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Defining the Riddle in Order to Solve It: There Is More Than One “Parkinson's Disease” |
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| Authors: | Tiago F Outeiro PhD Roy N Alcalay MD Angelo Antonini MD Johannes Attems MD Vincenzo Bonifati MD Francisco Cardoso MD Marie-Françoise Chesselet PhD John Hardy PhD Graziella Madeo MD Ian McKeith MD Brit Mollenhauer MD Darren J Moore PhD Olivier Rascol MD Michael G Schlossmacher MD Hermona Soreq PhD Leonidas Stefanis MD Joaquim J Ferreira MD |
| Institution: | 1. Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany;2. Neurological Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel;3. Department of Neurosciences (DNS), Padova University, Padova, Italy;4. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, United Kingdom;5. Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;6. Movement Disorders Unit, Neurology Service, Internal Medicine Department, The Federal University of Minas Gerais, Belo Horizonte, Brazil;7. Department of Neurology, University of California Los Angeles, Los Angeles, California, USA;8. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United Kingdom
UK Dementia Research Institute at UCL and Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, United Kingdom Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, United Kingdom UCL Movement Disorders Centre, University College London, London, United Kingdom Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong, China;9. Brain and Care Research Foundation, Rimini, Italy;10. Department of Neurology, University Medical Center, Göttingen, Germany;11. Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, Michigan, USA;12. Department of Neurosciences, Clinical Investigation Center CIC 1436, Parkinson Toulouse Expert Centre, NS-Park/FCRIN Network and Neuro Toul COEN Centre, Toulouse University Hospital, INSERM, University of Toulouse 3, Toulouse, France;13. Program in Neuroscience and Division of Neurology, The Ottawa Hospital, Ottawa, Ontario, Canada University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada;14. The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem, Israel;15. First Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece;16. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal |
| Abstract: | BackgroundMore than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central nervous system such as dementia, motor neuron disease, multiple sclerosis, and epilepsy. Clinicians, pathologists, and basic science researchers evolved arrange of concepts andcriteria for the clinical, genetic, mechanistic, and neuropathological characterization of what, in their best judgment, constitutes PD. However, these specialists have generated and used criteria that are not necessarily aligned between their different operational definitions, which may hinder progress in solving the riddle of the distinct forms of PD and ultimately how to treat them.ObjectiveThis task force has identified current in consistencies between the definitions of PD and its diverse variants in different domains: clinical criteria, neuropathological classification, genetic subtyping, biomarker signatures, and mechanisms of disease. This initial effort for “defining the riddle” will lay the foundation for future attempts to better define the range of PD and its variants, as has been done and implemented for other heterogeneous neurological syndromes, such as stroke and peripheral neuropathy. We strongly advocate for a more systematic and evidence-based integration of our diverse disciplines by looking at well-defined variants of the syndrome of PD.ConclusionAccuracy in defining endophenotypes of “typical PD” across these different but interrelated disciplines will enable better definition of variants and their stratification in therapeutic trials, a prerequisite for breakthroughs in the era of precision medicine. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. |
| Keywords: | Parkinson's disease neurodegeneration diagnostic criteria neuropathology biological definition biomarker Lewy body |