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Neurology. 2020 Mar 11. pii: 10.1212/WNL.0000000000009239. doi: 10.1212/WNL.0000000000009239. [Epub ahead of print]

Clinical significance of anti-NMDAR concurrent with glial or neuronal surface antibodies.

Author information

1
From the Neuroimmunology Program (E.M.-H., M.G., A.G.-S., E.M., H.A., T.A., A.S., F.G., J.D.), Institut d'Investigacions Biomediques August Pi i Sunyer; Neurology Department (E.M.-H., M.G., H.A., M.S., T.A., A.S., J.D.), Hospital Clinic, and Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Deu Children's Hospital, University of Barcelona; Centro de Investigaciones Biomedicas en Red de Enfermedades Raras (E.M.-H., M.G., T.A., J.D.), Madrid, Spain; Hospital Cayetano Heredia (A.P.R.), San Martin de Porres, Perú; Hadassah-Hebrew University Medical Center (T.B.-H.), Jerusalem, Israel; Department of Neurology (T.I.), Kitasato University School of Medicine, Sagamihara, Japan; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
2
From the Neuroimmunology Program (E.M.-H., M.G., A.G.-S., E.M., H.A., T.A., A.S., F.G., J.D.), Institut d'Investigacions Biomediques August Pi i Sunyer; Neurology Department (E.M.-H., M.G., H.A., M.S., T.A., A.S., J.D.), Hospital Clinic, and Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Deu Children's Hospital, University of Barcelona; Centro de Investigaciones Biomedicas en Red de Enfermedades Raras (E.M.-H., M.G., T.A., J.D.), Madrid, Spain; Hospital Cayetano Heredia (A.P.R.), San Martin de Porres, Perú; Hadassah-Hebrew University Medical Center (T.B.-H.), Jerusalem, Israel; Department of Neurology (T.I.), Kitasato University School of Medicine, Sagamihara, Japan; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain. jdalmau@clinic.cat.

Abstract

OBJECTIVE:

To determine the frequency and significance of concurrent glial (glial-Ab) or neuronal-surface (NS-Ab) antibodies in patients with anti-NMDA receptor (NMDAR) encephalitis.

METHODS:

Patients were identified during initial routine screening of a cohort (C1) of 646 patients consecutively diagnosed with anti-NMDAR encephalitis and another cohort (C2) of 200 patients systematically rescreened. Antibodies were determined with rat brain immunostaining and cell-based assays.

RESULTS:

Concurrent antibodies were identified in 42 patients (4% from C1 and 7.5% from C2): 30 (71%) with glial-Ab and 12 (29%) with NS-Ab. Glial-Ab included myelin oligodendrocyte glycoprotein (MOG) (57%), glial fibrillary acidic protein (GFAP) (33%), and aquaporin 4 (AQP4) (10%). NS-Ab included AMPA receptor (AMPAR) (50%), GABAa receptor (GABAaR) (42%), and GABAb receptor (8%). In 39 (95%) of 41 patients, concurrent antibodies were detected in CSF, and in 17 (41%), concurrent antibodies were undetectable in serum. On routine clinical-immunologic studies, the presence of MOG-Ab and AQP4-Ab was suggested by previous episodes of encephalitis or demyelinating disorders (8, 27%), current clinical-radiologic features (e.g., optic neuritis, white matter changes), or standard rat brain immunohistochemistry (e.g., AQP4 reactivity). GFAP-Ab did not associate with distinct clinical-radiologic features. NS-Ab were suggested by MRI findings (e.g., medial temporal lobe changes [AMPAR-Ab], or multifocal cortico-subcortical abnormalities [GABAaR-Ab]), uncommon comorbid conditions (e.g., recent herpesvirus encephalitis), atypical tumors (e.g., breast cancer, neuroblastoma), or rat brain immunostaining. Patients with NS-Ab were less likely to have substantial recovery than those with glial-Ab (5 of 10 [50%] vs 17 of 19 [89%], p = 0.03).

CONCLUSIONS:

Between 4% and 7.5% of patients with anti-NMDAR encephalitis have concurrent glial-Ab or NS-Ab. Some of these antibodies (MOG-Ab, AQP4-Ab, NS-Ab) confer additional clinical-radiologic features and may influence prognosis.

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