Use of a Robotic Walking Device for Home and Community Mobility in Parkinson Disease: A Randomized Controlled Trial.

BACKGROUND/PURPOSE: Gait impairments in Parkinson disease (PD) contribute to decreased quality of life. This randomized controlled trial examined immediate- and longer-term effects of a single joint robotic exoskeleton device (EXOD), the Honda Walking Assist device, on gait. METHODS: Participants (n = 45) with PD (Hoehn and Yahr stages 1-3) were randomized to a robotic-assisted gait training (RAGT) group (n = 23) or control (CON) group (n = 22). The RAGT group was tested with and without the EXOD at baseline and then received supervised in-home and community training with the EXOD twice weekly for 8 weeks. The CON group received no interventions. Outcome measures included gait speed (primary), gait endurance (6-minute walk test), perceived ease of walking, and questionnaires and logs assessing performance of daily activities, freezing of gait, and daily activity levels. RESULTS: Forty participants completed the study. No significant immediate impact of EXOD usage on participants' gait measures was found. Differences in gait speed and secondary outcome measures postintervention were not significantly different between the RAGT and CON groups. Participants with greater disease severity (worse baseline motor scores) had greater improvements in stride length during unassisted walking after the intervention than those with lower severity (mean difference: 3.22, 95% confidence interval: 0.05-6.40; P = 0.04). DISCUSSION AND CONCLUSIONS: All RAGT participants could use the EXOD safely. The RAGT treatment used in this mostly low impairment population of people with PD may be ineffective and/or was insufficiently dosed to see a positive treatment effect. Our findings suggest that RAGT interventions in PD may be more effective in individuals with greater motor impairments.

Immediate effects of treadmill walking in individuals with Lewy body dementia and Huntington's disease.

BACKGROUND: Treadmill training may improve gait disorders associated with neurodegenerative diseases. In Parkinson's disease (PD), treadmill training alters gait patterns after one session, and long-term training improves gait parameters, fall risk, and quality of life. RESEARCH QUESTION: What is the feasibility and safety of using this intervention for people with Lewy body dementia (LBD) or Huntington's disease (HD)? METHODS: In this observational study, 10 individuals with HD, 8 individuals with LBD, and 10 control individuals walked for 20 min on a treadmill using a speed dependent protocol starting at a slow comfortable speed and increasing incrementally toward their normal overground speed. Feasibility was determined by compliance to protocol and safety by no incidents of abnormal vital signs or expressions of distress. Changes in gait measures, Timed Up and Go (TUG) scores and quantitative motor function measures (Q-Motor; precision grasp force variability, finger and foot tapping frequency) before and after treadmill walking were analyzed using linear models. RESULTS: Treadmill training is feasible and safe in LBD and HD; although, participants could not initiate treadmill walking at their comfortable overground speeds, and only 3 participants with HD were able to achieve their overground walking speed within the 20-minute session. No changes in gait measures, TUG times, and Q-Motor measures were found among LBD and HD participants after treadmill walking, although control participants demonstrated significant increases in several gait measures, and foot tap frequency (estimated difference = 0.290; p = 0.026). SIGNIFICANCE: Longer and more frequent treadmill sessions may be needed to see gait and motor function effects in LBD and HD. Motor and cognitive impairments associated with these diseases may make them less amenable to the effects of treadmill training.

Age of onset and behavioral manifestations in Huntington's disease: An Enroll-HD cohort analysis.

Huntington's disease is associated with motor, cognitive and behavioral dysfunction. Behavioral symptoms may present before, after, or simultaneously with clinical disease manifestation. The relationship between age of onset and behavioral symptom presentation and severity was explored using the Enroll-HD database. Manifest individuals (n = 4469) were initially divided into three groups for preliminary analysis: early onset (<30 years; n = 479); mid-adult onset (30-59 years; n = 3478); and late onset (>59 years; n = 512). Incidence of behavioral symptoms reported at onset was highest in those with early onset symptoms at 26% (n = 126), compared with 19% (n = 678) for mid-adult onset and 11% (n = 56) for late onset (P < 0.0001). Refined analysis, looking across the continuum of ages rather than between categorical subgroups found that a one-year increase in age of onset was associated with a 5.6% decrease in the odds of behavioral symptoms being retrospectively reported as the presenting symptom (P < 0.0001). By the time of study enrollment, the odds of reporting severe behavioral symptoms decreased by 5.5% for each one-year increase in reported age of onset. Exploring environmental, genetic and epigenetic factors that affect age of onset and further characterizing types and severity of behavioral symptoms may improve treatment and understanding of Huntington's disease's impact on affected individuals.

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington's disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington's Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression.

Data-driven evolution of neurosurgical gene therapy delivery in Parkinson's disease.

Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson's disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. These challenges have recently been addressed during the evolution of novel techniques for vector delivery that include the use of intraoperative MRI. The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery.

Genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease.

BACKGROUND: The huntingtin gene (HTT) pathogenic cytosine-adenine-guanine (CAG) repeat expansion responsible for Huntington disease (HD) is phased with single nucleotide polymorphisms (SNPs), providing targets for allele-selective treatments. OBJECTIVE: This prospective observational study defined the frequency at which rs362307 (SNP1) or rs362331 (SNP2) was found on the same allele with pathogenic CAG expansions. METHODS: Across 7 US sites, 202 individuals with HD provided blood samples that were processed centrally to determine the number and size of CAG repeats, presence and heterozygosity of SNPs, and whether SNPs were present on the mutant HTT allele using long-read sequencing and phasing. RESULTS: Heterozygosity of SNP1 and/or SNP2 was identified in 146 (72%) individuals. The 2 polymorphisms were associated only with the mHTT allele in 61% (95% high density interval: 55%, 67%) of individuals. CONCLUSIONS: These results are consistent with previous reports and demonstrate the feasibility of genotyping, phasing, and targeting of HTT SNPs for personalized treatment of HD.

The Step Test Evaluation of Performance on Stairs (STEPS): Validation and reliability in a neurological disorder.

BACKGROUND: Individuals with neurological disorders often have difficulty negotiating stairs that can lead to injurious falls. Clinicians lack a clinical tool to identify impairments in stair negotiation and to assist their decision making regarding treatment plans to improve stair performance and safety. We developed a new tool called the Step Test Evaluation of Performance on Stairs (STEPS) that is designed to assess stair performance and safety in neurological populations. OBJECTIVES: This study aimed to determine interrater and intrarater reliability of STEPS and its concurrent content validity to various clinical balance and mobility measures using individuals with Huntington's disease (HD) as the first test population. METHODS: Forty individuals with HD (mean age 50.35) participated. Three observers rated live performances of the STEPS (interrater reliability) and seven observers rated videotaped performances twice (intrarater reliability). STEPS scores correlated with clinical mobility and balance test scores. RESULTS: Excellent inter- and intrarater reliability (ICCs = 0.91 and 0.89 respectively) and good internal consistency (α = 0.83) were found. Better STEPS performance correlated with better performance on co-administered motor and mobility measures and Stair Self-Efficacy scores. Per multivariable regression analysis, the Unified Huntington's Disease Rating Scale modified motor score and descent time were significant predictors of STEPS performance. CONCLUSIONS: The STEPS tool is easy to administer, requires no special devices and can be completed in less than five minutes. In the HD test population, it shows high reliability and validity making it a potentially useful tool for assessing maneuverability and safety on stairs in HD. The results suggest that the STEPS tool warrants further study to determine STEPS cut-off values for fall prediction in HD and may prove useful as an assessment tool for other neurological disorders.

Cognitive Dysfunction Contributes to Mobility Impairments in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder that results in a gradual decline in mobility and balance. Increasing evidence has documented an important role of executive function in the safe ambulation of the elderly and people with a variety of neurological disorders. Little is known about the contribution of cognitive deficits to decline in mobility over time in HD. OBJECTIVE: This study examined the relationships of mobility, motor and cognitive function measures at baseline, and of mobility and cognitive measures over four years. METHODS: A retrospective chart review was performed on 70 patients with genetically confirmed HD (age 20-75 years old) across 121 HD clinic visits. Correlations between Unified Huntington's Disease Rating Scale - Total Motor, Tinetti Mobility Test (TMT), and cognitive measures (Letter Verbal Fluency, Symbol Digit Modalities Test (SDMT), and Stroop Test) were analyzed. Longitudinal relationships between TMT and cognitive measures were examined using mixed effect regression models. RESULTS: Gait and balance measures representing domains of mobility (TMT scores) were significantly correlated with each of the cognitive measures with the exception of the Verbal Fluency score. Mixed effects regression modeling showed that the Stroop Interference sub-test and SDMT were significant predictors (p-values <0.01) of TMT total scores. CONCLUSIONS: Impairments in executive function measures correlate highly with measures of gait, balance and mobility in individuals with HD. Interventions designed to improve mobility and decrease fall risk should also address issues of cognitive impairments with particular consideration given to interventions that may focus on motor-cognitive dual task training.

Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea.

Importance: Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study. Objectives: To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD). Design, Setting, and Participants: In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control. Interventions: Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen. Main Outcomes and Measures: Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington's Disease Rating Scale total maximal chorea score and total motor score were efficacy end points. Results: Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001). Conclusions and Relevance: In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.

Quantitative biomechanical assessment of trunk control in Huntington's disease reveals more impairment in static than dynamic tasks.

Postural instability is common in individuals with Huntington's disease (HD), yet little is known about control of the trunk during static and dynamic activities. We compared the trunk motion of 41 individuals with HD and 36 controls at thoracic and pelvic levels during sitting, standing, and walking using wearable iPod sensors. We also examined the ability of individuals with HD to respond to an auditory cue to modify trunk position when the pelvis moved >8° in sagittal or frontal planes during sitting using custom software. We found that amplitude of thoracic and pelvic trunk movements was significantly greater in participants with HD, and differences were more pronounced during static (i.e. sitting, standing) than dynamic (i.e. walking) tasks. In contrast to the slow, smooth sinusoidal trunk movements of controls, individuals with HD demonstrated rapid movements with varying amplitudes that continuously increased without stabilizing. Ninety-seven percent of participants with HD were able to modify their trunk position in response to auditory cues. Our results demonstrate that wearable iPod sensors are clinically useful for rehabilitation professionals to measure and monitor trunk stability in persons with HD. Additionally, auditory cueing holds potential as a useful training tool to improve trunk stability in HD.

Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease.

BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.

Motor performance differentiates individuals with Lewy body dementia, Parkinson's and Alzheimer's disease.

INTRODUCTION: Differential diagnosis of dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease (PD) and Alzheimer's disease (AD) is challenging. Comparative motor profiles of these neurodegenerative disorders may aid in earlier diagnosis but have not been extensively studied. METHODS: Groups were rigorously matched by age, education, and sex. DLB/PDD participants were matched by Mini-Mental State Examination Score to individuals with AD and by Unified Parkinson's Disease Rating Scale motor scores to individuals with PD. Gait, balance, dual task walking and hand dexterity measures were compared between a combined group (n=21) of individuals with Lewy body dementia (LBD) consisting of those with DLB (n=11) and PDD (n=10) to individuals with PD (n=21) or AD (n=21). RESULTS: Individuals at the same disease stage with LBD walked significantly slower with shorter stride lengths (p<0.05), demonstrated poorer balance on both the Tinetti and Berg Balance Scale, and poorer performance on dual-task and figure-of-eight walking compared to PD and AD (p<0.05 for all) groups. Upper extremity coordination on the 9-hole peg test differentiated LBD from both PD and AD and was the only motor test in which individuals with AD performed worse than those with PD. Tinetti balance subscores were significantly lower in PDD compared to DLB participants (10.4±2.3 versus 12.8±2.3; p=0.027). CONCLUSIONS: Motor features distinguish individuals with LBD from those with AD and PD. Measures of gait, balance and finger dexterity provide an additional means of differentiating individuals with LBD from those with AD and PD.

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer's and Parkinson's Diseases.

Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) and Parkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea.

Impact of tetrabenazine on gait and functional mobility in individuals with Huntington's disease.

Chorea may contribute to balance problems and walking difficulties that lead to higher fall rates in individuals with Huntington's disease (HD). Few studies have examined the effects of tetrabenazine (TBZ), an anti-choreic drug, on function and mobility in HD. The purpose of this study was to compare: 1) gait measures in forward walking, 2) balance and mobility measures, and 3) hand and forearm function measures on and off TBZ. We hypothesized that use of TBZ would improve gait, transfers and hand and forearm function. Eleven individuals with HD on stable doses of TBZ were evaluated while off medication and again following resumption of medication. Significant improvements were found on the Unified Huntington's Disease Rating Scale (UHDRS) motor scores, Tinetti Mobility Test (TMT) total (t=4.20, p=0.002) and balance subscale (t=-4.61, p=0.001) scores, and the Five Times Sit-to-Stand test (5TSST, t=3.20, p=.009) when on-TBZ compared to off-TBZ. Spatiotemporal gait measures, the Six Condition Romberg test, and UHDRS hand and forearm function items were not changed by TBZ use. Improved TMT and 5TSST performance when on drug indicates that TBZ use may improve balance and functional mobility in individuals with HD.

Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease.

BACKGROUND AND PURPOSE: Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. METHODS: Participants with HD [n = 20; mean age ± SD=50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. RESULTS: Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. CONCLUSIONS: The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD.

Video game play (Dance Dance Revolution) as a potential exercise therapy in Huntington's disease: a controlled clinical trial.

OBJECTIVE: To investigate the feasibility, acceptability, and safety of a supervised video game exercise program administered via Dance Dance Revolution in individuals with Huntington's disease. DESIGN: A cross-over, controlled, single-blinded, six-week trial. SETTING: Home-based. PARTICIPANTS: Eighteen ambulatory individuals with Huntington's disease (seven male, mean age 50.7 SD 14.7). INTERVENTIONS: Participants played the Dance Dance Revolution game with supervision and the handheld game without supervision for 45 minutes, two days per week for six weeks. OUTCOME MEASURES: Game play performance and adherence, participant perceptions of the game, safety (vital signs, adverse health changes), spatiotemporal gait measures, Four-Square Step Test, Tinetti Mobility Test, Activities-Specific Balance Confidence Scale, and World Health Organization Quality of Life - Bref, before and after each intervention. RESULTS: Most participants improved on game play, enjoyed playing the game, and wanted to continue playing after study completion. After playing Dance Dance Revolution, participants showed significant reductions in double support percentage (adjusted mean difference (95% confidence intervals): -2.54% (-4.75, -0.34) for forward walking and -4.18 (-6.89, -0.48) for backward walking) and those with less severe motor symptoms had reductions in heel-to-heel base of support during forward walking. The remaining measures were not significantly impacted by the intervention. CONCLUSION: Dance Dance Revolution appears to be a feasible, motivating, and safe exercise intervention for individuals with Huntington's disease.

Assistive devices alter gait patterns in Parkinson disease: advantages of the four-wheeled walker.

Gait abnormalities are a hallmark of Parkinson's disease (PD) and contribute to fall risk. Therapy and exercise are often encouraged to increase mobility and decrease falls. As disease symptoms progress, assistive devices are often prescribed. There are no guidelines for choosing appropriate ambulatory devices. This unique study systematically examined the impact of a broad range of assistive devices on gait measures during walking in both a straight path and around obstacles in individuals with PD. Quantitative gait measures, including velocity, stride length, percent swing and double support time, and coefficients of variation were assessed in 27 individuals with PD with or without one of six different devices including canes, standard and wheeled walkers (two, four or U-Step). Data were collected using the GAITRite and on a figure-of-eight course. All devices, with the exception of four-wheeled and U-Step walkers significantly decreased gait velocity. The four-wheeled walker resulted in less variability in gait measures and had less impact on spontaneous unassisted gait patterns. The U-Step walker exhibited the highest variability across all parameters followed by the two-wheeled and standard walkers. Higher variability has been correlated with increased falls. Though subjects performed better on a figure-of-eight course using either the four-wheeled or the U-Step walker, the four-wheeled walker resulted in the most consistent improvement in overall gait variables. Laser light use on a U-Step walker did not improve gait measures or safety in figure-of-eight compared to other devices. Of the devices tested, the four-wheeled-walker offered the most consistent advantages for improving mobility and safety.

The impact of different types of assistive devices on gait measures and safety in Huntington's disease.

BACKGROUND: Gait and balance impairments lead to frequent falls and injuries in individuals with Huntington's disease (HD). Assistive devices (ADs) such as canes and walkers are often prescribed to prevent falls, but their efficacy is unknown. We systematically examined the effects of different types of ADs on quantitative gait measures during walking in a straight path and around obstacles. METHODS: Spatial and temporal gait parameters were measured in 21 subjects with HD as they walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6 commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3 or 4 wheeled walker). Subjects also were timed and observed for number of stumbles and falls while walking around two obstacles in a figure-of-eight pattern. RESULTS: Gait measure variability (i.e., coefficient of variation), an indicator of fall risk, was consistently better when using the 4WW compared to other ADs. Subjects also walked the fastest and had the fewest number of stumbles and falls when using the 4WW in the figure-of-eight course. Subjects walked significantly slower using ADs compared to no AD both across the GAITRite and in the figure-of-eight. Measures reflecting gait stability and safety improved with the 4WW but were made worse by some other ADs.