Treatment with Botulinum Neurotoxin Improves Activities of Daily Living and Quality of Life in Patients with Upper Limb Tremor

Background: Botulinum neurotoxin’s degree of effectiveness on upper limb tremor is subject to debate; although this treatment reduces the tremor’s amplitude, a clear functional benefit has not been demonstrated. The objective of this study was to assess the effect of botulinum neurotoxin type A treatment on activities of daily living and quality of life in patients with upper limb tremor. Methods: We retrospectively examined the medical records of 50 consecutive patients treated with botulinum neurotoxin for upper limb tremor that was refractory to oral medication. One month after the injection, the patient was evaluated according to the Quality of Life in Essential Tremor Questionnaire, and the Essential Tremor Embarrassment Assessment. Results: Full data sets were available for 38 patients suffering variously from essential tremor (n = 21), Holmes tremor secondary to a focal brain lesion (n = 8), idiopathic dystonic tremor (n = 4), primary writing tremor (n = 4), and Parkinson’s disease (n = 1). The Quality of Life Essential Tremor Questionnaire and the Essential Tremor Embarrassment Assessment scores improved significantly (p < 0.001) in the study population as a whole, and in the essential tremor and Holmes tremor subgroups. Discussion: Botulinum neurotoxin treatment of patients with upper limb tremor is associated with improved quality of life and activities of daily living, irrespective of the tremor’s etiology. Long-term treatment enables the physician to adjust the injection strategy to the patient’s needs. Our study was limited by its retrospective design. The results must therefore be confirmed in a prospective, double-blind, placebo-controlled, randomized clinical trial

Hedonic Deficits in Parkinson’s Disease: Is Consummatory Anhedonia Specific?

Background: Anhedonia, the lowered ability to experience pleasure, is one of the non-motor symptoms of Parkinson’s disease (PD) that is underdiagnosed and consequently undertreated. Few studies have investigated anhedonia in PD by taking into account the influence of socio-demographic variables and versus a control group composed of patients with a pure motor neurologic disease other than PD. The aim of this study was to investigate hedonic deficits in patients with PD compared to a control group of patients with non-Parkinson motor neurologic disease (OND), matched for age, gender, level of education, and inpatient/outpatient status. Distinctions between anticipatory and consummatory anhedonia and between endogenomorphic and non-endogenomorphic depression were taken into account. Methods: The study population comprised 49 PD patients and 40 subjects with OND. Anhedonia was rated by using the anticipatory [Temporal Experience Pleasure Scale (TEPS)-ANT] and consummatory (TEPS-CONS) subscales of the TEPS and two subscales extracted from the revised Physical Anhedonia Scale (PAS), measuring physical anticipatory (PAS-ANT) and physical consummatory (PAS-CONS) anhedonias. The Snaith–Hamilton Pleasure Scale (SHAPS) and the Beck Depression Inventory-II (BDI-II) were also used together with a subscale extracted from the BDI-II (ENDO-BDI-II) for the diagnosis of endogenomorphic depression. Statistical analyses were performed on the whole group and on the PD group. Results: As hypothesized, several anhedonia scores varied with age and gender in the whole population or in the PD group. On univariate or multivariate analyses, only PAS-CONS was specific for PD and only SHAPS scores differed between depression subtypes in the whole population or the PD group. Conclusion: This study suggests that physical consummatory anhedonia could be specific to PD subjects

The Livelihood Change of Fishermen Recipient Grant Program of Coalition Party in Lubuk Puding Village Buru District of Karimun Regency of Riau Islands Province

This study was conducted in January 2016 in the village of Lubuk Puding in the District of Buru Karimun Riau Islands Province. The objective of this study was to determine the characteristics of fishing grantees, to determine changes in fishing livelihoods after receiving the grant, and to determine the relationship characteristic of changes, livelihoods and grants program. The method used in this study was survey of 160 grantees fishermen population, in which this study taken as much as 15% of the 160 populations or 24 peoples.Based on the research result, the characteristics of grant recipient are productive fishermenage, low education and the number of family member of fishermen. The livelihood of fishermen grant recipients changed from the preparatory stage to the growth stage, while in food consumption and employment on a fixed income and sanitation and hygiene unchanged. Characteristics with real changes in the livelihoods of fishermen are age which have relationship with income and with the job opportunities, the number of family member has relationship with food consumption and grant, and food consumption have relationships with the grant

Neuroendocrine Disturbances in Huntington's Disease

BACKGROUND: Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized, in addition to neurological impairment, by weight loss suggesting endocrine disturbances. The aims of this study were to look for neuroendocrine disturbances in patients with Huntington's disease (HD) and to determine the relationship with weight loss seen in HD METHODS AND FINDING: We compared plasma levels of hormones from the five pituitary axes in 219 patients with genetically documented HD and in 71 sex- and age-matched controls. Relationships between hormone levels and disease severity, including weight-loss severity, were evaluated. Growth hormone (GH) and standard deviation score of insulin-like growth factor 1 (SDS IGF-1) were significantly higher in patients than in controls (0.25 (0.01-5.89) vs. 0.15 (0.005-4.89) ng/ml, p = 0.013 and 0.16+/-1.02 vs. 0.06+/-0.91, p = 0.039; respectively). Cortisol was higher (p = 0.002) in patients (399.14+/-160.5 nmol/L vs. 279.8+/-130.1 nmol/L), whereas no differences were found for other hormone axes. In patients, elevations in GH and IGF-1 and decreases in thyroid-stimulating hormone, free triiodothyronine and testosterone (in men) were associated with severity of impairments (Independence scale, Functional score, Total Functional Capacity, Total Motor score, Behavioral score). Only GH was independently associated with body mass index (beta = -0.26, p = 0.001). CONCLUSION: Our data suggest that the thyrotropic and in men gonadotropic axes are altered in HD according to the severity of the disease. The somatotropic axis is overactive even in patients with early disease, and could be related to the weight loss seen in HD patients

How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease.

The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington's disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington's Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington's Disease (RIL-HD). All were assessed with the Unified Huntington's Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required

Alloimmunisation to Donor Antigens and Immune Rejection Following Foetal Neural Grafts to the Brain in Patients with Huntington's Disease

BACKGROUND: The brain is deemed “immunologically privileged” due to sparse professional antigen-presenting cells and lymphatic drainage, and to the blood-brain barrier. Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation. This has led over the past fifteen years to the use of either short-term or even no immunosuppression in most clinical trials with foetal neural transplant in patients with Parkinson's and Huntington's disease. METHODOLOGY/PRINCIPAL FINDINGS: We report biological demonstration of alloimmunisation without signs of rejection in four grafted patients out of 13 studied during the course of a clinical trial involving fetal neural transplantation in patients with Huntington's Disease. Biological, radiological and clinical demonstration of an ongoing rejection process was observed in a fifth transplanted patient. The rejection process was, however, fully reversible under immunosuppressive treatment and graft activity recovered within six months. CONCLUSIONS/SIGNIFICANCE: There had been, up to date, no report of documented cases that could have cast a doubt on those procedures. Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts. It also suggests that some of the results obtained in past studies with foetal neural transplants may have been biased by an unrecognized immune response to donor cells

Brief Communication External globus pallidus stimulation modulates brain connectivity in Huntington&apos;s disease

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington&apos;s disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Caractéristiques cliniques des syndromes parkinsoniens avec tremblement rentrant dans le cadre des "scans without evidence of dopaminergic deficit"

INTRODUCTION : 4 à 15% des patients présentant les critères diagnostics actuels pour la maladie de Parkinson (MPI) ont une imagerie fonctionnelle dopaminergique normale. La majorité de ces patients, nommés Scans Without Evidence of Dopaminergic Deficit (SWEDDs), auraient un tremblement d origine dystonique. Notre objectif était de déterminer des caractéristiques cliniques et polygraphiques spécifiques permettant de suspecter un SWEDD trémulant devant un syndrome parkinsonien évocateur d une MPI. PATIENTS ET METHODE : il s agit d une étude rétrospective cas-contrôle portant sur 16 patients SWEDDs avec tremblement suivis au CHU d Amiens. Nous avons étudié les caractéristiques démographiques et cliniques, les données de l anamnèse et de l évolution, le degré de sensibilité aux traitements médicamenteux et à l alcool, les antécédents familiaux de tremblement ou de comorbidité psychiatrique, les données de la polygraphie du tremblement. Tous les DaTSCAN avaient été relus par le même opérateur. RESULTATS : un tremblement focal, spécifique de tâche, irrégulier en fréquence et en amplitude et un syndrome parkinsonien peu évolutif, fluctuant, s améliorant spontanément au cours du suivi et de sévérité moindre sont caractéristiques des patients SWEDDs trémulants. Les SWEDDs trémulants présentent pour la plupart des caractéristiques de tremblement dystonique, de tremblement psychogène et plus rarement de tremblement essentiel. L exploration polygraphique du tremblement ne constitue pas une aide majeure au diagnostic des SWEDDs trémulants. CONCLUSION : les patients SWEDDs trémulants présentent des caractéristiques cliniques spécifiques permettant de les différencier des patients parkinsoniens avant la réalisation du DaTSCAN.OBJECTIVE : 4 to 15 % of the patients fulfilling the current diagnosis criteria for Idiopathic Parkinson s Disease (IPD) have normal dopamine transporter (DaT) functional imaging. Most of these patients, named Scans Without Evidence of Dopaminergic Deficit (SWEDDs), might have dystonic tremor. Our objective was to determine which specific clinical and electrophysiological features enable to suspect a tremulous SWEDD when confronted to a parkinsonian syndrome suggesting IPD. PATIENTS AND METHODS : this is a retrospective case-control study of 16 tremulous SWEDDs patients followed-up in the Amiens University Hospital. We studied demographics, clinical features, the disease history and course, the alcohol and treatment responsiveness, the family history of tremor, the presence of psychiatric comorbidities and the tremor electrophysiological analysis datas. All the DaT-SPECT scans (DaTSCANs) were rewied by the same operator. RESULTS : a focal, task-specific tremor, with irregular frequency and amplitude; and a static or fluctuating parkinsonian syndrome, spontaneously remittent and with mild severity are characteristic of tremulous SWEDDs. Most of tremulous SWEDDs patients have dystonic tremor, psychogenic tremor and less frequently, essential tremor. The electrophysiological analysis of tremor could not help for the diagnosis of tremulous SWEDDs. CONCLUSION : tremulous SWEDDs patients have specific clinical features which allow distinguishing them from parkinsonian patients before the realization of the DaTSCAN.AMIENS-BU Santé (800212102) / SudocSudocFranceF