Orthostatic Tremor is Responsive to Bilateral Thalamic Deep Brain Stimulation: Report of Two Cases Performed Asleep

Background: Orthostatic tremor (OT) is a hyperkinetic movement disorder characterized by rapid tremor in the lower extremities or trunk upon standing. Case Report: We report two patients presenting with OT, whose symptoms improved markedly following asleep bilateral thalamic deep brain stimulation (DBS) surgery. Discussion: Medically refractory OT can respond favorably to asleep bilateral DBS surgery similar to awake surgery, and may have the advantages of less psychological trauma to the patient, shorter procedure times, and less exposure to anesthesia

Efficacy and Safety of IncobotulinumtoxinA in Subjects Previously Treated with Botulinum Toxin versus Toxin-Naïve Subjects with Cervical Dystonia

Background: To determine whether botulinum toxin treatment history affected the outcomes of a study comparing the safety and efficacy of incobotulinumtoxinA with placebo in subjects with cervical dystonia (CD). Methods: This was a prospective, double‐blind, randomized, placebo‐controlled, multicenter trial in botulinum toxin‐treated or toxin‐naïve CD subjects. Subjects received a fixed dose of either 120 U or 240 U of incobotulinumtoxinA or placebo. The primary outcome measure was change from baseline to Week 4 in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. Treatment‐emergent adverse events (TEAEs) were also evaluated. This report represents a subgroup analysis of botulinum toxin‐treated or toxin‐naïve subjects. Results: Participants (N = 233; 38.6% toxin‐naïve) had a mean age of 52.8 years. IncobotulinumtoxinA significantly improved TWSTRS total scores from baseline to Week 4 in both dose groups versus placebo, and the improvement persisted through the end of the study (≤20 weeks). Both the previously toxin‐treated and toxin‐naïve subjects demonstrated significant improvements in TWSTRS total scores at Week 4 compared to baseline. The most frequent TEAEs in the incobotulinumtoxinA groups were dysphagia, neck pain, and muscular weakness, which were generally mild. TEAEs were more common in the 240 U group and toxin‐naïve subjects. Discussion: Overall, incobotulinumtoxinA was safe and effective in CD, regardless of toxin therapy history. A lower starting dose may be better tolerated among toxin‐naïve subjects without sacrificing efficacy

Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes.

Potassium channel mutations have been described in episodic neurological diseases. We report that K+ channel mutations cause disease phenotypes with neurodevelopmental and neurodegenerative features. In a Filipino adult-onset ataxia pedigree, the causative gene maps to 19q13, overlapping the SCA13 disease locus described in a French pedigree with childhood-onset ataxia and cognitive delay. This region contains KCNC3 (also known as Kv3.3), encoding a voltage-gated Shaw channel with enriched cerebellar expression. Sequencing revealed two missense mutations, both of which alter KCNC3 function in Xenopus laevis expression systems. KCNC3(R420H), located in the voltage-sensing domain, had no channel activity when expressed alone and had a dominant-negative effect when co-expressed with the wild-type channel. KCNC3(F448L) shifted the activation curve in the negative direction and slowed channel closing. Thus, KCNC3(R420H) and KCNC3(F448L) are expected to change the output characteristics of fast-spiking cerebellar neurons, in which KCNC channels confer capacity for high-frequency firing. Our results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases

Comparing Notes: Recording and Criticism

This chapter charts the ways in which recording has changed the nature of music criticism. It both provides an overview of the history of recording and music criticism, from the advent of Edison’s Phonograph to the present day, and examines the issues arising from this new technology and the consequent transformation of critical thought and practice

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Wider Still and Wider: British Music Criticism since the Second World War

This chapter provides the first historical examination of music criticism in Britain since the Second World War. In the process, it also challenges the simplistic prevailing view of this being a period of decline from a golden age in music criticism

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Botulinum Toxin Therapy for Cervical Dystonia: The Science of Dosing

The first‐line treatment for cervical dystonia (CD) is botulinum toxin type A (BoNT‐A), which has been established as a highly effective and well‐tolerated therapy. However, this treatment is also complex and challenging to apply in clinical practice. Approximately 20% of patients discontinue therapy due to treatment failure, adverse effects, and other reasons. In addition, expert consensus recommendations are lacking to guide physicians in the optimal use of BoNT‐A for CD. Among the issues still to be clarified is the optimal dosing frequency. The generally accepted standard for intervals between BoNT‐A injections is ≥12 weeks; however, this standard is based primarily on the methodology of pivotal trials for the BoNT‐A products, rather than on evidence that it is optimal in comparison to other intervals. While some retrospective, observational studies of BoNT‐A used in clinical practice appear to support the use of ≥12‐week dosing intervals, it is often unclear in these studies how the need for reinjection was determined. In contrast, a prospective dose‐ranging trial in which patients were allowed to request reinjection as early as 8 weeks showed that about half of patients receiving abobotulinumtoxinA, at the currently recommended initial dose of 500 U, requested reinjection at 8 weeks. Moreover, results from an open‐label, 68‐week extension phase of the pivotal trial of incobotulinumtoxinA showed that 47.1% of patients had received reinjection at ≤12 weeks. Ongoing studies, such as the Cervical Dystonia Patient Registry for Observation of BOTOX® Efficacy (CD PROBE), may help clarify this question of optimal dosing intervals for BoNT‐A in CD

Comparing Cerebral White Matter Lesion Burdens between Parkinson’s Disease with and without Dementia

Cerebral white matter lesions (CWMLs) have been suggested to be associated with an increased risk of dementia, disability, and death. CWMLs are more common in individuals with Alzheimer’s disease (AD) than in normal elderly individuals of comparable age. Only a few studies have been done to determine whether CWMLs may influence cognitive decline in Parkinson’s disease (PD). Fully developed PD with concurrent AD was reported to likely cause impaired cognition in spite of accumulating evidence suggesting that PD with dementia (PDD) is more closely associated with Lewy body (LB) pathology. Currently, contradictory data on the neuropathology of dementia in PD require further prospective clinicopathological studies in larger cohorts to elucidate the impact of AD and α-synuclein (SCNA) pathologies on the cognitive status in these disorders. Previous reports did not suggest CWMLs to be associated with an increased risk of PDD. After adjusting for age at death, age at onset of PD, and duration of PD, our recent study investigating CWMLs in PDD via autopsy has shown a positive correlation between the burden of CWMLs and PDD. The frequent co-existence of both LB and AD lesions suggests that both pathologies independently or synergistically contribute to both movement disorders and cognitive impairment. The individual and cumulative burden of CWMLs, LB lesions, and AD lesions may synergistically contribute to cognitive decline in LB disorders such as PDD