Prodromal Spinocerebellar Ataxia Type 2 Subjects Have Quantifiable Gait and Postural Sway Deficits

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. © 2020 International Parkinson and Movement Disorder Society

Inertial Sensor Reliability and Validity for Static and Dynamic Balance in Healthy Adults: A Systematic Review

“…Fallers were identified as a subject group in four studies [ 28 , 29 , 30 , 31 ]. The majority of papers investigated postural sway in neurological conditions, including Parkinson’s disease (PD) [ 32 , 33 , 34 , 35 ], multiple sclerosis (MS) [ 36 , 37 ], Huntington’s disease [ 38 ], progressive supranuclear palsy [ 33 ], muscular dystrophy [ 39 ], cerebellar ataxia [ 40 , 41 ], and a single case study of person with a stroke [ 42 ]. Only one musculoskeletal condition was investigated: anterior cruciate ligament reconstruction rehabilitation [ 43 ].…”

“…No single clinical test was used consistently. Dynamic clinical measures also included walking tests (timed up and go [ 31 , 33 , 36 , 37 , 42 ], 10 m walk [ 41 ], six-minute walk test [ 34 ], 25-foot walk test [ 37 ], and jumping (dynamic postural stability index (DPSI)) [ 25 ].…”

“…Only one study used a dual axis accelerometer (antero-posterior and mediolateral) [ 32 ] while the remainder used triaxial sensors, providing accelerometry data for the additional vertical plane. Thirteen studies also used inertial sensors with inbuilt gyroscopes providing further rotational velocity information [ 26 , 28 , 29 , 33 , 34 , 35 , 36 , 37 , 41 , 42 , 43 ]. The most common inertial sensors were Opals and XSens, where accelerometry data measured concurrent input from multiple sensors placed on the trunk and extremities.…”

Turning movements in real life capture subtle longitudinal and preataxic changes in cerebellar ataxia

“…However, there is some inconsistency in the literature, with other studies having reported pre-ataxic changes in straight walking during clinical gait assessments 43, 44 . This discrepancy might most likely be explained with early clinical gait signs already present in these study cohorts 43,44 . None of the preataxic subjects in our cohort showed any clinical gait or balance sign, as indicated by a SARA posture&gait subscore = 0 for all preataxic subjects (Table 1).…”

Ataxin-2 gene: a powerful modulator of neurological disorders

“…No other clinical or cognitive changes were evidenced in this one-year longitudinal study. In the prodromal phase, mutation carriers had larger variability in both gait and postural sway control [ 37 ], suggesting deterioration of the vestibulocerebellar network. Furthermore, there is a gradual worsening of speech and swallowing [ 38 ].…”