Effects of brain polarization on reaction times and pinch force in chronic stroke

BACKGROUND: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1(affected hemisphere)) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. RESULTS: Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. CONCLUSION: tDCS of M1(affected hemisphere )can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels

Short-latency afferent inhibition during selective finger movement

During individual finger movement, two opposite phenomena occur at the level of the central nervous system that could affect other intrinsic hand muscle representations, unintentional co-activation, and surround inhibition (SI). At rest, excitability in the motor cortex (M1) is inhibited at about 20 ms after electric stimulation of a peripheral nerve [short-latency afferent inhibition (SAI)]. We sought to determine whether SAI changes during selective index finger movement. Effects were measured by the response to transcranial magnetic stimulation in two functionally distinct target muscles of the hand [abductor digiti minimi muscle (ADM), first dorsal interosseus muscle (FDI)]. An increase in SAI in the ADM during index finger movement compared to at rest could help explain the genesis of SI. Electrical stimulation was applied to either the little finger (homotopic for ADM, heterotopic for FDI) or the index finger (heterotopic for ADM, homotopic for FDI). During index finger movement, homotopic SAI was present only in the ADM, and the effect of peripheral stimulation was greater when there was less co-activation. Heterotopic SAI found at rest disappeared with movement. We conclude that during movement, homotopic SAI on the muscle in the surround of the intended movement may contribute to SI

Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected] Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from -5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 'for' and 10 'against' respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.info:eu-repo/semantics/publishedVersio

Treatment of Essential Tremor with Long-chain Alcohols: Still Experimental or Ready for Prime Time?

Aim:&nbsp;To review current literature on long‐chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET).&nbsp;Background:&nbsp;Currently available and recommended pharmacotherapies for ET are often limited by suboptimal treatment effects, frequent adverse effects, and drug interactions. While ethanol is reported to profoundly decrease tremor severity in the majority of patients with ET, preclinical experience suggests that long‐chain alcohols such as 1‐octanol might lead to a comparable tremor reduction without ethanol&rsquo;s typical side effects of sedation and intoxication. Here, we review the literature on the first clinical trials on 1‐octanol and its metabolite octanoic acid (OA) for the treatment of ET.Methods:&nbsp;The literature on preclinical and clinical trials on long‐chain alcohols as well as OA was reviewed and summarized, and an outlook given on next phases of development.Discussion:&nbsp;1‐octanol was demonstrated to be safe and effective in a double‐blind, placebo‐controlled low‐dose trial, and open‐label data showed excellent tolerability and dose‐dependent efficacy up to 128 mg/kg. Despite 1‐octanol&rsquo;s efficacy, its future viability as an effective therapy is limited by its pharmacological properties that require large volumes to be orally administered. Pharmacokinetic data indicate that OA is the active metabolite of 1‐octanol. Preclinical efficacy data for OA are positive, and human pilot data demonstrated excellent safety as well as efficacy in secondary outcome measures of tremor amplitudes. OA also has more favorable pharmacological properties for drug delivery; hence, OA may be worth developing as a pharmaceutical.</p

Dose-escalation study of octanoic acid in patients with essential tremor

BACKGROUND. Recently, 1-octanol has been shown to have efficacy in treating patients with essential tremor (ET). The primary metabolite of 1-octanol is octanoic acid (OA), which is now thought to be the active substance that mediates tremor suppression. Our aim was to describe the maximum tolerated dose (MTD) of oral OA in patients with ET and assess the pharmacokinetics (PK) and pharmacodynamics (PD) profile of OA. METHODS. The MTD was studied using an open-label, single-ascending 3 + 3 dose–escalation design. Predefined single doses ranged from 8 to 128 mg/kg, with grade 2 adverse events (AEs) defined as dose-limiting toxicity. Tremor was assessed using accelerometry, digital spiral analysis, and a standard clinical rating scale at baseline and up to 600 minutes after intake. Safety assessments and PK sampling were also performed. RESULTS. Dose-limiting toxicity was not reached. The most frequent AE was mild abdominal discomfort. Exposure (AUC) increased linearly with the dose. Secondary efficacy measures suggested a dose-dependent reduction of tremor. Accordingly, a single unified PK/PD model with an effect compartment and sigmoid maximum effect (E max ) response could be built that accounted well for the time profiles of plasma concentrations as well as effects on tremor severity across the 5 dose levels. CONCLUSION. Although our trial did not reach an MTD, a dose-dependent effect was demonstrated in the PK/PD model as well as in secondary efficacy outcomes. Future studies are needed to explore the safety in higher dose ranges and to confirm dose-dependent efficacy in a placebo-controlled design. TRIAL REGISTRATION. Clinicaltrials.gov NCT01468948 FUNDING. NINDS Intramural Research Program; TG Therapeutics Inc

Maximal voluntary contraction (MVC), 35% MVC force output (35%) and resting motor threshold (rMT) of the flexor policis brevis (FPB) for the trained and untrained hands during all interventions.

<p>Tr. = Trained; Ut. = Untrained. Values are means ± SD.</p

Motor evoked potentials (MEP) evoked in the flexor pollicis brevis (FPB; A and B) and flexor digitorum superficialis (FDS; C and D) muscles of the trained (A and C) and untrained hand (B and D) before and after the 15 min interventions.

<p>Data are means ± SE.</p

The error in force output production after the fifteen minute interventions (EX –15 min of force training with the trained hand; rTMS+EX –15 min of force training and rTMS over M1 region of the trained hand performed concurrently; rTMS –15 min of rTMS over M1 region corresponding to the trained hand; Rest – no intervention) in both the trained (open bars) and untrained (closed bars) hands.

<p>Data are means ± SE for 13 participants. * - P<0.05 trained vs. untrained hand.</p