Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.

Humans Male Aged Glutamate Decarboxylase / immunology Muscle Rigidity / etiology Autoantibodies / blood Encephalomyelitis / immunology Myoclonus / etiology Receptors, Glycine / immunology Stiff-Person Syndrome / immunology Fatal Outcome

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
Nov 2024
Historique:
medline: 31 8 2024
pubmed: 31 8 2024
entrez: 30 8 2024
Statut: ppublish

Résumé

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin). We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies. A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support. Immunotherapy comprised corticosteroids, IVIG, plasmapheresis, immunoadsorption, cyclophosphamide, and bortezomib. Intensive care treatment and permanent isoflurane sedation was required for more than 20 weeks. CNS tissue revealed neuronal loss, astrogliosis and microgliosis, representing a pallido-nigro-dentato-bulbar-spinal degeneration pattern, specifically along GlyR and GAD expression sites. Neurons showed pSTAT1, MHC class I, and GRP78 upregulation. Inflammation was moderate and characterized by CD8 A possible potentiating effect of pathogenic GlyR antibodies together with T cells directed against neurons may have led to the severe and progressive clinical course.

Identifiants

DOI: 10.1212/NXI.0000000000200298 PMID: 39213470
pubmed: 39213470
doi: 10.1212/NXI.0000000000200298
doi:

Substances chimiques

Glutamate Decarboxylase EC 4.1.1.15
Autoantibodies 0
glutamate decarboxylase 2 EC 4.1.1.15
Receptors, Glycine 0

Types de publication

Journal Article Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

e200298

Auteurs

Michael Winklehner (M)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Jonathan Wickel (J)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.
ORCID: 0000-0002-5854-3759

Ellen Gelpi (E)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Dirk Brämer (D)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.
ORCID: 0009-0008-3633-6047

Vera Rauschenberger (V)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Albrecht Günther (A)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Jan Bauer (J)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Anika Simonovska Serra (AS)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Philipp Jauk (P)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.

Carmen Villmann (C)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.
ORCID: 0000-0003-1498-6950

Romana Höftberger (R)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.
ORCID: 0000-0002-5769-1100

Christian Geis (C)

From the Division of Neuropathology and Neurochemistry (M.W., E.G., R.H.), Department of Neurology, Medical University of Vienna; Department of Neurology (M.W.), Johannes Kepler University Linz, Kepler University Hospital, Linz, Austria; Section of Translational Neuroimmunology (J.W., D.B., A.G., C.G.), Department of Neurology, Jena University Hospital, Germany; Comprehensive Center for Clinical Neurosciences and Mental Health (E.G., R.H.), Medical University of Vienna, Austria; Institute of Clinical Neurobiology (V.R., C.V.), University Hospital, Julius-Maximilians-University of Würzburg, Germany; Department of Neuroimmunology (J.B.), Center for Brain Research; and Center for Medical Physics and Biomedical Engineering (A.S.S., P.J.), Medical University of Vienna, Austria.
ORCID: 0000-0002-9859-581X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Lyases › Carbon-carbon lyases › Carboxy-lyases › Glutamate decarboxylase › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Manifestations neuromusculaires › Hypertonie musculaire › Raideur musculaire › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Maladies du système nerveux › Encéphalomyélite › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Dyskinésies › Myoclonie › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs aux acides aminés › Récepteur de la glycine › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Syndrome de l'homme raide › Progressive Encephalomyelitis With Rigidity...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Issue fatale › Progressive Encephalomyelitis With Rigidity...