Unmasking autoimmune GFAP astrocytopathy: longitudinally extensive myelitis with multifocal brain lesions

Abstract

Case Presentation: A 58-year-old man presented with a 2-month history of burning pain in the left lower limb and a 1-month history of ipsilateral hypoesthesia and gait imbalance. Additional symptoms included cervical electric-shock sensations, progressive dysphonia, tinnitus, and psychomotor slowing. Neurological examination disclosed left lower-limb sensory impairment, positive Romberg sign, tandem gait ataxia, subtle saccadic abnormalities in eye motility examination, and a left Babinski sign. During hospitalization, asymptomatic heart rate fluctuations were detected on cardiac monitoring, suggesting possible autonomic involvement. Magnetic resonance imaging (MRI) demonstrated multifocal supratentorial and infratentorial white matter, brainstem, and cerebellar lesions with nodular enhancement, along with a longitudinally extensive central intramedullary lesion from T2 to T4, with mild cord expansion and heterogeneous enhancement, consistent with inflammatory myelitis. Cerebrospinal fluid showed normal glucose and protein levels, no pleocytosis, and negative infectious studies. Serum AQP4-IgG and MOG-IgG were negative. CSF oligoclonal bands supported intrathecal IgG synthesis, and subsequent Anti-GFAP reactivity was detected in CSF and confirmed by cell-based assay (CBA). Given the association of this biomarker with malignancies, a comprehensive neoplastic screening workup was performed, including upper endoscopy, colonoscopy, videolaryngoscopy, tumor markers and thoracoabdominal tomography, with no evidence of underlying malignancy. Discussion: This case illustrates a subacute and multifocal presentation of GFAP astrocytopathy, combining myelitis and encephalic involvement. The presence of longitudinally extensive myelitis initially broadened the differential diagnosis to include NMOSD, MOGAD, infectious myelitis, paraneoplastic and other autoimmune inflammatory disorders. However, AQP4-IgG and MOG-IgG were negative, and infectious, autoimmune, and neoplastic investigations were unremarkable. Final Comments: The patient showed partial clinical improvement after high-dose intravenous methylprednisolone followed by intravenous immunoglobulin, particularly in gait, psychomotor slowing, and hypophonia, although residual hypoesthesia and neuropathic pain persisted. Given the incomplete response and persistent residual deficits, the treating team elected to proceed with rituximab as maintenance immunotherapy. Comprehensive neoplastic screening was unrevealing. This case underscores autoimmune GFAP astrocytopathy as a diagnostic consideration in patients presenting with longitudinally extensive inflammatory myelitis, multifocal brain lesions, and negative AQP4/MOG antibodies, even when CSF abnormalities are limited.