BACKGROUND AND PURPOSE: Dysfunction of the airway defence system in Huntington's disease (HD) is a significant but often overlooked problem. Although expiratory muscle strength training (EMST) is frequently utilized in cough effectiveness treatment, its specific impact in HD patients has not yet been explored. This study investigated the effects of EMST on voluntary peak cough flow (vPCF) in HD patients and evaluated the retention of potential gains post-intervention. METHODS: In this prospective case-controlled trial, 29 HD patients completed an 8-week wait-to-start period, which served to identify the natural development of expiratory muscle strength and vPCF. This was followed by 8 weeks of EMST training and an additional 8 weeks of follow-up. The study's outcome parameters, vPCF and maximum expiratory pressure (MEP), were measured against those of age- and sex-matched healthy controls. RESULTS: Huntington's disease patients had significantly lower MEP (p < 0.001) and vPCF (p = 0.012) compared to healthy controls at baseline. Following the EMST, significant improvements in MEP (d = 1.39, p < 0.001) and vPCF (d = 0.77, p = 0.001) were observed, with HD patients reaching the cough performance levels of healthy subjects. However, these gains diminished during the follow-up, with a significant decline in vPCF (d = -0.451, p = 0.03) and in MEP (d = -0.71; p = 0.002). CONCLUSIONS: Expiratory muscle strength training improves expiratory muscle strength and voluntary cough effectiveness in HD patients, but an ongoing maintenance programme is necessary to sustain the improvements.
- MeSH
- dechová cvičení metody MeSH
- dospělí MeSH
- dýchací svaly * patofyziologie MeSH
- Huntingtonova nemoc * patofyziologie komplikace rehabilitace MeSH
- kašel * patofyziologie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- odporový trénink metody MeSH
- prospektivní studie MeSH
- studie případů a kontrol MeSH
- svalová síla * fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: A declining cognitive performance is a hallmark of Huntington's disease (HD). The neuropsychological battery of the Unified HD Rating Scale (UHDRS'99) is commonly used for assessing cognition. However, there is a need to identify and minimize the impact of confounding factors, such as language, gender, age, and education level on cognitive decline. OBJECTIVES: Aim is to provide appropriate, normative data to allow clinicians to identify disease-associated cognitive decline in diverse HD populations by compensating for the impact of confounding factors METHODS: Sample data, N = 3267 (60.5% females; mean age of 46.9 years (SD = 14.61, range 18-86) of healthy controls were used to create a normative dataset. For each neuropsychological test, a Bayesian generalized additive model with age, education, gender, and language as predictors was constructed to appropriately stratify the normative dataset. RESULTS: With advancing age, there was a non-linear decline in cognitive performance. In addition, performance was dependent on educational levels and language in all tests. Gender had a more limited impact. Standardized scores have been calculated to ease the interpretation of an individual's test outcome. A web-based online tool has been created to provide free access to normative data. CONCLUSION: For defined neuropsychological tests, the impact of gender, age, education, and language as factors confounding disease-associated cognitive decline can be minimized at the level of a single patient examination.
- MeSH
- Bayesova věta MeSH
- Huntingtonova nemoc * komplikace diagnóza MeSH
- jazyk (prostředek komunikace) MeSH
- kognice MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- stupeň vzdělání MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: Motor speech alterations are a prominent feature of clinically manifest Huntington's disease (HD). Objective acoustic analysis of speech can quantify speech alterations. It is currently unknown, however, at what stage of HD speech alterations can be reliably detected. We aimed to explore the patterns and extent of speech alterations using objective acoustic analysis in HD and to assess correlations with both rater-assessed phenotypical features and biological determinants of HD. METHODS: Speech samples were acquired from 44 premanifest (29 pre-symptomatic and 15 prodromal) and 25 manifest HD gene expansion carriers, and 25 matched healthy controls. A quantitative automated acoustic analysis of 10 speech dimensions was performed. RESULTS: Automated speech analysis allowed us to differentiate between participants with HD and controls, with areas under the curve of 0.74 for pre-symptomatic, 0.92 for prodromal, and 0.97 for manifest stages. In addition to irregular alternating motion rates and prolonged pauses seen only in manifest HD, both prodromal and manifest HD displayed slowed articulation rate, slowed alternating motion rates, increased loudness variability, and unstable steady-state position of articulators. In participants with premanifest HD, speech alteration severity was associated with cognitive slowing (r = -0.52, p < 0.001) and the extent of bradykinesia (r = 0.43, p = 0.004). Speech alterations correlated with a measure of exposure to mutant gene products (CAG-age-product score; r = 0.60, p < 0.001). CONCLUSION: Speech abnormalities in HD are associated with other motor and cognitive deficits and are measurable already in premanifest stages of HD. Therefore, automated speech analysis might represent a quantitative HD biomarker with potential for assessing disease progression.
- MeSH
- biologické markery MeSH
- Huntingtonova nemoc * komplikace genetika psychologie MeSH
- kognitivní poruchy * komplikace MeSH
- lidé MeSH
- průřezové studie MeSH
- řeč MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- antidepresiva terapeutické užití MeSH
- antipsychotika terapeutické užití MeSH
- chorea * etiologie farmakoterapie MeSH
- depresivní poruchy farmakoterapie MeSH
- dospělí MeSH
- Huntingtonova nemoc * diagnóza farmakoterapie komplikace MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVE: Cognitive decline is a key characteristic of Huntington's disease (HD). This study aimed to investigate the diagnostic accuracy of a cognitive battery with six tests used by most HD research centers to assess cognitive impairment in HD. METHOD: In total, 106 HD patients in different disease stages with more (HD-CD, N = 30) and less cognitive impairments (HD-NC, N = 70) and 100 healthy controls (NC) were matched by age, sex, and education and were examined using a standardized protocol including cognitive, motor, and functional assessments. RESULTS: One-way between-groups analysis of variance showed that controls performed significantly better than HD patients and that HD-NC significantly outperformed HD-CD patients in all cognitive tests (NC > HD-NC > HD-CD), with all Games-Howell post-hoc tests p < .001. Analyses using area under the receiver-operating characteristic curve (AUC) disclosed the diagnostic accuracy of all tests included in the battery to discriminate between NC and HD patients with AUC ranging from 0.809 to 0.862 (all p < .001) and between HD-CD and HD-NC patients with AUC ranging from 0.833 to 0.899 (all p < .001). In both analysis, Stroop Color Naming Test showed the highest discriminative potential. Additional analyses showed that cognitive deficits in all domains progressed with disease duration. Moreover, cognitive performance correlated with the severity of motor and functional impairment (all p < .001) and with the Disease Burden Score regardless of disease duration and age. CONCLUSION: Our results indicate that the cognitive battery is a suitable tool for assessing cognitive impairment in HD.
- MeSH
- Huntingtonova nemoc * komplikace diagnóza MeSH
- kognice MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- osobní újma zaviněná nemocí MeSH
- tělesná a funkční výkonnost MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Huntington's disease (HD) is an inherited devastating neurodegenerative disease with no known cure to date. Several therapeutic treatments for HD are in development, but their safety, tolerability and efficacy need to be tested before translation to bedside. The monogenetic nature of this disorder has enabled the generation of transgenic animal models carrying a mutant huntingtin (mHTT) gene causing HD. A large animal model reflecting disease progression in humans would be beneficial for testing the potential therapeutic approaches. Progression of the motor, cognitive and behavioral phenotype was monitored in transgenic Huntington's disease minipigs (TgHD) expressing the N-terminal part of human mHTT. New tests were established to investigate physical activity by telemetry, and to explore the stress-induced behavioral and cognitive changes in minipigs. The longitudinal study revealed significant differences between 6- to 8-year-old TgHD animals and their wild-type (WT) controls in a majority of the tests. The telemetric study showed increased physical activity of 4.6- to 6.5-year-old TgHD boars compared to their WT counterparts during the lunch period as well as in the afternoon. Our phenotypic study indicates progression in adult TgHD minipigs and therefore this model could be suitable for longstanding preclinical studies of HD.This article has an associated First Person interview with the first author of the paper.
- MeSH
- chování zvířat fyziologie MeSH
- geneticky modifikovaná zvířata MeSH
- Huntingtonova nemoc komplikace patofyziologie MeSH
- jazyk MeSH
- kognice fyziologie MeSH
- kondiční příprava zvířat MeSH
- longitudinální studie MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- pohybová aktivita * MeSH
- prasata MeSH
- psychický stres komplikace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Huntingtonova choroba (Huntington disease; HD) je autozomálně dominantní, dědičné neurodegenerativní onemocnění s fatální prognózou. Kromě typicky progresivně se zhoršujících motorických funkcí lze u pacientů s HD pozorovat i kognitivní a behaviorální poruchy. Mezi nejčastější symptomy patří také poruchy spánku, které mají velmi závažný dopad na kvalitu života jak pacientů, tak jejich blízkých a které bývají asociovány s narušeným cirkadiánním systémem. Stabilizace délky i kvality spánku posílením cirkadiánního systému by mohla zmírnit či potlačit mnohé symptomy HD, jež mají sice přímou příčinu v etiologii HD, sekundárně mohou být ale zesíleny dlouhodobým nedostatečným spánkem či právě poruchami cirkadiánního systému. U premanifestujících pacientů by takové zásahy mohly vést k pomalejšímu rozvoji či nástupu zejména kognitivních symptomů nemoci. Terapie synchronizujícím jasným světlem, která se již osvědčila jako doplňkový nástroj k léčbě afektivních i některých neurodegenerativních nemocí, by mohla vést k radikálnímu zlepšení života pacientů alespoň v počátečních stadiích onemocnění.
Huntington disease (HD) is an autosomal-dominant, hereditary neurodegenerative disease with a fatal prognosis. Besides the typical progressive deterioration of motor functions, cognitive and behavioral disorders can also be observed in patients with HD. The most common symptoms also include sleep disorders that seriously affect the quality of life of the patients but also of their relatives and which are being associated with a disrupted circadian system. Stabilization of sleep lenght and quality by strengthening the circadian system could mitigate or suppress many HD symptoms, which, although being a direct result of the disease etiology, can secondarily be heightened by long-term insufficient sleep or circadian system disturbances. Such interventions could lead to slower especially cognitive symptom progression or onset in pre-manifesting patients. Synchronizing bright light therapy, which has already proven useful as a complementary tool for the treatment of affective disorders, as well as some neurodegenerative diseases, could lead to radical improvement of the patients‘ quality of life, at least in the early stages of disease development.
- Klíčová slova
- hodinové geny,
- MeSH
- cirkadiánní hodiny MeSH
- fototerapie metody MeSH
- Huntingtonova nemoc * komplikace terapie MeSH
- lidé MeSH
- poruchy spánku a bdění terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Cíl: Posturální instabilita a instabilita chůze patří mezi významné motorické symptomy Huntingtonovy nemoci (HN), které zvyšují riziko pádů. Rehabilitace je podstatnou součástí terapie instability. Cílem studie bylo zhodnotit, krátkodobý a dlouhodobý efekt multidisciplinárního rehabilitačního programu na posturální instabilitu i instabilitu chůze u HN a posoudit možnost provedení programu za hospitalizace. Metodika: 13 pacientů s HN bez těžšího kognitivního deficitu a deprese absolvovalo třítýdenní multidisciplinární rehabilitační program během hospitalizace, který byl specificky zaměřený na posturální stabilitu a stabilitu chůze. Vyšetření proběhla na začátku programu, po dokončení rehabilitace, po 1 a 3 měsících od dokončení. Testování zahrnovalo vyšetření stability chůze (Dynamic Gait Index; DGI), posturální stability pomocí posturografu na stabilní (PSS) and nestabilní 20% (PSU) plošině a motorické skóre pomocí Unified Huntington‘s Disease Rating Scale (UHDRS). Výsledky: PSS prokázalo statisticky významné zlepšení přetrvávající po dobu 3 měsíců a signifikantní zlepšení v DGI ihned po rehabilitaci. V motorickém skóre UHDRS a PSU statisticky významné zlepšení nalezeno nebylo. Závěr: Specifický rehabilitační program je bezpečný a dobře využitelný při terapii poruch stability u HN. Posturální stabilita dle PSS byla zlepšena po sledovanou dobu 3 měsíců. Zlepšení stability chůze dle DGI odeznělo do 1 měsíce. V PSU signifikantní zlepšení nebylo prokázáno. Tato studie nabízí návrh specifického rehabilitačního protokolu pro trénink stability u HN.
Aim: Postural and gait instability in Huntington‘s disease (HD) is a key component of the motor symptomatology which contributes to an increased risk of falls. Rehabilitation is considered beneficial in postural and gait stability treatment. We aimed to explore the feasibility and the short- and long-term effects of an inpatient multidisciplinary rehabilitation program on postural and gait stability in subjects with HD. Methods: A sample of 13 subjects with HD but with no severe cognitive deficit or depression underwent a 3-week specific inpatient rehabilitation program focused on postural and gait stability. Patients were examined at the baseline, after the completion of rehabilitation, and then 1 month and 3 months after the end of the program. The testing included: gait stability examination (Dynamic Gait Index; DGI), posturography examination of postural stability on a stable (PSS) and 20% unstable (PSU) platform and the total motor score evaluation by Unified Huntington‘s Disease Rating Scale (UHDRS). Results: There was a significant improvement lasting 3 months in PSS and a significant improvement in DGI immediately after the rehabilitation. There was no significant improvement in the PSU and UHDRS total motor score. Conclusion: Specific rehabilitation methods are safe and feasible and may be beneficial in the treatment of postural and gait instability in patients with early and mid-stage HD. The postural instability improvement measured by PSS persisted for at least 3 months. The gait stability improvement in DGI did not persist after 1 month. We found no improvement in PSU. This exploratory study offers a sample of a specific rehabilitation protocol for stability training in HD.
- Klíčová slova
- instabilita,
- MeSH
- chůze MeSH
- dospělí MeSH
- Huntingtonova nemoc * komplikace rehabilitace MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- rehabilitace metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
