Connie Marras1, Roy N Alcalay2, Chelsea Caspell-Garcia3, Christopher Coffey3, Piu Chan4, John E Duda5, Maurizio F Facheris6, Rubén Fernández-Santiago7, Javier Ruíz-Martínez8, Tiago Mestre1,9, Rachel Saunders-Pullman10, Claustre Pont-Sunyer11, Eduardo Tolosa11, Bjorg Waro12. 1. Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada. 2. Department of Neurology, Columbia University Medical Center, New York, New York, USA. 3. Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA. 4. Departments of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, China. 5. Parkinson's Disease Research, Education and Clinical Center, Michael J. Crescenz VA Medical Center and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 6. The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA. 7. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain. 8. Department of Neurology (Movement Disorders Unit), Hospital Universitario Donostia. Biodonostia Research Institute, Neurosciences area. San Sebastián, Guipúzcoa, Spain, and CIBERNED, Carlos III Health Institute, Madrid, Spain. 9. Parkinson's Disease and Movement Disorder Centre, Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. 10. Department of Neurology, Mount Sinai Beth Israel Medical Center and Icahn School of Medicine at Mount Sinai, New York, New York, USA. 11. Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institutd'InvestigacionsBiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. 12. Department of Neurology, Norwegian University of Science and Technology, Trondheim, Norway.
Abstract
BACKGROUND: Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD. METHODS: Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD. RESULTS: Five hundred sixteen PD patients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PD patients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PD patients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PD patients. LRRK2 G2019S PD patients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PD patients in adjusted analyses. CONCLUSIONS: G2385R and G2019S PD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019S PD or idiopathic PD.
BACKGROUND:Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD. METHODS: Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD. RESULTS: Five hundred sixteen PDpatients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PDpatients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PDpatients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PDpatients. LRRK2G2019SPDpatients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PDpatients in adjusted analyses. CONCLUSIONS:G2385R and G2019SPD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019SPD or idiopathic PD.
Authors: Rachel Saunders-Pullman; Anat Mirelman; Roy N Alcalay; Cuiling Wang; Roberto A Ortega; Deborah Raymond; Helen Mejia-Santana; Martha Orbe-Reilly; Brooke A Johannes; Avner Thaler; Laurie Ozelius; Avi Orr-Urtreger; Karen S Marder; Nir Giladi; Susan B Bressman Journal: JAMA Neurol Date: 2018-03-01 Impact factor: 18.302
Authors: Shu-Ying Liu; Daryl J Wile; Jessie Fanglu Fu; Jason Valerio; Elham Shahinfard; Siobhan McCormick; Rostom Mabrouk; Nasim Vafai; Jess McKenzie; Nicole Neilson; Alexandra Perez-Soriano; Julieta E Arena; Mariya Cherkasova; Piu Chan; Jing Zhang; Cyrus P Zabetian; Jan O Aasly; Zbigniew K Wszolek; Martin J McKeown; Michael J Adam; Thomas J Ruth; Michael Schulzer; Vesna Sossi; A Jon Stoessl Journal: Lancet Neurol Date: 2018-02-16 Impact factor: 44.182