We report two patients with meningoencephalomyelitis without evidence of extra central nervous system (CNS) involvement. Brain MRI showed linear perivascular radial gadolinium enhancement patterns and spinal cord MRI showed longitudinal extensive T2-hyperintensity lesions. Pathological findings from brain biopsies were angiocentric T-cell predominant lymphoid infiltrates that lacked Epstein-Barr virus-positive atypical B cells. The patients were initially suspected to have isolated CNS-lymphomatoid granulomatosis (LYG). Thereafter, glial fibrillary acidic protein (GFAP)-immunoglobulin G were detected in their cerebrospinal fluid. This finding suggested autoimmune GFAP astrocytopathy. We speculate there is a link between isolated CNS-LYG and autoimmune GFAP astrocytopathy.