A 55-year-old male otherwise healthy smoker presented with isolated headache for one week, without features of encephalitis or myelitis. Neurological examination was unremarkable. Gadolinium-enhanced brain MRI demonstrated increased T2-hyperintensity within the right sublenticular basal ganglia, with additional leptomeningeal enhancement along the bilateral perisylvian regions and mesial temporal lobes. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, matching oligoclonal bands, and negative infectious and cytology workup. Cell-based assays for anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, autoimmune encephalitis panel, and vasculitis workup were all negative, with the exception of CSF positivity for glial fibrillary acidic protein (GFAP) α antibody (detected at London Health Sciences Centre and confirmed at the Mayo Clinic, endpoint titer of 1:8). Oncological screening including CT chest, abdomen, pelvis and scrotal US did not reveal any abnormalities.  Immunotherapy with intravenous high-dose steroids for five days and subsequent weekly doses for four weeks resulted in symptom resolution. Repeat brain MRI showed striking radiographic resolution. There were no relapses at final follow-up six months after onset.