Background

Glial fibrillar acidic protein (GFAP) autoimmunity is a recently identified disease, at the frontier of auto-immune encephalitis and gliopathies. Clinical features associated to this new entity are still not fully evaluated; especially the risk of relapse and the disability outcome.

Objectives

To report the clinical, biological, imaging features, and the clinical course of a French cohort of patients with GFAP autoantibodies.

Methods

We retrospectively included all patients tested positive for GFAP antibodies since 2017, from two French referral centers (auto-immune encephalitis and rare inflammatory disorders of the brain and the spinal cord). GFAP autoantibodies were detected exclusively in the CSF, by immunohistochemistry and their specificity confirmed by cell-based assay using cells expressing human GFAPα.

Results

We identified 46 patients with GFAP antibodies. Median age at onset was 43 years and men were more affected (30/46). Infectious prodromal symptoms were found in 82% of cases. Other autoimmune diseases were found in 22% of cases and coexisting neural autoantibodies in 11% of cases, including MOG-IgG and AQP4-IgG positive cases. Tumors were present in 24%, and T cell dysfunction in 23% of cases, respectively. The most frequent presentation was acute/subacute menigoencephalitis (85%) with cerebellar dysfunction in 57% of cases. Other/associated clinical presentation included: myelitis (30%), visual tract involvement (35%) and peripheral nervous system involvement (28%). CSF showed pleocytosis (98%), oligoclonal bands (77%) and low glucose level (15%). MRI findings were heterogeneous: radial enhancement was found in 26%, periventricular diffuse T2 hyperintensity in 39%, brainstem involvement in 33%, leptomeningeal enhancement in 23%, and reversible splenial lesions in 4 cases.

39/46 patients have a monophasic course, associated to a good outcome at last follow-up (Rankin Score≤2: 89% at 15,5 months), despite a frequently severe clinical presentation (intensive care unit hospitalization: 42%). Seventy patients were treated with immunotherapy. 11/22 patients showed negativation of GFAP antibodies (median time: 2 months).

Conclusions

GFAP autoimmunity was generally associated to a good outcome and a low risk of relapse. Identification of factors associated to risk of relapse or disability, to monitor immunotherapy, is needed.

Background

Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown.

Objectives

The objective was to describe the clinical characteristics and outcomes of COVID-19 in patients with neuromyelitis optica and associated disorders and to identify the factors associated with COVID-19 severity.

Methods

We conducted a multi-center, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and June 30^th, 2020. Main outcome was COVID-19 severity score assessed on a 7-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death).

Results

Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower EDSS score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]).

Conclusions

COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19, however we recommend to maintain preventive measures to limit the risk of contamination with SARS-CoV-2 in this immunocompromised population.