Clinical findings, IgG subclass, and antibody effects in encephalitis associated with metabotropic glutamate receptor 5 (mGluR5) antibodies (P5.390)

Objective: To report the clinical features and outcome of 11 patients with anti-mGluR5 encephalitis, IgG antibody-subclass, and effects of the antibodies on cultured neurons. Background: Antibodies to mGluR5 have been reported in a few patients with autoimmune encephalitis and Hodgkin’s lymphoma; the potential pathogenicity of the antibodies is unknown. Design/Methods: Clinical information was provided by the authors or treating physicians. Antibodies and IgG subclass were determined using brain immunohistochemistry and cell-based assays; antibody pathogenic effects were determined in hippocampal neuronal cultures. Results: From January 2006 to May 2017, 11 patients, median age 29 years (range 6–75), 5/11 females, were identified. The main clinical features were psychiatric (10/11), cognitive (10/11), movement disorders (7/11), sleep dysfunction (7/11), and seizures (6/11). Median modified Rankin Scale at disease peak was 4.0; 6/11 patients required intensive care. Six patients had a tumor: 5 Hodgkin’s lymphoma, 1 small-cell lung cancer; the latter had progressive ophthalmoplegia, executive dysfunction, and ataxia. Of the 6 patients with tumor, 3 received immunotherapy and cancer treatment, and 3 cancer treatment only. At the last follow-up (median, 48 months) 6 patients had complete and 5 partial recovery. Neurologic relapse occurred in 2 patients. CSF showed pleocytosis (median WBC 22) in 11/11 patients; brain MRI was abnormal in 5/11 patients, involving limbic (1) or extra-limbic regions (4), and the EEG was abnormal in 5/11. Patients’ mGluR5 antibodies were IgG1, alone (2) or in combination with IgG2 (2) and IgG3 (3). Patients’ IgG caused a significant and specific decrease of total cell surface and synaptic mGluR5 clusters without altering PSD95 clusters. Conclusions: Anti-mGluR5 encephalitis is characterized by a complex neuropsychiatric syndrome, not restricted to limbic encephalitis, and can occur without tumor. Patients respond to immunotherapy and cancer treatment, but relapses can occur. The antibodies have pathogenic effects altering the levels of synaptic and extrasynaptic mGluR5. Study Supported by: MS received research support from the University of Lausanne and CHUV Hospital of Lausanne joint Foundation, Lausanne, Switzerland Disclosure: Dr. Spatola has nothing to disclose. Dr. Sabater has nothing to disclose. Dr. Planaguma has nothing to disclose. Dr. Iizuka has nothing to disclose. Dr. Pruss has nothing to disclose. Dr. Martinez-Hernandez has nothing to disclose. Dr Armangue has nothing to disclose. Dr. Rosenfeld has nothing to disclose. Dr. Graus has nothing to disclose. Dr. Dalmau has received personal compensation in an editorial capacity for Editor: Neurology, Neuroimmunology, Neuroinflammation; and UpToDate. Dr. Dalmau has received royalty, license fees, or contractual rights payments from Euroimmune. Dr. Dalmau has received research support from Euroimmun.