A Phenotypic Atlas for Huntington Disease Based on Data From the Enroll-HD Cohort Study.

Background And Objectives: The variable CAG repeat expansion in the huntingtin gene and its inverse relationship to motor dysfunction onset are fundamental features of Huntington disease (HD). However, the wider phenotype (including non-motor features) at particular CAG lengths, ages, and functional levels is less well-characterized. The large number of participants in the Enroll-HD observational study enables the development of a phenotype atlas that summarizes the range and distribution of HD phenotypes, including outliers and possible clusters, with respect to various CAG repeat lengths, age ranges, and declining functional levels.

Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: In this study, we aimed to evaluate the efficacy, safety, and tolerability of atogepant for the preventive treatment of chronic migraine.

Methods: We did this randomised, double-blind, placebo-controlled, phase 3 trial at 142 clinical research sites across the USA, the UK, Canada, China, Czech Republic, Denmark, France, Germany, Italy, Japan, South Korea, Poland, Russia, Spain, Sweden, and Taiwan. Adults aged 18-80 years with a 1-year or longer history of chronic migraine were randomly assigned (1:1:1) to receive oral atogepant 30 mg twice a day, oral atogepant 60 mg once a day, or placebo.

Expanding the Allelic Heterogeneity of -Associated Autosomal Recessive Cerebellar Ataxia.

Background And Objectives: The term autosomal recessive cerebellar ataxia (ARCA) encompasses a diverse group of heterogeneous degenerative disorders of the cerebellum. Spinocerebellar ataxia autosomal recessive 10 (SCAR10) is a distinct classification of cerebellar ataxia caused by variants in the gene. Little is known about the molecular role of ANO10 or its role in disease.

Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial.

Background: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life.

Objective: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy.

Methods: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1 : 1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo.

Efficacy and safety of onabotulinumtoxinA with standardized occupational therapy for treatment of pediatric upper limb spasticity: Phase III placebo-controlled randomized trial.

Background: This is the first large study of onabotulinumtoxinA as treatment for pediatric upper limb spasticity.

Objective: Evaluate efficacy and safety of a single treatment with onabotulinumtoxinA plus occupational therapy (OT).

Methods: In this registrational phase III, multinational study (NCT01603602), participants were randomized 1:1:1 to onabotulinumtoxinA 3 U/kg/OT, 6 U/kg/OT, or placebo/OT.

A Randomized, Double-Blind, Placebo-Controlled Trial of Vilazodone in Children and Adolescents with Major Depressive Disorder with Twenty-Six-Week Open-Label Follow-Up.

To evaluate the efficacy and long-term safety of vilazodone in children and adolescent outpatients with major depressive disorder (MDD). Children and adolescents aged 7-17 years of age with MDD were randomized 2:2:1 to 8 weeks of double-blind placebo, vilazodone 15 or 30 mg/day or fluoxetine 20 mg/day, respectively. The primary and secondary efficacy outcomes, respectively, were change from baseline to week 8 in Children's Depression Rating Scale-Revised (CDRS-R) score total score and Clinical Global Impressions-Severity (CGI-S) score analyzed using a mixed model for repeated measurement approach.

End of life: Expert care and support, not physician-hastened death.

In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine.

Late Onset Huntington Disease: Phenotypic and Genotypic Characteristics of 10 Cases in Argentina.

Background: Huntington's disease (HD) is a neurodegenerative disorder that includes motor, psychiatric and cognitive manifestations with typical onset of symptoms is in the forties. A percentage of patients (4.4% - 11.

Huntington Disease: The Complexities of Making and Disclosing a Clinical Diagnosis After Premanifest Genetic Testing.

The management of patients and families affected by Huntington disease (HD) is complicated by several factors, both practical and ethical. It can be difficult to determine the onset of clinically manifest HD (mHD). In addition, it can be challenging to decide when to disclose the diagnosis to the affected individual.

Medical management of motor manifestations of Huntington disease.

The motor and movement disorders of Huntington disease (HD) are managed in the context of the other disease features. Chorea and dystonia are the most common HD-associated movement disorders, and they can be assessed on research rating scales. However other motor manifestations have a significant impact.

What do we know about Late Onset Huntington's Disease?

Background: Although the typical age of onset for Huntington's disease (HD) is in the fourth decade, between 4.4-11.5% of individuals with HD have a late onset (over 60 years of age).

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD.

Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012.

Longitudinal Psychiatric Symptoms in Prodromal Huntington's Disease: A Decade of Data.

Objective: Psychiatric symptoms are a significant aspect of Huntington's disease, an inherited neurodegenerative illness. The presentation of these symptoms is highly variable, and their course does not fully correlate with motor or cognitive disease progression. The authors sought to better understand the development and longitudinal course of psychiatric manifestations in individuals who carry the Huntington's disease mutation, starting from the prodromal period prior to motor diagnosis.

Motor onset and diagnosis in Huntington disease using the diagnostic confidence level.

Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale.

Multivariate clustering of progression profiles reveals different depression patterns in prodromal Huntington disease.

Objective: Although Huntington disease (HD) is caused by an autosomal dominant mutation, its phenotypic presentation differs widely. Variability in clinical phenotypes of HD may reflect the existence of disease subtypes. This hypothesis was tested in prodromal participants from the longitudinal Neurobiological Predictors of Huntington Disease (PREDICT-HD) study.

Structural model of the open-closed-inactivated cycle of prokaryotic voltage-gated sodium channels.

In excitable cells, the initiation of the action potential results from the opening of voltage-gated sodium channels. These channels undergo a series of conformational changes between open, closed, and inactivated states. Many models have been proposed for the structural transitions that result in these different functional states.

Conserved disulfide bond is not essential for the adenosine A2A receptor: Extracellular cysteines influence receptor distribution within the cell and ligand-binding recognition.

G protein-coupled receptors (GPCRs) are integral membrane proteins involved in cellular signaling and constitute major drug targets. Despite their importance, the relationship between structure and function of these receptors is not well understood. In this study, the role of extracellular disulfide bonds on the trafficking and ligand-binding activity of the human A2A adenosine receptor was examined.

The many facets of unawareness in huntington disease.

Background: Unawareness or diminished awareness is present when a patient's perception of obvious disease manifestations and impact differ from that of observers such as clinicians or family members.

Methods: We examined studies that specifically investigate unawareness in Huntington disease (HD).

Results: Unawareness of motor, cognitive, behavioral, and functional aspects of HD has been documented throughout the disease course.

Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study.

There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials.