Magnetic Resonance Imaging of Autoimmune GFAP Astrocytopathy

Abstract

A 40-year-old woman with no medical history presented to the emergency department with rapid onset of numbness that spread from the right torso to the entire right side, including the face, body, and limbs. She also presented with a left facial droop, slurred speech, and confusion. The episode resolved after 90 minutes. She endorsed experiencing nausea, fatigue, and hand tremors for 1 month after a flu-like illness. Coronavirus disease 2019 (COVID-19) and Epstein–Barr virus serologies were negative. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis with negative HSV, VZV, Lyme, cryptococcal antigen, and autoimmune encephalitis panel. She was discharged with outpatient follow-up. Ten days later, she re-presented to the emergency department with a 60-minute acute episode of bilateral hand numbness, visual obscurations, and slurred speech. She also reported persistent retro-orbital headaches ever since her initial emergency department visit. Physical examination was notable for a mild right-sided intention tremor and difficulty with tandem walking. Her strength and sensation were intact. Ophthalmologic examination showed mild blurring of the disc margins bilaterally. Brain magnetic resonance imaging (MRI) showed radial perivascular enhancement extending from the ventricles (Fig A, B) with FLAIR hyperintensity (Fig C). Cervicothoracic spine MRI showed extensive longitudinal intramedullary T2-hyperintensity (Fig D, E) with speckled foci of cord enhancement (Fig F). Axial T2-weighted (Fig G) and postcontrast (Fig H) images confirmed these findings. The imaging appearance prompted testing for antiglial fibrillary acidic protein (GFAP) in the CSF, which was positive and confirmed the diagnosis of anti-GFAP astrocytopathy. She was treated with 5 days of intravenous steroids followed by a prolonged oral steroid taper. Six weeks later the patient’s headaches and tremors resolved with no further episodes of paresthesias. Follow-up brain and cervicothoracic spine MR examinations at 6 weeks showed resolution of both the enhancement in the neuroaxis and longitudinal T2-hyperintensity in the cord. In the brain, residual confluent white matter fluid-attenuated inversion recovery (FLAIR) hyperintensity remained. Anti-GFAP astrocytopathy is a relatively new entity, first described in 2016 by Fang et al. Antibodies target glial fibrillary acidic protein, a cytosolic intermediate filament protein expressed by astrocytes. Immunostaining localizes protein expression to the perivascular regions of the brain and around the central canal of the spinal cord, and these autoantibodies lead to lymphocytic inflammation corresponding to the distribution of enhancement seen on imaging. Its prevalence is unclear due to the rarity of the condition and is probably as yet underdiagnosed. There is a slight predominance of female patients and those over 40 years of age, although pediatric cases have also been reported. It classically presents with symptoms of meningoencephalomyelitis including headache, encephalopathy, optic papillitis, inflammatory myelitis, postural tremor, and ataxia. A viral prodrome is sometimes identified. It is thought in some cases to represent a paraneoplastic syndrome: in one study of 102 patients, 22 were diagnosed with neoplasm, 15 of which were ovarian teratoma. In addition to the characteristic radial pattern of perivascular enhancement in the white matter in the brain, MRI of the spine can show longitudinally extensive T2 hyperintensity and leptomeningeal or parenchymal enhancement. Most patients respond well to corticosteroids.