Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis.

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.