Objectives:To report the clinical, biological, imaging features, and the clinical course of a French cohort of patients with glial fibrillar acidic protein (GFAP) autoantibodies.Methods:We retrospectively included all patients tested positive for GFAP antibodies in the cerebrospinal fluid, by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα, since 2017, from two 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 auto-immune 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 presentation included myelitis (30%), 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. 33/40 patients had a monophasic course, associated to 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. 11/22 patients showed negative conversion of GFAP antibodies.Interpretation:GFAP auto-immunity 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.

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

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