Case report: When encephalitis is not an infection: two cases of autoimmune GFAP astrocytopathy mimicking infectious encephalitis

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare autoimmune inflammatory disease of the central nervous system that frequently mimics infectious meningoencephalitis. Because its clinical presentation, cerebrospinal fluid (CSF) findings, and inflammatory markers often resemble central nervous system infection, diagnosis may be delayed, postponing appropriate immunotherapy.

We describe two women with markedly different clinical presentations of GFAP astrocytopathy who were initially managed as suspected infectious meningoencephalitis. Both patients presented with inflammatory CSF findings, negative extensive microbiological investigations, and initial empirical antimicrobial treatment. In the first case, persistent aseptic meningitis with recurrent symptoms prompted autoimmune testing after repeated negative infectious work-up. In the second case, rapidly progressive encephalopathy requiring intensive care initially suggested severe infectious meningoencephalitis. In both patients, neuronal surface and paraneoplastic antibody testing was negative, whereas indirect immunofluorescence detected GFAP-IgG, supporting the diagnosis in the context of the clinical, CSF, neuroimaging, and microbiological findings. Both patients subsequently received corticosteroid treatment and experienced clinical improvement, although residual neurological symptoms persisted in the first patient.

These cases highlight the broad clinical spectrum of GFAP astrocytopathy and its potential to closely mimic infectious central nervous system disease. Earlier recognition of GFAP astrocytopathy may facilitate timely consideration of immunotherapy and help reduce diagnostic delay and unnecessary antimicrobial exposure in patients with inflammatory meningoencephalitic presentations and negative infectious investigations.