Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study

Abstract

Background and objectives: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.

Methods: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.

Results: We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.

Discussion: GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Figure 1. Brain MRI Features of Patients With Anti-GFAP Antibodies

Brain MRI of patients with anti–glial fibrillary acidic protein (GFAP) antibodies showing abnormal hyperintensity lesions on fluid-attenuated inversion recovery images (A.a–B.c) were observed in internal and external capsules (A.a, A.b, and A.c, arrowheads), basal ganglia (A.a and A.b, stars), thalami (A.a, A.b, and A.c, arrows), brainstem (B.a, B.b, and B.c, arrows), and temporal poles (B.b and B.c, arrowheads). Diffusion-weighted images (C.a–D.c) show splenial corpus callosum lesions (C.a and D.a, arrows) with the corresponding reduced diffusion (C.b and D.c, arrows) reversible at 15 days (C.c), involving anterior corpus callosum (D.a, star) and bilateral centrum semiovale (D.b, arrowheads), as respectively seen in mild encephalopathy/encephalitis with reversible splenial lesion type I and type II.

Figure 2. Enhancement Patterns and Evolution of MRI Abnormalities in Patients With Anti-GFAP–Associated Meningoencephalitis

Enhancement patterns (A.a–E.b) and evolution of MRI abnormalities (F.a–G.d) in patients with anti–glial fibrillary acidic protein (GFAP)–associated meningoencephalitis. Brain MRI of patients with anti-GFAP antibodies showing abnormal hyperintensity lesions on fluid-attenuated inversion recovery (FLAIR) images (A.a, A.c, B.a, and C.a), which enhance with a linear radially oriented or punctuate pattern in periventricular areas (A.b, arrowheads), centrum semiovale (A.d, arrowheads), cerebellum (B.b, arrowheads), and basal ganglia (C.b, arrowheads) on postgadolinium T1. Other enhancement patterns included ovoid (D.a and D.b, arrowheads) and periependymal (E.a and E.b, arrowheads). Whereas white matter FLAIR hyperintensities progressed towards extensive leukopathy at 7 months (F.a and F.c), brainstem leptomeningeal contrast enhancement receded 3 months after initial attack treatment (F.b and F.d). In another patient, while periventricular FLAIR hyperintensities expanded (G.a and G.c), periventricular radial enhancement receded at 2 months (G.b and G.d).

Figure 3. Spinal Cord MRI Features of Patients With Anti-GFAP Antibodies

Spine MRI of patients with anti–glial fibrillary acidic protein (GFAP) antibodies show longitudinally extensive (A.a) and most prominent centrally (A.b) abnormal T2 hyperintensity accompanied by central canal enhancement (A.c, arrowheads) and leptomeningeal enhancement (A.d, arrowheads), holocord longitudinally extensive T2 hyperintensity (B.a and B.b), and longitudinally extensive T2 hyperintensity (C.a) accompanied by patchy enhancement (C.b, arrowheads).