Encephalitis with mGluR5 antibodies: Symptoms and antibody effects.

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Cited 152 times in Scopus logo

Cited 116 times in Web of Science logo

Cited 75 times in Europe PMC logo

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This study was supported in part by Instituto Carlos III/FEDER (CD14/00155, E.M.-H.; FIS PI15/00377, F.G.; FIS PI14/00203, J.D.) and Centro de Investigacion Biomedica en Red de Enfermedades Raras No. CB15/00010, J.D.; NIH RO1NS077851, J.D.; Agaur SGR93, J.D.; Pla Estrategic de Recerca i Innovacio en Salut (PERIS, SLT002/16/00346), J.P.; University of Lausanne and University Hospital of Lausanne Joint Foundation (Lausanne, Switzerland), M.S.; Fundacion de Investigacion Medica Mutua Madrilena (AP162572016), T.A.; Fundacio La Marato de TV3 (20141830), F.G.; and Fundacio CELLEX, J.D.

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Spatola MAuthorSabater LAuthorPlanaguma JAuthorMartinez-Hernandez EAuthorArmangue TAuthorRosenfeld MrAuthorGraus FAuthorDalmau JCorresponding Author

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Article

Publicated to:Neurology. 90 (22): E1964-E1972 - 2018-05-29 90(22), DOI: 10.1212/wnl.0000000000005614

Authors: Spatola, Marianna; Sabater, Lidia; Planaguma, Jesus; Martinez-Hernandez, Eugenia; Armangue, Thais; Pruess, Harald; Iizuka, Takahiro; Caparo Oblitas, Ruben L; Antoine, Jean-Christophe; Li, Richard; Heaney, Nicholas; Tubridy, Niall; Munteis Olivas, Elvira; Rosenfeld, Myrna R; Graus, Francesc; Dalmau, Josep

Affiliations

Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland Beatson Oncology Centre - Author

Catalan Inst Res & Adv Studies, Barcelona, Spain - Author

Charite Univ Med Berlin, Expt Neurol, Berlin, Germany Free University of Berlin Charite Medical University of Berlin Humboldt University of Berlin - Author

Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain. CIBERER CIBER - Centro de Investigacion Biomedica en Red - Author

Ctr Invest Biomed Red Enfermedades Raras, Valencia, Spain CIBER - Centro de Investigacion Biomedica en Red CIBERER - Author

German Ctr Neurodegenerat Dis, Berlin, Germany Helmholtz Association German Center for Neurodegenerative Diseases (DZNE) - Author

Hosp del Mar, IMIM, Serv Neurol, Barcelona, Spain Institut Hospital del Mar d'Investigacions Mediques (IMIM) Hospital del Mar - Author

Hosp Nacl Edgardo Rebagliati Martins, Lima, Peru - Author

ICFO Inst Ciencies Foton, Barcelona, Spain Barcelona Institute of Science & Technology Institut de Ciencies Fotoniques (ICFO) - Author

Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. Hospital Clinic de Barcelona IDIBAPS University of Barcelona - Author

Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain Hospital Clinic de Barcelona University of Barcelona IDIBAPS - Author

Kitasato Univ, Sch Med, Dept Neurol, Sagamihara, Kanagawa, Japan Kitasato University - Author

Klin & Poliklin Neurol, Berlin, Germany - Author

Pamela Youde Nethersole Eastern Hosp, Hong Kong, Hong Kong, Peoples R China Pamela Youde Nethersole Eastern Hospital - Author

St Vincents Univ Hosp, Dept Neurol, Dublin, Ireland University College Dublin - Author

Univ Barcelona, Hosp Clin, Barcelona, Spain University of Barcelona Hospital Clinic de Barcelona - Author

Univ Barcelona, St Joan de Deu Childrens Hosp, Pediat Neuroimmunol Unit, Barcelona, Spain University of Barcelona - Author

Univ Hosp, Dept Neurol, St Etienne, France CHU de St Etienne - Author

Univ Lausanne, Dept Clin Neurosci, Lausanne, Switzerland University of Lausanne - Author

Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. University of Pennsylvania - Author

Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA University of Pennsylvania - Author

Catalan Inst Res & Adv Studies, Barcelona, Spain. - Author

Abstract

Objective To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. Methods Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques. Results From January 2005 to May 2017, 11 patients (median age 29 years, range 6-75 years, 5 female) were identified. The main clinical features were psychiatric (10), cognitive (10), movement disorders (7), sleep dysfunction (7), and seizures (6). Median modified Rankin Scale score at the peak of the disease was 4; 4 patients required intensive care. Five patients had Hodgkin lymphoma, and 1 had small cell lung cancer. CSF showed pleocytosis (median white blood cell count 22 mm(3)) in all patients; brain MRI was abnormal in 5, involving limbic (1) or extralimbic (4) regions. Treatments included immunotherapy and/or oncologic therapy; at the last followup (median 48 months), 6 patients had complete and 5 had partial recovery. Neurologic relapse occurred in 2 patients. Antibodies were IgG1 alone (4 of 9) or in combination with IgG2 (1 of 9), IgG3 (3 of 9), or both (1). Patients' IgG caused a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5 without altering the levels of postsynaptic density protein 95. Conclusions Anti-mGluR5 encephalitis associates with a complex neuropsychiatric syndrome, not restricted to limbic encephalitis, and can occur without tumor. Patients respond to treatment, but relapses can occur. The antibodies have pathogenic effects altering the levels of cell-surface mGluR5.

Keywords

afq056autoantibodiescase seriesdiseaseglutamate-receptorlimbic encephalitislong-term depressionmemoryophelia syndromeAdolescentAdultAfq056AgedAutoantibodiesCase seriesChildDiseaseEncephalitisFemaleGlutamate-receptorGrm5 protein, humanHek293 cellsHumansLimbic encephalitisLong-term depressionMaleMemoryMiddle agedNeuronsNmda-receptor encephalitisOphelia syndromeReceptor, metabotropic glutamate 5Retrospective studiesYoung adult

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Neurology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2018, it was in position 10/199, thus managing to position itself as a Q1 (Primer Cuartil), in the category Clinical Neurology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 4.55. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Weighted Average of Normalized Impact by the Scopus agency: 5.91 (source consulted: FECYT Feb 2024)
Field Citation Ratio (FCR) from Dimensions: 32.52 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-30, the following number of citations:

WoS: 116
Scopus: 152
Europe PMC: 75

Impact and social visibility

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: China; France; Germany; Japan; Peru; Switzerland; United Kingdom; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Spatola, Marianna) and Last Author (Dalmau Obrador, Josep).