Clinical and Radiological Advances in Autoimmune GFAP Astrocytopathy: Analysis of 387 Patients in Japan

Abstract

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disease. Recent neuropathological findings indicate that GFAP-specific cluster of differentiation (CD)8⁺ T cells are likely the effectors of GFAP-A. Of 387 individuals in Japan identified as having GFAP-A, most presented with headache and/or fever followed by neurological symptoms including consciousness disturbance, urinary dysfunction, hyperreflexia, movement disorders, and papilledema. Sixteen (5.9%) of the 270 GFAP-A patients tested had coexisting antibodies. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis and increased protein levels. Moreover, transiently increased CSF adenosine deaminase, decreased glucose, and positive oligoclonal band results were sometimes observed. Brain magnetic resonance imaging (MRI) occasionally showed T2-hyperintensity lesions. Linear perivascular radial gadolinium-enhancement patterns were observed and may be an imaging hallmark of GFAP-A. Spinal cord MRI sometimes exhibited T2-hyperintensity spinal cord lesions, most of which were longitudinally extensive. Most patients were treated with immunotherapies, including intravenous methylprednisolone pulse therapy with or without intravenous immunoglobulin therapy and/or plasma exchange; this was followed by oral corticosteroid therapy, which was gradually tapered. Some refractory patients received second-line immunotherapies including rituximab or cyclophosphamide. In 203 patients with follow-up ≥ 6 months, the median modified Rankin scale score at last follow-up was 1 (range: 0–6); however, 44 patients (21.7%) had scores of 3 or greater, and six patients died. The most common neurological finding at last follow-up was cognitive dysfunction, followed by urinary dysfunction; the recurrence rate was 10.5%. CSF GFAP-immunoglobulin G should be examined in patients who present with these characteristic clinical and radiological features.

Trial Registration: Autoimmune GFAP astrocytopathy registry (UMIN: 000054387).