Clinical features and pathogenesis of autoimmune GFAP astrocytopathy

Abstract

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP–A) was first reported as an autoimmune inflammatory central nervous system disorder associated with immunoglobulin G (IgG) antibodies that recognize GFAP, which is the main intermediate filament protein in mature astrocytes. In recent years, the clinical features of GFAP–A have become better understood. Approximately 10∼15% of patients complicate with neoplasm including ovarian teratoma. The common phenotype of this disorder includes meningoencephalitis with or without myelitis. The pathogenesis of GFAP–A is poorly understood. Pathologically, there is a marked lymphocytic infiltration of the meningeal and brain parenchyma, with many CD8+ and CD4+ T cells, especially in the perivascular area. GFAP–specific cytotoxic T cells are also likely effectors of this disorder. During the clinical course, patients present with consciousness disturbances, meningeal irritation, ataxia, involuntary movements such as tremor and myoclonus, urinary dysfunction, cognitive dysfunction, optic disc edema, area postrema syndrome, and respiratory failure. The cerebrospinal fluid (CSF) can be probed for lymphocyte–predominant pleocytosis and elevated protein levels. The positivity rate of oligoclonal bands was about 70%. The detection of CSF GFAP–IgG by tissue– and cell–based testing is essential for a diagnosis of GFAP–A. Brain magnetic resonance imaging (MRI) can show abnormal hyperintensity lesions on T2–weighted and fluid–attenuated inversion recovery images. Brain linear perivascular radial gadolinium–enhancement patterns, an imaging hallmark of GFAP–A, are observed in about half of all patients. Spinal cord MRI can show longitudinal extensive spinal cord lesions. While the response to corticosteroid therapy is typically good, some patients had poor prognosis. Patients with high mRS scores at peak and the elderly may have a poor prognosis. The relapse rate was about 10%. The main sequelae were cognitive and urinary dysfunctions.