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Publications

Journal Article Ahead of print

PubMed: 42831418 DOI: 10.1002/mdc3.70808

Defining the Clinical Phenotypic Ground Truth: Expert Interrater Agreement in Hyperkinetic Movement Disorders.

Mov Disord Clin Pract

Authors: Madelein van der Stouwe, Olof Vermeulen, Wieke Eggink, Tove Henriksen, Eavan McGovern, Marenka Smit, Selma Aybek, Agnita Boon, Rick Brandsma, Andres Deik, Roberto Erro, Alberto Espay, Cristian Falup-Pecurariu, Stephen Frucht, Christos Ganos, Emilia Gatto, Rick Helmich, Christine Klein, Hans Koelman, Vincent Odekerken, Lisette Koens, Abhimanyu Mahajan, Francesca Morgante, Alexander Münchau, Pattamon Panyakaew, Kathryn Peall, Bélen Pérez-Dueñas, Emanuel Roze, Anna Sadnicka, Susanne Schneider, Petra Schwingenschuh, Tereza Serranova, Matej Skorvanek, Maria Stamelou, Gertrúd Tamas, Michele Tinazzi, Anna Valadas, Wim Vandenberghe, Jeroen de Vries, Rodi Zutt, Sterre van der Veen, Rogier Luiken, Inge Tuitert, Marina Tijssen

Affiliations

  • Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Department of Neurology, Ommelander Ziekenhuis Groningen, Scheemda, the Netherlands.
  • Movement Disorder Clinic, University Hospital of Bispebjerg, Copenhagen, Denmark.
  • Department of Neurology, Beaumont Hospital, Dublin, Ireland.
  • School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Department of Neurology, Medical Clinic Velsen, Velsen-Noord, the Netherlands.
  • Department of Neurology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
  • Psychosomatic Medicine Unit, Department of Neurology, Inselspital Bern University Hospital, University of Bern, Bern, Switzerland.
  • Department of Neurology, Erasmus MC Rotterdam, Rotterdam, the Netherlands.
  • Department of Pediatric Neurology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Parkinson's Disease and Movement Disorders Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana," University of Salerno, Fisciano, Italy.
  • James J. and Joan A. Gardner Family Center For Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA.
  • Faculty of Medicine, Transilvania University, Brasov, Romania.
  • Department of Neurology, County Clinic Hospital, Brasov, Romania.
  • NYU Grossman School of Medicine, New York, New York, USA.
  • Division of Neurology, Department of Medicine, Movement Disorders Clinic, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada.
  • Krembil Brain Institute, Toronto, Ontario, Canada.
  • Department of Clinical Medicine, Sanatorio de la Trinidad Mitre, Affiliated to the Faculty of Medicine of the University of Buenos Aires, Buenos Aires, Argentina.
  • Parkinson's and Movement Disorders Section of the Institute of Neurosciences Buenos Aires, Buenors Aires, Argentina.
  • Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands.
  • Department of Neurology, Center of Expertise for Parkinson and Movement Disorders, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands.
  • Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
  • Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.
  • Department of Neurology and Clinical Neurophysiology, Martini Ziekenhuis, Groningen, the Netherlands.
  • Neurosciences and Cell Biology Institute, Neuromodulation and Motor Control Section, City St George's University of London, London, UK.
  • Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany.
  • Chulalongkorn Centre of Excellence for Parkinson's Disease and Related Disorders, Division of Neurology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital and Chulalongkorn University, Thai Red Cross Society, Bangkok, Thailand.
  • Laboratories of Neuroscience Research, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
  • Neuroscience and Mental Health Innovation Institute, Cardiff University, Cardiff, UK.
  • Innovative Therapies in Pediatric Neurology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
  • Department of Pediatrics, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Sorbonne University, INSERM, CNRS, Paris Brain Institute, AP-HP, Institute of Neurology, Paris, France.
  • Gatsby Computational Neuroscience Unit, University College London, London, UK.
  • Department of Clinical and Movement Neurosciences, University College London, London, UK.
  • National Hospital for Neurology and Neurosurgery, London, UK.
  • INSPIRE-PNRM+, Neuroimaging Center (NIC), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Department of Neurology, Medical University of Graz, Graz, Austria.
  • Department of Neurology, 1st Faculty of Medicine and General University Hospital in Prague, Charles University, Prague, Czech Republic.
  • Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic.
  • Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic.
  • Parkinson's Disease and Movement Disorders Department, HYGEIA, Athens, Greece.
  • Department of Neurology, Semmelweis University, Budapest, Hungary.
  • Biomedicine and Movement Sciences, Neurology Unit, Department of Neurosciences, University of Verona, Verona, Italy.
  • Department of Neurosciences and Mental Health, Neurology Hospital Santa Maria, CHLUN, Lisbon, Portugal.
  • Faculty of Medicine, Instituto de Medicina Molecular João Lobo Antunes, University of Lisbon, Lisbon, Portugal.
  • Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
  • Department of Neurosciences, KU Leuven, Leuven, Belgium.
  • Department of Neurology, HagaZiekenhuis, The Hague, the Netherlands.
  • Department of Rehabilitation Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Abstract

BACKGROUND

Reliable clinical phenotyping is crucial for diagnosis, treatment, and research in hyperkinetic movement disorders, yet its interrater reliability remains uncertain.

OBJECTIVES

To quantify interrater agreement in clinical phenotyping of hyperkinetic movement disorders among experts in a large, phenotypically diverse cohort.

METHODS

Within the NEMO project, 161 patients with hyperkinetic movement disorders underwent standardized video assessments. Each patient was independently classified by three international movement disorders experts in a structured, stepwise procedure. Experts first assessed videos alone, then received clinical history and examination, and finally diagnostic test results. At each step, they assigned primary and secondary phenotypes and rated their diagnostic confidence. Interrater agreement was assessed using Fleiss' and Cohen's kappa.

RESULTS

Across all phenotypes, interrater agreement on the primary phenotype increased with added information (κ = 0.457 to κ = 0.607). Agreement with the NEMO reference classification similarly improved (κ = 0.478 to κ = 0.656). Among patients with a single dominant phenotype, agreement reached κ = 0.78. In 93% of cases, at least two out of three experts reached consensus. Agreement was substantially lower in patients with mixed or complex presentations, such as myoclonus-dystonia and functional movement disorders. Diagnostic certainty rose throughout, though secondary phenotype agreement remained poor. Experts rarely revised initial impressions, suggesting robust pattern recognition but also potential confirmation bias.

CONCLUSIONS

Movement disorders specialists can reliably identify hyperkinetic phenotypes, even without in-person assessment. While complex, mixed and functional presentations remain diagnostically challenging, our findings reinforce the value of expert phenotyping in clinical care, training, and research, and provide a benchmark for future studies and computational approaches.

MeSH

Myoclonus, Tremor, Conversion Disorder, Phenotype, Dystonia, Movement Disorders, Research, Movement, Hyperkinesis