Disability in cerebellar ataxia syndromes is linked to cortical degeneration.

OBJECTIVE: We aimed to relate clinical measures of disability in chronic cerebellar degeneration to structural whole-brain changes using voxel-based and surface-based morphometry (vbm and sbm). We were particularly interested in remote effects of cerebellar degeneration in the cerebral cortex. METHODS: We recruited 30 patients with cerebellar degeneration of different aetiologies (downbeat nystagmus syndrome, DBN n = 14, spinocerebellar ataxia, SCA n = 9, sporadic adult late-onset ataxia, SAOA n = 7). All patients were thoroughly characterised in the motor, cognitive, vestibular and ocular-motor domains. Vbm and sbm were used to evaluate structural differences between cerebellar degeneration patients and a group of healthy age- and gender-matched volunteers. Linear regression models were used to correlate functional measures of disease progression and postural stability with whole brain volumetry. RESULTS: Patients with SCA and SAOA showed widespread volume loss in the cerebellar hemispheres and less prominently in the vermis. Patients with DBN showed a distinct pattern of grey matter volume (GMV) loss that was restricted to the vestibular and ocular-motor representations in lobules IX, X and V-VII. Falls were associated with brainstem white matter volume. VBM and SBM linear regression models revealed associations between severity of ataxic symptoms, cognitive performance and preferred gait velocity. This included extra-cerebellar (sub-)cortical hubs of the motor and locomotion network (putamen, caudate, thalamus, primary motor cortex, prefrontal cortex) and multisensory areas involved in spatial navigation and cognition. CONCLUSION: Functional disability in multiple domains was associated with structural changes in the cerebral cortex.

Multimodal Mobility Assessment Predicts Fall Frequency and Severity in Cerebellar Ataxia.

This cohort study aims to evaluate the predictive validity of multimodal clinical assessment and quantitative measures of in- and off-laboratory mobility for fall-risk estimation in patients with cerebellar ataxia (CA).Occurrence, severity, and consequences of falling were prospectively assessed for 6 months in 93 patients with hereditary (N = 36) and sporadic or secondary (N = 57) forms of CA and 63 healthy controls. Participants completed a multimodal clinical and functional fall risk assessment, in-laboratory gait examination, and a 2-week inertial sensor-based daily mobility monitoring. Multivariate logistic regression analyses were performed to evaluate the predictive capacity of all clinical and in- and off-laboratory mobility measures with respect to fall (1) status (non-faller vs. faller), (2) frequency (occasional vs. frequent falls), and (3) severity (benign vs. injurious fall) of patients. 64% of patients experienced one or recurrent falls and 65% of these severe fall-related injuries during prospective assessment. Mobility impairments in patients corresponded to a mild-to-moderate ataxic gait disorder. Patients' fall status and frequency could be reliably predicted (78% and 81% accuracy, respectively), primarily based on their retrospective fall status. Clinical scoring of ataxic symptoms and in- and off-laboratory gait and mobility measures improved classification and provided unique information for the prediction of fall severity (84% accuracy).These results encourage a stepwise approach for fall risk assessment in patients with CA: fall history-taking readily and reliably informs the clinician about patients' general fall risk. Clinical scoring and instrument-based mobility measures provide further in-depth information on the risk of recurrent and injurious falling.

Age-dependent perturbation of the perceptual and postural vertical by visual roll vection and susceptibility to motion sickness in children.

BACKGROUND: The visual contribution to the perceptual and postural vertical is mediated by a multisensory integration process and may relate to children's susceptibility to motion sickness that is hypothesized to arise from intersensory conflicts. OBJECTIVE: To analyze the maturation of visual contribution to the perceptual and postural vertical in conjunction with the motion sickness susceptibility in childhood. METHODS: In 81 healthy children (aged 2-17 years; 57 females), adjustments of the subjective visual vertical and posturographically tested mediolateral displacements of body sway were measured during free upright stance and large-field visual motion stimulation in the roll plane (roll vection). Motion sickness susceptibility was assessed by taking the history of parents and children. RESULTS: Vection-induced tilts of the visual vertical showed a linear age-dependent decrease with largest tilts in the youngest (2-7 years; median of 20°) and smallest tilts in the oldest age group (13-17 years; median of 9-10°). Analogously, postural tilts as measured by mediolateral body sway were greatest in the youngest and smallest in the oldest age group. In contrast, motion sickness susceptibility was lowest in the youngest and highest in the oldest age group and exhibited an inverse correlation with vection-induced tilts of the visual vertical. CONCLUSION: Roll vection-induced tilts of the visual and postural vertical exhibited a similar age-dependent course with the greatest effects in the youngest and the least effects in the oldest age group, the latter of which exhibited the highest susceptibility to motion sickness.

Fall prediction in neurological gait disorders: differential contributions from clinical assessment, gait analysis, and daily-life mobility monitoring.

OBJECTIVE: To evaluate the predictive validity of multimodal clinical assessment outcomes and quantitative measures of in- and off-laboratory mobility for fall-risk estimation in patients with different forms of neurological gait disorders. METHODS: The occurrence, severity, and consequences of falls were prospectively assessed for 6 months in 333 patients with early stage gait disorders due to vestibular, cerebellar, hypokinetic, vascular, functional, or other neurological diseases and 63 healthy controls. At inclusion, participants completed a comprehensive multimodal clinical and functional fall-risk assessment, an in-laboratory gait examination, and an inertial-sensor-based daily mobility monitoring for 14 days. Multivariate logistic regression analyses were performed to identify explanatory characteristics for predicting the (1) the fall status (non-faller vs. faller), (2) the fall frequency (occasional vs. frequent falls), and (3) the fall severity (benign vs. injurious fall) of patients. RESULTS: 40% of patients experienced one or frequent falls and 21% severe fall-related injuries during prospective fall assessment. Fall status and frequency could be reliably predicted (accuracy of 78 and 91%, respectively) primarily based on patients' retrospective fall status. Instrumented-based gait and mobility measures further improved prediction and provided independent, unique information for predicting the severity of fall-related consequences. INTERPRETATION: Falls- and fall-related injuries are a relevant health problem already in early stage neurological gait disorders. Multivariate regression analysis encourages a stepwise approach for fall assessment in these patients: fall history taking readily informs the clinician about patients' general fall risk. In patients at risk of falling, instrument-based measures of gait and mobility provide critical information on the likelihood of severe fall-related injuries.