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Late neurosyphilis and VZV meningoencephalitis coinfection. The incidence of syphilis has increasing recently, largely attributable to improved screening that may result in the diagnosis of chronic untreated infections. These patients can develop severe or subtle neurologic symptoms that can be missed and, therefore, detected accidentally while a patient is evaluated for other mimicking neurological infections. A 58-year-old man with diabetes presented with 2 days of aphasia, headache, chills and confusion. He had an MRI brain with evidence of a prior cerebrovascular accident. Subsequently, he developed a fever and thoracic dermatomal rash consistent with herpes zoster. A lumbar puncture was performed, and cerebrospinal fluid analysis revealed a lymphocytic pleocytosis, a reactive Venereal Disease Research Laboratory test and positive varicella-zoster virus (VZV) PCR. He was suspected to have both late neurosyphilis and acute meningoencephalitis from VZV. This paper will discuss how to approach the diagnosis of late neurosyphilis and possible associations with herpesvirus central nervous system infections.