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(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study.

Objective: Hemispatial neglect is a frequent condition usually following nondominant hemispheric brain injury. It strongly affects rehabilitation strategies and everyday life activities. It is associated with behavioral and cognitive disability with a strong impact on patient's life., Methods: We reviewed the published literature on the use of noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), and of noninvasive peripheral muscle stimulation, as therapeutic strategies for rehabilitation of neglect after acquired brain injury, such as in stroke or in traumatic injuries. The studies were grouped as controlled or uncontrolled studies in each stimulation techniques., Results: Thirty-four studies were identified and 16 on rTMS, 10 on tDCS, and 8 on vibration. All studies were conducted in adult patients who suffered a stroke, except for one that was conducted in a patient suffering traumatic acquired brain injury and another that was conducted in a patient with brain tumor. In spite of significant variability in treatment protocols, patients' features and assessment of neglect, improvement was reported in almost all studies with no side-effects., Conclusions: Noninvasive brain stimulation and neuromuscular vibration are promising therapeutic neuromodulatory approaches for neglect. Further randomized-controlled studies are needed to corroborate their effectiveness as separate and combined techniques., (© 2019 International Neuromodulation Society.)

Background: The excitability of brainstem interneuronal circuits is partly under control from descending inputs. Since high frequency repetitive transcranial magnetic stimulation (rTMS) modulates cortical output, we hypothesized that it will also modulate brainstem functions. Such modulation may be different in healthy subjects than in subjects with spinal cord injury (SCI), submitted to an altered integration of body afferent inputs., Methods: In this randomized, double-blind, sham-controlled trial, we recruited 22 subjects with SCI assigned to either real (n = 11) or sham (n = 11) rTMS and nine healthy subjects, who served as control group, receiving both real (at 20 Hz, with double cone coil over vertex) and sham rTMS separated by at least one week. We recorded the blink reflex (BR) to supraorbital nerve (SON) electrical stimulation and its modification by another conditioning SON, to study the BR excitability recovery (BRER), or a prepulse electrical stimulus to the right index finger, to study the BR inhibition by prepulse (BRIP). Subjects were examined immediately before and after either sham or real rTMS., Results: Real but not sham rTMS significantly reduced the area of the BR R2 response in both SCI and healthy subjects. There were no changes in BRER and BRIP., Conclusion: rTMS over the vertex modulates brainstem reflexes with no significant differences between SCI and healthy subjects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle., Methods: Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention., Results: Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle., Conclusion: Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle., Significance: Application of magnetic-PAS might be relevant for motor rehabilitation., (Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.)

Purpose: Maladaptive plasticity in the sensorimotor system, following neurological lesions or diseases, plays a central role in the generation and maintenance of neuropathic pain. Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief. Systematic reviews that evaluate the effectiveness and specificity of different protocols of repetitive magnetic stimulation to control neuropathic pain in clinical populations have the potential to improve the therapeutic applicability of this technique., Methods: Studies whose primary goal was to evaluate the effectiveness of repetitive magnetic stimulation for the treatment of various types of neuropathic pain published in PubMed until August 2015 have been included in this systematic review., Results: A total of 39 articles fulfilling the inclusion criteria were analyzed of which 37 studies investigated pain modulation using repetitive magnetic stimulation over the motor or non-motor cortices and two studies evaluated pain modulation using repetitive peripheral magnetic stimulation protocols., Conclusions: Repetitive transcranial magnetic stimulation of the primary motor cortex using high frequency stimulation protocols can effectively reduce neuropathic pain, particularly in individuals with pain related to non-cerebral lesions. The application of multiple sessions can lead to long-lasting pain modulation and cumulative effects. Implications for Rehabilitation Maladaptive plasticity plays a central role in sensitization of nociceptive pathways, generation and maintainance of neuropathic pain; Most neuropathic pain conditions are refractory to pharmacological therapies; Repetitive magnetic stimulation of the central and peripheral nervous system has gained relevance as noninvasive approach for neuromodulation and pain relief.

High-frequency rTMS combined with gait training improves lower extremity motor score (LEMS) and gait velocity in SCI subjects who are able to walk over ground. The aim of this study was to optimize the functional outcome in early phases of gait rehabilitation in SCI using rTMS as an additional treatment to physical therapy. The present study included 31 motor incomplete SCI subjects randomized to receive real or sham rTMS, just before Lokomat gait training (15 subjects for real, 16 for sham rTMS). rTMS consisted of one daily session for 20 days over vertex (at 20 Hz). The subjects were evaluated using modified Ashworth scale (MAS) for spasticity, upper and lower extremity motor score (UEMS and LEMS, respectively), ten meters walking test (10MWT) and Walking Index for SCI (WISCI-II) for gait at baseline, after last rTMS session, and during follow-up. UEMS and LEMS improved significantly after last session in both groups and during follow-up period. The improvement was greater in real than in sham rTMS group. At follow-up, 71.4 % of the subjects after real rTMS and 40 % of the subjects after sham rTMS could perform 10MWT without significant differences in gait velocity, cadence, step length and WISCI-II between both groups. We conclude that 20 sessions of daily high-frequency rTMS combined with Lokomat gait training can lead to clinical improvement of gait in motor incomplete SCI. Such combined treatment improved motor strength in lower extremity in incomplete SCI subjects and in upper extremity in those with cervical SCI.

Objective: Incomplete spinal cord injury (SCI) patients have the potential to regain some ambulatory function, and optimal reorganization of remaining circuits can contribute to this recovery. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) may promote active recovery of motor function during gait rehabilitation., Methods: A total of 17 incomplete SCI patients were randomized to receive active rTMS or sham stimulation coupled with rehabilitation therapy; 3 patients who began in the sham group crossed over to the active rTMS group after a washout period of more than 3 weeks. Active rTMS consisted of 15 daily sessions over the leg motor area (at 20 Hz). We compared lower-extremity motor score (LEMS), 10-m walking test for walking speed, timed up and go, Walking Index for SCI Scale, Modified Ashworth Scale, and Spinal Cord Injury Spasticity Evaluation Tool at baseline, after the last session, and 2 weeks later in the active rTMS and sham stimulation groups., Results: A significant improvement was observed after the last rTMS session in the active group for LEMS, walking speed, and spasticity. Improvement in walking speed was maintained during the follow-up period. Sham stimulation did not induce any improvement in LEMS, gait assessment, and spasticity after the last session and neither during follow-up., Conclusion: In incomplete SCI, 15 daily sessions of high-frequency rTMS can improve motor score, walking speed, and spasticity in the lower limbs. The study provides evidence for the therapeutic potential of rTMS in the lower extremities in SCI rehabilitation.

Background: Neuropathic pain (NP) is common in spinal cord injury (SCI) patients. One of its manifestations is a lowering of pain perception threshold in quantitative thermal testing (QTT) in dermatomes rostral to the injury level. Transcranial direct current stimulation (tDCS) combined with visual illusion (VI) improves pain in SCI patients. We studied whether pain relief with tDCS + VI intervention is accompanied by a change in contact heat- evoked potentials (CHEPs) or in QTT., Methods: We examined 18 patients with SCI and NP before and after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and 14 healthy subjects served as controls. We assessed NP intensity using a numerical rating scale (NRS) and determined heat and pain thresholds with thermal probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated their perception of evoked pain using NRS during CHEPs., Results: Thirteen patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI. Evoked pain perception was significantly higher than in the other two groups, and reduced significantly together with CHEPs amplitude after tDCS + VI with respect to baseline. Pain perception threshold was significantly lower than in the other two groups before tDCS + VI intervention, and increased significantly afterwards., Conclusion: Two weeks of tDCS + VI induced significant changes in CHEPs, evoked pain and heat pain threshold in SCI patients with NP. These neurophysiological tests might be objective biomarkers of treatment effects for NP in patients with SCI., (© 2012 European Federation of International Association for the Study of Pain Chapters.)

The aim of this study was to evaluate the analgesic effect of transcranial direct current stimulation of the motor cortex and techniques of visual illusion, applied isolated or combined, in patients with neuropathic pain following spinal cord injury. In a sham controlled, double-blind, parallel group design, 39 patients were randomized into four groups receiving transcranial direct current stimulation with walking visual illusion or with control illusion and sham stimulation with visual illusion or with control illusion. For transcranial direct current stimulation, the anode was placed over the primary motor cortex. Each patient received ten treatment sessions during two consecutive weeks. Clinical assessment was performed before, after the last day of treatment, after 2 and 4 weeks follow-up and after 12 weeks. Clinical assessment included overall pain intensity perception, Neuropathic Pain Symptom Inventory and Brief Pain Inventory. The combination of transcranial direct current stimulation and visual illusion reduced the intensity of neuropathic pain significantly more than any of the single interventions. Patients receiving transcranial direct current stimulation and visual illusion experienced a significant improvement in all pain subtypes, while patients in the transcranial direct current stimulation group showed improvement in continuous and paroxysmal pain, and those in the visual illusion group improved only in continuous pain and dysaesthesias. At 12 weeks after treatment, the combined treatment group still presented significant improvement on the overall pain intensity perception, whereas no improvements were reported in the other three groups. Our results demonstrate that transcranial direct current stimulation and visual illusion can be effective in the management of neuropathic pain following spinal cord injury, with minimal side effects and with good tolerability.

Motor preparation for execution of both simple and choice reaction time tasks (SRT and CRT) involves enhancement of corticospinal excitability (CE). However, motor preparation also implies changes in inhibitory control that have thus far been much less studied. Short-interval intracortical inhibition (SICI) has been shown to decrease before CE increases. Therefore we reasoned that, if SICI contributes to inhibitory control of voluntary movement during the preparatory phase, it would be larger in CRT than in SRT because of the need to keep the movement unreleased until the uncertainty resolves on which task is required. We measured changes in SICI and in CE at different time points preceding motor reaction in normal subjects. Single-pulse transcranial magnetic stimulation (spTMS) and paired-pulse transcranial magnetic stimulation (ppTMS) produced time-dependent changes in both SRT and CRT, with shortening when applied close to the presentation of the imperative signal ("early") and lengthening when applied near the expected reaction ("late"). In addition, at all stimulation time points, reaction time was shorter with ppTMS than that with spTMS, but there was no consistent association between the amount of SICI and reaction time changes. At early stimulation time points, CE was reduced in CRT but not in SRT. However, SICI in CRT was not different from SICI in SRT. At late stimulation time points, SICI decreased just before enhancement of CE. Our findings indicate that inhibitory circuits other than SICI are responsible for setting the level of CE at earlier parts of the reaction time period. Although the decrease in SICI may contribute to the increase in CE at the last part of the premotor period, the two phenomena are not dependent on each other.

Objective: Spasticity with increased tone and spasms is frequent in patients after spinal cord injury (SCI). Damage to descending corticospinal pathways that normally exert spinal segmental control is thought to play an important causal role in spasticity. The authors examined whether the modulation of excitability of the primary motor cortex with high-frequency repetitive transcranial magnetic stimulation (rTMS) could modify lower limb spasticity in patients with incomplete SCI., Methods: Patients were assessed by the Modified Ashworth Scale, Visual Analogue Scale, and the Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET) and neurophysiologically with measures of corticospinal and segmental excitability by the H(max)/M(max), T reflex, and withdrawal reflex. Fifteen patients received 5 days of daily sessions of active (n = 14) or sham (n = 7) rTMS to the leg motor area (20 trains of 40 pulses at 20 Hz and an intensity of 90% of resting motor threshold for the biceps brachii muscle)., Result: A significant clinical improvement in lower limb spasticity was observed in patients following active rTMS but not after sham stimulation.This improvement lasted for at least 1 week following the intervention. Neurophysiological studies did not change., Conclusions: High-frequency rTMS over the leg motor area can improve aspects of spasticity in patients with incomplete SCI.

Study Design: Prospective longitudinal study., Objectives: The aim of this study was to examine the effects of transcranial magnetic stimulation (TMS) on the soleus H reflex in patients with spinal cord injury (SCI) before and after locomotion training., Setting: Neurorehabilitation hospital in Barcelona, Spain., Methods: H reflex was elicited in 29 incomplete patients with SCI at 20, 50 and 80 ms after single vertex TMS, and compared with 13 healthy subjects. Patients were subdivided in two groups according to time since injury (<3 months, 3-12 months), and all received training with electromechanical systems. The H reflex modulation pattern to TMS was reassessed and the results were analyzed as a function of change in the patient clinical score., Results: Healthy subjects showed a significant H reflex facilitation at 20 ms (186.1%) and at 80 ms (190.6%) compared with the control H reflex. In patients, the H reflex facilitation at 20 ms was significantly reduced before training (142.5%, P=0.039) compared with healthy subjects. After training, patients with <3 months exhibited an increase in H reflex facilitation at 20 ms (170.7%, P=0.04), a greater gait velocity (P=0.014) and a positive correlation with the walking index for spinal cord injury (WISCI II) scale (P=0.050), compared with those with >3 months., Conclusions: TMS-induced H reflex modulation may help in the assessment of changes in the descending control of leg reflexes. Our results suggest that the changes on reflex modulation in patients with SCI occur within the first 3 months after injury.

Objective: To assess the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on lower extremities motor score (LEMS) and gait in patients with motor incomplete spinal cord injury (SCI). Method: The prospective longitudinal randomized, double-blind study assessed 17 SCI patients ASIA D. We assessed LEMS, modified Ashworth Scale (MAS), 10-m walking test (10MWT), Walking Index for SCI (WISCI II) scale, step length, cadence, and Timed Up and Go (TUG) test at baseline, after the last of 15 daily sessions of rTMS and 2 weeks later. Patients were randomized to active rTMS or sham stimulation. Three patients from the initial group of 10 randomized to sham stimulation entered the active rTMS group after a 3-week washout period. Therefore a total of 10 patients completed each study condition. Both groups were homogeneous for age, gender, time since injury, etiology, and ASIA scale. Active rTMS consisted of 15 days of daily sessions of 20 trains of 40 pulses at 20 Hz and an intensity of 90% of resting motor threshold. rTMS was applied with a double cone coil to the leg motor area. Results: There was a significant improvement in LEMS in the active group (28.4 at baseline and 33.2 after stimulation; P = .004) but not in the sham group (29.6 at baseline, and 30.9 after stimulation; P = .6). The active group also showed significant improvements in the MAS, 10MWT, cadence, step length, and TUG, and these improvements were maintained 2 weeks later. Following sham stimulation, significant improvement was found only for step length and TUG. No significant changes were observed in the WISCI II scale in either group. Conclusion: High-frequency rTMS over the leg motor area can improve LEMS, spasticity, and gait in patients with motor incomplete SCI. [ABSTRACT FROM AUTHOR]

Background We studied the effect of one session of high-frequency repetitive transcranial magnetic stimulation (rTMS) on brainstem stem excitability in patients with incomplete SCI. Methods The study was a randomized, double-blind, sham-controlled trial. We recruited 27 patients with SCI to be randomly distributed in two study groups: active or sham rTMS. We recorded the blink reflex (BR) induced with electrical stimulation at 15 times sensory threshold (ST) to the supraorbital nerve (SON). A prepulse electrical stimulus on BR (PP-BR), was delivered with ring electrodes to the right index finger at 2 times ST and applied 100 ms before the SON stimulus. We also examined the excitability recovery curve of the blink reflex (RC-BR), with pairs of stimuli at interstimuli intervals (ISI) of 160, 300, 500, and 1000 ms. Patients were examined at baseline, and after high-frequency vertex rTMS (20 Hz; 40 pulses/burst, 1800 pulses total over 20 min). Results Fifteen patients received active rTMS and 12 sham rTMS. The age between groups was not significant. At baseline, R2 area of BR and percentage changes (%) in RC-BR at all intervals were similar in both groups. Active but not sham rTMS significantly reduced the area of R2 in BR and decreased the % inhibition with respect to baseline ( p ⩽ 0.05), RC-BR did not change with any rTMS stimulation at any time. Conclusions High frequency-rTMS over motor cortex induces a decrease in brainstem reflex excitability and reduces inhibitory brainstem activity in patients with SCI. [ABSTRACT FROM AUTHOR]

Introduction: Single pulse transcranial magnetic stimulation (TMS) combined with electrical stimulation of a peripheral nerve induces changes in the excitability as a result of the so-called paired associative stimulation or PAS (Stefan et al., 2000; Castel-Lacanal et al., 2007). Based on this information, we studied the effect of double magnetic stimulation (TMS combined with repetitive peripheral magnetic stimulation=rPMS) on the corticospinal excitability and intracortical inhibition and facilitation. Method: Ten healthy subjects participated in the experiment. Their mean age was 37.5 (range: 29–64). rPMS was applied over the extensor carpi radialis (ECR). We delivered 5 stimuli at a frequency of 10Hz and an intensity of 70%, to produce a clear wrist dorsiflexion. This was followed 25ms later by a single pulse TMS (sTMS), delivered over the motor cortex of the dominant hemisphere at an intensity 120% of resting motor theshold (RMT). This conditioning paradigm was repeated during 10 min. We evaluated: (1) the size of the motor evoked potential (MEP); (2) the short latency intracortical inhibition (SICI) with interstimulus interval (ISI) of 2ms and (3) the short latency intracortical facilitation (SICF) with ISI of 15ms in the dominant hand. Result: The amplitude of the MEP increased and SICI decreased significantly after conditioning with respect to baseline, while no changes were observed in SICF. No changes were observed if sTMS was applied after either TMS alone or rPMS alone. Conclusion: The combination between rPMS and sTMS increases corticospinal excitability and decrease short latency intracortical inhibition in healthy subjects. This form of conditioning offers an alternative to PAS and may help revealing some of the physiological mechanisms underlying peripheral to central mechanisms of facilitation of corticospinal excitability. [Copyright &y& Elsevier]

Objective: Incomplete spinal cord injury (SCI) patients have the potential to regain some ambulatory function and optimal reorganization of remaining circuits can contribute to this recovery. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) may promote more active recovery of motor function at the beginning of gait training using electromechanical system. Methods: Seventeen incomplete SCI patients were randomized to receive active rTMS or sham stimulation coupled with rehabilitation therapy, when patients began gait training using electromechanical system. Active rTMS consisted of 20 daily sessions over the leg motor area (at 20Hz). We compared lower extremity motor score (LEMS), ten meter walking test (10MWT) for walking speed, timed up and go (TUG), Walking Index for SCI (WISCI II) scale, Modified Ashworth Scale (MAS) and Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET) at baseline, after the last session and 4weeks later, in the active rTMS and sham stimulation groups. Results: A significant improvement was observed after last rTMS session in the active group for LEMS and spasticity, but not for gait scales. Sham stimulation, did not induce any improvement in LEMS, gait assessment, neither in spasticity after last session. Conclusion: Twenty daily sessions of high-frequency rTMS can improve motor score and spasticity, but not walking speed in the lower limbs in incomplete SCI. The study provides evidence for the therapeutic potential of rTMS in the lower extremities in the early phase SCI rehabilitation. [Copyright &y& Elsevier]