Poster 4: The Functional Rating Scale Taskforce for Pre-Huntington's Disease: An Empirically-Driven Initiative for New Scale Development

2009 ◽  
Vol 6 (1) ◽  
pp. 205-205 ◽  
Author(s):  
K EVANS ◽  
K ANDERSON ◽  
B BOROWSKY ◽  
K DUFF ◽  
J GIULIANO ◽  
...  
Keyword(s):  
Scale Development ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale

scholarly journals Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 164-165
Author(s):  
Samuel Frank ◽  
Claudia M. Testa ◽  
David Stamler ◽  
Elise Kayson ◽  
David Oakes ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Study Drug ◽  
Motor Dysfunction ◽  
Open Label ◽  
Entire Treatment Period ◽  
End Of Treatment ◽  
Pharmaceutical Industries

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

scholarly journals Objectively characterizing Huntington’s disease using a novel upper limb dexterity test

2021 ◽  
Author(s):  
Samuel Woodgate ◽  
Philippa Morgan-Jones ◽  
Susanne Clinch ◽  
Cheney Drew ◽  
Rebecca Playle ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Severity ◽  
Convergent Validity ◽  
Rating Scale ◽  
Objective Assessment ◽  
Prognostic Index ◽  
Transfer Task ◽  
Clinical Expertise ◽  
Clinical Scores

Abstract Background The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington’s, that is not reliant on clinical expertise for administration. Methods One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington’s disease completed the Unified Huntington’s Disease Rating Scale and the C3t at baseline. Of these, thirty-three were followed up after 12 months. Regression was used to estimate baseline individual and composite clinical scores (including cognitive, motor, and functional ability) using baseline C3t scores. Correlations between C3t and clinical scores were assessed using Spearman’s R and visually inspected in relation to disease severity using scatterplots. Effect size over 12 months provided an indication of longitudinal behaviour of the C3t in relation to clinical measures. Results Baseline C3t scores predicted baseline clinical scores to within 9–13% accuracy, being associated with individual and composite clinical scores. Changes in C3t scores over 12 months were small ($$\Omega$$ Ω ≤ 0.15) and mirrored the change in clinical scores. Conclusion The C3t demonstrates promise as a simple, easy to administer, objective outcome measure capable of predicting impairment that is reflective of Huntington’s disease severity and offers a viable solution to support remote clinical monitoring. It may also offer utility as a screening tool for recruitment to clinical trials given preliminary indications of association with the prognostic index normed for Huntington’s disease.

scholarly journals Cognitive and Motor Norms for Huntington’s Disease

2020 ◽  
Vol 35 (6) ◽  
pp. 671-682
Author(s):  
James A Mills ◽  
Jeffrey D Long ◽  
Amrita Mohan ◽  
Jennifer J Ware ◽  
Cristina Sampaio
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Word Reading ◽  
Natural Aging ◽  
Color Naming ◽  
Stroop Interference ◽  
Healthy Controls ◽  
Aging Effects ◽  
Motor Score

Abstract Background The progression of Huntington’s disease (HD) for gene-expanded carriers is well-studied. Natural aging effects, however, are not often considered in the evaluation of HD progression. Objective To examine the effects of natural aging for healthy controls and to develop normative curves by age, sex, and education from the distribution of observed scores for the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Color Naming Test, Stroop Interference Test, Total Motor Score, and Total Functional Capacity (TFC) from the Unified Huntington’s Disease Rating Scale (UHDRS) along with a composite score. Methods After combining longitudinal REGISTRY and Enroll-HD data, we used quantile regression and natural cubic splines for age to fit models for healthy controls (N = 3,394; N observations = 8,619). Normative curves were estimated for the 0.05, 0.25, 0.50, 0.75, and 0.95 quantiles. Two types of reference curves were considered: unconditional curves were dependent on age alone, whereas conditional curves were dependent on age and other covariates, namely sex and education. Results Conditioning on education was necessary for the Symbol Digit, Stroop Word, Stroop Color, Stroop Interference, and composite UHDRS. Unconditional curves were sufficient for the Total Motor Score. TFC was unique in that the curve was constant over age with its intercept at the maximum score (TFC = 13). For all measures, sex effects were minimal, so conditioning on sex was unwarranted. Conclusions Extreme quantile estimates for each measure can be considered as boundaries for natural aging and scores falling beyond these thresholds are likely the result of disease progression. Normative curves and tables are developed and can serve as references for clinical characterization in HD.

Brain Bio-Energetic State Does Not Correlate to Muscle Mitochondrial Function in Huntington’s Disease

2020 ◽  
Vol 9 (4) ◽  
pp. 335-344
Author(s):  
Marcus P.J. van Diemen ◽  
Ellen P. Hart ◽  
Pieter W. Hameeteman ◽  
Emma M. Coppen ◽  
Jessica Y. Winder ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mitochondrial Function ◽  
Rating Scale ◽  
Pearson Correlation ◽  
Cag Repeats ◽  
Resonance Spectroscopy ◽  
Motor Score ◽  
Energetic State ◽  
Disease Modifying

Background: Huntington’s disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. Improving mitochondrial function has been proposed as an opportunity to treat HD, but it is not known how mitochondrial function in different tissues relates. Objective: We explored associations between central and peripheral mitochondrial function in a group of mild to moderate staged HD patients. Methods: We used phosphorous magnetic resonance spectroscopy (31P-MRS) to measure mitochondrial function in vivo in the calf muscle (peripheral) and the bio-energetic state in the visual cortex (central). Mitochondrial function was also assessed ex vivo in circulating peripheral blood mononuclear cells (PBMCs). Clinical function was determined by the Unified Huntington’s Disease Rating Scale (UHDRS) total motor score. Pearson correlation coefficients were computed to assess the correlation between the different variables. Results: We included 23 manifest HD patients for analysis. There was no significant correlation between central bio-energetics and peripheral mitochondrial function. Central mitochondrial function at rest correlated significantly to the UHDRS total motor score (R = –0.45 and –0.48), which increased in a subgroup with the largest number of CAG repeats. Discussion: We did not observe a correlation between peripheral and central mitochondrial function. Central, but not peripheral, mitochondrial function correlated to clinical function. Muscle mitochondrial function is a promising biomarker to evaluate disease-modifying compounds that improve mitochondrial function, but Huntington researchers should use central mitochondrial function to demonstrate proof-of-pharmacology of disease-modifying compounds.

scholarly journals Internal consistency of a Brazilian version of the unified Huntington's disease rating scale

2004 ◽  
Vol 62 (4) ◽  
pp. 977-982 ◽  
Author(s):  
Vitor Tumas ◽  
Sarah Teixeira Camargos ◽  
Paulo Samandar Jalali ◽  
Adriano de Paula Galesso ◽  
Wilson Marques Jr
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Internal Consistency ◽  
Negative Correlation ◽  
Clinical Characteristics ◽  
Rating Scale ◽  
Functional Evaluation ◽  
Brazilian Version ◽  
Disease Rating ◽  
High Degree

We evaluated the reliability of a translated Brazilian version of the Unified Huntington's Disease Rating Scale (UHDRS) to establish the reproducibility of the scale in a population that differs substantially from that on which the scale was originally validated. After a training period with the video and guidelines requested from the Huntington Study Group, we applied the UHDRS, except for the cognitive tests, to a group of 21 Brazilian patients with a molecular diagnosis of Huntington's disease (HD). We found a high degree of internal consistency of the motor section of the UHDRS (Cronbach's alpha= 0.841). There was a negative correlation between the total motor score and the functional assessment, the independence scale and the functional capacity. There was a positive correlation between these 3 scales of functional evaluation and a negative correlation between the age of onset of the disease and the number of CAG repeats. The behavioral scale and disease duration were not correlated with any factor. The clinical characteristics of this sample of patients as described by the UHDRS were roughly similar to those reported in the original validation studies and the correlations described were similar to those reported previously. We conclude that the Brazilian version of the UHDRS is reliable and valid to study patients with HD in the Brazilian setting, that this sample of Brazilian patients had clinical characteristics similar to those observed in other world regions, as expected, and that the clinical training method used for the application of the UHDRS was effective to insure a high degree of clinical reproducibility.

scholarly journals The unified huntington's disease rating scale for advanced patients: Validation and follow-up study

2013 ◽  
Vol 28 (14) ◽  
pp. 1995-2001 ◽  
Author(s):  
Katia Youssov ◽  
Guillaume Dolbeau ◽  
Patrick Maison ◽  
Marie-Françoise Boissé ◽  
Laurent Cleret de Langavant ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Follow Up Study ◽  
Disease Rating

scholarly journals Aggressive Behaviour in Huntington’s Disease: A Cross-Sectional Study in a Nursing Home Population

1993 ◽  
Vol 6 (1) ◽  
pp. 43-47 ◽  
Author(s):  
R. S. Shiwach ◽  
V. Patel
Keyword(s):  
Nursing Home ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Aggressive Behaviour ◽  
Rating Scale ◽  
Cross Sectional Study ◽  
Cognitively Impaired ◽  
Sectional Study ◽  
Nursing Home Population ◽  
Cross Sectional

We describe a cross-sectional study of aggressive behaviour in a sample of patients suffering from Huntington's disease in a residential nursing home. Data were obtained using the RAGE, a behaviourally oriented rating scale for measuring aggressive behaviour in cognitively impaired patients. Nursing staff rated 27 patients after a 3 day observation period. A third of the sample were rated to be at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were high. In contrast, the frequency of injuries sustained and the use of restraints and medication for aggressive behaviour were low. Aggressive behaviour was found to be significantly related to the degree of functional impairment. These data are compared with those reported in a study using the RAGE to assess aggressive behaviour in a sample of elderly patients with dementia.

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