Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease

BACKGROUND: Huntington\u27s disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. METHODS: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington\u27s Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. RESULTS: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. CONCLUSIONS: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. METHODS: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. RESULTS: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores

A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease

BACKGROUND: Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington\u27s disease. METHODS: Ninety-six patients with early-stage Huntington\u27s disease were randomized to 1200 mg delayed-release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed-effects model for repeated measures was used to assess treatment effect, expressed as the least-squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. RESULTS: At 18 months, the treatment effect was not statistically significant - least-squares mean difference, -1.5 ± 1.71 (P = 0.385) - although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. CONCLUSIONS: Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington\u27s disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society

First Sagittarius A* Event Horizon Telescope results. I. The shadow of the supermassive black hole in the center of the Milky Way

Galaxie

First Sagittarius A* event horizon telescope results. II. EHT and multiwavelength observations, data processing, and calibration

Instrumentatio

Subthalamic Deep Brain Stimulation Modulates Proprioceptive Integration in Parkinson’s Disease During a Postural Task

International audienc

Proprioceptive contribution of postural control as assessed from very slow oscillations of the support in healthy humans

International audienceMaintaining erect human posture depends on graviceptive information. This can come from at least of three origins: vestibular, visual and somaesthetic. We hypothesize here that subject's use proprioception rather than visual or vestibular cues for their control of upright body posture and this even when subjects stand on a tilting body support surface. In order to find experimental evidence for this hypothesis, we exclude in our experiments visual cues (eyes close) and by keeping frequency and amplitude of the tilt stimulus so low that it would be below the detection threshold for vestibular semi-circular canal stimuli. The orientations of body segments were analysed during various phases of the perturbation cycle. Segmental stabilisations were defined in terms of both the global anchoring index calculated during the whole perturbation cycle and an appropriate sequential anchoring index calculated during various phases in the perturbation cycle. We show that subjects tend to align their bodies with the space vertical and do so better for their heads than for their upper bodies and lower bodies. A further finding is that stabilisation is related to the tilt stimulus in the form that it is minimal at the turning points of the tilt, where peak tilt velocity is minimal with the sinusoidal stimulus used. These finding suggest first that proprioceptive cues are predominant in the control of body orientation in quasi-static condition and second that the head and trunk stabilisation strategies used as the basis of postural control depend on the properties of the moving support

Impaired vertical postural control and proprioceptive integration deficits in Parkinson’s disease

International audienceThe aim of the present study was to investigate how the orientation and stabilization components of postural control may be affected as the result of the impaired proprioceptive integration possibly occurring in Parkinson's disease. To determine the proprioceptive contribution to postural control, parkinsonian patients and control subjects were asked to maintain vertical stance while very slow sinusoidal oscillations were being applied in the lateral and antero-posterior planes to the platform on which they were standing. The amplitude and frequency of their movements were kept below the semicircular canal perception threshold. Data were collected with the ELITE automatic motion analyzer and the two postural components (orientation and segmental stabilization) were analyzed at head and trunk levels while the subjects were performing the task with their eyes open and closed. The results show that 1) the parkinsonian groups' performances were affected in terms of both the postural orientation and stabilization components in comparison with the control group, 2) the use of vision improved the parkinsonian patients' postural performances, and 3) both parkinsonian patients and control subjects achieved better postural performances when antero-posterior perturbations rather than lateral perturbations were applied to the foot support. These results suggest that Parkinson's disease is associated with proprioceptive impairment, which may be an important factor contributing to these patients' postural deficits. On the basis of these results, the visual dependence observed in parkinsonian patients is re-defined as an adaptive strategy partly compensating for the impaired proprioception