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October 05, 2021; 97 (14) Research Article

Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease

View ORCID ProfileCarles Gaig, View ORCID ProfileYaroslau Compta, View ORCID ProfileAnna Heidbreder, Maria J. Marti, View ORCID ProfileMaarten J. Titulaer, View ORCID ProfileYvette Crijnen, View ORCID ProfileBirgit Högl, Jan Lewerenz, View ORCID ProfileMaría Elena Erro, Juan Carlos García-Moncó, Pasquale Nigro, View ORCID ProfileNicola Tambasco, Maja Patalong-Ogiewa, Marcus Erdler, View ORCID ProfileStefan Macher, Evelyn Berger-Sieczkowski, View ORCID ProfileRomana Höftberger, Christian Geis, Markus Hutterer, Angela Milán-Tomás, View ORCID ProfileAntonio Martin-Bastida, Lydia Lopez Manzanares, Sonia Quintas, View ORCID ProfileGünter U. Höglinger, Nora Möhn, Florian Schöberl, View ORCID ProfileFranziska S. Thaler, View ORCID ProfileGian Maria Asioli, View ORCID ProfileFederica Provini, View ORCID ProfileGiuseppe Plazzi, View ORCID ProfileKoldo Berganzo, View ORCID ProfileMorten Blaabjerg, Norbert Brüggemann, Tarsis Farias, View ORCID ProfileChen Fei Ng, Caroline Giordana, Alejandro Herrero-San Martín, Lucio Huebra, Katya Kotschet, Herburg Liendl, Teresa Montojo, Carlos Morata, Jesus Pérez-Pérez, Inmaculada Puertas, View ORCID ProfileThomas Seifert-Held, View ORCID ProfileCaspar Seitz, Mateus Mistieri Simabukuro, Nieves Téllez, Javier Villacieros-Álvarez, View ORCID ProfileBarbara Willekens, Lidia Sabater, Alex Iranzo, View ORCID ProfileJoan Santamaria, Josep Dalmau, Francesc Graus
First published August 11, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012639
Carles Gaig
From the Neuroimmunology Program (C. Gaig, L.S., A.I., J.S.C., J.D., F.G.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Department of Neurology (C. Gaig, Y. Compta, M.J.M., A.I., J.S., J.D.), Multidisciplinary Sleep Disorders Unit (C. Gaig, A.I., J.S.), and Parkinson's Disease & Movement Disorders Unit (Y. Compta, M.J.M.), Hospital Clinic, Barcelona, Spain; Department of Neurology, Division of Sleep Medicine and Neuromuscular Disorders (A.H.), University Hospital Muenster, Germany; Department of Neurology (A.H., B.H.), Medical University of Innsbruck, Austria; Department of Neurology (M.J.T., Y. Crijnen), Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Neurology (J.L.), Ulm University, Germany; Neurology Department, Complejo Hospitalario de Navarra (M.E.E.), Navarra Institute for Health Research (IdiSNA), Pamplona; Neurology Department (J.C.G.-M.), Hospital Universitario de Basurto, Bilbao (formerly Department of Neurology, Hospital de Galdakao); Movement Disorders Center (P.N., N. Tambasco), Perugia General Hospital and University of Perugia, Italy; Department of Neurology and Neurorehabilitation (M.P.-O.), Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland; Department of Neurology (M.E.), Klinik Donaustadt, Karl-Landsteiner-Institut, Vienna; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology (S.M., E.B.-S.), Medical University of Vienna, Austria; Section Translational Neuroimmunology (C. Geis), Department of Neurology, Jena University Hospital, Germany; Department of Neurology 1 (M.H.), Neuromed Campus, Kepler Universitätsklinikum Linz; Department of Neurology with Stroke Unit and Acute Geriatrics (M.H.), Saint John of God Hospital Linz, Austria; Department of Neurology and Neurosciences (A.M.-T., A.M.-B.), Clínica Universidad de Navarra, Pamplona-Madrid; Department of Neurology (L.L., S.Q.), Hospital La Princesa, Madrid, Spain; Department of Neurology (G.U.H., N.M.), Hannover Medical School; Department of Neurology (F.S.) and Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center (F.S.T.), Ludwig-Maximilians-University, Munich, Germany; Department of Biomedical and NeuroMotor Sciences (DiBiNeM) (G.M.A., F.P.), Alma Mater Studiorum University of Bologna; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.P.); Department of Biomedical, Metabolic and Neural Sciences (G.P.), University of Modena and Reggio Emilia, Modena; IRCCS (G.P.), Institute of Neurological Sciences of Bologna, Italy; Neurology Department (K.B.), Cruces University Hospital, Barakaldo, Spain; Department of Neurology (M.B.), Odense University Hospital, Denmark; Department of Neurology and Institute of Neurogenetics (N.B.), University of Lübeck, Germany; Department of Neurology (T.F.), Medical Clinic of Hospital Geral Cleriston Andrade, Feira de Santana, Brazil; Neurology Unit, Department of Medicine (C.F.N.), Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; Department of Movement Disorders and Neurology (C. Giordana), CHU Nice, France; Department of Neurology (A.H.-S.M.), Hospital Universitario 12 de Octubre, Madrid, Spain; Department of Psychobiology (L.H.), Universidade Federal de São Paulo, Brazil; Clinical Neurosciences (K.K.), St Vincent's Hospital, Melbourne, Australia; Department of Neurology (H.L.), LKH Murtal, Standort Knittelfeld, Austria; Department of Neurology (T.M.), Fundación Jiménez Diaz, Madrid; Department of Neurology (C.M.), Hospital Universitari i Politècnic La Fe, Valencia; Department of Neurology (J.P.P.), Hospital de la Santa Creu i Sant Pau, Barcelona; Department of Neurology (I.P.), Hospital La Paz, Madrid, Spain; Department of Neurology (T.S.-H.), Medical University of Graz, Austria; Department of Neurology (C.S.), Mainz University Hospital, Mainz, Germany; Department of Neurology (M.M.S.), University of São Paulo Medical School, Brazil; Department of Neurology (N. Tellez), Hospital Clínico Universitario, Valladolid; Department of Neurology (J.V.-Á.), Hospital Universitario Rey Juan Carlos, Madrid, Spain; Department of Neurology (B.W.), Antwerp University Hospital and University of Antwerp, Belgium; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.
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Yaroslau Compta
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Anna Heidbreder
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Maria J. Marti
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Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease
Carles Gaig, Yaroslau Compta, Anna Heidbreder, Maria J. Marti, Maarten J. Titulaer, Yvette Crijnen, Birgit Högl, Jan Lewerenz, María Elena Erro, Juan Carlos García-Moncó, Pasquale Nigro, Nicola Tambasco, Maja Patalong-Ogiewa, Marcus Erdler, Stefan Macher, Evelyn Berger-Sieczkowski, Romana Höftberger, Christian Geis, Markus Hutterer, Angela Milán-Tomás, Antonio Martin-Bastida, Lydia Lopez Manzanares, Sonia Quintas, Günter U. Höglinger, Nora Möhn, Florian Schöberl, Franziska S. Thaler, Gian Maria Asioli, Federica Provini, Giuseppe Plazzi, Koldo Berganzo, Morten Blaabjerg, Norbert Brüggemann, Tarsis Farias, Chen Fei Ng, Caroline Giordana, Alejandro Herrero-San Martín, Lucio Huebra, Katya Kotschet, Herburg Liendl, Teresa Montojo, Carlos Morata, Jesus Pérez-Pérez, Inmaculada Puertas, Thomas Seifert-Held, Caspar Seitz, Mateus Mistieri Simabukuro, Nieves Téllez, Javier Villacieros-Álvarez, Barbara Willekens, Lidia Sabater, Alex Iranzo, Joan Santamaria, Josep Dalmau, Francesc Graus
Neurology Oct 2021, 97 (14) e1367-e1381; DOI: 10.1212/WNL.0000000000012639

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Abstract

Background and Objectives Anti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease.

Methods In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders.

Results Seventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases.

Discussion Movement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.

Glossary

CBA=
cell-based assay;
DAT=
dopamine transporter;
HLA=
human leukocyte antigen;
IgG=
immunoglobulin G;
MSA=
multiple system atrophy;
PSP=
progressive supranuclear palsy

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally to this work.

  • Editorial, page 661

  • Received April 29, 2021.
  • Accepted in final form July 20, 2021.
  • © 2021 American Academy of Neurology
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