Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.