–5 mg/l), and white blood cell count was 3.700/mm3 with a 70% of lymphocyte ratio. Blood glucose and liver function tests were normal. In lumbar puncture (LP), pressure in CSF was increased and a turbidity, pandy test (++) appearance turbidity, pandy test (++) appearance was observed. Leukocyte count was 455/mm3 with 36% of neutrophils and 64% of lymphocytes. Protein value of CSF was 148 mg/dl. Wright agglutination test was positive with a ratio of 1:1280 in blood. Gruber–Widal test was negative, and Wright and Rose Bengal test was positive. After the diagnosis of neurobrucellosis, an external ventricular drainage was performed and the catheter was removed, 10 days after the insertion.

e of CSF was 148 mg/dl. Wright agglutination test was positive with a ratio of 1:1280 in blood. Gruber–Widal test was negative, and Wright and Rose Bengal test was positive. After the diagnosis of neurobrucellosis, an external ventricular drainage was performed and the catheter was removed, 10 days after the insertion. Hydrocephalus did not relapse after the removal of catheter, and therefore there was no need to insert a ventriculoperitoneal (V–P) shunt during follow-up. Rifampicin 15 mg/kg/day, doxycycline 5 mg/kg/day, and gentamicin 5 mg/kg/day were given for 6 weeks as an antibiotic therapy. Dexamethasone was administered 12 mg/day in three doses for 7 days, then decreased gradually, and stopped. Repeated CSF cultures were negative. The ventricular catheter was removed after all the hydrocephalic findings disappeared on day 14. At the end of the 6-week therapy, blood and CSF cultures became negative. Patient was then discharged from the hospital after all of the laboratory tests became normal.

lly, and stopped. Repeated CSF cultures were negative. The ventricular catheter was removed after all the hydrocephalic findings disappeared on day 14. At the end of the 6-week therapy, blood and CSF cultures became negative. Patient was then discharged from the hospital after all of the laboratory tests became normal. Discussion Neurobrucellosis is a rare complication of brucellosis, but the course of the condition is very severe. It is seldom seen in children. Symptoms may include fever, headache, vomiting, fatigue, depression, back pain, muscle tension and spasms. Additionally, findings of meningeal irritation, deep tendon reflexes areflexia or positive Babinski plus, hyperreflexia and other findings of systemic brucellosis can be observed. Sensorial or motor abnormalities at different degrees, cranial nerve retention, convulsions, cerebellar dysfunction, coma and brain abscesses may worsen the condition.[67] Adult neurobrucellosis may present itself in an acute or chronic form. It may affect the central or peripheral nervous systems or, sometimes, may affect them both. Peripheral nervous system involvement may be seen alone or together with the CNS retention in nearly 1/3 of adult cases.[28]

s may worsen the condition.[67] Adult neurobrucellosis may present itself in an acute or chronic form. It may affect the central or peripheral nervous systems or, sometimes, may affect them both. Peripheral nervous system involvement may be seen alone or together with the CNS retention in nearly 1/3 of adult cases.[28] The principal clinic presentation of neurobrucellosis in children is displayed as an acute meningitis or meningoencephalitis. Usually, brucellosis may not be included in CSF assessment for differential diagnosis. Therefore, the diagnosis of the condition can be difficult. Regularly, CT is assessed as normal in radiological evaluation in children. Cerebral atrophy, thickening of optical nerves, dilation of the lateral ventricle or cerebellar abscess is scarcely seen.[9–12] In our case, cranial CT demonstrated a communicating hydrocephalus. In several studies, granulomatous inflammation of the meninges and brain parenchyma was reported in radiological evaluation of patients with brucellosis. The reason that caused communicating hydrocephalus was reported as granulomatous inflammation of arachnoid’s villus.[13] In a recent article published by Panagariya et al., it was reported that a similar condition known as a pseudo-tumor accompanied 4% of the patients with neurobrucellosis.[14] In neurobrucellosis, pathological modifications can always be present in the meninges. Such pathological changes are more significantly seen in basal regions and are characterized by thickening of meninges, which depends on connective cell proliferation or acute/chronic inflammatory cellular infiltration and diffused interaction.[13]

osis, pathological modifications can always be present in the meninges. Such pathological changes are more significantly seen in basal regions and are characterized by thickening of meninges, which depends on connective cell proliferation or acute/chronic inflammatory cellular infiltration and diffused interaction.[13] The literature of pediatric neurobrucellosis displays therapeutic regimes of various periods and management regarding the treatment of the condition. The mentioned regimes consist of two or three drug combinations. The recent recommendations announced for the treatment of acute brucellosis involves a-6-week course of the therapy and addition of an aminoglycoside to avoid relapses.[915] Steroids are administered to treat arachnoid and cranial nerve retentions, optic neuropathy, and papilloedema. The management of adult acute neurobrucellosis includes the administration of a triple combination of antibiotics, which are the newest consensus, similar to the treatment of pediatric neurobrucellosis. Aminoglycosides are administered for a period of 2–4 weeks, while tetracycline or cotrimoxazole and rifampicin combinations are administered for a period of 8–12 weeks. The reason is that two combined drugs may lead to relapses or failures.

e the newest consensus, similar to the treatment of pediatric neurobrucellosis. Aminoglycosides are administered for a period of 2–4 weeks, while tetracycline or cotrimoxazole and rifampicin combinations are administered for a period of 8–12 weeks. The reason is that two combined drugs may lead to relapses or failures. The most ideal anti-brucellosis therapy in children is using aminoglycosides (gentamicin) which can be administered during the first 2–4 weeks. Additionally, rifampicin and doxycyline can be administered to children above 8 years of age. Cotrimoxazole should be administered to children less than 8 years of age, instead of doxycycline. Therapy must continue for at least 6 weeks, and may be continued further in chronic cases. Even after an appropriate therapy, symptoms may worsen due to extreme output of Brucella antigens and immune response. Steroids are indicated in such circumstances.[16] In a study carried out by Tanir et al., pediatric neurobrucellosis was diagnosed in 2 out of 90 patients with neurobrucellosis and they were treated by means of a triple antibiotic therapy. Two patients were referred to our clinic due to symptoms related with meningoencephalitis and cerebral edema was determined by cranial CT.[16] In another study carried out by Mantur et al., three pediatric brucellosis patients out of 93 were diagnosed with neurobrucellosis, while three of the patients presented chorea, peripheral neuritis, and meningitis. It was reported that Wright tests were positive for CSF, but the cultures remained negative. These patients were also treated by a combination of triple antibiotics.[17]

rucellosis patients out of 93 were diagnosed with neurobrucellosis, while three of the patients presented chorea, peripheral neuritis, and meningitis. It was reported that Wright tests were positive for CSF, but the cultures remained negative. These patients were also treated by a combination of triple antibiotics.[17] The most frequent complications of neurobrucellosis are meningitis and meningoencephalitis. Furthermore, a wide spectrum of complications such as cranial nerve retention, aneurysm, hydrocephalus, myelitis and parkinsonism can also arise with the condition.[1819] In our case, we primarily preferred to apply a ventricular drainage because of the possibility of contaminating the patient’s abdomen via seeding, whereas we were aware that the hydrocephalus was a transient condition. Daily CSF drainage by ventricular catheter helped very much to track the responses to the treatment and provide regression in findings related to intracranial pressure increase. The catheter was removed when discoloration of the CSF and the absence of growth in the CSF culture occurred. No sign of hydrocephalus was encountered during the follow-up. Hence, we suggest that there is no need to rush to place a V–P shunt in hydrocephalus cases induced by neurobrucellosis. However, cases must be followed as usual. In our case, ventricular catheter, triple antibiotic management and steroid therapy were very successful in the treatment of neurobrucellosis.

the follow-up. Hence, we suggest that there is no need to rush to place a V–P shunt in hydrocephalus cases induced by neurobrucellosis. However, cases must be followed as usual. In our case, ventricular catheter, triple antibiotic management and steroid therapy were very successful in the treatment of neurobrucellosis. To conclude, early diagnosis and appropriate treatment may provide a dramatic response in pediatric neurobrucellosis with a better prognosis than adults. In endemic regions, neurobrucellosis should be scrutinized in patients with hydrocephalus. Source of Support: Nil Conflict of Interest: None declared

Introduction Osteoblastoma is a benign vascular bone-forming tumor. It was independently described by Lichtenstein[1] and Jaffe.[2] Imageologically, these are osteolytic lesions larger than 2 cm with little or no evidence of perifocal sclerosis. Osteoblastomas account for approximately 1% of all primary bone tumors. About 30–40% of all cases of osteoblastoma involve the spine. The most common area of involvement is the cervical spine (20–40%) followed by lumbar spine. In the spine, most often the osteoblastoma is confined to the posterior elements. The mean age of presentation is 20.4 years, with case reports from 5 to 72 years. The main clinical feature is pain, followed by neurological symptoms and scoliosis. Frequently, there is an invasion of the epidural space surrounding the nerve roots and the cord leading to radiculopathy or cord compression. Recurrence rates after resection are described up to 10%.[3–7] Some authors have reported the possibility of malignant transformation.[8–10] Surgery is aimed at complete resection and protection of the sensitive neuroanatomic structures. Case Report An 8 year old female child came to us in nov 2008 with complaints of back pain and restriction of lower back movements since 1 year. Initially, the pain was aggravated on standing and while walking. Later, she had rest pain. She also had tingling and numbness along the dorsal aspect of her left leg since 6 months. This sensory disturbance was associated with slippage of footwear while walking.

in and restriction of lower back movements since 1 year. Initially, the pain was aggravated on standing and while walking. Later, she had rest pain. She also had tingling and numbness along the dorsal aspect of her left leg since 6 months. This sensory disturbance was associated with slippage of footwear while walking. On examination, there was localized swelling in the L4 region on the left side. There was also paraspinal muscle spasm. Lumbar spine movements were restricted. Localized and diffuse tenderness was present. Muscle power in extensor hallucis longus and extensor digitorum longus was grade 4 out of 5 in the left lower limb. Superficial sensory functions in the left L5 dermatome were diminished. Muscle stretch reflex in the left ankle was sluggish.

spine movements were restricted. Localized and diffuse tenderness was present. Muscle power in extensor hallucis longus and extensor digitorum longus was grade 4 out of 5 in the left lower limb. Superficial sensory functions in the left L5 dermatome were diminished. Muscle stretch reflex in the left ankle was sluggish. Radiological Investigations We thoroughly investigated the patient with plain roentgenograms, computed tomography (CT) scan and magnetic resonance imaging (MRI). Plain roentgenogram showed expansion of the left fourth lumbar pedicle, superior articular facet and transverse process[Figure 1]. Flecks of calcification were noted. Expansive osteolytic lesion with thin rim of cortex was found in the CT scan involving the spinous process, lamina, pedicle, superior articular process, transverse process and even into the bodyp[Figure 2]. Calcification was well defined in the CT scan. MRI images demonstrated lesion in the posterior elements with edema extending into the spinal canal, L4, L5 vertebral bodies and intervening disc[Figure 3]. Compression of thecal sac and L5 nerve root were seen. According to the Enneking score of benign musculoskeletal lesions, our tumor was classified as grade 2. Figure 1 Plain X-ray showing expansion of the left fourth lumbar pedicle: transverse process and superior facet Figure 2 Computed tomography scan images shows expansive osteolytic lesion with thin rim of cortex involving the spinous process, lamina, pedicle, transverse process and even into the body. Calcification is well defined

Radiological Investigations We thoroughly investigated the patient with plain roentgenograms, computed tomography (CT) scan and magnetic resonance imaging (MRI). Plain roentgenogram showed expansion of the left fourth lumbar pedicle, superior articular facet and transverse process[Figure 1]. Flecks of calcification were noted. Expansive osteolytic lesion with thin rim of cortex was found in the CT scan involving the spinous process, lamina, pedicle, superior articular process, transverse process and even into the bodyp[Figure 2]. Calcification was well defined in the CT scan. MRI images demonstrated lesion in the posterior elements with edema extending into the spinal canal, L4, L5 vertebral bodies and intervening disc[Figure 3]. Compression of thecal sac and L5 nerve root were seen. According to the Enneking score of benign musculoskeletal lesions, our tumor was classified as grade 2. Figure 1 Plain X-ray showing expansion of the left fourth lumbar pedicle: transverse process and superior facet Figure 2 Computed tomography scan images shows expansive osteolytic lesion with thin rim of cortex involving the spinous process, lamina, pedicle, transverse process and even into the body. Calcification is well defined Figure 3 Magnetic resonance imaging images show the lesion in posterior elements with edema extending into the spinal canal, L4, L5 vertebral bodies and intervening disc

Figure 2 Computed tomography scan images shows expansive osteolytic lesion with thin rim of cortex involving the spinous process, lamina, pedicle, transverse process and even into the body. Calcification is well defined Figure 3 Magnetic resonance imaging images show the lesion in posterior elements with edema extending into the spinal canal, L4, L5 vertebral bodies and intervening disc Intraoperative Features We found a firm, reddish to brown mass extending from the spinous process to the pedicle. Pseudocapsule with little vascularity was seen surrounding the mass. The tumor mass was friable. Complete excision of the tumor was possible with pseudocapsule in toto. There was no evidence of any necrosis or cystic spaces in the tumor. Postoperative Course The patient was relieved of back pain. The patient was eased of signs of neurological compression of the 5th lumbar nerve. No fresh deficits were noted postoperatively. Histopathological Report Gross description Multiple grey white to grey brown soft tissue bits with bony spicules.

Intraoperative Features We found a firm, reddish to brown mass extending from the spinous process to the pedicle. Pseudocapsule with little vascularity was seen surrounding the mass. The tumor mass was friable. Complete excision of the tumor was possible with pseudocapsule in toto. There was no evidence of any necrosis or cystic spaces in the tumor. Postoperative Course The patient was relieved of back pain. The patient was eased of signs of neurological compression of the 5th lumbar nerve. No fresh deficits were noted postoperatively. Histopathological Report Gross description Multiple grey white to grey brown soft tissue bits with bony spicules. Microscopic description Multiple sections show irregular interconnecting trabeculae of woven bone within a fibrous stroma[Figure 4]. The trabeculae show prominent osteoblastic rimming and, at places, the osteoblasts show an epitheloid appearance[Figure 5]. Stroma consists of spindle cells, thin-walled capillaries and fibrous tissue. Focally, stromal spindle cells show a storiform pattern. Multinucleated osteoclast giant cells are also seen. In addition, there are foci showing an aneurismal bone cyst (ABC) change and osteoclast giant cells[Figure 6]. There is no significant pleomorphism and mitotic activity in any of the cellular components. The features are consistent with “osteoblastoma with secondary ABC changes.” Figure 4 Histological sections showed a lesion comprised of haphazardly arranged woven bone trabeculae within a richly vascular stroma (H and E, ×100)

There is no significant pleomorphism and mitotic activity in any of the cellular components. The features are consistent with “osteoblastoma with secondary ABC changes.” Figure 4 Histological sections showed a lesion comprised of haphazardly arranged woven bone trabeculae within a richly vascular stroma (H and E, ×100) Figure 5 Higher magnification showing bony trabeculae with osteoblastic rimming (H and E, ×200) Figure 6 Areas of secondary aneurysmal cyst change represented by dilated cystic spaces filled with red blood cells (H and E, ×100) Discussion Osteoblastoma is a rare bone tumor and accounts for approximately 0.5–1% of all primary bone tumors.[11–13] Spinal involvement is described in 30–40% of all cases.[1113–15] In 20–40% of those, the cervical spine is affected.[3131516] Lumbar spine is the next most common affected area. Osteoblastoma is most frequently found in the posterior elements.[1517–19] Pain is usually the main clinical symptom, followed by neurologic symptoms, scoliosis and torticollis.[131516] Compared to osteoid osteoma, there is a higher rate of neurological deficits.[4151620] The large tumor mass can be associated with compression of the vertebral arteries if the tumor arises in the cervical spine. Osteoblastoma should be ruled out if patients present with neurological symptoms and pain over extended periods of time, especially at night.

e is a higher rate of neurological deficits.[4151620] The large tumor mass can be associated with compression of the vertebral arteries if the tumor arises in the cervical spine. Osteoblastoma should be ruled out if patients present with neurological symptoms and pain over extended periods of time, especially at night. Delay of diagnosis is very common, and seems to occur on average 6–12 months or later following the initial presentation.[131621–23] The treatment of choice for osteoblastoma is complete surgical resection. Preoperative interdisciplinary cooperation is necessary among the radiologist, neurosurgeons, vascular surgeons and orthopedic surgeons. Recurrence rates are described up to 10%, especially in Enneking Grade 3 lesions.[34] In some cases, there is a possibility of malignant transformation.[8–10] If complete resection is not possible, radiotherapy and, in some cases, chemotherapy seem to be alternative treatment options.[24–29] Source of Support: Nil Conflict of Interest: None declared.

Introduction There are only few case reports describing the association of novel influenza A (H1N1) virus with encephalopathy or encephalitis in children.[12] We report a previously well child with confirmed H1N1 infection who presented with seizures, CSF pleocytosis, abnormal EEG and focal changes on CT brain. Case Report A previously healthy eight-year-old boy was brought to our institute during the current H1N1 pandemic with moderate fever, cough and occipital headache since five days and one episode of generalized tonic clonic convulsion, associated with fever, just before admission. Immediately after admission, he developed right-sided focal convulsions which were controlled with intravenous midazolam. On admission, the patient was afebrile with a blood pressure of 110/70 mmHg, a heart rate of 82 beats per minute and a respiratory rate of 24 per minute. Oxygen saturation measured by pulse oximetry was 97% on room air, and a rapid assay for glucose was 96 mg/dl. Child was drowsy with a GCS scale of 10/15. Pupils were 2 mm bilaterally and reactive. Terminal neck stiffness was present. Rest of the CNS examination was normal.

inute and a respiratory rate of 24 per minute. Oxygen saturation measured by pulse oximetry was 97% on room air, and a rapid assay for glucose was 96 mg/dl. Child was drowsy with a GCS scale of 10/15. Pupils were 2 mm bilaterally and reactive. Terminal neck stiffness was present. Rest of the CNS examination was normal. Routine hemogram, blood gas and serum electrolytes were normal. A CT and lumbar puncture were performed in view of focal seizures and no improvement of sensorium after 4 hours of admission. CT was performed before lumbar puncture and showed ill-defined hypodensities (CT value 16-23 HU) in the subcortical white matter in the posterior parietal lobes bilaterally suggestive of encephalitis [Figure 1]. Lumbar puncture showed 40 cells/mm3, proteins were 48 mg/dl and glucose was 71 mg/dl with no organisms seen on gram stain. A chest X-ray revealed a small focal consolidation in the right lower zone. Nasopharyngeal aspirate specimen tested for H1N1 by RT-PCR tested positive. CSF was negative for H1N1 (by RT-PCR). CSF PCR for Herpes simplex virus was negative. Additional viruses such as enterovirus, varicella zoster, cytomegalovirus and Epstein-Barr virus tests could not be done due to financial constraints. Broad spectrum IV antibiotic, oseltamivir and acyclovir treatment were initiated. EEG showed evidence of focal slowing and sharp activity from the left centroparietal region [Figure 2]. The sensorium improved after 48 h and there were no further seizures. The patient was given oseltamivir for five days. He was discharged after 10 days of hospitalization.

mivir and acyclovir treatment were initiated. EEG showed evidence of focal slowing and sharp activity from the left centroparietal region [Figure 2]. The sensorium improved after 48 h and there were no further seizures. The patient was given oseltamivir for five days. He was discharged after 10 days of hospitalization. Figure 1 CT brain showing ill-defi ned hypodensities in subcortical white matter in both parietal lobes. Figure 2 EEG showing focal slowing and sharp activity from the left centroparietal region. Discussion The incidence of seasonal influenza-related neurologic complications has been estimated at 4 cases per 100,000 children per year.[3] Neurologic complications appear more commonly in children under six years of age.[4] Neurologic manifestations include seizures, loss of consciousness, cranial nerve abnormalities, focal motor deficits and gait abnormalities, among others.[4] The pathogenesis of influenza-associated neurologic disease remains unclear. Influenza RNA is rarely detected in the CSF of encephalopathic patients.[5] Other possible hypothesis is systemic immune response. High levels of proinflammatory cytokines (like IL-6 or TNF alpha) have been demonstrated in the serum and in the cerebrospinal fluid of children with influenza-associated encephalopathy. Markedly elevated serum IL-6 may predict a poor outcome in these patients.[6] Some authors have suggested that underlying metabolic disorders or genetic susceptibility may play a role in the pathogenesis.[7]

n demonstrated in the serum and in the cerebrospinal fluid of children with influenza-associated encephalopathy. Markedly elevated serum IL-6 may predict a poor outcome in these patients.[6] Some authors have suggested that underlying metabolic disorders or genetic susceptibility may play a role in the pathogenesis.[7] Neurological complications (seizures, encephalopathy, encephalitis) associated with H1N1 have now been described from some countries.[12] The severity of the neurologic disease in most of these cases was discrete, with no deaths and no neurologic sequelae at discharge. Similarly, our patient presented a favorable outcome with full recovery within a few days. Recently, however, few cases have been reported with severe neurological symptoms and signs and dominant residual neurological sequelae.[89] It is noteworthy that both these patients were adults. There is a single case report of an adolescent with neuropsychiatric symptoms associated with novel influenza A (H1N1).[10] EEG abnormalities were commonly observed in seasonal influenza-related encephalitis (86%) of patients in review of Amin et al.[4] Generalized or focal slowing on EEG can be a clue to the early diagnosis of encephalitis.[6] Three of the four patients in CDC report[1] had abnormal electroencephalograms. Our patient had focal slowing and sharp activity from the left centroparietal region

ted encephalitis (86%) of patients in review of Amin et al.[4] Generalized or focal slowing on EEG can be a clue to the early diagnosis of encephalitis.[6] Three of the four patients in CDC report[1] had abnormal electroencephalograms. Our patient had focal slowing and sharp activity from the left centroparietal region Kimura et al divided influenza-related brain changes into five categories based on the MR imaging and CT findings: normal (category 1), diffuse involvement of the cerebral cortex (category 2), diffuse brain edema (category 3), symmetric involvement of the thalamus (category 4), and focal encephalitis (category 5). Our patient’s CT findings are consistent with category 5 i.e. focal encephalitis. Lyon et al. reported CT and MR imaging findings in a 12-year-old girl infected with influenza A (H1N1) whose clinical course was complicated by acute necrotizing encephalopathy. The authors reported T2 hyperintensity and restricted diffusion in the thalami, cerebellar hemispheres and brain stem. Haktanir A. reported similar abnormalities and also bilateral perirolandic changes and diffuse meningeal enhancements.

(H1N1) whose clinical course was complicated by acute necrotizing encephalopathy. The authors reported T2 hyperintensity and restricted diffusion in the thalami, cerebellar hemispheres and brain stem. Haktanir A. reported similar abnormalities and also bilateral perirolandic changes and diffuse meningeal enhancements. Treatment of seasonal influenza in children with zanamivir and oseltamivir provided a more rapid resolution of symptoms and illness from 0.5 to 1.5 days.[8] No randomized, controlled studies have examined the antiviral treatment on influenza-related neurologic complications and it is not clear whether the treatment resulted in any clinical improvement or whether the neurologic symptoms were self-limited. Nonetheless, antiviral treatment should be initiated as soon as possible for any patient with neurologic symptoms related to H1N1 virus. To the best of our knowledge, our patient is the first reported case of H1N1-related neurological manifestation from India. Clinicians should be alert to the potential for neurologic complications associated with H1N1. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Epidermoid cyst/tumor is a benign lesion that may arise in the spine or may arise intracranially. It may be intradural (extraaxial) or extradural (usually arising in the diplopic space of calvaria). Intracranial epidermoid cyst accounts for 1.8 -2 % of all brain tumors.[1–3] The most common intracranial location for epidermoid tumors is the cerebellopontine angle cistern, which accounts for approximately 40–50% of the cases.[4] The other locations include fourth ventricle,[5] parasellar region, intraparenchymal, the pineal gland, the thalamus and the septum pellucidum.[6] These tumors may also be seen intrinsically within the brainstem.[7] In rare cases, they have been reported in other locations such as the lateral ventricles.[8] The term “mutism” describes patients who lack spontaneous speech despite the appearance of alertness.[9] According to Benson, there are five neurological conditions causing muteness.[10] The first is damage to the Broca’s area, which may lead to total absence of speech. The second is damage to the supplementary motor area of the dominant hemisphere and the third damage to the reticular formation of the mesencephalon, which may also leave a patient mute in the context of akinetic mustism. The fourth is pseudobulbar palsy due to diffuse bilateral cerebral hemispheric dysfunction. Muteness has also been described following bilateral thalamotomy (fifth) for Parkinson’s disease. In addition to these conditions, there are a few cases that developed transient mutism following removal of large vermian or fourth ventricle tumors.[11–17]

palsy due to diffuse bilateral cerebral hemispheric dysfunction. Muteness has also been described following bilateral thalamotomy (fifth) for Parkinson’s disease. In addition to these conditions, there are a few cases that developed transient mutism following removal of large vermian or fourth ventricle tumors.[11–17] Mutism is more commonly related to surgery in the posterior fossa tumor. It may be immediate or delayed. Virtually all cases of mutism occur within the first week of surgery, with 50% occurring within the first 2 days. Overwhelmingly, mutism of cerebellar origin has been reported following surgical interventions in the posterior fossa for tumors. However, there are other etiologies reported in the literature, including posterior fossa trauma, cerebellitis (inflammation of the cerebellum), cerebellar hemorrhage, embolic event and arterio-venous malformations. However, epidermoid cysts of the quadrigeminal cistern presenting with mutism are not known. We report a rare case of quadrigeminal cistern epidermoid with mutism. The causes, mechanism, pathophysiology, and management of such cases are discussed here.

ebellar hemorrhage, embolic event and arterio-venous malformations. However, epidermoid cysts of the quadrigeminal cistern presenting with mutism are not known. We report a rare case of quadrigeminal cistern epidermoid with mutism. The causes, mechanism, pathophysiology, and management of such cases are discussed here. Case Report A 16-year-old female presented to us with a 10-month history of headache of mild to moderate severity. She gave history of occasional vomiting during the previous months. Her parents revealed that their daughter was failing to speak anything for the last 6 months. On examination, the child was fully conscious, following simple commands but not verbalizing at all, but she was able to gesticulate for most of the queries. She had upward gaze paresis with normal insight and reaction. Otherwise, the rest of the ocular movements remained unrestricted. Fundi showed mild papilloedema. Her routine investigations remained within normal limits. A magnetic resonance imaging image revealed a large homogeneously hypointense mass on the T1-weighted images, which was hyperintense on the T2-weighted image to occupy an entire quadrigeminal cistern [Figure 1]. It was a very large mass, expanding the cistern with extension into the supracerebellar cistern. It was almost compressing the entire third ventricle anteriorly and also the splenium as well as the posterior half of the corpus callosum superiorly. It was causing a mass effect over the upper part of the midbrain. Considering the diagnosis of quadrigeminal cistern epidermoid, the patient was planned for surgery via an infratentorial and supracerebellar approach. During surgery, the epidermoid was encountered in the supracerebellar cistern itself. The epidermoid was encircling the vessels of the cistern, i.e. vein of Galen, basal veins of Rosenthal and posterior part of the internal cerebral veins. The entire pearly material of the epidermoid was delivered from all the sites gradually, leaving the thin capsule behind at places [Figure 2]. A large cavity was created and cerebrospinal fluid (CSF) started pouring in from the posterior third ventricle. Once the quadrigeminal cistern became clear, a ventricular catheter was left in the cavity and the wound was closed as per the standard norms. The patient was extubated following surgery. It was very surprising to note that the patient started verbalizing immediately after complete recovery from anesthesia.

ventricle. Once the quadrigeminal cistern became clear, a ventricular catheter was left in the cavity and the wound was closed as per the standard norms. The patient was extubated following surgery. It was very surprising to note that the patient started verbalizing immediately after complete recovery from anesthesia. The ventricular drain was taken out after 24 h as the CSF drained was clear. She made an uneventful recovery without any neurological deficit. She was discharged on the 7th postoperative day. The patient was continued on steroids for the next 2 weeks in order to take care of chemical meningitis. At the follow-up of 6 months, the girl was perfectly well. Figure 1 Preoperative T1-weighted axial magnetic resonance imaging showing a giant epidermoid cyst in the quadrigeminal cistern Figure 2 Postoperative T1-weighted axial magnetic resonance imaging showing near-total excision of the tumor; the wall is left behind

The ventricular drain was taken out after 24 h as the CSF drained was clear. She made an uneventful recovery without any neurological deficit. She was discharged on the 7th postoperative day. The patient was continued on steroids for the next 2 weeks in order to take care of chemical meningitis. At the follow-up of 6 months, the girl was perfectly well. Figure 1 Preoperative T1-weighted axial magnetic resonance imaging showing a giant epidermoid cyst in the quadrigeminal cistern Figure 2 Postoperative T1-weighted axial magnetic resonance imaging showing near-total excision of the tumor; the wall is left behind Discussion There are numerous case reports of mutism in the literature. In a report, a 14-year-old girl with epidermoid cyst in the 3rd ventricle manifested mutism. The cyst was tapped three times and, after each tapping, the patient improved, but after a few days the symptoms recurred.[18] Therefore, excision of cyst was performed. Postoperatively, in the first week, her speech was mainly limited to yes or no. On discharge from the hospital after 8 weeks of operation, she was still drowsy. At the 8-month follow-up, there was no mutism, but she was forgetful, and at times incontinent to urine. Meanwhile, during the course of her illness, there were symptoms of raised intracranial pressure (ICP). Her symptoms could be related to the direct pressure on the diencephalon level, with involvement of the hypothalamic–thalamic communication, with impairment of the afferent impulse. In our case, the cyst was located in the quadrigeminal cistern, and improvement was dramatic. This signifies the importance of some anatomical substrate responsible for mutism in close vicinity of the quadrigeminal cistern.

involvement of the hypothalamic–thalamic communication, with impairment of the afferent impulse. In our case, the cyst was located in the quadrigeminal cistern, and improvement was dramatic. This signifies the importance of some anatomical substrate responsible for mutism in close vicinity of the quadrigeminal cistern. Transient mutism has been reported in three cases following removal of the lateral and third ventricular mass following a transcallosal approach.[19] Mutism may be a result of division of the corpus callosum in such cases. Suppression of the limbic system caused by a lesion in the anterior cingulate gyrus, septum pellucidum, fornix, supplementary motor cortex, thalamus and basal ganglion may be responsible for reduced speech production.

a transcallosal approach.[19] Mutism may be a result of division of the corpus callosum in such cases. Suppression of the limbic system caused by a lesion in the anterior cingulate gyrus, septum pellucidum, fornix, supplementary motor cortex, thalamus and basal ganglion may be responsible for reduced speech production. Transient mutism had also been reported in a 65-year-old man following resection of anterior falx meningioma; the lesion being at the supplementary motor area may be responsible for postoperative mutism in this area.[20] A 13-year-old girl with exophytic pontine glioma developed mutism after total excision of tumor, which resolved after 6 months.[21] Guidetti observed total inability to speak in two patients in whom simultaneous and bilateral lesions of the dentate nuclei were stereotactically created in order to treat spasticity.[22] According to Robertson, cerebellar mutism syndrome occurred in 107 (24%) of 450 children with medulloblastoma. The symptom intensity was judged to be severe in 43%, moderate in 49% and mild in 8% of 107 patients. Mutism and ataxia were the features most frequently judged as severe. In both cohorts, preoperative brainstem invasion was the only feature that correlated with risk of mutism.[23]

of 450 children with medulloblastoma. The symptom intensity was judged to be severe in 43%, moderate in 49% and mild in 8% of 107 patients. Mutism and ataxia were the features most frequently judged as severe. In both cohorts, preoperative brainstem invasion was the only feature that correlated with risk of mutism.[23] Jonathan reported two patients, each of whom developed cerebellar mutism after tumor resection, using a posterior fossa approach. The first patient underwent gross total resection of a pineal region tumor via a supracerebellar approach.[24] The second patient underwent posterior fossa decompression for a left cerebellar hemispheric renal cell carcinoma metastasis with adjacent hemorrhage.[25] One patient displayed a variant of cerebellar mutism with severe ataxic dysarthria without complete absence of speech, whereas the other demonstrated frank mutism. After neuroimaging studies confirmed the absence of a surgically treatable postoperative cause for the patients’ symptoms, they were managed in a supportive fashion (e.g., speech therapy) and improved within 3.5 months and 1 year, respectively.

ut complete absence of speech, whereas the other demonstrated frank mutism. After neuroimaging studies confirmed the absence of a surgically treatable postoperative cause for the patients’ symptoms, they were managed in a supportive fashion (e.g., speech therapy) and improved within 3.5 months and 1 year, respectively. Forty-six cases of cerebellar mutism with mean age ±10.4 years following posterior cranial fossa surgery were studied. The pathological lesions were medulloblastomas in 33, astrocytomas in seven, ependymomas in four, metastases tumor in one and arteriovenous malformation in one. All mass lesions were considered to be large or very large.[26] The latency for the development of mutism in these cases lasted from 4 days to 4 months (mean 6.8 weeks). Dysarthric speech ensued after the mutism was resolved in 35 of 46 patients. The mutism was transient in all the cases.

riovenous malformation in one. All mass lesions were considered to be large or very large.[26] The latency for the development of mutism in these cases lasted from 4 days to 4 months (mean 6.8 weeks). Dysarthric speech ensued after the mutism was resolved in 35 of 46 patients. The mutism was transient in all the cases. It is apparent from all the above reports that neither the occurrence of mutism was a sole manifestation in different cases nor the improvement was very dramatic following surgery. But, in our case report, mutism was the only presenting complaint with epidermoid cyst in the quadrigeminal cistern, and its improvement immediately after surgery denotes that some anatomical structure in this region is directly responsible for such a severe mutism, if compromised significantly. Although this epidermoid was not confined only to the quadrigeminal cistern, it was sizeable enough to cause a significant compression over the surrounding structures. It denotes that either one anatomical structure or bilateral involvement of one or more than one structure was responsible for such a severe mutism. The mutism in our case could be due to pressure at the reticular formation of the mesencephalon, posterior corpus callosum, bilateral fornices, bilateral thalami or a combination of all these structures.[27]

l structure or bilateral involvement of one or more than one structure was responsible for such a severe mutism. The mutism in our case could be due to pressure at the reticular formation of the mesencephalon, posterior corpus callosum, bilateral fornices, bilateral thalami or a combination of all these structures.[27] Mutism is a well known event after surgical intervention of tumors of the posterior fossa. This event is thought to be more evident in cases of tumors in which the brain stem is in some way mistreated during surgery, but it is clear that this type of mutism is speech disturbance, a motor disorder in which the cerebellum temporarily loses its capacity to poke the phonic nuclei function efficaciously to the point of anorthia and mutism.[28] However, there are other types of mutism, which are language alterations secondary to cerebellum lesions. It seems probable that cerebellar mutism (secondary to posterior fossa involvement) is relatively different in relation to supratentorial mutism. The structures involved in both of these may vary. Conclusion It seems probable that the anatomical substrate for mutism lies in close vicinity to the quadrigeminal cistern, which may be either reticular formation of midbrain, fornices, thalami or corpus callosum. However, the possibility of bilateral involvement of these paired anatomical structures cannot be denied. Compression of the midbrain may also be responsible for such an event. Source of Support: Nil Conflict of Interest: None declared

Dear sir, Pelizaeus-Merzbacher’s disease (PMD) is a rare X-linked inherited disorder affecting myelination of the central nervous system. Pathologically, PMD, in contrast to other leukodystrophies like metachromatic leukodystrophy, adrenoleukodystrophy and multiple sclerosis, is a dysmyelinating rather than a demyelinating disorder. In demyelinating disorders, myelin is formed, deposited around the axons and then destroyed later. In dysmyelinating disorders such as PMD, normal myelination does not occur.[1] Two brothers (11-years-old and 10-years-old) presented to the pediatrics department with complaints of delayed development, ataxia, mental retardation, language impairment and difficulty in walking, which was progressive. They were born at full-term gestation without any adverse antenatal or perinatal course. Both patients attained head holding at 3 years. There was also history of nystagmus since they were 1 year old. There was no significant family history. On detailed physical and neurological examination, there was mental retardation, vertical peduncular nystagmus, hypereflexia and spasticity in both upper and lower limbs (more in the lower limbs) in both siblings, with a positive Babinski sign. They could walk with support and there was severe ataxia. There also was language impairment with dysmetria in the sibling. The upper limbs were normal. Their auditory and visual somatosensory-evoked potentials were normal.

upper and lower limbs (more in the lower limbs) in both siblings, with a positive Babinski sign. They could walk with support and there was severe ataxia. There also was language impairment with dysmetria in the sibling. The upper limbs were normal. Their auditory and visual somatosensory-evoked potentials were normal. Chest radiograph and all routine hematological investigations were normal. The patients were sent for a magnetic resonance imaging (MRI) of brain. MRI was carried out on 0.2 tesla Signa (GE systems, Waukesha, Wisconsin, USA) MRI with T2W, T1W and FLAIR sequences in all three planes. On MRI, there was diffuse and symmetrical subtle high signal intensity on the T2W sequence in the bilateral supratentorial white matter, brainstem and cerebellum in both siblings [Figure 1–4]. Thalami, basal ganglia and corpus callosum were normal. Figure 1 Magnetic resonance imaging T2W sequence in a 11-year-old child showing diffuse white matter hyperintensity (arrow) in the supratentorial white matter Figure 2 Magnetic resonance imaging T2W axial sequence in a 11-year-old child showing white matter hyperintensity (arrow) in the medulla Figure 3 T2W axial magnetic resonance image in a 10-year-old child showing bilateral symmetrical subtle hyperintense lesions (arrow) in the white matter Figure 4 T2W axial magnetic resonance image in a 10-year-old child showing subtle hyperintense lesions in the pontine white matter (arrow) Thus, all these clinical and radiological findings were diagnostic of PMD.

Figure 3 T2W axial magnetic resonance image in a 10-year-old child showing bilateral symmetrical subtle hyperintense lesions (arrow) in the white matter Figure 4 T2W axial magnetic resonance image in a 10-year-old child showing subtle hyperintense lesions in the pontine white matter (arrow) Thus, all these clinical and radiological findings were diagnostic of PMD. PMD and X-linked spastic paraplegia type 2 (SPG2)are two sides of the same coin. Both arise from mutations in the gene encoding myelin proteolipid protein 1 (PLP1). The disease spectrum for PMD and spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of PMD featuring hypotonia, respiratory distress, stridor, nystagmus and profound myelin loss. The frequency is estimated to be 1 case per 100,000–1,000,000 population.[2]

c paraplegia type 2 is extraordinarily broad, ranging from a spastic gait in the pure form of spastic paraplegia type 2 to a severely disabling form of PMD featuring hypotonia, respiratory distress, stridor, nystagmus and profound myelin loss. The frequency is estimated to be 1 case per 100,000–1,000,000 population.[2] PMD typically affects males, but female heterozygotes can be clinically affected, especially those who carry alleles that are relatively mild in males. Based on the time of onset and the clinical severity, PMD has traditionally been divided into four categories: classic, connatal, transitional and adult forms. The classic and connatal forms are the most common. Classic PMD has its onset during late infancy. Early symptoms include nystagmoid, dancing or trembling eye movements and delayed motor development followed by involuntary movements and spasticity. The course is usually protracted and it is often misdiagnosed as cerebral palsy. Connatal PMD is a rarer and more severe variant that begins at birth or in early infancy and has a more severe clinical course. Abnormal nystagmoid eye movements, extrapyramidal hyperkinesia, spasticity, optic atrophy and seizures also occur during the early stage.[34] Both our patients presented with the classic form of PMD as both had developed head holding and could walk, although with ataxia and spastic gait. There was no history of seizure or signs of optic atrophy.

ements, extrapyramidal hyperkinesia, spasticity, optic atrophy and seizures also occur during the early stage.[34] Both our patients presented with the classic form of PMD as both had developed head holding and could walk, although with ataxia and spastic gait. There was no history of seizure or signs of optic atrophy. Severe clinical syndromes (the connatal form) are typically caused by missense and other small mutations that affect critical positions in PLP1, whereas the milder spastic paraplegia syndrome is caused by mutations that presumably affect less-critical regions of the protein. The most common mutations that cause PMD are duplications of a region of the X chromosome that includes the entire PLP1 gene.[15] MRI is a useful method for assessing the dysmyelination of the cerebral white matter in PMD. MRI can show a hypomyelination pattern, i.e., reversal of the white matter signal intensity on T1- and T2-weighted images. In PMD, MR images generally show either diffuse or patchy (tigroid) T2 hyperintensity in the cerebellar, brain stem and supratentorial white matter. This appearance is believed to be the result of the lack of formation of myelin (hypomyelination or dysmyelination). Diffuse, confluent involvement is usually seen in the severe connatal form, whereas the tigroid pattern is more common in the patients with SPG2. Atrophy and decreased white matter volume may also occur.[6] In our both cases, there was evidence of diffuse white matter T2W hyperintensity in the supratentorial white matter and brainstem white matter. There was mild cerebral atrophy.

nnatal form, whereas the tigroid pattern is more common in the patients with SPG2. Atrophy and decreased white matter volume may also occur.[6] In our both cases, there was evidence of diffuse white matter T2W hyperintensity in the supratentorial white matter and brainstem white matter. There was mild cerebral atrophy. Recently, few reports have described proton MRI spectroscopy findings in this disease, with diffuse or focal reductions in N-acetylaspartate in the affected white matter. These reductions seemed to be consistent with axonal damage. In addition, mild increases in choline and creatine levels were observed, which may have been due to astrocytic changes.[7] We cannot perform spectroscopy because of equipment limitation. In conclusion, the diagnosis of PMD should be considered in neonates or children with such clinical features and MRI findings.

Dear Sir, Abdominal epilepsy (AE) is an uncommon syndrome in which gastrointestinal complaints, mostly abdominal pain, are a result of a seizure activity. It is characterized by paroxysmally diverse abdominal symptoms, definite EEG abnormalities and favourable response to the introduction of epilepsy drugs[1] Gastrointestinal signs and symptoms may occur as the sole manifestation of a simple partial seizure or as the initial manifestation of a complex partial seizure. In the absence of impaired consciousness, the epileptic cause of these episodes can be difficult to diagnose and may lead to exhaustive gastrointestinal investigation. We report a patient with recurrent episodes of severe abdominal pain, without obvious associated symptoms suggestive of central nervous system (CNS) abnormalities, but with EEG abnormalities and a positive response to anticonvulsive therapy. A 14-year-old girl was referred to our hospital because of attacks of recurrent abdominal pain for the past 4 years. She was born after uncomplicated pregnancy and delivery and she had normal development and schooling. There was no prior significant illness. The father of the child suffered from peptic ulcer.

It is characterized by paroxysmally diverse abdominal symptoms, definite EEG abnormalities and favourable response to the introduction of epilepsy drugs[1] Gastrointestinal signs and symptoms may occur as the sole manifestation of a simple partial seizure or as the initial manifestation of a complex partial seizure. In the absence of impaired consciousness, the epileptic cause of these episodes can be difficult to diagnose and may lead to exhaustive gastrointestinal investigation. We report a patient with recurrent episodes of severe abdominal pain, without obvious associated symptoms suggestive of central nervous system (CNS) abnormalities, but with EEG abnormalities and a positive response to anticonvulsive therapy. A 14-year-old girl was referred to our hospital because of attacks of recurrent abdominal pain for the past 4 years. She was born after uncomplicated pregnancy and delivery and she had normal development and schooling. There was no prior significant illness. The father of the child suffered from peptic ulcer. The pain was colicky and paroxysmal in nature, distributed mainly in the epigastric region; it was nonradiating and had no apparent relationship with meals. This intense pain was almost always accompanied with pallor and dizziness. Several times, she reported occurrence of nausea, vomiting and diarrhea after these attacks of pain. There was no alteration of consciousness and she had not experienced headaches. She never had convulsions. Each episode used to last for 10–30 min, with spontaneous resolution of symptoms, and recurred three to four-times a month. During the examination at gastroenterology unit the girl was treated with analgesics, antihistaminic (H2 blockers) and unspecific and placebo therapy such as vitamin B6 without any clinical improvement.

pisode used to last for 10–30 min, with spontaneous resolution of symptoms, and recurred three to four-times a month. During the examination at gastroenterology unit the girl was treated with analgesics, antihistaminic (H2 blockers) and unspecific and placebo therapy such as vitamin B6 without any clinical improvement. Physical examination, including neurological status, was normal. Laboratory studies were within normal limits, including complete blood count, liver function tests, amylase, Helicobacter pylori IgG titer, stool examinations for ova and parasites. Abdominal ultrasound and upper gastrointestinal endoscopy were normal. She underwent an EEG examination, which revealed repetitive spikes, sharp waves over the right central and temporal electrodes with secondary generalization [Figures 1, 2]. Magnetic resonance imaging of the brain was performed (1-tesla field strength MRI- T1, T2 sequences plus FLAIR) which failed to detect any structural anomalies. The child was diagnosed as having temporal lobe – “abdominal” epilepsy – and treatment with carbamazepine was initiated. This was followed by a significant clinical improvement, and she has been asymptomatic during the following 2 years of follow-up. Figure 1 EEG record showing sharp waves and spikes from the right centrotemporal region Figure 2 EEG recorded on a regular ambulatory check up after introducing carbamazepine treatment. Sharp waves and spikes are seen over the right temporal region with secondary generalization

She underwent an EEG examination, which revealed repetitive spikes, sharp waves over the right central and temporal electrodes with secondary generalization [Figures 1, 2]. Magnetic resonance imaging of the brain was performed (1-tesla field strength MRI- T1, T2 sequences plus FLAIR) which failed to detect any structural anomalies. The child was diagnosed as having temporal lobe – “abdominal” epilepsy – and treatment with carbamazepine was initiated. This was followed by a significant clinical improvement, and she has been asymptomatic during the following 2 years of follow-up. Figure 1 EEG record showing sharp waves and spikes from the right centrotemporal region Figure 2 EEG recorded on a regular ambulatory check up after introducing carbamazepine treatment. Sharp waves and spikes are seen over the right temporal region with secondary generalization Recurrent episodes of abdominal pain are common in childhood. In a minority of patients in which an abdominal pathology is excluded, a neurological cause should be considered. Among the diagnostic possibilities are migraine and AE.[2] Pain as an ictal symptom – distinct from other sensory phenomena – is a rare epileptic feature. In Young and Blume’s study out of 858 epileptic patients, only 24 (2.8%) experienced pain as a prominent part of their seizures. Most of them reported headaches (11 of 24), or unilateral face and body pain (10 of 24). Only 3 of them or 0.3% of their patients with epilepsy had ictal abdominal pain.[3] Abdominal epileptic pain was usually described as a severe and sharp sensation (“like a knife”), mostly in the periumbilical localization, but it was also experienced in the whole abdomen or in just one quadrant of the abdomen with a variable duration.[3 4]

% of their patients with epilepsy had ictal abdominal pain.[3] Abdominal epileptic pain was usually described as a severe and sharp sensation (“like a knife”), mostly in the periumbilical localization, but it was also experienced in the whole abdomen or in just one quadrant of the abdomen with a variable duration.[3 4] Focal epilepsy presenting with gastrointestinal symptoms is now considered a definite clinical entity in the semiological seizure classification.[5] A review of the history of this syndrome yielded 36 cases reported in the English literature in the past 34 years.[1] The pathophysiology of abdominal epilepsy remains unclear. Several mechanisms relating brain electrical activity to abdominal pain have been suggested. One of the possible explanations is that temporal lobe seizure activity usually arises in or involves the amygdala. Therefore the patients who have the temporal lobe epilepsy may have gastrointestinal symptoms, since discharges arising in the amygdala can be transmitted to the gut via dense direct projections to the dorsal motor nucleus of the vagus. In addition, sympathetic pathways from the amygdala to the gastrointestinal tract can be activated via the hypothalamus.

emporal lobe epilepsy may have gastrointestinal symptoms, since discharges arising in the amygdala can be transmitted to the gut via dense direct projections to the dorsal motor nucleus of the vagus. In addition, sympathetic pathways from the amygdala to the gastrointestinal tract can be activated via the hypothalamus. Criteria for the diagnosis of AE are: (1) otherwise unexplained, paroxysmal gastrointestinal complaints, (2) symptoms of a CNS disturbance; (3) an abnormal EEG with findings specific for a seizure disorder and (4) improvement with anticonvulsant drugs. Gastrointestinal manifestations include recurrent abdominal pain, nausea, vomiting, bloating and diarrhea, and a similar diversity of CNS manifestations has also been reported, including confusion, fatigue, headache, dizziness and syncope. In patients with abdominal symptoms and headache, it is often difficult to differentiate abdominal migraine from AE because of the overlap of symptoms. The most obvious clinical difference is the duration of the symptoms, hours in migraine (4-72h) compared with several minutes in epilepsy.[6] Thus, EEG as a simple and noninvasive investigation may be helpful in differentiating between the two entities. Patients with AE usually have specific EEG abnormalities, particularly a temporal lobe seizure disorder, although some studies had reported an extratemporal origin (parietal or even frontal).[78] Sustained response to anticonvulsants has been accepted as one of the criteria for the diagnosis of AE. However, there are no recommendations on the choice of the anticonvulsant.

In patients with abdominal symptoms and headache, it is often difficult to differentiate abdominal migraine from AE because of the overlap of symptoms. The most obvious clinical difference is the duration of the symptoms, hours in migraine (4-72h) compared with several minutes in epilepsy.[6] Thus, EEG as a simple and noninvasive investigation may be helpful in differentiating between the two entities. Patients with AE usually have specific EEG abnormalities, particularly a temporal lobe seizure disorder, although some studies had reported an extratemporal origin (parietal or even frontal).[78] Sustained response to anticonvulsants has been accepted as one of the criteria for the diagnosis of AE. However, there are no recommendations on the choice of the anticonvulsant. Our patient felt paroxysmal episodes of severe abdominal pain, mostly as an isolated gastrointestinal symptom, without any obvious signs of CNS involvement, such as headaches and loss or alteration of consciousness. With EEG monitoring, these episodes of abdominal pain were identified as a prominent symptom of partial seizure generalized from the right temporal lobe discharges. There was also a positive response to anticonvulsant treatment with carbamazepine and thus our patient fulfilled all the criteria for the diagnosis of AE. As a conclusion, in patients who experience paroxysms of abdominal pain, nausea and vomiting with or without CNS manifestations, a possibility of AE should be considered after exclusion of more common etiologies for the presenting complaints.

Sir, Bloom’s syndrome is an autosomal recessive disorder characterized by distinctive faces, stunted growth, telangiectatic facial erythema, abnormal immune response and predisposition to various malignancies. Cytogenetically, it is characterized by increased frequency of spontaneous sister chromatid exchange. A 10-year-old boy born of third degree consanguineous parents was referred by pediatricians with complaints of rashes over face which started 6 months after birth. History suggestive of photosensitivity was present. Examination revealed erythematous scaly plaques with telangiectasia over butterfly area of face, neck, ears, and lower lip (mainly over the sun-exposed areas) [Figure 1]. The child also had prominent nose, narrow and slender faces. His physical growth was stunted. On the basis of the above mentioned features, we diagnosed Bloom’s syndrome in this patient. Figure 1 Patient of Bloom’s syndrome showing scaly plaques over malar area Cytogenetic study was done for the patient. Leukocyte culture of the individual showed a normal karyotype 46 XY but with 20% aberrant metaphases with chromosomes showing breaks, fragments, and micronucleus [Figures 2,3]. Fifty metaphases were analyzed. The frequency of satellite association (SA) was 32% [Figure 4]. Similar cytogenetic study was also done on four controls and results revealed average of only 11% SA. Figure 2 Quadriradial figure of chromosome Figure 3 Micronucleus detected Figure 4 Chromosomal fragments

Cytogenetic study was done for the patient. Leukocyte culture of the individual showed a normal karyotype 46 XY but with 20% aberrant metaphases with chromosomes showing breaks, fragments, and micronucleus [Figures 2,3]. Fifty metaphases were analyzed. The frequency of satellite association (SA) was 32% [Figure 4]. Similar cytogenetic study was also done on four controls and results revealed average of only 11% SA. Figure 2 Quadriradial figure of chromosome Figure 3 Micronucleus detected Figure 4 Chromosomal fragments In vitro leukocyte culture of the same child when exposed to ultraviolet (UV) radiation showed 80% aberrant metaphase with chromosomes showing quadriradial figure, multiple breaks, gaps, fragments, and increased incidence of micronucleus [Figure 5]. The frequency of SA also increased to 84%, confirming that when there is an increased evidence of unstable chromosome on exposure to UV radiation, there is also an increased incidence of SA, an indicator of defect in the DNA repair mechanism. Figure 5 Acrocentric association of chromosomes In acrocentric association, satellite chromosomes, that is, chromosomes nos. 13, 14, 15, 21, and 22, come closer at the tip of short arm due to some sticky substance formed during meiosis. Acrocentric association has been detected earlier in some syndromes including Down’s syndrome.[1] Acrocentric association results in increased incidence of chromosomal rearrangements and later on, can cause chromosomal diseases.[2]

come closer at the tip of short arm due to some sticky substance formed during meiosis. Acrocentric association has been detected earlier in some syndromes including Down’s syndrome.[1] Acrocentric association results in increased incidence of chromosomal rearrangements and later on, can cause chromosomal diseases.[2] Chromosomal breakage and rearrangement occur spontaneously in three disorders namely Bloom’s syndrome, Fanconi’s anemia, and Ataxia Telangiectasia.[3] Bloom’s syndrome is characterized by the presence of quadriradial chromosomes.[4] These are chromosome with four arms, formed by recombination between two chromosomes. It is found only in 0.5 to 14% of cases. The diagnosis is confirmed by the demonstration of spontaneously enhanced formation of sister chromatid exchange.[4] Micronucleus frequency in peripheral blood lymphocytes is extensively used in cytogenetics to evaluate the presence and extent of chromosomal damage.[5] It is regarded as the most sensitive and convenient method to detect chromosomal damage.[4] It is the result of chromosomal breakage due to malrepaired or unrepaired DNA lesion, or chromosomal malsegregation due to mitotic malfunction.[5] It originates from chromosome fragment or whole chromosome, not included in the main daughter nuclei during nuclear division.[5] Association between micronucleus induction and cancer development or cancer-prone congenital disease like Bloom’s syndrome has been supported by a number of observations.[5]

c malfunction.[5] It originates from chromosome fragment or whole chromosome, not included in the main daughter nuclei during nuclear division.[5] Association between micronucleus induction and cancer development or cancer-prone congenital disease like Bloom’s syndrome has been supported by a number of observations.[5] Authors feel that cytogenetic studies in genodermatoses like Bloom’s syndrome would help not only to prevent the severity of the disease with passage of time, but also to detect skin malignancies that are liable to occur.

The lesions of the pineal gland, posterior third ventricle and the dorsal midbrain have been approached by many approaches. All of them require precision and knowledge of the anatomy of this region. Horsley was the first to attempt surgery for these lesions. The credit for the first successful excision of tumors of this region goes to Krause in 1913 who utilized the infratentorial supracerebellar approach,[1] an approach revived by Stein in 1971. The alternative approaches to this region are Jamieson’s[2] and Poppen’s[3] occipital transtentorial approach, Van Wagenen’s posterior transventricular approach[4] and Dandy’s posterior transcallosal approach.[5–7] Infratentorial Supracerebellar Approach This is the commonly used approach for lesions of pineal gland, dorsal midbrain and superior vermis [Figures 1–5]. Figure 1 Patient 1: (A-C): This 8-year old boy presented with raised pressure, bilateral VIth nerve and upward gaze palsy of 8-months duration. His contrast enhanced CT scan showed a uniformly enhancing, infiltrative, posterior third ventricular lesion reaching the anterior third ventricle nearly until the foramen of Monro and causing hydrocephalus. The right ventriculoperitoneal shunt initially placed at another center got blocked and required revision.

tion. His contrast enhanced CT scan showed a uniformly enhancing, infiltrative, posterior third ventricular lesion reaching the anterior third ventricle nearly until the foramen of Monro and causing hydrocephalus. The right ventriculoperitoneal shunt initially placed at another center got blocked and required revision. Figure 2 Patient 1: A and B: Contrast enhanced axial T1-weighted MRI following the ventriculoperitoneal shunt revision showed the uniformly enhancing infiltrative lesion occupying the posterior third ventricular region and the quadrigeminal cistern. C: T2-weighted axial image showing the lesion to be heterogeneously iso- to hyperintense. D: Sagittal contrast enhanced T1 image showing the lesion occupying the third ventricle along the internal cerebral vein almost reaching upto the foramen of Monro. E: The coronal-enhanced T1 image showing the vertical extent of the lesion from the foramen of Monro to the midbrain. F: The diffusion-weighted image showing restriction of diffusion within the lesion.

g the lesion occupying the third ventricle along the internal cerebral vein almost reaching upto the foramen of Monro. E: The coronal-enhanced T1 image showing the vertical extent of the lesion from the foramen of Monro to the midbrain. F: The diffusion-weighted image showing restriction of diffusion within the lesion. Figure 3 Patient 1: Infratentorial, supracerebellar approach was adopted in sitting position. A: A midline linear incision through the skin and ligamentum nuchae exposed the occipital bone from the external occipital protuberance to the foramen magnum. The craniectomy revealed the exposed rim of the transverse and occipital sinus, and the dura covering bilateral cerebellar hemispheres and foramen magnum. B: The dura is opened with a “Y” shaped incision coagulating the occipital sinus and the annular sinus (the latter at the foramen magnum) and refl ected superiorly along the transverse sinus. C: The anastomotic veins between the superior surface of cerebellar hemispheres and the tentorium are coagulated allowing the cerebellum to fall with gravity away from the tentorium and creating the space for the surgical approach. D: The arachnoid covering the tumor in the posterior third ventricular region and the precentral cerebellar vein in the midline are seen due to gravity-assisted fall of the cerebellum.

m are coagulated allowing the cerebellum to fall with gravity away from the tentorium and creating the space for the surgical approach. D: The arachnoid covering the tumor in the posterior third ventricular region and the precentral cerebellar vein in the midline are seen due to gravity-assisted fall of the cerebellum. Figure 3 Patient 1: E: The precentral cerebellar vein is coagulated and divided. F: The arachnoid covering the tumor is removed exposing the tumor surface. G: The tumor is gently coagulated and removed in a piecemeal manner. H: The opening of the third ventricle following tumor removal drains CSF. Figure 4A Patient 1: Photomicrograph showing round to polygonal tumor cells disposed in groups, displaying conspicuous nucleoli at places and variable amount of pale to amphophilic cytoplasm. The groups of tumor cells are separated by fibrous septa infiltrated by small mature lymphocytes (H and E, ×400) Figure 4B Patient 1: Photomicrograph showing tumor cell positive for CD 117 (Immunohistochemical stain; ×400) Figure 4C Patient 1: Photomicrograph showing tumor cell positive for placenta-like alkaline phosphatase (PLAP) (Immunohistochemical stain; 400×) The histopathology and immunohistochemistry confirmed the presence of a GERMINOMA. Figure 5 A: Patient 1: Axial T2; B: axial contrast T1; and, C: Sagittal contrast T1-weighted images after surgery and radiotherapy showing a small nonenhancing component of the residual lesion with no hydrocephalus.

Figure 4C Patient 1: Photomicrograph showing tumor cell positive for placenta-like alkaline phosphatase (PLAP) (Immunohistochemical stain; 400×) The histopathology and immunohistochemistry confirmed the presence of a GERMINOMA. Figure 5 A: Patient 1: Axial T2; B: axial contrast T1; and, C: Sagittal contrast T1-weighted images after surgery and radiotherapy showing a small nonenhancing component of the residual lesion with no hydrocephalus. Advantage The midline trajectory of the approach to the tumor avoids injury to the deep venous channels (the internal cerebral veins draining into the vein of Galen that in turn drains into the straight sinus; and, the basal vein of Rosenthal that traverses the ambient cistern and drains into the vein of Galen) that usually are located superior to the lesion. The approach is toward the center of the tumor from where it may be extended eccentrically. There is a good exposure with minimal neural damage. The sitting position offers a good exposure with gravity-assisted drainage of blood and cerebrospinal fluid (CSF). Disadvantage Lesions with a significant component extending laterally upto the trigone of the lateral ventricle or lesions involving the corpus callosum are difficult to completely remove by this approach and require supratentorial approaches. The sitting position in which this surgery is usually performed increases the risk of air embolism, tension pneumocephalus and hyperflexion injury leading to quadriplegia.[7]

ral ventricle or lesions involving the corpus callosum are difficult to completely remove by this approach and require supratentorial approaches. The sitting position in which this surgery is usually performed increases the risk of air embolism, tension pneumocephalus and hyperflexion injury leading to quadriplegia.[7] Position The sitting position is the preferred position for this approach although a three-fourth prone or lateral decubitus position has also been used. The latter positions are used in the pediatric age group particularly under 2 years of age. The head in the sitting position must be adequately flexed to align the tentorium in the horizontal position for an adequate exposure of the supravermian infratentorial space. Incision A midline vertical incision extending from the C3 spinous process to 2-3 cm above the external occipital protuberance is utilized. The muscles of the suboccipital and posterior cervical region are retracted after dividing the avascular ligamentum nuchae in the midline. The pericranium covering the occipital bone is dissected off the bone. The suboccipital craniectomy or craniotomy exposes the rim of the torcula and the transverse sinus superiorly and reaches inferiorly until the foramen magum.

ervical region are retracted after dividing the avascular ligamentum nuchae in the midline. The pericranium covering the occipital bone is dissected off the bone. The suboccipital craniectomy or craniotomy exposes the rim of the torcula and the transverse sinus superiorly and reaches inferiorly until the foramen magum. Operative Steps The dura is opened in a “V” or a “Y” shaped manner with the base toward the transverse sinus. In case the surgical field of view is not adequate, the bridging veins from the dorsal cerebellar surface to the tentorium may be sacrificed to permit the gravity-dependent descent of the cerebellum. Gentle retraction with self-retaining retractors aids in depressing the cerebellum for establishment of the operative corridor between its superior vermian surface and the inferior surface of tentorium.

rsal cerebellar surface to the tentorium may be sacrificed to permit the gravity-dependent descent of the cerebellum. Gentle retraction with self-retaining retractors aids in depressing the cerebellum for establishment of the operative corridor between its superior vermian surface and the inferior surface of tentorium. The arachnoid of the quadrigeminal cistern is thickened and opaque. The midline precentral cerebellar vein traversing vertically downward in the midline just anterior to the thickened arachnoid may either be retracted or coagulated. This permits a trajectory toward the quadrigeminal cistern, velum interpositum, collicular plates and the third ventricle. Once the tumor is encountered, internal decompression is done followed by careful dissection from the surrounding structures including the deep venous system superiorly and the brain-stem, collicular plates and the thalamus anteriorly. Following tumor decompression, the third ventricular cavity and the lining ependyma is well-visualized right until the foramen of Monro. In case of dense adhesions of the tumor capsule to the surrounding vital structures, it is preferable to leave parts of the capsule than risk retraction injury by persisting with its complete removal. In patients with significant hydrocephalus, a preoperative CSF diverting procedure may be employed before the definitive surgery.

The arachnoid of the quadrigeminal cistern is thickened and opaque. The midline precentral cerebellar vein traversing vertically downward in the midline just anterior to the thickened arachnoid may either be retracted or coagulated. This permits a trajectory toward the quadrigeminal cistern, velum interpositum, collicular plates and the third ventricle. Once the tumor is encountered, internal decompression is done followed by careful dissection from the surrounding structures including the deep venous system superiorly and the brain-stem, collicular plates and the thalamus anteriorly. Following tumor decompression, the third ventricular cavity and the lining ependyma is well-visualized right until the foramen of Monro. In case of dense adhesions of the tumor capsule to the surrounding vital structures, it is preferable to leave parts of the capsule than risk retraction injury by persisting with its complete removal. In patients with significant hydrocephalus, a preoperative CSF diverting procedure may be employed before the definitive surgery. Complications Postoperative complications include CSF leak and acute or delayed hemorrhage.[6] This may be due to bleeding within the residual tumor. Alternatively, a point of bleeding may be missed during hemostasis due to gravity-dependent collapse of the bridging veins in sitting position. The rent may open up in the postoperative period when the patient is made supine and his blood pressure increases on reversal from anesthesia. Hemorrhagic venous infarction may also occur due to coagulation of a bridging vein.

uring hemostasis due to gravity-dependent collapse of the bridging veins in sitting position. The rent may open up in the postoperative period when the patient is made supine and his blood pressure increases on reversal from anesthesia. Hemorrhagic venous infarction may also occur due to coagulation of a bridging vein. Occipital transtentorial approach This approach [Figures 6–9] provides adequate exposure of both the superior and inferior surfaces of the tentorial notch and hence is excellent for tumors straddling the tentorial notch. This approach is also useful for tumors situated above the confluence of the deep venous system and for tumors extending laterally into the trigone of the lateral ventricle.[7] Figure 6 Patient 2: A, B: This 16-year-old girl presented with symptoms of raised intracranial pressure, Perinaud’s syndrome and gait ataxia. Her axial contrast T1-weighted images showed the nonenhancing irregular lesion in the posterior third ventricular region and the ambient and quadrigeminal cisterns. There is mild hydrocephalus with dilated anterior third ventricle and bilateral lateral ventricles. C: Sagittal, and D: Coronal contrast T1 images showing the vertical extent of the lesion along the brain stem and its extension into the supratentorial compartment after occupying the tentorial incisural space. The superior vermis of the cerebellum appears flattened by the lesion. E, F: Diffusion-weighted axial images showing the restriction of diffusion in the lesion.

ing the vertical extent of the lesion along the brain stem and its extension into the supratentorial compartment after occupying the tentorial incisural space. The superior vermis of the cerebellum appears flattened by the lesion. E, F: Diffusion-weighted axial images showing the restriction of diffusion in the lesion. Figure 7 Patient 2: A: Right occipital craniotomy, posterior interhemispheric, transtentorial approach adopted in prone position with the table tilted about 20-30° toward the side of approach to permit a gravity-dependent spontaneous retraction of the right parieto-occipital lobe facilitating the approach through the posterior interhemispheric corridor that is usually devoid of bridging veins. B: The dural exposure after the craniotomy that extends until the rim of the torcula and transverse sinus inferiorly and the posterior part of the superior sagittal sinus medially. The dura is cut in a square shape and refl ected medially based upon the superior sagittal sinus. C: Gentle lateral retraction of the right parieto-occipital lobe exposes the falx cerebri and its junction with the tentorium that encloses the straight sinus within its leaves at the junctional area. D: The tentorium is traced until its incisura parallel to the straight sinus. The epidermoid tumor is visible within its arachnoid covering at the incisura. E: The tentorial surface is coagulated and divided parallel and slightly away from the straight sinus and the arachnoidal covering of the epidermoid removed exposing the tumor. F: The tumor is removed in a piecemeal manner with the help of microdissectors, gentle irrigation and suction.

chnoid covering at the incisura. E: The tentorial surface is coagulated and divided parallel and slightly away from the straight sinus and the arachnoidal covering of the epidermoid removed exposing the tumor. F: The tumor is removed in a piecemeal manner with the help of microdissectors, gentle irrigation and suction. Figure 7 Patient 2: G: Following tumor removal, the superior surface of cerebellum and brain stem are exposed. The divided tentorium is being retracted with stay sutures providing an adequate corridor. There is a thin capsule of the epidermoid still lining the brain stem, and H: the superior surface of the cerebellum. I: The vein of Galen and basal vein of Rosenthal, and J: the posterior thalamus, collicular plate and the quadrigeminal cistern are visible following tumor removal. K: The cerebellum, brain stem, and, L: the lax brain after the procedure. A bridging vein at the anterior end of the corridor is protected with surgicel. Figure 8 Patient 2: Photomicrograph showing a cyst lined by thinned out stratified squamous epithelium filled with keratin material suggestive of epidermoid (H and E, ×400) Figure 9 Patient 2: A: axial T1; B: axial T2; C, D: sagittal T1; E: sagittal T2; and F: diffusion-weighted axial MR images showing the postoperative tumor cavity after total excision of the lesion. Position The patient is placed in prone position or lounging position. In prone position, the table is slightly tilted to the ipsilateral side to facilitate gravity-dependent retraction of the occipital lobe from the falx cerebri.

Figure 9 Patient 2: A: axial T1; B: axial T2; C, D: sagittal T1; E: sagittal T2; and F: diffusion-weighted axial MR images showing the postoperative tumor cavity after total excision of the lesion. Position The patient is placed in prone position or lounging position. In prone position, the table is slightly tilted to the ipsilateral side to facilitate gravity-dependent retraction of the occipital lobe from the falx cerebri. Incision A square or triangular scalp flap with the longitudinal limb being in the midline and extending from just below the external occipital protuberance to 6-8 cm superior to this point and curving laterally and downwards is used. Preferably the approach is carried out from the nondominant side. Operative steps The craniotomy is fashioned to expose the rim of the transverse sinus inferiorly, the superior sagittal sinus medially and it extends laterally upto 5-6 cm. The dural opening may be as two triangular flaps with the base toward the transverse and sagittal sinuses, respectively, or as a square flap medially toward the superior sagittal sinus. In case hydrocephalus is coexistent, the posterior horn of the lateral ventricle may be tapped to facilitate CSF drainage and brain retraction.

opening may be as two triangular flaps with the base toward the transverse and sagittal sinuses, respectively, or as a square flap medially toward the superior sagittal sinus. In case hydrocephalus is coexistent, the posterior horn of the lateral ventricle may be tapped to facilitate CSF drainage and brain retraction. The occipital lobe is gently retracted laterally. This maneuver is facilitated by the fact that bridging veins between the cerebellar surface and the superior sagittal sinus are few and small and may usually be divided with very little risk of venous infarction of the occipital lobe. The falx cerebri, the tentorium and the dural covering of the straight sinus at the junctional region of these dural folds are visualized from the region of the torcula to the tentorial incisura. The tentorium is coagulated parallel and lateral to the straight sinus (avoiding any venous lakes in close proximity to the straight sinus) and divided until the incisural edge thereby bringing the superior cerebellar surface in view. The divided leaflets of the tentorium are reflected using stay sutures. The opaque and tough arachnoid over the deep veins is left intact if the tumor is below their level. Working in the arachnoidal plane below the major veins, lesion of the posterior third ventricular regions are exposed. The tumor removal is then carried out in a piecemeal manner. Following tumor removal, the brain stem, the collicular plate and the posterior thalamic regions are well-visualized.

is below their level. Working in the arachnoidal plane below the major veins, lesion of the posterior third ventricular regions are exposed. The tumor removal is then carried out in a piecemeal manner. Following tumor removal, the brain stem, the collicular plate and the posterior thalamic regions are well-visualized. Advantage Adequate exposure both above and below the tentorial notch is available. Lesions reaching upto the trigone and corpus callosum are accessible. This approach is specially preferred in cases where the deep venous system is dorsally displaced as occurs in tentorial meningiomas. Disadvantage In tumors extending eccentrically to the contralateral side, complete removal is difficult. Care must be taken to avoid damage to the occipital lobe (that may precipitate homonymous hemianopia) and the splenium of corpus callosum (that may result in posterior disconnection syndrome). Neurological Complications Regardless of the approach, Perinaud’s syndrome with upward gaze palsy, pupillary and accommodation abnormalities with partial or complete oculomotor nerve palsy, trochlear nerve injury with diplopia or even alteration of sensorium due to brain stem injury may result.

Disadvantage In tumors extending eccentrically to the contralateral side, complete removal is difficult. Care must be taken to avoid damage to the occipital lobe (that may precipitate homonymous hemianopia) and the splenium of corpus callosum (that may result in posterior disconnection syndrome). Neurological Complications Regardless of the approach, Perinaud’s syndrome with upward gaze palsy, pupillary and accommodation abnormalities with partial or complete oculomotor nerve palsy, trochlear nerve injury with diplopia or even alteration of sensorium due to brain stem injury may result. Other Approaches The posterior interhemispheric transcallosal approach utilizes a parietal, interhemispheric approach to gain access to the lesions situated above the deep venous system and involving the posterior corpus callosum. The anterior transcallosal, transventricular approach is useful when the tumor occupies lateral ventricles and posterior third ventricles. It utilizes the conventional anterior interhemispheric approach to gain access into the lateral ventricle by creating a small opening in the corpus callosum. The access from the lateral to the third ventricle is gained by a subchoroidal approach or an approach medial to the choroid plexus by dividing the thin velum interpositum that is encountered and, by following a trajecteory that is directed posteriorly toward the pineal region infero-lateral to the internal cerebral veins traversing the roof of the third ventricle. Finally, lateral paramedian infratentorial approach in park-bench position traverses between the superior surface of cerebellar hemisphere and the lateral tentorium. The trajectory is directed superomedially toward the tentorial incisura. The bridging veins traversing this corridor may be divided to gain additional space.[7–9] Stereotactic or endoscopic biopsy may also be utilized to identify lesions that have an excellent response to radio- and chemotherapy, thus avoiding the need for a major surgery.

ected superomedially toward the tentorial incisura. The bridging veins traversing this corridor may be divided to gain additional space.[7–9] Stereotactic or endoscopic biopsy may also be utilized to identify lesions that have an excellent response to radio- and chemotherapy, thus avoiding the need for a major surgery. In conclusion, posterior third ventricular tumors are frequently encountered in children. Their surgical excision is technically demanding. The results, however, are gratifying as the tumors are often soft-suckable or well-marginated permitting total removal with minimal morbidity and mortality. The residual lesions, if any, may often have a good therapeutic response to radiotherapy and chemotherapy. Source of Support: Nil Conflict of Interest: None declared

Skin closure of a wide-based myelomeningoceles is still a surgical challenge. The difficulties are compounded by dysplastic skin, secondary infection, the wide base of the defect, and poor development of facial and muscular structures underneath. Conventionally, surgeons have used mobilization of skin flaps, relaxing incisions, and rotational flaps, which need team work with plastic surgeons. However, these techniques are associated with longer duration of surgery , blood loss, and morbidity in the form of wound dehiscence.[14] We report here a surgical technique on a child with a wide-based, thoraco-lumbar Myelomeningocele with dysplastic skin, wherein tissue expansion was used to achieve primary closure [Figures 1–4]. Figure 1 Myelomeningocele Figure 2 Saggital section of MRI Figure 3 Axial Section of MRI Figure 4 Axial section of MRI showing the spinal defect and the placode The expansion of skin was first reported in 1947 by Nuemann.[2] Expanders are available in variety of shapes and sizes and their selection depends on the size of the tissue required and the age of the child. The size and shape of the expander and the incision to be inserted need to be properly planned preoperatively. The surgery is performed in two stages 1. Insertion of the expander 2. Definitive procedure.[34]

ety of shapes and sizes and their selection depends on the size of the tissue required and the age of the child. The size and shape of the expander and the incision to be inserted need to be properly planned preoperatively. The surgery is performed in two stages 1. Insertion of the expander 2. Definitive procedure.[34] The child was positioned prone under general anesthesia and the part was prepared. A curvilinear incision was made just at the upper margin of the myelomeningocele. The subcutaneous tissue was dissected and a plane was created in the healthy area. A Eurosilicon tissue expander was inserted horizontally and the incision was closed, leaving an access port at one corner [Figure 5]. The child was discharged after being prescribed antibiotics. Usually, the expansion should start one to two weeks after the insertion, ensuring proper wound healing to avoid disruption of the incision during expansion. Biweekly injections of 50 mL of sterile saline through the port were carried out as recommended by the manufacturer until an expansion capacity of 300 mL was reached [Figures 6–10]. Then, an additional 200 mL was injected to overexpand the device as recommended. These saline injections were done as an outpatient procedure. The required expansion took six weeks in our case [Figure 11], the integrity of the skin being checked (as deemed mandatory) during each visit. Figure 5 Insertion of Euro silicon tissue expander Figure 6 Expansion in stages Figure 7 Expansion in stages Figure 8 Expansion in stages Figure 9 Expansion in stages Figure 10 Expansion in stages

The child was positioned prone under general anesthesia and the part was prepared. A curvilinear incision was made just at the upper margin of the myelomeningocele. The subcutaneous tissue was dissected and a plane was created in the healthy area. A Eurosilicon tissue expander was inserted horizontally and the incision was closed, leaving an access port at one corner [Figure 5]. The child was discharged after being prescribed antibiotics. Usually, the expansion should start one to two weeks after the insertion, ensuring proper wound healing to avoid disruption of the incision during expansion. Biweekly injections of 50 mL of sterile saline through the port were carried out as recommended by the manufacturer until an expansion capacity of 300 mL was reached [Figures 6–10]. Then, an additional 200 mL was injected to overexpand the device as recommended. These saline injections were done as an outpatient procedure. The required expansion took six weeks in our case [Figure 11], the integrity of the skin being checked (as deemed mandatory) during each visit. Figure 5 Insertion of Euro silicon tissue expander Figure 6 Expansion in stages Figure 7 Expansion in stages Figure 8 Expansion in stages Figure 9 Expansion in stages Figure 10 Expansion in stages Figure 11 Expansion in stages

The child was positioned prone under general anesthesia and the part was prepared. A curvilinear incision was made just at the upper margin of the myelomeningocele. The subcutaneous tissue was dissected and a plane was created in the healthy area. A Eurosilicon tissue expander was inserted horizontally and the incision was closed, leaving an access port at one corner [Figure 5]. The child was discharged after being prescribed antibiotics. Usually, the expansion should start one to two weeks after the insertion, ensuring proper wound healing to avoid disruption of the incision during expansion. Biweekly injections of 50 mL of sterile saline through the port were carried out as recommended by the manufacturer until an expansion capacity of 300 mL was reached [Figures 6–10]. Then, an additional 200 mL was injected to overexpand the device as recommended. These saline injections were done as an outpatient procedure. The required expansion took six weeks in our case [Figure 11], the integrity of the skin being checked (as deemed mandatory) during each visit. Figure 5 Insertion of Euro silicon tissue expander Figure 6 Expansion in stages Figure 7 Expansion in stages Figure 8 Expansion in stages Figure 9 Expansion in stages Figure 10 Expansion in stages Figure 11 Expansion in stages The child was later readmitted for definitive surgery where the incision was planned under general anesthesia by the plastic surgeons. The skin and the subcutaneous tissues were dissected [Figure 16], the dysplastic skin was totally excised [Figure 12], and the neuronal placode was isolated [Figures 13, 14], dissected around, and repositioned. The dural tube was reconstructed and the fascia was mobilized and covered over the dural tube [Figure 15]. There was a wide skin defect [Figure 18] and the incision was expanded to deliver the tissue expander in toto [Figures 19–21]. The expanded skin was now mobilized onto the defect to cover the skin defect over the myelomeningocele [Figure 17]. Thus, primary closure was achieved easily [Figure 22] and the wound healed well without any complications. We feel this is a well tolerated, sophisticated procedure with minimum morbidity for children with larger skin defects.

now mobilized onto the defect to cover the skin defect over the myelomeningocele [Figure 17]. Thus, primary closure was achieved easily [Figure 22] and the wound healed well without any complications. We feel this is a well tolerated, sophisticated procedure with minimum morbidity for children with larger skin defects. Figure 12 Excision of the dysplastic skin Figure 13 Dissection of the placode Figure 14 Separation of the Neuro structures Figure 15 Reconstruction of dural tube Figure 16 Dissection of subcutaneous tissues Figure 17 Creating a bed for the repair Figure 18 Wide skin defect Figure 19 Delivering of tissue expander Figure 20 Delivering of tissue expander Figure 21 Tissue expander fully loaded Figure 22 Primary closure of the skin Source of Support: Nil Conflict of Interest: None declared.

Introduction Atypical antipsychotics are increasingly being associated with neurological side effects. Risperidone, quetiapine, and aripiprazole have been associated with tardive dystonia among other side effects.[1] Similarly, olanzapine has also been associated with this troublesome effect. However, these reports are from cases of nonaffective psychosis, especially schizophrenia. Moreover, the usual age of onset of this neurological side effect has been reported to be in the midthirties or later. We present here a case of tardive dystonia associated with the use of olanzapine in an adolescent girl suffering from bipolar affective disorder. Case Report A a sixteen year-old girl, presented to our Outpatient department with the complaints of discomfort in the neck and lower back as well as restriction of body movements. She was not able to maintain an erect posture and would tend to fall on either side while standing up from a sitting position. She would keep her head turned to the right and upwards due to the sustained contraction of the neck muscles. There was a sideways bending of the back in the lumbar region. To counter the abnormal positioning of the back and neck, she would keep her limbs in a specific position to allow her body weight to be supported. Due to the restrictions with the body movements at the neck and in the lumbar region, she would require assistance in standing and walking. She would require her parents to help her with daily chores, including all activities of self-care.

keep her limbs in a specific position to allow her body weight to be supported. Due to the restrictions with the body movements at the neck and in the lumbar region, she would require assistance in standing and walking. She would require her parents to help her with daily chores, including all activities of self-care. She had been experiencing these difficulties for the past four months since when she was introduced to olanzapine tablets for the control of her exacerbated mental illness. This was not her first experience with this drug over the past seven years since she had been diagnosed with bipolar affective disorder. Her first episode of the affective disorder was that of mania at the age of eleven which was managed with the use of olanzapine tablets in 2.5–10 mg doses per day at different times. The patient developed pain and discomfort in her neck within the second week of being put on tablet olanzapine at a dose of 5 mg per day. This was associated with a sustained and abnormal contraction of the neck muscles that would pull her head to the right in an upward direction. These features had persisted for the first three years of her illness with a varying intensity, distress, and dysfunction which would tend to correlate with the dose of olanzapine. Apart from a brief period of around three weeks when she was given tablet trihexyphenidyl 4 mg per day for rigidity in her upper limbs, she was not prescribed any other psychotropic medication. The rigidity showed good response to this medication which was subsequently stopped. The introduction and subsequent withdrawal of this medication did not bring about any change in the sustained abnormal contraction of her neck muscles.

idity in her upper limbs, she was not prescribed any other psychotropic medication. The rigidity showed good response to this medication which was subsequently stopped. The introduction and subsequent withdrawal of this medication did not bring about any change in the sustained abnormal contraction of her neck muscles. Improvement and subsequent remission of the mood symptoms of the patient provided the treatment team with an opportunity to stop olanzapine. The discomfort in the neck and the abnormal movement of the neck muscles persisted over the next three months’ period when she was off olanzapine without any significant change, even with a trial of propranolol, trihexyphenidyl, and phenargan injection. Reintroduction of olanzapine (at a dose of 2.5 mg per day) after a gap of three months for the reemergence of some behavioral features led to a slight aggravation of the already existing abnormal movement and posturing of the neck.

cant change, even with a trial of propranolol, trihexyphenidyl, and phenargan injection. Reintroduction of olanzapine (at a dose of 2.5 mg per day) after a gap of three months for the reemergence of some behavioral features led to a slight aggravation of the already existing abnormal movement and posturing of the neck. With improvement in the clinical picture, olanzapine was reduced and stopped. She was put on tablet sodium valproate, 1000 mg per day during this period for the stabilization of her mood when she was also given escitalopram for a period of three months for her depressive features. The patient responded well to this change in medication, but she developed amenorrhea for which no cause was established after a detailed gynecological evaluation. Keeping in mind the possibility of valproate-induced menstrual disturbance, she was shifted to tablet lithium 450 mg per day. The patient was well maintained on this medication for a period of around two years. However, she developed hypothyroidism for which eltroxin was introduced at a dose of 50 micrograms per day.

. Keeping in mind the possibility of valproate-induced menstrual disturbance, she was shifted to tablet lithium 450 mg per day. The patient was well maintained on this medication for a period of around two years. However, she developed hypothyroidism for which eltroxin was introduced at a dose of 50 micrograms per day. During this period of two years and seven months, the abnormal contraction of the neck muscles and the abnormal positioning of the head improved slightly, and with the improvement, it would cause less discomfort and interference in her activities. However, these movements failed to disappear completely. Another exacerbation of the mood symptoms in the form of mania warranted a need for the introduction of olanzapine (by a different treatment team) and the patient was reintroduced to 10 mg olanzapine on a daily basis, which led to the current presentation as described earlier. After the case was seen at our institute, the psychotropic medications were stopped as her mood symptoms had remitted and she was put on tablet tetrabenazine (built up to 75 mg per day in divided doses) with which the patient had started showing some response with an improvement in abnormal movements of the muscles of the neck as well as the back. She is now able to stand with support and can do some daily chores on her own. The pain and discomfort in the back and neck have also reduced.

5 mg per day in divided doses) with which the patient had started showing some response with an improvement in abnormal movements of the muscles of the neck as well as the back. She is now able to stand with support and can do some daily chores on her own. The pain and discomfort in the back and neck have also reduced. During the course of the illness, the patient has been investigated for the presence of any neurological illness as the cause of her abnormal movements. Her MRI scan of the brain, serum and urine copper levels, slit lamp microscopy for the KF ring, complete blood count, TLC, DLC, and USG of the abdomen did not reveal any abnormalities. Her thyroid function tests were deranged subsequent to the introduction of tablet lithium carbonate which was restored to normal after the introduction of tablet eltroxin. Dystonia is a syndrome of sustained muscle contractions that produce twisting and repetitive movements or abnormal postures. The descriptions of the extent and severity of muscle involvement are variable, ranging from intermittent contraction limited to a single body region, to generalized dystonia involving the limbs and axial muscles.

rome of sustained muscle contractions that produce twisting and repetitive movements or abnormal postures. The descriptions of the extent and severity of muscle involvement are variable, ranging from intermittent contraction limited to a single body region, to generalized dystonia involving the limbs and axial muscles. Ever since the introduction of the term, “dystonia” by Oppenhiem in the early part of the twentieth century, it has been an area of focused attention of the neurologists. In 1973, Keegan and Rajput introduced the term, “dystonia tarda” to describe drug-induced, sustained muscle spasm causing repetitive movements or abnormal postures. “Tardive dystonia” was a term introduced by Burke in 1982, the description of which required the presence of chronic dystonia, a history of antipsychotic drug treatment preceding or concurrent with the onset of dystonia, the exclusion of known causes of secondary dystonia by appropriate clinical and laboratory evaluation, and a negative family history of dystonia for definitive diagnosis. The dystonia could be classified based on the region(s) of the body involved. Involvement of isolated regions like the face, neck, and arms would be labeled as focal dystonia, whereas simultaneous involvement of two or more contiguous areas would be called segmental dystonia. When the clinical picture is that of involvement of two or more noncontiguous regions, the label used is, “multifocal” and the involvement of one leg and one other body region makes it the generalized type.

al dystonia, whereas simultaneous involvement of two or more contiguous areas would be called segmental dystonia. When the clinical picture is that of involvement of two or more noncontiguous regions, the label used is, “multifocal” and the involvement of one leg and one other body region makes it the generalized type. The symptoms of tardive dystonia could begin even after a few days or weeks of exposure to the offending agent. Tardive dystonia is prevalent in 0.5–21.6% of the patients who are treated with neuroleptics. The syndrome of tardive dystonia has been reported with most of the typical antipsychotics.[2] It has been associated with the atypical antipsychotics, namely risperidone, olanzapine, quetiapine, and aripiprazole. Reports of tardive dystonia developing with the use of atypical antipsychotics have been predominantly in the cases of nonaffective psychosis and in the adult population in the age ranges of the midthirties and forties. Our case is the first case of an affective illness in an adolescent girl developing tardive dystonia on olanzapine. The aggravation of the clinical features with the inadvertent reintroduction of the medication suggests olanzapine is the offending agent. With the growing acceptance of olanzapine as the first-line therapy for the manic phase of bipolar illness and as a mood stabilizer for the maintenance therapy, one needs to be cautious about the emergence of this troublesome adverse effect of this therapy. The patient has shown some response to the introduction of tetrabenazine. Source of Support: Nil Conflict of Interest: None declared.

Introduction Holoprosencephaly is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation, with an estimated incidence of 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar, and alobar holoprosencephaly. Although hydrocephalus can occur during pre- or postnatal development, the cause of hydrocephalus remains to be elucidated. We report here a case of hydrocephalic holoprosencephaly who developed CSF ascites following a ventriculoperitoneal shunt (VP shunt) and discuss the possible factors involved in this development.

Although hydrocephalus can occur during pre- or postnatal development, the cause of hydrocephalus remains to be elucidated. We report here a case of hydrocephalic holoprosencephaly who developed CSF ascites following a ventriculoperitoneal shunt (VP shunt) and discuss the possible factors involved in this development. Case Report A five month-old male child presented with complaints of enlarging head size and poor feeding. The child was not fixing his gaze and had upward gaze palsy. The head circumference was 48 cm and the anterior fontanelle was open and bulging. A diagnosis of holoprosencephaly was established on performing a CT scan of the head [Figure 1]. Following this, a low-pressure VP shunt was inserted through the left occipital burr hole. The patient became symptomatically better after the shunt and a repeat CT scan of the head showed the shunt tip in situ [Figure 2]. One month after the shunt, the child presented with progressive distension of the abdomen and decreased feeding. There was no history of fever or vomiting and he was passing stools normally. On examination, he was found to have a grossly distended abdomen, fluid thrill and sluggish bowel sounds. The anterior and posterior fontanelles were open and full. The head circumference was 47 cm. A CT scan of the head revealed enlarged the shunt to still be in situ. A shunt tap was done and the ventricular end was freely aspirable. CSF analysis results were nonmeningitic and the culture was sterile. Ultrasound of the abdomen was done and revealed gross ascites. CT of the abdomen also showed gross ascites without any evidence of loculated fluid collection or lymphadenopathy [Figure 3]. Under ultrasound guidance, ascitic fluid was aspirated which was clear and transudative. Ascitic fluid culture was also sterile. The shunt was exteriorized from the abdominal end, following which abdominal distension decreased and there was improvement in feeding. A new VP shunt was done with the shunt valve upgraded to a medium pressure valve. Following this procedure, the child became asymptomatic and is presently on follow-up.

s also sterile. The shunt was exteriorized from the abdominal end, following which abdominal distension decreased and there was improvement in feeding. A new VP shunt was done with the shunt valve upgraded to a medium pressure valve. Following this procedure, the child became asymptomatic and is presently on follow-up. Figure 1 Plain CT scan of the head showing agenesis of bilateral cortical structures seen in alobar holoprosencephaly, along with associated hydrocephalus Figure 2 Plain CT scan of the head showing the shunt tip in situ with good visualization of sulcul space, suggestive of a well-functioning shunt Figure 3 Contrast CT of the abdomen showing the marked ascites in the abdominal cavity

Figure 1 Plain CT scan of the head showing agenesis of bilateral cortical structures seen in alobar holoprosencephaly, along with associated hydrocephalus Figure 2 Plain CT scan of the head showing the shunt tip in situ with good visualization of sulcul space, suggestive of a well-functioning shunt Figure 3 Contrast CT of the abdomen showing the marked ascites in the abdominal cavity Discussion CSF ascites has been defined as the ‘accumulation of excess CSF within the peritoneal cavity.’ It is a rare complication of the ventriculoperitoneal (VP) shunt. The exact cause of CSF ascites is still not clear. On review of literature, various possible mechanisms have been described: i) excessive CSF production in a cases of choroid plexus papilloma may cause CSF ascites after VP shunt due to imbalance between CSF production and peritoneum absorption.[12] ii) Infection has been proposed as a causative factor by some authors.[34] iii) Chronic inflammatory conditions like tuberculosis,[5] peritoneal inflammation by multiple shunt revisions,[6] or allergy to shunt material[7] decrease the absorptive capacity of peritoneum, leading to CSF ascites. iv) CSF ascites has also been reported in optic nerve gliomas and in craniopharyngioma. [8–12] v) In brain tumors, especially in astrocytoma, increased vascular permeability can cause microvascular extravasation of plasma into the peritoneal cavity and cause ascites.[1314] Despite all these postulated mechanisms, no satisfactory explanation has been given to date, and most of the reported cases have unknown etiology.[1516]

tumors, especially in astrocytoma, increased vascular permeability can cause microvascular extravasation of plasma into the peritoneal cavity and cause ascites.[1314] Despite all these postulated mechanisms, no satisfactory explanation has been given to date, and most of the reported cases have unknown etiology.[1516] Holoprosencephaly is a birth defect that occurs during the first few weeks of intrauterine life. There is incomplete or absent division of the embryonic forebrain (prosencephalon) into distinct lateral cerebral hemispheres. Variable degrees of facial deformities, mental retardation, epilepsy, or abnormalities of other organ systems such as the cardiac, skeletal, genitourinary, and gastrointestinal may be present. Microcephaly is the rule, and macrocephaly is suggestive of hydrocephalus. The reason for hydrocephalus remains unclear in alobar hloprosencephaly, and the formation of CSF ascites in our case offers an insight into the possible mechanisms involved in the formation of hydrocephalus in these patients. We hypothesize that that the primary problem lies in excessive CSF production, which may be actually excacerbating the holoprosencephaly by preventing the growth of the cortical mantle, besides leading to CSF ascites, as seen in our case. The cause of excessive CSF production may also have a molecular basis and it may be possible that the genes responsible for causing holoprosencephaly may also be responsible for upregulating the CSF production. The management of a patient with holoprosencephaly presenting with hydrocephalus remains complex. Although we achieved a satisfactory short-term outcome in our patient by upgrading the opening pressure of the shunt valve, this may not be desirable as it may lead to chronic hydrocephalus in these patients.

F production. The management of a patient with holoprosencephaly presenting with hydrocephalus remains complex. Although we achieved a satisfactory short-term outcome in our patient by upgrading the opening pressure of the shunt valve, this may not be desirable as it may lead to chronic hydrocephalus in these patients. Patients with holoprosencephaly can develop hydrocephalus, the etiology of which remains to be elucidated. These patients are a management dilemma and shunt placement may lead to CSF ascites. Research into the molecular change which occurs at genetic level may shed light on the etiopathogenesis of hydrocephalus in these patients. Source of Support: Nil Conflict of Interest: None declared.

Introduction The VP Shunt is a routine procedure in pediatric neurosurgery for hydrocephalus. ACM Type-II patients have anatomical intracranial anomalies and meningomyelocele with hydrocephalus before primary MMC repair shunting is done to decrease ICT. Respiratory depression has been rarely documented as complication. ACM is a clinical and anatomical processes that involves the hindbrain. Caudal herniation of the cerebellar vermis, brainstem, and IVth ventricle as well as other intracranial anomalies have been reported in ACM Type II cases, and almost all have myelomeningocele and hydrocephalus, which may be present at birth or a few days after surgery. The patient may present with the clinical symptoms of apnea, inspiratory wheeze or stridor, breath holding, retrocollis or opisthotonous, irritability, aspiration pneumonia, dysphagia, dysarthria, nystagamus, strabismus, and quadriparesis with hypotonia. ACM type II may also present postoperatively in the form of tense and bulging fontanels with features of lethargy, irritability, vomiting, or even respiratory depression. MMC associated with hydrocephalus requires the insertion of a VP shunt at the time of surgical repair.[6]

rabismus, and quadriparesis with hypotonia. ACM type II may also present postoperatively in the form of tense and bulging fontanels with features of lethargy, irritability, vomiting, or even respiratory depression. MMC associated with hydrocephalus requires the insertion of a VP shunt at the time of surgical repair.[6] Case Report Two male children, one a 45 day-old / 5 kg and the second a two month-old / 6 kg, presenting with lumbar meningomyelocele and hydrocephalus with no other congenital anomalies and normal neurological status, were posted for VP shunt insertion. The results of a systemic examination of the respiratory and cardiovascular systems were within normal limits. Results of hematological and biochemical investigations and of echocardiography were also within normal limits. The children were premedicated with syrup diazepam 0.1 mg/kg. After beginning the monitoring by ECG, NIBP, SPO2, temperature, and ETCO2, induction was done with Sevoflurane (mask induction)and IV access was secured. This was followed by the administration of injection fentanyl 10 mcg. Nasotracheal intubation with uncuffed endotracheal tube of size 3.5 was facilated with a depth of sevoflurane. Anesthesia was maintained with 66% nitrous oxide in oxygen and isoflurane 1–1.5%. After positioning, the ventilation was controlled with one dose of atracurium 4 mcg using a modified Jackson-Rees circuit with ETCO2 monitoring. Intraoperative 0.45 % Normal saline + 5%Dextrose fluid was administered (to prevent hypernatremia and hypoglycemia).

ed with 66% nitrous oxide in oxygen and isoflurane 1–1.5%. After positioning, the ventilation was controlled with one dose of atracurium 4 mcg using a modified Jackson-Rees circuit with ETCO2 monitoring. Intraoperative 0.45 % Normal saline + 5%Dextrose fluid was administered (to prevent hypernatremia and hypoglycemia). The procedures lasted 45 and 55 minutes each and were uneventful. After the procedure, there were no respiratory efforts or response to oral suction and both pupils were constricted and reacting. Naloxone 25 mcg was administered in divided dosage for suspected fentanyl sensitivity, but the pupil as well as respiratory efforts showed no changes. Also, there was no change in the level of consciousness or motor activity. After 2 h of ventilation, no limb movements appeared in response to painful stimuli. ABG was within normal limits and needed no correction. Reversal of the neuromuscular blockage was attempted with atropine 20 mcg/kg and neostigimine 50 mcg/kg but did not succeed. Hypothermia, hypoglycemia, and hypocalcemia were ruled out. An acute rise in intracranial pressure (ICP) was suspected and 20%mannitol 0.5 g/kg was administered intravenously; no pupillary changes were seen. After 2–3 h, the patients’ condition did not improve, so the patients were shifted to the Neuro ICU for elective ventilation with monitoring of the vitals and care. After six and eight hours, some respiratory efforts and limb movements were seen, so the children were weaned off gradually over the next two hours and extubated successfully. The children were fully conscious, crying normally, with stable vitals and temperature, and the ABG was normal; the rest of the postoperative monitoring was uneventful.

s, some respiratory efforts and limb movements were seen, so the children were weaned off gradually over the next two hours and extubated successfully. The children were fully conscious, crying normally, with stable vitals and temperature, and the ABG was normal; the rest of the postoperative monitoring was uneventful. After two weeks, the children were planneded for the repair of the meningomyelocele. General anesthesia was induced in the same fashion, with premedication, induction, and maintenance with the same doses of anesthetics as before in the VP shunt. Time taken for the repair was the same as before for the VP shunt; the repair was uneventful intraoperatively and the vitals were stable. Adequate respiratory efforts and limb movement occurred within five minutes of withdrawal of all anesthetics. This time, extubation was done successfully after the reversal of neuromuscular blockage. Recovery was good, the children opened eyes, and the vitalswere stable at the end of the surgery. Discussion Delayed awakening from anesthesia may be due to various causes, includeing overdose of intravenous and volatile anesthetics, opioids or neuromuscular blocking agents, hypoxia, hypothermia, metabolic and endocrine abnormalities, paradoxical air embolism into the cerebral circulation, or if any preexisting occult or overt ICH leads to herniation of the cerebral cortex across the tentorium cerebelli or the brainstem through the foramen magnum.[12]

oids or neuromuscular blocking agents, hypoxia, hypothermia, metabolic and endocrine abnormalities, paradoxical air embolism into the cerebral circulation, or if any preexisting occult or overt ICH leads to herniation of the cerebral cortex across the tentorium cerebelli or the brainstem through the foramen magnum.[12] Overdose of the anesthetic agent was ruled out as the cause in our case as the accidental administration or drug overdose was cross-checked. Hypoxia during the procedure was unlikely as the ETT position and bilateral air entry was checked before and after turning the patient. Also, continuous oxygen saturation was monitored to exclude out any desaturation.[3] Hypothermia and hypoglycemia were also excluded as possible causes.[5] Venous air embolism could have been a possibility, but it is usually associated with a decrease in ETCO2 and bradyarrythmias, which were not observed in our cases. Acute transtentorial herniation or ‘coning’ can be a possible explanation as it occurs following a sudden change in the pressure gradient across the tentorium. Increase in pressure in the supratentorial compartment or a decrease in the infratentorial compartment could lead to this condition, as in ill-advised lumbar punctures / VP shunts.[4] The uncal herniation initially causing oculomotor nerve irritation resulting in pupillary constriction followed by compression of the oculomotor nerve resulting in pupillary dilatation then subsequently,devlops coma ,it is not seen in our cases.

Acute transtentorial herniation or ‘coning’ can be a possible explanation as it occurs following a sudden change in the pressure gradient across the tentorium. Increase in pressure in the supratentorial compartment or a decrease in the infratentorial compartment could lead to this condition, as in ill-advised lumbar punctures / VP shunts.[4] The uncal herniation initially causing oculomotor nerve irritation resulting in pupillary constriction followed by compression of the oculomotor nerve resulting in pupillary dilatation then subsequently,devlops coma ,it is not seen in our cases. Central herniation, heralded by miotic pupils, causes progressive brainstem compression with sequential loss of pupillary responses and abnormal or absent eye movements.[4] (Ropper et al,). Herniation of the intracranial contents through the foramen magnum can clinically manifest as tachycardia and hypertension (due to pressure over the trigeminal or any sensory nerve nucleus) or reflex bradycardia, it can leads to sudden cessation of spontaneous respiratory efforts (due to pressure over the respiratory center). It can also causes pupillary constriction (due to oculomotor nerve irritation)and pupillary dilatation (due to oculomotor nerve paralysis), and papilloedema (due to defective drainage of CSF). (Ropper et al, 1998) Patients in deep metabolic coma may, however, show a total loss of eye movements but retain pupilary reflexes.

Central herniation, heralded by miotic pupils, causes progressive brainstem compression with sequential loss of pupillary responses and abnormal or absent eye movements.[4] (Ropper et al,). Herniation of the intracranial contents through the foramen magnum can clinically manifest as tachycardia and hypertension (due to pressure over the trigeminal or any sensory nerve nucleus) or reflex bradycardia, it can leads to sudden cessation of spontaneous respiratory efforts (due to pressure over the respiratory center). It can also causes pupillary constriction (due to oculomotor nerve irritation)and pupillary dilatation (due to oculomotor nerve paralysis), and papilloedema (due to defective drainage of CSF). (Ropper et al, 1998) Patients in deep metabolic coma may, however, show a total loss of eye movements but retain pupilary reflexes. The main cause of death in children with chiari II malformation and MMC, usually due to respiratory dysfunction and episodic symptoms of brain stem dysfunction are frequent. Neither surgical decompression nor intensive care prevented the fatal outcome, which was both unpredictable and inevitable.(Lopez-Pison et al., Nishino et al, Setz et al and Shiraishi et al,) Brain stem compression by the tonsillor herniation and caudal displacement of the brain stem may be the causes of delayed recovery and respiratory depression following the shunt in our two cases. Compression to the brain stem was relieved, hence, no such delayed recovery was found in subsequent procedures. Measures to prevent the increase in the transtentorial pressure gradient should be considered, such as the selection of appropriate anesthetic agents[7] and techniques[8] , avoidance of the sudden release of pressure from the sac, and adhering to a head-low position. Postoperative ventilatory support should be considered for every ACM patient.

ncrease in the transtentorial pressure gradient should be considered, such as the selection of appropriate anesthetic agents[7] and techniques[8] , avoidance of the sudden release of pressure from the sac, and adhering to a head-low position. Postoperative ventilatory support should be considered for every ACM patient. Source of Support: Nil Conflict of Interest: None declared.

Sir, Klein-Levin syndrome, usually found in adolescent males, is associated with episodic hypersomnolence, compulsive overeating, lack of sexual inhibition, and personality change, and most often, it represents a benign and self-limited entity and does not warrant extensive investigation or treatment. Female affection of the disease is very rare. A 13 year-old girl was brought by her parents with a complaint of periodic hypersomnolence. Her parents were concerned that her periodic hypersomnolence would affect her examinations. On further enquiry, she was found to have a history of sleeping for 18 to 20 hours a day, which would happen for continuously 6–7 days, seven to eight times a year for the past two years. Apparently, she had no warning symptoms and could not predict when she would have such episodes. In addition to sleeping for 18 to 20 hours a day, she was also reported to eat voraciously while awake. If woken up from sleep, she was rather irritable and went back to sleep quickly. Barring these episodes, she was a normal child with normal intelligence and behavior. She ranked in the top ten percentile in her class and had no other significant medical history. In particular, there was no history of trauma, seizure-like activity, snoring, or hypersomnolence at other times. Her age at menarche was 12 years. There was no significant family or psychosocial history.

gence and behavior. She ranked in the top ten percentile in her class and had no other significant medical history. In particular, there was no history of trauma, seizure-like activity, snoring, or hypersomnolence at other times. Her age at menarche was 12 years. There was no significant family or psychosocial history. On examination, her weight and height were found to be normal for her age. Results for investigations done prior to referral to the Sleep Center, including liver functions, renal functions, thyroid functions, blood sugar, growth hormone, prolactin levels, luteinizing hormone, follicular stimulation hormone, GnRH, and estradiol were all normal. The results of her MRI, EEG, and LP exam were normal. A 16 channel overnight polysomnography was done and found to be normal. In particular, the sleep architecture was normal and there was no evidence of sleep-disordered breathing or periodic limb movement disorder. A Multiple Sleep Latency test done the following day did not suggest hypersomnolence and there were no sleep-onset REM periods. Of note, the study was done during the days that were reported to be the patient's normal days and not during one of her ‘periodic’ abnormality, as the frequency of these was unpredictable. A diagnosis of Klein-Levin syndrome (KLS) was made. It was decided to start her on lithium (400–900 mg/day bid or at night) and to monitor the frequency of her symptoms.

days that were reported to be the patient's normal days and not during one of her ‘periodic’ abnormality, as the frequency of these was unpredictable. A diagnosis of Klein-Levin syndrome (KLS) was made. It was decided to start her on lithium (400–900 mg/day bid or at night) and to monitor the frequency of her symptoms. Klein-Levin syndrome is a rare disorder characterized by the need for an excessive amount of sleep (hypersomnolence), (i.e., up to 20 hours a day); excessive food intake (compulsive megaphagia); and an abnormally uninhibited sexual drive occurring almost exclusively in adolescent males, though there have been a few reports of its occurrence in females as well.[1] The mean age of onset is 15.8 ± 2.5 years and usually patients experience three to four episodes per year with a mean duration of 11.5 ± 6.6 days for a single hyper somnolence attack.[2] It has been noted that the disease usually lasts 8–10 years and is self limiting before adulthood. Although the cause is usually not known, it is believed that hereditary factors may cause some individuals to have a genetic predisposition to developing this disorder. There have been reports of two siblings who shared uncharacteristically prolonged episodes of hypersomnolence and the HLA-DR2 haplotype[3] Secondary Klein-Levin syndrome has been described after episodes of encephalitis[4] and trauma.[56] Differential diagnoses included seizure disorder and depression.

g this disorder. There have been reports of two siblings who shared uncharacteristically prolonged episodes of hypersomnolence and the HLA-DR2 haplotype[3] Secondary Klein-Levin syndrome has been described after episodes of encephalitis[4] and trauma.[56] Differential diagnoses included seizure disorder and depression. KLS is usually associated with compulsive overeating, lack of sexual inhibition, and personality change. Sexual responses though not always present include in appropriate sexual advances and overt masturbation, especially in males. Compulsive overeating with rapid weight gain may occur. Personality changes may include irritability, depersonalization, depression, confusion, occasional hallucinations, and impulsive behavior; the symptoms of KLS are typical. On recovery, total or partial loss of memory (amnesia) is usual, although disgust at overeating is common. Between episodes, physical and mental health is usually normal. It is not uncommon to note that these patients are seen by a variety of specialists including endocrinologists, psychiatrists, and neurologists before being evaluated by a sleep specialist. This meant a delay in diagnosing Klein-Levin syndrome of 3.8 ± 4.2 years.[2]

KLS is usually associated with compulsive overeating, lack of sexual inhibition, and personality change. Sexual responses though not always present include in appropriate sexual advances and overt masturbation, especially in males. Compulsive overeating with rapid weight gain may occur. Personality changes may include irritability, depersonalization, depression, confusion, occasional hallucinations, and impulsive behavior; the symptoms of KLS are typical. On recovery, total or partial loss of memory (amnesia) is usual, although disgust at overeating is common. Between episodes, physical and mental health is usually normal. It is not uncommon to note that these patients are seen by a variety of specialists including endocrinologists, psychiatrists, and neurologists before being evaluated by a sleep specialist. This meant a delay in diagnosing Klein-Levin syndrome of 3.8 ± 4.2 years.[2] Results of all imaging tests, except of SPECT, are usually normal. The subtracted SPECT studies may show hypoperfusion in the left hypothalamus, bilateral thalami, basal ganglia, bilateral medial and dorsolateral frontal regions, and the left temporal lobe during the symptomatic period.[7] CSF hypocretin-1 measurements performed during the periods of hypersomnia have also been found to be abnormal.[8]

ECT studies may show hypoperfusion in the left hypothalamus, bilateral thalami, basal ganglia, bilateral medial and dorsolateral frontal regions, and the left temporal lobe during the symptomatic period.[7] CSF hypocretin-1 measurements performed during the periods of hypersomnia have also been found to be abnormal.[8] Currently, there is no formal treatment for KSL due to the lack of knowledge regarding its underlying cause. Only lithium[9] has had a higher reported response rate (41%) for stopping relapses when compared to medical abstention (19%). The goal of treatment is to counsel the patient and family and also, to keep these episodes to a low level throughout the year. Most of these patients are either labeled as being lazy or classified as narcolepsy or idiopathic hypersomnia. But the absence of associated clinical features such as cataplexy, and characteristic polysomnographic features such as sleep-onset REM episodes and the presence of megaphagia facilitate the positive diagnosis. It is important that the diagnosis is suspected early, especially in adolescent males who present with recurrent episodes of somnolence, increased appetite, and abnormal behavior, as it most often represents a benign and self-limited entity and does not warrant extensive investigation or treatment. It is also important to distinguish this syndrome from more serious organic and psychiatric disorders with more serious prognosis. KLS remains particularly rare in girls and is challenging to diagnose as most girls have no prior physical, neurological, or psychiatric history.

Sir, We write to share our experience with the imaging of posterior fossa tumors in children and the common confusion between the imaging features of medulloblastoma and atypical teratoid/rhabdoid tumors (ATRT). We compared the imaging findings of three cases of a posterior fossa tumor in children of ages ranging from 2.5 to 3.5 years to the imaging findings in literature. We had reported all the three cases as medulloblastoma (PNET-MB), but the final pathological findings were of ATRT. Over the past decade, atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system have emerged as a distinct entity.[1] This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET)/medulloblastoma. The unique immunohistochemical profile of an ATRT helps to distinguish it from a PNET/medulloblastoma. This is of clinical importance because the prognosis of a patient with an ATRT is worse than that of a patient with PNET/medulloblastoma despite aggressive surgical treatment, with or without adjuvant chemotherapy and radiation therapy. There are no specific imaging features for intracranial AT/RT. However, a high tendency towards large size, a hyperdense solid component on the CT scan with calcification, hemorrhage, necrosis, and subarachnoid spread suggest that this tumor should be considered in the differential diagnoses of large, pediatric, intracranial tumors.[2]

ific imaging features for intracranial AT/RT. However, a high tendency towards large size, a hyperdense solid component on the CT scan with calcification, hemorrhage, necrosis, and subarachnoid spread suggest that this tumor should be considered in the differential diagnoses of large, pediatric, intracranial tumors.[2] Infratentorial, atypical teratoid/rhabdoid tumors tend to present at a younger age than do medulloblastomas. The roof of the fourth ventricle is a common site of involvement. CPA involvement and intratumoral hemorrhage are more common in atypical teratoid-rhabdoid tumors.[3] Poor prognosis is associated with the presence of MR imaging evidence of a disseminated leptomeningeal tumor. The striking heterogeneity shown by imaging studies of the atypical teratoid/rhabdoid tumor reflects the histopathological complexity of these tumors, and awareness of atypical teratoid/rhabdoid tumors is important in making the correct diagnosis of this uncommon, but probably underdiagnosed entity.[4] We conclude that ATRT has to be the first diagnosis in a posterior fossa tumor involving the roof of the 4th ventricle showing more heterogeneity on MRI (than medulloblastomas) and presenting in a younger age group (< 3 years).

Sir, Septo-optic dysplasia (SOD) is a rare developmental anomaly, characterized by optic nerve hypoplasia and septum pellucidum (SP) agenesis, which is frequently associated with hormonal deficiencies.[1] The combination of SOD and olfactory tract hypoplasia is very rare. We present here one such case of a four month-old male patient with the antenatal diagnosis of an SP cyst. The child had an otherwise unremarkable birth history and physical development, having appropriately reached all early childhood milestones. Transfontanelar ultrasonographic examination revealed absence of SP and mild enlargement of the lateral ventricles. MRI [Figure 1] confirmed complete SP absence and showed right optic nerve atrophy. Hypoplasia of the olfactory tract and sulci hypoplasia were also noted. There was diffuse white matter atrophy with thinning of the corpus callosum which was otherwise well formed, and large ventricles with squared-off appearance of the frontal horns. The pituitary gland was small and there was no evidence of schizencephaly. Ophthalmologic examination confirmed right optic disc hypoplasia whereas endocrine studies showed no abnormalities. Figure 1 a) Axial FLAIR shows mild ventricular enlargement secondary to diffuse white matter hypoplasia; b) Coronal T2 shows absence of septum pelucidum and hypoplasia of the right optic nerve; c) Sagital T1 shows thinning of the corpus calosum and a small hypophysis

The child had an otherwise unremarkable birth history and physical development, having appropriately reached all early childhood milestones. Transfontanelar ultrasonographic examination revealed absence of SP and mild enlargement of the lateral ventricles. MRI [Figure 1] confirmed complete SP absence and showed right optic nerve atrophy. Hypoplasia of the olfactory tract and sulci hypoplasia were also noted. There was diffuse white matter atrophy with thinning of the corpus callosum which was otherwise well formed, and large ventricles with squared-off appearance of the frontal horns. The pituitary gland was small and there was no evidence of schizencephaly. Ophthalmologic examination confirmed right optic disc hypoplasia whereas endocrine studies showed no abnormalities. Figure 1 a) Axial FLAIR shows mild ventricular enlargement secondary to diffuse white matter hypoplasia; b) Coronal T2 shows absence of septum pelucidum and hypoplasia of the right optic nerve; c) Sagital T1 shows thinning of the corpus calosum and a small hypophysis The diagnosis of SOD is established when optic disc hypoplasia is observed in association with agenesis of the septum pellucidum.[12] This case represents a very rare association of SOD and olfactory tract hypoplasia.

Figure 1 a) Axial FLAIR shows mild ventricular enlargement secondary to diffuse white matter hypoplasia; b) Coronal T2 shows absence of septum pelucidum and hypoplasia of the right optic nerve; c) Sagital T1 shows thinning of the corpus calosum and a small hypophysis The diagnosis of SOD is established when optic disc hypoplasia is observed in association with agenesis of the septum pellucidum.[12] This case represents a very rare association of SOD and olfactory tract hypoplasia. The etiology of SOD remains uncertain, with genetic abnormalities (in continuum with lobar holoprosencephaly) and intrauterine insults having nevertheless been proposed as etiological factors.[1] In several cases, mutations in the HESX1 gene were shown to be implicated with mild pituitary hypoplasia or SOD.[1] Transgenic mice lacking the homolog gene of human Hesx1 exhibit a phenotype, including SP abnormalities, hypoplastic optic vesicles, pituitary dysplasia, and defective olfactory development.[3] SOD also presents a highly variable phenotype in humans.[2] The authors believe that bulb and tract olfactory hypoplasia should be included in the variable phenotype of SOD.

Sir, Electrolyte disorders, especially hyponatremia, are common problems in patients with CNS disease. Although hyponatremia due to CNS disease is often attributed to SIADH, CSW and SIADH have similar laboratory findings and they overlap in their association with intracranial diseases.[12] In SIADH, there is a relatively volume-expanded state with hyponatremia, decreased serum osmolality, and inappropriately high ADH.[3] On the other hand, CSW is characterized by natriuresis with concomitant diuresis, decreased intravascular volume, and extracellular fluid depletion.[23] Thus, SIADH and CSW treatment require different approaches. SIADH treatment requires fluid restriction, whereas CSW treatment consists of fluid replacement with saline and mineralocorticoid.[45] Improper therapy can worsen the underlying condition and it is important that clinicians distinguish properly between CSW and SIADH.[67] A 16 year-old male was admitted to the hospital with nausea and vomiting. One week before admission, his oral intake had become poor and he had been vomiting 5–6 times a day for two weeks. Three to four days before the hospital admission, his stools were bloody. He was treated as Crohn disease patient for three months with sulfasalazin, ferrous sulphate, folic acid, and omega 3.

nd vomiting. One week before admission, his oral intake had become poor and he had been vomiting 5–6 times a day for two weeks. Three to four days before the hospital admission, his stools were bloody. He was treated as Crohn disease patient for three months with sulfasalazin, ferrous sulphate, folic acid, and omega 3. Physical examination revealed that the patient was dehydrated and lethargic. His temperature was 38.2°C, the pulse rate was 100 beats per minute, and the blood pressure 90/60 mm Hg. His weight was 31 kg (< 3 P) and his height was 153 cm (< 3 P). His eyes were sunken and there was tenting of the skin. Bowel movements were positive and increased bowel sounds were heard by auscultation. He had nuchal rigidity and positive Kernig and Brudzinski signs. The other results of the physical examination were normal. Laboratory tests performed after admission showed: the complete blood count WBC 6600/mm3, hemoglobin 9.7 g/dL, platelets 119000/mm3. A peripheric blood smear showed 87% neutrophils, 17% leukocytes, hypochromia, and anisocytosis. The serum contained 127 mmol/L sodium, 3.95 mmol/L potassium, 96.6 mmol/L chloride, 5 mg/dL urea, 0.4 mg/dL creatinine, and 0.7 mg/dL uric acid. Monteux test was negative and a computed tomographic (CT) scan of the head was normal. Cerebrospinal fluid examination revealed a lymphocytic picture (130 cells/mm3) with 65 mg/dL (0–45 normal) protein and 20 mg/dL glucose levels. Simultaneously performed laboratory tests revealed that levels of serum glucose and chloride were 90 mg/dL and 108 mmol/L respectively.

raphic (CT) scan of the head was normal. Cerebrospinal fluid examination revealed a lymphocytic picture (130 cells/mm3) with 65 mg/dL (0–45 normal) protein and 20 mg/dL glucose levels. Simultaneously performed laboratory tests revealed that levels of serum glucose and chloride were 90 mg/dL and 108 mmol/L respectively. Based on these findings indicating meningitis, intravenous ceftriaksone was started and 20 mL/kg normal saline was given in one hour for volume depletion. This was followed by hypertonic NaCl (3% NaCl) with an IV fluid dose of 2500 mL/m2/day. On day two, hemiplegia developed in the right side of the body and a CT scan of the head was repeated and found to be normal. Biochemical tests were repeated and severe hyponatremia was detected (Na: 118 mmol/L) despite saline resuscitation. Hypovolemia persisted without any source of GIS fluid loss; a normal serum urea level (4.8 mg/dL) and increased urine output (4.5 L/day) were also noted. Serum osmolality was 225 mOsm/kg and urine Na 294 mmol/L. However, SIADH was ruled out because of the increased fractional Na (3.1%) and uric acid (3.2%) excretion seen with the observed polyuria. The patient had the clinical and laboratory findings of CSW and was managed with IV fluids: hypertonic sodium solutions and IV corticosteroids (prednisolone 2 mg/kg/day). Serum sodium levels increased gradually to the level of 136 mmol/L [Figure 1]. On day 10, the patient became confused, developed respiratory distress, and died on day 11. Figure 1 Serum sodium level and urine output in the course of the disease

The patient had the clinical and laboratory findings of CSW and was managed with IV fluids: hypertonic sodium solutions and IV corticosteroids (prednisolone 2 mg/kg/day). Serum sodium levels increased gradually to the level of 136 mmol/L [Figure 1]. On day 10, the patient became confused, developed respiratory distress, and died on day 11. Figure 1 Serum sodium level and urine output in the course of the disease Electrolyte disorders are common problems in patients with central nervous system insult such as trauma, infection, or hemorrhage. The management of electrolyte and fluid balance in these patients can be difficult. The serum sodium levels, rapid alterations of sodium levels, and the duration of hyponatremia are factors that worsen the underlying CNS conditions. How common CSW is uncertain. Previous studies show that it is as common as SIADH whereas some studies say that it is overstated.[8] CSW is regarded as a rare entity[5] in childhood and its prevalence is insufficient, there being mostly isolated case reports and the report of one small series in literature.

Electrolyte disorders are common problems in patients with central nervous system insult such as trauma, infection, or hemorrhage. The management of electrolyte and fluid balance in these patients can be difficult. The serum sodium levels, rapid alterations of sodium levels, and the duration of hyponatremia are factors that worsen the underlying CNS conditions. How common CSW is uncertain. Previous studies show that it is as common as SIADH whereas some studies say that it is overstated.[8] CSW is regarded as a rare entity[5] in childhood and its prevalence is insufficient, there being mostly isolated case reports and the report of one small series in literature. Central nervous system infections, including tuberculosis meningitis, bacterial meningitis, and viral meningoencephalitis can cause cerebral salt wasting. However, there are a few case reports in literature that describe the association of CSW with infection.[9] The mechanism by which cerebral disease leads to renal salt wasting is not well known. Decisions regarding treatment can be taken by investigating the levels of natriuretic peptides (ADH, ANP, BNP, renin-aldosterone axis elements). AVP and BNP were shown to be elevated eight days after cerebral injury when compared to the controls.[4] However, this may not be an universal finding in all patients.[5] Controversy exists around the cause of hyponatremia in tuberculosis meningitis as some studies report the cause to be inappropriate secretion of ADH whereas others cite increased ANP levels as the cause.[1011]

ral injury when compared to the controls.[4] However, this may not be an universal finding in all patients.[5] Controversy exists around the cause of hyponatremia in tuberculosis meningitis as some studies report the cause to be inappropriate secretion of ADH whereas others cite increased ANP levels as the cause.[1011] Due to the distinction between CSW and SIADH, CWS responds to sodium and water replacement, whereas SIADH is treated by fluid restriction. Our case had symptomatic hyponatremia with polyuria and natriuresis. Urinary Na and fractional excretion of Na were also high. This salt-losing condition ruled out SIADH wherein urine output is usually high. This feature plays an important role in the diagnosis, as discussed in previous reports.[8] In our patient, a high urine output (> 4–5 litres per day) lasted for five days. A diagnosis of CSW was made on the basis of the following findings: 1. marked natriuresis with negative sodium and water balance, 2. the patient's hyponatremic and relatively salt-depleted state despite infusions of hypertonic saline solutions, and 3. persistent high fractional uric acid excretion rates throughout the course of the disease. There is no evidence in literature that Crohn disease and/or salazopryrine cause salt wasting.

Due to the distinction between CSW and SIADH, CWS responds to sodium and water replacement, whereas SIADH is treated by fluid restriction. Our case had symptomatic hyponatremia with polyuria and natriuresis. Urinary Na and fractional excretion of Na were also high. This salt-losing condition ruled out SIADH wherein urine output is usually high. This feature plays an important role in the diagnosis, as discussed in previous reports.[8] In our patient, a high urine output (> 4–5 litres per day) lasted for five days. A diagnosis of CSW was made on the basis of the following findings: 1. marked natriuresis with negative sodium and water balance, 2. the patient's hyponatremic and relatively salt-depleted state despite infusions of hypertonic saline solutions, and 3. persistent high fractional uric acid excretion rates throughout the course of the disease. There is no evidence in literature that Crohn disease and/or salazopryrine cause salt wasting. The key feature of CSW is the hyponatremia which is the initial marker that leads to the diagnosis. The next most important event is treating and protecting the patient from its negative effects by matching the Na and water input to their output. Mineralocorticoid therapy was found to be effective in most patients. Doses of 0.1–0.4 mg/day fludrocortisone with saline and water replacement increased Na concentrations to normal serum levels.[49] We could not obtain fludrocortisone and other steroids which have higher mineralocorticiod activity than prednisolone, therefore, 2 mg/kg/day prednisolone doses were used. Sodium levels increased to 136 mmol/L with this additional therapy.

ne and water replacement increased Na concentrations to normal serum levels.[49] We could not obtain fludrocortisone and other steroids which have higher mineralocorticiod activity than prednisolone, therefore, 2 mg/kg/day prednisolone doses were used. Sodium levels increased to 136 mmol/L with this additional therapy. In conclusion, one reason for hyponatremia in patients with meningitis can be cerebral salt wasting and management must take this situation into consideration.[12] Glucocorticosteroids can be used as alternatives for the mineralocorticoid, fludrocortisone, when it can not be obtained.

Sir, The Landau-Kleffner syndrome or the syndrome of acquired epileptic aphasia was first described in 1957.[1] The disorder is characterized by gradual or rapid loss of language in a previously normal child. While this disorder appears to be relatively uncommon, its frequency is questionable due to its unfamiliarity among health professionals, and the likelihood of misdiagnosis. It is imperative that communication specialists become alert to the characteristic symptoms of LKS. All pediatric LKS patients have abnormal EEG that is compatible with the diagnosis of epilepsy; however, only 70% have clinical seizures. We report here a case of this rare disorder and a review of the current literature concerning this disorder.

unication specialists become alert to the characteristic symptoms of LKS. All pediatric LKS patients have abnormal EEG that is compatible with the diagnosis of epilepsy; however, only 70% have clinical seizures. We report here a case of this rare disorder and a review of the current literature concerning this disorder. A 14 year-old female presented to us with the complaint of progressive loss of speech and seizure disorder for the past one year. According to the attendant accompanying the patient, the child was developmentally normal before the onset of the illness. However, after some trauma to the head, although the immediate period was uneventful, one month after the trauma, her speech progressively decreased and she started communicating with signs. Over a period of five to six months, the paucity of speech progressed to complete aphasia and the child also had abnormal behavior in the form of bouts of aggressiveness and hyperactivity. The child also had five episodes of generalized tonic-clonic seizures, which occurred during her sleep since the onset of the illness. Examination revealed that the child displayed abnormal behavior and attention deficit, and was not responding verbally to any command. The results of her general and systemic examination were normal. CNS examination results also were normal except for the abnormal behavior, attention deficit, auditory agnosia, and aphasia (both receptive and expressive). Fundus examination results were normal as were the CBC, LFT, RFT, and CSF. BERA was normal, and the EEG revealed generalized spikes bilaterally over the temporoparital region with background slow waves; the MRI was also normal. On the basis of the presentation, EEG, and the normal MRI, Landau-Kleffner syndrome was diagnosed and the child was started on sodium valproate, prednisolone, and speech therapy; the child is under follow-up.

eralized spikes bilaterally over the temporoparital region with background slow waves; the MRI was also normal. On the basis of the presentation, EEG, and the normal MRI, Landau-Kleffner syndrome was diagnosed and the child was started on sodium valproate, prednisolone, and speech therapy; the child is under follow-up. The Landau-Kleffner syndrome is a rare disorder characterized by an acquired receptive and expressive aphasia and epileptic seizures. It is also known as ‘a syndrome of acquired aphasia with convulsive disorder,’ or ‘acquired aphasia of childhood with epilepsy’.[23] It is defined on the basis of specific clinical and electroencephalography (EEG) criteria. It is almost certainly under-recognized and therefore, underdiagnosed. This syndrome was first described in 1957 by Dr. William M. Landau and Dr. Frank R. Kleffner, who identified six children with the disorder. Since then, almost 200 cases have been reported;[13] there appears to be a male preponderance in an approximate male: female ratio of 2:1.

ecognized and therefore, underdiagnosed. This syndrome was first described in 1957 by Dr. William M. Landau and Dr. Frank R. Kleffner, who identified six children with the disorder. Since then, almost 200 cases have been reported;[13] there appears to be a male preponderance in an approximate male: female ratio of 2:1. Over 50% of the affected children present between the ages of three and eight years with an apparent loss of auditory verbal understanding (agnosia) of speech. Deafness is frequently the initially considered diagnosis (this is the predominant reason why Landau-Kleffner syndrome is diagnosed late). In the vast majority of children with the syndrome, the agnosia/aphasia is acquired, occurring in a previously normal child. The aphasia may be primarily receptive or expressive, and auditory agnosia may be so severe that the child is oblivious to everyday sounds. Hearing is normal, but behavioral problems, including irritability and poor attention span, are particularly common. Formal testing often shows normal performance and visual-spatial skills, despite poor language. Seizures are reported to occur in 70–75% of all patients with Landau-Kleffner syndrome at some point in the evolution of the condition, and are usually complex-partial (with focal motor and atypical absence symptomatology), generalized tonic-clonic and atonic (‘drop’) seizures; tonic and myoclonic seizures are rare. Seizures may be infrequent or repeated (nocturnal) with (rarely) episodes of convulsive and nonconvulsive status epilepticus.[3]

ondition, and are usually complex-partial (with focal motor and atypical absence symptomatology), generalized tonic-clonic and atonic (‘drop’) seizures; tonic and myoclonic seizures are rare. Seizures may be infrequent or repeated (nocturnal) with (rarely) episodes of convulsive and nonconvulsive status epilepticus.[3] The final clinical manifestation of Landau-Kleffner syndrome is a behavioral disturbance, which may occur in almost 75% of the patients with the syndrome, and is frequently severe. Explanations for the behavioral difficulties may include a primary functional disinhibition at a limbic or diencephalic level, or as a secondary (frustration-induced) effect due to loss of comprehension. Unprovoked outbursts of rage and aggression may also occur; rarely, the child may appear autistic or psychotic” and hence, risk exclusion or suspension from school. It is this aspect that often leads to an initial diagnosis of a primary conduct disorder and referral to a psychiatrist.

fect due to loss of comprehension. Unprovoked outbursts of rage and aggression may also occur; rarely, the child may appear autistic or psychotic” and hence, risk exclusion or suspension from school. It is this aspect that often leads to an initial diagnosis of a primary conduct disorder and referral to a psychiatrist. The pathogenesis and etiology of Landau-Kleffner syndrome are unknown and probably complex. The agnosia/aphasia may represent an ‘epileptic’ phenomenon caused by a paroxysmal spike and slow-wave activity within the appropriate temporal lobe.[3] However, this may be difficult to accept in the absence of clinically occurring epileptic seizures. An alternative hypothesis is that there is an underlying brain pathology in an area or areas concerned with speech, which may be responsible both for the comprehension/speech difficulties and the abnormal EEG findings and subsequently, for the development of epileptic seizures. What the precise nature of this ‘underlying pathology’ is, is also unclear. Children have developed normally and are usually healthy with no preceding illness/infection before the onset of the syndrome and there is no obvious genetic predisposition. Inflammatory head trauma and postinfectious causes have been implicated, but have not been consistently demonstrated or confirmed by neuroradiological or neuropathological investigations, including cerebrospinal fluid analysis. It remains unclear as to whether the underlying pathology is simply functional or due to a subtle structural lesion. The available evidence and the natural history of Landau-Kleffner syndrome would tend to suggest the former hypothesis, possibly on the basis of an impaired or dysfunctional ‘loop’ within the speech cortex: hearing-verbal integration-spoken language.

pathology is simply functional or due to a subtle structural lesion. The available evidence and the natural history of Landau-Kleffner syndrome would tend to suggest the former hypothesis, possibly on the basis of an impaired or dysfunctional ‘loop’ within the speech cortex: hearing-verbal integration-spoken language. EEG reveals a high-amplitude spike, and wave discharges predominate and tend to be bitemporal, but they can be multifocal or generalized. The EEG findings may be normal in the evolutionary stages of the condition. The spike discharges are always more apparent during nonrapid eye movement (REM) sleep; thus, a child suspected of LKS should have an EEG during sleep, particularly if the awake record is normal. If the sleep EEG is normal but a high index of suspicion for the diagnosis of LKS continues, the child should be referred to a tertiary pediatric epilepsy center for prolonged EEG recording and specific neuroimaging studies. CT and MRI studies typically yield normal results, and positron-emission tomography (PET) scans have demonstrated either unilateral or bilateral hypo- or hypermetabolism .[4] Microscopic examination of surgical specimens has shown minimal gliosis, but no evidence of encephalitis.

ding and specific neuroimaging studies. CT and MRI studies typically yield normal results, and positron-emission tomography (PET) scans have demonstrated either unilateral or bilateral hypo- or hypermetabolism .[4] Microscopic examination of surgical specimens has shown minimal gliosis, but no evidence of encephalitis. The diagnosis of Landau-Kleffner syndrome depends largely on being aware that the condition exists, and its usual pattern of presentation. Differential diagnoses include deafness, an acute behavioral or psychiatric disorder (including elective mutism), or epilepsy in which there is a transient postictal dysphasia or aphasia, but without the profound agnosia and behavioral dysfunction. Valproic acid is the anticonvulsant of choice; however, some children require a combination of valproic acid and clobazam to control their seizures. If the seizures and aphasia persist, a trial of steroids should be considered. One recommended schedule consists of oral prednisone, 2 mg/kg/24 h for 1 month, tapered to 1 mg/kg/24 h for an additional month. With clinical improvement, the prednisone is reduced further to 0.5 mg/kg/24 h for up to 6–12 months. It is imperative to initiate speech therapy and maintain treatment for several years, because improvement in language function occurs only over a prolonged period. Some centers advocate an operative procedure—subpial transection—when medical management fails.[5]

reduced further to 0.5 mg/kg/24 h for up to 6–12 months. It is imperative to initiate speech therapy and maintain treatment for several years, because improvement in language function occurs only over a prolonged period. Some centers advocate an operative procedure—subpial transection—when medical management fails.[5] In conclusion, although the Landau-Kleffner syndrome is uncommon, there is a need for an increased awareness of the disorder, particularly among those professionals to whom are commonly referred children with acute or subacute loss of speech and language—hospital and community pediatricians; audiologists; personnel in the ear, nose, and throat department; psychiatrists, and pediatric neurologists. Once considered, the diagnosis may be confirmed by sleeping EEG activity. A short course of corticosteroids would seem reasonable, but the role of the newer antiepileptic drugs requires further evaluation. Speech therapy and educational rehabilitation should be introduced as early as possible and a neurosurgical referral should be considered for those children with persisting aphasia and drug-resistant seizures.

Sir, We report here an interesting case of a two and a half year-old boy who presented with features of Delleman syndrome with Goldenhar overlap. Delleman syndrome includes orbital cysts or microopthalmia, focal skin defects and central nervous system cysts, and/or hydrocephalus (oculocerebrocutaneous syndrome)[1] whereas Goldenhar syndrome includes a triad of epibulbar dermoid, accessory auricular appendages, and preauricular fistulae.[2] Various CNS, cardiac, vertebral, pulmonary, GIT, and facial defects have been later added to Goldenhar syndrome.[3]

rvous system cysts, and/or hydrocephalus (oculocerebrocutaneous syndrome)[1] whereas Goldenhar syndrome includes a triad of epibulbar dermoid, accessory auricular appendages, and preauricular fistulae.[2] Various CNS, cardiac, vertebral, pulmonary, GIT, and facial defects have been later added to Goldenhar syndrome.[3] This two and a half year-old boy presented with complaints of a large head, absent right eye, right ear, and right facial hemiatrophy. Examination revealed his head circumference to be 49 cm; the anterior and posterior fontanelles were open and tense. He had a 2 cm soft, nontender, nonpulsatile, transilluminant swelling with a cough impulse in the scalp, over the right medial parietal region. He had an absent right eye with partially formed eyelids but a normal left eye [Figure 1]. The right ear pinna was absent with no visible external auditory meatus. There was a skin tag in the region of the right ear whereas the left ear was low set and the pinna malformed with an abnormal preauricular skin tag. He had right facial hemiatrophy [Figure 2] and the palate was high-arched. He had a dimple in the midline lumbar region superior to the natal cleft with no skin tethering, hair tuft, lipoma, sinus, hyperpigmented patch, or spina bifida. There were no other anomalies or neurocutaneous markers. The fundus was normal in the left eye and there were no focal neurological deficits. Figure 1 This clinical picture shows an absent right eye with partially formed eyelids and a normal left eye. The left ear is low set with a malformed pinna

This two and a half year-old boy presented with complaints of a large head, absent right eye, right ear, and right facial hemiatrophy. Examination revealed his head circumference to be 49 cm; the anterior and posterior fontanelles were open and tense. He had a 2 cm soft, nontender, nonpulsatile, transilluminant swelling with a cough impulse in the scalp, over the right medial parietal region. He had an absent right eye with partially formed eyelids but a normal left eye [Figure 1]. The right ear pinna was absent with no visible external auditory meatus. There was a skin tag in the region of the right ear whereas the left ear was low set and the pinna malformed with an abnormal preauricular skin tag. He had right facial hemiatrophy [Figure 2] and the palate was high-arched. He had a dimple in the midline lumbar region superior to the natal cleft with no skin tethering, hair tuft, lipoma, sinus, hyperpigmented patch, or spina bifida. There were no other anomalies or neurocutaneous markers. The fundus was normal in the left eye and there were no focal neurological deficits. Figure 1 This clinical picture shows an absent right eye with partially formed eyelids and a normal left eye. The left ear is low set with a malformed pinna Figure 2 This clinical picture shows that the right ear pinna is absent with no external auditory meatus seen. There is a skin tag seen in the region of the right ear. Right facial hemiatrophy also can be appreciated

Figure 1 This clinical picture shows an absent right eye with partially formed eyelids and a normal left eye. The left ear is low set with a malformed pinna Figure 2 This clinical picture shows that the right ear pinna is absent with no external auditory meatus seen. There is a skin tag seen in the region of the right ear. Right facial hemiatrophy also can be appreciated CT of the brain [Figures 3a and b] showed obstructive hydrocephalus with dilated lateral and third ventricles but a normal fourth ventricle. The bony orbit was present on the right side although there was no globe seen within. The bony part of the right external auditory canal was not visualized. The patient underwent a medium-pressure, right, ventriculoperitoneal shunt. Postoperatively, the fontanelles became lax and the parietal scalp swelling also decreased in size. The child was asymptomatic at one year follow-up. Figures 3a and b CT brain showing obstructive hydrocephalus with dilated lateral and third ventricles and normal fourth ventricle

CT of the brain [Figures 3a and b] showed obstructive hydrocephalus with dilated lateral and third ventricles but a normal fourth ventricle. The bony orbit was present on the right side although there was no globe seen within. The bony part of the right external auditory canal was not visualized. The patient underwent a medium-pressure, right, ventriculoperitoneal shunt. Postoperatively, the fontanelles became lax and the parietal scalp swelling also decreased in size. The child was asymptomatic at one year follow-up. Figures 3a and b CT brain showing obstructive hydrocephalus with dilated lateral and third ventricles and normal fourth ventricle Oculocerebrocutaneous syndrome or Delleman syndrome is a multiple congenital anomaly syndrome characterized by orbital cysts, cerebral anomalies, and focal dermal hypoplasia.[1] A more severe form of oculocerebrocutaneous syndrome can have anophthalmia, congenital hydrocephalus, as well as cleft lip and palate. This is a rare and sporadic disorder and possible etiological hypotheses include the survival of a lethal mutation by mosaicism and external causal factors.[4] Disruption of the anterior neuroectodermal plate seems to be the most probable pathogenic mechanism. A primarily unilateral involvement of this syndrome has been emphasized.[4] A postzygotic or somatic mutation resulting in a mosaic state might account for the primarily ectodermal involvement, unilateral predominance, and the sporadic nature of this syndrome.[4] One report from India has been that of a 4 year-old male child who presented with oculocerebrocutaneous syndrome featuring focal alopecia on the left side of the scalp, left periorbital skin appendages, a left-sided orbital dermoid, a large left-sided intracranial cyst, and optic atrophy.[5] Cases of Delleman syndrome need to be differentiated from encephalo-cranio-cutaneous lipomatosis.[5]

ted with oculocerebrocutaneous syndrome featuring focal alopecia on the left side of the scalp, left periorbital skin appendages, a left-sided orbital dermoid, a large left-sided intracranial cyst, and optic atrophy.[5] Cases of Delleman syndrome need to be differentiated from encephalo-cranio-cutaneous lipomatosis.[5] Goldenhar syndrome, first described by Von Arct and later by Goldenhar, represent morphological abnormalities involving the first and the second branchial arches. Due to the anomalies of the eye, ear, and vertebral column, Goldenhar syndrome is also known as oculoauriculovertebral syndrome.[6] Goldenhar syndrome have also been reported with rare associations.[7] Definitive etiology has not been described—the proposed factors are abnormal mezoblastic development and abnormal embryonic vascular supply of the first arch.[8] Although most cases are sporadic, autosomal dominant and autosomal recessive modes of inheritance have been described. Trisomy of 7, 22 have been described in association with Goldenhar syndrome.[9] The syndrome usually has a male predominance and the right side is preferentially involved. Goldenhar syndrome needs to be differentiated from Treacher Collins and Pierre-Robin syndromes.[10]

essive modes of inheritance have been described. Trisomy of 7, 22 have been described in association with Goldenhar syndrome.[9] The syndrome usually has a male predominance and the right side is preferentially involved. Goldenhar syndrome needs to be differentiated from Treacher Collins and Pierre-Robin syndromes.[10] In our case, the possibility of Dellemans syndrome with Goldenhar overlap was considered because of the absent right eye and hydrocephalus (features of Dellemans syndrome) and absent right ear, preauricular skin tags, and right facial hemiatrophy (features of Goldenhar syndrome). Multiple variants of these syndromes have been described, but, to the best of our knowledge, the combination of features described in our case has not been reported to date. A detailed clinical examination is required in these cases to document all the abnormalities and a multidisciplinary approach is usually required in the appropriate management and rehabilitation of these cases.

Sir, A 12 year-old girl presented with progressive weakness of both lower limbs, difficulty in walking, and numbness in her legs since the last two months. She had become bedridden for the last one week. Clinical examination did not reveal any stigmata such as dimples, hair, fistulae, or any mass on her spine. Neurological examination showed spastic paraplegia with 0/5 grade bilateral power. All sensations were markedly diminished below the D5 level. MRI scans revealed a hyperintense, elongated mass lesion on the saggital T1W and T2W images between the D3–D8 segments [Figure 1]. Axial T1W image showed that the lipoma was situated dorsal to the spinal cord [Figure 2]. A D3-D8 laminectomy was done and the duramater was opened in the midline and retracted. A lipoma was identified on the posterior aspect of the cord and there was no clear surgical cleavage between the cord and the tumor. Subtotal excision was carried out. No significant improvement was seen in the neurological status at the six months’ follow-up and the patient was referred for physiotherapy and rehabilitation. However, the patient was lost to follow-up subsequently. Figure 1 Sagittal T1- and T2-weighted images showing hyperintense lesion extending from D3–D8 level (arrow) Figure 2 Axial T1W image showing the hyperintense lipoma situated posterior to the spinal cord

A 12 year-old girl presented with progressive weakness of both lower limbs, difficulty in walking, and numbness in her legs since the last two months. She had become bedridden for the last one week. Clinical examination did not reveal any stigmata such as dimples, hair, fistulae, or any mass on her spine. Neurological examination showed spastic paraplegia with 0/5 grade bilateral power. All sensations were markedly diminished below the D5 level. MRI scans revealed a hyperintense, elongated mass lesion on the saggital T1W and T2W images between the D3–D8 segments [Figure 1]. Axial T1W image showed that the lipoma was situated dorsal to the spinal cord [Figure 2]. A D3-D8 laminectomy was done and the duramater was opened in the midline and retracted. A lipoma was identified on the posterior aspect of the cord and there was no clear surgical cleavage between the cord and the tumor. Subtotal excision was carried out. No significant improvement was seen in the neurological status at the six months’ follow-up and the patient was referred for physiotherapy and rehabilitation. However, the patient was lost to follow-up subsequently. Figure 1 Sagittal T1- and T2-weighted images showing hyperintense lesion extending from D3–D8 level (arrow) Figure 2 Axial T1W image showing the hyperintense lipoma situated posterior to the spinal cord Intradural spinal lipoma (ISL) constitutes approximately 1% of all spinal tumors and is usually associated with lumbo-sacral spinal dysraphism.[1] ISLs unassociated with spinal dysraphism are rare with only a few cases being reported in literature.[2–6] They are seen in children and young adults and are situated on the posterior aspect of the spinal cord in the cervico-thoracic or thoracic regions. They show equal gender incidence but are reported to show aggravation of symptoms during or after pregnancy.[3] The patients usually present with a long history of disability followed by a rapid progress of symptoms. The presenting complaints are spastic weakness in the extremities, dysestheic sensory changes, and gait difficulties. The neurological deficits are initially subtle and the history can span many years before the patient seeks medical attention. Theories about their pathogenesis are controversial, but the malformation theory wherein inclusion of the misplaced adipocytes during the formation of the neural tube causes the growth of lipoma . Thus, this is a hamartoma rather than a true neoplasm, which also explains the dorsal location of the lipoma.[3] Some believe intraspinal lipomas are congenital lesions and would not only compress, but also replace normal tissue during development.[6] A spinal lipoma without dysraphism has only a small space for expansion and thus, has an early presentation of symptoms as seen in our case.

ns the dorsal location of the lipoma.[3] Some believe intraspinal lipomas are congenital lesions and would not only compress, but also replace normal tissue during development.[6] A spinal lipoma without dysraphism has only a small space for expansion and thus, has an early presentation of symptoms as seen in our case. ISLs adhere so closely to the adjacent spinal cord that they cannot be excised completely. Most symptomatic patients do not show any significant improvement in the neurological function after surgery. Hence, the operative principle should be decompression before symptom progression and subtotal resection wherever necessary.

Neuroendoscopy has revolutionized the management of hydrocephalus. Endoscopic third ventriculostomy is gaining popularity as a technique with several advantages. However, proper selection of the patient based on the age, pathology and imaging is necessary to achieve the best surgical results. In addition, it is important to follow meticulous steps during surgery in order to avoid complications. On the basis of pathology and images the site for the burrhole is chosen. After a detailed study of images, particularly sagittal MRI sections [Figure 1], a precoronal burrhole in the midpupillary line is made for the third ventriculostomy. The burrhole position may be shifted forward or backward depending on the necessity to examine the aqueduct or other third ventricular regions. The child is positioned supine under general anesthesia. The part that has to be operated is prepared and draped [Figure 2]. A curvilinear skin incision, about 1.5 cm long is made in the precoronal region. A small skin flap is raised [Figure 3]. The periostium is separated [Figure 4] and a burrhole is made using either a high-speed drill or Hudson's brace [Figure 5]. The dura is opened cruciately. It is advisable to introduce the ventricular cannula and examine the depth and intraventricular pressure [Figure 6]. The outer sheath and stillet is passed through a cortical incision in the direction of the lateral ventricle till a “give way” is felt upon entering the ventricle [Figure 7]. A preassembled operating scope, initially “0°,” is then passed through the sheath [Figure 8]. As the scope is passing through, the parenchyma and the ventricular cavity is seen successively. In the lateral ventricle, it is important to have the proper anatomical orientation. The camera is thus adjusted accordingly. We need to identify the lateral wall, floor and the septum pellucidum [Figure 9]. At the junction of the septum and the floor, the choroid plexus is identified. The choroid plexus is an important and constant landmark to follow. It leads anteriorly to the foramen of Monroe [Figure 10]. At the foramen, one can see the choroid plexus entering the third ventricle.

and the septum pellucidum [Figure 9]. At the junction of the septum and the floor, the choroid plexus is identified. The choroid plexus is an important and constant landmark to follow. It leads anteriorly to the foramen of Monroe [Figure 10]. At the foramen, one can see the choroid plexus entering the third ventricle. The thalamostriate vein and the anterior fornix are also important landmarks. At this juncture, the structures in the third ventricles will be faintly visible [Figure 11]. The scope is then gently advanced into the third ventricle through the foramen of Monroe. The structures of the floor of the third ventricle are now clearly visible [Figure 12]. Tuber cinereum is a bright red spot located anteriorly in the midline. The paired mamillary bodies are located posteriorly. Dorsum sella and basilar artery pulsations can also be seen if the floor is very thin. The ideal landmark for ventriculostomy is in the midline just anterior to the mamillary bodies. The floor is thinnest here. Initially, either bipolar or monopolar probe is used to perforate the floor by making “half twist” movements [Figure 13]. A Fogarty catheter, size 4 French units, is subsequently passed through the perforated floor. The balloon is gently inflated to enlarge the opening in the floor, and then deflated [Figure 14]. This inflation and deflation is repeated with saline till the required size of the opening is created [Figure 15]. It is essential to ensure that the floor is completely opened including the deeper arachnoid membrane in order to achieve successful result [Figure 16]. One can visualize the basilar artery and other prepontine structures by advancing the scope through the opening in the floor [Figure 17]. With a 30° angled scope one can look at the posterior part of the third ventricle, the massa intermedia and the aqueduct of Sylvius [Figure 18]. After ensuring that meticulous hemostasis the scope is gently removed from the third ventricle to lateral ventricle [Figure 19] and completely from further up. Throughout the procedure the ventricle is continuously irrigated with Ringer's lactate solution at body temperature. The cortical opening is filled with an absorbable gelatin (Gelfoam) sponge to reduce cerebrospinal fluid leak and subdural collection [Figure 20]. The skin over the burrhole is closed in two layers [Figure 21]. This procedure when performed correctly, in a properly selected child, yields rewarding results [Figure 22].

The cortical opening is filled with an absorbable gelatin (Gelfoam) sponge to reduce cerebrospinal fluid leak and subdural collection [Figure 20]. The skin over the burrhole is closed in two layers [Figure 21]. This procedure when performed correctly, in a properly selected child, yields rewarding results [Figure 22]. Figure 1 MRI sagittal section Figure 2 Preparation of the part Figure 3 Skin flap Figure 4 Periosteum elevation Figure 5 Burrhole Figure 6 Ventricular cannulation Figure 7 Introduction of outer sheath Figure 8 Introduction of endoscope Figure 9 View of the lateral ventricle Figure 10 Foramen of monroe Figure 11 Structures in the floor of the third ventricle Figure 12 Tuber cinereum and the mamillary bodies, with a thin floor of third ventricle Figure 13 Perforation of the floor Figure 14 Inflating the balloon Figure 15 Enlarging the ventriculostomy Figure 16 Enlarging the ventriculostomy close up view Figure 17 Visualization of basilar artery and its branches in the prepontine cistern Figure 18 Aqueduct and massa intermedia Figure 19 Withdrawal of the scope back into the lateral ventricle Figure 20 Plugging the corticotomy with a Gelfoam roll Figure 21 Wound closure Figure 22 Follow-up Safety tips Assemble the endoscope properly, adjust focus, magnification and white balance Orient yourself correctly Ensure good illumination and clear visualization throughout the procedure Maintain irrigation and ensure that the exit channels are open to avoid raised ICP Do not panic in case of hemorrhage Abandon the procedure when you are in doubt Be prepared to do a craniotomy if there is an eventuality Source of Support: Nil

Orient yourself correctly Ensure good illumination and clear visualization throughout the procedure Maintain irrigation and ensure that the exit channels are open to avoid raised ICP Do not panic in case of hemorrhage Abandon the procedure when you are in doubt Be prepared to do a craniotomy if there is an eventuality Source of Support: Nil Conflict of Interest: None declared.

Introduction Cranially conjoined twins (craniopagus) are regarded as one of the rarest human malformations. Craniopagus represents 2 to 6% of conjoined twins and is the rarest type of disorder.[1] A conventional angiogram with three dimensions is needed to confirm the exact extent of sharing of the arterial / venous tree. 3D angiography was first proposed by CORNELIUS[2] and advanced into clinical practice by VOIGT in 1975.[2] We present a case of craniopagus vertical type II twins, evaluated for cerebral circulation. Case Report TWIN I and TWIN II both female twins aged four (D.O.B - 15/10/2003) were referred to our institution for digital subtraction angiography. 3D angiographic evaluation was done for the craniopagus vertical type II twins, to assess the cerebral vasculature and to identify the different variations in cerebral circulation, which is essential for surgical planning. An angiogram was performed by selective, individual, as well as simultaneous injections of internal, external, and vertebral arteries of both twins. A 3 D rotational angiogram was also performed, to study the anatomic variations in detail. Simultaneous and sequential injections of both the twins was performed by positioning TWIN I on the caudal end of the angiography table, head being turned in the right lateral position with nose to right, while TWIN II was positioned on the cranial end of the table with head in Anteroposterior position. Table Cerebral circulation

Simultaneous and sequential injections of both the twins was performed by positioning TWIN I on the caudal end of the angiography table, head being turned in the right lateral position with nose to right, while TWIN II was positioned on the cranial end of the table with head in Anteroposterior position. Table Cerebral circulation Four-year-old craniopagus twins, both female, were evaluated for their detailed cerebral circulation. The angiographic machine used for the same was Advantax LCN + (GE Biplane system). Retrograde seldingers method, through right femoral puncture of both twins, was used as a technique to study the variations in the arterial and venous cerebral circulation of the craniopagus twins. TWIN I: The predominant venous drainage of TWIN I was through the left Transverse-Sigmoid system, draining out through the left internal jugular vein and through the circular sinus into TWIN II's Transverse-Sigmoid Jugular system bilaterally. The deep venous system was not identified. The arterial as well as the capillary drainage was normal. TWIN II: TWIN II had venous drainage through the circular sinus into the Transverse-Sigmoid Jugular system bilaterally and to the occipital sinus. A significant portion of the venous drainage was shunting into TWIN I's left transverse sinus. The deep venous system was not identified clearly in this twin also. The external carotid angiogram of TWIN II showed a significant crossover of the external carotid arterial territory, to supply TWIN I's scalp [Figures 1–8]. Figure 1 Craniopagus vertical type II twins

Jugular system bilaterally and to the occipital sinus. A significant portion of the venous drainage was shunting into TWIN I's left transverse sinus. The deep venous system was not identified clearly in this twin also. The external carotid angiogram of TWIN II showed a significant crossover of the external carotid arterial territory, to supply TWIN I's scalp [Figures 1–8]. Figure 1 Craniopagus vertical type II twins Figure 2 Internal carotid angiogram showing normal arterial phase(A) and capillary phase (B)of the twin I Figure 3 Showing the venous drainage of the twin I through the left transverse sigmoid system(arrow head) and circular sinus(arrow) into the twin II s transverse sigmoid jugular system bilaterally Figure 4 Internal carotid angiogram showing the normal arterial(A) and capillary phases(B) of the twin II Figure 5 Venous drainage is through the circular sinus(arrow) into Transverse - Sigmoid -Jugular system bilaterally and the occipital sinus. Deep Venous system is not identifi ed clearly Figure 6 External carotid angiogram of twin II shows signifi cant cross over of ECA territory to supply Twin I scalp Figure 7 Simulataneous and sequential injections of both the twins showing normal arterial and capillary phases Figure 8 Venous drainage is through the circular sinus into Transverse - Sigmoid -Jugular system bilaterally and the occipital sinus.A signifi cant portion of the venous drainage is shunted into Twin I s left transverse sinus. Deep Venous system is not identifi ed clearly

Figure 7 Simulataneous and sequential injections of both the twins showing normal arterial and capillary phases Figure 8 Venous drainage is through the circular sinus into Transverse - Sigmoid -Jugular system bilaterally and the occipital sinus.A signifi cant portion of the venous drainage is shunted into Twin I s left transverse sinus. Deep Venous system is not identifi ed clearly Discussion Conjoined twins are rare and the estimated prevalence in the literature varies widely from 1:50,000 to 1:200,000.[3] An increased prevalence is observed in parts of Southeast Asia and Africa, with reported occurrence ranging from 1:14,000 to 1:25,000.[4] Forty to 60% of conjoined twins are stillborn and almost 35% of live births do not survive even for 24 hours.[4] The craniopagus type (joined at the head) is exceedingly rare, with an incidence of one in 2.5 million births.[1] The conjoined twins are monozygotic, monoamniotic, and monochorionic. The chorion differentiates approximately four days after fertilization and the amnion differentiates approximately eight days after fertilization.[5] A conjoined twin occurs as a result of the failure of complete separation (fission) of a single fertilized ovum between 13 and 17 days of gestation. Due to the incomplete division of the embryonic disc of the blastocyst, conjoining occurs in the second week.

fferentiates approximately eight days after fertilization.[5] A conjoined twin occurs as a result of the failure of complete separation (fission) of a single fertilized ovum between 13 and 17 days of gestation. Due to the incomplete division of the embryonic disc of the blastocyst, conjoining occurs in the second week. The other theory states that the abnormality is due to the result of fusion of two separate embryos, with the junction occurring in the open cranial neuropore before the fourth week after fertilization.[6] Conjoined twins are always genetically identical and share the same sex. Females are more commonly affected, with a male / female ratio of 1:4.[7] These twins can be joined at the vertex, at the side, or at the forehead; the vertical type being the most common. O’Connell's classification denotes three anatomical types for vertical craniopagus, based on relative facial orientation (type 1: face same direction; type 2: face opposite direction (140 – 180 degrees) and type 3: intermediate angle of rotation of the long axis of one head on that of the other).[89] This congenital defect results in an area of absent cranial cutaneous ectoderm (scalp) and ectomeninx of varying severity and extent in the region where the developing telencephalic vesicles meet. The accurate assessment of cerebral circulation is crucial for surgical planning. Digital Subtracted Angiography (DSA) with Biplane and 3D is very important for the assessment of this complex vasculature.

The other theory states that the abnormality is due to the result of fusion of two separate embryos, with the junction occurring in the open cranial neuropore before the fourth week after fertilization.[6] Conjoined twins are always genetically identical and share the same sex. Females are more commonly affected, with a male / female ratio of 1:4.[7] These twins can be joined at the vertex, at the side, or at the forehead; the vertical type being the most common. O’Connell's classification denotes three anatomical types for vertical craniopagus, based on relative facial orientation (type 1: face same direction; type 2: face opposite direction (140 – 180 degrees) and type 3: intermediate angle of rotation of the long axis of one head on that of the other).[89] This congenital defect results in an area of absent cranial cutaneous ectoderm (scalp) and ectomeninx of varying severity and extent in the region where the developing telencephalic vesicles meet. The accurate assessment of cerebral circulation is crucial for surgical planning. Digital Subtracted Angiography (DSA) with Biplane and 3D is very important for the assessment of this complex vasculature. In our case the predominant venous drainage is through the circular sinus into the Transverse-Sigmoid-Jugular system bilaterally and the occipital sinus, which is demonstrated on the injection of TWIN II. Hyperdynamic circulation is seen in the TWIN II.

The accurate assessment of cerebral circulation is crucial for surgical planning. Digital Subtracted Angiography (DSA) with Biplane and 3D is very important for the assessment of this complex vasculature. In our case the predominant venous drainage is through the circular sinus into the Transverse-Sigmoid-Jugular system bilaterally and the occipital sinus, which is demonstrated on the injection of TWIN II. Hyperdynamic circulation is seen in the TWIN II. Conclusion Digital subtraction angiogram with biplane and 3D rotation is essential to evaluate the complex vascular anatomy and anatomical variations in such cases, as it gives a complete picture of the entire circulation, which is required to take any further steps in the treatment planning of craniopagus twins. Source of Support: Nil Conflict of Interest: None declared.

Introduction Kernicterus is now a rare disorder; however, we came across this case. Kernicterus is a neurological condition in the neonates characterized by cerebral deposition of unconjugated bilirubin.[1] Also known as bilirubin encephalopathy, it is a rare complication of infantile hyperbilirubinemia which results from preferential deposition of bilirubin in the globus pallidus, subthalamic nuclei, hippocampus, putamen, thalamus, and cranial nerve nuclei (especially III, IV, and VI).[2] We report the magnetic resonance (MR) findings in an infant with clinical and laboratory evidence of bilirubin encephalopathy. Case Report This term neonate (normal, spontaneous vaginal delivery, Apgar score of 8 at 1 and 5 minutes) was seen at 7 days of age with irritability, opisthotonus, and severe jaundice 1 year back. The initial total bilirubin level was 40 mg/dL. Immediate exchange transfusions reduced the total bilirubin to 24 mg/ dL. By the 15th day, the bilirubin level had dropped to 5.5 mg/dL. The cause of the hyperbilirubinemia was unknown, but was presumed to be of hemolytic in nature. The child was discharged at that time when bilirubin level reduced to normal. No further investigation was done.

usions reduced the total bilirubin to 24 mg/ dL. By the 15th day, the bilirubin level had dropped to 5.5 mg/dL. The cause of the hyperbilirubinemia was unknown, but was presumed to be of hemolytic in nature. The child was discharged at that time when bilirubin level reduced to normal. No further investigation was done. Parents brought the child at the age of 1 year with a complaint of seizures and abnormal movements. The MR examination was performed to detect any neurological abnormality. High signals on T2-weighted images were found in the globus pallidus bilaterally, with no evidence of mass effect [Figures 1a and b]. Similar changes were also noted in FLAIR images in the globus pallidus on both sides [Figure 2]. Figure 1a and b Axial T2WIs and coronal T2WIs showing bilateral, symmetrical hyperintense signals in globus pallidi without any mass effect Figure 2 Axial FLAIR image showing bilateral, symmetrical hyperintensities in the globus pallidus The changes in the globus pallidus were consistent with the deposition of unconjugated bilirubin and a complaint of abnormal movements. Because of the increased risk of hearing loss in infants with hyperbilirubinemia, a brain-stem evoked response examination was performed. This examination showed bilateral severe sensorineural hearing loss. The diagnosis of kernicterus was thus made.

tion of unconjugated bilirubin and a complaint of abnormal movements. Because of the increased risk of hearing loss in infants with hyperbilirubinemia, a brain-stem evoked response examination was performed. This examination showed bilateral severe sensorineural hearing loss. The diagnosis of kernicterus was thus made. Discussion Kernicterus is a neurological condition resulting from the deposition of unconjugated bilirubin within the brain. The term kernicterus was originally coined by Schmorl in 1903, who reported the postmortem pathologic finding of canary yellow staining of circumscribed areas of the basal ganglia in infants to be associated with neonatal jaundice.[3] Pathology and pathogenesis The exact pathogenesis of kernicterus is not clear; however, factors implicated in concert are hyperbilirubinemia, reduced serum bilirubin binding capacity, opening of the blood brain barrier, and damage to the brain tissue. Hyperbilirubinemia (kernicterus) can be caused by Rh incompatibility, ABO incompatibility, sepsis, or other hemolytic anemias such as glucose 6-phosphate dehydrogenase deficiency.

oncert are hyperbilirubinemia, reduced serum bilirubin binding capacity, opening of the blood brain barrier, and damage to the brain tissue. Hyperbilirubinemia (kernicterus) can be caused by Rh incompatibility, ABO incompatibility, sepsis, or other hemolytic anemias such as glucose 6-phosphate dehydrogenase deficiency. There is considerable evidence that hyperbilirubinemia unaccompanied by isomerization cannot cause kernicterus even under extreme conditions. Kernicterus can develop in breast-fed infants in the absence of isoimmune or hemolytic anemias. Kernicterus is rare in adults even with extreme values of bilirubin. The regions most commonly affected are basal ganglia, particularly the globus pallidus, subthalamic nucleus, dentate nucleus, sector H2, H3 of hippocampus, cerebellar vermis, and cranial nerve nuclei, notably the oculomotor, vestibular, and cochlear nuclei. Associated destructive lesions in the white matter, such as periventricular infarcts, have also been reported.[1] The cerebral cortex is spared.[2] The most accepted theory explaining kernicterus is that kernicterus results from antecedent or concomitant damage to the central nervous system with the breakdown of the blood brain barrier and uptake of albumin-bound bilirubin by the brain.

There is considerable evidence that hyperbilirubinemia unaccompanied by isomerization cannot cause kernicterus even under extreme conditions. Kernicterus can develop in breast-fed infants in the absence of isoimmune or hemolytic anemias. Kernicterus is rare in adults even with extreme values of bilirubin. The regions most commonly affected are basal ganglia, particularly the globus pallidus, subthalamic nucleus, dentate nucleus, sector H2, H3 of hippocampus, cerebellar vermis, and cranial nerve nuclei, notably the oculomotor, vestibular, and cochlear nuclei. Associated destructive lesions in the white matter, such as periventricular infarcts, have also been reported.[1] The cerebral cortex is spared.[2] The most accepted theory explaining kernicterus is that kernicterus results from antecedent or concomitant damage to the central nervous system with the breakdown of the blood brain barrier and uptake of albumin-bound bilirubin by the brain. The microscopic alterations point to the cell membrane as the primary target of injury with secondary involvement of mitochondria. Spongy degeneration and gliosis are most commonly observed anomalies in the bilirubin-stained part of the brain. At autopsy, the most common findings are marked neuronal loss with demyelination and astrocytic replacement.

t to the cell membrane as the primary target of injury with secondary involvement of mitochondria. Spongy degeneration and gliosis are most commonly observed anomalies in the bilirubin-stained part of the brain. At autopsy, the most common findings are marked neuronal loss with demyelination and astrocytic replacement. Plasma albumin normally binds bilirubin rendering it nontoxic; however, free bilirubin is cytotoxic and induces immediate and marked disturbances in brain energy metabolism. Bilirubin can enter the brain, when the serum bilirubin exceeds the normal binding capacity of albumin. In the premature infants, the kernicterus occurs at lower serum bilirubin levels perhaps due to the reduced amount of blood albumin levels. Disturbed albumin-bilirubin equilibrium results in an increase in the concentration of bilirubin with increased chances of entry of bilirubin in the brain. Greater permeability of the blood brain barrier in patients of asphyxia is another proposed mechanism of entry of bilirubin in the damaged areas of the brain.[1] The role of bilirubin-albumin binding in facilitating the bilirubin entry in the brain is stressed by the fact that kernicterus does not develop in analbuminemic persons.

eability of the blood brain barrier in patients of asphyxia is another proposed mechanism of entry of bilirubin in the damaged areas of the brain.[1] The role of bilirubin-albumin binding in facilitating the bilirubin entry in the brain is stressed by the fact that kernicterus does not develop in analbuminemic persons. Clinical features A neonate with jaundice usually becomes drowsy on the second to fifth day of life. Initial signs may be just fever, monotonus cry and loss of Moro's reflex mimicking sepsis, asphyxia, or hypoglycemia.[1] In approximately 10% of neonates who will develop kernicterus, no signs could be seen. Seizures are uncommon at an early stage. By 2 weeks of age, the infant develops hypertonia with opisthotonus and severe muscle spasm. Later on, hypotonia ensues with the development of syndrome of kernicterus at about 4 years of age. The posticteric clinical syndrome of kernicterus is related with basal ganglia and consists of an invariable presence of athetosis, often with rigidity and dystonia. Gaze palsy especially involving vertical gaze is another important finding. Auditory problems in the form of hearing loss and receptive aphasia may occur. Vestibular portion of the eighth nerve may also be involved. Severe mental retardation is uncommon; almost 50% of the patients have IQ between 90 and 110 and in approximately 25%, it is between 70 and 90. In about 25% patients, IQ will be less than 70.[45]

ms in the form of hearing loss and receptive aphasia may occur. Vestibular portion of the eighth nerve may also be involved. Severe mental retardation is uncommon; almost 50% of the patients have IQ between 90 and 110 and in approximately 25%, it is between 70 and 90. In about 25% patients, IQ will be less than 70.[45] Brain stem auditory evoked responses are also used for screening in high-risk infants. A correlation can be observed between maximum unbound bilirubin levels and abnormal central conduction times. The MRI findings in this neonate reflect the typical pathologic findings of kernicterus. In acute hyperbilirubinemia, the findings are hyperintense globus pallidus in T1WIs.[6] Hyperintense signals in T2WIs and FLAIR images in both globus pallidi correspond well with areas of preferential deposition of unconjugated bilirubin in chronic cases of kernicterus. In kernicterus, only subthalamic nuclei are involved with sparing of thalami. This helps to differentiate this condition from ischemic and metabolic disorders. The important differential diagnoses of acute cases are hypoxia, hypoglycemia, carbon monoxide poisoning, and encephalitis while of chronic cases are dysmyelinating disorders, inborn errors of metabolism, and various degenerative diseases. Hyperintense signals in the globus pallidus are nonspecific findings; however, along with proper clinical history, examination, and investigation they can establish the diagnosis of kernicterus.

The important differential diagnoses of acute cases are hypoxia, hypoglycemia, carbon monoxide poisoning, and encephalitis while of chronic cases are dysmyelinating disorders, inborn errors of metabolism, and various degenerative diseases. Hyperintense signals in the globus pallidus are nonspecific findings; however, along with proper clinical history, examination, and investigation they can establish the diagnosis of kernicterus. Recently, proton MRS has also been used in the evaluation of kernicterus as a possible metabolic signature.[7] In patients with kernicterus, compared with normal values Tau/Cr, Glx/Cr, and mI/Cr were significantly elevated whereas Cho/Cr was significantly decreased. NAA/Cr was not significantly different from normal values. Preterm very low weight infants will have low values of blood albumin, and can develop globus pallidal injury which can be confirmed on MRI along with and hearing loss. Serial MRI may be carried out to document a shift from T1W hyperintense signals in acute cases to permanent T2W hyperintense signals in chronic cases.[8] Two therapeutic modalities, phototherapy and exchange transfusions, have significantly reduced the prevalence of bilirubin encephalopathy.[2] Source of Support: Nil Conflict of Interest: None declared.

Kernicterus is an encephalopathy resulting from the cerebral deposition of unconjugated bilirubin in the neonatal period. The most common finding on magnetic resonance imaging (MRI) is increased signal intensity of the globus pallidus on T2-weighted images.[1] We present a case of kernicterus where MRI demonstrated bilateral symmetric high signal intensity and volume loss in the hippocampus in addition to globus pallidus and subthalamic nucleus hyperintensity on T2-weighted images.

e imaging (MRI) is increased signal intensity of the globus pallidus on T2-weighted images.[1] We present a case of kernicterus where MRI demonstrated bilateral symmetric high signal intensity and volume loss in the hippocampus in addition to globus pallidus and subthalamic nucleus hyperintensity on T2-weighted images. A 9-year-old black girl was admitted for investigation of dystonia and severe developmental delay. She was born after a term pregnancy and normal delivery. Her mother had malaria during pregnancy and had been treated with chloroquine. The patient had no history of perinatal asphyxia, metabolic abnormalities, or ABO/Rh isoimmunization. At the third postnatal day, she presented with jaundice (the level of total bilirubin is unknown), fever, and irritability. She underwent antibiotics and phototherapy. After treatment, axial hypotonia and limitation of vertical gaze movements were noted. At 6 months old age, serious psicomotor delay and generalized dystonia developed. Currently, neurological examination revealed mental retardation, dystonia, and spastic tetraparesis. Brain MRI demonstrated bilaterally symmetric hyperintensities in the globus pallidus and subthalamic nucleus. Bilateral hippocampal volume loss and high signal, resembling bilateral mesial temporal sclerosis, were also observed [Figure 1]. Blood analyses were normal, including copper and ceruloplasmin; bacterial cultures and polymerase chain reactions studies for CMV, toxoplasma, and HSV were negative. The screening for mitochondrial disorders, including muscle biopsy, respiratory chain enzymes activity, and analysis for mutations of mitochondrial DNA, was negative. The patient was treated with trihexyphenidyl (Artane®) until 30 mg/day, with improvement of the generalized dystonia.

toxoplasma, and HSV were negative. The screening for mitochondrial disorders, including muscle biopsy, respiratory chain enzymes activity, and analysis for mutations of mitochondrial DNA, was negative. The patient was treated with trihexyphenidyl (Artane®) until 30 mg/day, with improvement of the generalized dystonia. Figure 1 (a) Axial T2-weighted image reveals symmetric hyperintensity in globus pallidus. (b) Coronal fl uid attenuated inversion recovery (FLAIR) demonstrates symmetric high signal intensity in globus pallidus (double white arrows) and nucleus subthalamic bilaterally (black arrow). In addition, it shows bilateral atrophy and high signal intensity in the hippocampus (white arrow)

tensity in globus pallidus. (b) Coronal fl uid attenuated inversion recovery (FLAIR) demonstrates symmetric high signal intensity in globus pallidus (double white arrows) and nucleus subthalamic bilaterally (black arrow). In addition, it shows bilateral atrophy and high signal intensity in the hippocampus (white arrow) The widespread use of phototherapy and exchange transfusion has greatly reduced the incidence of kernicterus. MRI findings in chronic kernicterus are characteristic, with bilateral high signal of the pallida and subthalamic nucleus, but non-specific, and can be found in various disorders, such as hypoxic ischemic encephalopathy, mitochondrial disorders, inborn errors of metabolism, hemolytic uremic syndrome, and carbon monoxide poisoning.[2] Although mesial temporal sclerosis is a common pathological finding in patients with kernicterus, it is only exceptionally described in MRI reports.[3] Interestingly, as in our patient, none of those had epilepsy. This is in contradistinction to the pallidal involvement that shows a good clinical correlation, as movement disorders are typical. Nevertheless, we believe that hippocampal sclerosis, demonstrated by MRI, plays a role in adding specificity to the imaging diagnosis of kernicterus. Source of Support: Nil Conflict of Interest: None declared.

Introduction A number of complications may occur after ventriculo peritoneal shunt insertion for management of hydrocephalus. These include infection, blockage, malfunction or migration of the shunt. Migration may occur into the lateral ventricle, mediastinum, chest, gastrointestinal tract, abdominal wall, bladder, vagina, and scrotum.[126–8101214] We present a case which presented various complications at intervals during the whole course. Case Report A 14-month-old boy presented with erythema along the tract of his ventriculoperitoneal. shunt 6 months after its insertion. It was not associated with any shunt malfunction. The patient was given antibiotics and he responded. Three months later, he presented with recurrent vomiting and signs of lower end of shunt obstruction. Revision of shunt was done. Seven months later, the patient presented with right-sided scrotal swelling with some hard tube-like structure within. Cough impulse was present. An X-ray of the abdomen was done which showed the coiled end of shunt in the scrotum [Figure 1]. The patient was operated, and a reduction in the hernial sac containing a ventriculoperitoneal shunt with herniotomy was done. Six months later, the patient presented with pain in the abdomen, lump in the abdomen around umbilicus for six months. Exploratory laparotomy with decompression of the pseudocyst around the peritoneal end of the ventriculoperitoneal shunt with a repositioning of peritoneal catheter was done. Presently, the patient is asymptomatic and still in follow-up.

nted with pain in the abdomen, lump in the abdomen around umbilicus for six months. Exploratory laparotomy with decompression of the pseudocyst around the peritoneal end of the ventriculoperitoneal shunt with a repositioning of peritoneal catheter was done. Presently, the patient is asymptomatic and still in follow-up. Figure 1 X-ray of the abdomen A-P erect showing shunt migration into the scrotum Discussion There are many complications listed which may be seen after v-p shunt insertion.[34913] Most of these patients present with abdominal signs and/or intracranial sepsis.[9] Inguinal hernia and/or hydrocele may follow the insertion of a ventriculoperitoneal shunt with a frequency ranging from a minimum of 3.8% to a maximum of 16.8%.[413] Grosfeld was the first to report this.[8] The complication may occur at a variable length of time after operation (from 1 day to 1 year).[2] Yamasaki et al. reported two cases of spontaneous dissection of a Raimondi catheter among 23 cases, and several similar cases were reported.[1121365] Oktem et al.[10] have reported migration of the peritoneal catheter into the scrotum through the unobliterated processus vaginalis; however, the tube was not dissected in all of those cases. Peritoneal CSF pseudocysts are an infrequent but important complication in patients with ventriculoperitoneal shunts. Their incidence is regarded as ranging between 1 and 4.5%.[411] In our case, we encountered multiple complications, at intervals, i.e., shunt infection followed by transcrotal migration and finally peritoneal CSF pseudocysts formation.

infrequent but important complication in patients with ventriculoperitoneal shunts. Their incidence is regarded as ranging between 1 and 4.5%.[411] In our case, we encountered multiple complications, at intervals, i.e., shunt infection followed by transcrotal migration and finally peritoneal CSF pseudocysts formation. I am extremely grateful to the Medical Superintendent of the Subharthi Medical College Hospital for permitting me to report this case. Source of Support: Nil Conflict of Interest: None declared.

Introduction The Dandy-Walker malformation is a congenital brain malformation, typically involving the fourth ventricle and the cerebellum. This syndrome has been described in association with schizophrenia,[1] obsessive-compulsive disorder,[1] and bipolar II disorder.[2] However, to date, the Dandy-Walker syndrome has not been described in association with bipolar disorder type I mania, and therefore we briefly report a case of a Dandy-Walker variant associated with acute mania. Case Report A 10-year-old boy, was brought by his mother to the outpatient clinic of the Department of Psychiatry of a tertiary care hospital, with excessive cheerfulness. He was disinhibited in speech and behavior, restless, talking fast and loudly, singing songs at times, disobeying parents and doctors, had poor sleep and appetite, and was difficult to manage at home. His mental status examination revealed psychomotor agitation and elated mood, but no delusional ideas or hallucinations. His manner was friendly but uncooperative and he had no insight. A complete physical examination revealed malformed teeth, pallor, poor nutritional status, and the neurological examination was unremarkable. Exploration of the patient's developmental history from the mother revealed an uneventful antenatal history, a full-term vaginal delivery, history of birth asphyxia, and all milestones were delayed. He had received all his immunizations appropriately. He had stopped going to school after the third grade, due to poor academic abilities. There was no family history of any neurological or psychiatric illness.

Case Report A 10-year-old boy, was brought by his mother to the outpatient clinic of the Department of Psychiatry of a tertiary care hospital, with excessive cheerfulness. He was disinhibited in speech and behavior, restless, talking fast and loudly, singing songs at times, disobeying parents and doctors, had poor sleep and appetite, and was difficult to manage at home. His mental status examination revealed psychomotor agitation and elated mood, but no delusional ideas or hallucinations. His manner was friendly but uncooperative and he had no insight. A complete physical examination revealed malformed teeth, pallor, poor nutritional status, and the neurological examination was unremarkable. Exploration of the patient's developmental history from the mother revealed an uneventful antenatal history, a full-term vaginal delivery, history of birth asphyxia, and all milestones were delayed. He had received all his immunizations appropriately. He had stopped going to school after the third grade, due to poor academic abilities. There was no family history of any neurological or psychiatric illness. Upon consent and request from his mother, he was admitted into the child psychiatry unit with his mother. He was reviewed by senior psychiatrists and a diagnosis of bipolar affective disorder, mania without psychotic symptoms, first episode, was confirmed along with possible mental subnormality, pending IQ assessment. After obtaining informed consent from his mother, routine blood tests was done. His blood hemoglobin levels were 8.0g/dl, liver and renal functions, electrocardiogram, an echocardiograph, and an abdominal ultrasound was normal. Interestingly, the MRI brain scan [Figure 1] of the patient showed a posterior fossa cystic lesion, a giant cisterna magna communicating with the fourth ventricle and mild hypoplasia of the cerebellar vermis, with the rest of the structures being normal and no signs of hydrocephalus. These findings showed that the patient had a Dandy-Walker variant.

an [Figure 1] of the patient showed a posterior fossa cystic lesion, a giant cisterna magna communicating with the fourth ventricle and mild hypoplasia of the cerebellar vermis, with the rest of the structures being normal and no signs of hydrocephalus. These findings showed that the patient had a Dandy-Walker variant. Figure 1 Magnetic resonance imaging of the patient. Midsagittal view of the brain, note severe hypoplastic cerebellar vermis and dilatation of the fourth ventricle, with a posterior fossa cyst He was prescribed valproate and olanzepine to control his acute manic symptoms. After two weeks of admission, the psychomotor agitation had reduced and he was less friendly than before. His sleep improved, but his appetite was still poor. In subsequent reviews, he was more manageable, however, the symptoms still persisted. He continues to receive the above medications now. Even though the incidence of associated malformations range between 50 and 70%, our case had only malformed teeth with overriding. His low hemoglobin levels were due to poor nutrition and he was prescribed iron supplements. A clinical diagnosis of mild mental retardation was made, but could not be confirmed by proper neuropsychological assessment, as the patient was highly uncooperative.

and 70%, our case had only malformed teeth with overriding. His low hemoglobin levels were due to poor nutrition and he was prescribed iron supplements. A clinical diagnosis of mild mental retardation was made, but could not be confirmed by proper neuropsychological assessment, as the patient was highly uncooperative. Discussion Dandy-Walker malformation may occur as part of Mendelian disorders and chromosomal aberrations. Environmental factors including viral infections, alcohol, and diabetes have also been suggested to play a role in the genesis of Dandy-Walker malformation, but the evidence is uncertain. Clinically this syndrome can present with mental retardation, cerebellar ataxia, and symptoms of hydrocephalus. This patient had none of the direct complications as described above, except for mental retardation, which could also be explained by the history of birth asphyxia. Morphometric[34] and functional[5] neuroimaging studies have demonstrated a link between the cerebellum and mood symptoms in bipolar patients. All this suggests a possible direct causal relationship between the pathophysiology of bipolar disorder and the Dandy-Walker variant with cerebellar vermian hypoplasia. It can even be speculated that this syndrome could influence the poor response of the bipolar illness to treatment, as seen in this case.

lar patients. All this suggests a possible direct causal relationship between the pathophysiology of bipolar disorder and the Dandy-Walker variant with cerebellar vermian hypoplasia. It can even be speculated that this syndrome could influence the poor response of the bipolar illness to treatment, as seen in this case. Acknowledgments As the primary author of this report, I am grateful to Professor Gyaneshwar Sharma, the Head of the Department of Psychiatry, who is also my current supervisor, for his support and advice that encouraged me to write up this report. I also thank the patient and his parents who have given me this opportunity to share the knowledge with my peers purely for the purpose of scientific improvement. I owe my gratitude to them for signing the consent form as per the journal requirements, helping me to submit the clinical information. I wish to thank Dr. Vinayak and Dr. John Dinesh for showing keen interest in treating the patient while in the ward. Source of Support: Nil Conflict of Interest: None declared.

Sir, A 7 year old male child presented with a progressive illness characterized by fever (4 months), headache (2 months), vomiting (1 month), altered sensorium (7 days) and generalized tonic clonic seizures for a day. There was a family history of tuberculosis. He had neck rigidity with brisk deep tendon reflexes. CT scan revealed hydrocephalus due to an obstruction between the third and the fourth ventricle with basal exudates. Lumbar CSF showed 120 cells with 90% lymphocytes, proteins of 208 mg% and CSF sugar of 31 mg% against blood sugar of 61 mg%. CSF smears and cultures were negative. On the basis of prolonged history, positive family history and lymphocytic predominance in CSF, a diagnosis of tubercular meningitis was made. The child was started on four-drug anti-tubercular therapy (rifampicin, isoniazid, pyrazinamide and ethambutol) and compliance to drug therapy was ensured. A ventriculo-peritoneal shunt was inserted and it resulted in a significant neurological improvement. He remained well for about 6 months after which he presented with headache for 10 days, difficulty in walking for 7 days and fever for 4 days. The sensorium was normal. There were no signs of meningeal irritation or raised intracranial pressure. There was right-sided ptosis, marked truncal ataxia with some signs of limb ataxia, more so on the right side. The representative sections of MRI of the head are illustrated in the [Figures 1–3]. Figure 1 MRI head, T1 weighted axial image Figure 2 MRI Head, T1 weighted postcontrast axial image Figure 3 MRI Head, T2 weighted axial image

A 7 year old male child presented with a progressive illness characterized by fever (4 months), headache (2 months), vomiting (1 month), altered sensorium (7 days) and generalized tonic clonic seizures for a day. There was a family history of tuberculosis. He had neck rigidity with brisk deep tendon reflexes. CT scan revealed hydrocephalus due to an obstruction between the third and the fourth ventricle with basal exudates. Lumbar CSF showed 120 cells with 90% lymphocytes, proteins of 208 mg% and CSF sugar of 31 mg% against blood sugar of 61 mg%. CSF smears and cultures were negative. On the basis of prolonged history, positive family history and lymphocytic predominance in CSF, a diagnosis of tubercular meningitis was made. The child was started on four-drug anti-tubercular therapy (rifampicin, isoniazid, pyrazinamide and ethambutol) and compliance to drug therapy was ensured. A ventriculo-peritoneal shunt was inserted and it resulted in a significant neurological improvement. He remained well for about 6 months after which he presented with headache for 10 days, difficulty in walking for 7 days and fever for 4 days. The sensorium was normal. There were no signs of meningeal irritation or raised intracranial pressure. There was right-sided ptosis, marked truncal ataxia with some signs of limb ataxia, more so on the right side. The representative sections of MRI of the head are illustrated in the [Figures 1–3]. Figure 1 MRI head, T1 weighted axial image Figure 2 MRI Head, T1 weighted postcontrast axial image Figure 3 MRI Head, T2 weighted axial image The possible reasons for the secondary deterioration were:

A 7 year old male child presented with a progressive illness characterized by fever (4 months), headache (2 months), vomiting (1 month), altered sensorium (7 days) and generalized tonic clonic seizures for a day. There was a family history of tuberculosis. He had neck rigidity with brisk deep tendon reflexes. CT scan revealed hydrocephalus due to an obstruction between the third and the fourth ventricle with basal exudates. Lumbar CSF showed 120 cells with 90% lymphocytes, proteins of 208 mg% and CSF sugar of 31 mg% against blood sugar of 61 mg%. CSF smears and cultures were negative. On the basis of prolonged history, positive family history and lymphocytic predominance in CSF, a diagnosis of tubercular meningitis was made. The child was started on four-drug anti-tubercular therapy (rifampicin, isoniazid, pyrazinamide and ethambutol) and compliance to drug therapy was ensured. A ventriculo-peritoneal shunt was inserted and it resulted in a significant neurological improvement. He remained well for about 6 months after which he presented with headache for 10 days, difficulty in walking for 7 days and fever for 4 days. The sensorium was normal. There were no signs of meningeal irritation or raised intracranial pressure. There was right-sided ptosis, marked truncal ataxia with some signs of limb ataxia, more so on the right side. The representative sections of MRI of the head are illustrated in the [Figures 1–3]. Figure 1 MRI head, T1 weighted axial image Figure 2 MRI Head, T1 weighted postcontrast axial image Figure 3 MRI Head, T2 weighted axial image The possible reasons for the secondary deterioration were: Ventriculo-peritoneal shunt malfunction: Headache and cerebellar signs could be explained due to shunt malfunction but right eye ptosis couldn’t be explained.

Figure 1 MRI head, T1 weighted axial image Figure 2 MRI Head, T1 weighted postcontrast axial image Figure 3 MRI Head, T2 weighted axial image The possible reasons for the secondary deterioration were: Ventriculo-peritoneal shunt malfunction: Headache and cerebellar signs could be explained due to shunt malfunction but right eye ptosis couldn’t be explained. Development of stroke in posterior circulation on the top of the basilar artery territory. There was no history of acute onset to suggest stroke. Moreover, the stroke in tuberculous meningitis tends to manifest during the early part of the disease process, whereas the secondary deterioration in the index case occurred after an asymptomatic period of 6 months. Similarly, secondary resistance of mycobacterium tuberculosis to antitubercular drugs is unlikely as there was an excellent response. There were no signs of meningeal irritation. The child enjoyed an asymptomatic period of 6 months before secondary deterioration. Moreover, the compliance to anti-tubercular therapy was ensured. The paradoxical appearance of tuberculomas, whilst on antitubercular therapy seems most likely. A greater severity of truncal vis-à-vis limb ataxia denotes vermian or paravermian cerebellar involvement or its connecting pathway.[1] Right eye ptosis without extraoccular muscle paresis or pupillary abnormalities indicates partial third nerve palsy or levator palpebral superioris subnucleus involvement in the high midbrain (intra-axial). Lesion in the supranuclear pathway on the opposite site can also explain predominantly unilateral ptosis.[2]

.[1] Right eye ptosis without extraoccular muscle paresis or pupillary abnormalities indicates partial third nerve palsy or levator palpebral superioris subnucleus involvement in the high midbrain (intra-axial). Lesion in the supranuclear pathway on the opposite site can also explain predominantly unilateral ptosis.[2] T1 weighted axial section [Figure 1] shows hypo intense lesions in left side of midbrain, cerebellar vermian region and in the anterior part of the left temporal lobe. The right temporal horn of the lateral ventricle is dilated. On gladolinium enhancement [Figure 2], there are conglomerate ring enhancing lesions in the above-mentioned areas. In T2 weighted axial section [Figure 3], there is hyper intensity in the above-mentioned areas and most of the left temporal lobe. In addition, there are a few lesions with a central hyperintensity and a peripheral hypointense ring; these findings are consistent with a radiological diagnosis of multiple tuberculomas.[3]

n T2 weighted axial section [Figure 3], there is hyper intensity in the above-mentioned areas and most of the left temporal lobe. In addition, there are a few lesions with a central hyperintensity and a peripheral hypointense ring; these findings are consistent with a radiological diagnosis of multiple tuberculomas.[3] The development of tuberculomas in cases of tuberculous meningitis whilst on anti-tubercular therapy, and in spite of satisfactory compliance is designated as paradoxical response or therapeutic paradox. This therapeutic aberration usually occurs in the initial 2-3 months of therapy and generally coincides with the tapering of steroids.[4] However, cases have been reported up to 18 months after starting anti-tubercular therapy.[5] The probable explanation for development of fresh tuberculomas or an increase in size of pre-existing lesions, in spite of effective chemotherapy, is a consequence of interplay between the hosts‘immune responses and the effects of mycobacterial products. Active tuberculosis can result in suppression of delayed type hypersensitivity responses (anergy). Once active TB is under control and immunosuppression is resolved, enhanced delayed type of hypersensitivity can lead to activation and accumulation of lymphocytes and macrophages at the site of bacillary deposition or toxin production when the bacilli die. If the activation occurs at the site of microscopic foci in CNS, tuberculomas appear. If it occurs at the site of macroscopic tuberculomas, they enlarge.[6]

persensitivity can lead to activation and accumulation of lymphocytes and macrophages at the site of bacillary deposition or toxin production when the bacilli die. If the activation occurs at the site of microscopic foci in CNS, tuberculomas appear. If it occurs at the site of macroscopic tuberculomas, they enlarge.[6] The introduction of oral steroids leads to a very good response. In the index case, the headache became passive within 2 days and the gait abnormalities started improving to become passive over a few days after the addition of steroids to same anti tubercular drug regimen. Right eye ptosis disappeared and truncal and limb ataxia also became passive. There is no evidence that a change in anti-tubercular drug regimen therapy is warranted as exemplified in our case. The anti-inflammatory effects of steroids diminish the neurological symptoms over a short period.[6] Final Diagnosis Paradoxical appearance of tuberculomas whilst on antitubercular therapy. Learning points Appearance or increase in the size of tuberculomas may occur during therapy. The phenomenon usually manifests within initial few months, but is known to occur till as late as 18 months after start of anti-tubercular therapy. The phenomenon has an immunological basis and responds to a short course of steroids. A change in therapy or a prolonged duration of therapy is not warranted

Sir, Exencephaly is a rare malformation of the neural tube with a large amount of protruding brain tissue and absence of calvarium. It is considered to be an embryological precursor of anencephaly where the facial structures and the base of brain are always present. Most cases are stillborn. We report a case of Exencephaly in a live full term fetus which succumbed after 3 hours. A 21 yr old gravid, primipara was admitted with a history of post maturity. Ultrasound of the abdomen revealed a single live fetus with breech presentation and a suspicion of anencephaly. She was given a trial labour with no response. Hence an elective caesarean section was performed. Intra-operatively minimal liquor was detected and the presentation was complete breech. The female infant was 3kgs in weight and had an APGAR score of 6 to 8. The infant expired after 3 hours. At autopsy the fetal skull vault was absent and the brain was covered by a thick membrane with visible tortuous blood vessels [Figure 1]. Three other swellings were noted in the occipital region, one extending up to the cervical vertebrae [Figure 2]. The fetus had a normal forehead and the eyes were protruding. The ears, oral cavity and nasal cavity were normal. No other external anomalies were seen [Figure 3]. Figure 1 Cerebrum covered by highly vascularized tissue Figure 2 Three occipital masses composed of cerebellar tissue Figure 3 Exencephalic fetus with protruding eyeballs and no other external anomalies

At autopsy the fetal skull vault was absent and the brain was covered by a thick membrane with visible tortuous blood vessels [Figure 1]. Three other swellings were noted in the occipital region, one extending up to the cervical vertebrae [Figure 2]. The fetus had a normal forehead and the eyes were protruding. The ears, oral cavity and nasal cavity were normal. No other external anomalies were seen [Figure 3]. Figure 1 Cerebrum covered by highly vascularized tissue Figure 2 Three occipital masses composed of cerebellar tissue Figure 3 Exencephalic fetus with protruding eyeballs and no other external anomalies Internal autopsy showed the brain and overlying tissue being covered by a highly vascular layer below which was a layer of loose connective tissue 2 to 4 cms thick [Figure 1]. When this layer was removed, two roughly symmetrical cerebral hemispheres were seen. In the cerebral cortex the gyri were flattened, sulci were shallower and all surfaces were highly vascular. Cut sections of the cerebrum showed a single large ventricular chamber lined by numerous multi lobular soft tissue masses with a vague corpus callosum like white area. The average cortical thickness of the cerebrum was 2cms. The occipital nodules also showed similar findings. All thoracic and abdominal organs were normal and well formed. Lungs floatation test was positive.

ricular chamber lined by numerous multi lobular soft tissue masses with a vague corpus callosum like white area. The average cortical thickness of the cerebrum was 2cms. The occipital nodules also showed similar findings. All thoracic and abdominal organs were normal and well formed. Lungs floatation test was positive. On microscopic examination, the layer between the cortical surface and meninges was composed of loose connective tissue containing numerous tortuous vascular channels and focal nodules of dysplastic neural elements. The cerebral tissue contained scattered neurons, neuroblasts and glial elements with a thinned out layer of cortical tissue. The nodules in the occipital region showed cerebellar tissue composed of nodules of dysplastic neural elements and was also covered by a highly vascular layer. Spinal subarachnoid space also showed foci of dysplastic neural tissue.

red neurons, neuroblasts and glial elements with a thinned out layer of cortical tissue. The nodules in the occipital region showed cerebellar tissue composed of nodules of dysplastic neural elements and was also covered by a highly vascular layer. Spinal subarachnoid space also showed foci of dysplastic neural tissue. Exencephaly is characterized by the absence of cranial cavity and scalp with a large amount of protruding brain tissue covered by a membrane, and with prominent bulging eyeballs. Exencephaly is considered to lie somewhere on the spectrum between anencephaly and encephalocoele.[12] It is much less common than anencephaly but it has the same etiology and recurrence risk as other neural tube defects.[3] Exencephaly is an uncommon malformation of the cranium that characteristically involves a large disorganized mass of brain tissue. The flat bones of calvaria are absent and the brain mass is left uncovered .It is a clinical entity which is incompatible with life.1Neural tube defects account for most CNS malformations. Failure of a portion of neural tube to close or reopening of a region of the tube after successful closure, may lead to one of the several deformities. In our case the primary diagnosis of anencephaly was ruled out on the basis that the flat bones of calvarium were absent. The marked dysplasia and disorganized development of cerebrum were atypical of meningoencephalocoele.[3] Exencephaly is rarely reported in human embryos. Anencephaly occurs in 1 in 5 per 1000 live births, more commonly in females.[4] It is thought to develop at 28 wks of gestation. As with anencephaly, exencephaly is also incompatible with life.[12] Forebrain development is disrupted and all that remains is the area cerebrovasculosa with a flattened remnant of disorganized brain tissue admixed with ependymal, choroid plexus and meningothelial cells.[4]

s thought to develop at 28 wks of gestation. As with anencephaly, exencephaly is also incompatible with life.[12] Forebrain development is disrupted and all that remains is the area cerebrovasculosa with a flattened remnant of disorganized brain tissue admixed with ependymal, choroid plexus and meningothelial cells.[4] Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. The brain in these cases consist of a disorganized, anarchic outgrowth of nervous tissue with polymicrogyria and nodules of heterotopias. In our case all the macroscopic and microscopic findings were as described in literature, although we could not explain the persistence of exencephaly late in pregnancy and survival of the fetus for 3 hours.

Sir, Congenital cystic eye is a very rare condition, first described by Ida Mann in 1937 for an ocular malformation formed by a cavity lined by neuroglial tissue[12]. This is a primary developmental abnormality of the globe which presents at birth as a bluish orbital mass that usually pushes the upper lid forward[1]. It is rarely associated with intracranial anomalies or other systemic anomalies[13]. However, its association with a meningocele is extremely rare and can pose a difficult management issue to neurosurgeons. A 2 year old boy presented with a progressively enlarging swelling in the right orbit since birth which was cystic, non tender, and trans-illuminant occupying and protruding out of the right orbit [Figure 1]. The upper eyelid was stretched and displaced forwards. The cornea and sclera were not visualized. The lesion was not compressible and there was impulse on crying. The left eye was normal. Figure 1 Right congenital cystic eye

A 2 year old boy presented with a progressively enlarging swelling in the right orbit since birth which was cystic, non tender, and trans-illuminant occupying and protruding out of the right orbit [Figure 1]. The upper eyelid was stretched and displaced forwards. The cornea and sclera were not visualized. The lesion was not compressible and there was impulse on crying. The left eye was normal. Figure 1 Right congenital cystic eye His MRI revealed a multiloculated cystic lesion in the right orbit with variable intensities [Figure 2A,B]. The visual apparatus could not be identified separately. The posterior cystic component was hyperintense on T2 weighted images, inverting on FLAIR and probably communicating with the intracranial CSF space through the optic foramen, suggestive of an optic nerve sheath meningocoele. The brain was not seen to be herniating into the orbit through this defect. The anterior cystic component was also hyper intense on T2 weighted images but not inverting on FLAIR. Its wall was enhancing on contrast. Brain and the opposite eye were normal. CT scan with reconstruction showed that the right bony orbit was larger than the normal left orbit with thinning of the sphenoid wing and enlargement of the superior orbital fissure and orbital foramen on this side [Figure 3]. Figure 2(A) MRI T2W coronal images Figure 2(B) MRI T2W coronal images Figure 3 CT coronal reconstruction, bone window

His MRI revealed a multiloculated cystic lesion in the right orbit with variable intensities [Figure 2A,B]. The visual apparatus could not be identified separately. The posterior cystic component was hyperintense on T2 weighted images, inverting on FLAIR and probably communicating with the intracranial CSF space through the optic foramen, suggestive of an optic nerve sheath meningocoele. The brain was not seen to be herniating into the orbit through this defect. The anterior cystic component was also hyper intense on T2 weighted images but not inverting on FLAIR. Its wall was enhancing on contrast. Brain and the opposite eye were normal. CT scan with reconstruction showed that the right bony orbit was larger than the normal left orbit with thinning of the sphenoid wing and enlargement of the superior orbital fissure and orbital foramen on this side [Figure 3]. Figure 2(A) MRI T2W coronal images Figure 2(B) MRI T2W coronal images Figure 3 CT coronal reconstruction, bone window A clinical diagnosis of congenital cystic eye with sphenoid wing dysplasia and meningocele was made. An anterior trans-orbital approach was used to excise the orbitalcyst. The histopathological examination showed it to be a congenital cystic eye, lined by a layer of neural tissue. His postoperative recovery was complicated by profuse CSF leak through the orbit which required transcranial and transorbital repair procedures and a thecoperitoneal shunt.

h was used to excise the orbitalcyst. The histopathological examination showed it to be a congenital cystic eye, lined by a layer of neural tissue. His postoperative recovery was complicated by profuse CSF leak through the orbit which required transcranial and transorbital repair procedures and a thecoperitoneal shunt. Disturbance of morphogenetic pathway that controls eye development has been well documented[5]. Congenital cystic eye is one such rare malformation, which occurs when the development is arrested at the optic vesicle stage (2 to 7 mms). Complete or partial failure of the invagination of the primary optic vesicle gives rise to a congenital cystic eye lined by neuroglial tissue with no evidence of normal ocular structures, such as lens, ciliary body, choroid, or retina[1]. It usually presents as a cystic swelling in the upper lid compared to a microphthalmos with a cyst, which usually presents as a bulge in the lower lid[2]. The MRI scan is the gold standard in diagnosing the condition along with associated lesions like encephalocele , optic nerve sheath meningocele , absence of septum pellucidum ,transsphenoidal encephalocele, hydrocephalus etc.[34]. Usually, the bony orbit does not develop in congenital cystic eye requiring conformers for expanding it[13].

gold standard in diagnosing the condition along with associated lesions like encephalocele , optic nerve sheath meningocele , absence of septum pellucidum ,transsphenoidal encephalocele, hydrocephalus etc.[34]. Usually, the bony orbit does not develop in congenital cystic eye requiring conformers for expanding it[13]. However, in this case the orbit was enlarged probably due to the presence of the meningocele, pushing the cyst forwards. Identifying the presence of the meningocele before surgery is important in planning the management. Baghdassarian et al observed an optic nerve–like structure that was continuous with neuroglial tissue in the posterior aspect of a cyst[6]. During the primary excision, we also had noted transcient CSF leak from the rudimentary optic nerve head. Non ocular abnormalities like sphenoid bone malformation have been reported to be associated with congenital cystic eye[7]. Dysplasia of the greater wing of sphenoid with enlargement of the superior orbital fissure was seen in our case. However, the presence of optic nerve sheath meningocoele is a rare association. By far, the most accepted management is to keep the cyst till the socket enlarges (usually up to 5 years of age) and excision of the congenital cystic eye followed by implantation of a prosthesis[13]. Early surgery is contemplated in large cysts with cosmetic deformity as in our case[3]. The other reported treatment modality is repeated aspiration of the cyst. This is not associated with complications like CSF leak, but may require many sittings of aspiration and may not be curative[1].

antation of a prosthesis[13]. Early surgery is contemplated in large cysts with cosmetic deformity as in our case[3]. The other reported treatment modality is repeated aspiration of the cyst. This is not associated with complications like CSF leak, but may require many sittings of aspiration and may not be curative[1]. Our case demonstrates that surgical excision of the cystic eye carries a high risk of complications like CSF leak. Identifying any associated meningocele pre-operatively and repairing it during the surgery can prevent this. A trans cranial repair of the meningocele in such a case can be difficult and morbid. Alternatively, a subtotal excision, preserving the posterior part of the cyst may avoid formation of a communication with the intracranial cavity. Per operative institution of a lumbar drain which is retained till wound healing is another strategy to prevent formation of a CSF fistula. However, in the case of formation of such a fistula, periorbital tissue has to be mobilised all around the bone dura defect for closure. Ideally, this has to be done primarily while decompressing or excising the cyst.

Sir, Kawasaki disease (KD) is a generalized vasculitis of unknown etiology and a leading cause of acquired heart disease among children living in developed countries, but is still enigmatic in India. There is no laboratory test which can help the clinician in arriving at or confirming a diagnosis of KD. The difficulty is further compounded by the fact that the clinical features gradually evolve over a period of days to a few weeks, and the entire clinical spectrum is not seen at any one particular point of time and sometimes KD may present with atypical presentation. Moreover, it may be difficult to distinguish KD from other common febrile illnesses of childhood and is usually misdiagnosed as viral exanthem more so due to lack of awareness among physicians. Since untreated cases may have coronary abnormalities, including coronary aneurysms about one fourth of the cases and may be fatal if not treated. Hence we are reporting a case of Kawasaki disease presenting as meningoencephlitis.

usually misdiagnosed as viral exanthem more so due to lack of awareness among physicians. Since untreated cases may have coronary abnormalities, including coronary aneurysms about one fourth of the cases and may be fatal if not treated. Hence we are reporting a case of Kawasaki disease presenting as meningoencephlitis. A 9 month old male child presented with history of high grade fever (1040F) for seven days with an erythematous rash over the face and trunk for three days and abnormal movements and unconsciousness for one day. On examination child was comatose responding only to deep painful stimuli, erythematous rash was present over the face, neck and abdomen, Throat was hyperemic with tonsillar enlargement and had strawberry tongue, puffiness of hand and feet was noted. On systemic examination child was comatose responding only to deep painful stimuli, Neck rigidity was present, there were no other meningeal signs and rest of the CNS examination was normal. Spleen was just palpable. Respiratory and cardiovascular system examination was unremarkable except for tachycardia. No family history of seizures or febrile convulsion was present. Possibility of viral encephalitis was kept and child was managed symptomatically.

ingeal signs and rest of the CNS examination was normal. Spleen was just palpable. Respiratory and cardiovascular system examination was unremarkable except for tachycardia. No family history of seizures or febrile convulsion was present. Possibility of viral encephalitis was kept and child was managed symptomatically. Child started improving on symptomatic management and was conscious on second day of admission but was irritable and febrile and on fourth day of admission had massive peeling of skin all over the body. On Investigations ESR was 90 mm, CRP was increased, normocytic normochromic anemia, Polymorphonuclear leucocytosis with polymorphs showing toxic granulation and dohle bodies, platelet count initially were 380000/cmm and increased to 5,99000/cmm after 11 days of illness, CSF examination revealed lymphocytic pleocytosis with mildly elevated proteins and sugar was normal, ASO was negative, Throat culture, urine culture and blood culture were negative, CXR was normal .ECG showed tachycardia and non specific ST changes. Echocardiography was normal. After analyzing the clinical course of the disease and investigation revised diagnosis of atypical Kawasaki disease was kept and child was started on intravenous immunoglobulin infusion (2gm/kg) as single infusion and high dose aspirin (100mg/kg) for two weeks and then dose of aspirin was tapered to 5mg/kg/day for next 6 weeks. Child improved dramatically on starting the treatment. Repeat echo done after 2 weeks and 6 weeks were normal. Child is on follow up and is well.

venous immunoglobulin infusion (2gm/kg) as single infusion and high dose aspirin (100mg/kg) for two weeks and then dose of aspirin was tapered to 5mg/kg/day for next 6 weeks. Child improved dramatically on starting the treatment. Repeat echo done after 2 weeks and 6 weeks were normal. Child is on follow up and is well. After Henoch-Schonlein purpura, KD is the commonest vasculitic disorder of children[12]. Albeit the number of cases reported from India remains minuscule and is largely confined to typical KD. It is likely that many cases of KD and more so of Incomplete Kawasaki Disease (IKD) go unnoticed, especially so in the absence of a precise diagnostic test. KD is a clinical diagnosis based on the characteristic history and physical findings. The diagnosis of classic Kawasaki disease (KD) requires fever of at least 5 days duration and the presence of 4 of the following.[1] Non exudative conjunctival infection[2] Oral involvement including strawberry tongue, mucosal hyperemia and cracked or erythematous lips[3] Changes in peripheral extremities, including edema or desquamation in convalescence[4] polymorphous rash and[5] acute cervical Lymphadenopathy > 1.5 cms in diameter. Marked irritability out of proportion to the degree of fever is usually present which responds dramatically to treatment. There is no laboratory test which can help the clinician in arriving at or confirming a diagnosis of KD . The difficulty is further compounded by the fact that the clinical features gradually evolve over a period of days to a few weeks, and the entire clinical spectrum is not seen at any one particular point of time.

. There is no laboratory test which can help the clinician in arriving at or confirming a diagnosis of KD . The difficulty is further compounded by the fact that the clinical features gradually evolve over a period of days to a few weeks, and the entire clinical spectrum is not seen at any one particular point of time. However, “atypical” or “incomplete” cases of Kawasaki disease, in which patients have fewer than four of the five principal features and presence of atypical features like aseptic meningitis, hepatitis, arthritis which are not described in the classical presentation of KD are difficult to diagnose and untreated may lead to cardiac morbidity. The present case presented as meningoencephlities and was eventually diagnosed as Kawasaki disease only after ruling out other causes and presence of strawberry tongue, edema hand and feet, rash and desquamation of skin and presence of increased acute phase reactants and thrombocytosis. Neurological complications in Kawasaki disease are found in 1.1-3.7% of cases, It is considered that meningoencephlitis in KD may develop in cases having more severe and prolonged inflammatory changes; the clinical findings revealed a serious form of KD. This might be due to vasculitis of small arteries, arterioles, capillaries, and venules, which consists of infiltration of lymphocytes and large mononuclear cells, and edema[34]. Diagnosing classical KD is difficult enough. Recognizing cases that do not fully meet the diagnostic criteria and present with atypical manifestation like meningoencephlitis offers an even greater challenge. Nevertheless it is important to be aware of this entity, as an unaware clinician may face a diagnostic dilemma. On one hand, there is just not enough clinical evidence for diagnosing KD. On the other hand, waiting endlessly could lead to irreversible complications such as coronary artery aneurysms and subsequent propensity to develop cardiac problems.

e aware of this entity, as an unaware clinician may face a diagnostic dilemma. On one hand, there is just not enough clinical evidence for diagnosing KD. On the other hand, waiting endlessly could lead to irreversible complications such as coronary artery aneurysms and subsequent propensity to develop cardiac problems. To help clinicians to arrive at the diagnosis, Japanese and North American groups have evolved diagnostic criteria[56]. The Japanese workers deem presence of any four of the six clinical criteria sufficient for the diagnosis of IKD while the North American workers consider the presence of three criteria to be sufficient for the diagnosis of IKD provided echocardiography or angiography reveals coronary artery changes due to arteritis. As coronary lesions are often present by day 9 or 10 of illness, various workers have attempted to find out if any of the laboratory criteria could help in diagnosing atypical or incomplete forms of KD. Levy et al found that thrombocytosis was present consistently in atypical forms with peak thrombocytosis occurring at 13.5±5.9 days of illness and concluded that presence of thrombocytosis should be considered compatible with the diagnosis of IKD[7]. Albeit waiting for detecting thrombocytosis and coronary lesion to confirm the diagnosis of IKD can adversely affect the prognosis. For prevention of the complications, the physician has to start therapy much earlier. Hence, it is imperative that one diagnoses KD early and institutes treatment promptly. This is true of IKD too as this form has the tendency to develop all the complications of the classic KD[89]. Unless a high index of suspicion is kept the patients with IKD will continue to escape our attention.

Sir, Nonconvulsive status epilepticus is a specific form of status epilepticus characterized by alteration in the mental status and persistent seizure activity on electroencephalogram (EEG), with or without motor phenomena. Herpes simplex encephalitis (HSE) is one of the causes of it.[1] Herein, we report an infant- developed nonconvulsive status epilepticus following HSE.

m of status epilepticus characterized by alteration in the mental status and persistent seizure activity on electroencephalogram (EEG), with or without motor phenomena. Herpes simplex encephalitis (HSE) is one of the causes of it.[1] Herein, we report an infant- developed nonconvulsive status epilepticus following HSE. An 11-month-old girl, who had unremarkable medical history, was admitted to a local hospital with fever and seizure. She had otitis media and was hospitalized there for intravenous antibiotic therapy for 1 week before being referred to our hospital. She was unconscious, and responsive to only painful stimuli at admission. Left central facial paralysis was detected and she had no swallow reflex or no gag reflex. Brain computed tomography (CT) revealed a low-density lesion in the right frontal lobe. Cerebrospinal fluid (CSF) revealed 40/mm3 leukocyte (100% lymphocyte); protein was 36 mg/dl and glucose 47 mg/dl. Ceftriaxone (100 mg/kg/day) and acyclovir (30 mg/kg/day) therapies were administered to the patient on account of encephalitis or inadequately treated bacterial meningitides. An electroencephalogram (EEG) pointed out diffuse slow-wave activity without focal changes. Phenytoin and midazolam treatment were administered in order to cease right focal motor seizures. Magnetic resonance imaging (MRI) on the second day of hospitalization revealed increased signal intensity in the cortical–subcortical region of frontal lobes bilaterally on T2-weighted images and a decreased signal intensity on T1-weighted images [Figure 1]. Lesions were extended bilaterally to frontotemporal lobes on MRI in the second week of hospitalization [Figure 2]. CSF examination yielded increased herpes simplex virus (HSV) Ig M (4.7 RU/ ml, N: 01 RU/ml) and Ig G (33.7 RU/ml, N: 0–20 RU/ml) antibodies. Acyclovir therapy was administered for 3 weeks. The patient improved remarkably. Focal seizures were under control on the fifth day of therapy. She was conscious on the sixth day, and facial paralysis had disappeared. Patient was discharged on the 21st day of hospitalization with a complete recovery. Twenty days after her discharge, she was readmitted to the hospital with bizarre movements’ affecting limbs. Her parents complained about her reduced level of consciousness. CSF examination revealed 300/mm3 erythrocytes, and CSF protein and glucose levels were 40 mg/dl and 60 mg/dl, respectively. EEG pointed out a persistent epileptic activity [Figure 3].

was readmitted to the hospital with bizarre movements’ affecting limbs. Her parents complained about her reduced level of consciousness. CSF examination revealed 300/mm3 erythrocytes, and CSF protein and glucose levels were 40 mg/dl and 60 mg/dl, respectively. EEG pointed out a persistent epileptic activity [Figure 3]. Acyclovir readjusted for recurrent HSE over 21 days. Midasolam infusions and valproat were used in order to control the epileptic activity. There was no alteration on the MRI findings. CSF examination for HSV polymerase chain reaction (PCR) and the HSV IgM antibody was negative; besides, the HSV IgG antibody level was increased up to 92.7 RU/ml (N: 0-0.20 RU/ml). The epileptic activity was decreased during hospitalization and the patient was discharged with antiepileptic medications. Figure 1 Cortical-subcortical increased signal intensity in bilaterally frontal lobes on T1-weighted images on cranial MRI on the second day of hospitalization Figure 2 Extended leisons on bilaterally frontotemporal lobes on MRI on the second week of hospitalization Figure 3 Persistent epileptic activity on EEG at the second hospitalization

Figure 1 Cortical-subcortical increased signal intensity in bilaterally frontal lobes on T1-weighted images on cranial MRI on the second day of hospitalization Figure 2 Extended leisons on bilaterally frontotemporal lobes on MRI on the second week of hospitalization Figure 3 Persistent epileptic activity on EEG at the second hospitalization HSE is one of the most devastating infections of the central nervous system (CNS). Despite specific antiviral therapies, serious neurological deficits occur in 18-42% of the survivors of HSE.[23] The common neurological sequelae include memory impairment, behavioral and cognitive abnormality, and secondary epilepsy. Besides, relapse of HSE has been reported in 3.8-26% of the patients.[4–6] The three most common clinical manifestations of HSE relapse are altered mental status, fever, and involuntary movements, usually choreo -athetoid or ballismic.[7–9] Status epilepticus may also be the first manifestation of relapsing herpes encephalitis, which is difficult to distinguish from secondary epilepsy.[2] Moreover, herpes encephalitis is one of the causes of nonconvulsive status epilepticus.[1] Our patient was readmitted to the hospital with choreiform movements and persistent seizure activity on EEG 20 days after HSE. She was conscious, but lethargic. It is difficult to differentiate that this clinical findings was due to the relapse of HSE or due to secondary epilepsy following HSE. Thirty-eight pediatric relapsing herpes encephalitis cases have been studied, and the average age at primary infection is established as 36 months (3 days-16 years), and 65.8% of the cases were under 24 months of age. A relapse occurred within 2 weeks after the end of the treatment of the initial episode in 52% of the patients reported.[7] Also our patient was 11 month old, and she had choreiform movements and status epilepticus occurred within 20 days after the end of the treatment. These findings suggest that this condition was due to the relapse of herpes encephalitis, but laboratory findings did not support the relapsing HSE diagnosis. The detection of the CSF for HSV PCR was negative and the CSF anti-HSV Ig M antibody had become negative at the second hospitalization, and MRI findings revealed no new alteration, so the status epilepticus might be a finding of secondary epilepsy.

s, but laboratory findings did not support the relapsing HSE diagnosis. The detection of the CSF for HSV PCR was negative and the CSF anti-HSV Ig M antibody had become negative at the second hospitalization, and MRI findings revealed no new alteration, so the status epilepticus might be a finding of secondary epilepsy. On the other hand, CSF HSV PCR positivity has been reported in only 56% of the patients with relapse encephalitis.[7] It has been reported that negative PCR results might be correlated with low CSF protein and white blood cell levels, as well as with the presence of anti-HSV antibodies in the CSF.[10] Besides, immunology-mediated mechanisms might have a major role in the pathogenesis of the relapse, and not direct viral cytotoxicity.[11] On the other hand, should patients have chronic active encephalitis? Progressive mental and behavioral deterioration following herpes encephalitis has been reported.[2] Most of these patients developed intractable seizures, slowly progressive hemiparesis, and cognitive decline in a few years after contracting the disease, and neuropathological studies of these patients showed chronic active encephalitis.[2] We could not perform brain biopsy to our patient, and it is difficult to make a decision about the exact cause of the clinical picture. Acyclovir therapy is suggested in patients who are presented with status epilepticus after herpes encephalitis, because the patient may be experiencing a relapse of the encephalitis, and we gave a second cycle of acyclovir therapy to the patient.[278]

On the other hand, should patients have chronic active encephalitis? Progressive mental and behavioral deterioration following herpes encephalitis has been reported.[2] Most of these patients developed intractable seizures, slowly progressive hemiparesis, and cognitive decline in a few years after contracting the disease, and neuropathological studies of these patients showed chronic active encephalitis.[2] We could not perform brain biopsy to our patient, and it is difficult to make a decision about the exact cause of the clinical picture. Acyclovir therapy is suggested in patients who are presented with status epilepticus after herpes encephalitis, because the patient may be experiencing a relapse of the encephalitis, and we gave a second cycle of acyclovir therapy to the patient.[278] The prognosis of relapsing HSE cases is poor. The outcome of the majority of patients is either death, or moderate-to-severe neurological impairment. Valencia et al.[7] reported two cases of relapse encephalitis and both of them progressed to a neurovegetative state. Some clinical improvement has been obtained in our patient, but not a complete recovery. It has been suggested that young age (< 2 years) and a lower total dose of acyclovir treatment are the risk factors for recurrence.[27] But even in patients, who were given acyclovir treatment at a dosage of 60 mg/kg/day for 21 days, a relapse of herpes encephalitis has been reported.[12] Our patient was under 2 years and she was admitted to our hospital 2 weeks after the beginning of the symptoms.

vir treatment are the risk factors for recurrence.[27] But even in patients, who were given acyclovir treatment at a dosage of 60 mg/kg/day for 21 days, a relapse of herpes encephalitis has been reported.[12] Our patient was under 2 years and she was admitted to our hospital 2 weeks after the beginning of the symptoms. In conclusion, herpes encephalitis should bear in mind as a cause of nonconvulsive status epilepticus. Since the recurrent or chronic infections and complications due to HSV are frequent, especially young children should be monitored carefully. A better understanding of the relapse mechanism is required in order to propose a more efficient treatment.

Sir, Rotavirus infection is usually characterised by diarrhea, vomiting and dehydration.[1] Recently central nervous system (CNS) involvement has also been reported in patients with rotavirus gastroenteritis.[23] A previously healthy 13-month-old girl infant was admitted to our clinic with the complaints of a 3-4 days history of watery, non-bloody diarrhea, vomiting, mild fever and loss of conciousness. She had also manifested generalised tonic-clonic (GTC) convulsions within last twelve hours. She was born at term after an uneventful pregnancy. There were no convulsive disorders in her family history. Her developmental milestones were normal. She was lethargic on admission and her physical examination was consistent with mild dehydratation.

generalised tonic-clonic (GTC) convulsions within last twelve hours. She was born at term after an uneventful pregnancy. There were no convulsive disorders in her family history. Her developmental milestones were normal. She was lethargic on admission and her physical examination was consistent with mild dehydratation. Laboratory examination revealed the following laboratory values: C-reactive protein 6.8 mg/dl, aspartate aminotransferase 66 IU/L, alanine aminotransferase 51 IU/L, blood urea nitrogen 31 mg/dl, creatinine 0.5 mg/dl. Hemogram, serum sodium, potassium, glucose, albumin, calcium, and magnesium levels were also normal. Cerebrospinal fluid (CSF) sample showed normal cell counts, glucose and protein levels. Rotavirus antigen was detected in stools by latex agglutination. Cultures of blood, CSF, urine, throat, and stool samples were negative. The serum and urine aminoacids and organic acid analysis in urine were no abnormality. Magnetic resonance imaging (MRI) of the brain and inter-ictal electroencephalogram (EEG) were normal. The diagnosis of mild dehydration, acute encephalopathy and seizure due to rotavirus infection was made, and the patient was treated with intravenous hydration and short lasting phenobarbitale. Rotavirus is the primary cause of severe gastroenteritis in children in the winter and spring. Infection is localized in the intestine, and only rare reports suggest any morbidity resulting from extraintestinal involvement. Recently, however a number of investigators have reported CNS complications in association with rotavirus gastroenteritis.[23]

of severe gastroenteritis in children in the winter and spring. Infection is localized in the intestine, and only rare reports suggest any morbidity resulting from extraintestinal involvement. Recently, however a number of investigators have reported CNS complications in association with rotavirus gastroenteritis.[23] There are many reports indicating the incidence of CNS involvement at rotavirus gastroenteritis as 2-5.3%. Concomination of CNS involvement to rotavirus infection can represent by different clinical findings. Menengitis, encephalitis, encephalopathy, febrile and afebrile convulsions, hemorrhagic shock, Guillian Barre syndrome and Reye syndrome are the reported neurological antites untill now.[3] Our patient showed a neurological involvement of encephalopathy and seizures during gastroenteritis. Encephalopathic findings started after the diarrhea, addiationaly as CSF and serum electrolyties and cranial imagining findings were normal; diagnose of encephalopathy was corrected.

neurological antites untill now.[3] Our patient showed a neurological involvement of encephalopathy and seizures during gastroenteritis. Encephalopathic findings started after the diarrhea, addiationaly as CSF and serum electrolyties and cranial imagining findings were normal; diagnose of encephalopathy was corrected. Until now, although some hypothesis about the mechanism of rotavirus CNS involvement, it is unclear. Ushijima et al.[4] established rotavirus both at intestinal and CSF observation; so by this knowledge rotavirus seem to make CNS invasion after a primer intestinal enfection. McCormak.[5] reported concominance of rashes at a rate of 5% with rotavirus gastroenteritis. This concominance may indicate CNS involvement by viremia. But viremia is thought to be at least three days later. Our patient showed encephalopathy signs after the 3-4 days of diarrhea, but no rashes. Minami et al.[6] measured elevation at serum IL-6 and TNF- α, CSF IL-6 and IL-8 levels so relationaly reported the cause of encephalopaty as systemic immune response to cytotoxicity. Rotavirus may cause damage directly at neuronal cells by replication or indirectly to neurological complications by enterotoxine spreading to CNS. Ball et al.[7] reported that virus and its’ particules can spread to CSF by destruction of the blood-brain barier. An other hypothesis is establishment of rotavirus at CSF and gaita; can represent that rotavirus has an affinity to neuronal cells and it is neurotropic.[2]

complications by enterotoxine spreading to CNS. Ball et al.[7] reported that virus and its’ particules can spread to CSF by destruction of the blood-brain barier. An other hypothesis is establishment of rotavirus at CSF and gaita; can represent that rotavirus has an affinity to neuronal cells and it is neurotropic.[2] Concominance of febril and afebrile convulsions to rotavirus gastroenteritis reported as 1.2-6.4 % at studies. Chen et al.[8] at Taiwan reported the incidences of convulsions as 6.4%, Lynch et al.[2] at US as 4%, Wong[9] at Hong Kong as 3.5%, Abe et al.[3] at Japan as 2.6%, and Swanson et al.[10] as 1.2% at US. Electrolyte imbalances, destructıon of bood-brain barier by fever or encephalopaty and encephalitis are the causes for occurence of convulsions.[3] Usually recürrence convulsions and encephalopathy at rotavirus enfection show a benýng course. In our patient recurrrence convulsions occured at the 3-4.th day of gastroenteritis and didn’t repeated at the following 3 month of controls and the EEG and neurological signs seem to be normal. Convulsions due to rotavirus are reported to be tonic clonic and GTC.[9] In our patient GTC convulsions were observed. As previously our patients’ had a normal mental motor development, the observed convulsions were GTC; serum electrolyties, CSF, EEG and neuroimaging were normal, prognosis was well and at gaita examination ratovirus was determıned the clinic findings thought to be due to rotavirus related encephalopathy.

were observed. As previously our patients’ had a normal mental motor development, the observed convulsions were GTC; serum electrolyties, CSF, EEG and neuroimaging were normal, prognosis was well and at gaita examination ratovirus was determıned the clinic findings thought to be due to rotavirus related encephalopathy. In conclusion; rotavirus gastroenteritis seem frequently in our country and can show different clinical courses. If diarrhea is concominated with encaphalopathy and convulsions at child; rotavirus must to be thought at etiologic.

Sir, A 4-year old boy presented with delayed mental growth, speech disturbances and abnormal size of head. Physical examination revealed macrocephaly. There was incomplete achievement of mental milestones. Computed tomographic (CT) scan of brain revealed bilateral frontotemporal atrophy [Figure 1], bilateral enlarged sylvian fissures and few hypodensities in the lentiform nuclei. History did not reveal any evidence of accidental or non-accidental head injury. Biochemical investigations clinched the diagnosis. Figure 1 Frontoemporal atrophy and widened CSF spaces Glutaric aciduria type 1 (GA-1) is an autosomal recessive inborn error of lysine, hydroxylysine and tryptophan metabolism that results from a deficiency of glutaryl-CoA dehydrogenase. Common features on neuroimaging include increased spaces anterior to the frontotemporal lobes [Figure 2] (vs. frontotemporal atrophy) wide sylvian fissures, (giving a “bat-wing” formation) and prominent interhemispheric fissures[1]. There may be diffuse hypodensity of the basal ganglia. Widening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of GA-1. If combined with abnormalities of the basal ganglia and white matter, GA-1 should be strongly suspected[2]. Figure 2 “Bat-wing” dilatation of the sylvian fissures and prominent interhemispheric fissure

Common features on neuroimaging include increased spaces anterior to the frontotemporal lobes [Figure 2] (vs. frontotemporal atrophy) wide sylvian fissures, (giving a “bat-wing” formation) and prominent interhemispheric fissures[1]. There may be diffuse hypodensity of the basal ganglia. Widening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of GA-1. If combined with abnormalities of the basal ganglia and white matter, GA-1 should be strongly suspected[2]. Figure 2 “Bat-wing” dilatation of the sylvian fissures and prominent interhemispheric fissure A prominent clinical feature of infants and children with glutaric aciduria type 1 is macrocephaly[3]. The finding of very widely open opercula suggests glutaric acidemia type I, and if combined with basal ganglia lesions is almost pathognomonic, especially in a child with macrocephaly[1]. Conventional T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of the brain showed hyperintensity in the caudates and putamina bilaterally with subtle involvement of the medial frontal lobes. Diffusion-weighted magnetic resonance images showed striking restricted diffusion in the caudates and putamina consistent with acute necrosis.[4]

Introduction Meningiomas occur most commonly in the fifth decade of life, accounting for approximately 15-20% of primary intracranial tumors.[1] Intracranial meningiomas in children and adolescents are rare tumors. In most large series, the incidence of meningiomas before the age of 16 years ranges from 0.4 to 4.6% of all primary brain tumors in this age group.[2–7] They account for 0.9-3.1% of all intracranial meningiomas.[8–10] The female preponderance found in adult patients is not seen in children, the reported male- to-female ratio in children being 1.2:1.[111] Risk factors for the development of meningiomas include the diagnosis of neurofibromatosis type two (NF-2) and a history of radiation therapy, the so-called radiation- induced meningiomas.[12] Meningiomas in children have been considered by some to be more aggressive than their adult counterparts.[13–16]

ng 1.2:1.[111] Risk factors for the development of meningiomas include the diagnosis of neurofibromatosis type two (NF-2) and a history of radiation therapy, the so-called radiation- induced meningiomas.[12] Meningiomas in children have been considered by some to be more aggressive than their adult counterparts.[13–16] Materials and Methods Eighteen consecutive cases of meningioma in patients under 18 years of age admitted and operated at Bombay hospital institute of medical sciences, Mumbai, India, by senior author (Dr. SNB) between the years 1974-2005 were included in this study. All cases were confirmed by radiological, operative, and histopathological findings. We have tried to retrospectively analyze the epidemiological profile, clinical features, radiological findings, type of excision, histopathological findings, and overall management profile of these patients. All patients/relatives were called for the follow- up or an attempt was made to at least get an interview on telephone. As and where possible, we have made an attempt to determine the differentiating features between adult and pediatric meningiomas. Results Incidence We operated a total of 934 meningioma cases between the years 1974-2005, of which 18 cases were in the age group of 0-18 years. Thus, childhood meningiomas accounted for 1.92% of total meningiomas in our study.

Materials and Methods Eighteen consecutive cases of meningioma in patients under 18 years of age admitted and operated at Bombay hospital institute of medical sciences, Mumbai, India, by senior author (Dr. SNB) between the years 1974-2005 were included in this study. All cases were confirmed by radiological, operative, and histopathological findings. We have tried to retrospectively analyze the epidemiological profile, clinical features, radiological findings, type of excision, histopathological findings, and overall management profile of these patients. All patients/relatives were called for the follow- up or an attempt was made to at least get an interview on telephone. As and where possible, we have made an attempt to determine the differentiating features between adult and pediatric meningiomas. Results Incidence We operated a total of 934 meningioma cases between the years 1974-2005, of which 18 cases were in the age group of 0-18 years. Thus, childhood meningiomas accounted for 1.92% of total meningiomas in our study. Sex and Age Age at diagnosis varied from 9 months to 18 years. We had only one child with presentation under 1 year of age. The maximum incidence of meningiomas was seen in the second decade of life. Thirteen out of 18 cases presented in the second decade. The mean age at presentation was 12.81 years. There were 11 males and 7 females in our series. The male-to-female ratio was 1.57:1.

d only one child with presentation under 1 year of age. The maximum incidence of meningiomas was seen in the second decade of life. Thirteen out of 18 cases presented in the second decade. The mean age at presentation was 12.81 years. There were 11 males and 7 females in our series. The male-to-female ratio was 1.57:1. Presenting symptoms and signs The most common presenting signs and symptoms were due to raised intracranial pressure or seizure. The main presenting symptoms were seizure (8 patients), headache (6 patients), impairment of vision (2 patients), vomiting (3 patients), proptosis (2 patients), increased head size (1 patient), and occipital swelling (1 patient). The median pre-operative duration of symptoms was 1.2 years. The most common clinical sign seen was papilledema (7 patients) followed by monoparesis (4 patients), marked impairment of vision (2 patients), proptosis (2 patients), tense anterior fontanelle (1 patient), occipital swelling (1 patient), and neurofibromatosis (2 patients). Neuro-radiology Our series includes patients operated between the years 1974 and 2005. Hence, patients were investigated with varied available neuroradiological modalities such as plain X-ray of skull (1 patient with calcified tumor), cerebral angiography (2 patients), CT scan (11 patients), MRI (2 patients), and CT scan + MRI (2 patients).

ries includes patients operated between the years 1974 and 2005. Hence, patients were investigated with varied available neuroradiological modalities such as plain X-ray of skull (1 patient with calcified tumor), cerebral angiography (2 patients), CT scan (11 patients), MRI (2 patients), and CT scan + MRI (2 patients). Location Seventeen cases were supratentorial and 1 case was infratentorial in location. The tumors were located in the cerebral convexity in six patients, intraventricular in four patients, skull base in three patients, Falcine in two cases, parasellar in one patient, tentorial in one case and in posterior fossa in one patient. Lesion characteristics Tumor was homogenous in appearance in most of the cases visualized with CT/MRI. Intra-tumoral calcification was seen in two cases. Intra-tumoral cystic changes were seen in two cases. Hyperostosis was seen in three cases. Tumor excision Total excision of tumor was achieved in all cases. In 14 patients, total excision was achieved in one stage. Three patients required two-stage surgeries for total excision and one patient required three-stage surgeries to achieve complete excision. Peri-operative mortality One patient expired postoperatively due to brainstem disturbances. He turned out to have malignant meningioma on histopathology. The mean peri-operative mortality was 5.5%.

Tumor excision Total excision of tumor was achieved in all cases. In 14 patients, total excision was achieved in one stage. Three patients required two-stage surgeries for total excision and one patient required three-stage surgeries to achieve complete excision. Peri-operative mortality One patient expired postoperatively due to brainstem disturbances. He turned out to have malignant meningioma on histopathology. The mean peri-operative mortality was 5.5%. Histopathology Histopathology showed fibroblastic meningioma in three patients, meningothelial in one patient, transitional in eight patients, angioblastic in three patients, sarcomatous in one patient, aggressive syncitial in one patient, and malignant meningioma in one patient. Adjuvant therapy Postoperative adjuvant radiotherapy was given to four patients; three patients with histopathology suggestive of angioblastic meningioma and one patient with aggressive syncitial meningioma. One patient with sarcomatous meningioma could not be given radiation, as the age at diagnosis was only 9 months. However, patient had no recurrence even at 14 years of follow-up.

four patients; three patients with histopathology suggestive of angioblastic meningioma and one patient with aggressive syncitial meningioma. One patient with sarcomatous meningioma could not be given radiation, as the age at diagnosis was only 9 months. However, patient had no recurrence even at 14 years of follow-up. Follow up and recurrence An attempt was made to get follow-up of all patients. The period of follow-up ranged from 1 to 26 years with a mean follow-up of 6.1 years. We documented two recurrences in our series on follow-up. The histopathology in patients with recurrence was aggressive syncytial in one patient and transitional in the other patient. Both the patients had a total excision during their first surgery. The patient with transitional meningioma had a falcine meningioma and may be some microscopic remnant must have been left behind, as falx was not excised. During his redo surgery, we achieved a total excision of falx. In a patient with aggressive syncytial meningioma, recurrence was seen after 2 years and in a patient with transitional meningioma, recurrence was seen after 5 years.[Figure 1,2] Figure 1 MRI Brain with Gadolinium: Axial view showing intensely enhancing falcine meningioma Figure 2 MRI brain with gadolinium: Coronal view showing the same falcine meningioma

Follow up and recurrence An attempt was made to get follow-up of all patients. The period of follow-up ranged from 1 to 26 years with a mean follow-up of 6.1 years. We documented two recurrences in our series on follow-up. The histopathology in patients with recurrence was aggressive syncytial in one patient and transitional in the other patient. Both the patients had a total excision during their first surgery. The patient with transitional meningioma had a falcine meningioma and may be some microscopic remnant must have been left behind, as falx was not excised. During his redo surgery, we achieved a total excision of falx. In a patient with aggressive syncytial meningioma, recurrence was seen after 2 years and in a patient with transitional meningioma, recurrence was seen after 5 years.[Figure 1,2] Figure 1 MRI Brain with Gadolinium: Axial view showing intensely enhancing falcine meningioma Figure 2 MRI brain with gadolinium: Coronal view showing the same falcine meningioma Discussion Meningiomas are uncommon neoplasms in the pediatric age group and differ in various clinical and biological aspects from meningiomas in the adult population.[17] It was reported that the frequency was less than 5% of all pediatric brain tumors.[12] Its incidence as reported by Mendiratta et al.[7] is 1.5% of total meningiomas seen in the population. In our series of childhood meningiomas, i.e. meningiomas in children under 18 years of age, the incidence was 1.92%.

pulation.[17] It was reported that the frequency was less than 5% of all pediatric brain tumors.[12] Its incidence as reported by Mendiratta et al.[7] is 1.5% of total meningiomas seen in the population. In our series of childhood meningiomas, i.e. meningiomas in children under 18 years of age, the incidence was 1.92%. Children with meningiomas present late in the first decade or early in the second decade of life.[10111819] In our series, the mean age at presentation was 12.81 years. Infantile meningioma is extremely rare. Less than 30 cases of meningiomas in infants less than 12 months of age have been reported.[101920] The incidence of infantile meningiomas in different series of childhood meningiomas varies from 2.4%[10] to 6.9%[8–10] In our series, only one case (5.5%) of infantile meningioma was seen. In contrast to adult meningiomas where a female preponderance is seen,[21] childhood meningiomas showed a distinct male predominance.[8910121722] In our series, there were 11 males and 7 females. The male-to-female ratio was 1.57:1. The greater occurrence of meningiomas in males could be related to an absence of the effect of sex hormones on corticosteroid receptors in meningioma cells for low blood concentrations.[23–25] This suggests that different pathogenic factors might account for the occurrence of meningiomas in children and adults. Some studies on genetic aberrations in meningiomas in children show no differences from meningiomas in adults.[22]

on corticosteroid receptors in meningioma cells for low blood concentrations.[23–25] This suggests that different pathogenic factors might account for the occurrence of meningiomas in children and adults. Some studies on genetic aberrations in meningiomas in children show no differences from meningiomas in adults.[22] Signs and symptoms related to raised intracranial pressure are most common in childhood meningiomas. Meningiomas in children grow faster and occur more frequently in the ventricles than those in adults; therefore, cerebrospinal fluid circulation can be easily obstructed in the early stage, which results in increased intracranial pressure.[19] The incidence of seizure in childhood meningiomas(25%)[8–10] is lower than that in adult meningiomas (29-40%).[1] In our series, seizure was seen in 44.4% of cases (eight cases), i.e., an incidence similar to adult patients.[21] Focal seizure occurs more commonly in adults, whereas generalized seizure occurs more in children.[26] In our series, six patients presented with generalized seizures and only two patients presented with focal seizure. In different series in the literature, 0-41% of childhood meningiomas are associated with neurofibromatosis,[8–10] while the Figure is only 0.35% for adult meningiomas.[21] In Erdincler et al. series, 41% of childhood meningiomas were associated with multiple neurofibromatosis, of which 58% were NF-1 and 42% NF-2. In our series, we had one case each with NF-1 and NF-2, i.e. an incidence of 11.11%.

ated with neurofibromatosis,[8–10] while the Figure is only 0.35% for adult meningiomas.[21] In Erdincler et al. series, 41% of childhood meningiomas were associated with multiple neurofibromatosis, of which 58% were NF-1 and 42% NF-2. In our series, we had one case each with NF-1 and NF-2, i.e. an incidence of 11.11%. The frequency of intraventricular meningiomas is very high (12%)[22] as compared to 0.5-4.5% in adults.[2728] The propensity for growth into the ventricular system is explained by the inclusion of arachnoid cells in the choroid plexus and velum interpositum.[2930] In our series, 22.22% of cases had an intraventricular meningioma. The lack of dural attachment is another frequent occurrence in pediatric meningiomas (28.5%), whereas it is extremely rare in adult patients.[1315] This lack of dural attachment is probably due to derivation of the tumor from leptomeningeal elements lodging within the parenchyma or in or near the ventricles rather than from the dura mater.[31]

ent is another frequent occurrence in pediatric meningiomas (28.5%), whereas it is extremely rare in adult patients.[1315] This lack of dural attachment is probably due to derivation of the tumor from leptomeningeal elements lodging within the parenchyma or in or near the ventricles rather than from the dura mater.[31] An important feature distinguishing childhood meningiomas from adult meningiomas is their peculiar location. Convexity meningiomas are most common in adult meningiomas, while childhood meningiomas have other peculiar location that increases complexity in their management.[1132] In our series of 18 cases, only 6 cases were having convexity meningiomas, 4 skull base, 4 intraventricular, 1 tentorial, 1 posterior fossa, 2 falcine and one case was parasellar in location. In children, meningiomas have also been rarely reported to occur in the third ventricle[33] intraparenchymally[34] and in sylvian fissure.[35] Various series in the literature have also documented a high incidence of cystic changes in meningiomas in children.[1136] In our series, we had two patients with cystic changes in meningiomas. In series of Tufan et al., 4 out of 11 meningiomas showed cystic changes.[36]

An important feature distinguishing childhood meningiomas from adult meningiomas is their peculiar location. Convexity meningiomas are most common in adult meningiomas, while childhood meningiomas have other peculiar location that increases complexity in their management.[1132] In our series of 18 cases, only 6 cases were having convexity meningiomas, 4 skull base, 4 intraventricular, 1 tentorial, 1 posterior fossa, 2 falcine and one case was parasellar in location. In children, meningiomas have also been rarely reported to occur in the third ventricle[33] intraparenchymally[34] and in sylvian fissure.[35] Various series in the literature have also documented a high incidence of cystic changes in meningiomas in children.[1136] In our series, we had two patients with cystic changes in meningiomas. In series of Tufan et al., 4 out of 11 meningiomas showed cystic changes.[36] Surgical excision has been the treatment of choice for these tumors. Surgical management poses a formidable challenge considering their peculiar location, larger size at presentation, relatively less blood volume in children, and the risks of prolonged surgery like hypothermia, massive blood transfusion, etc. Nevertheless, with progress in microneurosurgical and anesthesiological techniques and considering the benign nature of disease, surgical excision remains the modality of choice. Also in children with residual tumor or regrowth, the risk of radiation to the developing brain favors redo surgery over radiation therapy. Pre-operative embolization is not routinely practised in children and there are no conclusive data on its benefits in children.[3738] However, the morbidity of the procedure due to small caliber of vessels in children should be kept in mind. In our series, pre-operative Digital subtraction angiography (DSA) with tumor embolization was done only in one case with skull base meningioma.[Figure 3]

are no conclusive data on its benefits in children.[3738] However, the morbidity of the procedure due to small caliber of vessels in children should be kept in mind. In our series, pre-operative Digital subtraction angiography (DSA) with tumor embolization was done only in one case with skull base meningioma.[Figure 3] Figure 3 MRI brain: Axial view showing skull base meningioma In our series, surgical excision was done in all cases. Gross total excision was achieved in 14 cases (77.78%) in the first attempt. In three patients, the biopsy was done first followed by a second stage complete excision. In one patient, complete excision was done in three stages, i.e. biopsy followed by partial excision followed by complete excision in third stage. We had only one patient with 5.5% peri-operative mortality rate. Various studies in the literature between the years 1970 and 2006 have shown a peri-operative mortality rate of 0.3-10%.[22] Various interventions have been advised in the literature to reduce the peri-operative mortality like pre- operative CSF diversion, anti-edema measures, anti- epileptic prophylaxis, use of postoperative ventilation, etc.[22]

ture between the years 1970 and 2006 have shown a peri-operative mortality rate of 0.3-10%.[22] Various interventions have been advised in the literature to reduce the peri-operative mortality like pre- operative CSF diversion, anti-edema measures, anti- epileptic prophylaxis, use of postoperative ventilation, etc.[22] Histopathological examination revealed fibroblastic meningioma in three cases, meningothelial meningioma in one, eight were transitional, three were angioblastic, one was sarcomatous, one was aggressive syncytial meningioma, and one case was malignant type. Histopathology of these tumors in the pediatric population varied from those in the adult population. Overall, most series have shown a high incidence of atypical and anaplastic meningiomas in children as compared to the adult population.[17] In our series, six patients (33.33%) had an atypical or anaplastic histopathology. In the literature, adjuvant therapy has been advised in these patients in the form of radiation therapy.[17] In series of Perry et al., they noted a high frequency of brain invasion in pediatric meningiomas and reported them to be phenotypically and genotypically aggressive as compared to the tumors in adults.[39] Immunohistochemical proliferative markers have been studied by Sandberg et al.[40] They documented higher MIB-1 LI in atypical or malignant tumors as compared to tumors without atypia. On the other hand, median MIB-1 for pediatric meningiomas without histopathological atypia did not differ significantly from that for adult meningiomas without atypia.

e markers have been studied by Sandberg et al.[40] They documented higher MIB-1 LI in atypical or malignant tumors as compared to tumors without atypia. On the other hand, median MIB-1 for pediatric meningiomas without histopathological atypia did not differ significantly from that for adult meningiomas without atypia. In our cases with atypical and aggressive histopathologies, four were given adjuvant radiotherapy. One patient with malignant meningioma expired postoperatively and one patient with sarcomatous meningioma could not be given radiation, as age at the time of surgery was only 9 months. This patient was followed up closely and has not shown any recurrence even after 14 years. We documented two recurrences in our series during the follow-up. The period of follow-up ranged from 1 to 26 years with a mean follow-up of 6.1 years. Histopathology in patients with recurrence showed aggressive syncytial in one case and transitional in the other case. Different series in the literature have shown a recurrence rate of approximately 13%.[22] Recurrence seems to be strictly related to incomplete resection and/or histologic subtype of the meningioma. Atypical, aggressive, and meningiomas with cortical invasion show a higher rate of recurrence. Overall, 16 patients improved neurologically postoperatively, one remained static, and one patient died postoperatively.

Different series in the literature have shown a recurrence rate of approximately 13%.[22] Recurrence seems to be strictly related to incomplete resection and/or histologic subtype of the meningioma. Atypical, aggressive, and meningiomas with cortical invasion show a higher rate of recurrence. Overall, 16 patients improved neurologically postoperatively, one remained static, and one patient died postoperatively. Conclusion Meningiomas in children are rare tumors and account for 1.92% of total meningiomas. Meningiomas in children show some characteristic differences when compared with their adult counterparts. These include slight preponderance in male subjects, higher incidence of intraventricular and skull base location, and frequent cystic changes. Pediatric meningiomas tend to present with features of raised intracranial pressure and seizure. An increased incidence of meningiomas is seen in patients with neurofibromatosis. Total surgical excision should be performed wherever feasible, even if it requires staged resection. Advances in microneurosurgical and anesthesiological management have considerably reduced the operative morbidity and mortality. There is a higher incidence of atypical and aggressive histological subtypes in the pediatric population. Children with complete resection of meningioma and a typical benign histology have a good prognosis like their adult counterparts. Source of Support: Nil. Conflict of Interest: None declared.

potential therapeutic impact in seizure patients. Glutamate and γ-amino-butyric-acid (GABA) can be measured using MRS editing techniques. Intracellular glutamate concentrations remain elevated in the epileptogenic hippocampus and neocortex, and contribute to the epileptic state by increasing cellular excitability.[15] Surgical treatment of refractory focal seizure has been an important and effective means for seizure control. However, the surgical outcome is dependent on precise localization of epiletogenic focus and functional areas of the brain. The fMRI, plays a very important role in preoperative localization of epileptogenic focus and assessment of cognitive function in patients with refractory epilepsy. During focal seizure, cerebral blood flow and metabolism is considerably increased. fMRI using blood oxygen level dependent (BOLD) technique can detect these cerebral hemodynamic changes. The excellent spatial resolution of fMRI helps to study cortical activation during epileptic activity and define epileptogenic focus in originally activated area. The recent development of EEG-triggered fMRI which allows interpretable electroencephalographic data to be recorded during MRI scanning, has advantage of combining the spatial resolution of imaging with the temporal resolution of electrophysiology in precise localization of seizure foci, thus increasing the rate of successful resection of the epileptogenic focus. The EEG-triggered fMRI is highly reliable, repeatable and noninvasive tool in localization of the seizure foci of patients with intractable focal seizure. Combined video-EEG and fMRI in localization of seizure foci has also shown good results.[1617] Long-term epileptic activity in patients with epilepsy results in atypical distribution of cognitive function areas because of reorganization of cortical language and memory areas. Accurate localization of cognitive functional areas is necessary, to avoid their resection at the time of surgery, to modify surgical approaches for those patients at risk of language and memory deficit and to predict postoperative cognitive deficit after resection of seizure foci.[18]

rtical language and memory areas. Accurate localization of cognitive functional areas is necessary, to avoid their resection at the time of surgery, to modify surgical approaches for those patients at risk of language and memory deficit and to predict postoperative cognitive deficit after resection of seizure foci.[18] The diffusion-weighted signal reflects the molecular motion of water in the intra and extracellular environments. In tissue components such as CSF, molecular motion is not restricted in any direction and is known as isotropic diffusion, detected by DWI. In tissues with linear arrangement of myelinated fibers such as white matter tracts, the molecular motion is restricted to the axis along the white tracts and is known as anisotropic diffusion, detected by DTI or tractography. In epilepsy, DWI is used to assess acute cerebral ischemia, tumors or infections, while DTI has been used to assess the degree of distortion of white matter tracts in case of developmental abnormalities and other lesions responsible for seizure. Anisotropy is reduced in areas of structural abnormalities suggesting structural disorganization of white matter.[1920]

bral ischemia, tumors or infections, while DTI has been used to assess the degree of distortion of white matter tracts in case of developmental abnormalities and other lesions responsible for seizure. Anisotropy is reduced in areas of structural abnormalities suggesting structural disorganization of white matter.[1920] Magnetoencephalography (MEG), also known as MSI when combined with structural imaging, has proved to be a new noninvasive tool for localization of epileptic focus. MSI is similar to EEG, but unlike EEG it detects magnetic rather than electric signal and is more accurate for localizing abnormal focus. It is increasingly useful for presurgical localization of epileptogenic lesions and stimulus-induced normal neuronal function to minimize postoperative neurological deficits.[21]

Your journal – Journal of Pediatric Neurosciences – has completed five years of publication. Over these years the journal has grown from strength to strength. In 2005, there was a desire by the Indian Society of Pediatric Neurosurgery Executive Committee and its members to have a journal of their own – one of the first neurosurgical sub-specialities to plan one. The aim was to increase academic interaction and to enhance the development of pediatric neurosurgery in our country. Dr. Suresh Sankhla was entrusted with the responsibility for this herculean task and how well he has responded to this challenge! Single handedly, over the next four years, he transformed this nascent journal into a world class one. From a stage where he had to cajole and persuade friends to write articles – we have now reached a stage where we can be selective. The journal has acquired such a reputation that we are regularly getting articles from Turkey, Iraq, Africa, South America, and Europe. Not only neurosurgeons, but also neurologists and pediatricians, are contributing articles regularly. Dr. Sankhla has continued to guide the journal as the Executive Editor for the past year, while I have been involved and will, I am sure, continue to do so in the future.

urkey, Iraq, Africa, South America, and Europe. Not only neurosurgeons, but also neurologists and pediatricians, are contributing articles regularly. Dr. Sankhla has continued to guide the journal as the Executive Editor for the past year, while I have been involved and will, I am sure, continue to do so in the future. I am happy to inform you that your journal is now indexed with PUBMED. We received 80 articles last year and had an acceptance rate of 75%. In 2011, we have already received 82 articles. Our impact factor, however, is only 0.304 and we have to work hard to improve it. Our e-publication is successful and regularly precedes the printed version. We are also linking the articles to videos hosted on the internet, so that demonstrative videos can enhance the presentations. In all these endeavors I must acknowledge the efforts of the team at Medknow Publications who have been most supportive. I am also grateful to our reviewers who have responded very well to our proddings. Most of all I would like to thank our contributors and readers for their loyalty and patronage.

e the presentations. In all these endeavors I must acknowledge the efforts of the team at Medknow Publications who have been most supportive. I am also grateful to our reviewers who have responded very well to our proddings. Most of all I would like to thank our contributors and readers for their loyalty and patronage. However, it is not yet time to rest on our laurels – but to strive for greater heights. Much needs to be done to popularize the journal further and improve its circulation. We plan to bring out a special issue in October to showcase Indian pediatric neurosurgery, on the occasion of the Thirty-ninth Annual Conference of the International Society of Pediatric Neurosurgery, in Goa. We also hope that maybe by next year we will increase the frequency of publication from two issues per year to three issues per year. A new editorial team is in place – which I am sure will work sincerely to improve our journal. We also have a new look – a colorful cover showing the complex network of neurons and a frolicking boy and girl playing happily – which is how we want all our patients to be!

Introduction A seizure is defined as a paroxysmal alteration in neurologic function due to excessive electrical discharge from the central nervous system. Epilepsy is defined as a condition of recurrent seizures, and medical intractability as recurrent seizures despite optimal treatment under the direction of an experienced neurologist over a 2-3-year period. Determining the underlying cause of a patient's seizure is the fundamental goal in the workup of epilepsy. Imaging of the brain provides valuable information in this regard. The main purposes of neuroimaging in epilepsy patients are to identify underlying structural or metabolic abnormalities that require specific treatment and to aid in formulating a syndromic or etiological diagnosis. Neuroimaging is even more important for those patients who have medically intractable seizures. Advances in technology to localize epileptogenic focus, especially with high resolution magnetic resonance imaging (MRI), have substantially improved the success of surgical treatment.

g a syndromic or etiological diagnosis. Neuroimaging is even more important for those patients who have medically intractable seizures. Advances in technology to localize epileptogenic focus, especially with high resolution magnetic resonance imaging (MRI), have substantially improved the success of surgical treatment. Structural disorders associated with seizure and detected on imaging can be categorized into the following groups [Figures 1–21]: hippocampal or mesial temporal sclerosis, cortical developmental malformations or neuronal migration disorders (cortical dysplasias, heterotopias, hemimegalencephaly, lissencephaly, schizencephaly, pachygyria, polymicrogyria, Rasmussen encephalitis), phakomatoses (Tuberous sclerosis, Sturge Weber syndrome, neurofibromatosis), vascular abnormalities (arteriovenous malformation, cavernous hemangiomas), infections (tuberculoma, neurocysticercosis), neoplasms (ganglioglioma, dysembryoplastic neuroepithelial tumor, low-grade gliomas, and cerebral metastasis in adults), stroke, post-traumatic epilepsy and miscellaneous conditions (gliosis, encephalocele). Figure 1 T2-weighted oblique coronal images of brain of 17-year-old male with mesial temporal sclerosis showing marked atrophy, sclerosis and loss of normal morphology of right hippocampus with dilated ipsilateral temporal horn. Left hippocampus also shows mild atrophy and minimal sclerosis with prominent ipsilateral temporal horn

weighted oblique coronal images of brain of 17-year-old male with mesial temporal sclerosis showing marked atrophy, sclerosis and loss of normal morphology of right hippocampus with dilated ipsilateral temporal horn. Left hippocampus also shows mild atrophy and minimal sclerosis with prominent ipsilateral temporal horn Figure 2 T2-weighted axial image of brain of 20-year-old male with heterotopia shows mass of heterotopic gray matter in left fronto-temporo-parietal region indenting the body of lateral ventricle Figure 3 T2-weighted axial image of brain of 9-month-old male child with non-lissencephalic cortical dysplasia shows shallow sylvian fissures giving figure eight appearance, polymicrogyria with shallow sulci and relative paucity of underlying white matter Figure 4 T2-weighted FLAIR coronal image of brain of 7-month-old male child with focal lissencephalic cortical dysplasia shows agyric, severely disorganized thickened left temporal lobe cortex with poor corticomedullary differentiation and associated ipsilateral heterotopic grey matter Figure 5 T2-weighted coronal image of brain of 6-year-old male child with Rasmussen's encephalitis, who had intractable seizures, shows unihemispheric focal cortical atrophy with grey and white matter hyperintensity Figure 6 Axial noncontrast CT scan of brain of 6-month-old male child with tuberous sclerosis shows both subependymal and parenchymal calcifications

Figure 5 T2-weighted coronal image of brain of 6-year-old male child with Rasmussen's encephalitis, who had intractable seizures, shows unihemispheric focal cortical atrophy with grey and white matter hyperintensity Figure 6 Axial noncontrast CT scan of brain of 6-month-old male child with tuberous sclerosis shows both subependymal and parenchymal calcifications Figure 7 Axial noncontrast CT scan of brain of 3-month-old male child with Sturge Weber Syndrome shows hemispheric cerebral atrophy, ipsilateral parieto-occipital cortical calcification and enlarged bilateral choroid plexuses Figure 8 Axial contrast enhanced T1W MRI of brain of 52-year-old male shows left frontal parenchymal arteriovenous malformation associated with large ipsilateral temporo-parietal bleed. The AVM nidus is seen as multiple intensely enhancing round and serpentine lesions with enlarged subependymal and superficial cortical draining veins. The arterial feeders were from left middle cerebral artery Figure 9 T2-weighted coronal image of brain of 19-year-old male, who presented with seizure, shows small left posterior parietal lobe cavernoma Figure 10 T1-weighted post contrast axial image of brain of 15-year-old female, who presented with seizure, shows left temporal lobe tuberculoma as two small conglomerate ring enhancing lesions Figure 11 T1-weighted postcontrast sagittal image of brain of 17-year-old male, who presented with seizure, shows vesicular stage of neurocysticercosis as solitary high parietal ring enhancing lesion with eccentric nodule and minimal perifocal edema

Figure 10 T1-weighted post contrast axial image of brain of 15-year-old female, who presented with seizure, shows left temporal lobe tuberculoma as two small conglomerate ring enhancing lesions Figure 11 T1-weighted postcontrast sagittal image of brain of 17-year-old male, who presented with seizure, shows vesicular stage of neurocysticercosis as solitary high parietal ring enhancing lesion with eccentric nodule and minimal perifocal edema Figure 12 T2-weighted and T1-weighted postgadolinium axial images of the brain of 15-year-old male, who presented with recurrent seizure, show left temporal lobe cystic lesion with eccentric enhancing mural nodule and mild perifocal edema. On histopathology the lesion proved to be ganglioglioma Figure 13 T2-weighted and T1-weighted postgadolinium coronal images of brain of 13-year-old male, who presented with gradually increasing seizure, show right frontotemporal lobe mass with mass effect. The lesion show no enhancement on corresponding post-gad image. Stereotactic biopsy showed the lesion to be low-grade astrocytoma Figure 14 T2-weighted FLAIR and T1-weighted postgadolinium coronal images of brain of 30-year-old male, who presented with increasing seizure, show relatively well-defined infiltrative predominantly right frontal lobe mass with contiguous extension into adjacent temporal lobe, genu of corpus callosum, and contralateral frontal lobe. The lesion show focal areas of hemorrhages but no enhancement in post-gad images. Stereotactic biopsy showed the lesion to be diffuse infiltrating astrocytoma

nfiltrative predominantly right frontal lobe mass with contiguous extension into adjacent temporal lobe, genu of corpus callosum, and contralateral frontal lobe. The lesion show focal areas of hemorrhages but no enhancement in post-gad images. Stereotactic biopsy showed the lesion to be diffuse infiltrating astrocytoma Figure 15 T2-weighted FLAIR coronal image of brain of 60-year-old male with renal cell carcinoma and recent onset seizure shows solitary right frontal lobe hemorrhagic metastasis with disproportional large perifocal edema and mass effect Figure 16 T2-weighted FLAIR coronal image of brain of 45-year-old male who presented with sudden onset right-sided hemiplegia and seizure, shows left frontotemporal lobe acute infarct (DWI not shown) Figure 17 T2-weighted axial GRE image of brain of 25-year-old male with post-traumatic seizure shows left frontal lobe hemorrhagic contusion Figure 18 T2-weighted FLAIR coronal image of brain of 30-year-old male who presented with seizure shows bilateral old gliotic infarcts Figure 19 T2-weighted axial image of brain of 13-year-old male with recurrent seizure shows basi-frontal meningo-encephalocele with schizencephaly Figure 20 Plain (a) Axial FLAIR/sagittal T1W/coronal T2W and postcontrast (b) axial/sagittal/coronal MRI of brain of 19-year-old male who presented with seizure demonstrate heterogeneous cortical/subcortical, T2W/FLAIR hyperintense and T1W hypointense, left parietal region mass showing no postcontrast enhancement. Diagnosis of dysembryoplastic neuroepithelial tumor (DNET) was confirmed on histopathological examination

MRI of brain of 19-year-old male who presented with seizure demonstrate heterogeneous cortical/subcortical, T2W/FLAIR hyperintense and T1W hypointense, left parietal region mass showing no postcontrast enhancement. Diagnosis of dysembryoplastic neuroepithelial tumor (DNET) was confirmed on histopathological examination Figure 21 Plain (a) Axial T2W/T1W/coronal FLAIR and postcontrast (b) axial/sagittal/coronal images of brain of 15-year-old male who presented with epilepsy demonstrate a multiloculated cystic, cortex-based, right temporal lobe mass giving honeycomb appearance. The septae within the cystic mass show mild contrast enhancement. Diagnosis of DNET was confirmed on histopathology

contrast (b) axial/sagittal/coronal images of brain of 15-year-old male who presented with epilepsy demonstrate a multiloculated cystic, cortex-based, right temporal lobe mass giving honeycomb appearance. The septae within the cystic mass show mild contrast enhancement. Diagnosis of DNET was confirmed on histopathology The role of imaging, in particular MRI, in dysembryoplastic neuroepithelial tumor (DNET) is important as this condition is encountered in significant number of patients undergoing surgery for intractable epilepsy. DNETs are benign tumors of young adults. Temporal lobe is the most common location, followed by frontal and parietooccipital lobes. Imaging [Figures 20 and 21] shows a predominantly cortical based gyral or nodular configuration mass, appearing hypodense on NCCT, hypointense on T1WI, hyperintense on T2WI and showing contrast enhancement in about 20-50% cases. They may resemble a simple or complex cyst showing peripheral ring enhancement or soap bubble appearance, respectively. These lesions lack edema and mass effect, and there is little or no white matter extension. Hemorrhage and calcification are uncommon. Diffusion-weighted imaging (DWI) and corresponding ADC mapping shows no diffusion restriction. MR spectroscopy (MRS) finding is non-specific although an elevated choline peak may be present. Important differential diagnosis include ganglioglioma and low-grade astrocytoma.[12]

Hemorrhage and calcification are uncommon. Diffusion-weighted imaging (DWI) and corresponding ADC mapping shows no diffusion restriction. MR spectroscopy (MRS) finding is non-specific although an elevated choline peak may be present. Important differential diagnosis include ganglioglioma and low-grade astrocytoma.[12] Imaging Modalities This article highlights the specific role of various imaging modalities in patients with epilepsy, and their practical applications in the management of epileptic patients. The major utility of computed tomography (CT) scanning is in the initial evaluation of seizures, particularly in trauma, hemorrhage, infarction, tumors, calcified lesions and major structural changes. In perioperative patients, it is the imaging technique of choice as it can detect the bleed, hydrocephalus and assess electrode placement. However, the overall sensitivity of CT in patients with epilepsy is low (~ 30%), and because of poor resolution in the temporal fossa, CT is of no use in detecting mesial temporal sclerosis, the most common pathology in intractable temporal lobe epilepsy.[3]

tect the bleed, hydrocephalus and assess electrode placement. However, the overall sensitivity of CT in patients with epilepsy is low (~ 30%), and because of poor resolution in the temporal fossa, CT is of no use in detecting mesial temporal sclerosis, the most common pathology in intractable temporal lobe epilepsy.[3] MRI, with its excellent spatial resolution, soft tissue contrast, and multiplanar capabilities, is the imaging modality of choice in investigating patients with seizure disorder. The sensitivity of MRI in identifying epileptogenic foci in patients with medically refractory patients has been reported to be more than 80%. However, in patients with idiopathic generalized epilepsy, MRI has not been shown to be useful. The correlation of the MRI finding with clinical and electroencephalography (EEG) findings are essential to avoid false positive localization of epileptogenic focus.[4]

ractory patients has been reported to be more than 80%. However, in patients with idiopathic generalized epilepsy, MRI has not been shown to be useful. The correlation of the MRI finding with clinical and electroencephalography (EEG) findings are essential to avoid false positive localization of epileptogenic focus.[4] Routine scanning protocol for a patient with refractory epilepsy may include axial or coronal T1 and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR) imaging, and 3D volume acquisition sequences. Common 3D acquisition sequences include high-resolution T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) and fast spoiled GRASS (3D-FSPGR), where GRASS is gradient recalled echo acquisition in steady state. T1-weighted sequences are used to define the brain anatomy, and T2-weighted or FLAIR sequences are used to detect the brain pathologies. High-resolution 3D volume acquisition provides good T1-weighted contrast between gray and white matter and helps to detect subtle cortical dysplasias and internal structure of hippocampus in case of mesial temporal sclerosis.[5–7] For optimal assessment of hippocampus the imaging should be in hippocampal axis (oblique coronal plane) with thin slices and good signal-to-noise ratio. The application of contrast agent is indicated if there is suspicion of primary or metastatic tumor, infection or inflammatory lesion. The specialized protocol includes quantitative volumetry and T2 relaxometry, MRS, functional MRI (fMRI), DWI and diffusion tensor imaging (DTI), and magnetic source imaging (MSI).

Routine scanning protocol for a patient with refractory epilepsy may include axial or coronal T1 and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR) imaging, and 3D volume acquisition sequences. Common 3D acquisition sequences include high-resolution T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) and fast spoiled GRASS (3D-FSPGR), where GRASS is gradient recalled echo acquisition in steady state. T1-weighted sequences are used to define the brain anatomy, and T2-weighted or FLAIR sequences are used to detect the brain pathologies. High-resolution 3D volume acquisition provides good T1-weighted contrast between gray and white matter and helps to detect subtle cortical dysplasias and internal structure of hippocampus in case of mesial temporal sclerosis.[5–7] For optimal assessment of hippocampus the imaging should be in hippocampal axis (oblique coronal plane) with thin slices and good signal-to-noise ratio. The application of contrast agent is indicated if there is suspicion of primary or metastatic tumor, infection or inflammatory lesion. The specialized protocol includes quantitative volumetry and T2 relaxometry, MRS, functional MRI (fMRI), DWI and diffusion tensor imaging (DTI), and magnetic source imaging (MSI). High resolution T1-weighted 3D volume gradient echo sequences are also used for quantitative measurement of volume of any particular region of interest. In the case of epilepsy this is usually the hippocampus. Volumetric analysis of the hippocampus can be performed both in adults and children with epilepsy, to detect more subtle volume deficits (atrophy) that may be missed by visual assessment alone. Volumetric measurements can be performed manually or with half or fully automated software, however, needs good knowledge of anatomical details. Longitudinal studies done to assess the progression of volumetric changes correlate with the seizure-associated damage.[8] T2 relaxometry is the quantitative determinant of the T2 relaxation time. To achieve this, several T2-weighted images are acquired at different echo times, and with these values an exponential decay curve is obtained to estimate the T2 decay rate of the imaged tissue. The tissues that have prolonged T2 are considered abnormal. In epileptic patients with hippocampal sclerosis, signal increase on T2-weighted images is typically observed in the hippocampus. The measured values of the hippocampal volume and the T2 times are correlated with each other, indicating that a marked volume loss is associated with a significant increase in T2 relaxation, reflecting the complex pathology of hippocampal sclerosis.[9]

se on T2-weighted images is typically observed in the hippocampus. The measured values of the hippocampal volume and the T2 times are correlated with each other, indicating that a marked volume loss is associated with a significant increase in T2 relaxation, reflecting the complex pathology of hippocampal sclerosis.[9] Proton MR spectroscopy (MRS) has proven to be a sensitive measure to detect metabolic dysfunction in patients with temporal lobe epilepsy (TLE), particularly mesial temporal sclerosis (MTS) involving hippocampus. Twenty percent of patients with TLE have normal structural MRI scan and the findings in children generally tend to be more subtle than those in adults. MRS metabolite abnormalities may be found even in the absence of detectable structural abnormalities. NAA, NAA/Cho, NAA/Cr, and NAA/(Cho+Cr) all are decreased in atrophic hippocampi, as well as in nonatrophic hippocampi with abnormal EEG findings. Reduced N-acetylaspartate concentration suggests neuronal loss or dysfunction. TLE patients may also show increased choline and myoinositol signals, suggestive of gliosis. Studies of patients during or immediately after seizures (within 6 hours) may also show lactate increase in the epileptogenic focus. MRS also has promising role in the evaluation of patients with extratemporal epilepsy (frontal lobe epilepsy).[1011] In patients with structural MR evidence of malformations of cortical development (MCD) or neuronal migration disorders (NMD), MRS provides insight into both the pathology and true extent of the disease processes. Abnormally decreased NAA/Cr and Cho/Cr ratios have been noted in these lesions, as well as in the normal appearing brain contralateral to the lesion, when compared with gray and white matter of neurological controls.[1213] MRS is of particular importance in patients with brain tumors. The characteristic elevation of choline makes MRS a valuable tool for the diagnosis of tumors and their differentiation from other lesions. There is also evidence that MRS can differentiate between tumor types.[14] Neurotransmitter MRS studies have potential therapeutic impact in seizure patients. Glutamate and γ-amino-butyric-acid (GABA) can be measured using MRS editing techniques. Intracellular glutamate concentrations remain elevated in the epileptogenic hippocampus and neocortex, and contribute to the epileptic state by increasing cellular excitability.[15]

us. MSI is similar to EEG, but unlike EEG it detects magnetic rather than electric signal and is more accurate for localizing abnormal focus. It is increasingly useful for presurgical localization of epileptogenic lesions and stimulus-induced normal neuronal function to minimize postoperative neurological deficits.[21] Besides purely structural imaging techniques like MRI, functional imaging studies like interictal positron emission tomography (PET), and ictal and interictal single photon emission computed tomography (SPECT) may provide additional information in some patients and thus aid in clinical decision making. PET and SPECT are usually not indicated for the majority of patients with epilepsy but has important role in the surgical candidates. The detection of cryptogenic lesions is the main goal of functional epilepsy imaging with PET or SPECT. PET utilizes an injection of tracer 18F-labeled deoxyglucose (18FDG) to measure brain metabolism. Interictal PET shows hypometabolism in the seizure focus, especially in TLE. Ictal PET is not practical due to extremely short half-life of the radiotracers used. PET remains a diagnostic modality for presurgical localization of the focus in temporal lobe and extratemporal epilepsy when MRI is normal.[22] SPECT utilizes injection of radio-labeled tracer Technetium99m hexamethyl-propyleneamineoxime (Tc-HMPAO) or ethyl cysteinate dimer (Tc ECD), which has very slow distribution once in the brain. The tracer is stable for several hours, allowing delayed imaging. The most useful study for presurgical evaluation is an ictal SPECT, which usually reveals increased blood flow at site of seizure onset. Interictal studies often show relative hypoperfusion at the site of seizure onset. The substraction of the interictal from the ictal SPECT, and then coregistration of the resulting images onto MRI (substraction ictal SPECT coregistration MRI - SISCOM) has shown to increase the accuracy of this method.[23]

eizure onset. Interictal studies often show relative hypoperfusion at the site of seizure onset. The substraction of the interictal from the ictal SPECT, and then coregistration of the resulting images onto MRI (substraction ictal SPECT coregistration MRI - SISCOM) has shown to increase the accuracy of this method.[23] Source of Support: Nil. Conflict of Interest: None declared.

Introduction Glioma is a deadly neurological tumor. For modern management of glioma, glioma vaccinotherapy is the new concept. Tumor vaccine is the hope.[1] The immunomanipulation is believed to be better than classical invasive neurological approach. It is also applicable in neurological tumor. Djedid et al., mentioned that vaccinotherapy is the hope for glioma treatment.[2] New peptide-based vaccine is the aim in the present vaccine research.[3] Yang et al., said that “Preclinical animal models have shown the feasibility of an active immunotherapy approach through the utilization of tumor vaccines, and recently several clinical studies have also been initiated.”[4] Based on present biomedical technique, the identification of T-cell epitopes via major histocompatibility complex (MHC) mapping can help clarify the inter-relationship of tumor and immune system. This process can be performed based on advanced immunoinformatics technique.[5] The clarification on the inter-relationship of tumor and immune system is the basic requirement for development of a new vaccine.[6] The use of immunoinformatics can shorten the overall period for epitopes searching. Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2 based on a novel bioinformatics tool. After complete manipulation on EPHA2 molecules, the best five epitopes were derived.

se of immunoinformatics can shorten the overall period for epitopes searching. Here, the author performs an immunoinformatics analysis to find alternative epitopes for glioma-related antigen, EPHA2 based on a novel bioinformatics tool. After complete manipulation on EPHA2 molecules, the best five epitopes were derived. Materials and Methods In this work, potential T-cell epitopes searching on EPHA2 molecule was done using a new referenced immunoinformatics tool, created by Parker et al., which could help detect peptide binding to MHCs.[7] The protocol for this immunoinformatics research is the standard published protocol in the previous studies on cancer vaccine searchings.[8–10] The input sequence in this work was EPHA2, which was directly quoted from PubMed (www.pubmed.com). The focus is finding for the best five epitopes with the highest immunogeneticity. Results After manipulation on the studied molecule, EPHA2, the best five epitopes are “160TLADFDPRV”, “238SLLGLKDQV”, “202FMAAGYTAI”, “83VMWEVMTYG,” and “150KLIRAPDSL”.

Materials and Methods In this work, potential T-cell epitopes searching on EPHA2 molecule was done using a new referenced immunoinformatics tool, created by Parker et al., which could help detect peptide binding to MHCs.[7] The protocol for this immunoinformatics research is the standard published protocol in the previous studies on cancer vaccine searchings.[8–10] The input sequence in this work was EPHA2, which was directly quoted from PubMed (www.pubmed.com). The focus is finding for the best five epitopes with the highest immunogeneticity. Results After manipulation on the studied molecule, EPHA2, the best five epitopes are “160TLADFDPRV”, “238SLLGLKDQV”, “202FMAAGYTAI”, “83VMWEVMTYG,” and “150KLIRAPDSL”. Discussion The glioma vaccine is a novel therapeutic approach for glioma treatment. There are some interesting reports from vaccine trials on animal models.[1112] Recently, some new vaccines were also tested in human beings. Ardon et al., reported a study on immunotherapy consisting of vaccination with autologous dendritic cells loaded with autologous tumor lysate and concluded that “CD127 staining is a fast, well-suited and reproducible Treg monitoring tool in HGG patients treated with immunotherapy.”[13] In addition, Sampson et al., reported their study on another new epidermal growth factor receptor variant III-targeted vaccine and found that this vaccine was safe and immunogenic in patients with glioblastoma multiforme.[14] Jian et al., concluded that “Current vaccine therapies are in clinical trials and are showing beneficial responses.”[15]

., reported their study on another new epidermal growth factor receptor variant III-targeted vaccine and found that this vaccine was safe and immunogenic in patients with glioblastoma multiforme.[14] Jian et al., concluded that “Current vaccine therapies are in clinical trials and are showing beneficial responses.”[15] However, relevant literature does not show great benefit with the lymphocytic arm for the glioma immune regulation. This might be due to the limitation of the knowledge on this topic. Indeed, understanding on T-cell immunity can lead to the most effective therapeutic strategy to treat malignant glioma.[16] Yamanaka et al., concluded that “it may be necessary to evaluate the molecular genetic abnormalities in individual patient tumors and design novel immunotherapeutic strategies based on the pharmacogenomic findings.”[17] Nevertheless, searching for the common epitopes that can effectively induce antitumor immunity to glioma seems to be a more important process in new glioma vaccine development.[18]

enetic abnormalities in individual patient tumors and design novel immunotherapeutic strategies based on the pharmacogenomic findings.”[17] Nevertheless, searching for the common epitopes that can effectively induce antitumor immunity to glioma seems to be a more important process in new glioma vaccine development.[18] Prediction of peptide binding to MHC molecules is the first step of vaccine searching. In this work, the author describes a preliminary study on glioma vaccine search. Basically, advanced computational immunomics approach via several algorithms can help assess the epitopes within the studied molecules.[7] Some recent cancer vaccine researches[8–10] also use the immunoinformatics approach for searching for primary epitopes for many oncological disorders. The multiple epitopes searching in this work can help further finding a new glioma multi-epitope vaccine. The usefulness of this technique in either cancerous[8–10] or non-cancerous disorders[19] is already approved in the previous reports. In this work, EPHA2, which is accepted as a highlighted molecule with high possibility for using in glioma vaccine production,[20] is focused. Targeting at EPHA2 via RNA interference process is proven to result in cancer reduction.[21] Indeed, the attempt to develop EPHA2-based vaccine for glioma has been proposed for many years. In the past, when there was no advanced bioinformatics technique, the crude whole EPHA2 vaccine was studied. The quoted referenced work is the study by Hatano et al.[22] In that work,[22] success in using the vaccine for attacking melanoma is mentioned.

p EPHA2-based vaccine for glioma has been proposed for many years. In the past, when there was no advanced bioinformatics technique, the crude whole EPHA2 vaccine was studied. The quoted referenced work is the study by Hatano et al.[22] In that work,[22] success in using the vaccine for attacking melanoma is mentioned. Source of Support: Nil. Conflict of Interest: None declared.

A 15-year-old boy presented with history of coarse tremors of right hand and dysarthric speech since 1 year. Neurologic examination revealed Kayser–Fleischer rings in both the eyes and dystonic tremor of the right hand. Serum ceruloplasmin and urine copper studies established the diagnosis of Wilson's disease. No evidence of jaundice or cirrhosis was seen to imply hepatic involvement. Liver function tests were within normal limits. Magnetic resonance (MR) imaging showed T2 and FLAIR hyperintense lesions involving bilateral thalami, midbrain, and pons. The lesions were hypointense on T1-weighted sequence and showed no evidence of restricted diffusion. Only subtle hyperintense signal on T2/FLAIR images was seen in the lentiform nuclei [Figure 1]. Caudate nuclei, cerebellar white matter, centrum semiovale and subcortical white matter were not involved. Involvement of the midbrain demonstrated that the characteristic magnetic resonance imaging (MRI) appearance of the “face of the giant panda” and dorsal pontine signal abnormalities resembled the face of a cub [Figures 2 and 3]. Face of the giant panda and her cub constitute the “double panda sign”[1] which is characteristic for this disease and has been described only in few reports. Figure 1 T2-weighted axial MRI demonstrates hyperintense signal in the bilateral thalami and putamen Figure 2 T2-weighted axial MRI demonstrates the “face of the giant panda” in the midbrain with high signal in tegmentum and normal red nuclei (arrow)

Magnetic resonance (MR) imaging showed T2 and FLAIR hyperintense lesions involving bilateral thalami, midbrain, and pons. The lesions were hypointense on T1-weighted sequence and showed no evidence of restricted diffusion. Only subtle hyperintense signal on T2/FLAIR images was seen in the lentiform nuclei [Figure 1]. Caudate nuclei, cerebellar white matter, centrum semiovale and subcortical white matter were not involved. Involvement of the midbrain demonstrated that the characteristic magnetic resonance imaging (MRI) appearance of the “face of the giant panda” and dorsal pontine signal abnormalities resembled the face of a cub [Figures 2 and 3]. Face of the giant panda and her cub constitute the “double panda sign”[1] which is characteristic for this disease and has been described only in few reports. Figure 1 T2-weighted axial MRI demonstrates hyperintense signal in the bilateral thalami and putamen Figure 2 T2-weighted axial MRI demonstrates the “face of the giant panda” in the midbrain with high signal in tegmentum and normal red nuclei (arrow) Figure 3 T2-weighted axial MRI reveals the “face of the miniature panda” in pons with hypointensity of central tegmental tracts (arrow) with hyperintensity of aqueductal opening to fourth ventricle

Figure 2 T2-weighted axial MRI demonstrates the “face of the giant panda” in the midbrain with high signal in tegmentum and normal red nuclei (arrow) Figure 3 T2-weighted axial MRI reveals the “face of the miniature panda” in pons with hypointensity of central tegmental tracts (arrow) with hyperintensity of aqueductal opening to fourth ventricle Wilson's disease is an inborn error of copper metabolism that is characterized by deficiency of ceruloplasmin, the serum transport protein for copper. Copper is collected in the liver, and after hepatic binding sites are saturated, it is released. Systemic disease then develops and there is abnormal accumulation of copper in the brain, particularly in the putamen and globus pallidus.[2] The neurologic manifestations associated with Wilson's disease are understood to be secondary to buildup of cerebral copper at levels adequate to destroy nerve cells. Edema, necrosis, and spongiform degeneration are the histopathological changes that are observed in Wilson's disease involving the brain.[3] MRI not only provides biochemical information on heavy metal distribution in brain tissue but also gives an insight into the pathologic and anatomic correlates of clinical signs and symptoms in Wilson's disease. Interval changes seen on follow-up MR imaging have good correlation with clinical symptoms and can be useful in evaluating the clinical response to treatment of children with Wilson's disease.[4]

ue but also gives an insight into the pathologic and anatomic correlates of clinical signs and symptoms in Wilson's disease. Interval changes seen on follow-up MR imaging have good correlation with clinical symptoms and can be useful in evaluating the clinical response to treatment of children with Wilson's disease.[4] The midbrain “face of the giant panda” sign[5] consists of high signal intensity in the tegmentum, preservation of signal intensity of the lateral portion of the pars reticulata of the substantia nigra and red nucleus (arrowhead), and hypointensity of the superior colliculus. In addition, a “face of panda cub” is seen within the dorsal part of pons. “Eyes of the panda” are formed from the relative hypointensity of the central tegmental tracts (CTT) (arrowhead) in contrast with the hyperintensity of the aqueduct opening into the fourth ventricle (“nose and mouth of the panda”) bounded inferiorly by the superior medullary velum. The panda's “cheeks” are formed from the superior cerebellar peduncles.[1] Source of Support: Nil. Conflict of Interest: None declared.

Introduction The potential use of the affected upper extremity of children with hemiplegia often fails due to “learned non-use phenomenon”.[1] Constraint-induced movement therapy (CIMT) is one of the treatment strategies which utilizes the principles of neural plasticity to help acquire motor skills of the affected upper extremity.[2–7] This therapeutic approach involves constraining of the unaffected upper extremity using sling, plaster cast, mitt or splints and intensive training of the affected upper extremity with task-specific, goal-oriented activities by reinforcement (shaping technique).[89] Case Report A five-year-old female child presented with right hemiplegia with the history of delayed motor milestones and limited motor skills of the right upper extremity since birth. The history given by parents was suggestive of birth asphyxia. The objective details of the cause of hemiplegia could not be established as there were no medical records available. The child had no history of seizure or any other form of developmental delay. The child had not undergone any physical therapy interventions earlier. Presently, she has achieved the highest level of functional independence (able to walk and run independently). She displayed no voluntary effort to initiate any motor skills of the right upper extremity unless verbally prompted, even otherwise initiating only minimal response suggesting learned non-use phenomenon. The following criteria were considered for use of CIMT in this child (adapted from Cochrane review study).[10] Observed learned non-use of affected upper extremity.

Case Report A five-year-old female child presented with right hemiplegia with the history of delayed motor milestones and limited motor skills of the right upper extremity since birth. The history given by parents was suggestive of birth asphyxia. The objective details of the cause of hemiplegia could not be established as there were no medical records available. The child had no history of seizure or any other form of developmental delay. The child had not undergone any physical therapy interventions earlier. Presently, she has achieved the highest level of functional independence (able to walk and run independently). She displayed no voluntary effort to initiate any motor skills of the right upper extremity unless verbally prompted, even otherwise initiating only minimal response suggesting learned non-use phenomenon. The following criteria were considered for use of CIMT in this child (adapted from Cochrane review study).[10] Observed learned non-use of affected upper extremity. A possible movement of at least 10° extension at metacarpophalangeal and inter-phalangeal joints and 20° extension at wrist of the affected upper extremity. No cognitive impairment and shall cooperate with treatment.

Case Report A five-year-old female child presented with right hemiplegia with the history of delayed motor milestones and limited motor skills of the right upper extremity since birth. The history given by parents was suggestive of birth asphyxia. The objective details of the cause of hemiplegia could not be established as there were no medical records available. The child had no history of seizure or any other form of developmental delay. The child had not undergone any physical therapy interventions earlier. Presently, she has achieved the highest level of functional independence (able to walk and run independently). She displayed no voluntary effort to initiate any motor skills of the right upper extremity unless verbally prompted, even otherwise initiating only minimal response suggesting learned non-use phenomenon. The following criteria were considered for use of CIMT in this child (adapted from Cochrane review study).[10] Observed learned non-use of affected upper extremity. A possible movement of at least 10° extension at metacarpophalangeal and inter-phalangeal joints and 20° extension at wrist of the affected upper extremity. No cognitive impairment and shall cooperate with treatment. Outcome measure: Quality of upper extremity skills test The Quality of Upper Extremity Skills Test (QUEST) is a criterion-referenced measure that evaluates the quality of upper extremity function in four domains: dissociated movements (19 items with one level of response for each item), grasps (six items with three to five levels of response for each item), weight-bearing (five items with six levels of response for each item) and protective extension (three items with six levels of response for each item). It is designed to be used with children who exhibit neuromotor dysfunction with spasticity and has been validated with children 18 months to eight years of age. The data collected during the Neuro Developmental Therapy/Casting study by Law et al., were used to analyze the validity and responsiveness of the QUEST.[11]

. It is designed to be used with children who exhibit neuromotor dysfunction with spasticity and has been validated with children 18 months to eight years of age. The data collected during the Neuro Developmental Therapy/Casting study by Law et al., were used to analyze the validity and responsiveness of the QUEST.[11] Intervention procedure The parents of the child were counseled for the treatment approach that could improve the motor skills of the affected right upper extremity. The parents were interested and were keen in subjecting their child to this treatment approach and gave informed consent. The pre-intervention assessments of the right upper extremity motor skills were measured using QUEST. The unaffected left upper extremity was constrained with posterior slab plaster cast extending above the elbow to the interphalangeal joints of fingers and supported with a sling. The parents were instructed to maintain the constraint for at least two weeks. The affected right upper extremity was then subjected to task-specific goal-oriented activities that aimed to improve reaching, grasps, manipulation and release of the object using the arm and hand. The activities were encouraged using play way method and reinforcements using visual (postural mirror) and verbal feedback. The therapy session usually lasted for one hour a day for five days a week. The parents were instructed to constantly encourage the same activities that were carried out during the treatment session in daily activities. At the end of the two-week period, post-intervention assessment of the right upper extremity was done using QUEST. As there was an incremental response in the outcome measure, the investigators convinced the parent to continue the treatment for another week. At the end of three weeks, once again post-intervention assessment was done.

he two-week period, post-intervention assessment of the right upper extremity was done using QUEST. As there was an incremental response in the outcome measure, the investigators convinced the parent to continue the treatment for another week. At the end of three weeks, once again post-intervention assessment was done. Results As the QUEST measure analyzes the quality of motor skills of both the right and left extremity, it may be noted that the pre-intervention percentage score was 53.04% indicating full percentage score of unaffected left upper extremity and marginal percentage score of affected right upper extremity [Table 1]. Following intervention, increments in percentage score by 26.79% and 07.51% were observed at the end of two weeks and three weeks respectively which should be attributed to the improvements in the quality of motor skills of the affected right upper extremity. It may also be noted that the grasp percentage score was greater than other domains indicating better improvement in fine motor skills than gross motor skills. The overall increment observed was 34.30%. Table 1 Summary of QUEST scores

Results As the QUEST measure analyzes the quality of motor skills of both the right and left extremity, it may be noted that the pre-intervention percentage score was 53.04% indicating full percentage score of unaffected left upper extremity and marginal percentage score of affected right upper extremity [Table 1]. Following intervention, increments in percentage score by 26.79% and 07.51% were observed at the end of two weeks and three weeks respectively which should be attributed to the improvements in the quality of motor skills of the affected right upper extremity. It may also be noted that the grasp percentage score was greater than other domains indicating better improvement in fine motor skills than gross motor skills. The overall increment observed was 34.30%. Table 1 Summary of QUEST scores Discussion The main concern for the parents in the use of CIMT for improving the motor skills of the affected upper extremity in infantile hemiplegia was the fact that it restricts the use of the unaffected extremity. The success of the use of CIMT in infantile hemiplegia depends on the parents, their proper understanding of the concept of the approach and their deep motivation in carrying out home exercises. The increments in percentage scores observed in this case report are attributed to the increased demands for the use of the affected upper extremity while constraining the unaffected upper extremity through task-specific goal-oriented activities that were reinforced with visual and verbal feedback.

out home exercises. The increments in percentage scores observed in this case report are attributed to the increased demands for the use of the affected upper extremity while constraining the unaffected upper extremity through task-specific goal-oriented activities that were reinforced with visual and verbal feedback. Conclusion The observation of this case report indicates that the use of CIMT could reverse the learned non-use phenomenon of the affected upper extremity in infantile hemiplegia and thus reduce disability to greater extent. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Vein of galen aneurismal malformation (VOGAM) is a rare congenital anomaly with a reported incidence of 30% of pediatric malformations.[12] Jaeger et al., first published a reported case of VOGAM in literature.[3] In the choroidal stage of development of the cerebral vascular system,[4] the venous drainage is mainly by the median venous structure, the MProsV of Markowski.[5] This median vein of prosencephalon usually involutes as the internal cerebral vein develops. The posterior segment of the MProsV persists as the vein of Galen. Vein of galen aneurismal malformation is a cluster of arteriovenous fistulas (AVFs) draining into the dilated median vein of the prosencephalon. The arterial feeders are usually from the anterior and posterior choroidal arteries, the pericallosal artery, and the transmesencephalic branches of the basilar tip. The VOGAM is mainly divided into mural and choroidal types. In the mural type (simple type), there is a direct high flow shunt located within the wall. In the choroidal type (complex type), there is interposition of the arterial feeders and the venous aneurysm. Clinically, the mural types of VOGAM present later in infants with macrocephaly or failure to thrive and may be associated with mild cardiac failure or asymptomatic cardiomegaly. The choroidal types of VOGAM usually cause heart failure in newborns.

there is interposition of the arterial feeders and the venous aneurysm. Clinically, the mural types of VOGAM present later in infants with macrocephaly or failure to thrive and may be associated with mild cardiac failure or asymptomatic cardiomegaly. The choroidal types of VOGAM usually cause heart failure in newborns. Pathophysiology On account of a sustained increased flow, enlarged arteries can be associated with aneurysms or occlusions. On the venous side, there is re-routing of the venous flow into the cortical veins. Impairment of the outflow causes increased venous hypertension and increases the risk of intracranial hemorrhage. Communicating hydrocephalus occurs due to impaired absorption of the cerebrospinal fluid by the arachnoid villi. Case Reports Case 1 An 11-month-old male child presented with macrocrania. Antenatal scans in the third trimester revealed vein of galen aneurysmal malformation. Eventually the child was followed up with serial imaging. Computed tomography (CT) and magnetic resonance (MR) imaging [Figure 1] done at the time of presentation showed the VOGAM in the posterior interhemispheric fissure, causing a compression of the third ventricle and the cerebral aqueduct, leading to hydrocephalus. Subsequently, an angiogram was done, which revealed a mural type of VOGAM [Figure 2a, b]. Figure 1 Contrast-enhanced MR images showing the vein of galen aneurysm in the midline causing compression of the third ventricle, leading to hydrocephalus

Case Reports Case 1 An 11-month-old male child presented with macrocrania. Antenatal scans in the third trimester revealed vein of galen aneurysmal malformation. Eventually the child was followed up with serial imaging. Computed tomography (CT) and magnetic resonance (MR) imaging [Figure 1] done at the time of presentation showed the VOGAM in the posterior interhemispheric fissure, causing a compression of the third ventricle and the cerebral aqueduct, leading to hydrocephalus. Subsequently, an angiogram was done, which revealed a mural type of VOGAM [Figure 2a, b]. Figure 1 Contrast-enhanced MR images showing the vein of galen aneurysm in the midline causing compression of the third ventricle, leading to hydrocephalus Figure 2 Pre-embolization vertebral artery angiogram of the anteroposterior and lateral views (a,b), demonstrating the mural type of fistula (arrow), Post embolization vertebral artery angiogram (c,d) shows complete obliteration of the fistula with good visualization of the posterior cerebral artery (arrow) Procedure: Under general anesthesia, using the retrograde Seldinger technique, right femoral access was taken. Using a 5F envoy guiding catheter, the right posterior cerebral artery (PCA) was selectively catheterized with a micro catheter and micro wire combination (Excel14 / Transcend wire) and the fistula was occluded, with 80% N-butyl cyanoacrylate (NBCA). A post-procedure angiogram revealed complete occlusion of the fistula and better visualization of the PCA branches [Figure 2c, d].

al artery (PCA) was selectively catheterized with a micro catheter and micro wire combination (Excel14 / Transcend wire) and the fistula was occluded, with 80% N-butyl cyanoacrylate (NBCA). A post-procedure angiogram revealed complete occlusion of the fistula and better visualization of the PCA branches [Figure 2c, d]. The child had an uneventful course in the ward. On the follow-up of three months, six months, and one year there was decrease in the macrocrania. On the two-year follow-up there was significant decrease in the macrocrania, with normal developmental milestones for age. Case 2 A 15-month-old female child presented with abnormally dilated neck veins and delayed milestones. A diagnostic angiogram revealed a choroidal type of VOGAM. Numerous arterial feeders were seen from the bilateral posterior choroidal arteries [Figure 3a, b, c]. In order to reduce the risk of contrast and fluid overload, and to prevent the occurrence of hyperperfusion breakthrough, endovascular treatment in multiple sessions was planned. In the first session, the right posterior choroidal feeders were embolized with 33 and 24% NBCA causing 25% flow reduction in the fistulous connection. The child was asked to come for follow-up after three months. At the age of 18 months, a second session of embolization of the left posterior choroidal feeders was done using 33 and 25% NBCA resulting in 50% reduction in the flow [Figure 4a, b]. The child tolerated the procedure well and was followed up after a three-month interval.

asked to come for follow-up after three months. At the age of 18 months, a second session of embolization of the left posterior choroidal feeders was done using 33 and 25% NBCA resulting in 50% reduction in the flow [Figure 4a, b]. The child tolerated the procedure well and was followed up after a three-month interval. Figure 3 Digital substraction angiogram showing multiple feeders from the posterior choroidal arteries (arrows) in the choroidal type of VOGAM (a,b), with venous drainage into a large ectatic vein (c) Figure 4 Vertebral angiogram demonstrating reduction in the flow to the malformation after the third session of embolization by NBCA (arrow) (a, b). Further reduction in the flow following the fifth session of embolization (c,d)

Figure 3 Digital substraction angiogram showing multiple feeders from the posterior choroidal arteries (arrows) in the choroidal type of VOGAM (a,b), with venous drainage into a large ectatic vein (c) Figure 4 Vertebral angiogram demonstrating reduction in the flow to the malformation after the third session of embolization by NBCA (arrow) (a, b). Further reduction in the flow following the fifth session of embolization (c,d) At the age of 21 months a third session of embolization was done. The right posterior choroidal feeder was accessed and embolized with 25% NBCA. On a post-procedure angiogram there was 60% reduction in the abnormal flow through the VOGAM. On account of the contrast dose limitation, the procedure was terminated at this stage. The child was taken up for the fourth session after an 11-day interval and embolization of the residual thalamoperforators and posterior choroidal feeders was done with 25% NBCA with 70% decrease in the flow to the VOGAM. The child tolerated the session well and was followed up after a two-month interval. The child was taken up for the fifth session, and embolization of the residual feeders was done [Figure 4c, d]. There was 85% reduction of the flow to the VOGAM. The child was doing well, with clinical improvement in the symptoms and normal developmental milestones for the age, on a follow-up of two years. The child is being followed up regularly with us, to date.

and embolization of the residual feeders was done [Figure 4c, d]. There was 85% reduction of the flow to the VOGAM. The child was doing well, with clinical improvement in the symptoms and normal developmental milestones for the age, on a follow-up of two years. The child is being followed up regularly with us, to date. Discussion Recent advances in the field of intervention neuroradiology has changed the treatment and prognosis of children with VOGAM.[5–8] Therapeutic options available for a VOGAM include no treatment, open surgery, endovascular treatment, and stereotactic radiosurgery. The therapeutic options should be individualized with consideration of age, clinical manifestation of the lesion and the angioarchitecture. In the past, surgery was done for VOGAM, which offered little improvement and fatal outcomes.[910] Endovascular treatment has improved the results of treatment in recent years. The transarterial approach is preferred and more effective in controlling the symptoms of VOGAM.[7] NBCA is the embolic agent used which is premixed with lipiodol (to increase the radio opacity) In our first case, which was a mural type of fistula, we used high concentrated glue, which was fast setting and highly effective in the high flow variety. In our second case, staged embolization is done, to reduce the risk of fluid overload and prevent the perfusion breakthrough. In this child 33 and 25% NBCA was used for better penetration in the choroidal feeders. NBCA allowed precise targeting of the AV shunt and was preferred over other embolic agents like microcoils.[11]

r second case, staged embolization is done, to reduce the risk of fluid overload and prevent the perfusion breakthrough. In this child 33 and 25% NBCA was used for better penetration in the choroidal feeders. NBCA allowed precise targeting of the AV shunt and was preferred over other embolic agents like microcoils.[11] The presence of pre-existing brain damage characterized by severe atrophy and parenchymal calcifications indicated a poor prognosis, with bad outcomes[12] The transvenous approach was described in literature, but it was associated with increased risks of bleeding complications.[1213] Lasjunias et al., described the largest cohort study of these lesions treated using the endovascular method, at their center, in a period of 11 years, with variable outcomes.[14] Introduction of endovascular techniques modified the prognosis in patients with VOGAM. With the recent advances of technology of endovascular management, these children can be well-managed with a fairly good outcome. Conclusion We presented two cases of vein of galen aneurysms. The treatment plan was individualized with consideration to the clinical manifestations and angioarchitecture of the lesion. The goal of the treatment was clinical improvement of the patients presenting with the symptoms and not an angiographic cure. Endovascular treatment was proven as an effective method of treatment with acceptable risk. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Anterior sacral meningocele (ASM) is an anomaly where the meninges protrude into retroperitoneal and presacral space through an anterior sacral defect. Most of the cases present in adult age and diagnosis in childhood is rare. Common presentations include infection, meningitis and obstetric problems. We report a 19-month-old child with ASM presenting with constipation and urinary problems which improved after surgery through abdominal approach. Bilateral rib and vertebral defects seen in our patient have not been described in literature earlier. Case Report A 19-month-old female child presented to the hospital with complaints of constipation since 6 months of age and difficulty in passing urine for last 6 months. Parents had noticed lower abdominal fullness for last 1 year. The child was born out of non-consanguineous marriage between young parents at full term by an uncomplicated vaginal delivery. Antenatal ultrasound screening had not been performed. There was no history suggestive of birth asphyxia or trauma. The parents gave history of increasing constipation for which laxatives and enemas had been advised but did not provide relief. The child passed small amounts of urine at short intervals.

aginal delivery. Antenatal ultrasound screening had not been performed. There was no history suggestive of birth asphyxia or trauma. The parents gave history of increasing constipation for which laxatives and enemas had been advised but did not provide relief. The child passed small amounts of urine at short intervals. The child weighed 7.2 kg and other anthropometric parameters including head circumference were appropriate for age. Chest examination revealed multiple rib defects on both sides but air entry was normal without any added sounds. Abdominal examination revealed a cystic mass in the suprapubic region arising out of pelvis and reaching up to umbilicus. Digital rectal examination showed normal tone of the normally placed anus but a large cystic mass was felt posteriorly which precluded higher examination. Examination of the spine at the back did not show any bony defects. There was no neurological deficit. Hematological investigations showed hemoglobin of 11.2 g/dL, TLC of 12,000 per cc and platelets of 117×103 per mm3. Kidney function tests were normal.

The child weighed 7.2 kg and other anthropometric parameters including head circumference were appropriate for age. Chest examination revealed multiple rib defects on both sides but air entry was normal without any added sounds. Abdominal examination revealed a cystic mass in the suprapubic region arising out of pelvis and reaching up to umbilicus. Digital rectal examination showed normal tone of the normally placed anus but a large cystic mass was felt posteriorly which precluded higher examination. Examination of the spine at the back did not show any bony defects. There was no neurological deficit. Hematological investigations showed hemoglobin of 11.2 g/dL, TLC of 12,000 per cc and platelets of 117×103 per mm3. Kidney function tests were normal. X-ray chest [Figure 1] showed multiple segmentation anomalies of cervicodorsal vertebrae along with fusion anomalies of ribs on both sides. Echocardiogram did not show any associated cardiac anomaly. Ultrasound of abdomen demonstrated a cystic lesion posterior to urinary bladder measuring 9×4 cm with well-defined dome shaped upper margin and tapering inferiorly. No internal echoes were seen within the lesion. Urinary bladder was pushed anteriorly. There was no evidence of hydroureteronephrosis. Barium enema demonstrated Scimitar sign along with increased presacral space, displacement of the rectum anteriorly and sigmoid colon to the right [Figure 2a and b]. Computed tomography [Figure 3a and b] showed an anterior sacral dysraphic defect with large cystic mass in presacral region displacing the urinary bladder anteriorly and to the right side. Posteriorly, mass was seen entering the spinal canal through large sacral bone defect. There was no hydrocephalus. Both the kidneys were displaced and rotated through their axis but there was no evidence of hydronephrosis.

cystic mass in presacral region displacing the urinary bladder anteriorly and to the right side. Posteriorly, mass was seen entering the spinal canal through large sacral bone defect. There was no hydrocephalus. Both the kidneys were displaced and rotated through their axis but there was no evidence of hydronephrosis. Figure 1 Plain X-ray chest showing multiple segmentation anomalies of cervicodorsal vertebrae along with fusion anomalies of ribs on both sides Figure 2 Barium enema showing a) Scimitar sign; and b) increased presacral space and displacement of rectum Figures 3 (a,b) Computed tomography showing anterior sacral meningocele with a) communication with the sacral defect; and b) displacement of urinary bladder to the left

Figure 1 Plain X-ray chest showing multiple segmentation anomalies of cervicodorsal vertebrae along with fusion anomalies of ribs on both sides Figure 2 Barium enema showing a) Scimitar sign; and b) increased presacral space and displacement of rectum Figures 3 (a,b) Computed tomography showing anterior sacral meningocele with a) communication with the sacral defect; and b) displacement of urinary bladder to the left An exploratory laparotomy was performed by a suprapubic transverse incision with intent to excise the meningocele from anterior route. A cystic lesion measuring about 8×4 was seen emerging within the leaves of sigmoid mesocolon from the anterior part of sacrum in the pelvis. The sigmoid colon was pushed to the right while urinary bladder was pushed to the left side [Figure 4]. The sac was dissected till the base. The sac was opened at the apex, clear cerebrospinal fluid (CSF) was aspirated and the sac was excised with watertight closure of the tapering base saving the nerve roots and controlling epidural veins. Closed dural defect was checked for leakage of CSF and hemostasis and then covered with local tissue. CSF was sent for culture and sac was sent for histopathological examination (HPE). The CSF culture was reported as sterile while HPE report showed fibrocollagenous and fibrofatty tissue with few entrapped blood vessels and occasional nerve fibers. Figure 4 Operative photograph showing the anterior sacral meningocele with displacement of urinary bladder and sigmoid colon

An exploratory laparotomy was performed by a suprapubic transverse incision with intent to excise the meningocele from anterior route. A cystic lesion measuring about 8×4 was seen emerging within the leaves of sigmoid mesocolon from the anterior part of sacrum in the pelvis. The sigmoid colon was pushed to the right while urinary bladder was pushed to the left side [Figure 4]. The sac was dissected till the base. The sac was opened at the apex, clear cerebrospinal fluid (CSF) was aspirated and the sac was excised with watertight closure of the tapering base saving the nerve roots and controlling epidural veins. Closed dural defect was checked for leakage of CSF and hemostasis and then covered with local tissue. CSF was sent for culture and sac was sent for histopathological examination (HPE). The CSF culture was reported as sterile while HPE report showed fibrocollagenous and fibrofatty tissue with few entrapped blood vessels and occasional nerve fibers. Figure 4 Operative photograph showing the anterior sacral meningocele with displacement of urinary bladder and sigmoid colon There was no neurological deficit in the immediate postoperative period. There was no evidence of constipation, urinary complaints or hydrocephalus at 6 months of follow-up. Although the rib defects have not caused any clinical problem till now, the child remains in follow-up to manage if need arises.

Figure 4 Operative photograph showing the anterior sacral meningocele with displacement of urinary bladder and sigmoid colon There was no neurological deficit in the immediate postoperative period. There was no evidence of constipation, urinary complaints or hydrocephalus at 6 months of follow-up. Although the rib defects have not caused any clinical problem till now, the child remains in follow-up to manage if need arises. Discussion ASM is an exceedingly rare form of spinal dysraphism characterized by protrusion of dural sac anterior through a defect in the anterior aspect of sacrum.[12] These are labeled as Type 1B according to Nabors’ classification.[3] Very few cases have been described in early childhood. ASMs mostly result from failure of fusion of the sacrum with subsequent herniation of the sacrum meninges into the sacral hollow. North et al.,[4] have classified the possible mechanisms leading to ASM as: a) Congenital: Sacral bone defect Proliferation of arachnoid Connective tissue disorders b) Degenerative: Ischemic lesion c) Traumatic: Nerve root avulsion or hemorrhage d) Iatrogenic: During surgery ASM may be associated with syndrome like Currarino syndrome which includes anorectal malformations, sacral bony defect and presacral mass; and Marfan's syndrome wherein the etiology may be disorder of collagen biosynthesis and structure at the dural level.[3] Bilateral multiple rib defects seen in the present case have not been described in the available English literature till now. Autosomal dominant transmission of the disease has been said to cause familial occurrence of ASM.[5–7]

the etiology may be disorder of collagen biosynthesis and structure at the dural level.[3] Bilateral multiple rib defects seen in the present case have not been described in the available English literature till now. Autosomal dominant transmission of the disease has been said to cause familial occurrence of ASM.[5–7] Owing to occult nature, these lesions usually present later in life. These could present with constipation, urological symptoms or rarely neurological symptoms. More than three-fourth cases are seen in women of reproductive age who are more likely to have diagnosis of asymptomatic ASM during pelvic examination. In this group of patients, ASM may lead to infertility and difficult labor. Young children mostly present with chronic constipation or retention of urine.[8] A child with constipation may be treated with laxatives for long periods or misdiagnosed as Hirschsprung's disease. This can be avoided by often ignored digital rectal examination. The cysts may become secondarily infected leading to meningitis[9] and to pyocele. Associated tethered cord could present with neurological signs.[10] Rarely, these can be occupied by epidermoid cyst[11] or could rupture into the rectum. ASM has been reported to be misdiagnosed as ovarian cyst at many occasions.[12]

n. The cysts may become secondarily infected leading to meningitis[9] and to pyocele. Associated tethered cord could present with neurological signs.[10] Rarely, these can be occupied by epidermoid cyst[11] or could rupture into the rectum. ASM has been reported to be misdiagnosed as ovarian cyst at many occasions.[12] Radiological investigations include plain and contrast radiographs, ultrasound, computed tomography and magnetic resonance imaging (MRI). ‘Scimitar’ sign, a smooth curved unilateral sacral defect simulating shape of Arabic sabre on plain X-ray, is considered to be pathognomonic of ASM.[13] Contrast enema, which may show displacement of rectum, sigmoid colon and urinary bladder, is now obsolete for diagnosis. Abdominal and spinal sonography should be the first diagnostic investigation and can diagnose ASM and differentiate it from other cystic lesions in the pelvis.[14] Imaging for screening for ASM and presacral teratoma should be directed at identifying the presacral mass rather than sacral bony defect. Thus computed tomography or MRI is recommended as the screening modality.[15] Computed tomography, diagnostic in the present case, has been replaced by MRI as the radiological investigation of choice. Good clinical examination and radiological investigations should be able to differentiate ASM from other causes of cystic presacral masses in children which include a) sacrococcygeal teratoma (Altman type 4); b) tumors like dermoid, lipomas, neuroblastoma; c) neuroectodermal cyst; d) rectal duplication cyst; e) ovarian cyst and f) pelvic kidney among others.

al investigations should be able to differentiate ASM from other causes of cystic presacral masses in children which include a) sacrococcygeal teratoma (Altman type 4); b) tumors like dermoid, lipomas, neuroblastoma; c) neuroectodermal cyst; d) rectal duplication cyst; e) ovarian cyst and f) pelvic kidney among others. Surgery is the mainstay for management of ASM. Surgery should aim to obliterate the communication between meningocele and the spinal subarachnoid space; to decompress the pelvic structures by meningocele excision; and to untether the spinal cord, if necessary.[1617] Standard approach for ASM is through posterior sacral laminectomy. This route permits ligation of the base, to disrupt its connection with the thecal sac and also manage tethered cord if present. Dural fibrin patch may be used to close the open defect.[18] One has to be careful to preserve nerve roots in the vicinity to prevent post operative neurological complications. An open anterior transperitoneal abdominal approach was used in our case as the large ASM was reaching up to the umbilicus and had a large neck. Anticipated difficulty in managing the large ASM, excellent exposure available, and previous experience of this approach guided in preferring this approach. Limitation of this procedure is the management of caudal spinal cord anomalies as deep pelvic dissection is difficult.[1920]

to the umbilicus and had a large neck. Anticipated difficulty in managing the large ASM, excellent exposure available, and previous experience of this approach guided in preferring this approach. Limitation of this procedure is the management of caudal spinal cord anomalies as deep pelvic dissection is difficult.[1920] Laparoscopic approach for surgical management of ASM is increasingly being used.[2122] This is especially useful for narrow-based ASM which may be suture ligated. A posterior sagittal approach may be useful in management of ASM associated with anorectal malformations in Currarino syndrome.[2324] Source of Support: Nil. Conflict of Interest: None declared.

Introduction In an attempt to develop a uniform classification of the most common demyelinating disorder of childhood, the International Pediatric Multiple Sclerosis Study Group proposes the definition of acute disseminated encephalomyelitis (ADEM) as “the first clinical event with a polysymptomatic encephalopathy, with acute or subacute onset, showing focal or multifocal hyperintense lesions predominantly affecting the CNS white matter”. Beyond that, evidences of previous destructive white matter changes or clinical setting of a demyelinating event must not be present in the patient's history.[1] The risk of developing multiple sclerosis after ADEM has been focused by many studies in the literature.[1–3] The clinical features of ADEM are well known among pediatric neurologists and the outcome usually shows complete recovery in up to 50%, even in those patients who are not treated.[1] Nevertheless, some forms of presentation have peculiarities and they might be a challenge. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM's presentation due to acute brain vasculitis. Immediate and aggressive treatment is required because this clinical scenario shows high mortality.[1] Herein, the authors report a case of AHEM with remarkable abnormalities of brain magnetic resonance imaging (MRI) who had an unfavorable outcome. Besides, a review of similar pediatric cases previously reported in the literature has been given.

The clinical features of ADEM are well known among pediatric neurologists and the outcome usually shows complete recovery in up to 50%, even in those patients who are not treated.[1] Nevertheless, some forms of presentation have peculiarities and they might be a challenge. Acute hemorrhagic encephalomyelitis (AHEM) is considered a rare form of ADEM's presentation due to acute brain vasculitis. Immediate and aggressive treatment is required because this clinical scenario shows high mortality.[1] Herein, the authors report a case of AHEM with remarkable abnormalities of brain magnetic resonance imaging (MRI) who had an unfavorable outcome. Besides, a review of similar pediatric cases previously reported in the literature has been given. Case Report A 2-year-old, previously healthy girl was admitted to the hospital with a 1 week history of extreme irritability. Associated with irritability, her parents noticed progressive difficulty in walking. She did not have any antecedent history of infection or vaccination preceding the present symptoms. The neurological examination on the first evaluation showed impairment of consciousness, ranging from irritability to numbness. She was unable to walk without support due to cerebellar ataxia. Brisk deep tendon reflexes, bilateral Babinski sign and ankle clonus were present. Computed tomography scan was normal and the cerebrospinal fluid showed the following: white cell count 15 cells/mm3(92% lymphocytes, 3% monocytes, 3% neutrophils), red blood cells 15/mm3, protein levels 70 mg/dL, gamma globulin levels 18.3% on protein electrophoresis, and glucose levels 47 mg/dL. Acid-fast bacilli staining was negative as was polymerase chain reaction for herpes simplex and cytomegalovirus. Fungal and bacterial cultures were negative. The first MRI showed hyperintense FLAIR/T2 lesions in cerebellar white matter [Figure 1a], and also in central, periventricular and juxtacortical white matter [Figure 1b and c].

li staining was negative as was polymerase chain reaction for herpes simplex and cytomegalovirus. Fungal and bacterial cultures were negative. The first MRI showed hyperintense FLAIR/T2 lesions in cerebellar white matter [Figure 1a], and also in central, periventricular and juxtacortical white matter [Figure 1b and c]. Figure 1 First Brain MRI. Axial FLAIR images demonstrating hyperintense extensive and confluent lesions in cerebellar white matter (a), affecting the corpus callosum (b) and compromising the central and juxtacortical white matter (c) She had significant improvement after IV administration of high-dose intravenous methylprednisolone (30 mg/kg/day) for 5 days, followed by oral prednisolone (2 mg/kg/day) taper for 6 weeks.

Figure 1 First Brain MRI. Axial FLAIR images demonstrating hyperintense extensive and confluent lesions in cerebellar white matter (a), affecting the corpus callosum (b) and compromising the central and juxtacortical white matter (c) She had significant improvement after IV administration of high-dose intravenous methylprednisolone (30 mg/kg/day) for 5 days, followed by oral prednisolone (2 mg/kg/day) taper for 6 weeks. After 2 months of the initial symptoms, she had recurrence of her symptoms, associated with rapidly progressive refractory status epilepticus. An electroencephalogram obtained showed delta wave activity that was consistent with diffuse, severe encephalopathy. Continuous sharp waves on parasagittal and right temporal regions were observed in the records. It was necessary to administer IV midazolam (23 μg/kg/min) followed by thiopental (50 mg/kg/hour) to control the seizures. The second MRI, in addition to the impairment of cerebral and cerebellar white matter [Figure 2a and b], showed hemorrhagic lesions in the corpus callosum and right centrum semiovale [Figure 2c and d]. She was submitted to a new high-dose IV steroid therapy and IV immunoglobulin, but no improvement was observed and she died after a nosocomial pneumonia following 2 months of intubation.

llar white matter [Figure 2a and b], showed hemorrhagic lesions in the corpus callosum and right centrum semiovale [Figure 2c and d]. She was submitted to a new high-dose IV steroid therapy and IV immunoglobulin, but no improvement was observed and she died after a nosocomial pneumonia following 2 months of intubation. Figure 2 Second brain MRI. Axial FLAIR image (a) demonstrating hyperintense extensive and confluent lesions in central and juxtacortical white matter (dense arrow). Sagittal reformation (b) shows involvement of pericallosal and cerebellar white matter, sparing the U-fibers (dense arrows). Axial T2 gradient echo-weighted images (c and d) showing areas of very low signal, corresponding to breakdown products of hemoglobin (thin arrows), in the corpus callosum (c) and in the right centrum semiovale (d) Discussion Whereas ADEM is more commonly diagnosed in children, AHEM is seen most frequently among adults.[45] AHEM is usually fatal, whereas full recovery is the rule for patients with ADEM.[16]

Figure 2 Second brain MRI. Axial FLAIR image (a) demonstrating hyperintense extensive and confluent lesions in central and juxtacortical white matter (dense arrow). Sagittal reformation (b) shows involvement of pericallosal and cerebellar white matter, sparing the U-fibers (dense arrows). Axial T2 gradient echo-weighted images (c and d) showing areas of very low signal, corresponding to breakdown products of hemoglobin (thin arrows), in the corpus callosum (c) and in the right centrum semiovale (d) Discussion Whereas ADEM is more commonly diagnosed in children, AHEM is seen most frequently among adults.[45] AHEM is usually fatal, whereas full recovery is the rule for patients with ADEM.[16] In 1997, Rosman et al. reported a pediatric case of AHEM with a good outcome, and they did a review of the cases published before,[5] since the first description by Hurst in 1941.[7] At that time, there were nine pediatric cases published with pathological or radiologic confirmation.[5] After 2000, the largest ADEM series in childhood have demonstrated only three cases of AHEM.[28] In Tenembaum and coworkers’ series, 2 of 84 patients showed some degree of hemorrhage into the large demyelinating lesions. One of the two patients with AHEM had complete recovery with normal neurological examination. One patient showed Expanded Disability Status Scale scores of 3.0–4.5.[8] Dale et al. have published 35 cases of ADEM, and only one scan had evidence of secondary hemorrhage.[2] Three additional cases were published as case reports by Leake,[4] Takeda,[9] and Mader in 2004.[10] The patients were 10, 15 and 10 years old, respectively.[4910] Overall, 16 pediatric cases have been reported, including the one on this report [Table 1]. The mortality of these 16 cases was 50% (8/16). Among the eight survivors, clinical information was available in seven: four patients recovered with sequelae and three patients made a full recovery. Despite the severe presentation of most ADEM cases, the outcome of nonhemorrhagic forms usually is favorable in childhood, with full recovery to normal neurological state in more than 50–60% of patients, as previously demonstrated by the main series.[1268]

ecovered with sequelae and three patients made a full recovery. Despite the severe presentation of most ADEM cases, the outcome of nonhemorrhagic forms usually is favorable in childhood, with full recovery to normal neurological state in more than 50–60% of patients, as previously demonstrated by the main series.[1268] Table 1 Pediatric cases of acute hemorrhagic encephalomyelitis Because of the epidemiological data, and especially the outcome between ADEM and AHEM, some authors have tried to separate these conditions.[45917] However, distinction between ADEM and AHEM is not well established and they may be a continuation of disease spectrum.[151017] The case presented herein is in agreement with the concept that both disorders are considered as autoimmune-mediated entities, with pathological features of prominent multifocal perivascular demyelination. The patient had a typical presentation of ADEM with an initial good response to steroids, and in an unexpected way, she relapsed with recurrence of symptoms associated with refractory status epilepticus, and a new MRI disclosing hemorrhagic features. As the relapse took place within the first 3 months from the initial event, it was considered temporally related to the same acute monophasic condition,[1] but with subsequent vessel occlusion leading to a secondary hemorrhage. Even though some authors have reported favorable neurologic outcome in adult patients, the high rate of AHEM mortality mandates a quick and aggressive treatment using combinations of corticosteroids, immunoglobulin, cyclophosphamide, and plasma exchange.[14517–19]

Because of the epidemiological data, and especially the outcome between ADEM and AHEM, some authors have tried to separate these conditions.[45917] However, distinction between ADEM and AHEM is not well established and they may be a continuation of disease spectrum.[151017] The case presented herein is in agreement with the concept that both disorders are considered as autoimmune-mediated entities, with pathological features of prominent multifocal perivascular demyelination. The patient had a typical presentation of ADEM with an initial good response to steroids, and in an unexpected way, she relapsed with recurrence of symptoms associated with refractory status epilepticus, and a new MRI disclosing hemorrhagic features. As the relapse took place within the first 3 months from the initial event, it was considered temporally related to the same acute monophasic condition,[1] but with subsequent vessel occlusion leading to a secondary hemorrhage. Even though some authors have reported favorable neurologic outcome in adult patients, the high rate of AHEM mortality mandates a quick and aggressive treatment using combinations of corticosteroids, immunoglobulin, cyclophosphamide, and plasma exchange.[14517–19] The case reported here emphasizes that ADEM may present a severe outcome, making this well-known condition a challenge. AHEM must be properly investigated with MRI whenever a patient presents with unexpected neurological worsening. Aggressive therapeutic management is required in order to avoid fatal outcome. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Ophthalmoplegic migraine (OM) is characterized by recurrent attacks of migrainous headache, associated with paresis of one or more ocular cranial nerves with absence of demonstrable intracranial lesions, other than Magnetic Resonance Imaging (MRI) of the brain changes within the affected nerve. From the recent observations, it has been considered to be a type of recurrent demyelinating cranial neuropathy. International Headache Classification (IHCD-II) has reclassified OM from a variant of migraine to the category of neuralgia. We report an adolescent girl with OM, who had been treated with steroid and showed dramatic improvement. Case Report An 11-year-old girl presented with abrupt unilateral (right) ptosis and diplopia for 3 weeks [Figure 1]. At the beginning, it was associated with severe throbbing headache, pain in the right eye, nausea and recurrent vomiting. Within 7 days, except ptosis and diplopia, all other symptoms had spontaneously subsided. She had denied having trauma, fever, diurnal variation of ptosis, tinnitus, transient visual blurring or limb weakness. Past history revealed that she had experienced similar attacks 5–6 times in the past 4 years. In each episode, ptosis was unilateral and involved mostly right eyelid, but left eyelid was involved in one occasion. All episodes had been spontaneously resolved within 10–14 days. No family history of similar disease or migraine was obtained. Figure 1 Image of face showing right sided ptosis

Case Report An 11-year-old girl presented with abrupt unilateral (right) ptosis and diplopia for 3 weeks [Figure 1]. At the beginning, it was associated with severe throbbing headache, pain in the right eye, nausea and recurrent vomiting. Within 7 days, except ptosis and diplopia, all other symptoms had spontaneously subsided. She had denied having trauma, fever, diurnal variation of ptosis, tinnitus, transient visual blurring or limb weakness. Past history revealed that she had experienced similar attacks 5–6 times in the past 4 years. In each episode, ptosis was unilateral and involved mostly right eyelid, but left eyelid was involved in one occasion. All episodes had been spontaneously resolved within 10–14 days. No family history of similar disease or migraine was obtained. Figure 1 Image of face showing right sided ptosis Ophthalmologic examination revealed incomplete ptosis of the right eyelid and paresis of the right, upward and downward gaze. Pupil size was normal in the left eye and dilated in the right eye. Pupillary constriction was normal in the left eye and sluggish in the right eye to both direct and consensual light stimulation. There was absence of proptosis or congestion of both eyes. Acuity of vision without correction and intraocular pressure in both eyes were within normal limit. Fundus examination showed no pallor or edema of disc. Anterior and posterior segment examination as well as macula, vessels and periphery were normal. Neurological examination did not detect any other cranial nerve abnormality or limb weakness. Other systemic examinations yielded no abnormality.

re within normal limit. Fundus examination showed no pallor or edema of disc. Anterior and posterior segment examination as well as macula, vessels and periphery were normal. Neurological examination did not detect any other cranial nerve abnormality or limb weakness. Other systemic examinations yielded no abnormality. Investigations including complete blood counts, erythrocyte sedimentation rate (ESR) and C-reactive protein, fasting blood sugar (FBS), thyroid function tests, antinuclear antibody (ANA) were within normal limits. MRI brain (plain and contrast) was also normal. OM was taken as diagnosis and oral prednisolone (2 mg/kg/day) was started, which resulted in resolution of painful ophthalmoplegia within 7 days. Steroid was continued for weeks and then tapered off and antimigraine prophylaxis (flunarizine) was started. On follow-up, she is now attack free for the last 18 months.

Investigations including complete blood counts, erythrocyte sedimentation rate (ESR) and C-reactive protein, fasting blood sugar (FBS), thyroid function tests, antinuclear antibody (ANA) were within normal limits. MRI brain (plain and contrast) was also normal. OM was taken as diagnosis and oral prednisolone (2 mg/kg/day) was started, which resulted in resolution of painful ophthalmoplegia within 7 days. Steroid was continued for weeks and then tapered off and antimigraine prophylaxis (flunarizine) was started. On follow-up, she is now attack free for the last 18 months. Discussion Ophthalmoplegic migraine was named by Charcot in 1890; since then, it was being considered as a variant of migraine.[1] Clinical criteria for oculomotor OM are: 1) childhood onset, 2) headache preceding and ipsilateral to the third nerve paresis, 3) a dilated pupil, 4) ophthalmoplegia that may be permanent and rarely accompanied by aberrant oculomotor regeneration, 5) a minimum of two episodes and 6) no evidence for a structural lesion.[2] Recently, different pathogenic mechanisms, which include compressive, ischemic and inflammatory, have been suggested.[3] In some cases, MRI shows gadolinium uptake in the cisternal part of the affected cranial nerve. This suggests that the condition may be recurrent demyelinating cranial neuropathies. The recent revision of the IHCD-II has reclassified OM from a subtype of migraine to the category of neuralgia.[4] OM constitutes only 0.16% of childhood migraine.[5] Unlike our patient, it has a male predominance or occurs equally in both the sexes. Family history of typical OM is rarely positive. However, other varieties of migraine like “Common” or “Classic” are invariably found in family. Onset of disease in our patient was about 7 years of age, but majority of the patients experience initial attack in the first decade, usually before 5 years of age. Thus, the first attack is incorrectly attributed to aneurysm, trauma, infection or recent immunization; only when the condition resolves and recurs again, correct diagnosis is made. Rarely, patients experience their first attack in adulthood, but such patients mostly have a history of typical migraine headaches with or without aura since childhood or a family history of migraine or both. Approximately, 86% of patients of OM have transient, reversible MRI contrast enhancement of the affected cranial nerve.[3] Enhancement of the cisternal segment of the oculomotor nerve may be seen. Contrast-enhanced studies also showed focal thickening at the exit of the nerve in the interpeduncular cistern without enhancement of the cavernous sinus or adjacent dura. Enhancement is almost completely resolved about 7–9 weeks later.

nerve.[3] Enhancement of the cisternal segment of the oculomotor nerve may be seen. Contrast-enhanced studies also showed focal thickening at the exit of the nerve in the interpeduncular cistern without enhancement of the cavernous sinus or adjacent dura. Enhancement is almost completely resolved about 7–9 weeks later. Although enhancement is associated with OM, it is not a sine qua non for the diagnosis of OM, as in our patient normal neuroimaging may be seen in OM.[6]

nerve.[3] Enhancement of the cisternal segment of the oculomotor nerve may be seen. Contrast-enhanced studies also showed focal thickening at the exit of the nerve in the interpeduncular cistern without enhancement of the cavernous sinus or adjacent dura. Enhancement is almost completely resolved about 7–9 weeks later. Although enhancement is associated with OM, it is not a sine qua non for the diagnosis of OM, as in our patient normal neuroimaging may be seen in OM.[6] The differential diagnoses of OM include intracranial aneurysms or tumors, oculomotor nerve schwannoma, sphenoidal sinus mucoceles, raised intracranial tension (ICT) with brain herniation, Tolosa Hunt Syndrome (THS), myasthenia gravis (MG), and diabetic neuropathy. Although reported in a young child, intracranial aneurysm is extremely rare below 14 years of age. In our patient, the normal MRI brain excludes that diagnosis. In the case of oculomotor nerve schwannoma, slowly progressive weakness of the third nerve over the years is expected. That is also a less likely diagnosis because the patient's diplopia was recurrent and she was absolutely normal in between episodes. Mucocele of the sphenoidal sinus or tumors or inflammatory lesions that invade the cavernous sinus can cause painful ophthalmoplegia. However, the headache in such disorders is of rather gradual onset and is usually accompanied by systemic symptoms or signs of other cranial nerve palsies. In the index case, such types of lesions were excluded by proper neuroimaging. Raised ICT can cause herniation of hippocampal gyrus, producing an oculomotor paresis which may be transient, recurrent and associated with severe headache. In our patient, normal fundoscopic examination and absence of findings of brain herniation in MRI ruled out that diagnosis. Granulomatous diseases such as sarcoidosis or THS can cause oculomotor nerve palsy. THS is usually associated with meningeal enhancement on MRI. Evidence of inflammation in the superior orbital apex and cavernous sinus region supports a diagnosis of THS. However, proximal enlargement with gadolinium enhancement of the oculomotor nerve within the prepontine cistern has been reported both in OM and THS.[7] The girl had normal MRI brain; so, it was difficult to differentiate OM from THS on the basis of neuroimaging in our patient. However, THS is a disease of adults, associated with retro-orbital pain and is slow to resolve, especially without prednisone. In our patient, the previous histories of a recurrent third nerve palsy which resolved spontaneously and whose onset was associated with headache also made OM a more likely diagnosis.

patient. However, THS is a disease of adults, associated with retro-orbital pain and is slow to resolve, especially without prednisone. In our patient, the previous histories of a recurrent third nerve palsy which resolved spontaneously and whose onset was associated with headache also made OM a more likely diagnosis. Ocular MG was a less likely diagnosis because there was absence of diurnal variations of ptosis and presence of pupil abnormality. If MG is highly suspected, then tensilon test may be done. Ophthalmoparesis due to uncontrolled diabetes mellitus (DM) rarely occurs in children. Besides DM, patients with hypertension, giant cell arteritis or other systemic vasculopathies may have ophthalmoparesis. However, that persisted longer than the ophthalmoplegia associated with OM. Normal FBS, ESR and CRP ruled out those possibilities. Although differential diagnosis is rather large, most other possible causes of ophthalmoplegia and headache have distinctive clinical presentations. As in our case, other causes should be excluded by proper neuroimaging. Optimal prophylactic and acute treatment is still unclear, but migraine prophylactic medications such as beta blockers and calcium channel blockers have been proposed. Steroids have been used with mixed results.[8] As in our case, systemic steroids have shown promising results in other reports.[5] Prognosis is good because symptoms almost always resolve, but after several episodes, some deficits may persist. Source of Support: Nil. Conflict of Interest: None declared.

Introduction Megalencephalic leukoencephalopathy with subcortical cysts is clinically characterized by macrocephaly, mild motor developmental delay, and seizures. Later in life, patients may develop gradual onset of ataxia and pyramidal features. Mental capacities are usually preserved but there may be a mild deterioration later. A combination of clinical features and MRI features is required for arriving at the diagnosis. The condition is inherited in an autosomal recessive pattern and the gene locus has been mapped as MLC 1 gene at chromosome 22q. The condition has been originally reported from India. In a meeting in Japan in 1991, Singhal et al. described 18 patients with megalencephalic leukodystrophy from India.[1] This was the first series to be reported. Van der Knaap et al. group from Netherlands later published a series of eight patients and described the clinical and MRI features.[2] Their description earned them the eponym Van der Knaap disease first used by Cavalcanti and Nogueira.[3] A Turkish study of 12 patients[4] soon followed and established the genetic nature of the disease with autosomal recessive inheritance and a locus at 22q. From India, Gorospe, Singhal and co-workers did detailed genetic analysis and established this disease as a distinct clinicopathological entity with common locus at MLC 1 gene in all the 31 patients described in the Agarwal community.[5] We recently identified four patients of this disease. There was marked diversity in clinical presentation and striking similarity in MRI findings of these patients.

The condition has been originally reported from India. In a meeting in Japan in 1991, Singhal et al. described 18 patients with megalencephalic leukodystrophy from India.[1] This was the first series to be reported. Van der Knaap et al. group from Netherlands later published a series of eight patients and described the clinical and MRI features.[2] Their description earned them the eponym Van der Knaap disease first used by Cavalcanti and Nogueira.[3] A Turkish study of 12 patients[4] soon followed and established the genetic nature of the disease with autosomal recessive inheritance and a locus at 22q. From India, Gorospe, Singhal and co-workers did detailed genetic analysis and established this disease as a distinct clinicopathological entity with common locus at MLC 1 gene in all the 31 patients described in the Agarwal community.[5] We recently identified four patients of this disease. There was marked diversity in clinical presentation and striking similarity in MRI findings of these patients. Case Reports Case 1 A 16-year-old boy presented with seizures and difficulty in walking since four years [Table 1]. This boy originally hailed from rural Bihar but was now settled in Delhi. He had complex partial seizures with semiology suggestive of right temporal lobe with secondary generalization around 80% of the times. At the time of presentation, his seizures were under control with carbamazepine since 9 months. The difficulty in walking was due to spasticity. He had decline of the mental ability with a progressive loss of acquired knowledge and he had to be withdrawn from school. Developmental history was normal in the first few years, except an increased head size noted during infancy. His examination revealed a head size of 59.4 cm. He had spasticity of all four limbs and hyperreflexia with extensor planter response. He had mild handgrip weakness and proximal lower limb power of 4/5. He had no ataxia or sensory impairment. His MRI is shown in Figure 1a.

t an increased head size noted during infancy. His examination revealed a head size of 59.4 cm. He had spasticity of all four limbs and hyperreflexia with extensor planter response. He had mild handgrip weakness and proximal lower limb power of 4/5. He had no ataxia or sensory impairment. His MRI is shown in Figure 1a. Table 1 Clinical and MRI characteristics of the four patients Figure 1 (a) Axial T2 W image of case 1 showing multiple subcortical cysts and hyperintense white matter changes. (b) Sagittal T2W images of case 2 showing multiple temporal and frontal cysts and white matter changes. (c) Axial T1W image of case 3 showing characteristic cystic subcortical white matter appearing hypointense on T1

a) Axial T2 W image of case 1 showing multiple subcortical cysts and hyperintense white matter changes. (b) Sagittal T2W images of case 2 showing multiple temporal and frontal cysts and white matter changes. (c) Axial T1W image of case 3 showing characteristic cystic subcortical white matter appearing hypointense on T1 Case 2 A 5-year-old girl presented with progressive difficulty in walking and tightness of all limbs [Table 1]. She had mild developmental delay in the form of delayed sitting and walking and she could never run or climb stairs. She had clumsiness and frequent falls while walking. She had seizures of simple partial motor type beginning with right lower limb jerking and followed by generalization since 8 months of age. The seizures responded well to treatment with carbamazepine. The child had moderate impairment of cognitive and language abilities and could not go to school. Her brother (case 3) had similar features but much milder clinical course. Megalencephaly was not noted till presentation. The head circumference was 56 cm which was above the 95th percentile for age. The mental examination was suggestive of severe language impairment. The motor system examination was suggestive of severe spasticity with grade 4 power of all limbs. She had exaggerated reflexes and bilateral planters were extensor. She had severe incoordination much more than could be attributed to the mild limb weakness. She had a scissoring gait and walked on her toes. Her MRI [Figure 1b] showed temporal polar subcortical cysts along with other characteristic features suggestive of the disease.