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Original research
Functional movement disorder gender, age and phenotype study: a systematic review and individual patient meta-analysis of 4905 cases
  1. Sarah C. Lidstone1,2,
  2. Michael Costa-Parke1,
  3. Emily J. Robinson3,4,
  4. Tommaso Ercoli5,
  5. Jon Stone6
  6. FMD GAP Study Group
    1. 1Integrated Movement Disorders Program, University Health Network, Toronto, Ontario, Canada
    2. 2Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    3. 3Royal Marsden Clinical Trials Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK
    4. 4King’s College London, School of Population Health and Environmental Sciences, London, UK
    5. 5Department of Medical Sciences and Public Health, Institute of Neurology, University of Cagliari, Cagliari, Italy
    6. 6Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
    1. Correspondence to Dr Sarah C. Lidstone, Neurology, University of Toronto, Toronto, ON M5S 1A1, Canada; sarah.lidstone{at}uhnresearch.ca

    Abstract

    Functional movement disorder (FMD) is a common manifestation of functional neurological disorder presenting with diverse phenotypes such as tremor, weakness and gait disorder. Our current understanding of the basic epidemiological features of this condition is unclear. We aimed to describe and examine the relationship between age at onset, phenotype and gender in FMD in a large meta-analysis of published and unpublished individual patient cases. An electronic search of PubMed was conducted for studies from 1968 to 2019 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Individual patient data were collected through a research network. We described the distribution of age of onset and how this varied by gender and motor phenotype. A one-stage meta-analysis was performed using multilevel mixed-effects linear regression, including random intercepts for country and data source. A total of 4905 individual cases were analysed (72.6% woman). The mean age at onset was 39.6 years (SD 16.1). Women had a significantly earlier age of onset than men (39.1 years vs 41.0 years). Mixed FMD (23.1%), tremor (21.6%) and weakness (18.1%) were the most common phenotypes. Compared with tremor (40.7 years), the mean ages at onset of dystonia (34.5 years) and weakness (36.4 years) were significantly younger, while gait disorders (43.2 years) had a significantly later age at onset. The interaction between gender and phenotype was not significant. FMD peaks in midlife with varying effects of gender on age at onset and phenotype. The data gives some support to ‘lumping’ FMD as a unitary disorder but also highlights the value in ‘splitting’ into individual phenotypes where relevant.

    • functional neurological disorder
    • meta-analysis
    • systematic reviews

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • Twitter @sarahlidstone, @ercolitommaso, @jonstoneneuro

    • Correction notice This article has been corrected since it first published. Affiliations have been added to the Collaborator section.

    • Collaborators The FMD GAP Study Group includes the following authors: Omar Ahmad, Royal North Shore Hospital, Sydney, Australia; Sepideh Akbaripanahi. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA; Alberto Albanese, Department of Neurology, IRCCS Humanitas Research Hospital, Rozzano Milano, Italy; Selma Aybek, University Hospital Inselspital, Bern University, Bern, Switzerland; José Fidel Baizabal-Carvallo, Department of Sciences and Engineering, University of Guanajuato, Leon, Mexico; Peter J. Beek, Department of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Kailash P. Bhatia, FRCP University College London, Institute of Neurology, Department of Clinical and Movement Neuroscience, Queen Square, London, UK; Verónica Cabreira, Department of Neurology, Centro Hospitalar Universitário de São João and Faculty of Medicine University of Porto, Porto, Portugal; Alan J Carson, Center for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Anna Castagna, IRCCS Fondazione Don Carlo Gnocchi Onlus, Milano, Italy; Russell C. Dale, Kids Neuroscience Centre, University of Sydney, Sydney, Australia; Carlo Dallocchio, Neurology Unit, Department of Medical Area, Pavia, Italy; Giovanni Defazio, Department of Medical Sciences and Public Health, University of Cagliari, Italy; Bertrand Degos, Department of Neurology, Avicenne University Hospital, Sorbonne Paris Nord University, Bobigny, France; Benedetta Demartini, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy; Günther Deuschl, Department of Neurology, Christian-Albrechts University, Kiel, Germany; Galina Diukova, Loginov Moscow Clinical Scientific Center, Moscow, Russia; Kevin R. Duque, Department of Neurology and Rehabilitation Medicine, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA; Mark J Edwards, Neuroscience Research Centre, St George's University of London, Cranmer Terrace, London, UK; Steven A. Epstein, Georgetown University School of Medicine and MedStar Health, Washington DC, USA; Alberto J. Espay, Department of Neurology and Rehabilitation Medicine, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA; Stewart A Factor, Jean and Paul Amos Parkinson's Disease and Movement Disorders Program, Emory University, Atlanta, Georgia, USA; Beatrice Garcin, Department of Neurology, Avicenne University Hospital, Sorbonne Paris Nord University, Bobigny, France; Christian Geroin, Neurology Unit, Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; Muriel Hagenaars, Utrecht University, Utrecht, The Netherlands; Mark Hallett, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA; Thomas Hassa, Lurija Institute for Rehabilitation and Health Sciences, Allensbach, Germany; Anhar Hassan, Mayo Clinic, Rochester, Minnesota, USA; Lorena D. Herbert, University of Texas Southwestern, Dallas, Texas, USA; Samantha K. Holden, University of Colorado Anschutz Medical Campus, Denver, Colorado, USA; Joseph Jankovic, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas, USA; Richard A. Kanaan, Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; C.A. (Lianne) Kempe, Department of Mood Disorders, PsyQ, Parnassia Groep, The Hague, The Netherlands; Maja Kojovic, Department of Neurology, University Clinical Centre Ljubljana, Slovenia; Katie Kompoliti, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA; Vladimir S. Kostić, School of Medicine, University of Belgrade, Belgrade, Serbia; Kevin Kyle, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Kathrin LaFaver, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Anthony E. Lang, Edmond J. Safra Program in Parkinson's Disease, the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital and the Division of Neurology, University of Toronto Lindsey MacGillivray PhD, MD Department of Psychiatry, University Health Network, University of Toronto, Canada; Davide Martino, Department of Clinical Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, Canada; João Massano, Department of Neurology, Centro Hospitalar Universitário de São João and Faculty of Medicine University of Porto, Porto, Portugal; Carine W. Maurer, Stony Brook University School of Medicine, Stony Brook, New York, USA; Laura McWhirter, Centre for Clinical Brain Sciences, University of Edinburgh, Edinbugh, UK; Raja Mehanna, University of Texas Health Science Center at Houston and McGovern Medical School, Houston, Texas, USA; Francine Mesrati, Neurophysiology Department, Hospital Pitié Salpêtrière, AP-HP, Paris, France; John C. Morris, Washington University School of Medicine, St. Louis, Missouri, USA; Glenn Nielsen, Neuroscience Research Centre, Institute of Molecular and Clinical Sciences, St Georges University of London, London, UK; Anastasia Obukhova, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Sanjay Pandey, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, JLN Marg, New Delhi, India; David L. Perez, Departments of Neurology and Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Igor Petrović, Medical Faculty, University of Belgrade, Serbia; Seth L. Pullman, Columbia University Irving Medical Center, New York, New York, USA; Angelo Quartarone, Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy; Karin Roelofs, Radboud University, Behavioural Science Institute and Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Anette Schrag, Queen Square Institute of Neurology, University College London, London, UK; Yury Seliverstov, Research Center of Neurology, Moscow, Russia; Tereza Serranová, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic; Ulf Søgaard, Psychiatric Research Unit, Slagelse, Denmark; Petr Sojka, Department of Psychiatry, Faculty of Medicine, Masaryk University Brno and University Hospital Brno, Brno, Czech Republic; Maria Stamelou, Parkinson’s Disease and Movement Disorders Department, Hygeia Hospital, Athens, Greece. European University of Cyprus, Nicosia, Cyprus. Philipps University, Marburg, Germany; Christopher D. Stephen, Movement Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; John F. Stins, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Michele Tinazzi, Department of Neurosciences, Biomedicine and Movement, University of Verona, Verona, Italy; Aleksandra Tomić, Neurology Clinic, Clinical Center of Serbia, and Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Anabela Valadas, Serviço de Neurologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal; Valerie Voon, Department of Psychiatry, University of Cambridge, Cambridge, UK; Jeff L. Waugh, University of Texas Southwestern, Dallas, Texas, USA; Allan D Wu, University of California Los Angeles, Los Angeles, California, USA.

    • Contributors SL—guarantor of overall content, conceptualisation, data curation, methodology, project administration, supervision, data validation, writing (original draft, review and editing). MC-P—data curation, project administration, data validation, writing (original draft, review and editing). TE—data curation, project administration, writing (original draft, review and editing). EJR—formal analysis, writing (original draft, review and editing). JS—conceptualisation, methodology, supervision, data validation, writing (original draft, review and editing). FMD-GAP Study Group—data sharing, feedback on initial manuscript, editorial, critical appraisal.

    • Funding SL and MC-P were supported by an anonymous donation to the Toronto Western Hospital Movement Disorders Clinic. JS was supported by an NHS Scotland NRS Career Fellowship.

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    • Competing interests JS reports royalties from UpToDate for articles on FND and runs a free self-help website for people with FND. He carries out independent expert medicolegal work including in relation to FND. He is secretary of the FND society and on the medical advisory board for FND Hope and FND Action.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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