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

Abstract

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.

• Authors: Marianna Spatola, Mar Petit Pedrol, Estibaliz Maudes, Mateus Simabukuro, Sergio Muñiz-Castrillo, Anne-Laurie Pinto, Klaus-Peter Wandinger, Juliane Spiegler, Peter Schramm, Lívia Almeida Dutra, Raffaele Iorio, Cornelia Kornblum, Christian G Bien, Romana Höftberger, Frank Leypoldt, Maarten J Titulaer, Peter Sillevis Smitt, Jérôme Honnorat, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
• Journal: Neurology (Neurology) Vol. 95 Issue 22 Pg. e3012-e3025 (12 01 2020) ISSN: 1526-632X [Electronic] United States
• PMID: 32928978 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Academy of Neurology.

Chemical References

• Autoantibodies
• Immunoglobulin G
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor type 1

Topics

• Adult
• Aged
• Animals
• Atrophy (pathology)
• Autoantibodies (immunology)
• Autoimmune Diseases of the Nervous System (complications, diagnosis, immunology)
• Cells, Cultured
• Cerebellar Diseases (diagnosis, etiology, immunology, pathology)
• Child
• Embryo, Mammalian
• Encephalitis (complications, diagnosis, immunology)
• Female
• Follow-Up Studies
• Hippocampus (cytology)
• Humans
• Immunoglobulin G (classification)
• Immunotherapy
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neurons
• Prognosis
• Rats
• Receptors, Metabotropic Glutamate (immunology)