Chronic Incomplete Spinal Cord Injury Research Articles

Combining Neuromodulation Strategies to Improve Locomotor Function in SCI: A Proof of Concept Case Study

<h3>Research Objectives</h3> Acute intermittent hypoxia (AIH) and transcutaneous spinal cord stimulation (tSCS) are two non-invasive neuromodulation treatments that have been shown to individually induce spinal plasticity in persons with chronic incomplete spinal cord injury (iSCI). However, these two interventions have never been tested in combination to see if their combined effect is greater than each intervention alone. This proof of concept case study investigated how AIH combined with tSCS during ambulation training may facilitate improvements in walking function in individuals with iSCI. <h3>Design</h3> Single-blind, randomized, crossover trial. <h3>Setting</h3> Outpatient, Rehabilitation Hospital. <h3>Participants</h3> 1 participant (male, 70 years) with chronic iSCI. <h3>Interventions</h3> The participant completed 3 arms, in random order: 1. AIH+tSCS 2. Sham-AIH+Sham-tSCS 3. Sham-AIH+tSCS Each arm consisted of 5 treatment sessions on consecutive days. <h3>Main Outcome Measures</h3> Assessments were performed at Baseline, Post-intervention (Post), and 1-week follow-up (1WFU), with a 4-week wash out between arms. Changes in gait performance were measured using the 10-meter walk test (10MWT) for fast and comfortable speeds, and the 6-minute walk test (6MWT). <h3>Results</h3> Overall, the participant showed potential improvements in his walking performance with AIH+tSCS at Post, relative to Baseline (10MWT-Fast: 5.6%; 10MWT-Comfortable: 7.0%; 6MWT: 15.6%), with further improvements at 1WFU (10MWT-Fast: 6.9%; 10MWT-Comfortable: 19.2%; 6MWT: 19.3%). The participant also showed potential improvements at Post, relative to Baseline with Sham-AIH+Sham-tSCS (10MWT-Fast: 12.2%; 10MWT-Comfortable: 6.6%; 6MWT: 15.1%) and with Sham-AIH+tSCS (10MWT-Fast: -2.5%; 10MWT-Comfortable: 15.3%; 6MWT: 6.0%). However, sustained improvements were not present at 1WFU with the Sham-AIH+Sham-tSCS (10MWT-Fast: 3.8%; 10MWT-Comfortable: -2.5%; 6MWT: 8.3%) or Sham-AIH+tSCS (10MWT-Fast: -3.9%; 10MWT-Comfortable: -5.5%; 6MWT: -2.1%), suggesting the combined intervention yielded retention effects. <h3>Conclusions</h3> AIH +tSCS with gait training may promote persistent improvements in walking function compared to tSCS with gait training or gait training alone in persons with iSCI. Further studies are warranted to investigate this novel, combinational neuromodulation strategy. <h3>Author(s) Disclosures</h3> The authors have no conflicts of interest to disclose.

Walking improvement in chronic incomplete spinal cord injury with exoskeleton robotic training (WISE): a randomized controlled trial

Study designClinical trial.ObjectiveTo demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).SettingOutpatient rehabilitation or research institute.MethodsMulti-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI (>1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary outcomes included: Timed-Up-and-Go (TUG), 6-min walk test (6MWT), Walking Index for Spinal Cord Injury (WISCI-II) (assistance and devices), and treating therapist NASA-Task Load Index.ResultsTwenty-five participants completed the assessments and training as assigned (9 Ekso, 10 Active Control, 6 Passive Control). Mean change in gait speed at the primary endpoint was not statistically significant. The proportion of participants with improvement in clinical ambulation category from home to community speed post-intervention was greatest in the Ekso group (>1/2 Ekso, 1/3 Active Control, 0 Passive Control, p < 0.05). Improvements in secondary outcome measures were not significant.ConclusionsTwelve weeks of exoskeleton robotic training in chronic SCI participants with independent stepping ability at baseline can improve clinical ambulatory status. Improvements in raw gait speed were not statistically significant at the group level, which may guide future trials for participant inclusion criteria. While generally safe and tolerable, larger gains in ambulation might be associated with higher risk for non-serious adverse events.

The effects of virtual soccer game on balance, gait function, and kick speed in chronic incomplete spinal cord injury: a randomized controlled trial.

Participant-blinded comparative pre-post randomized controlled trial. To evaluate the effects of virtual soccer game on balance, gait function, and kick speed in individuals with spinal cord injuries. Forty participants with incomplete spinal cord injury (SCI) were included. The participants were randomized into either an experimental group (EG) or a control group for treatment 3 days/week over 4 weeks. The clinical outcomes included the results of the chair stand test (CST), timed up-and-go (TUG) test, and 10 m walking test (10MWT). The virtual reality (VR) content outcome measure was kick speed. The independent t-test results indicated that the participants in the EG exhibited superior performances in the CST, TUG test, 10MWT, and kick speed test (all P < 0.05). Our results provide novel, promising clinical evidence that VR rehabilitation improves both dynamic and static balance and reduces the risk of falls in patients with incomplete SCI of Asia impairment scale grades C-D.

Nerve root magnetic stimulation improves locomotor function following spinal cord injury with electrophysiological improvements and cortical synaptic reconstruction.

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5-L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

Walking with and without a robotic exoskeleton in people with incomplete spinal cord injury compared to a typical gait pattern.

Robotic exoskeleton (RE) enables individuals with lower extremity weakness or paralysis to stand and walk in a stereotypical pattern. Examine whether people with chronic incomplete spinal cord injury (SCI) demonstrate a more typical gait pattern when walking overground in a RE than when walking without. Motion analysis system synchronized with a surface electromyographic (EMG) was used to obtain temporospatial gait parameters, lower extremity kinematics, and muscle activity in ambulatory individuals with SCI and healthy adults. Temporospatial parameters and kinematics for participants with SCI (n = 12; age 41.4±12.5 years) with and without RE were significantly different than a typical gait (healthy adults: n = 15; age 26.2±8.3 years). EMG amplitudes during the stance phase of a typical gait were similar to those with SCI with and without RE, except the right rectus femoris (p = 0.005) and left gluteus medius (p = 0.014) when participants with SCI walked with RE. EMG amplitudes of participants with SCI during the swing phase were significantly greater compared to those of a typical gait, except for left medial hamstring with (p = 0.025) and without (p = 0.196) RE. First-time walking in a RE does not appear to produce a typical gait pattern in people with incomplete SCI.

The Rehabilitation Effects of Myoelectric Powered Wearable Orthotics on Improving Upper Extremity Function in Persons with SCI.

Upper extremity (UE) weakness and/or paralysis following spinal cord injury (SCI) can lead to a limited capacity to perform activities of daily living (ADL). Such disability significantly reduces an individual's level of independence. Further, restoration of UE motor function in people with SCI remains a high priority in rehabilitation and the field of assistive technology. The overall goal of this study was to evaluate the effects of a myoelectric-powered wearable orthosis (MPWO) manufactured by MyoMo, Inc. (Boston, MA) for UE movement assistance on ameliorating UE motor function in order to improve ADL and quality of life in people with SCI. Two male participants with chronic incomplete SCI (iSCI), a 75- and a 31-year-old with AIS D and B, respectively, underwent 18 sessions (over 6 weeks) of UE movement rehabilitation using the MPWO. Handgrip strength, active range of motion (AROM) of the hand, response time to initiate a movement, and muscles activations were examined before and after the rehabilitation training using the MPWO. The response time to initiate UE movements decreased, and handgrip strength and AROM improved after training with the MPWO. These preliminary data suggest that rehabilitation with the use of the UE-MPWO device could enhance the participants' UE activities that led to improved function.Clinical Relevance- These preliminary results from two individuals with iSCI suggest that training with UE-MPWO assistive devices may improve UE utilization during ADL for individuals with muscle weakness or paralysis but still possessing residual voluntary muscle activation capabilities.

Operant Conditioning of the Motor Evoked Potentials for Sensorimotor Rehabilitation

<h3>Research Objectives</h3> The corticospinal pathway and its plasticity are essential in sensorimotor function recovery after neuromuscular injuries. To determine if operant up-conditioning of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) can increase corticospinal excitability and enhance sensorimotor rehabilitation, we are testing this neuromodulation approach in three different ongoing subprojects. We hypothesized that MEP up-conditioning can improve corticospinal activation of the targeted muscle and thereby improve functions in which that muscle participates. <h3>Design</h3> Each subproject utilizes operant MEP up-conditioning methodology. Standard MEP conditioning protocol consists of 6 baseline and 24 conditioning sessions (3/week, 30-45 min each). In each session, 250 single-pulse MEPs are elicited using TMS with or without operant conditioning (i.e., feedback on performance). Before and after conditioning, electrophysiological, kinematic, and functional assessments are performed. <h3>Setting</h3> Controlled laboratory. <h3>Participants</h3> Volunteers with chronic incomplete spinal cord injury (SCI), or with early-stage knee osteoarthritis (OA). <h3>Interventions</h3> See Design. <h3>Main Outcome Measures</h3> Target muscle MEP size, EMG, kinematics. <h3>Results</h3> Dorsiflexor MEP conditioning in people with chronic incomplete SCI: We hypothesize up-conditioning of the tibialis anterior (TA) MEP induces CNS plasticity that affects TA activation and improves locomotion. Initial studies found up-conditioning can increase TA MEP size and improve locomotion. Our current work aims to characterize cortical and corticospinal mechanisms of changes in MEP, locomotor EMG, and kinematics. Forearm extensor MEP conditioning in people with SCI: We hypothesize that corticospinal excitability for the wrist extensors can be increased through MEP conditioning and that it will help improve forearm motor function. Initial results support such possibilities in individuals with chronic incomplete cervical SCI. Quadriceps MEP conditioning in people with knee OA: We hypothesize that up-conditioning can increase quadriceps MEP size and improve quadriceps activation in individuals with early-stage knee OA. We are developing a protocol to examine the effects of MEP up-conditioning on quadriceps activation and function. <h3>Conclusions</h3> These projects will facilitate the dissemination of MEP conditioning as a neurorehabilitation tool to enhance functional recovery after neuromuscular injuries. <h3>Author(s) Disclosures</h3> Authors listed have no conflicts of interest to declare.

Altered Modulation of Locomotor Cutaneous Reflexes in Ambulatory Individuals With Chronic Spinal Cord Injury

<h3>Research Objectives</h3> The purpose of this study was to examine lower limb cutaneous (CUT) reflexes during walking in people with chronic incomplete spinal cord injury (SCI). In neurologically intact individuals, CUT reflexes to non-noxious stimulus are phase-dependently modulated during walking with nerve specificity, so as to avoid stumbling and falling [1]. Currently, CUT reflexes in ambulatory individuals with SCI are not well understood. <h3>Design</h3> CUT reflexes were elicited by stimulating the sural (SR), superficial peroneal (SP), or tibial nerve (TN) near the ankle of the clinically more spastic leg. For each nerve stimulation, a 5 × 1-ms pulse train (200 Hz) at ≈1.7 x radiating threshold was delivered pseudo-randomly across the entire step cycle while the participant walked on a treadmill at his/her comfortable speed. Electromyography (EMG) was recorded from the soleus and tibialis anterior (TA) bilaterally, and medial and lateral gastrocnemius, vastus lateralis, and biceps femoris in the stimulated leg. <h3>Setting</h3> University. <h3>Participants</h3> Eight individuals with chronic incomplete SCI volunteered to participate in this study. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Medium (80-120 ms post-stimulus) latency CUT reflexes were quantified in 8 equal bins of the step cycle. <h3>Results</h3> CUT reflexes are phase-dependently modulated in ambulatory individuals with SCI, with less nerve specificity than that in people without injuries [2]. Nerve specificity was clear for the ipsilateral TA, which showed strong excitation in the early swing phase following TN (56% max non-stimulated EMG) but suppression following SR (-4%) and SP (-13%). Contralateral TA was suppressed during late swing uniformly following TN (-15%), SR (-14%), and SP (-18%). <h3>Conclusions</h3> The presence and patterns of CUT reflex modulation could be useful measures of neuroplasticity in people with SCI. <h3>Author(s) Disclosures</h3> No conflicts.

Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury

Persons living with incomplete spinal cord injuries (SCI) often struggle to regain independent walking due to deficits in walking mechanics. They often dedicate many weeks of gait training before benefits to emerge, with additional training needed for benefits to persist. Recent studies in humans with SCI found that daily bouts of breathing low oxygen (acute intermittent hypoxia, AIH) prior to locomotor training elicited persistent (weeks) improvement in overground walking speed and endurance. AIH-induced improvements in overground walking may result from changes in control strategies that also enhance intralimb coordination; however, this possibility remains untested. Here, we examined the extent to which daily AIH combined with walking practice (AIH + WALK) improved overground walking performance and intralimb motor coordination in persons with chronic, incomplete SCI. MethodsWe recruited 11 persons with chronic (> 1 year), incomplete SCI to participate in a randomized, double-blind, balanced, crossover study. Participants first received either daily (5 consecutive days) AIH (15, 90-s episodes of 10.0% O2 with 60s intervals at 20.9% O2) or SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) followed by 30-min of overground walking practice. They received the second treatment after a minimum 2-week washout period. We quantified overground walking performance, in terms of speed and endurance, using the 10-Meter Walk Test (10MWT) and 6-Minute Walk Test (6MWT), respectively. We quantified intralimb motor coordination using kinematic variability measures of foot trajectory (i.e., endpoint variability, EV) and of inter-joint coupling between the hip and knee, as well as between the knee and ankle joints (i.e., angular coefficient of correspondence, ACC). We compared the changes in walking performance relative to baseline (BL) between daily AIH + WALK and daily SHAM+WALK on treatment day 5 (T5), 1-week follow-up (F1), and 2-weeks follow-up (F2). We also compared these changes between participants who used bilateral walking aids (N = 5) and those who did not. To assess the effects of daily AIH + WALK on intralimb coordination, we compared potential treatment-induced changes in EV and ACC relative to BL at F1 and F2. ResultsParticipants improved overground walking performance (speed and endurance) after daily AIH + WALK, but not SHAM+WALK. Following daily AIH + WALK, participants decreased their 10MWT time at T5 by 28% (95% CI 0.2–10.1 s, p = 0.04), F1 by 28% (95% CI 1.1–13.5 s, p = 0.01), and F2 by 27% (95% CI 1.4–13.9 s, p = 0.01) relative to BL. The greatest decreases in the 10MWT occurred in participants who used bilateral walking aids (p < 0.05). We also found daily AIH + WALK resulted in an increase in 6MWT distance at T5 by 22% (95% CI 13.3–72.6 m, p = 0.001), F1 by 21% (95% CI 13.1–72.5 m, p = 0.001), and F2 by 16% (95% CI 2.9–62.2 m, p = 0.02). However, measures of EV and ACC during self-selected walking conditions did not change following daily AIH + WALK (all p-values >0.50). ConclusionsConsistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in participants who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.

Cerebellar contribution to sensorimotor adaptation deficits in humans with spinal cord injury

Humans with spinal cord injury (SCI) show deficits in associating motor commands and sensory feedback. Do these deficits affect their ability to adapt movements to new demands? To address this question, we used a robotic exoskeleton to examine learning of a sensorimotor adaptation task during reaching movements by distorting the relationship between hand movement and visual feedback in 22 individuals with chronic incomplete cervical SCI and 22 age-matched control subjects. We found that SCI individuals showed a reduced ability to learn from movement errors compared with control subjects. Sensorimotor areas in anterior and posterior cerebellar lobules contribute to learning of movement errors in intact humans. Structural brain imaging showed that sensorimotor areas in the cerebellum, including lobules I–VI, were reduced in size in SCI compared with control subjects and cerebellar atrophy increased with increasing time post injury. Notably, the degree of spared tissue in the cerebellum was positively correlated with learning rates, indicating participants with lesser atrophy showed higher learning rates. These results suggest that the reduced ability to learn from movement errors during reaching movements in humans with SCI involves abnormalities in the spinocerebellar structures. We argue that this information might help in the rehabilitation of people with SCI.

Omitting TMS component from paired associative stimulation with high-frequency PNS: A case series of tetraplegic patients

ObjectivesEarlier studies have shown how chronic spinal cord injury (SCI) patients have benefitted from paired associative stimulation (PAS), consisting of high-frequency peripheral nerve stimulation (PNS) and high-intensity transcranial magnetic stimulation (TMS). Since high-frequency PNS is poorly characterized, its therapeutic effect without TMS should be evaluated. We tested the effect of PNS combined with motor imagery in chronic SCI patients using the same parameters of PNS as in earlier PAS-based studies that also used TMS. MethodsFive patients with chronic incomplete SCI and tetraplegia received a 6-week treatment of PNS combined with motor imagery to the weaker upper limb. Patients were evaluated with Manual Muscle Testing (MMT), hand function tests (Box and block, grip and pinch strength dynamometry), and spasticity. ResultsThere was no significant change in hand function tests or spasticity. MMT values improved significantly immediately after the PNS period (0.59 ± 0.17, p = 0.043) and in the 1-month follow-up visit (0.87 ± 0.18, p = 0.043). However, improvement of MMT values was weaker than in chronic tetraplegic patients in a corresponding PAS study that used identical PNS stimulation but also included the TMS component omitted here (Tolmacheva et al., 2019a, Clin Neurophysiol Pract). ConclusionsThe lack of effect on functional hand tests with the protocol presented here suggests that the synergistic effect of PNS and TMS components is essential for the full therapeutic effect previously observed with PAS intervention. The moderate improvement of the MMT score suggests the possible usefulness of PNS and motor imagery for some of those tetraplegic SCI patients who have contraindications to TMS. SignificanceThese results add to the understanding of the PAS therapeutic mechanism by highlighting the importance of dual stimulation for achieving the full therapeutic effect of long-term PAS with a high-frequency PNS component.

Effects of Bilateral Transcutaneous Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Spinal Cord Injury: A Urodynamic Study

ObjectiveTo study the short-term effect of bilateral transcutaneous tibial nerve stimulation (TTNS) on urodynamic study (UDM) parameters in spinal cord injury (SCI) patients with neurogenic detrusor overactivity (NDO). DesignSingle-blinded sham-controlled study. SettingRehabilitation center. ParticipantsSCI patients with NDO (N=17) were recruited. Fifteen patients (mean age, 40±18y) completed the study. Most of the patients had chronic incomplete SCI. InterventionsUDM was performed 3 times. The first UDM was performed after taking anticholinergics for 1 hour to assess the effects of medication. After stopping anticholinergics for a 5 half-lives, the second UDM was performed immediately after a 20-minute sham TTNS (switch on for 30s at the beginning, switch off for 20min, and switch on for 30s before stopping). The third UDM was performed immediately after a 20-minute bilateral TTNS. Main Outcome MeasuresReflex volume (mL), cystometric capacity (mL), maximum pressure detrusor (mmH2O), and bladder compliance (mL/mmH2O). ResultsUDM tracings were interpreted by 2 blinded assessors. This study used per-protocol analysis and repeated measures Analysis of variance with Bonferroni post hoc analysis. When compared with sham stimulation, bilateral TTNS and anticholinergics produced greater increases in reflex volume (136.1±99.88, 212.2±112.82, and 226.3±111.52 mL; P<.001), cystometric capacity (218.3±137.66, 319.1±143.74, and 350.7±163.43 mL; P<.001), and compliance (5.8±6.81, 7.9±6.74, 9.7±8.12 mL/cmH2O; P=.02). No significant differences were found in reflex volume, cystometric capacity, or compliance between bilateral TTNS and anticholinergics (P>.05). The maximum pressure detrusor was not significantly different between groups (P>.05). ConclusionBilateral TTNS may be an effective short-term intervention to improve UDM parameters in SCI with NDO. Further study is necessary to determine the long-term effects and benefits of combined bilateral TTNS with anticholinergics.

Spatial Characteristics Of Reactive Stepping Among People Living With Chronic Incomplete Spinal Cord Injury

Spatial Characteristics Of Reactive Stepping Among People Living With Chronic Incomplete Spinal Cord Injury

Acute intermittent hypoxia boosts spinal plasticity in humans with tetraplegia

Paired corticospinal-motoneuronal stimulation (PCMS) elicits spinal synaptic plasticity in humans with chronic incomplete cervical spinal cord injury (SCI). Here, we examined whether PCMS-induced plasticity could be potentiated by acute intermittent hypoxia (AIH), a treatment also known to induce spinal synaptic plasticity in humans with chronic incomplete cervical SCI.During PCMS, we used 180 pairs of stimuli where corticospinal volleys evoked by transcranial magnetic stimulation over the hand representation of the primary motor cortex were timed to arrive at corticospinal-motoneuronal synapses of the first dorsal interosseous (FDI) muscle ~1–2 ms before the arrival of antidromic potentials elicited in motoneurons by electrical stimulation of the ulnar nerve. During AIH, participants were exposed to brief alternating episodes of hypoxic inspired gas (1 min episodes of 9% O2) and room air (1 min episodes of 20.9% O2). We examined corticospinal function by measuring motor evoked potentials (MEPs) elicited by cortical and subcortical stimulation of corticospinal axons and voluntary motor output in the FDI muscle before and after 30 min of PCMS combined with AIH (PCMS+AIH) or sham AIH (PCMS+sham-AIH). The amplitude of MEPs evoked by magnetic and electrical stimulation increased after both protocols, but most after PCMS+AIH, consistent with the hypothesis that their combined effects arise from spinal plasticity. Both protocols increased electromyographic activity in the FDI muscle to a similar extent. Thus, PCMS effects on spinal synapses of hand motoneurons can be potentiated by AIH. The possibility of different thresholds for physiological vs behavioral gains needs to be considered during combinatorial treatments.

Gait training with Achilles ankle exoskeleton in chronic incomplete spinal cord injury subjects

Gait training with Achilles ankle exoskeleton in chronic incomplete spinal cord injury subjects

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report

IntroductionPaired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) and induces plastic changes in the human corticospinal tract. We have previously shown that PAS consisting of TMS pulses given at 100% of stimulator output and high-frequency PNS is beneficial for motor rehabilitation of patients with a chronic incomplete spinal cord injury (SCI). The therapeutic possibilities of this PAS variant for walking rehabilitation of paraplegic patients are unexplored.Case presentationA 47-year old man with traumatic incomplete paraplegia (AIS D, neurological level T7) received PAS to his left leg for 3 months at 12 months post injury (PAS1) and for an additional 3 months at 24 months post injury (PAS2). The right leg had normal AIS scores and was not stimulated. Before PAS, the patient was nonambulatory, could not stand without weight support, and was consequently not eligible for conventional walking rehabilitation. After PAS1, the patient could stand for 1.5 min and take 13 steps (24 steps in follow up) on parallel bars without weight support and was enrolled into conventional walking rehabilitation. He achieved independent walking ability with a rollator. During PAS2, walking distance increased 2.4 times faster than during the preceding year. The left leg AIS score and spinal cord independence measure mobility subscore increased. No adverse effects were detected.DiscussionThis is the first report of PAS with a high-frequency peripheral component that enabled and promoted walking rehabilitation. Together with previous reports on this technique, this result encourages further research into its therapeutic potential and mechanism.

The Potential of Corticospinal-Motoneuronal Plasticity for Recovery after Spinal Cord Injury.

This review focuses on a relatively new neuromodulation method where transcranial magnetic stimulation over the primary motor cortex is paired with transcutaneous electrical stimulation over a peripheral nerve to induce plasticity at corticospinal-motoneuronal synapses. Recovery of sensorimotor function after spinal cord injury largely depends on transmission in the corticospinal pathway. Significantly damaged corticospinal axons fail to regenerate and participate in functional recovery. Transmission in residual corticospinal axons can be assessed using non-invasive transcranial magnetic stimulation which combined with transcutaneous electrical stimulation can be used to improve voluntary motor output, as was recently demonstrated in clinical studies in humans with chronic incomplete spinal cord injury. These two stimuli are applied at precise inter-stimulus intervals to reinforce corticospinal synaptic transmission using principles of spike-timing dependent plasticity. We discuss the neural mechanisms and application of this neuromodulation technique and its potential therapeutic effect on recovery of function in humans with chronic spinal cord injury.

Cosine tuning determines plantarflexors' activities during human upright standing and is affected by incomplete spinal cord injury.

Plantarflexors such as the soleus (SOL) and medial gastrocnemius (MG) play key roles in controlling bipedal stance; however, how the central nervous system controls the activation levels of these plantarflexors is not well understood. Here we investigated how the central nervous system controls the plantarflexors' activation level during quiet standing in a cosine tuning manner where the maximal activation is achieved in a preferred direction (PD). Furthermore, we investigated how spinal cord injury affects these plantarflexors' activations. Thirteen healthy adults (AB) and thirteen individuals with chronic, incomplete spinal cord injury (iSCI) performed quiet standing trials. Their body kinematics and kinetics as well as electromyography signals from the MG and SOL were recorded. In the AB group, we found that the plantarflexors followed the cosine tuning manner during quiet standing. That is, MG was most active when the ratio of plantarflexion torque to knee extension torque was ~2:-3, whereas SOL was most active when the ratio was ~2:1. This suggests that the SOL muscle, despite being a monoarticular muscle, is sensitive to both ankle plantarflexion and knee extension during quiet standing. The difference in the PDs accounts for the phasic activity of MG and for the tonic activity of SOL. Unlike the AB group, the MG's activity was similar to the SOL's activity in the iSCI group, and the SOL PDs were similar to those in the AB group. This result suggests that chronic iSCI affects the control strategy, i.e., cosine tuning, for MG, which may affect standing balance in individuals with iSCI.NEW & NOTEWORTHY Soleus muscle shows a tonic activity whereas medial gastrocnemius muscle shows a phasic activity during quiet standing. Cosine tuning and their preferred direction account for the different muscle activation patterns between these two muscles. In individuals with chronic incomplete spinal cord injury, the preferred direction of gastrocnemius medial head is affected, which may result in their deteriorated standing balance.

Wearable exoskeleton control modes selected during overground walking affect muscle synergies in adults with a chronic incomplete spinal cord injury.

Case series. Changes in the number of muscle synergies (MSs) and in the weighting of muscles composing each MS are typically altered following an incomplete spinal cord injury (iSCI). Wearable robotic exoskeletons (WRE) represent a promising rehabilitation option, though the effects of various WRE control modes on MSs still remain unknown. This case series characterizes how WRE control modes affect the number of MSs and the weighting of muscles composing each MS in individuals with iSCI. Pathokinesioly laboratory of a rehabilitation research center. Three participants with a chronic iSCI walked at a self-selected comfortable speed without and with a WRE set in two trajectory-controlled (Total Assistance, TOT; Assistance-as-Needed, ADAPT) and three non-trajectory controlled modes (High Assistance, HASSIST; High Resistance, HRESIST; NEUTRAL). Surface EMG of eight lower extremity (L/E) muscles was recorded and used to extract MSs using a nonnegative matrix factorization algorithm. Cosine similarity and weighting relative differences characterized similarities in MSs between individuals with iSCI and able-bodied controls. The mode providing movement assistance within a self-selected L/E trajectory (HASSIST) best replicated MSs in able-bodied controls during overground walking. MSs extracted with the trajectory-controlled modes differed to the greatest extent from able-bodied group MSs. Most WRE control modes did not replicate the motor control required for typical L/E muscle coordination during stereotypical overground walking. These results highlight the need to gain a better understanding of the effects of various control modes on L/E motor control for rehabilitation professionals to incorporate research evidence when selecting WRE control mode(s) during WRE locomotor interventions.

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia.

An increasing number of studies supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes functional recovery in humans with spinal cord injury (SCI). However, the neural mechanisms contributing to these effects remain poorly understood. Here we examined motor-evoked potentials in arm muscles elicited by cortical and subcortical stimulation of corticospinal axons before and after 20 min of TESS (30 Hz pulses with a 5 kHz carrier frequency) and sham-TESS applied between C5 and C6 spinous processes in males and females with and without chronic incomplete cervical SCI. The amplitude of subcortical, but not cortical, motor-evoked potentials increased in proximal and distal arm muscles for 75 min after TESS, but not sham-TESS, in control subjects and SCI participants, suggesting a subcortical origin for these effects. Intracortical inhibition, elicited by paired stimuli, increased after TESS in both groups. When TESS was applied without the 5 kHz carrier frequency both subcortical and cortical motor-evoked potentials were facilitated without changing intracortical inhibition, suggesting that the 5 kHz carrier frequency contributed to the cortical inhibitory effects. Hand and arm function improved largely when TESS was used with, compared with without, the 5 kHz carrier frequency. These novel observations demonstrate that TESS influences cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. We hypothesized that these parallel effects contribute to further the recovery of limb function following SCI.SIGNIFICANCE STATEMENT Accumulating evidence supports the view that transcutaneous electrical stimulation of the spinal cord (TESS) promotes recovery of function in humans with spinal cord injury (SCI). Here, we show that a single session of TESS over the cervical spinal cord in individuals with incomplete chronic cervical SCI influenced in parallel the excitability cortical and spinal networks, having an excitatory effect at the spinal level and an inhibitory effect at the cortical level. Importantly, these parallel physiological effects had an impact on the magnitude of improvements in voluntary motor output.