Intermittent Electrical Stimulation Research Articles

Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial

BackgroundPressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing.MethodsThe Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time.DiscussionSacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries.Trial registrationClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Intermittent electrical stimulation removes mixed antibiotics and associated antibiotic resistance genes at low temperatures

Biotechnology has limited effectiveness in terms of removing mixed antibiotics at low temperatures, leading to ecological risks arising from the presence of antibiotics in environmental waters. In this study, the removal of tetracycline (TCs) and sulfonamide (SAs) from antibiotic wastewater was improved by the intermittent electrical stimulation of anaerobic-aerobic-coupled upflow bioelectrochemical reactors (AO-UBERs) at low temperatures. The removal effects of oxytetracycline and tetracycline were 48.6 ± 3.5% and 71.5 ± 2.9%, respectively. Under 0.9V, the removal rates of oxytetracycline, tetracycline, and trimethoprim were significantly increased in both the aerobic-cathodic and anaerobic anodic chambers, with a more obvious increase at low temperatures. Compared with the blank control group, the removal efficiency of oxytetracycline, trimethoprim and tetracycline in the electric group was increased by 11.8 ± 2.5%, 27.8 ± 10.5% and 11.2 ± 5.8%. The anaerobic chamber contributed more to the removal of TCs and trimethoprim than the aerobic chamber. Furthermore, electrical stimulation selectively enriched electroactive bacteria (Methylophage and Pleuromonas), drug-resistant bacteria (Proteobacteria), and nitrifying bacteria associated with biodegradation. The abundance of antibiotic-resistance genes is related to the distribution of potential hosts and mobile genetic elements (sul1), and electrical stimulation induces the enrichment of both. This suggests that while potentially effective for treating TCs- and SAs-containing wastewater at low temperatures, AO-UBERs may lead to the accumulation of antibiotic-resistance genes.

Subdiaphragmatic Vagal Nerve Stimulation Attenuates the Development of Hypertension and Alters NTS Transcriptional Networks in the SHR.

Augmented vagal signaling may be therapeutic in hypertension. Most studies to date employed stimulation of the cervical vagal branches. Here, we investigated the effects of chronic intermittent electric stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on long term blood pressure (BP), immune markers, and gut microbiota in the spontaneously hypertensive rat (SHR), a rodent model of hypertension characterized by vagal dysfunction, gut dysbiosis and low-grade inflammation. We evaluated the effects of sdVNS on transcriptional networks in the nucleus of the solitary tract (NTS), a major cardioregulatory brain region with direct gut vagal projections. Male juvenile SHR were implanted with radiotelemetry transmitters and vagal nerve cuffs for chronic intermittent electric sdVNS, applied three times per day for seven consecutive weeks followed by one week of no stimulation. BP was measured once a week using telemetry in the sdVNS group as well as the age-matched Sham-stimulated SHR controls. At endpoint, colonic and circulating inflammatory markers and corticosterone, and circulating catecholamines were investigated. Bacterial 16s sequencing measured gut bacterial abundance and composition. RNAseq evaluated the effects of sdVNS on transcriptional networks in the NTS. SHRs that received sdVNS exhibited attenuated development of hypertension compared to the Sham. No changes in peripheral inflammatory markers, corticosterone or catecholamines, and no major differences in gut bacterial diversity and composition were observed following sdVNS, apart from decreased abundance of Defluviitaleaceale bacterium detected in the sdVNS SHR compared to the Sham. RNAseq revealed significant sdVNS-dependent modulation of select NTS transcriptional networks, including catecholaminergic and corticosteroid networks.

Student Competition (Technology Innovation) ID 1985239

Background Deep vein thrombosis (DVT) is a blood clot that forms in the deep veins and is the third most common cardiovascular disease today. One of the causes of DVT is venous stasis. Current methods of DVT prevention include anticoagulants and mechanical prophylaxis. Anticoagulant use is contraindicated in individuals with bleeding risks and mechanical interventions are often cumbersome and uncomfortable. Objective The overall goal of this project is to investigate a novel method for DVT prevention, termed intermittent electrical stimulation (IES). The current study investigated the effects of IES on healthy typical as well as post-stroke persons. Method Of the 32 participants, 22 were healthy subjects from Edmonton, and 10 were inpatient post-stroke subjects at the Glenrose Rehabilitation Hospital, Edmonton. A two-channel stimulator was used to administer IES through electrodes placed on the posterior and anterior sides of the leg and was applied in increasing stimulation amplitudes to the gastrocnemius muscle and the resulting plantar flexion force and changes in popliteal and femoral venous velocities were recorded for each stimulation respectively using B-mode ultrasound. Results IES-induced contractions produced significant increases in venous flow compared to baseline. Small contractions induced by comfortable levels of stimulation in typical and in post-stroke persons were sufficient to increase flow in the popliteal and femoral veins. Conclusion The results indicate that IES can sufficiently increase venous flow to prevent venous stasis and is comfortable for end users. Incorporation of IES into a clinical device could provide a feasible and effective alternative for DVT prophylaxis.

Enhanced biodegradation of fluoroquinolones and the changes of bacterial communities and antibiotic-resistant genes under intermittent electrical stimulation

In this study, an anaerobic–aerobic coupling system under intermittent electrical stimulation was used to improve the biodegradation of synthetic wastewater containing fluoroquinolones (FQs). The effect of electrical stimulation on FQ removal performance is more pronounced with appropriate voltage and hydraulic retention time. In addition, the combination of anaerobic-anodic and aerobic-cathodic chambers is more conducive to improving the removal efficiency of FQs. Under 0.9 V, the removal efficiencies of ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin were significantly improved in the anaerobic–anodic and aerobic–cathodic system. The contribution of the anaerobic/aerobic anodic chambers to FQ removal was greater than that of the anaerobic/aerobic cathodic chambers. Electrical stimulation selectively enriched electroactive bacteria related to biodegradation (Desulfovibrio and Terrimonas), antibiotic-resistant bacteria (Atopobium and Neochlamydia), and nitrifying bacteria (SM1A02 and Reyranella). This study indicated the potential effectiveness of intermittent electrical stimulation in treating fluoroquinolone-containing wastewater in a biofilm reactor. However, electrical stimulation led to an increase in mobile genetic elements , induced horizontal gene transfer and enriched resistant bacteria, which accelerated the spread of antibiotic-resistant genes (ARGs) in the system, indicating that the diffusion of ARGs remains a challenge.

AMPK activation is sufficient to increase skeletal muscle glucose uptake and glycogen synthesis but is not required for contraction-mediated increases in glucose metabolism

The AMP-activated protein kinase (AMPK) is a cellular sensor of energetics and when activated in skeletal muscle during contraction can impart changes in skeletal muscle metabolism. Therapeutics that selectively activate AMPK have been developed to lower glucose levels through increased glucose disposal rates as an approach to abrogate the hyperglycemic state of diabetes; however, the metabolic fate of glucose following AMPK activation remains unclear. We have used a combination of in vivo evaluation of glucose homeostasis and ex vivo skeletal muscle incubation to systematically evaluate metabolism following pharmacological activation of AMPK with PF-739, comparing this with AMPK activation through sustained intermittent electrical stimulation of contraction. These methods to activate AMPK result in increased glucose uptake but divergent metabolism of glucose: pharmacological activation results in increased glycogen accumulation while contraction-induced glucose uptake results in increased lactate formation and glucose oxidation. These results provide additional evidence to support a role for AMPK in control of skeletal muscle metabolism and additional insight into the potential for AMPK stimulation with small molecule direct activators.

Vagus nerve stimulation for focal seizures.

This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy. For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery. We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes. VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.

Rhythmicity of Prefrontal Local Field Potentials after Nucleus Basalis Stimulation

The action of acetylcholine in the cortex is critical for cognitive functions and cholinergic drugs can improve functions such as attention and working memory. An alternative means of enhancing cholinergic neuromodulation in primates is the intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. NB stimulation generally increases firing rate of neurons in the prefrontal cortex, however its effects on single neurons are diverse and complex. We sought to understand how NB stimulation affects global measures of neural activity by recording and analyzing local field potentials (LFPs) in monkeys as they performed working memory tasks. NB stimulation primarily decreased power in the alpha frequency range during the delay interval of working memory tasks. The effect was consistent across variants of the task. No consistent modulation in the delay interval of the task was observed in the gamma frequency range, which has previously been implicated in the maintenance of working memory. Our results reveal global effects of cholinergic neuromodulation via deep brain stimulation, an emerging intervention for the improvement of cognitive function.

Nucleus basalis stimulation enhances working memory by stabilizing stimulus representations in primate prefrontal cortical activity.

SUMMARYAcetylcholine plays a critical role in the neocortex. Cholinergic agonists and acetylcholinesterase inhibitors can enhance cognitive functioning, as does intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. Here we show in two male monkeys how NB stimulation affects working memory and alters its neural code. NB stimulation increases dorsolateral prefrontal activity during the delay period of spatial working memory tasks and broadens selectivity for stimuli but does not strengthen phasic responses to each neuron’s optimal visual stimulus. Paradoxically, despite this decrease in neuronal selectivity, performance improves in many task conditions, likely indicating increased delay period stability. Performance under NB stimulation does decline if distractors similar to the target are presented, consistent with reduced prefrontal selectivity. Our results indicate that stimulation of the cholinergic forebrain increases prefrontal neural activity, and this neuromodulatory tone can improve cognitive performance, subject to a stability-accuracy tradeoff.

The combination of intermittent electrical stimulation with acute intermittent hypoxia strengthens genioglossus muscle discharge in chronic intermittent hypoxia-pretreated rats

ObjectiveExploring whether the genioglossus discharge in chronic intermittent hypoxia(CIH) – pretreated rats could be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH). MethodsRats were pretreated with CIH for 4 weeks and then were randomly divided into 6 groups: time control, intermittent electric stimulation, AIH, intermittent electric stimulation + AIH, continuous electric stimulation and continuous hypoxia exposure. The genioglossus discharges were recorded and compared before and after stimulation. Normoxic-treated rats were grouped and treated with the same stimulation protocols. ResultsIntermittent electrical stimulation or AIH temporarily increased the activity of the genioglossus discharge, in which the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation, AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats, in which the degree of the increase was significantly higher than in rats induced by a single intermittent electric stimulation. ConclusionIntermittent electrical stimulation combined with AIH strengthens the genioglossus plasticity in CIH-pretreated rats.

Electrical stimulation on biodegradation of phenolics in a novel anaerobic–aerobic-coupled upflow bioelectrochemical reactor

• An anaerobic–aerobic-coupled upflow bioelectrochemical reactor was constructed. • Intermittent electrical stimulation mode promoted phenolics degradation. • Aerobic cathodic chamber showed high contribution to the phenolics removal. • Specific microbes were enriched in the cathodic and anodic chambers of the system. Phenolics were widespread in the effluents of coal gasification plants and oil refineries processes, while the impact of electrical stimulation on phenolics degradation in the combined biological processes remained unclear. Here, a novel anaerobic–aerobic–coupled upflow bioelectrochemical reactor (AO-UBER) was used to treat phenol-containing synthetic wastewater and simulated phenolic wastewater. The AO-UBER could treat phenolic compounds effectively via electrical stimulation. Phenol and total phenol removal efficiencies in the intermittently electrically stimulated system with a hydraulic retention time of 6 h were about 22.6% and 31.1%, respectively, higher than that in the biological system not exposed to voltage. The contribution of the aerobic cathodic chamber to the removal of phenolic compounds was higher than that of the anaerobic anodic chamber under the intermittent voltage application mode. High-throughput sequencing analysis indicated that electrical stimulation selectively enriched Acinetobacter , Cloacibacterium , Acidovorax, and Zoogloea in the phenol-containing synthetic wastewater treatment process, and Rhodococcus , Achromobacter , Chryseobacterium, and PSB-M-3 in the simulated phenolic wastewater treatment process. These results demonstrate that the AO-UBER under intermittent voltage application mode holds good potential for efficient phenolic wastewater treatment.

Impact of electrical stimulation modes on the degradation of refractory phenolics and the analysis of microbial communities in an anaerobic-aerobic-coupled upflow bioelectrochemical reactor

An electrically stimulated anaerobic–aerobic coupled system was developed to improve the biodegradation of refractory phenolics. Expected 4-nitrophenol, 2, 4-dinitrophenol, and COD removals in the system with aerobic cathodic and anaerobic anodic chambers were approximately 53.7%, 45.4%, 22.3% (intermittent mode) and 37.9%, 19.8%, 17.3% (continuous mode) higher than that in the control system (26.0 ± 6.4%, 30.7 ± 7.1%, 49.8 ± 3.0%). 2, 4-dichlorophenol removal in the system with aerobic anodic and anaerobic cathodic chambers was approximately 28.5% higher than that in the control system (71.4 ± 5.7%). The contribution of the aerobic cathodic/anodic chambers to the removal of phenolic compounds was higher than that of the anaerobic cathodic/anodic chambers. The species related to phenolic biodegradation (Rhodococcus, Achromobacter, PSB-M-3, and Sphingobium) were enriched in the cathodic and anodic chambers of the system. These results showed that intermittent electrical stimulation could be a potential alternative for the efficient degradation of refractory phenolics.

Cerebellopontine Angle Surgery Assisted by Continuous Mapping of the Facial Nerve Via the Ultrasonic Aspirator.

Cerebellopontine angle (CPA) surgery carries the risk of lesioning the facial nerve. The goal of preserving the integrity of the facial nerve is usually pursued with intermittent electrical stimulation using a handheld probe that is alternated with the resection. We report our experience with continuous electrical stimulation delivered via the ultrasonic aspirator (UA) used for the resection of a series of vestibular schwannomas. A total of 17 patients with vestibular schwannomas, operated on between 2010 and 2018, were included in this study. A constant-current stimulator was coupled to the UA used for the resection, delivering square-wave pulses throughout the resection. The muscle responses from upper and lower face muscles triggered by the electrical stimulation were displayed continuously on multichannel neurophysiologic equipment. The careful titration of the electrical stimulation delivered through the UA while tapering the current intensity with the progression of the resection was used as the main strategy. All operations were performed successfully, and facial nerve conduction was maintained in all patients except one, in whom a permanent lesion of the facial nerve followed a miscommunication to the neurosurgeon. The coupling of the electrical stimulation to the UA provided the neurosurgeon with an efficient and cost-effective tool and allowed a safe resection. Positive responses were obtained from the facial muscles with low current intensity (lowest intensity: 0.1 mA). The availability of a resection tool paired with a stimulator allowed the surgeon to improve the surgical workflow because fewer interruptions were necessary to stimulate the facial nerve via a handheld probe.

Vagus nerve stimulation as adjunctive therapy in patients with difficult-to-treat depression (RESTORE-LIFE): study protocol design and rationale of a real-world post-market study

BackgroundDepressive illness is associated with significant adverse consequences for patients and their families, and for society. Clinical challenges are encountered in the management of patients suffering from depression whether they are designated difficult-to-treat or treatment-resistant. Prospective serial depression treatment trials have shown that less than 40% of patients with major depressive disorder remit with an initial pharmacotherapy trial, and a progressively smaller proportion of patients remit with each subsequent trial. For patients who suffer from difficult-to-treat depression (DTD), treatments should focus on patient-centred symptom control, patient functioning, and improving patient quality of life. Among the treatment options for patients with DTD is Vagus Nerve Stimulation (VNS) Therapy. VNS Therapy involves intermittent electrical stimulation of the left cervical vagus nerve and has been shown to be efficacious for long-term management of patients with DTD.MethodsRESTORE-LIFE is a prospective, observational, multi-site, global post-market study intended to assess short-, mid-, and long-term effectiveness and efficiency outcomes in a ‘real-world’ setting among patients with DTD treated with adjunctive VNS Therapy. A minimum of 500 patients will be implanted with a VNS Therapy System at up to 80 global sites. Eligible patients will participate in a baseline visit between 1 and 6 weeks before device implant and will be followed for a minimum of 36 months and a maximum of 60 months. The diagnosis of depression and comorbid disorders will be determined using the Mini-International Neuropsychiatric Interview (MINI). The primary endpoint is response rate, defined as a decrease of ≥50% in Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to 12 months post-implant.DiscussionA standardized approach in the management of DTD may not be appropriate for the treatment of such a complex heterogenous patient population. This study has been designed to evaluate whether VNS Therapy meaningfully improves and sustains clinical and depressive symptom outcomes in patients with DTD. This study will investigate the durability of VNS response in DTD and utility of VNS for long-term disease management of DTD. In addition, the study results will potentially clarify clinical, functional, and health economic questions in a real-world patient population with DTD.Trial registrationClinicalTrials.gov NCT03320304. Registered 25 October 2017

Phase-specific manipulation of rhythmic brain activity by transcranial alternating current stimulation

BackgroundOscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, modulation of neural activity by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the phase-specificity of tACS effects in humans is still critically debated. ObjectiveHere, we investigated the phase-specificity of tACS on visually evoked steady state responses (SSRs) in 24 healthy human participants. MethodsWe used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. A neural network model served to validate the plausibility of experimental findings. ResultsWe observed a modulation of SSR amplitudes dependent on the phase shift between flicker and tACS. The tACS effect size was negatively correlated with the strength of flicker-evoked activity. Supported by simulations, data suggest that strong network synchronization limits further neuromodulation by tACS. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with SSR phase delays in the tACS target region. ConclusionsOverall, our data provide electrophysiological evidence for phase-specific modulations of rhythmic brain activity by tACS in humans. As the optimal timing of tACS application was dependent on cortical SSR phase delays, our data suggest that tACS effects were not mediated by retinal co-stimulation. These findings highlight the potential of tACS for controlled, phase-specific modulations of neural activity.

Abstract 12: Strategies To Optimize Functional Recovery In Distal Nerve Transfers For Common Fibular Nerve Injuries

Purpose: Footdrop secondary to injury of the common fibular nerve has significant implications on patient function and quality of life. Outcomes following distal nerve transfers (DNT) for restoration of common fibular nerve function are unsatisfactory and often unpredictable. A perioperative technique to improve regeneration and reinnervation of end-targets is therefore of significant clinical interest. We investigated the effects of conditioning electrical stimulation (CES) and daily exercise therapy on regeneration and functional recovery in a rodent model of a DNT. Methods: Sprague Dawley rats were equally divided into a) CES, b) training, c) CES + training, and d) DNT. One week prior to DNT, animals randomized to a CES-cohort received one hour of intermittent electrical stimulation. In keeping with current clinical practice, DNT was performed by identifying the branch of the tibial nerve supplying the lateral gastrocnemius muscle, which was transected and coapted to the distal stump of the denervated common fibular nerve. Post-operatively, animals randomized to a training cohort had one-hour of treadmill training daily for 1 month at 10m/min. Length of axonal extension was quantified after two weeks of regeneration, and motor reinnervation was evaluated weekly by gait analysis of kinetic and kinematic outcomes and skilled locomotion testing. Results: Animals treated with CES prior to DNT had significantly greater regeneration and functional recovery. Two weeks postoperative, the length of axon extension in CES-treated nerves was, significantly longer than in non-conditioned control DNTs (p<0.001). By 8 weeks of regeneration, animals treated with CES+training had significantly higher foot placement scores on the horizontal ladder test (4.3 + 0.3) than DNT-controls (2.6 + 0.2, p<0.001)Animals treated with CES+training had the earliest return of dorsiflexion. By 12 weeks of regeneration, animals treated with CES+training (12.6 ± 2.8o) or with CES (11.2 ± 3.5o), had significantly greater recovery of dorsiflexion when compared to those animals trained only (3.9 ± 2.5o, p<0.001) or DNT controls (no dorsiflexion, p<0.001). Restoration to a more symmetrical gait pattern was significantly improved (p<0.001) among CES+training treated animals; with increased weight bearing (vertical peak forces 0.7 ± 0.03) and increased contact time of the affected limb (duty factor= contralateral - ipsilateral contact time; 0.039 ± 0.007) compared to the other groups (p<0.001). By week 12 of regeneration, CES treated animals exhibited a recovery to symmetry with increased vertical peak forces injured limb (0.65 + 0.02) and reduced differences between limb duty factors (0.046 + 0.05) compared to all other cohorts (p<0.05). Conclusion: Preoperative CES with and without exercise enhances functional recovery with improved dorsiflexion and accelerated restoration of normal gait following DNT for reinnervating common fibular nerve targets. As electrical stimulation has already been proven to be safe in a human patient population, and given that DNTs are performed electively and thus preoperative intervention is possible, delivery of CES in the footdrop patient population may significantly improve the efficacy and reliability in patients undergoing a distal nerve transfer.

A brief period of moderate noxious stimulation induces hemorrhage and impairs locomotor recovery after spinal cord injury

Spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma) that provides a source of pain input. Our studies suggest that this pain input may be detrimental to long-term recovery. In a rodent model, we have shown that engaging pain (nociceptive) fibers caudal to a lower thoracic contusion SCI impairs recovery of locomotor function and increases tissue loss (secondary injury) and hemorrhage at the site of injury. In these studies, nociceptive fibers were activated using intermittent electrical stimulation. The stimulation parameters were derived from earlier studies demonstrating that 6 min of noxious stimulation, at an intensity (1.5 mA) that engages unmyelinated C (pain) fibers, induces a form of maladaptive plasticity within the lumbosacral spinal cord. We hypothesized that both shorter bouts of nociceptive input and lower intensities of stimulation will decrease locomotor function and increase spinal cord hemorrhage when rats have a spinal cord contusion. To test this, the present study exposed rats to electrical stimulation 24 h after a moderate lower thoracic contusion SCI. One group of rats received 1.5 mA stimulation for 0, 14.4, 72, or 180 s. Another group received six minutes of stimulation at 0, 0.17, 0.5, and 1.5 mA. Just 72 s of stimulation induced an acute disruption in motor performance, increased hemorrhage, and undermined the recovery of locomotor function. Likewise, less intense (0.5 mA) stimulation produced an acute disruption in motor performance, fueled hemorrhage, and impaired long-term recovery. The results imply that a brief period of moderate pain input can trigger hemorrhage after SCI and undermine long-term recovery. This highlights the importance of managing nociceptive signals after concurrent peripheral and central nervous system injuries.

Intermittent vagus nerve stimulation allows preventing the “escape” effect of heart rhythm changes

Background.Vagus nerve stimulation has been proposed for the treatment of a number of diseases. The positive effects of vagus nerve stimulation on ischemic and reperfusion myocardial injury has been tested in experimental models. However, the escape effect of vagus activation on heart rate and the methodology to overcome this effect have not been reported properly.Objective. The purpose of the study is to evaluate parameters of prolonged stimulation that decrease heart rate and allow overcoming the escape effect of vagus nerve activation.Design and methods. We used Wistar rats (n = 9). Cervical section was performed under general anesthesia. Left vagus nerve isolated from adjacent tissue was contacted with custom stimulation electrodes and a custom pulse generator. Blood pressure was measured in the right common carotid artery. Limb electrocardiogram was continuously recorded. First, stimulation parameters repeatedly evoking vagal reaction (decrease in heart rate) without nerve damage were evaluated. Second, parameters of intermittent stimulation that allowed repeat and consistent heart rate decrease were assessed.Results. During experiments, in 5 animals the following parameters leading to sustained 30 ± 20 % heart rate reduction were found: rectangular pulse, 30 Hz, 0,5 ms, 1–2 V (0,6– 0,8 mA). Stimulation with 50 Hz frequency led to nerve damage in 1 case. Stimulation with 20 Hz frequency led to heart rate over-suppression of heart rate and blood pressure. Intermittent nerve stimulation was tested in 4 animals and led to repeated heart rate decrease by 38 ± 15 %. The parameters which helped to avoid escape effect on heart rate change were the following: the length of stimulation episode of 45 s and interruption of stimulation for 15 s.Conclusion. Intermittent electrical stimulation evokes vagal reactions on heart rate and allows overcoming the escape effect of vagal activation.

S57 Novel measures for EEG monitoring in coma

Objectives In deep comatose states, the EEG appears discontinuous, consisting of bursts of activity on a flat electrical background referred to as the burst-suppression (BS) pattern. We aimed to develop a quantitative EEG measure that can be applied to both BS and continuous EEG coma. Methods We recoded EEG changes in response to intermittent photic or electrical nerve stimulation epochs lasting 1 min. The multi-channel EEG was reduced to a binary signal of alternating stimulus processing and default classes. A default class ratio could then be defined for continuous EEG by analogy with the suppression ratio of BS. A global EEG reactivity index was derived to measure the relative reduction in default class ratio during (effects) and immediately following stimulation (after-effects). Results We found that in patients with BS coma, the EEG reactivity index correlated with clinical coma evaluation and prognostication scales. The same reactivity index measured during BS induced by general anesthesia, was found to reflect the degree of brain injury in experimental rodent models. Ongoing studies indicate that the EEG reactivity index also correlates with the clinical severity of coma with continuous EEG. Discussion Our data suggest that during BS, the bursts reflect stimulus-evoked activity whereas the suppression reflects the missing default activity. Conclusions We propose a novel EEG reactivity index that can be measured in BS and continuous EEG coma alike. Significance Our EEG reactivity index could provide a continuous measure for monitoring recovery from coma and the post-comatose disorders of consciousness. This work was supported by grants of the Romanian National Authority for Scientific Research, CNCS – UEFISCDI, project number PN-II-ID-PCE-2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290 and PN-III-P2-2.1-PTE-2016-0114 to MM.

A Feasibility Study of Intermittent Electrical Stimulation to Prevent Deep Tissue Injury in the Intensive Care Unit.

Objective: The primary goal of this study was to investigate the feasibility of utilizing intermittent electrical stimulation (IES) in an intensive care environment as a potential method for preventing pressure ulcers. Furthermore, we wished to evaluate the practicality of the innovation and end-user acceptability. Approach: Twenty immobile subjects, age ranging from 19 to 86 years old with a Braden Scale score ranging from 9 to 16 (very high to moderate risk of developing pressure ulcers), were enrolled. Intermittent 35 Hz electrical stimulation was administered through surface electrodes to the gluteal muscles causing them to contract for 10 s every 10 min. Subjects utilized IES on a program that increased from 4 to 24 h per day over 8 days and lasted up to a maximum of 4 weeks. Results: Bedside nurses reported that IES was simple to use, took an average of 6 min to apply, and 2 min to remove. Furthermore, IES could be easily incorporated into routine patient care. No pressure ulcers occurred in any subject during the study. No untoward reactions or adverse events had occurred directly as a result of IES. Innovation: IES represents a potential method of preventing bedsores. This study represents a necessary pilot study, investigating safety and feasibility before proceeding with a larger randomized controlled trial to determine efficacy. Conclusion: Our results suggest that IES is both safe and feasible to implement in intensive care units.