Search

Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, psychiatric, and behavioral impairments that eventually affect work-role functioning. There is limited research regarding predictors of workplace disability in HD. The authors examined predictors of work impairment and disability in a cross-sectional cohort of employed persons with symptomatic HD participating in the worldwide Enroll-HD study.The study sample (N=316) comprised individuals with manifest HD and a CAG repeat length range between 39 and 60 and were currently engaged in paid full- or part-time employment. Univariate and multivariate logistic regression analyses identified predictors and the effect of all predictors in a fully adjusted model.Of the sample, 20.3% reported missing work due to HD, 60.1% reported experiencing impairment while working due to HD, 79.1% reported having work-related activity impairment due to HD, and 60.8% reported impairment in overall work productivity due to HD. Individuals had 25% higher odds of missing work time if they had a higher level of functional impairment (odds ratio=0.76, 95% CI=0.64, 0.91) and had three times greater odds of missing work if they were current alcohol drinkers, compared with nondrinkers (odds ratio=2.86, 95% CI=1.62, 5.03). Individuals with lower self-perceived mental health were also 5% more likely to experience impairment at work due to HD. Motor impairment was not a strong predictor of workplace disability.These findings provide important new knowledge that can inform the development of strategies or targeted intervention trials to support persons with symptomatic HD to maintain their work roles.

Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that presents with a spectrum of clinical manifestations from infancy and childhood or in early or mid-adulthood. Progressive neurological symptoms including ataxia, dystonia and vertical gaze palsy are a hallmark of the disease, and psychiatric symptoms such as psychosis and mood disorders are common. These latter symptoms often present early in the course of NPC and thus these patients are often diagnosed with a major psychotic or affective disorder before neurological and cognitive signs present and the diagnosis is revised. The commonalities and characteristics of psychotic symptoms in both NPC and schizophrenia may share neuronal pathways and mechanisms and provide potential targets for research in both disorders. The neurobiology of NPC and its relationship to the pattern of neuropsychiatric and cognitive symptoms is described in this review. A number of neurobiological models are proposed as mechanisms by which NPC causes psychiatric and cognitive symptoms, informed from models proposed in schizophrenia and other metabolic disorders. There are a number of symptomatic and illness-modifying treatments for NPC currently available. The current evidence is discussed; focussing on two medications which have shown promise, miglustat and hydroxypropyl-β-cyclodextrin.

Younger-onset dementia (YOD) presents with heterogeneous symptoms, has a variety of etiologies, and can be difficult to diagnose. The authors conducted a rapid review of longitudinal YOD cohorts and their related substudies to evaluate current literature that may inform the clinical information provided to patients about the progression and duration of illness and to highlight areas for future research. Searches were conducted using MEDLINE, CINAHL, PubMed, PsycINFO, and Web of Science for articles published between January 1966 and June 2018. Four longitudinal YOD cohort studies and their related substudies were identified. Alzheimer's disease (AD) was reported as the most frequently occurring YOD. The age at onset reported for two cohorts ranged from 53.8 to 60.2 years, depending on the dementia type. Three cohorts yielded substudies that focused on other aspects of YOD, including caregiver outcomes, neuropsychiatric symptoms, and psychotropic drug use. There were conflicting data regarding whether AD or frontotemporal dementia had the greatest rate of cognitive decline. The authors identified a restricted amount of clinical information that may be useful for patients and their families. Limitations included relatively short follow-up periods and types of dementia included. There was also a lack of information on longitudinal changes in neuropsychiatric symptoms and their relationship to biomarkers. These aspects are important considerations for future research, because they may yield information relevant to early diagnosis and disease progression, with improved clinical care for patients with YOD and their families. Streamlining data collection may also improve the ability to generalize results.

Huntington disease (HD) is a neurodegenerative condition with prominent motor (including oculomotor), cognitive, and psychiatric effects. While neuropsychological deficits are present in HD, motor impairments may impact performance on neuropsychological measures, especially those requiring a speeded response, as has been demonstrated in multiple sclerosis and schizophrenia. The current study is the first to explore associations between oculomotor functions and neuropsychological performance in HD. Participants with impaired oculomotor functioning performed worse than those with normal oculomotor functioning on cognitive tasks requiring oculomotor involvement, particularly on psychomotor speed tasks, controlling for covariates. Consideration of oculomotor dysfunction on neuropsychological performance is critical, particularly for populations with motor deficits.

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through "Large Deformation Diffeomorphic Metric Mapping" of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico-basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.

Peduncular hallucinations are generally associated with lesions in the midbrain. They have rarely been associated with central pontine myelinolysis, a condition associated with rapid alterations in serum sodium and chronic alcoholism. Described herein is the case of a 46-year-old man who developed typical peduncular hallucinations, whose imaging demonstrated central pontine myelinolysis. After alcohol cessation and neuroimaging resolution, the patient's hallucinatory phenomena abated.

Background: PBT2 is a metal protein-attenuating compound that might reduce metal-induced aggregation of mutant huntingtin and has prolonged survival in a mouse model of Huntington's disease. We aimed to assess the safety, tolerability, and efficacy of PBT2 in patients with Huntington's disease. Methods: In this 26-week, randomised, double-blind, placebo-controlled trial, adults ( ≥ 25 years old ) with early-stage to mid-stage Huntington's disease were randomly assigned ( 1:1:1 ) by a centralised interactive response system to once daily PBT2 250 mg, PBT2 100 mg, or placebo. Randomisation was stratified by site with a block size of three. Participants, carers, the steering committee, site investigators, study staff, and the study sponsor were masked to treatment assignment. Primary endpoints were safety and tolerability. The safety population consisted of all participants who were randomly assigned and had at least one dose of study drug. The principal secondary endpoint was cognition, measured by the change from baseline to week 26 in the main composite Z score of five cognitive tests ( Category Fluency Test, Trail Making Test Part B, Map Search, Symbol Digit Modalities Test, and Stroop Word Reading Test ) and scores on eight individual cognitive tests ( the five aforementioned plus the Trail Making Test Part A, Montreal Cognitive Assessment, and the Speeded Tapping Test ). The intention-to-treat population comprised participants who were randomly assigned and had at least one efficacy assessment after administration of study drug. This trial is registered with [http://clinicaltrials.gov/] ClinicalTrials.gov, [http://clinicaltrials.gov/show/NCT01590888] NCT01590888. Findings: Between April 18, 2012, and Dec 14, 2012, 109 participants were randomly assigned to PBT2 250 mg ( n=36 ), PBT2 100 mg ( n=38 ), or placebo ( n=35 ) at 19 research centres in Australia and the USA. 32 ( 89% ) individuals on PBT2 250 mg, 38 ( 100% ) on PBT2 100 mg, and 34 ( 97% ) on placebo completed the study. Six serious adverse events ( acute coronary syndrome, major depression, pneumonia, suicide attempt, viral infection, and worsening of Huntington's disease ) occurred in five participants in the PBT2 250 mg group, three ( fall with subdural haematoma, suicide attempt, and hospital admission for stabilisation of Huntington's disease ) occurred in two participants in the PBT2 100 mg group, and one ( increasing aggression ) occurred in a participant in the placebo group. The site investigators deemed all, except the worsening of Huntington's disease, as unrelated to study drug. 32 ( 89% ) participants on PBT2 250 mg, 30 ( 79% ) on PBT2 100 mg, and 28 ( 80% ) on placebo had at least one adverse event. Compared with placebo, neither PBT2 100 mg ( least-squares mean 0·02, 95% CI −0·10 to 0·14; p=0·772 ) nor PBT2 250 mg ( 0·07, −0·05 to 0·20; p=0·240 ) significantly improved the main composite cognition Zscore between baseline and 26 weeks. Compared with placebo, the Trail Making Test Part B score was improved between baseline and 26 weeks in the PBT2 250 mg group ( 17·65 s, 0·65–34·65; p=0·042 ) but not in the 100 mg group ( 0·79 s improvement, −15·75 to 17·32; p=0·925 ); neither dose significantly improved cognition on the other tests. Interpretation: PBT2 was generally safe and well tolerated in patients with Huntington's disease. The potential benefit on executive function will need to be confirmed in a larger study. Funding: Prana Biotechnology Limited.