Luis Velázquez-Pérez1,2, Roberto Rodriguez-Labrada1,3, Yasmani González-Garcés1, Eduardo Arrufat-Pie4, Reidenis Torres-Vega1, Jacqueline Medrano-Montero1, Beatriz Ramirez-Bautista5, Yaimeé Vazquez-Mojena1,3, Georg Auburger6, Fay Horak7, Ulf Ziemann8,9, Christopher M Gomez10. 1. Department of Clinical Neurophysiology, Centre for the Research and Rehabilitation of Hereditary Ataxias, Holguín, Cuba. 2. Cuban Academy of Sciences, La Habana Vieja, Cuba. 3. Department of Molecular Biology, Cuban Neuroscience Centre, Playa, Cuba. 4. Department of Neurorehabilitation, Clinical & Surgical Hospital "Manuel Piti Fajardo,", Plaza de la Revolución, Cuba. 5. Department of Gastroenterology, University Hospital "Carlos Font,", Banes, Holguín, Cuba. 6. Experimental Neurology, Department of Neurology, Experimental Neurology, Medical School, Goethe University, Frankfurt am Main, Germany. 7. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA. 8. Department of Neurology & Stroke, University of Tübingen, Tübingen, Germany. 9. Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 10. Department of Neurology, University of Chicago, Chicago, Illinois, USA.
Abstract
BACKGROUND: The search for valid preclinical biomarkers of cerebellar dysfunction is a key research goal for the upcoming era of early interventional approaches in spinocerebellar ataxias. This study aims to describe novel preclinical biomarkers of subtle gait and postural sway abnormalities in prodromal spinocerebellar ataxia type 2 (pre-SCA2). METHODS: Thirty pre-SCA2 patients and their matched healthy controls underwent quantitative assessments of gait and postural sway using a wearable sensor-based system and semiquantitative evaluation of cerebellar features by SARA (Scale for the Assessment and Rating of Ataxia) score. RESULTS: Quantitative analysis of natural gait showed a significantly larger variability of the swing period, toe-off angle and toe-out angle in pre-SCA2, and larger mean coronal and transverse ranges of motion of the trunk at the lumbar location and of the sagittal range of motion of the trunk at the sternum location compared to controls. During tandem gait, pre-SCA2 subjects showed larger lumbar, trunk, and arm ranges of motion than controls. Postural sway analysis showed excessive body oscillation that was increased in tandem stance. Overall, these abnormalities were detected in pre-SCA2 patients without clinical evidence of abnormalities in SARA. The toe-off angle and swing time variability were significantly correlated with the time to ataxia onset, whereas the toe-off angle and transverse range of motion at trunk position during tandem gait were significantly associated with the SARA score. CONCLUSIONS: This study demonstrates early alteration of gait and postural sway control in prodromal SCA2 using a wearable sensor-based system. This offers new pathophysiological hints into this early disease stage and provides novel potential biomarkers for future clinical trials.
BACKGROUND: The search for valid preclinical biomarkers of cerebellar dysfunction is a key research goal for the upcoming era of early interventional approaches in spinocerebellar ataxias. This study aims to describe novel preclinical biomarkers of subtle gait and postural sway abnormalities in prodromal spinocerebellar ataxia type 2 (pre-SCA2). METHODS: Thirty pre-SCA2patients and their matched healthy controls underwent quantitative assessments of gait and postural sway using a wearable sensor-based system and semiquantitative evaluation of cerebellar features by SARA (Scale for the Assessment and Rating of Ataxia) score. RESULTS: Quantitative analysis of natural gait showed a significantly larger variability of the swing period, toe-off angle and toe-out angle in pre-SCA2, and larger mean coronal and transverse ranges of motion of the trunk at the lumbar location and of the sagittal range of motion of the trunk at the sternum location compared to controls. During tandem gait, pre-SCA2 subjects showed larger lumbar, trunk, and arm ranges of motion than controls. Postural sway analysis showed excessive body oscillation that was increased in tandem stance. Overall, these abnormalities were detected in pre-SCA2patients without clinical evidence of abnormalities in SARA. The toe-off angle and swing time variability were significantly correlated with the time to ataxia onset, whereas the toe-off angle and transverse range of motion at trunk position during tandem gait were significantly associated with the SARA score. CONCLUSIONS: This study demonstrates early alteration of gait and postural sway control in prodromal SCA2 using a wearable sensor-based system. This offers new pathophysiological hints into this early disease stage and provides novel potential biomarkers for future clinical trials.
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