Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease.
Gian Pal,Deborah A. Hall,Bichun Ouyang,J. Phelps,Roy N. Alcalay,Michael W. Pauciulo,William C. Nichols,Lorraine N. Clark,Helen Mejia-Santana,Lucia M. Blasucci,Christopher G. Goetz,Cynthia L. Comella,Amy Colcher,Ziv Gan-Or,Ziv Gan-Or,Guy A. Rouleau,Guy A. Rouleau,Karen Marder +17 more
TLDR
In a cohort of patients with young‐onset Parkinson's disease, the authors assessed the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs.Abstract:
Objective
In a cohort of patients with young-onset Parkinson's disease (PD), the authors assessed (1) the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs and (2) specific genetic and clinical predictors of DBS enrollment.
Methods
Subjects were participants from 3 sites (Columbia University, Rush University, and the University of Pennsylvania) in the Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The analyses presented here focus on glucocerebrosidase (GBA), leucine-rich repeat kinase 2 (LRRK2), and parkin (PRKN) mutation carriers. Mutation carrier status, demographic data, and disease characteristics in individuals who did and did not enroll in DBS were analyzed. The association between mutation status and DBS placement was assessed in logistic regression models.
Results
Patients who had PD with either GBA, LRRK2, or PRKN mutations were more common in the DBS group (n = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively; P = 0.02). In a multivariate logistic regression model, GBA mutation status (odds ratio, 2.1; 95% confidence interval, 1.0–4.3; P = 0.05) was associated with DBS surgery enrollment. However, when dyskinesia was included in the multivariate logistic regression model, dyskinesia had a strong association with DBS placement (odds ratio, 3.8; 95% confidence interval, 1.9–7.3; P < 0.0001), whereas the association between GBA mutation status and DBS placement did not persist (P = 0.25).
Conclusions
DBS populations are enriched with genetic mutation carriers. The effect of genetic mutation carriers on DBS outcomes warrants further exploration.read more
Citations
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Journal ArticleDOI
GBA-Associated Parkinson's Disease and Other Synucleinopathies.
TL;DR: The structure and function of GBA is described, recent literature on the clinical phenotype of G BA PD is reviewed, and future directions for research, counseling, and treatment are suggested.
Journal ArticleDOI
Association of Subthalamic Deep Brain Stimulation With Motor, Functional, and Pharmacologic Outcomes in Patients With Monogenic Parkinson Disease: A Systematic Review and Meta-analysis
Carlo Alberto Artusi,Alok Dwivedi,Alberto Romagnolo,Gian Pal,Marcelo Andrés Kauffman,Ignacio F. Mata,Dhiren Patel,Joaquin A. Vizcarra,Andrew P. Duker,Luca Marsili,Binith Cheeran,Daniel Woo,Maria Fiorella Contarino,Leonard Verhagen,Leonardo Lopiano,Alberto J. Espay,Alfonso Fasano,Alfonso Fasano,Aristide Merola +18 more
TL;DR: Genetic screening for LRRK2, GBA, and PRKN mutations in patients with Parkinson disease who are candidates for subthalamic deep brain stimulation may serve to inform outcomes.
Journal ArticleDOI
Juvenile parkinsonism: Differential diagnosis, genetics, and treatment
Nicki Niemann,Joseph Jankovic +1 more
TL;DR: Although the mainstay of treatment remains levodopa, other symptomatic therapies such as botulinum toxin for focal dystonia, supportive medical therapies, and deep brain stimulation in select cases, may also be used to provide the most optimal long-term outcomes.
Book ChapterDOI
Clinical Features of LRRK2 Carriers with Parkinson's Disease.
Meir Kestenbaum,Roy N. Alcalay +1 more
TL;DR: The demographics and motor and non-motor symptoms of LRRK2 carriers with PD, as well as symptoms in non-manifesting carriers are summarized, and more sensitive biomarkers to identify mutation carriers at risk of developing PD are required.
Journal ArticleDOI
Motor complications in Parkinson's disease: 13‐year follow‐up of the CamPaIGN cohort
Han-Joon Kim,Sarah L Mason,Thomas Foltynie,Sophie Winder-Rhodes,Roger A. Barker,Caroline H. Williams-Gray +5 more
TL;DR: Long‐term population‐representative data on motor fluctuations and levodopa‐induced dyskinesias in Parkinson's disease is lacking.
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W. M. M. Schuepbach,Jörn Rau,Karina Knudsen,Jens Volkmann,Paul Krack,Lars Timmermann,Thomas D. Hälbig,Helke Hesekamp,S. M. Navarro,Niklaus Meier,Daniela Falk,Maximilian Mehdorn,S. Paschen,Mohammad Maarouf,Michael T. Barbe,Gereon R. Fink,Andreas Kupsch,Doreen Gruber,G.-H. Schneider,Eric Seigneuret,Andrea Kistner,Patrick Chaynes,Fabienne Ory-Magne,C. Brefel Courbon,Jan Vesper,Alfons Schnitzler,Lars Wojtecki,Jean-Luc Houeto,Benoit Bataille,David Maltête,P. Damier,Sylvie Raoul,F. Sixel-Doering,D. Hellwig,Alireza Gharabaghi,Rejko Krüger,M. O. Pinsker,Florian Amtage,J. Regis,Tatiana Witjas,Stéphane Thobois,Patrick Mertens,Manja Kloss,Andreas Hartmann,Wolfgang H. Oertel,Bart Post,Hans Speelman,Yves Agid,Carmen Schade-Brittinger,Günther Deuschl +49 more
TL;DR: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications and time with good mobility and no dyskinesia.
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