@article{cd334e9ec7c54030bebb22427aa46ce6,
title = "Gait variability as digital biomarker of disease severity in Huntington{\textquoteright}s disease",
abstract = "Background: Impaired gait plays an important role for quality of life in patients with Huntington{\textquoteright}s disease (HD). Measuring objective gait parameters in HD might provide an unbiased assessment of motor deficits in order to determine potential beneficial effects of future treatments. Objective: To objectively identify characteristic features of gait in HD patients using sensor-based gait analysis. Particularly, gait parameters were correlated to the Unified Huntington{\textquoteright}s Disease Rating Scale, total motor score (TMS), and total functional capacity (TFC). Methods: Patients with manifest HD at two German sites (n = 43) were included and clinically assessed during their annual ENROLL-HD visit. In addition, patients with HD and a cohort of age- and gender-matched controls performed a defined gait test (4 × 10 m walk). Gait patterns were recorded by inertial sensors attached to both shoes. Machine learning algorithms were applied to calculate spatio-temporal gait parameters and gait variability expressed as coefficient of variance (CV). Results: Stride length (− 15%) and gait velocity (− 19%) were reduced, while stride (+ 7%) and stance time (+ 2%) were increased in patients with HD. However, parameters reflecting gait variability were substantially altered in HD patients (+ 17% stride length CV up to + 41% stride time CV with largest effect size) and showed strong correlations to TMS and TFC (0.416 ≤ rSp ≤ 0.690). Objective gait variability parameters correlated with disease stage based upon TFC. Conclusions: Sensor-based gait variability parameters were identified as clinically most relevant digital biomarker for gait impairment in HD. Altered gait variability represents characteristic irregularity of gait in HD and reflects disease severity.",
keywords = "Gait analysis, Gait variability, Huntington{\textquoteright}s disease, Regularity of gait, Wearable sensors",
author = "Heiko Ga{\ss}ner and Dennis Jensen and F. Marxreiter and Anja Kletsch and Stefan Bohlen and Robin Schubert and Muratori, {Lisa M.} and Bjoern Eskofier and Jochen Klucken and J{\"u}rgen Winkler and Ralf Reilmann and Zacharias Kohl",
note = "Funding Information: HG, BE, JK and JW received institutional research grants from the Emerging Field Initiative of the Friedrich Alexander-University Erlangen-N{\"u}rnberg (EFI Moves, 2 Med 03), from the Bavarian State Ministry for Education, Science and the Arts, Munich, Germany (MotionLab@Home, E|Home Center), and from the Bavarian Ministry of Economic Affairs and Media, Energy and Technology, Germany (Medical Valley Award 2016, Fall Risk PD). HG, FM, RR, and ZK received an institutional research grant by the Huntington-Stiftung of the Deutsche Huntington Hilfe e.V. FM is supported by the Interdisciplinary Center for Clinical Research of the FAU, Clinician Scientist programme. HG, BE, and JK are supported by Mobilise-D from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 820820. HG received support by the Medical Research Foundation at the University Hospital Erlangen outside of the submitted work. BE holds ownerships of Portabiles HealthCare Technologies GmbH and Portabiles GmbH, received compensation and honoraria from serving on scientific advisory boards for Abbvie GmbH, Adidas GmbH, Bosch Sensortec GmbH, and ST Sportservice GmbH. Further, he gratefully acknowledges the support of the German Research Foundation (DFG) within the framework of the Heisenberg professorship programme (grant number ES 434/8-1). JK holds ownerships of Portabiles HealthCare Technologies GmbH and Portabiles GmbH, received compensation and honoraria from serving on scientific advisory boards for LicherMT GmbH, Abbvie GmbH, UCB Pharma GmbH, GlaxoSmithKline GmbH & Co. KG, Athenion GmbH, and Thomashilfen GmbH; as well as lecturing from UCB Pharma GmbH, TEVA Pharma GmbH, Licher MT GmbH, Desitin GmbH, Abbvie GmbH, Solvay Pharmaceuticals, and Ever Neuro Pharma GmbH. JW reports personal fees outside of the submitted work from Desitin Arzneimittel GmbH and Biogen GmbH. ZK reports personal fees outside of the submitted work from Desitin Arzneimittel GmbH and UCB Pharma. Acknowledgements Funding Information: Open Access funding provided by Projekt DEAL. The authors would like to thank all patients that participated in this study. The present work is part of the doctoral thesis of Dennis Jensen in the frame of obtaining the degree “Dr. med.” at the University Hospital Erlangen, Friedrich-Alexander University Erlangen-N{\"u}rnberg (FAU). This study was supported by the Huntington-Stiftung of the Deutsche Huntington Hilfe e.V. We further acknowledge the Enroll-HD staff for their support and collaboration. Bjoern Eskofier gratefully acknowledges the support of the German Research Foundation (DFG) within the framework of the Heisenberg professorship programme (Grant Number ES 434/8–1). Funding Information: The study was supported and performed at the Department of Molecular Neurology (University Hospital Erlangen, Erlangen, Germany), and the George-Huntington Institute (GHI) GmbH, M{\"u}nster, Germany. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = jun,
day = "1",
doi = "10.1007/s00415-020-09725-3",
language = "English",
volume = "267",
pages = "1594--1601",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "D. Steinkopff-Verlag",
number = "6",
}