A novel modulation strategy to increase stimulation duration in neuromuscular electrical stimulation

Introduction: Neuromuscular electrical stimulation (NMES) has been shown to be an effective treatment for muscular dysfunction. Yet, a fundamental barrier to NMES treatments is the rapid onset of muscle fatigue. The purpose of this study is to examine the effect of feedback‐based frequency modulation on the closed‐loop performance of the quadriceps during repeated dynamic contractions. Methods: In the first experiment, subjects completed four different frequency modulation NMES protocols utilizing the same amplitude modulation control to compare the successful run times (SRTs). A second experiment was performed to determine the change in muscle response to high‐ and low‐frequency stimulation. Results: Compared with constant‐frequency stimulation, results indicate that using an error‐driven strategy to vary the stimulation frequency during amplitude modulation increases the number of successful contractions during non‐isometric conditions. Conclusion: Simultaneous frequency and amplitude modulation increases the SRT during closed‐loop NMES control. Muscle Nerve 44: 382–387, 2011     

压力性尿失禁动物模型的建立及效果评价

背景：目前治疗压力性尿失禁的方法有药物治疗、物理-行为治疗及手术治疗等多种,但仍在探索优化中。 目的：探索通过截断双侧阴部神经及支配髂骨尾骨肌、耻骨尾骨肌的盆底神经肌友,建立稳定的压力性尿失禁动物模型的方法。 方法：6周龄SD雌性大鼠18只,体质量(199.44±8.41) g。随机分为3组,正常组、模型组和假手术组各6只。对模型组大鼠作双侧阴部神经及盆底神经肌支截断,假手术组分离暴露上述神经但不作截断,正常组大鼠不作特殊处理。术后2周测定3组大鼠的漏尿点压力。压力测定后取正常大鼠及模型大鼠的膀胱颈尿道交界部的横截面作组织学分析。 结果与结论：假手术组1只大鼠于术后1周死亡。余大鼠皆存活并顺利测定漏尿点压力。与正常大鼠相比,模型组大鼠平均漏尿点压力下降约33%(P < 0.05),而假手术组大鼠与正常组大鼠平均漏尿点压力差异无显著性意义(P > 0.05)。组织学检查显示,与正常大鼠比较,模型组大鼠尿道横纹肌排列疏松,而肌纤维也出现一定的萎缩。提示截断双侧阴部神经及盆底神经肌支可建立较为稳定的压力性尿失禁动物模型。     

Sacral Neuromodulation Changes Pelvic Floor Activity in Overactive Bladder Patients—Possible New Insights in Mechanism of Action: A Pilot Study

ObjectivesTo evaluate if electrodiagnostic tools can advance the understanding in the effect of sacral neuromodulation (SNM) on pelvic floor activity, more specifically if SNM induces changes in pelvic floor muscle (PFM) contraction.Materials and MethodsSingle tertiary center, prospective study (October 2017–May 2018) including patients with overactive bladder syndrome undergoing SNM. Electromyography of the PFM was recorded using the Multiple Array Probe Leiden. The procedure consisted of consecutive stimulations of the lead electrodes with increasing intensity (1–3, 5, 7, 10 V). Recordings were made after electrode placement (T0) and three weeks of SNM (T1). Patients with >50% improvement were defined as responders, others as nonresponders. For the analyses, the highest electrical PFM response (EPFMR), defined as the peak-to-peak amplitude of the muscle response, was identified for each intensity. The sensitivity (intensity where the first EPFMR was registered and the normalized EPFMR as percentage of maximum EPFMR) and the evolution (EMFPR changes over time) were analyzed using linear mixed models.ResultsFourteen patients were analyzed (nine responders, five nonresponders). For nonresponders, the PFM was significantly less sensitive to stimulation after three weeks (T0: 1.7 V, T1: 2.6 V). The normalized EPFMR was (significantly) lower after three weeks for the ipsilateral side of the PFM for the clinically relevant voltages (1 V: 36%–23%; p = 0.024, 2 V: 56%–29%; p = 0.00001; 3 V: 63%–37%; p = 0.0002). For the nonresponders, the mean EPFMR was significantly lower at 8/12 locations at T1 (T0: 109 μV, T1: 58 μV; mean p = 0.013, range <0.0001–0.0867). For responders, the sensitivity and evolution did not change significantly.ConclusionsThis is the first study to describe in detail the neurophysiological characteristics of the PFM, and the changes over time upon sacral spinal root stimulation, in responders and nonresponders to SNM. More research is needed to investigate the full potential of EPFMR as a response indicator.     

Endurance neuromuscular electrical stimulation training improves skeletal muscle oxidative capacity in individuals with motor‐complete spinal cord injury

Introduction: Spinal cord injury (SCI) results in skeletal muscle atrophy, increases in intramuscular fat, and reductions in skeletal muscle oxidative capacity. Endurance training elicited with neuromuscular electrical stimulation (NMES) may reverse these changes and lead to improvement in muscle metabolic health. Methods: Fourteen participants with complete SCI performed 16 weeks of home‐based endurance NMES training of knee extensor muscles. Skeletal muscle oxidative capacity, muscle composition, and blood metabolic and lipid profiles were assessed pre‐ and post‐training. Results: There was an increase in number of contractions performed throughout the duration of training. The average improvement in skeletal muscle oxidative capacity was 119%, ranging from –14% to 387% (P = 0.019). There were no changes in muscle composition or blood metabolic and lipid profiles. Conclusion: Endurance training improved skeletal muscle oxidative capacity, but endurance NMES of knee extensor muscles did not change blood metabolic and lipid profiles. Muscle Nerve 55: 669–675, 2017     

Comparing the force ripple during asynchronous and conventional stimulation

Introduction: Asynchronous stimulation has been shown to reduce fatigue during electrical stimulation; however, it may also exhibit a force ripple. We quantified the ripple during asynchronous and conventional single‐channel transcutaneous stimulation across a range of stimulation frequencies. Methods: The ripple was measured during 5 asynchronous stimulation protocols, 2 conventional stimulation protocols, and 3 volitional contractions in 12 healthy individuals. Results: Conventional 40 Hz and asynchronous 16 Hz stimulation were found to induce contractions that were as smooth as volitional contractions. Asynchronous 8, 10, and 12 Hz stimulation induced contractions with significant ripple. Conclusions: Lower stimulation frequencies can reduce fatigue; however, they may also lead to increased ripple. Future efforts should study the relationship between force ripple and the smoothness of the evoked movements in addition to the relationship between stimulation frequency and NMES‐induced fatigue to elucidate an optimal stimulation frequency for asynchronous stimulation. Muscle Nerve 50: 549–555, 2014     

H‐reflexes reduce fatigue of evoked contractions after spinal cord injury

Introduction: Neuromuscular electrical stimulation (NMES) over a muscle belly (mNMES) generates contractions predominantly through M‐waves, while NMES over a nerve trunk (nNMES) can generate contractions through H‐reflexes in people who are neurologically intact. We tested whether the differences between mNMES and nNMES are present in people with chronic motor‐complete spinal cord injury and, if so, whether they influence contraction fatigue. Methods: Plantar‐flexion torque and soleus electromyography were recorded from 8 participants. Fatigue protocols were delivered using mNMES and nNMES on separate days. Results: nNMES generated contractions that fatigued less than mNMES. Torque decreased the least when nNMES generated contractions, at least partly through H‐reflexes (n = 4 participants; 39% decrease), and torque decreased the most when contractions were generated through M‐waves, regardless of NMES site (nNMES 71% decrease, n = 4; mNMES, 73% decrease, n = 8). Conclusions: nNMES generates contractions that fatigue less than mNMES, but only when H‐reflexes contribute to the evoked contractions. Muscle Nerve 50:224–234, 2014     

Mechanosensitivity may be enhanced in skeletal muscles of spinal cord–injured versus able‐bodied men

We investigated the effects of an acute bout of neuromuscular electrical stimulation–induced resistance exercise (NMES‐RE) on intracellular signaling pathways involved in translation initiation and mechanical loading–induced muscle hypertrophy in spinal cord–injured (SCI) versus able‐bodied (AB) individuals. AB and SCI individuals completed 90 isometric knee extension contractions at 30% of maximum voluntary or evoked contraction, respectively. Muscle biopsies were collected before, and 10 and 60 min after NMES‐RE. Protein levels of α7‐ and β1‐integrin, phosphorylated and total GSK‐3α/β, S6K1, RPS6, 4EBP1, and FAK were assessed by immunoblotting. SCI muscle appears to be highly sensitive to muscle contraction even several years after the injury, and in fact it may be more sensitive to mechanical stress than AB muscle. Heightened signaling associated with muscle mechanosensitivity and translation initiation in SCI muscle may be an attempted compensatory response to offset elevated protein degradation in atrophied SCI muscle. Muscle Nerve 50: 599–601, 2014     

Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats

Introduction: Age‐related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age‐related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found after NMES. Methods: Fifty‐four young, middle‐aged, and old 344/Brown Norway rats were included in this study. Twenty‐four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles were examined. Results: Compared with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half‐decay times, and increased twitch and tetanic tension. Increased type I MHC was found, except for in GG in old and middle‐aged rats. Conclusion: Transitions in tongue muscle contractile properties and phenotype were found after NMES. Muscle Nerve, 2013     

Pelvic Floor Muscle Electromyography as a Guiding Tool During Lead Placement and (Re)Programming in Sacral Neuromodulation Patients: Validity,Reliability, and Feasibility of the Technique

PurposeTo assess the validity, reliability, and feasibility of electromyography (EMG) as a tool to measure pelvic floor muscle (PFM) contractions during placement and (re)programming of the tined lead electrodes in sacral neuromodulation (SNM) patients.Materials and MethodsSingle tertiary center, prospective study conducted between 2017 and 2019 consisting of three protocols including a total of 75 patients with overactive bladder (wet/dry) or nonobstructive urinary retention. PFM EMG was recorded using the multiple array probe (MAPLe), placed intravaginally. All stimulations (monophasic pulsed square wave, 210 μsec, 14 Hz) were performed using Medtronic’s standard SNM stimulation equipment. During lead implantation, all four lead electrodes were stimulated with fixed increasing stimulation intensities (1-2-3-5-7-10 V). During lead electrode (re)programming, five bipolar lead electrode configurations were stimulated twice up to when an electrical PFM motor response (EPFMR), sensory response, and pain response were noted (i.e., the threshold), respectively. Additionally, amplitude and latency of the EPFMRs were determined. Validity, reliability, and feasibility were statistically analyzed using the intraclass correlation coefficient, weighted Cohen’s kappa and linear regression, respectively.ResultsValidity: EPFMRs were strongly associated with visually detected PFM motor responses (κ = 0.90). Reliability: EPFMR amplitude (ICC = 0.99) and latency (ICC = 0.93) showed excellent repeatability. Feasibility: linear regression (EPFMR threshold = 0.18 mA + 0.76 * sensory response threshold) showed an increase in the sensory response threshold is associated with a smaller increase in EPFMR threshold, with the EPFMR occurring before or on the sensory response threshold in 83.8% of all stimulations.ConclusionsMeasuring PFM contractions with EMG during placement and (re)programming of lead electrodes in SNM patients is valid, reliable, and feasible. Therefore, the use of PFM EMG motor responses could be considered as a tool to assist in these procedures.     

Neuromuscular electrical stimulation in early rehabilitation of Guillain-Barré syndrome: A pilot study

Introduction: In Guillain-Barré syndrome (GBS), patients often develop muscle atrophy from denervation and immobilization. We, therefore, conducted a pilot study of neuromuscular electrical stimulation (NMES) to evaluate feasibility, safety, and effect on muscle wasting in the early phase of GBS. Methods: Seventeen patients were randomized to receive 20 min of muscle fiber stimulation followed by 40 min of NMES of the right or left quadriceps muscle with the untreated side as control. Cross-sectional area (CSA) of the muscle measured by ultrasound and isometric knee extensor strength were the primary and secondary outcome measures. Results: No treatment related adverse effects were recorded. Change in CSA was -0.25 cm² (confidence interval [CI], -0.93–0.42) on the stimulated side versus -0.60 cm² (CI, -1.32–0.11) on the nonstimulated side (P = 0.08). No effect was observed on muscle strength. Conclusions: NMES seems safe and feasible in the early phase of GBS. Further studies are needed to explore effect on muscle function. Muscle Nerve 59:481–484, 2019     

Maximal versus submaximal intensity stimulation with variable patterns

It is essential to determine optimal parameters of stimulation to maintain muscle force during neuromuscular electrical stimulation (NMES). Protocols that increase in frequency and include doublets can prolong force output over time. However, stimulation intensity level could differentially affect muscle force output during variable-frequency NMES. We compared three intermittent stimulation patterns at maximal and submaximal intensities of stimulation of the median nerve: (1) a constant 20-HZ pattern; (2) 90 s at 20 HZ followed by a 90-s increase from 20 to 40 HZ; and (3) 90 s at 20 HZ followed by 90 s of doublets at 20 HZ. At submaximal intensities, the doublet pattern produced the highest overall force-time integral (FTI). At maximal intensities, the doublet pattern produced the lowest FTI and the increasing frequency pattern produced the least amount of fatigue. Thus, double-pulse stimulation was more effective during submaximal than maximal intensity NMES. These data demonstrate that intensity level must be taken into consideration when programming frequency patterns for NMES devices.     

Effect of neuromuscular electrical stimulation frequency on muscles of the tongue

Introduction: Neuromuscular electrical stimulation (NMES) for the treatment of swallowing disorders is delivered at a variety of stimulation frequencies. We examined the effects of stimulation frequency on tongue muscle plasticity in an aging rat model. Methods: Eighty‐six young, middle‐aged, and old rats were assigned to either bilateral hypoglossal nerve stimulation at 10 or 100 Hz (5 days/week, 8 weeks), sham, or no‐implantation conditions. Muscle contractile properties and myosin heavy chain (MyHC) composition were determined for hyoglossus (HG) and styloglossus (SG) muscles. Results: Eight weeks of 100‐Hz stimulation resulted in the greatest changes in muscle contractile function with significantly longer contraction and half‐decay times, the greatest reduction in fatigue, and a transition toward slowly contracting, fatigue‐resistant MyHC isoforms. Discussion: NMES at 100‐Hz induced considerable changes in contractile and phenotypic profiles of HG and SG muscles, suggesting higher frequency NMES may yield a greater therapeutic effect. Muscle Nerve, 2018     

Twitch potentiation after voluntary contraction and neuromuscular electrical stimulation at various frequencies in human quadriceps femoris

Introduction: In this study we aimed to compare the extent of twitch potentiation (TP) after voluntary contraction and percutaneous electrical stimulation of muscles (neuromuscular electrical stimulation: NMES) with various stimulation frequencies at equivalent target levels. Methods: Isometric knee extensions of 10 s were performed at a 40% maximal voluntary contraction level by voluntary or NMES conditioning contractions at 20, 40, and 80 HZ of the quadriceps femoris muscle. Twitch responses were elicited by stimulating the femoral nerve transcutaneously at supramaximal intensity. Results: NMES at 80 HZ induced significantly less TP (128.7 ± 17.1%) than voluntary contraction (156.2 ± 23.1%), whereas no statistical difference was found in TP among voluntary and 20‐ and 40‐HZ NMES conditioning contractions (170.8 ± 21.1% and 162.7 ± 16.9% for 20‐ and 40‐HZ NMES, respectively). Conclusion: Stimulation frequency of NMES determines whether NMES can induce TP comparable to that after voluntary contraction. Muscle Nerve 45: 110–115, 2012     

Constipation: a potential cause of pelvic floor damage?

Background Pelvic floor damage is a major clinical problem usually attributed to obstetric injury. We speculated that constipation may also be an aetiological and preventable factor resulting from repeated stress on the perineum over many years, and this study aimed to test this hypothesis. Methods A total of 600 women attending a gynaecological clinic were assessed using a structured questionnaire gathering data on pelvic floor damage, constipation and obstetric trauma. Complete data were available on 596 subjects. Key Results The prevalence of pelvic floor damage was 10% (61/596). In this group, constipation was identified in 31% (19/61) of women and obstetric trauma in 31% (19/61). In the group without pelvic floor damage, constipation was present in 16% (86/535) and obstetric trauma in 16% (83/535). In univariate analysis, pelvic floor damage was associated with age (OR: 1.05; 95% CI: 1.03–1.08; P < 0.0001), constipation (OR: 2.36; 95% CI: 1.31–4.26; P < 0.0001) and obstetric trauma (OR: 2.46; 95% CI: 1.37–4.45; P < 0.0028). In multivariate analysis, the OR for age was 1.05 (95% CI: 1.03–1.08; P < 0.0001), for constipation 2.35 (95% CI: 1.27–4.34; P < 0.0001) and for obstetric trauma 1.37 (95% CI: 0.72–2.62; P = 0.3398). Conclusions & Inferences Constipation appears to be as important as obstetric trauma in the development of pelvic floor damage. Thus, a more proactive approach to recognizing and treating constipation might significantly reduce the prevalence of this distressing problem.     

Cocaine- and Amphetamine-Regulated Transcript Peptide (CARTp): Distribution and Function in Rat Urinary Bladder

We investigated the distribution of CARTp_(55-102) in rat lower urinary tract and evaluated its effect on urinary bladder function in vitro. Immunohistochemistry and a vertical isolated tissue bath system were used. Neurons, clusters of nonneuronal endocrine cells, and nerve fibers stained positive for CARTp_(55-102) in young adult rat urinary bladder. The CARTp-expressing neuronal elements were nitric oxide synthase (NOS)- and tyrosine hydroxylase (TH)-IR, whereas all nonneuronal CARTp-IR elements stained positively only for TH (100 %). In isolated bladder strips, CARTp significantly increased the amplitude of electric field stimulation (EFS)-induced detrusor contractions at stimulation frequencies ≤12.5 Hz (p?≤?0.001) as well as amplitude and frequency of spontaneous phasic urinary bladder smooth muscle (UBSM) contractions (p?≤?0.05). The responses to CARTp stimulation were dose-dependent and increased in the presence of the urothelium. To determine if the CARTp increase in nerve-mediated contractions may involve an action of CARTp on specific neural pathways, we blocked cholinergic, purinergic, and adrenergic pathways and determined CARTp actions on EFS-medicated contractions. CARTp enhancement of EFS-mediated contractions does not involve alteration in purinergic, adrenergic, or cholinergic pathways. The study demonstrates that CARTp_(55-102) is highly expressed in rat urinary bladder. CARTp increased the amplitude of EFS-induced detrusor contractions as well as the amplitude and frequency of spontaneous phasic urinary bladder smooth muscle contractions. We conclude that CARTp may alter the release of compounds from the urothelium that leads to an enhancement of UBSM contractility/excitability.     

Test–retest reliability of wide‐pulse high‐frequency neuromuscular electrical stimulation evoked force

Introduction: We compare forces evoked by wide‐pulse high‐frequency (WPHF) neuromuscular electrical stimulation (NMES) delivered to a nerve trunk versus muscle belly and assess their test–retest intraindividual and interindividual reliability. Methods: Forces evoked during 2 sessions with WPHF NMES delivered over the tibial nerve trunk and 2 sessions over the triceps surae muscle belly were compared. Ten individuals participated in 4 sessions involving ten 20‐s WPHF NMES contractions interspaced by 40‐s recovery. Mean evoked force and force time integral of each contraction were quantified. Results: For both nerve trunk and muscle belly stimulation, intraindividual test–retest reliability was good (intraclass correlation coefficient > 0.9), and interindividual variability was large (coefficient of variation between 140% and 180%). Nerve trunk and muscle belly stimulation resulted in similar evoked forces. Discussion: WPHF NMES locations might be chosen by individual preference because intraindividual reliability was relatively good for both locations. Muscle Nerve 57 : E70–E77, 2018.     

Neuromuscular electrical stimulation in neurorehabilitation

This review provides a comprehensive overview of the clinical uses of neuromuscular electrical stimulation (NMES) for functional and therapeutic applications in subjects with spinal cord injury or stroke. Functional applications refer to the use of NMES to activate paralyzed muscles in precise sequence and magnitude to directly accomplish functional tasks. In therapeutic applications, NMES may lead to a specific effect that enhances function, but does not directly provide function. The specific neuroprosthetic or "functional" applications reviewed in this article include upper- and lower-limb motor movement for self-care tasks and mobility, respectively, bladder function, and respiratory control. Specific therapeutic applications include motor relearning, reduction of hemiplegic shoulder pain, muscle strengthening, prevention of muscle atrophy, prophylaxis of deep venous thrombosis, improvement of tissue oxygenation and peripheral hemodynamic functioning, and cardiopulmonary conditioning. Perspectives on future developments and clinical applications of NMES are presented.     

Restoration of micturition using microelectric current in experimentally induced spastic urinary bladder in rabbits

The 29 rabbits used in this study were divided into three groups, A (A1 and A2), B, and C. In subgroup A1, 4 animals were used in order to verify whether the contact of an electrode to the sacral nerves results in some abnormality of voiding reflex. In subgroups A1 and A2 (4 animals each) we further studied the micturition function using three parameters: (i) urinary bladder fluoroscopy and radiography, (ii) cystomanometry, and (iii) electromyography of the pelvic floor muscles (external sphinter). In group B (9 rabbits) spastic paraplegia and micturition disturbances resulted from spinal cord compression that was induced by inserting a balloon catheter into the T11-T12 intervertebral foramen. In this group the parameters studied revealed a spastic urinary bladder in all animals. Finally, the 12 animals of group C were rendered paraplegic as described in group B, and microelectrodes were placed over the sacral nerves as in subgroup A1. By applying a specific sequence of sacral nerve stimulation we succeeded in satisfactory urinary bladder emptying as confirmed by the micturition parameters studied: The urinary bladder pressure decreased from 65 +/- 3 to 28 +/- 3 mm Hg. The pelvic floor muscle amplitude was lowered from 130 +/- 7 to 20 +/- 3 microV, and finally the radiological bladder size also decreased from 38 cm2 before voiding to 18 +/- 3 cm2 after voiding. These results indicate that microelectric current stimulation of the sacral nerves, when applied under a specific sequence, could rather satisfactorily restore micturition disturbances, at least in this experimental animal.     

Influence of joint position on synergistic muscle activity after fatigue of a single muscle head

Introduction: We investigated synergistic muscle activity after fatigue of a single muscle in different joint positions. Methods: Two experimental groups (n = 12 each) performed maximal voluntary contractions (MVCs) before and after fatiguing the gastrocnemius lateralis (GL), using neuromuscular electrical stimulation (NMES). Neuromuscular tests, including muscle activity during MVC, H‐reflex, and twitch interpolation, were performed. One group completed the experiment in a knee‐extended position with the second group in a knee‐flexed position. Results: In the knee‐flexed position, the muscle activity increased in non‐stimulated synergistic muscles. In contrast, in the knee‐extended position, muscle activity of the synergistic muscles remained unaltered. The MVC force remained unaltered in the flexed position and decreased in the extended position. Conclusions: Synergistic muscles compensate for the fatigued muscle in the flexed position but not in the extended position. Compensation mechanisms seem to depend on joint position. Muscle Nerve 51 : 259–267, 2015