Travis Cruickshank

The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage Huntington's disease: a pilot study

Despite advances in the understanding of Huntingtons disease (HD), treatment remains symptomatic. Multidisciplinary rehabilitation, however, appears to impact disease progression. Here we show the feasibility, safety and efficacy of a 9‐month multidisciplinary rehabilitation programme in a small cohort of patients with early‐to‐middle‐stage HD.

The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington's disease: An exploratory study

There is a wealth of evidence detailing gray matter degeneration and loss of cognitive function over time in individuals with Huntingtons disease (HD). Efforts to attenuate disease‐related brain and cognitive changes have been unsuccessful to date. Multidisciplinary rehabilitation, comprising motor and cognitive intervention, has been shown to positively impact on functional capacity, depression, quality of life and some aspects of cognition in individuals with HD. This exploratory study aimed to evaluate, for the first time, whether multidisciplinary rehabilitation can slow further deterioration of disease‐related brain changes and related cognitive deficits in individuals with manifest HD.

A systematic review and meta-analysis of strength training in individuals with multiple sclerosis or parkinson disease

AbstractStrength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis.This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis.A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014.English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis.Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling).Included articles were critically appraised using the Physiotherapy Evidence Database scale.Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training.The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis.

Novel Nut and Bolt Task Quantifies Motor Deficits in Premanifest and Manifest Huntington's Disease

Background: We investigated the use of a simple novel nut and bolt task in premanifest and manifest Huntington’s disease (HD) patients to detect and quantify motor impairments at all stages of the disease. Methods: Premanifest HD (n=24), manifest HD (n=27) and control (n=32) participants were asked to screw a nut onto a bolt in one direction, using three different sized bolts with their left and right hand in turn. Results: We identified some impairments at all stages of HD and in the premanifest individuals, deficits in the non-dominant hand correlated with disease burden scores. Conclusion: This simple, cheap motor task was able to detect motor impairments in both premanifest and manifest HD and as such might be a useful quantifiable measure of motor function for use in clinical studies.

Surface electromyograph activity of submental muscles during swallowing and expiratory muscle training tasks in Huntington's disease patients

INTRODUCTION Huntingtons disease (HD) patients have difficulty in swallowing, leading to aspiration pneumonia, which is a major cause of death. It seems possible that submental muscles that are crucial for preventing an escape of a bolus into the airway, are affected by HD, but no previous studies have investigated this. OBJECTIVE To assess surface electromyograph (sEMG) activity of submental muscles during swallowing and expiratory muscle training (EMT) tasks in HD patients in comparison to healthy volunteers. METHODS sEMG activities of submental muscles during saliva, water swallowing, EMT tasks performed at 25% and 75% of maximum expiratory pressure were recorded and normalised by the sEMG activity during an effortful swallow in 17 early to mid stage HD patients and 17 healthy volunteers. RESULTS sEMG activity was greater (p<0.05) during EMT tasks than saliva and water swallowing, but was not significantly different between groups for saliva, water swallowing and EMT at 25%. HD patients had lower sEMG activity for EMT at 75% (p<0.05). CONCLUSION Decreases in submental muscle activity were not evident in HD patients except during EMT at 75%. This suggests that relative submental muscle weakness is observed only during a high intensity task in early to mid stage HD patients.

Respiratory muscle training on pulmonary and swallowing function in patients with Huntington’s disease: a pilot randomised controlled trial

Objective: To examine the effects of 4-month of respiratory muscle training on pulmonary and swallowing function, exercise capacity and dyspnoea in manifest patients with Huntington’s disease. Design: A pilot randomised controlled trial. Setting: Home based training program. Participants: Eighteen manifest Huntington’s disease patients with a positive genetic test and clinically verified disease expression, were randomly assigned to control group (n=9) and training group (n=9). Intervention: Both groups received home-based inspiratory (5 sets of 5 repetitions) and expiratory (5 sets of 5 repetitions) muscle training 6 times a week for 4 months. The control group used a fixed resistance of 9 centimeters of water, and the training group used a progressively increased resistance from 30% to 75% of each patient’s maximum respiratory pressure. Main measures: Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, six minutes walk test, dyspnoea, water-swallowing test and swallow quality of life questionnaire were assessed before, at 2 and 4 months after training. Results: The magnitude of increases in maximum inspiratory (d=2.9) and expiratory pressures (d=1.5), forced vital capacity (d=0.8), forced expiratory volume in 1 second (d=0.9) and peak expiratory flow (d=0.8) was substantially greater for the training group in comparison to the control group. Changes in swallowing function, dyspnoea and exercise capacity were small (d≤0.5) for both groups without substantial differences between groups. Conclusions: A home-based respiratory muscle training program appeared to be beneficial to improve pulmonary function in manifest Huntington’s disease patients but provided small effects on swallowing function, dyspnoea and exercise capacity.

Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies.

Huntingtons disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways.

Investigating the relationships between hypothalamic volume and measures of circadian rhythm and habitual sleep in premanifest Huntington's disease

Objective Pathological changes within the hypothalamus have been proposed to mediate circadian rhythm and habitual sleep disturbances in individuals with Huntington’s disease (HD). However, investigations examining the relationships between hypothalamic volume and circadian rhythm and habitual sleep in individuals with HD are sparse. This study aimed to comprehensively evaluate the relationships between hypothalamic pathology and circadian rhythm and habitual sleep disturbances in individuals with premanifest HD. Methods Thirty-two individuals with premanifest HD and twenty-nine healthy age- and gender-matched controls participated in this dual-site, cross-sectional study. Magnetic resonance imaging scans were performed to evaluate hypothalamic volume. Circadian rhythm and habitual sleep were assessed via measurement of morning and evening cortisol and melatonin levels, wrist-worn actigraphy, the Consensus Sleep Diary and sleep questionnaires. Information on mood, physical activity levels and body composition were also collected. Results Compared to healthy controls, individuals with premanifest HD displayed significantly reduced grey matter volume in the hypothalamus, decreased habitual sleep efficiency and increased awakenings; however, no alterations in morning cortisol or evening melatonin release were noted in individuals with premanifest HD. While differences in the associations between hypothalamic volume and cortisol and melatonin output existed in individuals with premanifest HD compared to healthy controls, no consistent associations were observed between hypothalamic volume and circadian rhythm or habitual sleep outcomes. Conclusion While significant differences in associations between hypothalamic volume and cortisol and melatonin existed between individuals with premanifest HD and healthy controls, no differences in circadian markers were observed between the groups. This suggests that circadian regulation is maintained despite hypothalamic pathology, perhaps via neural compensation. Longitudinal studies are required to further understand the relationships between the hypothalamus and circadian rhythm and habitual sleep disturbances in HD as the disease course lengthens.

Computerised Dynamic Posturography in Premanifest and Manifest individuals with Huntington’s Disease

Evidence from small-scale studies indicates that impairments in postural stability are an early and disabling feature of Huntington’s disease (HD) and may be a useful clinical endpoint for disease modifying trials. Larger studies are needed to confirm these preliminary findings and the suitability of postural stability outcomes as clinical endpoints. Static and dynamic postural stability were evaluated in 54 premanifest HD, 36 manifest HD and 45 healthy individuals using the Sensory Organization Test (SOT) and Limits of Stability (LOS) test. Manifest HD displayed significantly lower scores on all SOT conditions and on the SOT composite score and had more falls than healthy and premanifest HD (p < 0.05). Premanifest and manifest HD demonstrated significantly lower endpoint excursion (p < 0.001), maximum excursion (p ≤ 0.001), and directional control (p ≤ 0.004) values than healthy individuals on the LOS test. Deficits in LOS were found to manifest on the left side of premanifest HD. Significant but low associations were observed between UHDRS-TMS, disease burden score, diagnostic confidence level, SOT conditions and SOT composite score. We confirm here that individuals with premanifest and manifest HD display significant impairments in static and dynamic postural stability. Dynamic posturography assessments should be considered as clinical endpoints for future disease modifying trials.

Effects of multidisciplinary therapy on physical function in Huntington's disease

The primary objective of this trial was to evaluate the effects of outpatient multidisciplinary therapy, compared to usual care, on measures of physical function and muscle strength in patients with manifest Huntingtons disease (HD).