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Defining the Riddle in Order to Solve It: There Is More Than One "Parkinson's Disease"

Lookup NU author(s): Professor Tiago OuteiroORCiD, Professor Johannes Attems, Professor Ian McKeith



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Background: More 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. Objective: This 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. Conclusion: Accuracy 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.

Publication metadata

Author(s): Outeiro TF, Alcalay RN, Antonini A, Attems J, Bonifati V, Cardoso F, Chesselet M-F, Hardy J, Madeo G, McKeith I, Mollenhauer B, Moore DJ, Rascol O, Schlossmacher MG, Soreq H, Stefanis L, Ferreira JJ

Publication type: Review

Publication status: Published

Journal: Movement Disorders

Year: 2023

Volume: 38

Issue: 7

Pages: 1127-1142

Print publication date: 01/07/2023

Online publication date: 08/05/2023

Acceptance date: 05/04/2023

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley and Sons Inc


DOI: 10.1002/mds.29419