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      Case Report: Guillain-Barré Syndrome Characterized by Severe Headache Associated With Metabotropic Glutamate Receptor 5 Antibody

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          Abstract

          Autoantibodies to metabotropic glutamate receptor 5 (mGluR5) are known to be the cause of autoimmune encephalitis, particularly limbic encephalitis, closely related to Hodgkin’s lymphoma (HL). The involvement of peripheral neuropathy is rarely reported. In our case, mGluR5 antibody was found in a Guillain-Barré syndrome (GBS) patient accompanied by severe headache but without neuropsychiatric manifestations or HL. Presenting with severe headache, the patient developed progressive bilateral limb weakness, areflexia, and cranial nerve involvement consisting of eye movement disorder, restricted mouth opening and chewing, bilateral facial paralysis and bulbar palsy. Cerebrospinal fluid (CSF) revealed elevated CSF protein level and normal cell count, known as “albumino-cytological dissociation”. Oligoclonal IgG bands were found in both the CSF and serum. Electrophysiological studies revealed symmetrical sensory and motor neuropathy with a mixture of axonal and demyelinating features. Brain and spinal cord magnetic resonance imaging (MRI), as well as the electroencephalogram, were normal. The mGluR5 antibody was positive in both serum and CSF with a Cell-Based Assay (CBA). The patient responded well to intravenous gammaglobulin therapy, correlated with a reduction of mGluR5 antibody titer from 1:30 to 1:10 in the serum. After 6 months, the patient recovered completely without any sign of recurrence or neoplasm. This first case of mGluR5 antibody-associated GBS accompanied by severe headache shows that mGluR5-associated disorders are not limited to manifestations of limbic encephalitis and HL.

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          Most cited references20

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          Metabotropic glutamate receptors: physiology, pharmacology, and disease.

          The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
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            Guillain-Barré syndrome.

            Guillain-Barré syndrome is the most common and most severe acute paralytic neuropathy, with about 100,000 people developing the disorder every year worldwide. Under the umbrella term of Guillain-Barré syndrome are several recognisable variants with distinct clinical and pathological features. The severe, generalised manifestation of Guillain-Barré syndrome with respiratory failure affects 20-30% of cases. Treatment with intravenous immunoglobulin or plasma exchange is the optimal management approach, alongside supportive care. Understanding of the infectious triggers and immunological and pathological mechanisms has advanced substantially in the past 10 years, and is guiding clinical trials investigating new treatments. Investigators of large, worldwide, collaborative studies of the spectrum of Guillain-Barré syndrome are accruing data for clinical and biological databases to inform the development of outcome predictors and disease biomarkers. Such studies are transforming the clinical and scientific landscape of acute autoimmune neuropathies.
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              Diagnosis and management of Guillain–Barré syndrome in ten steps

              Guillain–Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                21 March 2022
                2022
                : 13
                : 808131
                Affiliations
                [1] 1 Department of Neurology, The Second Xiangya Hospital, Central South University , Changsha, China
                [2] 2 Department of Urology, Xiangya Hospital, Central South University , Changsha, China
                Author notes

                Edited by: Ravi Misra, University of Rochester, United States

                Reviewed by: Richard Hughes, University College London, United Kingdom; Haruki Koike, Nagoya University, Japan; Hongliang Zhang, National Natural Science Foundation of China, China

                *Correspondence: Chunyu Wang, wangchunyu@ 123456csu.edu.cn

                This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.808131
                8977415
                35386694
                30053b66-4ad1-4af1-aaf3-7c502c375901
                Copyright © 2022 Yan, Zhao, Zhang, Hu and Wang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 November 2021
                : 16 February 2022
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 20, Pages: 5, Words: 2214
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Funded by: Natural Science Foundation of Hunan Province , doi 10.13039/501100004735;
                Categories
                Immunology
                Case Report

                Immunology
                mglur5 antibody,guillain-barré syndrome,limbic encephalitis,headache,hodgkin’s lymphoma

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