Journal of Huntington's Disease - Volume 6, issue 3

Authors: Leavitt, Blair R. | Thompson, Leslie M.

Article Type: Editorial

DOI: 10.3233/JHD-179003

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 167-167, 2017

Authors: Jona, Celine M.H. | Labuschagne, Izelle | Mercieca, Emily-Clare | Fisher, Fiona | Gluyas, Cathy | Stout, Julie C. | Andrews, Sophie C.

Article Type: Research Article

Abstract: Background: Family functioning in Huntington’s disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. Objective: The aim of the current study was to assess family functioning in HD families. Methods: We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; …Roles; and General Family Functioning. Results: The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members , the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants . In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. Conclusion: These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD. Show more

Keywords: Affective involvement, communication, family, family functioning, Huntington’s disease, problem solving

DOI: 10.3233/JHD-170250

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 169-177, 2017

Authors: Montojo, María Teresa | Aganzo, Miguel | González, Nieves

Article Type: Review Article

Abstract: Although Huntington’s disease (HD) is primarily considered a rare neurodegenerative disorder, it has been linked to glucose metabolism alterations and diabetes, as has been described in other neuro syndromes such as Friedreich’s ataxia or Alzheimer’s disease. This review surveys the existing literature on HD and its potential relationship with diabetes, glucose metabolism-related indexes and pancreas morphology, in humans and in animal’s models. The information is reported in chronological sequence. That is, studies performed before and after the identification of the genetic defect underlying HD (CAG: encoding glutamine ≥36 repeats located in exon 1 of the HTT gene) and with the …development and evolution of HD animal models. The aim of the review is to evaluate whether impaired glucose metabolism contributes to the development of HD, and whether optimized glycemic control may ameliorate the symptoms of HD. Show more

Keywords: Chorea, diabetes, glucose metabolism, Huntington’s disease, neurosyndromes

DOI: 10.3233/JHD-170253

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 179-188, 2017

Authors: McGarry, Andrew | Kieburtz, Karl | Abler, Victor | Grachev, Igor D. | Gandhi, Sanjay | Auinger, Peggy | Papapetropoulos, Spyridon | Hayden, Michael

Article Type: Research Article

Abstract: Background: Open-HART is an open-label extension of HART, a randomized, placebo-controlled, dose-ranging, parallel-group study. Objective: To evaluate safety and exploratory efficacy of open-label pridopidine over 36 months in subjects with Huntington’s disease (HD). Methods: Open-HART subjects were treated with pridopidine 45 mg twice daily (BID). After initial evaluation by telephone (Week 1) and in person (Month 1), in-person visits occurred every 3 months, alternating between safety and clinical visits (safety plus Unified Huntington’s Disease Rating Scale [UHDRS] assessment). The UHDRS was performed for pre-specified analysis as a secondary outcome measure. Adverse events (AEs), laboratory values, and electrocardiography …were monitored throughout. Results: Most subjects (89%) reported at least one AE, with 30% experiencing treatment-related AEs. The most common AEs during the first year were falls (12.7%), anxiety (9.3%), insomnia (8.5%), irritability (6.8%), and depression (5.9%). Ninety-nine percent of subjects took concomitant medications. Two seizures were reported as AEs. No arrhythmias or suicide attempts were reported. Five deaths occurred, all considered treatment unrelated. Secondary exploratory analyses of subjects on pridopidine demonstrated motor deterioration (as measured by the UHDRS total motor score) consistent with HD’s natural history, as shown in large observational studies. A post-hoc , exploratory analysis of TFC performance compared to placebo groups from other long-term HD studies demonstrated no significant effect for pridopidine on TFC progression after correction for multiple comparisons. Conclusions: Pridopidine 45 mg BID was generally safe and tolerable in HD subjects over 36 months. TMS declined in a manner consistent with the known natural history of HD. Show more

Keywords: Dopamine agents, Huntington’s disease, movement disorders, pridopidine

DOI: 10.3233/JHD-170241

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 189-199, 2017

Authors: Boileau, Nicholas R. | Stout, Julie C. | Paulsen, Janes S. | Cella, David | McCormack, Michael K. | Nance, Martha A. | Frank, Samuel | Lai, Jin-Shei | Carlozzi, Noelle E.

Article Type: Research Article

Abstract: Background: Huntington’s disease (HD), is a neurodegenerative disorder that is associated with cognitive, behavioral, and motor impairments that diminish health related quality of life (HRQOL). The HD-PRO-TRIADTM is a quality of life measure that assesses health concerns specific to individuals with HD. Preliminary psychometric characterization was limited to a convenience sample of HD participants who completed measures at home so clinician-ratings were unavailable. Objectives: The current study evaluates the reliability and validity of the HD-PRO-TRIADTM in a well-characterized sample of individuals with HD. Methods: Four-hundred and eighty-two individuals with HD (n  = 192 prodromal, n … = 193 early, and n  = 97 late) completed the HD-PRO-TRIADTM questionnaire. Clinician-rated assessments from the Unified Huntington Disease Rating Scales, the short Problem Behaviors Assessment, and three generic measures of HRQOL (WHODAS 2.0, RAND-12, and EQ-5D) were also examined. Results: Internal reliability for all domains and the total HD-PRO-TRIADTM was excellent (all Cronbach’s α >0.93). Convergent and discriminant validity were supported by significant associations between the HD-PRO-TRIADTM domains, and other patient reported outcome measures as well as clinician-rated measures. Known groups validity was supported as the HD-PRO-TRIADTM differentiated between stages of the disease. Floor and ceiling effects were generally within acceptable limits. There were small effect sizes for 12-month change over time and moderate effect sizes for 24-month change over time. Conclusions: Findings support excellent internal reliability, convergent and discriminant validity, known groups validity, and responsiveness to change over time. The current study supports the clinical efficacy of the HD-PRO-TRIADTM . Future research is needed to assess the test-retest reliability of this measure. Show more

Keywords: HD-PRO-TRIADTM, health-related quality of life, Huntington’s disease, patient reported outcome (PRO), psychometric, reliability, validity

DOI: 10.3233/JHD-170238

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 201-215, 2017

Authors: Fritz, Nora E. | Rao, Ashwini K. | Kegelmeyer, Deb | Kloos, Anne | Busse, Monica | Hartel, Lynda | Carrier, Judith | Quinn, Lori

Article Type: Research Article

Abstract: Background: A number of studies evaluating physical therapy and exercise interventions in Huntington’s disease have been conducted over the past 15 years. However, an assessment of the quality and strength of the evidence in support of these interventions is lacking. Objective: The purpose of this systematic review was to investigate the effectiveness of physical therapy and exercise interventions in people with Huntington’s disease, and to examine the perceptions of patients, families and caregivers of these interventions. Methods: This mixed-methods systematic review utilized the Joanna Briggs Institute (JBI) approach and extraction tools to evaluate the literature from …January 2003 until May 2016. The review considered interventions that included exercise and physical therapy interventions, and included both quantitative and qualitative outcome measures. Results: Twenty (20) studies met the inclusion criteria, including eighteen (18) that had quantitative outcome measures and two (2) that utilized qualitative methods. JBI Levels of evidence for the 18 quantitative studies were as follows: Eight studies were at evidence Level 1, seven were at Level 2, two were at Level 3, and one was at Level 4. Conclusions: Our review suggests that there is preliminary support for the benefits of exercise and physical activity in Huntington’s disease in terms of motor function, gait speed, and balance, as well as a range of physical and social benefits identified through patient-reported outcomes. Variability in mode of intervention as well as outcome measures limits the interpretability of these studies, and high-quality studies that incorporate adaptive trial designs for this rare disease are needed. Show more

Keywords: Huntington’s disease, exercise, physical therapy, physiotherapy, physical activity, movement system, classifications

DOI: 10.3233/JHD-170260

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 217-235, 2017

Authors: Pearl, Jocelynn R. | Heath, Laura M. | Bergey, Dani E. | Kelly, John P. | Smith, Corrie | Laurino, Mercy Y. | Weiss, Avery | Price, Nathan D. | LaSpada, Albert | Bird, Thomas D. | Jayadev, Suman

Article Type: Research Article

Abstract: Background: Huntington’s disease (HD) is a fatal progressive neurodegenerative disease characterized by chorea, cognitive impairment and psychiatric symptoms. Retinal examination of HD patients as well as in HD animal models have shown evidence of retinal dysfunction. However, a detailed retinal study employing clinically available measurement tools has not been reported to date in HD. Objective: The goal of this study was to assess retinal responses measured by electroretinogram (ERG) between HD patients and controls and evaluate any correlation between ERG measurements and stage of disease. Methods: Eighteen patients and 10 controls with inclusion criteria of ages …18–70 years (average age HD subjects: 52.1 yrs and control subjects: 51.9 yrs) were recruited for the study. Subjects with previous history of retinal or ophthalmologic disease were excluded. Retinal function was examined by full-field ERG in both eyes of each subject. Amplitudes and latencies to increasing flash intensities in both light- and dark-adaptation were measured in all subjects. Statistical analyses employed generalized estimating equations, which account for repeated measures per subject. Results: We analyzed the b-wave amplitudes of ERG response in all flash intensities and with 30 Hz flicker stimulation. We found statistically significant increased amplitudes in HD patients compared to controls at light-adapted (photopic) 24.2 and 60.9 cd.sec/m2 intensities, dark-adapted (scotopic, red flash) 0.22 cd.sec/m2 intensity, and a trend toward significance at light-adapted 30 Hz flicker. Furthermore, we found a significant increase in light-adapted ERG response from female compared to male HD patients, but no significant difference between gender amongst controls. We also noted a positive association between number of CAG repeats and ERG response at the smallest light adapted intensity (3.1 cd.sec/m2 ). Conclusions: ERG studies revealed significantly altered retinal responses at multiple flash intensities in subjects with an HD expansion allele compared to controls. Significant differences were observed with either light-adapted tests or the dark-adapted red flash which suggests that the enhanced responses in HD patients is specific to the cone photoreceptor pathway. Show more

Keywords: Cone photoreceptor, electroretinogram, Huntington’s disease, retina

DOI: 10.3233/JHD-170255

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 237-247, 2017

Authors: Maskevich, Svetlana | Jumabhoy, Ria | Dao, Pierre D.M. | Stout, Julie C. | Drummond, Sean P.A.

Article Type: Research Article

Abstract: Sleep disturbance occurs early in Huntington’s disease (HD). Consumer- and research-grade activity monitors may enable routine assessment of sleep disturbances in HD. We compared Actiwatch Spectrum Pro, Jawbone UP2 and Fitbit One to the gold standard, polysomnography, in four late presymptomatic and three early HD participants. Compared to polysomnography, all ambulatory monitors overestimated total sleep time by >60 minutes and sleep efficiency by ∼15%. Thus, for assessment of specific sleep parameters in HD, none of the activity monitors are sufficiently accurate to replace polysomnography, although they may be sufficient for estimating overall sleep-wake patterns. Larger sample replication is …required. Show more

Keywords: Huntington’s disease, sleep, actigraphy, ambulatory monitoring, validation

DOI: 10.3233/JHD-170251

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 249-253, 2017

Authors: Rodrigues, Filipe B. | Wild, Edward J.

Article Type: Research Article

Abstract: Clinical Trials Corner of Journal of Huntington’s Disease will regularly review ongoing and recently completed clinical trials in Huntington’s disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx , and cover two recently finished trials: Amaryllis and Pride-HD.

Keywords: Clinical trials, Huntington’s disease

DOI: 10.3233/JHD-170262

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 255-263, 2017

Article Type: Meeting Report

DOI: 10.3233/JHD-179004

Citation: Journal of Huntington's Disease, vol. 6, no. 3, pp. 265-266, 2017