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

Objective:To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR)1 encephalitis, identify prognostic factors, and study the IgG subclasses and effects of antibodies on neuronal mGluR1 clusters.Methods:Clinical information of new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons.Results:Eleven new patients were identified (10 adults, 1 child), 4 females. In these and 19 previously reported cases (n=30, median age 55) the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurological symptoms. A tumor was found in 3/26 (11%). Brain MRI was abnormal in 7/19 (37%) at onset and showed cerebellar atrophy in 10/12 (83%) at follow-up. Twenty-five/30 (83%) patients received immunotherapy. Follow-up was available from 25: 13 (52%) had clinical stabilization, 10 (40%) significant improvement, and 2 died. At the peak of the disease, patients with bad outcome (mRS>2, n=7) were more likely to have higher degree of initial disability, as reflected by a worse SARA (Scale for Assessment and Rating of Ataxia) score, and the more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons.Conclusions:Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.