Minimal reporting guideline for research involving eye tracking (2023 edition).

A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.

Pinch Strength Measurements in Adolescents With Pediatric Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a degenerative disease with typical onset between 20 and 50 years of age. An increase in MS cases has been found in the adolescent US population. Adolescents require fine motor manipulation skills for their functional and academic performance. Deficits in the major components of manipulation skills may result in insufficient function. This study examined the 2-point, 3-point, and lateral pinch strength of adolescents diagnosed as having MS. METHODS: Seventy-four adolescents, 37 with a diagnosis of relapsing-remitting MS and a control group of 37 age-matched peers, participated in this study. Data on 2-point, 3-point, and lateral pinch strength in both hands were collected using a pinch meter. Analyses of covariance were used to describe differences across the 2 groups, and effect sizes (Cohen d) were calculated by finding the mean difference between the study groups divided by the pooled SD. RESULTS: A significant difference was found in the 2-point pinch strength of the right hand of participants with pediatric MS compared with age- and sex-matched control participants. There were no significant differences in 2-point pinch strength of the left hand or in 3-point or lateral pinch strength of the right and left hands. CONCLUSIONS: Pinch grasp strength was differentially affected in adolescents with MS. Pinch strength should be assessed and considered in adolescents with MS for a better understanding of their functional performance of fine motor tasks in activities of daily living and academics.

Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

INTRODUCTION: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention. METHODS: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments. RESULTS: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies. CONCLUSION: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered. CLINICALTRIALS: GOV: NCT03344601.

Immersive Technology for Cognitive-Motor Training in Parkinson's Disease.

Background: Parkinson's disease (PD) is a neurodegenerative disease in which the progressive loss of dopaminergic neurons (DA) leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body's center of mass over an ever-changing base of support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided. Methods: In this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment (MoCA), Verbal Fluency (Fruit, Vegetable, and Animal) and the Symbol Digit Modality Test (SDMT). Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U-test. Results: This novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive (p = 0.05) and those changes were greater than the control group (between group p = 0.040). The experimental group also improved scores on MoCA (p = 0.007) and SDMT (p = 0.01) cognitive outcome measures while the control group did not. Conclusion: The use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD.

Postural control and gait measures derived from wearable inertial measurement unit devices in Huntington's disease: Recommendations for clinical outcomes.

BACKGROUND: Postural control impairments begin early in Huntington's disease yet measures most sensitive to progression have not been identified. The aims of this study were to: 1) evaluate postural control and gait in people with and without Huntington's disease using wearable sensors; and 2) identify measures related to diagnosis and clinical severity. METHODS: 43 individuals with Huntington's disease and 15 age-matched peers performed standing with feet together and feet apart, sitting, and walking with wearable inertial sensors. One-way analysis of variance determined differences in measures of postural control and gait between early and mid-disease stage, and non-Huntington's disease peers. A random forest analysis identified feature importance for Huntington's disease diagnosis. Stepwise and ordinal regressions were used to determine predictors of clinical chorea and tandem walking scores respectively. FINDINGS: There was a significant main effect for all postural control and gait measures comparing early stage, mid stage and non-Huntington's disease peers, except for gait cycle duration and step duration. Total sway, root mean square and mean velocity during sitting, as well as gait speed had the greatest importance in classifying disease status. Stepwise regression showed that root mean square during standing with feet apart significantly predicted clinical measure of chorea, and ordinal regression model showed that root mean square and total sway standing feet together significantly predicted clinical measure of tandem walking. INTERPRETATIONS: Root mean square measures obtained in sitting and standing using wearable sensors have the potential to serve as biomarkers of postural control impairments in Huntington's disease.

Variability of objective gait measures across the expanded disability status scale in people living with multiple sclerosis: A cross-sectional retrospective analysis.

BACKGROUND: The Expanded Disability Status Scale (EDSS) is widely utilized in clinical trials and routine care to evaluate disease burden and progression among people with multiple sclerosis (pwMS). However, instrumental gait measures may be more suitable than EDSS to track walking disability in pwMS. In this cross-sectional study, we aimed to quantify the variability of spatiotemporal gait measures within homologous EDSS categories. METHODS: A total of 205 pwMS (age=46.5[SD=10.5] years, 72.2% female, EDSS range=1.0-6.5) were studied in this retrospective analysis. Participants underwent walking assessments through the GAITRite system and the following spatiotemporal gait measures were recorded: gait speed, mean normalized velocity (MNV), base of support, stride length, step length, percentage of gait cycle spent in double support and single support, and functional ambulation profile. The EDSS was evaluated by a certified neurologist. RESULTS: All gait measures exhibited fair to very strong correlations with scores on the EDSS (-0.81≤ρs≤0.25) and poor to fair correlations with disease duration (-0.32≤ρs≤0.17). Overall, the percent variability of gait measures increased across EDSS categories, with coefficients of variation ranging from 6.9% to 37.2% in the minimal disability group (EDSS≤2.5), 8.1% to 33.4% and 22.3% to 53.8% in the moderate (2.54.5) disability groups, respectively. CONCLUSION: Spatiotemporal gait measures have great variability within homologous EDSS categories. The high percent variability of gait speed and MNV (up to more than 50%) suggests that walking ability varies substantially within and across disability levels. Therefore, in addition to the EDSS, more comprehensive (multidimensional), objective patient-centric metrics would be needed to accurately evaluate disability in pwMS.

Quantification of Daily-Living Gait Quantity and Quality Using a Wrist-Worn Accelerometer in Huntington's Disease.

Background: Huntington's disease (HD) leads to altered gait patterns and reduced daily-living physical activity. Accurate measurement of daily-living walking that takes into account involuntary movements (e.g. chorea) is needed. Objective: To evaluate daily-living gait quantity and quality in HD, taking into account irregular movements. Methods: Forty-two individuals with HD and fourteen age-matched non-HD peers completed clinic-based assessments and a standardized laboratory-based circuit of functional activities, wearing inertial measurement units on the wrists, legs, and trunk. These activities were used to train and test an algorithm for the automated detection of walking. Subsequently, 29 HD participants and 22 age-matched non-HD peers wore a tri-axial accelerometer on their non-dominant wrist for 7 days. Measures included gait quantity (e.g., steps per day), gait quality (e.g., regularity) metrics, and percentage of walking bouts with irregular movements. Results: Measures of daily-living gait quantity including step counts, walking time and bouts per day were similar in HD participants and non-HD peers (p > 0.05). HD participants with higher clinician-rated upper body chorea had a greater percentage of walking bouts with irregular movements compared to those with lower chorea (p = 0.060) and non-HD peers (p < 0.001). Even after accounting for irregular movements, within-bout walking consistency was lower in HD participants compared to non-HD peers (p < 0.001), while across-bout variability of these measures was higher (p < 0.001). Many of the daily-living measures were associated with disease-specific measures of motor function. Conclusions: Results suggest that a wrist-worn accelerometer can be used to evaluate the quantity and quality of daily-living gait in people with HD, while accounting for the influence of irregular (choreic-like) movements, and that gait features related to within- and across-bout consistency markedly differ in individuals with HD and non-HD peers.

Measures of postural control and mobility during dual-tasking as candidate markers of instability in Huntington's disease.

BACKGROUND: Individuals with Huntington's disease (HD) have impairments in performing dual-tasks, however, there is limited information about the effects of changing postural and cognitive demands as well as which measures are best suited as markers of underlying motor-cognitive interference. METHODS: Forty-three individuals with HD and 15 healthy controls (HC) completed single tasks of walking (Timed Up & Go (TUG), 7 m walk), standing (feet together, feet apart and foam surface) and seated cognitive performance (Stroop, Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (DKEFS) Sorting test) and dual cognitive-motor tasks while standing (+ Stroop) and walking (+ DKEFS, TUG cognitive). APDM Opal sensors recorded measures of postural sway and time to complete motor tasks. RESULTS: Individuals with HD had a greater increase in standing postural sway compared to HC from single to dual-tasks and with changes to support surface. Both groups demonstrated a decrease in gait performance during the TUG cognitive, however, this difference was greater in people with HD compared to HC. While those with HD showed a greater dual-task motor cost compared to HC, both groups behaved similarly as condition complexity increased. CONCLUSIONS: Standing postural sway is a more sensitive marker of instability than change in standard gait speed, particularly under dual-task conditions. The more complex TUG cognitive is a sensitive measure of walking dual-task performance. The results of this study provide insights about the nature of motor-cognitive impairments in HD and provide support for a distinction between static and dynamic postural control mechanisms during performance of dual-tasks.

Evaluation of gait initiation using inertial sensors in Huntington's Disease: insights into anticipatory postural adjustments and cognitive interference.

BACKGROUND: Understanding the contribution of anticipatory postural adjustments (APA) to walking ability in individuals with Huntington's disease (HD) may provide insight into motor planning and the functional consequences of HD-specific cortical-basal ganglia pathway dysfunctions. RESEARCH QUESTION: How do inertial measurement unit (IMU)-derived APAs and first step parameters differ between individuals with HD and non-HD peers under no load and cognitive load conditions, and what is their relationship to gait speed and clinical measures? METHODS: 33 individuals with manifest HD and 15 non-HD peers wore three Opal APDM IMUs during a 14-meter walk under no load and cognitive load conditions. APA acceleration amplitudes, APA durations, first step range of motion (ROM), and first step durations were compared, along with their relationship to gait speed. RESULTS: Individuals with HD had greater APA acceleration amplitudes, smaller first step ROM and longer first step durations compared to non-HD peers. No differences in APA durations were present between groups in both conditions. Cognitive loading influenced first step ROM but not other APA parameters. Mediolateral APA acceleration amplitudes were a significant predictor of gait speed and were related to disease-specific measures. SIGNIFICANCE: Larger acceleration amplitudes and smaller first step ROMs of greater duration, accompanied by the preservation of APA durations, reveal a discrepancy in movement scaling in HD. Additionally, the mediolateral component of the APA is likely a rate-limiting factor that drives a compensatory response in gait initiation. Further research is needed to explore the neural correlates of HD-related movement scaling.

Correction to: Gait variability as digital biomarker of disease severity in Huntington's disease.

The original version of this article unfortunately contained a mistake. The name of one author is not presented correctly in the author group.

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

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 × 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 ≤ rSp ≤ 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.

Music to One's Ears: Familiarity and Music Engagement in People With Parkinson's Disease.

Parkinson's disease (PD) is a complex diagnosis commonly associated with motor dysfunction, but known to comprise cognitive, psychiatric, and mood disturbances as well. Music has been successfully used to address motor and non-motor symptoms of PD. Still, little is known about the nature of an individual with PD's experience and relationship with music on conceptual and emotional levels, which may factor into their engagement in music-based techniques to ameliorate impairments. Two surveys were administered to 19 individuals with PD and 15 individuals without PD in order to gauge their subjective impressions and valuations of music. Participants completed The Brief Music Experience Questionnaire (BMEQ), a standard self-report measure pertaining to the role of music in one's life, prior to performing a perception task which involved listening to and making sound adjustments to three music recordings. Following the perception task, a custom Exit Survey was administered to evaluate the experience of listening to and engaging with the music in the perception task. In all six dimensions of the BMEQ, examining aspects of music experience including commitment to music, self-reported musical aptitude, social uplift, affective reactions, positive psychotropic effects, and reactive musical behavior (RMB, pertaining to actions or behaviors in response to music), the mean and the median were greater for the control group than for the PD group, but the difference was only statistically significant in the RMB dimension. On the Exit Survey, both groups assessed recent, specific, and interactive music listening more positively than the imagined, hypothetical or general music experiences addressed on the BMEQ. Additionally, familiarity had a greater effect on listening pleasure for participants with PD than those without PD. We conclude that people with PD may perceive less of an automatic connection between music and activity than their healthy peers. Additionally, they may receive more pleasure and value from music than they anticipate. Taken together, our results suggest that people with PD may require encouragement to participate as well as empowerment to choose familiar selections in order to better access music-based interventions and the benefits they can offer.

Physical Activity and Exercise Outcomes in Huntington Disease (PACE-HD): Protocol for a 12-Month Trial Within Cohort Evaluation of a Physical Activity Intervention in People With Huntington Disease.

BACKGROUND: Exercise is emerging as an important aspect in the management of disease-related symptoms and functional decline in people with Huntington disease (HD). Long-term evaluation of physical activity and exercise participation in HD has yet to be undertaken. OBJECTIVE: The objective is to investigate the feasibility of a nested randomized controlled trial (RCT) alongside a longitudinal observational study of physical activity and exercise outcomes in people with HD. DESIGN: This will be a 12-month longitudinal observational study (n = 120) with a nested evaluation of a physical activity intervention (n = 30) compared with usual activity (n = 30) using a "trial within a cohort" design. SETTING: The study will take place in HD specialist clinics in Germany, Spain, and the United States, with intervention delivery in community settings. PARTICIPANTS: The participants will have early-mid-stage HD and be participating in the Enroll-HD study. INTERVENTION: This will be a 12-month physical activity behavioral change intervention, delivered by physical therapists in 18 sessions, targeting uptake of aerobic exercise and increased physical activity. MEASUREMENTS: All participants (n = 120) will complete Enroll-HD assessments (motor, cognitive, behavioral, and quality of life) at baseline and at 12 months. Additional Physical ACtivity and Exercise Outcomes in Huntington Disease (PACE-HD) assessments include fitness (predicted maximal oxygen uptake [V o2max]), self-reported and quantitative measures of physical activity, disease-specific symptoms, and walking endurance. RCT participants (n = 60) will complete an additional battery of quantitative motor assessments and a 6-month interim assessment. Enroll-HD data will be linked to PACE-HD physical activity and fitness data. LIMITATIONS: The limitations include that the embedded RCT is open, and assessors at RCT sites are not blinded to participant allocation. CONCLUSION: PACE-HD will enable determination of the feasibility of long-term physical activity interventions in people with HD. The novel "trial within a cohort" design and incorporation of data linkage have potential to reduce participant burden. This design could be applied to other neurological diseases and movement disorders where recruitment and retention are challenging.

Biological Motion Perception in Huntington's Disease.

BACKGROUND: The ability of healthy individuals to detect biological motion by using a small number of moving points is well established in animals and humans. Perception of human movements may depend on internal models that drive self-generated movements and influence motion discrimination (Reed CL et al. 1995 and 2007). As a person's motor repertoire deteriorates, the accuracy of these models may also decrease. OBJECTIVE: Determine if people with symptomatic Huntington's disease (HD) have difficulty perceiving movements. METHODS: In this study point-light displays were created with a Vicon Motion Capture System by recording one individual with (impaired) and one individual without (healthy) Parkinson's disease using a 13 joint marker set. Participants were asked to distinguish between three movements and determine if the movement was impaired or healthy. The ability of participants with and without HD to distinguish movement patterns and the time to perception were recorded. RESULTS: Analyses found participants with HD had a decreased ability to correctly detect movements and point-light image type. The stair climbing motion showed the largest effect as participants with HD had more difficulty correctly identifying both the movement and whether it was impaired or healthy. In addition, the participants without HD showed an improvement as trials progressed which could not be observed in the HD cohort. CONCLUSIONS: As people with symptomatic HD have difficulty perceiving movements further investigations using point-light displays should be done to determine if these impairments might serve as an easily administered, non-invasive marker of disease state.

Cognitive-Motor Interference in Neurodegenerative Disease: A Narrative Review and Implications for Clinical Management.

This paper provides a narrative review of cognitive motor interference in neurodegeneration, including brain imaging findings specific to interference effects in neurodegenerative disease, and dual task assessment and intervention in Parkinson's disease (PD), multiple sclerosis (MS), and Huntington's disease (HD). In a healthy central nervous system the ability to process information is limited. Limitations in capacity to select and attend to inputs influence the ability to prepare and perform multiple tasks. As a result, the system balances demands, switching attention to the most task-relevant information as it becomes available. Limitations may become more apparent in persons with neurodegenerative diseases (ND) with system-specific impairments in PD, MS, and HD. These ND affect both cognitive and motor function and are thus particularly susceptible to dual task interference. Issues related to performer and task characteristics and implications of these findings for both the standard assessment of dual task abilities as well as development and evaluation of interventions aimed at improving dual task ability are discussed. In addition, we address the need for optimizing individualized assessment, intervention and evaluation of dual task function by choosing cognitive and motor tasks and measures that are sensitive to and appropriate for the individual's level of function. Finally, we use current evidence to outline a 5-step process of clinical decision making that uses the dual task taxonomy as a framework for assessment and intervention.

Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the Huntington Gene?

BACKGROUND: Large animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. Recently, analysis of voice and speech production was established to characterise HD patients. OBJECTIVE: The aim of this study was to investigate whether vocalisation could also serve as a viable marker for phenotyping minipigs transgenic for Huntington's disease (tgHD) and whether tgHD minipigs reveal changes in this domain compared to wildtype (wt) minipigs. METHODS: While conducting behavioural testing, incidence of vocalisation was assessed for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were performed using Fisher's Exact Test for group comparisons and McNemar's Test for intra-visit differences between tgHD and wt minipigs. RESULTS: Vocalisation can easily be documented during phenotyping assessments of minipigs. Differences in vocalisation incidences across behavioural conditions were detected between tgHD and wt minipigs. Influence of the genotype on vocalisation was detectable during a period of 1.5 years. CONCLUSION: Vocalisation may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Documentation of vocalisation provides a non-invasive opportunity to capture potential disease signs and explore phenotypic development including the age of disease manifestation.

Behavioral Assessment of Stress Compensation in Minipigs Transgenic for the Huntington Gene Using Cortisol Levels: A Proof-of-Concept Study.

BACKGROUND: Huntington's disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder with motor, cognitive, behavioral and metabolic symptoms. HD patients exhibit an altered response to stress which is reflected in changes of cortisol levels. Large animal models of HD such as the Libechov minipig are currently explored in preclinical studies to improve translational reliability and assessing behavior is of interest. OBJECTIVE: This study aimed to investigate whether cortisol metabolism and response to stress are changed in minipigs transgenic for the Huntington gene (tgHD) compared to wildtype (wt) animals suggesting that cortisol may be used as a marker for stress in minipigs. METHODS: Thirty-two Libechov minipigs (14 tgHD and 18 wt) were tested before, during and after a stressor, i.e., a hoof trimming procedure, was applied at baseline and after one year. A total of six saliva samples were collected at each assessment and cortisol was measured. In addition, body temperature and respiratory rate were assessed at three pre-determined points during each hoof trimming procedure. RESULTS: All minipigs showed a rise of cortisol in response to the hoof trimming stressor similarly to cortisol changes induced by stress observed in humans. No relevant differences were detected between tgHD and wt minipigs. CONCLUSION: Cortisol testing for the assessment of stress compensation, e.g., during hoof trimming, is feasible and well tolerated in wt and tgHD minipigs. To elucidate the time profile of cortisol responses to stressors further studies with assessments at multiple time points and exploration of the diurnal profiles of cortisol in minipigs are recommended.

Objective assessment of gait and posture in premanifest and manifest Huntington disease - A multi-center study.

BACKGROUND: Deficits in posture and gait are known to contribute to the complex motor phenotype of Huntington disease (HD). Objective and quantitative measures of posture and gait provided by posturography and GAITRite® assessments may supplement categorical rating scales such as the UHDRS-TMS and increase power and sensitivity of clinical trials. OBJECTIVES: To investigate whether posturography and GAITRite® measures reveal (1) changes in manifest or premanifest HD mutation-carriers, (2) a correlation to the UHDRS-TMS and functional measures in manifest HD, and (3) a correlation to the disease-burden-score (based on CAG-repeat-length and age). METHODS: Posturography and GAITRite® were applied in premanifest (n = 26) and manifest HD gene-mutation-carriers (n = 40) in different paradigms compared to age-matched controls (n = 30) in a cross-sectional multi-site study conducted in three centers. Subjects were assessed clinically with the UHDRS Total-Motor-Score, Total-Functional-Capacity and Functional-Assessment-Scale. RESULTS: Several posturography measures were able to discriminate between controls, premanifest, and manifest mutation-carriers in both conditions assessed. Only one GAITRite® measure separated controls and premanifest participants, while discrimination between controls and manifest same as between premanifest and manifest participants was possible in several measures. Correlation with all clinical measures was seen in only one measure per device while correlations to the disease-burden-score seen in posturography only. CONCLUSION: Overall the results suggests that posturography detects alterations in premanifest and manifest mutation-carriers more reliably than GAITRite® measures. Correlations with clinical assessment scores are limited; correlation with disease-burden-score is seen in posturography only. Data acquisition and analysis was easier with posturography than GAITRite® assessments in out-patient settings.