Mid-stage Huntington's Disease Research Articles

Effect of a specific inpatient multidisciplinary rehabilitation program on postural and gait stability in Huntington's disease – Pilot study

Postural and gait instability in Huntington's disease (HD) is an essential part of the motor symptomatology causing falls contributing to morbidity and mortality. Rehabilitation (Rhb) is considered beneficial in stability treatment. However, the number of studies is still limited. This is the first multidisciplinary inpatient study using a specific program aimed at postural and gait stability in HD. We aimed to evaluate the short-and long-term effects of an inpatient multidisciplinary rehabilitation program on postural and gait instability in HD. A sample of 16 HD subjects without severe cognitive deficit or depression were included, 13 subjects completed the full course. They underwent a 3-week specific inpatient rehabilitation focused on stability. The examination was at baseline, after the completion, 1 and 3 months after the rehabilitation. The testing included: gait stability examination (Dynamic Gait Index; DGI), posturography examination of postural stability Limits of Stability on a stable (PSS) and 20% unstable (PSU) platform and the motor function evaluation by Unified Huntington's Disease Rating Scale (UHDRS-TMS). There was a significant improvement in DGI immediately after the Rhb and a significant 3 months lasting improvement in PSS. There was no significant improvement in PSU and UHDRS-TMS. Specific Rhb methods improved postural and gait instability in early- and mid-stage HD patients. The improvement in PSS persisted 3 months. We found no improvement in PSU, which is probably a too difficult test for this degree of stability impairment. The improvement in DGI does not persist after 1 month. This study offers a verified specific Rhb protocol for stability training in HD.

Fat-free mass and its predictors in Huntington's disease.

The causes of weight loss in Huntington's disease (HD) are not entirely clear. The aim was to identify risk factors that are associated with a loss of metabolically active tissues, i.e. fat-free mass. A consecutive cohort of non-diabetic HD participants (manifest HD, n = 43; CAG: mean 43.6.0 ± 3.6; preHD, n = 10; CAG: mean 41.4 ± 1.4) and 36 healthy controls was recruited. Twenty-five HD participants were early-stage HD (UHDRS Total Functional Capacity [TFC] stages I and II), 12 mid-stage HD (TFC stage III), and 6 participants were in late-stage HD (TFC stages IV and V). Food intake, basic metabolic rate and glucose homeostasis were assessed. In addition, fat-free mass was determined using bioelectric impedance analysis, and leptin, insulin and ghrelin as key metabolic regulators. Sex ratio and age were similar in HD participants (71 % women; age 50.6 ± 10.9) and controls (66 % women; age 46.4 ± 14.5). Body mass index (BMI) was lower in HD participants than controls (median 24.1 vs. 25.9, p = 0.04). However, fat-free mass and basic metabolic rate were not statistically different between groups and showed no association with disease burden. In controls and HD participants, leptin was the most important predictor of fat-free mass. While BMI was lower in HD participants, fat-free mass was similar to controls with leptin as its most important predictor. Leptin levels and fat-free mass measurements using bioelectric impedance analysis may be good screening tools to identify HD patients at risk for weight loss.

Task-specific training in Huntington disease: a randomized controlled feasibility trial.

Task-specific training may be a suitable intervention to address mobility limitations in people with Huntington disease (HD). The aim of this study was to assess the feasibility and safety of goal-directed, task-specific mobility training for individuals with mid-stage HD. This study was a randomized, blinded, feasibility trial; participants were randomly assigned to control (usual care) and intervention groups. This multisite study was conducted in 6 sites in the United Kingdom. Thirty individuals with mid-stage HD (13 men, 17 women; mean age=57.0 years, SD=10.1) were enrolled and randomly assigned to study groups. Task-specific training was conducted by physical therapists in participants' homes, focusing on walking, sit-to-stand transfers, and standing, twice a week for 8 weeks. Goal attainment scaling was used to individualize the intervention and monitor achievement of personal goals. Adherence and adverse events were recorded. Adjusted between-group comparisons on standardized outcome measures were conducted at 8 and 16 weeks to determine effect sizes. Loss to follow-up was minimal (n=2); adherence in the intervention group was excellent (96.9%). Ninety-two percent of goals were achieved at the end of the intervention; 46% of the participants achieved much better than expected outcomes. Effect sizes on all measures were small. Measurements of walking endurance were lacking. The safety of and excellent adherence to a home-based, task-specific training program, in which most participants exceeded goal expectations, are encouraging given the range of motivational, behavioral, and mobility issues in people with HD. The design of the intervention in terms of frequency (dose), intensity (aerobic versus anaerobic), and specificity (focused training on individual tasks) may not have been sufficient to elicit any systematic effects. Thus, a larger-scale trial of this specific intervention does not seem warranted.

Effects of a Two-Year Intensive Multidisciplinary Rehabilitation Program for Patients with Huntington's Disease: a Prospective Intervention Study.

Objective: To assess effects of a two year intensive, multidisciplinary rehabilitation program for patients with early- to mid-stage Huntington’s disease. Design: A prospective intervention study. Setting: One inpatient rehabilitation center in Norway. Subjects: 10 patients, with early- to mid-stage Huntington’s disease. Interventions: A two year rehabilitation program, consisting of six admissions of three weeks each, and two evaluation stays approximately three months after the third and sixth rehabilitation admission. The program focused on physical exercise, social activities, and group/teaching sessions. Main outcome measures: Standard measures for motor function, including gait and balance, cognitive function, including MMSE and UHDRS cognitive assessment, anxiety and depression, activities of daily living (ADL), health related quality of life (QoL) and Body Mass Index (BMI). Results: Six out of ten patients completed the full program. Slight, but non-significant, decline was observed for gait and balance from baseline to the evaluation stay after two years. Non-significant improvements were observed in physical QoL, anxiety and depression, and BMI. ADL-function remained stable with no significant decline. None of the cognitive measures showed a significant decline. An analysis of individual cases revealed that four out of the six participants who completed the program sustained or improved their motor function, while motor function declined in two participants. All the six patients who completed the program reported improved or stable QoL throughout the study period. Conclusion: Our findings suggest that participation in an intensive rehabilitation program is well tolerated among motivated patients with early to mid-stage HD. The findings should be interpreted with caution due to the small sample size in this study.

Q13 Perspectives of participating in a 12-week exercise programme for people with early -mid stage Huntington's disease

Regular involvement in physical activity is associated with health benefits, but little is known about supporting and encouraging regular exercise for people with Huntington's Disease (HD). This study aimed to...

Q12 A randomised feasibility study of a 12-week exercise programme in Huntington's disease (HD)

BackgroundThis multi-centre controlled study [ISRCTN 59910670] evaluated a 12-week exercise programme in mid stage HD in terms of adherence and potential benefit.Methods31 subjects (16 male) [mean (SD) age 50.4 (11.4)...

Q19 Intensive rehabilitation for Huntington's disease: a qualitative study of participants' and health professionals' experiences

BackgroundIn 2010, a multidisciplinary, group-based, intensive rehabilitation programme for individuals with early to mid-stage Huntington's disease (HD) was established at two rehabilitation centres in Norway. The programme included intensive physical...

A four-year prospective study of cognitive functioning in Huntington's disease

The contribution of neurologic, genetic, and demographic variables to decline in cognition was examined in 70 early- to mid-stage patients with Huntington's disease (HD) using random effects modeling. Study participants were followed prospectively at baseline and at four annual reevaluations. Only modest decline was noted on most neuropsychological variables. Neurologic dysfunction, assessed using the Quantified Neurologic Examination (QNE), proved to be the strongest predictor of cognitive decline. While significantly predictive of more rapid decline in neurologic functioning, CAG repeat length was not generally related to cognitive decline after adjusting for QNE, with the exception of performance on a single test of visual scanning and psychomotor speed (i.e., Trail Making Test, Part A). We propose that CAG repeat length is more closely linked with changes in basal ganglia that predominate in early- to mid-stage HD than with cortical degeneration seen later in disease progression. Such a relationship would explain the predictive value that CAG repeat length plays in changes associated with automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but not in dysfunction on tasks requiring higher-order processing.

A four-year prospective study of cognitive functioning in Huntington's disease

The contribution of neurologic, genetic, and demographic variables to decline in cognition was examined in 70 early- to mid-stage patients with Huntington's disease (HD) using random effects modeling. Study participants were followed prospectively at baseline and at four annual reevaluations. Only modest decline was noted on most neuropsychological variables. Neurologic dysfunction, assessed using the Quantified Neurologic Examination (QNE), proved to be the strongest predictor of cognitive decline. While significantly predictive of more rapid decline in neurologic functioning, CAG repeat length was not generally related to cognitive decline after adjusting for QNE, with the exception of performance on a single test of visual scanning and psychomotor speed (i.e., Trail Making Test, Part A). We propose that CAG repeat length is more closely linked with changes in basal ganglia that predominate in early- to mid-stage HD than with cortical degeneration seen later in disease progression. Such a relationship would explain the predictive value that CAG repeat length plays in changes associated with automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but not in dysfunction on tasks requiring higher-order processing. (JINS, 2006, 12, 445–454.)

Energy balance in early-stage Huntington disease

Huntington disease (HD) is a genetic neurologic disorder. Weight loss is common in HD and is related to progression of the disease, but the cause of weight loss remains unclear. The study objective was to compare 24-h energy expenditure (EE) and energy intake in persons with early midstage HD with those of matched control subjects to determine how HD affects energy balance. EE was assessed in 13 subjects with early-stage HD and in 9 control subjects via indirect calorimetry in a human respiratory chamber. Energy intake was determined by weighing all food provided and all leftovers from an ad libitum diet. Body composition was measured via air-displacement plethysmography. Stage of disease was estimated on the basis of the Unified Huntington's Disease Rating Scale and modified Mini-Mental Status examinations. Regression analysis included all 13 HD subjects; t tests were used for the comparisons between matched HD and control subjects. 24-h EE was 11% higher in the HD subjects than in the control subjects (NS). This difference was due to a higher (P = 0.043) waking metabolic rate, which was related to a significantly greater displacement of the center of mass by HD subjects than by control subjects (P = 0.028). On average, both groups were in positive energy balance and exceeded their energy expenditure by 2510-2929 kJ. Higher 24-h EE in persons with early midstage HD is due to increased physical activity, both voluntary and involuntary. However, HD subjects are able to maintain positive energy balance when offered adequate amounts of food in a controlled setting.