Abstract
Objective
We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson’s disease (PD).
Methods
Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD.
Results
At onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old).
Conclusions
Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.
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Acknowledgements
Authors acknowledge the contribution of the “Fondazione Grigioni per il Morbo di Parkinson”, Milan, Italy.
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AM: study concept and design, analysis and interpretation of data, drafting/revising the manuscript for content. AR: study concept and design, acquisition and interpretation of data, drafting/revising the manuscript for content. AKD: analysis and interpretation of data, drafting/revising the manuscript for content. AP: interpretation of data, revising the manuscript for content. DB: interpretation of data, revising the manuscript for content. PJG-R: acquisition of data, revising the manuscript for content. MF: acquisition of data, revising the manuscript for content. CAA: acquisition of data, revising the manuscript for content. MZ: acquisition of data, revising the manuscript for content. LL: interpretation of data, revising the manuscript for content. AP: acquisition of data, revising the manuscript for content. SB: acquisition of data, revising the manuscript for content. FM: interpretation of data, revising the manuscript for content. KZ: acquisition of data, revising the manuscript for content. CG: acquisition of data, revising the manuscript for content. ES: interpretation of data, revising the manuscript for content. FR-P: acquisition of data, revising the manuscript for content. MK: interpretation of data, revising the manuscript for content. PT: acquisition of data, revising the manuscript for content. LMO: acquisition of data, revising the manuscript for content. GP: acquisition of data, revising the manuscript for content. ES: acquisition of data, revising the manuscript for content. FDS: acquisition of data, revising the manuscript for content. SB: acquisition of data, revising the manuscript for content. RS: interpretation of data, revising the manuscript for content. RPM: interpretation of data, revising the manuscript for content. RC: interpretation of data, revising the manuscript for content. RC: study concept and design, interpretation of data, revising the manuscript for content. AE: study concept and design, interpretation of data, revising the manuscript for content. All the co-authors listed above gave their final approval of this manuscript version. All the co-authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Dr Merola is supported by NIH (KL2 TR001426) and has received speaker honoraria from CSL Behring, Abbvie, and Cynapsus Therapeutics. He has received grant support from Lundbeck. Dr Romagnolo has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco, Chiesi Farmaceutici, Medtronic, and UCB Pharma. Dr. Dwivedi is supported as a co-investigator by the NIH (1R01HL125016-01), (1 R21 HL143030-01) and (1R21 AI133207) grants and as a collaborator in NIH R21 AI118228 grant. He has been also serving as a statistician in CPRIT grants (PP180003, PP170068, PP170004, PP140164, 140211, PP110156, PP150031, and PP130083), CCTST K12 (consultant) award, Coldwell (co-investigator) and TMF (co-investigator). Dr. Dwivedi is a director of Biostatistics & Epidemiology Consulting Lab at the TTUHSC EP. Dr. Padovani has received grant support from Ministry of Health (MINSAL) and Ministry of Education, Research and University (MIUR), from CARIPLO Foundation; personal compensation as a consultant/scientific advisory board member for Avanir, Lundbeck, Eli-Lilly, Neuraxpharma, Biogen, GE Health. Dr. Berg reports grants from Janssen Pharmaceutica, grants from Damp foundation, grants from German Parkinson’s Disease Association (dPV), grants from BMWi, grants from BMBF, grants from Parkinson Fonds Deutschland GmbH, grants and speaker’s honoraria from and consultancies for UCB Pharma GmbH, grants from Novartis Pharma GmbH, grants and speaker’s honoraria from and consultancies for Lundbeck, speaker’s honoraria from and consultancies for BIAL, grants from the EU, speaker’s honoraria from and consultancies for Biogen, and speaker’s honoraria from AbbVie, Zambon and Desitin. Dr. Garcia-Ruiz has received research support from Allergan and UCB, personal compensation as a consultant/scientific advisory board from Italfarmaco, Britannia, Bial, Zambon, and speaker’s honoraria from Italfarmaco, UCB, Zambon, Allergan and Abbvie. Dr. Fabbri has no financial conflicts to disclose. Dr. Artusi has received travel grants from Zambon and Abbvie. Dr. Zibetti has received honoraria from Medtronic, Zambon Pharma and AbbVie. Dr. Lopiano has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma, and AbbVie. Dr. Pilotto has received speaker honoraria from BioMarin Pharmaceutical, Chiesi Pharmaceuticals, Nutricia Pharmaceuticals, UCB Pharma and Zambon Pharmaceuticals. He received grants from the Italian Ministry of Health, Zambon Italia, Vitaflo Germany. Dr. Bonacina has no financial conflicts to disclose. Dr. Morgante has received speaking honoraria from Medtronic, Zambon, Chiesi, Abbvie, Merz, Bial; personal compensation as a consultant/scientific advisory board member from Merz, Abbvie, Bial, Medtronic. Dr. Zeuner has received research support from an intramural grant from the Christian-Albrechts-University of Kiel, from the Benign Essential Blepharospasm Research Foundation and with an unrestricted grant from Ipsen. She has received lecture fees from Allergan, Merz, AbbVie and Bayer outside the submitted work. She has served as a consultant and received fees from Merz and Ipsen. Dr. Griewin has no financial conflicts to disclose. Dr. Schaeffer has received intramural research funding from the University of Kiel and speaker’s honoraria from Bayer Vital GmbH and Novartis. Dr. Rodriguez-Porcel has no financial conflicts to disclose. Dr. Kauffman is an employee of the CONICET. He has received grant support from Ministry of Science and Technology of Argentina and Ministry of Health of Buenos Aires. He has received honoraria payments for educational activities from Janssen Pharmaceuticals and Bago Pharmaceuticals. Dr. Turcano has no financial conflicts to disclose. Dr. de Oliveira has no financial conflicts to disclose. Dr. Palermo has no financial conflicts to disclose. Ms. Shanks has no financial conflicts to disclose. Dr. Del Sorbo has no financial conflicts to disclose. Dr. Bonvegna has no financial conflicts to disclose. Dr. Savica has received research support from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Mayo Clinic Small Grants Program National Center for Advancing Translational Sciences (NCATS), and unrestricted grant from ACADIA Pharmaceuticals, INC. Dr. Munhoz has no financial conflicts to disclose. Dr. Ceravolo has received fees for speech by Abbvie, General Electric, Zambon, UCB, Lusofarmaco. Dr. Cilia has has received speaking honoraria from Zambon, UCB, Bial; personal compensation as a consultant from Roche. Dr. Espay has received grant support from the NIH, Great Lakes Neurotechnologies and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, TEVA, Impax, Acadia, Acorda, Intrance, Cynapsus/Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from Abbvie, UCB, USWorldMeds, Lundbeck, Acadia, the American Academy of Neurology, and the Movement Disorders Society.
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The study received IRB/ethics committee approval at all participating centers and was conducted in accordance with the Good Clinical Practice and the International Conference on Harmonization guidelines and any applicable national and local regulations. The authors declare that they acted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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Merola, A., Romagnolo, A., Dwivedi, A.K. et al. Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications. J Neurol 267, 2949–2960 (2020). https://doi.org/10.1007/s00415-020-09954-6
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DOI: https://doi.org/10.1007/s00415-020-09954-6