Movements Mimicking Myoclonus Associated with Spinal Cord Pathology: Is This a "Pure Motor Restless Legs Syndrome"?

Background: The neuroanatomic substrate of restless legs syndrome (RLS) is poorly understood, and the diagnosis is clinically made based upon subjective sensory symptoms, although a motor component is usually present. Case Report: We report two cases of elderly patients with spinal pathology who were referred by neurologists for myoclonus. Both had semi-rhythmic leg movements that partially improved while standing, but denied any urge to move. These movements improved dramatically with pramipexole, a dopamine agonist used for RLS. Discussion: We propose that this "myoclonus" is actually the isolated stereotypic motor component of RLS

Thalamic Deep Brain Stimulation for Orthostatic Tremor

Background: Orthostatic tremor is an uncommon disorder manifest by high frequency, low amplitude leg tremor upon weight bearing. Treatment with oral tremor agents is inconsistent and usually not satisfactory. Methods: We implanted bilateral ventralis intermedius nuclei deep brain stimulators into an 82-year-old male with refractory orthostatic tremor. Results: The patient had a marked subjective and objective improvement in leg and arm tremor, mainly manifested by an improved ability to stand. Discussion: Bilateral thalamic deep brain stimulation may be considered in refractory cases of orthostatic tremor

Systematic Literature Review of Quetiapine for the Treatment of Psychosis in Patients With Parkinsonism

Objective: The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism. Methods: Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias. Results: A total of 17,615 unique records were identified, and seven RCTs (total N=241) met inclusion criteria. Five RCTs were placebo controlled, and two compared quetiapine against clozapine. The mean study duration was 12 weeks, and the mean daily quetiapine dose was 103 mg per day (range, 12.5–300 mg). In four of five placebo-controlled RCTs, quetiapine failed to demonstrate significant improvement of psychosis in parkinsonism compared with placebo. In two clozapine-comparator RCTs, quetiapine was better tolerated but no more effective than clozapine. Across all RCTs, the mean completion rates for quetiapine, clozapine, and placebo were 66%, 68.5%, and 66%, respectively. Quetiapine did not significantly worsen motor function. Conclusions: The efficacy of quetiapine in RCTs for psychosis in parkinsonism is no better than that for placebo or clozapine. On the basis of novel data, clinicians should reevaluate traditional viewpoints on the benefits of quetiapine for psychosis in parkinsonism

Consensus guidelines on the construct validity of rodent models of restless legs syndrome.

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS

Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study

OBJECTIVE: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD). METHODS: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change. RESULTS: For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] -3.0 [0.45] vs -1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group. CONCLUSIONS: In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in ∼1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56014/1/21343_ftp.pd

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of \u27severe\u27 or \u27moderate\u27 patients improving to \u27mild\u27 or \u27slight\u27. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients

Pantropical modelling of canopy functional traits using Sentinel-2 remote sensing data

Funding Information: This work is a product of the Global Ecosystems Monitoring (GEM) network (gem.tropicalforests.ox.ac.uk). J.A.G. was funded by the Natural Environment Research Council (NERC; NE/T011084/1 and NE/S011811/1) and the Netherlands Organisation for Scientific Research (NWO) under the Rubicon programme with project number 019.162LW.010. The traits field campaign was funded by a grant to Y.M. from the European Research Council (Advanced Grant GEM-TRAIT: 321131) under the European Union‘s Seventh Framework Programme (FP7/2007-2013), with additional support from NERC Grant NE/D014174/1 and NE/J022616/1 for traits work in Peru, NERC Grant ECOFOR (NE/K016385/1) for traits work in Santarem, NERC Grant BALI (NE/K016369/1) for plot and traits work in Malaysia and ERC Advanced Grant T-FORCES (291585) to Phillips for traits work in Australia. Plot setup in Ghana and Gabon were funded by a NERC Grant NE/I014705/1 and by the Royal Society-Leverhulme Africa Capacity Building Programme. The Malaysia campaign was also funded by NERC GrantNE/K016253/1. Plot inventories in Peru were supported by funding from the US National Science Foundation Long-Term Research in Environmental Biology program (LTREB; DEB 1754647) and the Gordon and Betty Moore Foundation Andes-Amazon Program. Plots inventories in Nova Xavantina (Brazil) were supported by the National Council for Scientific and Technological Development (CNPq), Long Term Ecological Research Program (PELD), Proc. 441244/2016-5, and the Foundation of Research Support of Mato Grosso (FAPEMAT), Project ReFlor, Proc. 589267/2016. During data collection, I.O. was supported by a Marie Curie Fellowship (FP7-PEOPLE-2012-IEF-327990). GEM trait data in Gabon was collected under authorisation to Y.M. and supported by the Gabon National Parks Agency. D.B. was funded by the Fondation Wiener-Anspach. W.D.K. acknowledges support from the Faculty Research Cluster ‘Global Ecology’ of the University of Amsterdam. M.S. was funded by a grant from the Ministry of Education, Youth and Sports of the Czech Republic (INTER-TRANSFER LTT19018). Y.M. is supported by the Jackson Foundation. We thank the two anonymous reviewers and Associate Editor G. Henebry for their insightful comments that helped improved this manuscript.Peer reviewedPostprin

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1

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