Gait variability as digital biomarker of disease severity in Huntington's disease

被引:36
作者
Gassner, Heiko [1 ]
Jensen, Dennis [1 ]
Marxreiter, F. [1 ]
Kletsch, Anja [2 ]
Bohlen, Stefan [2 ]
Schubert, Robin [2 ]
Muratori, Lisa M. [2 ,3 ]
Eskofier, Bjoern [4 ]
Klucken, Jochen [1 ,5 ,6 ]
Winkler, Juergen [1 ]
Reilmann, Ralf [2 ,7 ,8 ,9 ]
Kohl, Zacharias [1 ,10 ,11 ]
机构
[1] Friedrich Alexander Univ Erlangen Nurnberg FAU, Univ Hosp Erlangen, Dept Mol Neurol, Schwabachanlage 6, D-91054 Erlangen, Germany
[2] George Huntington Inst GHI GmbH, Munster, Germany
[3] SUNY Stony Brook, RRAMP Lab, Stony Brook, NY 11794 USA
[4] Friedrich Alexander Univ Erlangen Nurnberg FAU, Machine Learning & Data Analyt Lab, Erlangen, Germany
[5] Med Valley Digital Hlth Applicat Ctr GmbH, Bamberg, Germany
[6] Fraunhofer Inst Integrated Circuits IIS, Erlangen, Germany
[7] Univ Munster, Dept Radiol, Munster, Germany
[8] Univ Tubingen, Dept Neurodegenerat Dis, Tubingen, Germany
[9] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany
[10] Univ Hosp Erlangen, Ctr Rare Dis Erlangen, Erlangen, Germany
[11] Univ Regensburg, Dept Neurol, Regensburg, Germany
关键词
Huntington's disease; Gait analysis; Wearable sensors; Gait variability; Regularity of gait; PARKINSONS-DISEASE; OBJECTIVE ASSESSMENT; END-POINTS; PREMANIFEST; MOTOR; PROGRESSION; DISORDERS; MOVEMENTS;
D O I
10.1007/s00415-020-09725-3
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Impaired gait plays an important role for quality of life in patients with Huntington'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'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 x 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 <= r(Sp) <= 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.
引用
收藏
页码:1594 / 1601
页数:8
相关论文
共 38 条
[1]   Wearable Sensors in Huntington Disease: A Pilot Study [J].
Andrzejewski, Kelly L. ;
Dowling, Ariel V. ;
Stamler, David ;
Felong, Timothy J. ;
Harris, Denzil A. ;
Wong, Cynthia ;
Cai, Hang ;
Reilmann, Ralf ;
Little, Max A. ;
Gwin, Joseph T. ;
Biglan, Kevin M. ;
Dorsey, E. Ray .
JOURNAL OF HUNTINGTONS DISEASE, 2016, 5 (02) :199-206
[2]  
[Anonymous], 2016, SENSORS
[3]   Stride Segmentation during Free Walk Movements Using Multi-Dimensional Subsequence Dynamic Time Warping on Inertial Sensor Data [J].
Barth, Jens ;
Oberndorfer, Caecilia ;
Pasluosta, Cristian ;
Schuelein, Samuel ;
Gassner, Heiko ;
Reinfelder, Samuel ;
Kugler, Patrick ;
Schuldhaus, Dominik ;
Winkler, Juergen ;
Klucken, Jochen ;
Eskofier, Bjoern M. .
SENSORS, 2015, 15 (03) :6419-6440
[4]   Tapping linked to function and structure in premanifest and symptomatic Huntington disease [J].
Bechtel, N. ;
Scahill, R. I. ;
Rosas, H. D. ;
Acharya, T. ;
van den Bogaard, S. J. A. ;
Jauffret, C. ;
Say, M. J. ;
Sturrock, A. ;
Johnson, H. ;
Onorato, C. E. ;
Salat, D. H. ;
Durr, A. ;
Leavitt, B. R. ;
Roos, R. A. C. ;
Landwehrmeyer, G. B. ;
Langbehn, D. R. ;
Stout, J. C. ;
Tabrizi, S. J. ;
Reilmann, R. .
NEUROLOGY, 2010, 75 (24) :2150-2160
[5]   Analysis of gait and balance through a single triaxial accelerometer in presymptomatic and symptomatic Huntington's disease [J].
Dalton, Anthony ;
Khalil, Hanan ;
Busse, Monica ;
Rosser, Anne ;
van Deursen, Robert ;
OLaighin, Gearoid .
GAIT & POSTURE, 2013, 37 (01) :49-54
[6]   Role of hypokinesia and bradykinesia in gait disturbances in Huntington's disease -: A biomechanical study [J].
Delval, A ;
Krystkowiak, P ;
Blatt, JL ;
Labyt, E ;
Dujardin, K ;
Destée, A ;
Derambure, P ;
Defebvre, L .
JOURNAL OF NEUROLOGY, 2006, 253 (01) :73-80
[7]   Technology in Parkinson's disease: Challenges and opportunities [J].
Espay, Alberto J. ;
Bonato, Paolo ;
Nahab, Fatta B. ;
Maetzler, Walter ;
Dean, John M. ;
Klucken, Jochen ;
Eskofier, Bjoern M. ;
Merola, Aristide ;
Horak, Fay ;
Lang, Anthony E. ;
Reilmann, Ralf ;
Giuffrida, Joe ;
Nieuwboer, Alice ;
Horne, Malcolm ;
Little, Max A. ;
Litvan, Irene ;
Simuni, Tanya ;
Dorsey, E. Ray ;
Burack, Michelle A. ;
Kubota, Ken ;
Kamondi, Anita ;
Godinho, Catarina ;
Daneault, Jean-Francois ;
Mitsi, Georgia ;
Krinke, Lothar ;
Hausdorff, Jeffery M. ;
Bloem, Bastiaan R. ;
Papapetropoulos, Spyros .
MOVEMENT DISORDERS, 2016, 31 (09) :1272-1282
[8]   The Diagnostic Scope of Sensor-Based Gait Analysis in Atypical Parkinsonism: Further Observations [J].
Gassner, Heiko ;
Raccagni, Cecilia ;
Eskofier, Bjoern M. ;
Klucken, Jochen ;
Wenning, Gregor K. .
FRONTIERS IN NEUROLOGY, 2019, 10
[9]   Gait and Cognition in Parkinson's Disease: Cognitive Impairment Is Inadequately Reflected by Gait Performance during Dual Task [J].
Gassner, Heiko ;
Marxreiter, Franz ;
Steib, Simon ;
Kohl, Zacharias ;
Schlachetzki, Johannes C. M. ;
Adler, Werner ;
Eskofier, Bjoern M. ;
Pfeifer, Klaus ;
Winkler, Juergen ;
Klucken, Jochen .
FRONTIERS IN NEUROLOGY, 2017, 8
[10]   Coordination of prehensile forces during precision grip in Huntington's disease [J].
Gordon, AM ;
Quinn, L ;
Reilmann, R ;
Marder, K .
EXPERIMENTAL NEUROLOGY, 2000, 163 (01) :136-148