Spinal Motor-evoked Potentials Research Articles

Transcutaneous Electrical Neuromodulation of the Cervical Spinal Cord Depends Both on the Stimulation Intensity and the Degree of Voluntary Activity for Training. A Pilot Study

Electrical enabling motor control (eEmc) through transcutaneous spinal cord stimulation offers promise in improving hand function. However, it is still unknown which stimulus intensity or which muscle force level could be better for this improvement. Nine healthy individuals received the following interventions: (i) eEmc intensities at 80%, 90% and 110% of abductor pollicis brevis motor threshold combined with hand training consisting in 100% handgrip strength; (ii) hand training consisting in 100% and 50% of maximal handgrip strength combined with 90% eEmc intensity. The evaluations included box and blocks test (BBT), maximal voluntary contraction (MVC), F wave persistency, F/M ratio, spinal and cortical motor evoked potentials (MEP), recruitment curves of spinal MEP and cortical MEP and short-interval intracortical inhibition. The results showed that: (i) 90% eEmc intensity increased BBT, MVC, F wave persistency, F/M ratio and cortical MEP recruitment curve; 110% eEmc intensity increased BBT, F wave persistency and cortical MEP and recruitment curve of cortical MEP; (ii) 100% handgrip strength training significantly modulated MVC, F wave persistency, F/M wave and cortical MEP recruitment curve in comparison to 50% handgrip strength. In conclusion, eEmc intensity and muscle strength during training both influence the results for neuromodulation at the cervical level.

The muscle evoked potential after epidural electrical stimulation of the spinal cord as a monitor for the corticospinal tract: studies by collision technique and double train stimulation.

To study if spinal motor evoked potentials (SpMEPs), muscle responses after electrical stimulation of the spinal cord, can monitor the corticospinal tract. Study 1 comprised 10 consecutive cervical or thoracic myelopathic patients. We recorded three types of muscle responses intraoperatively: (1) transcranial motor evoked potentials (TcMEPs), (2) SpMEPs and (3) SpMEPs + TcMEPs from the abductor hallucis (AH) using train stimulation. Study 2 dealt with 5 patients, who underwent paired train stimulation to the spinal cord with intertrain interval of 50-60ms for recording AH SpMEPs. We will also describe two illustrative cases to demonstrate the clinical value of AH SpMEPs for monitoring the motor pathway. In Study 1, SpMEPs and SpMEPs + TcMEPs recorded from AH measured nearly the same, suggesting the collision of the cranially evoked volleys with the antidromic signals induced by spinal cord stimulation via the corticospinal tracts. In Study 2, the first and second train stimuli elicited almost identical SpMEPs, indicating a quick return of transmission after 50-60ms considered characteristic of the corticospinal tract rather than the dorsal column, which would have recovered much more slowly. Of the two patients presented, one had no post-operative neurological deteriorations as anticipated by stable SpMEPs, despite otherwise insufficient IONM, and the other developed post-operative motor deficits as predicted by simultaneous reduction of TcMEPs and SpMEPs in the face of normal SEPs. Electrical stimulation of the spinal cord primarily activates the corticospinal tract to mediate SpMEPs.

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury.

Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6weeks after injury, rats were tested on these tasks with and without buspirone (1-2mg/kg) or fluoxetine (1-5mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2weeks after injury and plateaued over the next 4weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.

Free radical scavenger edaravone produces robust neuroprotection in a rat model of spinal cord injury

We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.

Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats

Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6– C8+ and C6+ C8–) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6– Ref+ and C8– Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.

19. Central motor conduction time along the phrenic nerve pathway in patients with cervical syringomyelia

The aim of this study was to investigate phrenic central motor conduction time (CMCT) in patients affected by Syringomyelia (Syr) and Chiari Malformation (CM) to point out subclinical phrenic pathway alterations. Forty-two patients (12 M, 30 F, age 18–71 years, mean 49.43 ± 13.56) without clinical signs of respiratory impairment were included and divided into subgroups according to different clinical phenotypes (cervical Syr, cervical-dorsal Syr, Syr with CM). TMS was bilaterally performed, recording by surface electrodes from hemidiaphragm; latency/amplitude of cortical and spinal motor-evoked potentials (Cx-MEP/Sp-MEP) and CMCT were measured in all patients. No adverse local or systemic reactions were reported. Neurophysiological data were analyzed and compared with 16 healthy subjects (T-test). CMCT was significantly prolonged ( p p

Diagnostic transcranial magnetic stimulation as a prognostic tool in children with acute transverse myelitis.

We performed transcranial magnetic stimulation (TMS) in children with sequelae of acute transverse myelitis. Single-pulse TMS protocol was implemented. Twenty controls and 24 patients with myelitis were enrolled. TMS was performed on 12-24 day after the onset of the first symptoms, average on 16th day. The objective of our study was to evaluate motor pathways in children with viral myelitis using the TMS technique. All investigations were performed in Scientific Research Institute for Children's Infections, Russia. There were statistically significant differences between the groups on central motor conduction time and motor evoked potential (MEPs) amplitudes. MEP thresholds were elevated, and MEP shape was abnormal in 96% of patients with myelitis (n=23). Three neurophysiologic patterns were observed: the presence of both cortical and spinal MEP, the absence of cortical MEP with the spinal MEP present and the total absence of both cortical and spinal MEP. Last finding was associated with paraplegia, resistant to any sort of treatment. Thus, myelitis in 96% of the cases causes neurophysiologic changes, which may be detected by TMS; the method may be used as a predicting tool.

Nrf2 Activation in Astrocytes Contributes to Spinal Cord Ischemic Tolerance Induced by Hyperbaric Oxygen Preconditioning

In this study, we investigated whether nuclear factor erythroid 2-related factor 2 (Nrf2) activation in astrocytes contributes to the neuroprotection induced by a single hyperbaric oxygen preconditioning (HBO-PC) against spinal cord ischemia/reperfusion (SCIR) injury. In vivo: At 24 h after a single HBO-PC at 2.5 atmospheres absolute for 90 min, the male ICR mice underwent SCIR injury by aortic cross-clamping surgery and observed for 48 h. HBO-PC significantly improved hindlimb motor function, reduced secondary spinal cord edema, ameliorated the reactivity of spinal motor-evoked potentials, and slowed down the process of apoptosis to exert neuroprotective effects against SCIR injury. At 12 h or 24 h after HBO-PC without aortic cross-clamping surgery, Western blot, enzyme-linked immunosorbent assay, realtime-polymerase chain reaction and double-immunofluorescence staining were used to detect the Nrf2 activity of spinal cord tissue, such as mRNA level, protein content, DNA binding activity, and the expression of downstream gene, such as glutamate-cysteine ligase, γ-glutamyltransferase, multidrug resistance protein 1, which are key proteins for intracellular glutathione synthesis and transit. The Nrf2 activity and downstream genes expression were all enhanced in normal spinal cord with HBO-PC. Glutathione content of spinal cord tissue with HBO-PC significantly increased at all time points after SCIR injury. Moreover, Nrf2 overexpression mainly occurs in astrocytes. In vitro: At 24 h after HBO-PC, the primary spinal astrocyte-neuron co-cultures from ICR mouse pups were subjected to oxygen-glucose deprivation (OGD) for 90 min to simulate the ischemia-reperfusion injury. HBO-PC significantly increased the survival rate of neurons and the glutathione content in culture medium, which was mainly released from asctrocytes. Moreover, the Nrf2 activity and downstream genes expression induced by HBO-PC were mainly enhanced in astrocytes, but not in neurons. In conclusion, our findings demonstrated that spinal cord ischemic tolerance induced by HBO-PC may be mainly related to Nrf2 activation in astrocytes.

Neurosurgical procedures, Spinal nerve roots – one stage removal of thoracic dumb-bell tumor: role of spinal evoked potential

We report a rare case of benign thoracic dumb-bell tumor in the upper posterior mediastinum, which was successfully removed by posterolateral thoracotomy and foraminotomy, using intraoperative monitoring of spinal motor-evoked potentials. This technique has many advantages including minimal morbidity and mortality, a single incision, one-step complete resection with adequate exposure, spinal stabilization, avoidance of laminectomy, nerve root identification, and good predicted postoperative function.

Disruption of Nrf2 exacerbated the damage after spinal cord injury in mice

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional factor for antioxidant response element-regulated genes. After spinal cord injury (SCI), the Nrf2-antioxidant response element pathway is activated in the spinal cord. However, the function of Nrf2 after SCI has not yet been studied. Spinal cord compression injury of Nrf2 knockout (KO) and wild-type (WT) mice was induced by the application of vascular clips (force of 10 g) to the dura. Neurologic function was assayed by the Basso open-field motor score, footprint analysis, and spinal motor-evoked potentials. Degenerating neuronal cells were stained with Fluoro Jade C and observed by a confocal microscopy. Nrf2 DNA-binding activity was assessed by electrophoretic mobility shift assay. The mRNA levels of interleukin (IL)-6, IL-1β, NAD(P)H: quinone oxidoreductase (NQO)-1, and glutathione S-transferase (GST)-α1 were detected by reverse transcriptase-polymerase chain reaction. Enzyme-linked immunosorbent assay was used to detect IL-6 and IL-1β protein expression, and colorimetric method was used to detect the enzyme activity of NQO1 and GST-α1. Nrf2 KO mice developed severer hindlimb motor dysfunction and neuronal death after SCI compared with WT mice. In correlation with neurologic deficits, the release of IL-6 and IL-1β in the spinal cord of KO mice was higher than that in WT mice, whereas the Nrf2 banding activity, the expression and activity of NQO1 and GST-α1 were all lesser in KO mice 24 hours after SCI compared with WT mice. Genetic ablation of Nrf2 exacerbated the neurologic deficit and inflammation after SCI in mice. These findings raise the possibility that Nrf2 could be relevant in improving outcome after SCI.

The cortico-diaphragmatic pathway involvement in amyotrophic lateral sclerosis: Neurophysiological, respiratory and clinical considerations

Cortico-diaphragmatic pathway was investigated by means of transcranial magnetic stimulation (TMS), in 14 patients affected by definite amyotrophic lateral sclerosis (ALS) without clinical signs of respiratory impairment. Spirometry, gas analysis, and measurement of static inspiratory and expiratory pressures were performed in all patients. Forced vital capacity, forced expiratory volume at the first and second peak expiratory flow, sniff effort from FRC level (SNIP), maximal inspiratory and expiratory pressure at mouth (MIP/MEP), maximal transdiaphragmatic pressure (Pdimx) were considered. TMS was performed, recording by surface electrodes from hemidiaphragm, bilaterally. Latency of cortical and spinal motor-evoked potentials (Cx-MEP/Sp-MEP) and central motor conduction time (CMCT) were measured. None of the patients showed altered spirometry and gas levels. Seven patients showed decreased Pdimx and eight of MEP values. Four patients showed a delayed Sp-MEP. In one patient the Cx-MEP was abolished while the mean values of both Cx-MEP and CMCT were significantly increased (19.2 ± 4.1 ms, P < 0.0001; 10.8 ± 4.8 ms, P < 0.0001). Cx-MEP and CMCT did not show significant correlations with any of the respiratory measures. The patients with prolonged Sp-MEP, showed longer disease duration, lower Norris score, lower Pdimx and MEP values. In conclusion, cortico-diaphragmatic study is a sensitive measure to reveal subclinical diaphragmatic impairment although not correlated to respiratory measures.

Intra-aortic injection of propofol prevents spinal cord injury during aortic surgery☆

We investigated whether propofol, a widely used anesthetic, injected into clamped aortic segments quickly attenuated transcranial spinal motor-evoked potential (MEP) amplitudes and protected against spinal cord injury during thoracoabdominal aortic surgery. Eighteen beagle dogs were divided into three groups (n=6, each group): group 1 (20 ml of saline, intra-aortic injection), group 2 (1.5 mg/kg of propofol, intravenous injection), and group 3 (1.5 mg/kg of propofol, intra-aortic injection). Aortic cross-clamping was performed for 30 min. In each group, MEP amplitudes were recorded before, during, and after aortic cross-clamping. Tarlov score and histopathological examination were used to evaluate the protective effects of intra-aortic propofol injections. MEP amplitudes in group 3 attenuated to a value that was 60% of the control in just a minute after aortic cross-clamping, but maintained 40% of the control value during aortic cross-clamping. However, MEP amplitudes in groups 1 and 2 gradually attenuated and almost disappeared. Groups 1 and 2 amplitudes were lower than those in group 3, 30 min after aortic cross-clamping (p<0.001). Twenty-four hours after ischemia, the Tarlov score in group 3 was 3.5+/-0.5 and was higher than scores from groups 1 and 2, which were 0.5+/-0.5 and 1.3+/-1.2 (mean+/-SD, p<0.001, and p<0.001), respectively. Histopathologically, normal spinal cord motor neurons in group 3 were preserved to a significantly greater extent than in groups 1 and 2 (p=0.0031, and p=0.0282, respectively). There was a strong correlation between Tarlov scores at 24h and the number of normal motor neurons in the anterior horns of spinal cords (r=0.897; p<0.001). Intra-aortic propofol injections produce the quick suppression of MEP amplitudes and protect spinal cords from ischemia during aortic cross-clamping.

Influence of fentanyl, alfentanil, and sufentanil on motor evoked potentials.

The effects of the opioids fentanyl, alfentanil, and sufentanil on motor pathways were studied in a total of 30 rabbits. Compound muscle action potentials (CMAP) were recorded from the extensor muscles of the upper extremity as well as evoked spinal cord potentials (ESCP) from the thoracic epidural space in response to electrical stimulation of the motor cortex. After establishing stable baseline values, an equipotent intravenous bolus of one of the three opioids was applied that abolished reflex motor response to noxious stimulation. Motor evoked potentials (MEP) were recorded from the time of bolus administration until recovery of MEP amplitudes and latencies. Afterwards, the opioids were administered continuously with cumulative dosage up to total absence of motor evoked response. Our results show a dose-dependent suppression of the CMAP: When reflex movement to noxious stimulation was extinguished, we found a significant (P < .001) reduction of the amplitudes to 34+/-18% (mean +/- SD) in the fentanyl group, to 43+/-24% in the alfentanil group, and to 53+/-20% of baseline values in the sufentanil group. Increasing opioid plasma levels were associated with complete extinction of the CMAP. We hypothesize that the descending volleys within motor pathways are mainly inhibited at a spinal level, because ESCP, particularly the number of spinal I-waves, are not severely affected even when CMAP are completely suppressed. In conclusion, intraoperative monitoring of descending pathways by means of MEP during anesthesia with opioids is feasible at anesthetic plasma concentrations maintaining a surgical level of analgesia. Even with high opioid plasma levels, a valid MEP monitoring could be performed evaluating neural activity of spinal MEP.

Intraoperative Monitoring of Spinal Cord Function Using Motor Evoked Potentials via Transcutaneous Epidural Electrode During Anterior Cervical Spinal Surgery

Because false-positive results are not infrequent when monitoring somatosensory evoked potentials during surgery, monitoring of motor evoked potentials (MEPs) has been proposed and successfully used during the removal of spinal cord tumors. However, this often requires direct visual placement of an epidural electrode after a laminectomy. We evaluated the use of MEPs, recorded via a transcutaneously placed epidural electrode, to monitor motor pathway functional integrity during surgery on the anterior cervical spine. Sixteen patients underwent anterior cervical vertebral decompression and fusion for cervical myelopathy and/or radiculopathy. Before surgery, an epidural monitoring electrode was placed transcutaneously at the midthoracic level and was used to record MEPs after transcranial cortical electrical stimulation. Electrode placement was successful in all patients but one, and satisfactory baseline spinal MEPs were obtained except for one patient who had cerebral palsy with significant motor dysfunction. Patients showed no significant changes in spinal MEPs during surgery, and all had baseline or better motor function postoperatively. None had complications from epidural electrode placement or electrical stimulation. We conclude that motor pathways can be monitored safely during anterior cervical spinal surgery using spinal MEPs recorded via a transcutaneously placed epidural electrode, that MEP preservation during surgery correlates with good postoperative motor function, and that cerebral palsy patients may possess too few functional motor fibers to allow MEP recording.

Temporal summation--the key to motor evoked potential spinal cord monitoring in humans.

Spinal motor evoked potentials (SMEP) were recorded from tibialis anterior muscle after epidural stimulation of the spinal cord at the low cervical or high thoracic level during scoliosis surgery. By using a double stimulus pulse to produce temporal summation within the spinal cord a maximal CMAP response was readily achieved despite good surgical anaesthesia.

Changes in spinal cord function evaluated by evoked potentials and spinal cord blood flow from a lateral retraction post-cervical laminectomy

We induced ischemia and stretching by retraction of the spinal cord after laminectomy in 12 anesthetized mongrel adult cats, recorded spinal motor evoked potential (SpMEP) and spinal somatosensory evoked potential (SpSSEP) and determined the spinal cord blood flow (SCBF). The results showed a correlation between progressive deterioration of the function and a decrease in SCBF. Comparing the abnormal findings of both the peak and interpeak latencies in evoked potentials, useful data were more frequently obtained using SpSSEP than SpMEP. Factors involved in their deteriorations seem to be a moderate ischemia by compression, and a stretching by the retraction of the spinal cord. From these results, we conclude that SCBF and SpSSEP are important for monitoring the impulse propagation during retraction of the cervical cord.

&lt;I&gt;Spinal and Muscle Motor Evoked Potentials Following Magnetic Stimulation in Cats&lt;/I&gt;

Motor evoked potentials (MEP) from transcranial magnetic stimulation were successfully recorded from the spinal cord and gastrocnemius muscle in cats. The spinal MEP consisted of four negative peaks, N1 through N4, and subsequent small, multiphasic waves. The conduction velocity calculated from N1 corresponded to that of the nonpyramidal cerebellar evoked potential. After ablation of the pyramidal tract at various levels, N1 through N3 persisted, whereas N4 disappeared. The muscle MEP showed the same latency as that of MEP obtained by direct cortical electrical stimulation and disappeared after similar ablation. These findings suggest that the first three peaks of the spinal MEP are responses of the nonpyramidal cerebellospinal pathways and that the fourth peak of the spinal MEP and the muscle MEP are pyramidal tract responses. Spinal and muscle MEP from magnetic stimulation may be valuable in the qualitative evaluation of the function of the pyramidal and nonpyramidal pathways.