Winfried Ilg1,2, Zofia Fleszar1,2, Cornelia Schatton1,2, Holger Hengel3,4, Florian Harmuth5, Peter Bauer5, Dagmar Timmann6, Martin Giese1,2, Ludger Schöls3,4, Matthis Synofzik3,4. 1. Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research, Tübingen, Germany. 2. Centre for Integrative Neuroscience (CIN), Tübingen, Germany. 3. Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and Centre of Neurology, Tübingen, Germany. 4. German Research Center for Neurodegenerative Diseases, University of Tübingen, Germany. 5. Department of Medical Genetics, University of Tübingen, Tübingen, Germany. 6. Department of Neurology, University of Duisburg-Essen, Germany.
Abstract
BACKGROUND: Movement changes in autosomal-dominant spinocerebellar ataxias are suggested to occur many years before clinical manifestation. Detecting and quantifying these changes in the preclinical phase offers a window for future treatment interventions and allows the clinician to decipher the earliest dysfunctions starting the evolution of spinocerebellar ataxia. We hypothesized that quantitative movement analysis of complex stance and gait tasks allows to (i) reveal movement changes already at early stages of the preclinical phase when clinical ataxia signs are still absent and to (ii) quantify motor progression in this phase. METHODS: A total of 46 participants (14 preclinical spinocerebellar ataxia mutation carriers [spinocerebellar ataxias 1,2,3,6], 9 spinocerebellar ataxia patients at an early stage; 23 healthy controls) were assessed by quantitative movement analyses of increasingly complex stance and walking tasks in a cross-sectional design. RESULTS: Body sway in stance and spatiotemporal variability in tandem walking differentiated between preclinical mutation carriers and healthy controls (P < .01). Complex movement conditions allowed one to discriminate even those mutation carriers without any clinical signs in posture and gait (SARAposture&gait = 0; P < .04). Multivariate regression analysis categorized preclinical mutation carriers on a single-subject level with 100% accuracy within a range of 10 years to the estimated onset. Movement features in stance and gait correlated significantly with genetically estimated time to onset, indicating a gradual increase of motor changes with increasing proximity to disease manifestation. CONCLUSION: Our results provide evidence for subclinical motor changes in spinocerebellar ataxia, which allow to discriminate patients without clinical signs even on a single-subject basis and may help capture disease progression in the preclinical phase.
BACKGROUND: Movement changes in autosomal-dominant spinocerebellar ataxias are suggested to occur many years before clinical manifestation. Detecting and quantifying these changes in the preclinical phase offers a window for future treatment interventions and allows the clinician to decipher the earliest dysfunctions starting the evolution of spinocerebellar ataxia. We hypothesized that quantitative movement analysis of complex stance and gait tasks allows to (i) reveal movement changes already at early stages of the preclinical phase when clinical ataxia signs are still absent and to (ii) quantify motor progression in this phase. METHODS: A total of 46 participants (14 preclinical spinocerebellar ataxia mutation carriers [spinocerebellar ataxias 1,2,3,6], 9 spinocerebellar ataxiapatients at an early stage; 23 healthy controls) were assessed by quantitative movement analyses of increasingly complex stance and walking tasks in a cross-sectional design. RESULTS: Body sway in stance and spatiotemporal variability in tandem walking differentiated between preclinical mutation carriers and healthy controls (P < .01). Complex movement conditions allowed one to discriminate even those mutation carriers without any clinical signs in posture and gait (SARAposture&gait = 0; P < .04). Multivariate regression analysis categorized preclinical mutation carriers on a single-subject level with 100% accuracy within a range of 10 years to the estimated onset. Movement features in stance and gait correlated significantly with genetically estimated time to onset, indicating a gradual increase of motor changes with increasing proximity to disease manifestation. CONCLUSION: Our results provide evidence for subclinical motor changes in spinocerebellar ataxia, which allow to discriminate patients without clinical signs even on a single-subject basis and may help capture disease progression in the preclinical phase.
Authors: W Ilg; M Branscheidt; A Butala; P Celnik; L de Paola; F B Horak; L Schöls; H A G Teive; A P Vogel; D S Zee; D Timmann Journal: Cerebellum Date: 2018-10 Impact factor: 3.847
Authors: Pierre Cabaraux; Sunil K Agrawal; Huaying Cai; Rocco Salvatore Calabro; Carlo Casali; Loic Damm; Sarah Doss; Christophe Habas; Anja K E Horn; Winfried Ilg; Elan D Louis; Hiroshi Mitoma; Vito Monaco; Maria Petracca; Alberto Ranavolo; Ashwini K Rao; Serena Ruggieri; Tommaso Schirinzi; Mariano Serrao; Susanna Summa; Michael Strupp; Olivia Surgent; Matthis Synofzik; Shuai Tao; Hiroo Terasi; Diego Torres-Russotto; Brittany Travers; Jaimie A Roper; Mario Manto Journal: Cerebellum Date: 2022-04-12 Impact factor: 3.847