To describe a single-center prospective cohort of 6 patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

GFAP astrocytopathy is an inflammatory autoimmune disorder described in 2016 in a group of patients with corticosteroid-responsive meningoencephalitis with or without myelitis. While most patients have a favorable response to steroids, relapse rates of approximately 20% often necessitate initiation of steroid-sparing therapies. Typical symptoms include altered mentation, meningitis, weakness and sensory changes, but atypical presentations can introduce diagnostic challenges.

Patients were enrolled in the Autoimmune, Paraneoplastic, and Inflammatory Neurologic Disease Registry from 2017-2023 and were followed prospectively. Demographic data, antibody titers, neuroimaging findings, acute and maintenance therapy, and patient outcomes at most recent follow-up visit were recorded.

Six patients (mean age: 62, range 45-88) were followed longitudinally (average = 31 months). Four presented with fever. CSF GFAP IgG was detected in five patients (median titer = 1:64), the one patient had a positive serum GFAP IgG only (IFA titer = 1:1920). Initially, five MRIs showed no abnormalities. Two revealed changes after one and five months, with one displaying classic findings and the other showing cauda equina nerve root enhancement. Three had malignancies (ependymoma, prostate carcinoma, and melanoma) and one had systemic sarcoidosis. Five patients received high-dose steroids acutely, one received plasma exchange followed by IVIg. Subsequently, four patients received steroid-sparing therapy. One patient died from cancer complications. All patients demonstrated clinical improvement at follow up. None of the patients on steroid-sparing therapies have had a clinical relapse.

This prospective case series highlights possible diagnostic challenges in GFAP astrocytopathy, given the concerns for infectious mimics in the setting of prominent fevers and potential delays in MRI abnormalities. Rarely, peripheral manifestations have been reported; our series uniquely presents isolated nerve root involvement. Out of the surviving patients, all had favorable long-term response to immunosuppressive therapies.