Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe 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.ResultsWe 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.DiscussionGFAP 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

The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort

International audienceBackgroundThe association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC.MethodsAll participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n = 1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer.ResultsThe global executive function score was related to the BPF (sß: 0.091, P < 0.001) and CT in the right supramarginal (sß: 0.060, P = 0.041) and right isthmus cingulate (sß: 0.062, P = 0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P < 0.001) and CT in the left parsorbitalis region (sß: 0.045, P = 0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P < 0.001) and CT in the right supramarginal region (sß: 0.061, P = 0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P = 0.045) and CT in the right precuneus (sß: 0.073, P = 0.019) and right isthmus cingulate region (sß: 0.054, P = 0.032).ConclusionsIn a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD