Comparison of the Clinical Spectrum of Juvenile- and Adult-Onset Huntington Disease: A National Cohort and Enroll-HD Observational Study.

Background And Objectives: Differences in clinical characteristics between juvenile-onset Huntington disease (JHD) and adult-onset HD (AHD) are hypothesized but not directly compared. This study compares clinical characteristics occurrence and severity across age-at-onset (AO) subtypes.

Methods: Using the national juvenile-onset HD patient cohort and the international Enroll-HD registry (NCT01574053), we compared childhood-onset JHD (cJHD; AO 0-10), adolescent-onset JHD (aJHD; AO 11-20), and adult-onset HD (AHD; AO 21-65) on proportions of clinical characteristics at onset and psychiatric characteristics in pooled datasets.

Huntington's disease at work: The effect of profession-specific requirements as related to clinical characteristics on work outcome.

Background: In most Huntington's disease expanded gene carriers (HDEGC), losing work capacity is the first sign of functional decline. Cognitive deterioration, motor dysfunction, and psychiatric disturbances are associated with or predict work outcomes in HD. The role of profession-specific requirements, however, has not been investigated.

Cognitive impairment predicts medication discrepancies in Huntington's Disease: patient self-report compared to pharmacy records.

Background: Proper medication reconciliation (= comparing the accuracy of patient-reported medication use with pharmacy records) could prevent potentially dangerous situations such as drug-drug interactions and hospitalization. This is particularly important when patients rely on multiple medications, such as in neurodegenerative disorders like Huntington's Disease (HD). Currently, it is unknown how often medication discrepancies occur in HD patients and which factors contribute to the discrepancies.

Prevalence of Juvenile-Onset and Pediatric Huntington's Disease and Their Availability and Ability to Participate in Trials: A Dutch Population and Enroll-HD Observational Study.

Background: Juvenile-onset Huntington's disease (JHD) represents 1-5% of Huntington's disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials.

Progressive alterations in white matter microstructure across the timecourse of Huntington's disease.

Background: Whole-brain longitudinal diffusion studies are crucial to examine changes in structural connectivity in neurodegeneration. Here, we investigated the longitudinal alterations in white matter (WM) microstructure across the timecourse of Huntington's disease (HD).

Methods: We examined changes in WM microstructure from premanifest to early manifest disease, using data from two cohorts with different disease burden.

The Many Faces of Huntington's Chorea Treatment: The Impact of Sudden Withdrawal of Tiapride after 40 Years of Use and a Systematic Review.

Huntington's Disease (HD) is a rare, neurodegenerative disorder characterized by chorea, cognitive decline, and behavioral changes. Despite wide clinical use since the mid-1980s, tiapride was recently withdrawn from the Dutch market without rationale. Although alternatives are available, many patients experienced dysregulation after this unwanted change.

Huntington's disease influences employment before and during clinical manifestation: A systematic review.

Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working.

Falls, Fear of Falling, and Preventive Measures in Huntington's Disease: The Perspectives of Individuals with Huntington's Disease and Caregivers in Long-Term Care.

Background: Falls are common in Huntington's disease (HD), which can have serious consequences and may therefore lead to fear of falling (FoF). There is little knowledge about falls or FoF in individuals with HD or about formal and informal caregivers' fear about falls in individuals with HD.

Objective: To explore prevalence of falls, FoF and fall preventive measures both those applied and those not included in managing falls in individuals with HD and their formal and informal caregivers, and to identify the relationship between FoF and, anxiety, awareness and cognitive functioning respectively.

Juvenile-Onset Huntington Disease Pathophysiology and Neurodevelopment: A Review.

Huntington disease is an autosomal dominant inherited brain disorder that typically becomes manifest in adulthood. Juvenile-onset Huntington disease refers to approximately 5% of patients with symptom onset before the age of 21 years. The causal factor is a pathologically expanded CAG repeat in the Huntingtin gene.

The prevalence of pain in Huntington's disease in a large worldwide cohort.

Introduction: Pain could be an unknown non-motor symptom in Huntington's Disease (HD). The aim is therefore, to study the prevalence of pain interference, painful conditions and analgesic use across the different stages of HD and compare these levels to non-HD gene mutation carriers.

Methods: A cross-sectional analysis of the Enroll-HD study was conducted in premanifest, manifest HD gene mutation carriers (n = 3989 and n = 7,485, respectively) and in non-HD gene mutation carriers (n = 3719).

Validating Automated Segmentation Tools in the Assessment of Caudate Atrophy in Huntington's Disease.

Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials. Using a cohort of early Huntington's disease (HD) patients ( = 46) and controls ( = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD.

Disease Onset in Huntington's Disease: When Is the Conversion?

Background: Determination of disease onset in Huntington's disease is made by clinical experience. The diagnostic confidence level is an assessment regarding the certainty about the clinical diagnosis based on motor signs. A level of 4 means the rater has ≥99% confidence motor abnormalities are unequivocal signs of disease.

Predictors of Working Capacity Changes Related to Huntington's Disease: A Longitudinal Study.

Background: Huntington's disease (HD) is an inherited neurodegenerative disorder that is characterized by motor, cognitive, and psychiatric symptoms. Although 65%of HD expanded gene carriers report changes in employment as the first functional loss, little is known about the predictors leading to changes of working capacity. Given the impact on quality of life, understanding of these factors is of great clinical value.

Composite UHDRS Correlates With Progression of Imaging Biomarkers in Huntington's Disease.

Background: The composite Unified Huntington's Disease Rating Scale (cUHDRS) is a multidimensional measure of progression in Huntington's disease (HD) being used as a primary outcome in clinical trials investigating potentially disease-modifying huntingtin-lowering therapies.

Objective: Evaluating volumetric and structural connectivity correlates of the cUHDRS.

Methods: One hundred and nineteen premanifest and 119 early-HD participants were included.

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

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.

Safety, pharmacokinetics and pharmacodynamics of SBT-020 in patients with early stage Huntington's disease, a 2-part study.

Aims: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT-020, a novel compound to improve mitochondrial function, in a 2-part study in early stage HD patients.

Longitudinal Structural MRI in Neurologically Healthy Adults.

Background: Structural brain MRI measures are frequently examined in both healthy and clinical groups, so an understanding of how these measures vary over time is desirable.

Purpose: To test the stability of structural brain MRI measures over time.

Population: In all, 112 healthy volunteers across four sites.

Predictive genetic testing in Huntington's disease: should a neurologist be involved?

International guidelines on Huntington's Disease recommend neurological examination in the predictive testing trajectory. Experiences and personal wishes of persons at risk of Huntington's Disease regarding this topic have never been evaluated. The objective was to provide an overview of the experiences of Dutch at-risk persons, opting for predictive testing, in consulting a neurologist before and after DNA analysis.

Diagnosing Juvenile Huntington's Disease: An Explorative Study among Caregivers of Affected Children.

To investigate the reasons for the diagnostic delay of juvenile Huntington's disease patients in the Netherlands. : This study uses interpretative phenomenological analysis. Eligible participants were parents and caregivers of juvenile Huntington's disease patients.

Measuring the quality of care in nursing home residents with early-onset neurodegenerative diseases: a scoping review.

Background: Nursing home residents with early-onset neurodegenerative diseases are often younger in comparison with other residents, and need different, often more complex care. Accordingly, the measurements currently used for measuring quality of care in nursing homes may not be suitable for use in this target group. Little is known about the experiences of these residents and of their (in) formal caregivers regarding the quality of care they receive.