Role of transcutaneous electrical nerve stimulation in temporomandibular joint disorders.

OBJECTIVE: To co mpare the e ffica cy of transcutaneous elec trica l ner ve stimulation with commercially ava ilab le analgesics in alleviating symptoms of temporomandibular disorders. Methods: The cross-sectional, interventional study was conducted from March 11, 2020, to August 31, 2023, at the Oral and Maxillofa cial S urger y Department of the Armed Forces Institute o f Den tist r y, Rawalpindi, Pakistan, and comprised patients aged 18-65 years who were experiencing pain or distress in the temporomandibular joint region. The par ticipants were divided into intervention group A and control group B. Group A treatment involved applying electrodes near the temporomandibular joint, with parameters adjusted as per the treatment guidelines. Group B subjects received only analgesics along with basic care recommendations. Pain intensit y was assessed using visual analogue scale, while functional impairment and adverse effects were monitored. Data was analysed using SPSS 24. RESULTS: Of the 130 patients initially assessed, 100(77%) were included; 50(50%) in each group. In group A, there were 33(66.0%) fema les and 17(34.0 %) male s wit h overal l mean age 42.8±10.12 years. In group B, there were 30(60%) females and 20(40%) males with overall mean age 46.98±14.09 years. Pain intensity was significantly lower in group A compared to group B post-inter vention (p=0.009). Group A sub jec ts also showed significant post-intervention improvement in terms of mouth opening compared to group B patients (p<0.05). There was no significant intergroup difference with respect to adverse effects (p>0.05). Conclusion: Transcutaneous electrical nerve stimulation was significantly more effective than commercially available analgesics in alleviating symptoms of temporomandibular disorders.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Target engagement of the subgenual anterior cingulate cortex with transcranial temporal interference stimulation in major depressive disorder: a protocol for a randomized sham-controlled trial.

Background: Transcranial temporal interference stimulation (tTIS) is a new, emerging neurostimulation technology that utilizes two or more electric fields at specific frequencies to modulate the oscillations of neurons at a desired spatial location in the brain. The physics of tTIS offers the advantage of modulating deep brain structures in a non-invasive fashion and with minimal stimulation of the overlying cortex outside of a selected target. As such, tTIS can be effectively employed in the context of therapeutics for the psychiatric disease of disrupted brain connectivity, such as major depressive disorder (MDD). The subgenual anterior cingulate cortex (sgACC), a key brain center that regulates human emotions and influences negative emotional states, is a plausible target for tTIS in MDD based on reports of its successful neuromodulation with invasive deep brain stimulation. Methods: This pilot, single-site, double-blind, randomized, sham-controlled interventional clinical trial will be conducted at St. Michael's Hospital - Unity Health Toronto in Toronto, ON, Canada. The primary objective is to demonstrate target engagement of the sgACC with 130 Hz tTIS using resting-state magnetic resonance imaging (MRI) techniques. The secondary objective is to estimate the therapeutic potential of tTIS for MDD by evaluating the change in clinical characteristics of participants and electrophysiological outcomes and providing feasibility and tolerability estimates for a large-scale efficacy trial. Thirty participants (18-65 years) with unipolar, non-psychotic MDD will be recruited and randomized to receive 10 sessions of 130 Hz tTIS or sham stimulation (n = 15 per arm). The trial includes a pre- vs. post-treatment 3T MRI scan of the brain, clinical evaluation, and electroencephalography (EEG) acquisition at rest and during the auditory mismatch negativity (MMN) paradigm. Discussion: This study is one of the first-ever clinical trials among patients with psychiatric disorders examining the therapeutic potential of repetitive tTIS and its neurobiological mechanisms. Data obtained from this trial will be used to optimize the tTIS approach and design a large-scale efficacy trial. Research in this area has the potential to provide a novel treatment option for individuals with MDD and circuitry-related disorders and may contribute to the process of obtaining regulatory approval for therapeutic applications of tTIS. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05295888.

A millimetre-scale capacitive biosensing and biophysical stimulation system for emerging bioelectronic bone implants.

Bioelectronic bone implants are being widely recognized as a promising technology for highly personalized bone/implant interface sensing and biophysical therapeutic stimulation. Such bioelectronic devices are based on an innovative concept with the ability to be applied to a wide range of implants, including in fixation and prosthetic systems. Recently, biointerface sensing using capacitive patterns was proposed to overcome the limitations of standard imaging technologies and other non-imaging technologies; moreover, electric stimulation using capacitive patterns was proposed to overcome the limitations of non-instrumented implants. We here provide an innovative low-power miniaturized electronic system with ability to provide both therapeutic stimulation and bone/implant interface monitoring using network-architectured capacitive interdigitated patterns. It comprises five modules: sensing, electric stimulation, processing, communication and power management. This technology was validated using in vitro tests: concerning the sensing system, its ability to detect biointerface changes ranging from tiny to severe bone-implant interface changes in target regions was validated; concerning the stimulation system, its ability to significantly enhance bone cells' full differentiation, including matrix maturation and mineralization, was also confirmed. This work provides an impactful contribution and paves the way for the development of the new generation of orthopaedic biodevices.

Electrodiagnosis for mitigating false-negative non-responsiveness in electrical evoked contractions: A case series exploring probable polyneuromyopathy induced by nonuse.

INTRODUCTION: The revised international standards for neurological classification of spinal cord injury (ISNCSCI) have facilitated the documentation of non-spinal cord injury-related impairments, such as chronic peripheral nerve injuries and muscle weakness due to immobility. This advancement addresses potential biases in muscle strength examinations. Utilizing electrically evoked contractions from paralyzed muscles, enhanced by electrodiagnosis, holds promise in identifying false-negative diagnoses of non-responsiveness to neuromuscular electrical stimulation. This concept prompts the exploration of polyneuromyopathy arising from nonuse in paralyzed muscles. CASE SERIES PRESENTATION: To substantiate our hypothesis, we recruited nine participants for a case series aimed at elucidating the potential benefits of incorporating the stimulus electrodiagnostic test (SET) to mitigate non-responsiveness during preparation for functional electrical stimulation (FES)-assisted cycling. In our convenience sample (n = 5), we conducted neurological mapping based on ISNCSCI and applied SET on the quadriceps. The SET guided optimal dosimetry for evoking contractions and revealed responses similar to those observed in peripheral neuropathies, with α coefficients equal to or lower than 2.00. This observation is likely attributable to nonuse of paralyzed muscles, indicative of an ongoing polyneuropathy in individuals with chronic spinal cord injury (SCI). DISCUSSION: Among the nine initially recruited subjects, seven exhibited responsiveness to neuromuscular electrical stimulation (78% responsiveness), with two participants excluded based on exclusion criteria. In the final five reported cases, all displayed α coefficient values indicating impaired neuromuscular accommodation, and one presented no α coefficient within the normal range. The inclusion of electrodiagnosis appears effective in averting non-responsiveness, suggesting the presence of ongoing polyneuropathies in paralyzed muscles.

Electrographic seizures during low-current thalamic deep brain stimulation in mice.

BACKGROUND: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT). OBJECTIVES: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice. METHODS: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration. RESULTS: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 µA. CONCLUSION: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings.

Successful spinal cord stimulation using fast-acting sub-perception therapy for postoperative neuropathic pain of syringomyelia with Chiari malformation type 1: a case report and literature review.

BACKGROUND: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). CASE PRESENTATION: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. CONCLUSION: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.

Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury.

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin-eosin) and immunohistochemistry for NeuN, ß-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for ß-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in ß-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.

Stimulation of the internal superior laryngeal nerve as a potential therapy for obstructive sleep apnea in a porcine model.

Impaired pharyngeal sensing of negative pressure (NP) can lead to a blunted response of the upper airway dilator muscles and contribute to the development of obstructive sleep apnea (OSA). This response is modulated by the nerve fibers in the internal branch of the superior laryngeal nerve (iSLN), mediating negative pressure sensation. Artificial excitation of these fibers could be a potential treatment target for OSA. To evaluate this, electrostimulation of the iSLN was performed in a porcine-isolated upper airway model. Artificial obstructions were induced by varying the levels of negative pressure, and the ability of the animal to resolve these obstructions was evaluated. The pressure at which the animal was still able to resolve the obstruction was quantified as "Resolvable Pressure." Thereby, the effects on pharyngeal patency (n = 35) and the duration of the therapeutic effect outlasting the stimulation (n = 6) were quantified. Electrostimulation before the introduction of an artificial obstruction improved the median resolvable pressure from -28.3 cmH2O [IQR: -45.9; -26.1] to -92.6 cmH2O [IQR: -105.1; -78.6]. The median therapeutic effect was found to outlast the last stimulation burst applied by 163 s when five stimulation bursts were applied in short succession [IQR: 58; 231], 58 s when two were applied [IQR: 7; 65], and 6 s when one was applied [IQR: 0; 51]. Stimulation of the iSLN increased electromyography (EMG) in the genioglossus (GG). The proposed treatment concept can improve pharyngeal patency in the model. Transfer of the results to clinical application could enable the development of a new neuromodulation therapy for OSA.NEW & NOTEWORTHY Electrostimulation before the introduction of an artificial obstruction to induce artificial sleep apnea in the pig model improves the response of the upper airway to negative pressure (NP). The electrostimulation creates a sustained therapeutic effect that outlasts the initial electrostimulation. The use of this therapy in clinical practice has the potential to treat obstructive sleep apnea (OSA).

Using Physiological Markers to Assess Comfort during Neuromuscular Electrical Stimulation Induced Muscle Contraction in a Virtually Guided Environment: Pilot Study for a Path toward Combating ICU-Acquired Weakness.

We assessed the feasibility of implementing a virtually guided Neuromuscular Electrical Stimulation (NMES) protocol over the tibialis anterior (TA) muscle while collecting heart rate (HR), Numeric Pain Rating Scale (NPRS), and quality of contraction (QoC) data. We investigated if HR, NPRS, and QoC differ ON and OFF the TA motor point and explored potential relationships between heart rate variability (HRV) and the NPRS. Twelve healthy adults participated in this cross-sectional study. Three NMES trials were delivered ON and OFF the TA motor point. HR, QoC, and NPRS data were collected. There was no significant difference in HRV ON and OFF the motor point (p > 0.05). The NPRS was significantly greater OFF the motor point (p < 0.05). The QoC was significantly different between motor point configurations (p < 0.05). There was no correlation between the NPRS and HRV (p > 0.05, r = -0.129). We recommend non-electrical methods of measuring muscle activity for future studies. The NPRS and QoC can be administered virtually. Time-domain HRV measures could increase the validity of the protocol. The variables should be explored further virtually to enhance the protocol before eventual ICU studies.

What are the novel rehabilitation methods in knee arthroplasty? A bibliographic review.

BACKGROUND: Total knee arthroplasty (TKA) is a common procedure for treating end-stage degenerative knee osteoarthritis (OA). Despite the generally excellent outcomes, postoperative complications such as loss of muscle strength and joint limitation can occur. Therefore, postoperative physical rehabilitation is crucial for regaining strength, functionality, and managing pain. Various rehabilitation strategies employ different methods to reduce pain severity, regain muscle strength, assist patients in returning to daily activities, and increase functionality. In recent years, technological advancements have transformed rehabilitation methods. In addition to traditional applications, new methods have been incorporated into treatment plans. OBJECTIVE: This study aimed to evaluate novel physical rehabilitation methods and options following OA. METHODS: A literature review was conducted to identify and investigate recent and commonly used novel rehabilitation methods. The search terms "Total Knee Arthroplasty," "New Rehabilitation TKA," "Novel Rehabilitation" "Novel Rehabilitation in Arthroplasty" and "Technology Knee Rehabilitation" were searched across PubMed and Google Scholar databases, covering literature from the past 15 years. Studies on telerehabilitation, functional electric stimulation, virtual reality, yoga, and their reported outcomes were evaluated using specific keywords. The results of various studies on novel rehabilitation methods were gathered and compared to traditional treatment plans based on functionality and applicability. RESULTS: Several studies reported that telerehabilitation was not inferior to traditional rehabilitation, with some showing positive outcomes. Telerehabilitation following TKA demonstrated positive effects on functionality and patient satisfaction. Functional electric stimulation showed significant improvements in muscle strength and pain reduction. Virtual reality demonstrated superior effects on proprioception and posture outcomes. The use of yoga in rehabilitation also resulted in improved proprioception and pain reduction. CONCLUSION: In addition to traditional rehabilitation methods, new approaches have shown significant positive outcomes for patients who have received TKA. We are in an era of digital development, and as such, new rehabilitation techniques, particularly those involving digital advancements, will continue to emerge. With the trend toward personalized approaches in medicine, more new techniques or methods will be incorporated into rehabilitation plans, leading to better recovery outcomes from TKA.

Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia. METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach. DISCUSSION: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42023410645.

Low-frequency dorsal root stimulation is effective for various pain etiologies and pain locations.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) has emerged as a novel therapeutic approach for managing chronic neuropathic pain. AIMS: This study aims to compare the effectiveness of 4-20 Hz DRG-S through a retrospective analysis of a cohort of 28 patients with various neuropathic pain etiologies and pain locations. MATERIALS AND METHODS: Patient responses to both stimulation frequencies were examined using the Numeric Rating Scale (NRS) and Patient Global Impression of Change (PGIC) assessments. Factors such as patient preference and satisfaction were also evaluated. RESULTS: The results indicate that 4 Hz DRG-S is not only as effective as 20 Hz stimulation but may also surpass it. Among the 28 patients, 26 assessed 4 Hz stimulation to be at least as effective as 20 Hz, with the majority (22 out of 26) considering 4 Hz stimulation superior. After trying 4 Hz stimulation, 24 out of 28 patients chose it over 20 Hz, while two patients opted for a combination of both settings. Only two patients reverted to their original 20 Hz stimulation program. A statistically significant pain reduction of 24% was observed when comparing the effects of 4 Hz versus 20 Hz. DISCUSSION: The study highlights the broader applicability of low-frequency DRG-S, extending its benefits beyond the realm of low back pain. Patients with diverse pain etiologies and locations experienced comparable positive outcomes, suggesting that the advantages of low-frequency stimulation are not confined to specific pain types or locations. CONCLUSION: This study emphasizes the potential of 4 Hz DRG-S as a valuable alternative to the standard 20 Hz stimulation. Although the exact mechanisms require further investigation, the observed clinical benefits and patient preferences for low-frequency stimulation suggest its viability across diverse pain indications and locations. Additional research is necessary to substantiate these findings and assess the durability and economic implications of low-frequency DRG-S.

Sacral neuromodulation therapy for urinary and defecatory disorders: experience in a Latin American public hospital.

Objective: To show the experience of a Latin American public hospital, with SNM in the management of either OAB, NOUR or FI, reporting feasibility, short to medium-term success rates, and complications. Methods: A retrospective cohort was conducted using data collected prospectively from patients with urogynecological conditions and referred from colorectal surgery and urology services between 2015 and 2022. Results: Advanced or basic trial phases were performed on 35 patients, 33 (94%) of which were successful and opted to move on Implantable Pulse Generator (GG) implantation. The average follow-up time after definitive implantation was 82 months (SD 59). Of the 33 patients undergoing, 27 (81%)reported an improvement of 50% or more in their symptoms at last follow-up. Moreover, 30 patients (90%) with a definitive implant reported subjective improvement, with an average PGI-I "much better" and 9 of them reporting to be "excellent" on PGI-I. Conclusion: SNM is a feasible and effective treatment for pelvic floor dysfunction. Its implementation requires highly trained groups and innovative leadership. At a nation-wide level, greater diffusion of this therapy among professionals is needed to achieve timely referral of patients who require it.

The Impact of Baseline Pain Intensity on the Effectiveness of Whole-Body Electromyostimulation (WB-EMS) for Nonspecific Chronic Back Pain.

INTRODUCTION: Recent clinical studies confirmed that whole-body electromyostimulation (WB-EMS) training is a safe and time-efficient therapeutic method for patients with nonspecific chronic back pain (NSCBP). However, significant variations in initial pain intensity among subjects in these studies have been observed. This study aims to determine if patients with differing initial pain intensities experience varying degrees of benefit from WB-EMS and to assess the overall correlation between initial pain levels and pain reduction. METHODS: Pain intensity datasets from two studies were combined. The pooled data included 121 NSCBP patients (38 males and 83 females) with an average age of 55.1 years (±11.8 years). Data was categorized by baseline pain intensity on the numeric rating scale (NRS) into seven groups: 0 to 2, >2 to 3, >3 to 4, >4 to 5, >5 to 6, >6 to 7, and >7. Both absolute and relative changes were analyzed. Additionally, a Spearman rho correlation test was performed on the entire dataset to evaluate the relationship between initial pain level and pain reduction. RESULTS: Significant improvements were noted across all NRS11 categories, with strong effect sizes (p) in all classes above 2, ranging from 0.56 to 0.90. The >7 category exhibited the highest rate of clinically significant changes (80%) and an average improvement of 3.72 points. The overall group from >1 to 10 showed an average improvement of 1.33 points, with 37% of the participants experiencing clinically significant improvements. The Spearman rho correlation test revealed a moderate positive relationship between initial pain level and pain reduction (r_s = 0.531, p < 0.001), indicating that, generally, higher initial pain levels are associated with greater pain reduction. CONCLUSION: The findings support the hypothesis that NSCBP patients with higher baseline NRS values benefit more substantially from WB-EMS. Those with NRS values above 7 show the greatest improvement and highest rate of clinical significance. The overall positive correlation between initial pain intensity and pain reduction further underscores the efficacy of WB-EMS in managing NSCBP across different pain intensities.

The assistive potential of functional electrical stimulation to support object manipulation in functional upper extremity movements after stroke: A randomized cross-over study.

Background: After standard care, 55%-75% of patients after stroke show a persistent paresis of the upper limb (UL). Assistive devices are developed to increase the patients' level of independence in daily life. Objectives: To investigate the potential of Functional Electrical Stimulation (FES) to assist object manipulation in activities of daily life. Design: Seventeen patients after stroke were tested and analyzed in a randomized cross-over design. Methods: Functional grasping was assessed by means of the Action Research Arm Test (ARAT) and the modified Box and Block Test (mBBT), in one session with and another without FES assistance. The order of sessions was randomized. Patients' motivation was assessed after each session. Task performance and motivation were compared between conditions using the Wilcoxon test and subgroup analyses were performed for impairment severity by distribution-based mixed-factor analyses. Results: When analyzing the total ARAT, FES did not effectively assist the overall performance (P = .142), but did assist the performance of objects of the Grasp category (P = .020). Impairment severity showed an interaction with the orthotic effect (P = .012), as severely impaired patients profited from FES assistance and mild-moderately impaired did not. When focusing on the more functional items of the ARAT (i.e., excluding scores from thumb-middle and thumb-ring finger combinations), there was a significant orthotic effect of FES on task performance (P = .023). Further, there was an orthotic effect for the number of transported blocks in the mBBT (P = .033), exclusively prominent in the group of severely impaired patients. Functional Electrical Stimulation did not increase the patients' motivation (P = .959), which was high after both conditions. Conclusion: Functional Electrical Stimulation has the potential to support object manipulation, but is dependent on impairment severity and object type. To observe a consistent orthotic effect, features of the stimulator should be further developed to generate appropriate grasps and forces across subjects and objects. Trial Registration: The trial was registered with the German Clinical Trials Register (DRKS00025889).

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

BACKGROUND: Pressure 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. METHODS: The 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. DISCUSSION: Sacral 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 REGISTRATION: ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Acute Autonomic Nervous System Response to Direct Sacral Nerve Root Stimulation in Lower Urinary Tract Dysfunction: A New Approach to Understand the Mechanism of Action of Sacral Nerve Modulation.

PURPOSE: Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction. MATERIALS AND METHODS: In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods. RESULTS: Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA. CONCLUSIONS: Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

Biophysics of Frequency-Dependent Variation in Paresthesia and Pain Relief during Spinal Cord Stimulation.

The neurophysiological effects of spinal cord stimulation (SCS) for chronic pain are poorly understood, resulting in inefficient failure-prone programming protocols and inadequate pain relief. Nonetheless, novel stimulation patterns are regularly introduced and adopted clinically. Traditionally, paresthetic sensation is considered necessary for pain relief, although novel paradigms provide analgesia without paresthesia. However, like pain relief, the neurophysiological underpinnings of SCS-induced paresthesia are unknown. Here, we paired biophysical modeling with clinical paresthesia thresholds (of both sexes) to investigate how stimulation frequency affects the neural response to SCS relevant to paresthesia and analgesia. Specifically, we modeled the dorsal column (DC) axonal response, dorsal column nucleus (DCN) synaptic transmission, conduction failure within DC fiber collaterals, and dorsal horn network output. Importantly, we found that high-frequency stimulation reduces DC fiber activation thresholds, which in turn accurately predicts clinical paresthesia perception thresholds. Furthermore, we show that high-frequency SCS produces asynchronous DC fiber spiking and ultimately asynchronous DCN output, offering a plausible biophysical basis for why high-frequency SCS is less comfortable and produces qualitatively different sensation than low-frequency stimulation. Finally, we demonstrate that the model dorsal horn network output is sensitive to SCS-inherent variations in spike timing, which could contribute to heterogeneous pain relief across patients. Importantly, we show that model DC fiber collaterals cannot reliably follow high-frequency stimulation, strongly affecting the network output and typically producing antinociceptive effects at high frequencies. Altogether, these findings clarify how SCS affects the nervous system and provide insight into the biophysics of paresthesia generation and pain relief.