F08 Huntington’s disease burden of illness (HDBOI): study methodology, sample representativeness and fieldwork risk mitigation strategy during the COVID-19 pandemic

Abstract Background Huntington’s disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. Results We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. Conclusions There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

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Evaluation of Blood Glial Fibrillary Acidic Protein as a Potential Marker in Huntington's Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.779890 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huajing You ◽

Tengteng Wu ◽

Gang Du ◽

Yue Huang ◽

Yixuan Zeng ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Disease Burden ◽

Rating Scale ◽

Word Reading ◽

Acidic Protein ◽

Clinical Severity ◽

Healthy Controls ◽

Mutation Carriers

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD.Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity.Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2.Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.

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Modeling Manifest Huntington’s Disease Prevalence Using Diagnosed Incidence and Survival Time

Neuroepidemiology ◽

10.1159/000516767 ◽

2021 ◽

pp. 1-8

Author(s):

Valerie Crowell ◽

Richard Houghton ◽

Akanksha Tomar ◽

Tricia Fernandes ◽

Ferdinando Squitieri

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Disease Burden ◽

Epidemiological Data ◽

Incidence Rates ◽

Simulated Patients ◽

Published Data ◽

The Usa ◽

Probability Of Death ◽

The Uk

Introduction: Understanding the epidemiology of Huntington’s disease (HD) is key to assessing disease burden and the healthcare resources required to meet patients’ needs. We aimed to develop and validate a model to estimate the diagnosed prevalence of manifest HD by the Shoulson-Fahn stage. Methods: A literature review identified epidemiological data from Brazil, Canada, France, Germany, Italy, Spain, the UK, and the USA. Data on staging distribution at diagnosis, progression, and mortality were derived from Enroll-HD. Newly diagnosed patients with manifest HD were simulated by applying annual diagnosed incidence rates to the total population in each country, each year from 1950 onwards. The number of diagnosed prevalent patients from the previous year who remained in each stage was estimated in line with the probability of death or progression. Diagnosed prevalence in 2020 was estimated as the sum of simulated patients, from all the incident cohorts, still alive. Results: The model estimates that in 2020, there were 66,787 individuals diagnosed with HD in the 8 included countries, of whom 62–63% were in Shoulson-Fahn stages 1 and 2 (with less severely limited functional capacity than those in stages 3–5). Diagnosed prevalence is estimated to be 8.2–9.0 per 100,000 in the USA, Canada, and the 5 included European countries and 3.5 per 100,000 in Brazil. Conclusion: The modeled estimates generally accord with the previously published data. This analysis contributes to better understanding of the epidemiology of HD and highlights areas of uncertainty.

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Rate of torque development and striatal shape in individuals with prodromal Huntington's disease

Scientific Reports ◽

10.1038/s41598-020-72042-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Travis Cruickshank ◽

Alvaro Reyes ◽

Timothy S. Pulverenti ◽

Tim Rankin ◽

Danielle M. Bartlett ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Disease Burden ◽

Joint Torque ◽

Healthy Controls ◽

Isokinetic Dynamometry ◽

Future Studies ◽

Rate Of Torque Development ◽

Healthy Control ◽

Torque Development

Abstract The aim of the present study was to quantify explosive joint torque or the ability to develop joint torque rapidly, typically measured as the rate of torque development, in individuals with prodromal Huntington’s disease and healthy controls and its associations with measures of disease burden and striatal pathology. Twenty prodromal Huntington’s disease and 19 healthy control individuals volunteered for this study. Plantar flexor isometric rate of torque development values were evaluated using isokinetic dynamometry. Pathological changes in striatal shape were evaluated using magnetic resonance imaging. Disease burden was evaluated using the disease burden score and cytosine-adenine-guanine age product score. No statistical differences in the rate of torque development were observed between individuals with prodromal Huntington’s disease and healthy controls. However, significant associations were observed between the rate of torque development values and measures of disease burden (r = −0.42 to −0.69) and striatal pathology (r = 0.71–0.60) in individuals with prodromal Huntington’s disease. We found significant associations between lower rate of torque development values and greater striatal shape deflation and disease burden and striatal pathology in individuals with prodromal Huntington’s disease. While no significant differences in the rate of torque development were found between prodromal Huntington’s disease and healthy controls, the noted associations suggest that differences may emerge as the disease advances, which should be investigated longitudinally in future studies.

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Genetics Modulate Gray Matter Variation Beyond Disease Burden in Prodromal Huntington’s Disease

Frontiers in Neurology ◽

10.3389/fneur.2018.00190 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Jingyu Liu ◽

Jennifer Ciarochi ◽

Vince D. Calhoun ◽

Jane S. Paulsen ◽

H. Jeremy Bockholt ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Gray Matter ◽

Disease Burden

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Safety and feasibility of research lumbar puncture in Huntington's disease: the HDClarity cohort and bioresource

10.1101/2021.07.30.21261340 ◽

2021 ◽

Author(s):

Filipe B Rodrigues ◽

Gail Owen ◽

Swati Sathe ◽

Elena Pak ◽

Dipinder Kaur ◽

...

Keyword(s):

Adverse Events ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Disease Burden ◽

Target Engagement ◽

Clinical Assessments ◽

Gene Expansion ◽

Disease Spectrum ◽

The Brain ◽

Hd Gene

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington's disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objectives: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity (NCT02855476) is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e. CSF was collected), amounting to 10,610mL of CSF and 8,200mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusions: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now established as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.

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