Autonomic nervous system function in Huntington's disease

Andrich, Jürgen

doi:10.1136/jnnp.72.6.726

Cited by 104 publications

(110 citation statements)

References 31 publications

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“…The obtained differences in the HRV variables between patients with HD and their controls are in accordance with previous clinical studies, suggesting that a profound ANS dysfunction often accompanies HD (Andrich et al., 2002). The potential cardiac consequences and possible mechanisms of ANS dysfunction in patients with HD have, however, received little attention.…”

Section: Discussionmentioning

confidence: 99%

“…The potential cardiac consequences and possible mechanisms of ANS dysfunction in patients with HD have, however, received little attention. HRV has been shown to be altered in HD subjects (Andrich et al., 2002; Kobal et al., 2010). An inverse correlation between the severity of clinical HD symptoms assessed by UHDRS and the modulation of cardiovagal activity has been found (Andrich et al., 2002).…”

Section: Discussionmentioning

confidence: 99%

“…HRV has been shown to be altered in HD subjects (Andrich et al., 2002; Kobal et al., 2010). An inverse correlation between the severity of clinical HD symptoms assessed by UHDRS and the modulation of cardiovagal activity has been found (Andrich et al., 2002). Disrupted circadian rhythms can alter central autonomic pathways, such as blood pressure changes and loss in the circadian control of heart rate.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were divided into four groups according to their UHDRS motor score (Huntington Study Group, 1996) and groups cutoffs according to Andrich et al. (2002): presymptomatic HD (PHD) subjects, score 0–4; early symptomatic HD patients (EHD), score 6–23; midsymptomatic HD patients (MHD), score 25–41; and late symptomatic HD patients (LHD), score 53–88. Two of the enrolled patients with HD were later excluded due to a left bundle branch block observed on an ECG recording.…”

Section: Methodsmentioning

confidence: 99%

“…Studies investigating heart involvement in patients with HD have focused mostly on the determination of altered autonomic nervous system (ANS) activity via assessment of heart rate variability (HRV), specifically demonstrated as an inverse correlation between the severity of clinical HD symptoms as assessed by the Unified Huntington Disease Rating Scale (UHDRS) and the modulation of the cardiovagal activity (Andrich et al., 2002). Increased sympathetic activity has also been observed in presymptomatic HD mutation carriers (Kobal et al., 2010).…”

Section: Introductionmentioning

confidence: 99%

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Evidence of cardiac electrical remodeling in patients with Huntington disease

et al. 2018

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ObjectiveAlthough Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement.Materials and MethodsWe measured conventional and advanced resting ECG indices. Thirtyone subjects with a confirmed huntingtin gene mutation and 31 age‐ and gender‐matched controls were included. The HD subjects were divided into four groups based on their Unified Huntington Disease Rating Scale (UHDRS) motor score.ResultsWe detected changes in advanced ECG variables connected with electrical ventricular remodeling (t test, p < 0.01). The increase in the unexplained part of both QT variability and the standard deviation of normal‐to‐normal QT intervals, presumably reflecting beat‐to‐beat changes in repolarization, was most pronounced. Further, both variables correlated with the product of the cytosine–adenine–guanine (CAG) triplets’ repeat length and the subjects’ age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity.ConclusionsBoth autonomic nervous system dysfunction and cardiac electrical remodeling are present in patients with HD. The changes in advanced ECG variables observed in the study evolve with HD progression. The increased values of QT unexplained variability may be a marker of temporal inhomogeneity in ventricular repolarization associated with malignant ventricular arrhythmias.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence of cardiac electrical remodeling in patients with Huntington disease

et al. 2018

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Natural History of Huntington Disease

et al. 2013

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untington disease (HD) is an autosomal-dominant neurodegenerative disorder resulting from an unstable cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene 1 that is clinically characterized by involuntary movements, cognitive decline, and behavioral changes. 2-4 Several studies have previously described the natural history of the disease. 4-22 Many, however, have been either small, narrowly focused, short in duration, or uncontrolled. Highquality longitudinal data will inform the design of clinical trials aimed at slowing progression and may inform patients and clinicians about the disease course. We, therefore, analyzed longitudinal data from the recently concluded, prospective, multicenter, observational study Cooperative Huntington's Observational Research Trial (COHORT). Methods Study The Johns Hopkins Medicine institutional review board reviewed and approved this analysis of COHORT study data. All COHORT study participants provided written informed consent or, if unable, had an authorized representative provide consent on their behalf. The COHORT project was an observational study that collected phenotypic and genotypic data from individuals with HD and their families from February 14, 2006, until June 30, 2011. The study design and initial baseline characteristics have been previously described. 23 In brief, the study, which was conducted at 44 research sites in Aus-IMPORTANCE Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. OBJECTIVE To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. DESIGN, SETTING, AND PARTICIPANTS Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n = 4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. MAIN OUTCOMES AND MEASURES Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. RESULTS Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P < .001). CONCLUSIONS AND RELEVANCE Over 3 years, the cardinal features of Huntington disease all d...

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β-Blocker Use and Delayed Onset and Progression of Huntington Disease

Schultz,

Ogilvie,

Harshman

et al. 2024

JAMA Neurol

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ImportanceHuntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD.ObjectiveTo evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms.Design, Setting, and ParticipantsThis observational, longitudinal multicenter study used the Enroll-HD platform database (initiated September 2011 to present), including propensity score–matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) who were either users or nonusers of β-blockers. Participants included patients with genetically confirmed preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) who were taking a β-blocker and were matched to similar non–β-blocker users.ExposureUninterrupted use of a β-blocker for more than 1 year.Main Outcomes and MeasuresFor PreHD: risk of receiving a motor diagnosis of HD over time. For mmHD: progression rate of total motor score, total functional capacity score, and the symbol digit modalities test. Post hoc analyses were performed to test additional clarifying hypotheses after the primary analyses were completed.ResultsThis study included 174 preHD β-blocker users (59 males; 115 females) with a mean age of 46.4 (SD, 13.1) years and a mean cytosine-adenine guanine repeat length of 41.1 (SD, 2.4) who were well matched to 174 preHD non–β-blocker users. The preHD β-blocker users showed a statistically significant reduction in the annualized hazard of receiving a motor diagnosis compared with nonusers (n = 174) (hazard ratio, 0.66; 95% CI, 0.46-0.94; P = .02). There were 149 mmHD β-blocker users (86 males; 60 females) with a mean age of 58.9 (SD, 11.3) years and a mean cytosine-adenine guanine repeat length of 42.0 (SD, 2.3) matched to 149 mmHD non–β-blocker users. The β-blocker users had a slower mean annualized worsening in total motor score (mean difference [MD], −0.45; 95% CI, −0.85 to −0.06; q = 0.025), total functional capacity score (MD, 0.10; 95% CI, 0.02-0.18; q = 0.025), and symbol digit modalities test (MD, 0.33; 95% CI, 0.10-0.56; q = 0.017) compared with matched nonusers.Conclusions and RelevanceIn this study, β-blocker use was associated with delayed motor onset in preHD and reduced the rate of worsening of symptoms in mmHD. These findings demonstrated that β-blockers may have a therapeutic role in HD but further studies are required.

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Autonomic nervous system function in Huntington's disease

Cited by 104 publications

References 31 publications

Evidence of cardiac electrical remodeling in patients with Huntington disease

Evidence of cardiac electrical remodeling in patients with Huntington disease

Natural History of Huntington Disease

β-Blocker Use and Delayed Onset and Progression of Huntington Disease

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