Clinical characteristics of autoimmune GFAP astrocytopathy with concomitant Epstein-Barr virus positivity: a case series of 12 patients and literature review.

BACKGROUND

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a novel autoimmune central nervous system (CNS) disorder. Epstein-Barr virus (EBV) has been implicated in various neurological diseases, yet GFAP-A with concomitant Epstein-Barr virus positivity is poorly understood.

METHODS

We retrospectively analyzed 12 patients with concomitant EBV and GFAP positivity admitted between January 2022 and September 2025, and performed a literature review. Clinical, imaging, laboratory features, treatments, and outcomes were evaluated.

RESULTS

In our cohort, the median age at onset was 52.5 years (58% male). The predominant phenotype was meningo-encephalomyelitis (33%), with headache (100%) and fever (92%) as common symptoms. Peripheral nervous system involvement was noted in 16%. CSF analysis showed pleocytosis (100%) and elevated protein levels. MRI revealed T2/FLAIR hyperintensities in 67%, mainly in white matter and brainstem, and spinal lesions in 73%, including longitudinally extensive transverse myelitis (27%). All received antiviral and immunotherapy, with most showing improvement after intravenous methylprednisolone (± IVIG). At a median 32-month follow-up, only one relapsed, two died, and 80% of survivors achieved good outcomes (mRS < 3). Literature review (32 cases) showed similar features and immunotherapy responsiveness. Overall recurrence and mortality rates were both 7%.

CONCLUSIONS

In this small series, cases with concomitant EBV and GFAP positivity showed overlapping clinical features with classical GFAP-A and generally favorable responses to immunotherapy. Early recognition and CSF-based GFAP antibody testing may help improve patient outcomes; however, further studies are needed to confirm these findings.