Quantitative assessment of daytime motor activity provides a responsive measure of functional decline in patients with Huntington's disease

Pain was rarely studied in Huntington’s disease (HD). We presently aimed to extend our previous study on pain pathways functions by laser evoked potentials (LEPs) to a larger cohort of early unmedicated HD patients and a small group of presymptomatic HD (PHD) subjects. Forty-two early HD patients, 10 PHD patients, and 64 controls were submitted to LEPs by right-hand stimulation. Two series of 30 laser stimuli were delivered, and artifact-free responses were averaged. The N1, N2, and P2 latencies were significantly increased and the N2P2 amplitude significantly reduced in HD patients compared to controls. In the HD group, the LEPs abnormalities correlated with functional decline. PHD subjects showed a slight and insignificant increase in LEPs latencies, which was inversely correlated with the possible age of HD clinical onset. Data of the present study seem to suggest that the functional state of nociceptive pathways as assessed by LEPs may be a potential biomarker of disease onset and progression. The assessment of pain symptoms in premanifest and manifest HD may also open a new scenario in terms of subtle disturbances of pain processing, which may have a role in the global burden of the disease.

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A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease

Neurology ◽

10.1212/wnl.57.3.397 ◽

2001 ◽

Vol 57 (3) ◽

pp. 397.1-404 ◽

Cited By ~ 214

Author(s):

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Controlled Trial ◽

Coenzyme Q ◽

Functional Decline ◽

Double Blind ◽

Clinical Trial Research ◽

Parallel Group ◽

To Receive ◽

Primary Measure

Objectives: To determine whether chronic treatment with coenzyme Q10 or remacemide hydrochloride slows the functional decline of early Huntington’s disease (HD).Methods: The authors conducted a multicenter, parallel group, double-blind, 2 × 2 factorial, randomized clinical trial. Research participants with early HD (n = 347) were randomized to receive coenzyme Q10 300 mg twice daily, remacemide hydrochloride 200 mg three times daily, both, or neither treatment, and were evaluated every 4 to 5 months for a total of 30 months on assigned treatment. The prespecified primary measure of efficacy was the change in total functional capacity (TFC) between baseline and 30 months. Safety measures included the frequency of clinical adverse events.Results: Neither intervention significantly altered the decline in TFC. Patients treated with coenzyme Q10 showed a trend toward slowing in TFC decline (13%) over 30 months (2.40- versus 2.74-point decline, p = 0.15), as well as beneficial trends in some secondary measures. There was increased frequency of nausea, vomiting, and dizziness with remacemide and increased frequency of stomach upset with coenzyme Q10.Conclusions: Neither remacemide nor coenzyme Q10, at the dosages studied, produced significant slowing in functional decline in early HD.

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Increased numbers of motor activity peaks during light cycle are associated with reductions in adrenergic α2-receptor levels in a transgenic Huntington's disease rat model

Behavioural Brain Research ◽

10.1016/j.bbr.2009.06.031 ◽

2009 ◽

Vol 205 (1) ◽

pp. 175-182 ◽

Cited By ~ 21

Author(s):

Felix J. Bode ◽

Michael Stephan ◽

Sara Wiehager ◽

Huu Phuc Nguyen ◽

Maria Björkqvist ◽

...

Keyword(s):

Motor Activity ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Rat Model ◽

Light Cycle

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PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline

Annals of Neurology ◽

10.1002/ana.410200305 ◽

1986 ◽

Vol 20 (3) ◽

pp. 296-303 ◽

Cited By ~ 180

Author(s):

Anne B. Young ◽

John B. Penney ◽

Simon Starosta-Rubinstein ◽

Dorene S. Markel ◽

Stanley Berent ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Functional Decline ◽

Pet Scan ◽

Neurological Features

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Huntington's disease in Venezuela: Neurologic features and functional decline

Neurology ◽

10.1212/wnl.36.2.244 ◽

1986 ◽

Vol 36 (2) ◽

pp. 244-244 ◽

Cited By ~ 117

Author(s):

A. B. Young ◽

I. Shoulson ◽

J. B. Penney ◽

S. Starosta-Rubinstein ◽

F. Gomez ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Functional Decline

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Huntington's disease in Venezuela: Neurologic features and functional decline

Neurology ◽

10.1212/01.wnl.0000397841.29139.d7 ◽

2011 ◽

Vol 76 (17) ◽

pp. 1484-1484

Author(s):

A. B. Young ◽

I. Shoulson ◽

J. Penney ◽

S. Starosta-Rubinstein ◽

F. Gomez ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Functional Decline

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Huntington’s Disease Integrated Staging System (HD-ISS): A Novel Evidence-Based Classification System For Staging

10.1101/2021.09.01.21262503 ◽

2021 ◽

Author(s):

Sarah J. Tabrizi ◽

Scott Schobel ◽

Emily C. Gantman ◽

Alexandra Mansbach ◽

Beth Borowsky ◽

...

Keyword(s):

Clinical Research ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Critical Path ◽

Functional Decline ◽

Signs And Symptoms ◽

Staging System ◽

Regulatory Science ◽

Cross Sectional ◽

Evidenced Based

ABSTRACTBackgroundDespite the monogenic autosomal dominant nature of Huntington’s disease (HD), the current research paradigm is still based on overt clinical phenotypes and does not address disease pathobiology and biomarkers that are evident decades before functional decline. A new research framework is needed to standardize clinical research and enable interventional studies earlier in the course of HD.MethodsThe HD Regulatory Science Consortium (HD-RSC), a precompetitive Critical Path Institute initiative that includes 37 member organizations, created the Regulatory Science Forum working group (RSF), which includes industry and academic representatives. To generate a new evidenced-based HD Integrated Staging System (HD-ISS) using a formal consensus methodology, the RSF considered prognostic biomarkers, signs, and symptoms of HD, and performed empirical data analysis. We used observational data to calculate healthy-control-based landmark variable cut-offs for Stage classification and to internally validate the framework.FindingsThe HD-ISS starts with Stage 0, which comprises individuals with ≥ 40 cytosine-adenine-guanine repeats (CAG) in the huntingtin gene (HTT), before detectable indications of disease. We concluded that detectable HD progression is verified with measurable indicators of underlying pathophysiology (Stage 1), proceeds to a detectable clinical phenotype (Stage 2), and continues to a decline in function (Stage 3). Operationally, individuals can be unambiguously classified into Stages 1-3 based on CAG-independent thresholds of landmark assessments. Both cross-sectional status and longitudinal HD-ISS Stage progress align with HD natural history, and Stage transitions accelerate as CAG increase.InterpretationThe HD-ISS encompasses the full course of HD starting at birth, defined by the presence of the genetic expansion. This new framework aims to standardize language for clinical research and its immediate use will enable further validation. The HD-ISS provides structure to harmonize clinical study populations and facilitates the clinical assessment of interventions earlier in HD to prevent or slow disease progression.FundingCHDI Foundation Inc.

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