tVNS in Stroke: A Narrative Review on the Current State and the Future.

Ischemic stroke is a leading cause of disability and there is a paucity of therapeutic strategies that promote functional recovery after stroke. Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as a tool to reduce infarct size in animal models of hyperacute stroke. In chronic stroke, tVNS paired with limb movements has been shown to enhance neurological recovery. In this review, we summarize the current evidence for tVNS in preclinical models and clinical trials in humans. We highlight the mechanistic pathways involved in the beneficial effects of tVNS. We critically evaluate the current gaps in knowledge and recommend the key areas of research required to translate tVNS into clinical practice in acute and chronic stroke.

Effect of Exercise Interventions on Health-Related Quality of Life After Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

Exercise interventions have been shown to help physical fitness, walking, and balance after stroke, but data are lacking on whether such interventions lead to improvements in health-related quality of life (HRQoL). In this systematic review and meta-analysis, 30 randomized controlled trials (n=1836 patients) were found from PubMed, OVID MEDLINE, Web of Science, CINAHL, SCOPUS, The Cochrane Library, and TRIP databases when searched from 1966 to February 2020 that examine the effects of exercise interventions on HRQoL after stroke or transient ischemic attack. Exercise interventions resulted in small to moderate beneficial effects on HRQoL at intervention end (standardized mean difference, -0.23 [95% CI, -0.40 to -0.07]) that appeared to diminish at longer-term follow-up (standardized mean difference, -0.11 [95% CI, -0.26 to 0.04]). Exercise was associated with moderate improvements in physical health (standardized mean difference, -0.33 [95% CI, -0.61 to -0.04]) and mental health (standardized mean difference, -0.29 [95% CI, -0.49 to -0.09]) domains of HRQoL while effects on social or cognitive composites showed little difference. Interventions that were initiated within 6 months, lasted at least 12 weeks in duration, involved at least 150 minutes per week, and included resistance training appeared most effective. Exercise can lead to moderate beneficial effects on HRQoL and should be considered an integral part of stroke rehabilitation.

Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions.

Stroke is one of the leading causes of death and disability globally. A significant proportion of stroke survivors are left with long term neurological deficits that have a detrimental effect on personal wellbeing and wider socioeconomic impacts. As such, there is an unmet need for novel therapies that improve neurological recovery after stroke. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve upper limb motor function in chronic stroke. However, invasive VNS requires a surgical procedure and therefore may not be suitable for all stroke patients. Non-invasive, transcutaneous VNS (tVNS) via auricular vagus nerve stimulation in the ear (taVNS) and cervical vagus nerve stimulation in the neck (tcVNS) have been shown to activate similar vagal nerve projections in the central nervous system to invasive VNS. A number of pre-clinical studies indicate that tVNS delivered in acute middle cerebral artery occlusion reduces infarct size through anti-inflammatory effects, reduced excitotoxicity and increased blood-brain barrier integrity. Longer term effects of tVNS in stroke that may mediate neuroplasticity include microglial polarisation, angiogenesis and neurogenesis. Pilot clinical trials of taVNS indicate that taVNS paired with rehabilitation may improve upper limb motor and sensory function in patients with chronic stroke. In this review, we summarise and critically appraise the current pre-clinical and clinical evidence, outline the major ongoing clinical trials and detail the challenges and future directions regarding tVNS in acute and chronic stroke.

22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium.

This corrects the article DOI: 10.1038/ejhg.2016.36.

22 Years of predictive testing for Huntington's disease: the experience of the UK Huntington's Prediction Consortium.

Huntington's disease (HD) is a progressive neurodegenerative condition. At-risk individuals have accessed predictive testing via direct mutation testing since 1993. The UK Huntington's Prediction Consortium has collected anonymised data on UK predictive tests, annually, from 1993 to 2014: 9407 predictive tests were performed across 23 UK centres. Where gender was recorded, 4077 participants were male (44.3%) and 5122 were female (55.7%). The median age of participants was 37 years. The most common reason for predictive testing was to reduce uncertainty (70.5%). Of the 8441 predictive tests on individuals at 50% prior risk, 4629 (54.8%) were reported as mutation negative and 3790 (44.9%) were mutation positive, with 22 (0.3%) in the database being uninterpretable. Using a prevalence figure of 12.3 × 10(-5), the cumulative uptake of predictive testing in the 50% at-risk UK population from 1994 to 2014 was estimated at 17.4% (95% CI: 16.9-18.0%). We present the largest study conducted on predictive testing in HD. Our findings indicate that the vast majority of individuals at risk of HD (>80%) have not undergone predictive testing. Future therapies in HD will likely target presymptomatic individuals; therefore, identifying the at-risk population whose gene status is unknown is of significant public health value.

Major geographical variations in elective coronary revascularization by stents or surgery in England.

OBJECTIVES: Revascularization in stable coronary artery disease (CAD) can be achieved through percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) depending on the anatomical pattern of CAD, comorbidities and patient preference. Recent studies in the USA, Canada and Australia show marked local variation in the PCI/CABG ratio that is unexplained by patient-related factors. This current study assesses the geographical variation in elective coronary revascularization interventions across England and discusses its appropriateness. METHODS: The rates and actual procedure numbers of total CABG, total PCIs and elective PCIs were collated for each of 151 primary care trusts (PCTs). The 'elective PCI/total CABG ratio' was taken as an indicator of elective coronary revascularization practices. The Index of Multiple Deprivation (IMD) for PCTs was taken as a marker of deprivation. RESULTS: In 2010/2011, the degree of variation in elective PCI/total CABG ratios across 151 PCTs in England was >13-fold (min = 0.36, max = 4.74, median = 1.19, interquartile range = 0.98, 1.73). The ratio was not correlated to the IMD 2010 rank of the PCTs (Spearman's ρ = 0.08, P = 0.36) and was not explained by the volume of interventions performed. CONCLUSIONS: Despite clear evidence-based guidelines for intervention, marked geographical variation in elective coronary revascularization practices also exists in England. This variation is unexplained by procedure volume or deprivation, suggesting the contribution of unwarranted influences which may include practitioner preference. To reduce this level of unwarranted variation, we suggest that all interventions should be underpinned by internationally recognized guidelines or approved by a multidisciplinary team approach (The Heart Team).