Dimitra Papadimitriou1,2, Roubina Antonelou3, Michael Miligkos4, Matina Maniati2, Nikolaos Papagiannakis2,3, Sevasti Bostantjopoulou5, Athannassios Leonardos3, Christos Koros3, Athina Simitsi3, Sokratis G Papageorgiou3, Elisabeth Kapaki6, Roy N Alcalay7, Alexandros Papadimitriou1, Aglaia Athanassiadou8, Maria Stamelou3,9,10, Leonidas Stefanis2,3. 1. Henry Dunant Hospital Center, Athens, Greece. 2. Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece. 3. Second Department of Neurology, "Attikon" University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 4. Laboratory of Biomathematics, School of Medicine University of Thessaly, Larissa, Greece. 5. Third University Department of Neurology of the Aristotle University of Thessaloniki, Greece. 6. First Department of Neurology, "Eginition" University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 7. Columbia University Medical Center, New York, New York, USA. 8. Department of General Biology, Medical Faculty, University of Patras, Rio, Greece. 9. Neurology Clinic, Philipps University, Marburg, Germany. 10. Movement Disorders Department, Hygeia Hospital, Athens, Greece.
Abstract
BACKGROUND: G209A SNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209A SNCA mutation carriers. METHODS: Longitudinal clinical assessments over 2 years were collected in 22 symptomatic and 8 asymptomatic G209A SNCA mutation carriers. Motor and nonmotor rating scales were administered. Correlations were performed between clinical variables and disease duration or age. Penetrance was calculated using Kaplan-Meier survival curves. RESULTS: Asymptomatic carriers did not manifest clear premotor symptoms, but symptomatic carriers often reported that olfactory dysfunction and rapid eye movement sleep behavior disorder preceded motor symptoms. Prominent motor decline and deterioration of autonomic and cognitive function occurred at follow-up; such nonmotor features correlated with disease duration, but not age. Disease penetrance was estimated at around 90%. CONCLUSIONS: This study may help to inform clinical trials and provide the basis for studies of disease modifiers in genetic synucleinopathy cohorts.
BACKGROUND:G209ASNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209ASNCA mutation carriers. METHODS: Longitudinal clinical assessments over 2 years were collected in 22 symptomatic and 8 asymptomatic G209ASNCA mutation carriers. Motor and nonmotor rating scales were administered. Correlations were performed between clinical variables and disease duration or age. Penetrance was calculated using Kaplan-Meier survival curves. RESULTS: Asymptomatic carriers did not manifest clear premotor symptoms, but symptomatic carriers often reported that olfactory dysfunction and rapid eye movement sleep behavior disorder preceded motor symptoms. Prominent motor decline and deterioration of autonomic and cognitive function occurred at follow-up; such nonmotor features correlated with disease duration, but not age. Disease penetrance was estimated at around 90%. CONCLUSIONS: This study may help to inform clinical trials and provide the basis for studies of disease modifiers in genetic synucleinopathy cohorts.
Authors: J A Obeso; M Stamelou; C G Goetz; W Poewe; A E Lang; D Weintraub; D Burn; G M Halliday; E Bezard; S Przedborski; S Lehericy; D J Brooks; J C Rothwell; M Hallett; M R DeLong; C Marras; C M Tanner; G W Ross; J W Langston; C Klein; V Bonifati; J Jankovic; A M Lozano; G Deuschl; H Bergman; E Tolosa; M Rodriguez-Violante; S Fahn; R B Postuma; D Berg; K Marek; D G Standaert; D J Surmeier; C W Olanow; J H Kordower; P Calabresi; A H V Schapira; A J Stoessl Journal: Mov Disord Date: 2017-09 Impact factor: 10.338
Authors: Cornelis Blauwendraat; Demis A Kia; Lasse Pihlstrøm; Ziv Gan-Or; Suzanne Lesage; J Raphael Gibbs; Jinhui Ding; Roy N Alcalay; Sharon Hassin-Baer; Alan M Pittman; Janet Brooks; Connor Edsall; Sun Ju Chung; Stefano Goldwurm; Mathias Toft; Claudia Schulte; Dena Hernandez; Andrew B Singleton; Mike A Nalls; Alexis Brice; Sonja W Scholz; Nicholas W Wood Journal: Neurobiol Aging Date: 2017-12-20 Impact factor: 4.673
Authors: Megan C Bakeberg; Anastazja M Gorecki; Abigail L Pfaff; Madison E Hoes; Sulev Kõks; P Anthony Akkari; Frank L Mastaglia; Ryan S Anderton Journal: NPJ Parkinsons Dis Date: 2021-07-07
Authors: Luis M A Oliveira; Thomas Gasser; Robert Edwards; Markus Zweckstetter; Ronald Melki; Leonidas Stefanis; Hilal A Lashuel; David Sulzer; Kostas Vekrellis; Glenda M Halliday; Julianna J Tomlinson; Michael Schlossmacher; Poul Henning Jensen; Julia Schulze-Hentrich; Olaf Riess; Warren D Hirst; Omar El-Agnaf; Brit Mollenhauer; Peter Lansbury; Tiago F Outeiro Journal: NPJ Parkinsons Dis Date: 2021-07-26