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Huntington’s disease (HD) patients suffer from progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep-wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and excessive fatigue. The BACHD mouse model exhibits many HD core symptoms including circadian dysfunction. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. We evaluated the effects of time-restricted feeding (TRF) on the BACHD mouse model. At 3 months of age, the animals were divided into 2 groups: ad lib and TRF. The TRF-treated BACHD mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle (ZT 15-21) of the period when mice are normally active (ZT 12-24). Following 3 months of treatment (when mice reached the early disease stage), the TRF-treated BACHD mice showed improvements in their locomotor activity and sleep behavioral rhythms. Furthermore, we found improved heart rate variability, suggesting that their autonomic nervous system dysfunction was improved. On a molecular level, TRF altered the phase but not the amplitude of the PER2::LUC rhythms measured in vivo and in vitro. Importantly, treated BACHD mice exhibited improved motor performance compared with untreated BACHD controls, and the motor improvements were correlated with improved circadian output. It is worth emphasizing that HD is a genetically caused disease with no known cure. Lifestyle changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of circadian-based treatment strategies in a preclinical model of HD. [ABSTRACT FROM AUTHOR]

Objectives: Huntington's disease (HD) is a profoundly incapacitating, and ultimately fatal, neurodegenerative disease. HD is presently incurable, so the current goal is to allow affected individuals to live as well as possible with the illness, to maximise functional independence and quality of life for the person with HD, their carers and family members. This clinical update review focuses on the common neuropsychiatric manifestations in HD, and outlines and evaluates the various neuropsychiatric facets of HD, including the aetiology, symptoms and diagnosis.Conclusions: Neuropsychiatric symptoms can precede the classic motor clinical symptoms of HD (prodromal HD) by decades, and cause significant functional impairment. HD provides key insights and understanding into the organic psychiatric disorders, including contemporary clinical insights into the process of neurodegeneration and manifestation of neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Objectives: This clinical update review focuses on the management of the neuropsychiatric manifestations of Huntington's disease (HD). The review highlights current issues regarding pharmacological and non-pharmacological treatment, putative therapeutics and recent relevant research findings in this area.Conclusions: Neuropsychiatric symptoms may precede the classic motor clinical symptoms of HD (prodromal HD) by decades and cause significant functional impairment. Early recognition and comprehensive non-pharmacological, usually in combination with pharmacological, treatment is essential. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a study that determines the effectiveness of the video game Dance Dance Revolution as an exercise therapy in patients with Huntington's disease. It outlines the method of the study that observes 18 ambulatory individuals with Huntington's disease. It notes the result of the study which reveals that the Dance Dance Revolution can serve as safe exercise intervention for patients with Hungtington's disease.

The article offers information on a study carried out to explore feasibility, safety and outcome of an exercise intervention in people with Huntington's disease. Patients in an intervention group were asked to perform exercises at home and the control group received their usual care. Differences between groups were observed in gait speed, balance, function and level of physical activity. It was found that exercise programmes are feasible, beneficial and safe for Huntington disease patients.

Huntington’s disease (HD) is an inherited neurodegenerative disorder with a prevalence of 1 in 10 000. It is an autosomal dominant condition characterized by involuntary movements, changes in behaviour and cognition as well as psychiatric manifestations. There are currently no treatments that will cure or slow its progression. But, direct mutation testing allows a definitive diagnosis to be given and at-risk individuals to undergo predictive testing if they so wish. HD can be multigenerational in its impact upon a family which means GPs are in a unique position to educate, support and coordinate care for these patients. The aim of this article is to give an overview of HD, including its genetics, clinical features, different types of genetic testing and reproductive options as well as to introduce some of the ethical issues that can arise during a consultation. Many of the concepts covered are applicable to other genetic conditions that GPs may come across in their practice. [ABSTRACT FROM AUTHOR]

Early diagnosis and follow-up of neurodegenerative diseases are often hampered by the lack of reliable biomarkers. Neuroimaging techniques like magnetic resonance spectroscopy (MRS) offer promising tools to detect biochemical alterations at early stages of degeneration. Intracellular pH, which can be measured noninvasively by 31P-MRS, has shown variations in several brain diseases. Our purpose has been to evaluate the potential of MRS-measured pH as a relevant biomarker of early degeneration in Huntington's disease (HD). We used a translational approach starting with a preclinical validation of our hypothesis before adapting the method to HD patients. 31P-MRS-derived cerebral pH was first measured in rodents during chronic intoxication with 3-nitropropionic acid (3NP). A significant pH increase was observed early into the intoxication protocol (pH=7.17±0.02 after 3 days) as compared with preintoxication (pH=7.08±0.03). Furthermore, pH changes correlated with the 3NP-induced inhibition of succinate dehydrogenase and preceded striatum lesions. Using a similar MRS approach implemented on a clinical MRI, we then showed that cerebral pH was significantly higher in HD patients (n=7) than in healthy controls (n=6) (7.05±0.03 versus 7.02±0.01, respectively, P=0.026). Altogether, both preclinical and human data strongly argue in favor of MRS-measured pH being a promising biomarker for diagnosis and follow-up of HD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of an intensive, inpatient rehabilitation programme on individuals affected by Huntington's disease. Design: A pilot study. Within-subjects design. Setting: Inpatient rehabilitation home of the Italian welfare system. Subjects: Forty patients, early and middle stage of the disease, were recruited to an intensive, inpatient rehabilitation protocol. Interventions: The treatment programme included respiratory exercises and speech therapy, physical and occupational therapy and cognitive rehabilitation exercises. The programme involved three-week admission periods of intensive treatment that could be repeated three times a year. Main measures: A standard clinical assessment was performed at the beginning of each admission using the Zung Depression Scale, Mini-Mental State Examination (MMSE), Barthel Index, Tinetti Scale and Physical Performance Test (PPT). Tinetti and PPT were also used at the end of each admission to assess the outcomes in terms of motor and functional performance. Results: Each three-week period of treatment resulted in highly significant (P < 0.001) improvements of motor performance and daily life activities. The average increase was 4.7 for Tinetti and 5.21 for PPT scores. No carry-over effect from one admission to the next was apparent but at the same time, no motor decline was detected over two years, indicating that patients maintained a constant level of functional, cognitive as well as motor performance. Conclusions: Intensive rehabilitation treatments may positively influence the maintenance of functional and motor performance in patients with Huntington's disease. [ABSTRACT FROM AUTHOR]

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We present the case of a patient with advanced Huntington's disease treated with minocycline. Minocycline (but not tetracycline which does not cross the blood-brain barrier) appears to increase longevity in an animal model for Huntington's disease. The patient has been maintained on minocycline for more than 1 year with positive effects. Cessation of minocyclin for 3 weeks resulted in an exacerbation of symptoms. The animal studies have suggested that minocycline may prevent progression of Huntington's disease and other neurological disorders. By contrast, this present result suggests that minocycline may benefit those with advanced Huntington's disease and can be used safely in these patients. [ABSTRACT FROM AUTHOR]