Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis
Marianna Spatola1, Mar Petit Pedrol2, Estibaliz Maudes2
1From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (M. Spatola, M.P.P., E.M., M.R.R., F.G., J.D.), Barcelona, Spain; Ragon Institute of MGH, MIT and Harvard Medical School (M. Spatola), Cambridge, MA; Interdisciplinary Institute for Neuroscience (M.P.P.), University of Bordeaux, France; Neurology Division (M. Simabukuro), University of São Paulo, School of Medicine, Brazil; Centre de Référence des Syndromes Neurologiques Paranéoplasiques et des Encéphalites Autoimmunes (S.M.-C., A.L.P., J.H.), Hospices Civils de Lyon, Université de Lyon, Université Claude Bernard Lyon1, INMG, Inserm U1217/CNRS UMR 5310, France; Institute of Clinical Chemistry and Department of Neurology (K.-P.W.), Department of Neuropediatrics (J.S.), and Department of Neuroradiology (P.S.), University Hospital Schleswig Holstein, Lübeck, Germany; Faculdade Israelita de Ciências da Saúde Albert Einstein and General Neurology Division (L.A.D.), Federal University of São Paulo, Brazil; Institute of Neurology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS (R.I.), Rome, Italy; Department of Neurology (C.K.), University Hospital Bonn; Epilepsy Center Bethel (C.G.B.), Krankenhaus Mara, Bielefeld, Germany; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Neuroimmunology (F.L.), Institute of Clinical Chemistry and Department of Neurology, University Hospital Schleswig Holstein, Kiel, Germany; Department of Neurology (M.J.T., P.S.S.), Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; University Hospital Clínic (F.G.), University of Barcelona; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain. marianna.spatola@gmail.com.
Objective:
To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters.
Methods:
Clinical information on 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 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and 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.
More Related Videos
07:20A Simple Cell-based Immunofluorescence Assay to Detect Autoantibody Against the N-Methyl-D-Aspartate NMDA Receptor in Blood
Published on: January 9, 2018
08:20Hippocampal Neuronal Cultures to Detect and Study New Pathogenic Antibodies Involved in Autoimmune Encephalitis
Published on: June 2, 2022
Related Concept Videos
01:26Rocky Mountain Spotted Fever
01:18Viral Meningitis
01:25Arboviral Encephalitis
01:22Bacterial Meningitis I: Introduction
01:19Encephalitis l: Introduction
01:26Encephalitis ll: Pathophysiology