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

OBJECTIVES: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints which capture change in ataxia severity in patients real life. This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real life turning movements which are sensitive for changes both longitudinally and at the preataxic stage. METHODS: Combined cross-sectional (n=30) and longitudinal (n=14, 1 year interval) observational study in degenerative cerebellar disease (including 8 pre-ataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements. RESULTS: Measures which quantified dynamic balance during turning, lateral velocity change (LVC) and outward acceleration, but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life with high effect size (δ=0.68), with LVC also differentiating preataxic against healthy subjects (δ=0.53). LVC was highly correlated with clinical ataxia severity (SARA score, effect size ρ=0.79) and subjective balance confidence (ABC score, ρ=0.66). Moreover, LVC in real life but not general turning measures, gait measures, or the SARA score allowed detecting significant longitudinal change in one-year follow-up with high effect size (rprb=0.66). CONCLUSIONS: Measures of turning allow to capture specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers for capturing change in real life, even in the highly treatment-relevant early stages of degenerative cerebellar disease.

Effects of a Perturbation-Based Balance Training on Compensatory Postural Responses to Backward Loss of Balance in Patients with Cerebellar Disease: A Case Study

OBJECTIVES The damage to the cerebellum primarily results in balance-related abnormalities that may affect performance of locomotion and postural adjustments, eventually contributing to an increased risk of fall and fear of falling in patients with cerebellar disease. The purpose of the present study was to investigate the effect of a perturbation-based training that induced backward loss of balance on compensatory postural responses in patients with cerebellar disease.METHODS The participant was a 51-year-old female diagnosed with spinocerebellar ataxia and had the disease for 19 years. The perturbation-based backward balance training was performed over 8 weeks (a total of 24 training sessions) in order to facilitate the perception of postural perturbation onset and execution of rapid compensatory responses.RESULTS The patient demonstrated a noticeable reduction in the number of steps required to recover body balance after postural disturbances. The reduction of multi-step reactions in recovering balance could be attributed to improvements in the body center-of-mass displacement and trunk control during the landing of step. Besides, there were also improvements in subjective measures of functional mobility and psychological well-being after the balance training.CONCLUSION Although current research evidence of balance rehabilitation for cerebellar patients is lacking, this study offers the feasibility of adaptive training to improve postural stability through task-specific training intervention.

Pathological Prosody

Prosody in speech arises from fundamental frequency (f0), temporal measures, amplitude, and voice quality. These parameters in various combinations signal linguistic, emotional-attitudinal, and personal identity information. Prosodic processing engages cortical, subcortical, cerebellar, and brainstem systems, and damage to any of these can result in dysprosody. Despite the crucial role played by prosody in communication, little attention has been paid to clinical evaluation and even less to treatment. Numerous research studies of deficient emotional prosodic production and recognition reveal temporal deficits in association with left hemisphere damage and pitch processing failure in right hemisphere damage. Limited attempts at linguistic-prosodic testing suggest that damage to either cerebral hemisphere or to subcortical systems can affect production as well as comprehension. Treatment of linguistic dysprosody has revealed challenges in protocol design and performance evaluation. Prosodic insufficiency, present in cortical, subcortical, and cerebellar disease, has substantial implications for communicative function and deserves to be a strong focus of future research.

Real-life gait assessment in degenerative cerebellar ataxia

ObjectivesWith disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid motor biomarkers are highly warranted. In this observational study, we aimed to unravel and validate markers of ataxic gait in real life by using wearable sensors.MethodsWe assessed gait characteristics of 43 patients with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA] 9.4 ± 3.9) compared with 35 controls by 3 body-worn inertial sensors in 3 conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n = 21). Movement analysis focused on measures of spatiotemporal step variability and movement smoothness.ResultsA set of gait variability measures was identified that allowed us to consistently identify ataxic gait changes in all 3 conditions. Lateral step deviation and a compound measure of spatial step variability categorized patients vs controls with a discrimination accuracy of 0.86 in real life. Both were highly correlated with clinical ataxia severity (effect size ρ = 0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the clinical SARAposture&gait subscore, with highest effect sizes for real-life walking (d = 0.67).ConclusionsWe identified measures of ataxic gait that allowed us not only to capture the gait variability inherent in ataxic gait in real life, but also to demonstrate high sensitivity to small differences in disease severity, with the highest effect sizes in real-life walking. They thus represent promising candidates for motor markers for natural history and treatment trials in ecologically valid contexts.Classification of evidenceThis study provides Class I evidence that a set of gait variability measures, even if accessed in real life, correlated with the clinical severity of ataxia in patients with degenerative cerebellar disease.