Monitoring spinal cord motor and somatosensory evoked potentials in anesthetized primates

Abstract

Monitoring Motor Evoked Potential (MEP) to Transcranial Stimulation (TMS) monitoring (MEP) is a growing technique to assess motor function under anesthesia. The following primate study was conducted to analyze the non-myogenic spinal motor and sensory volleys and to examine their reproducibility under nitrous oxide-methohexidone anesthesia. The traveling periodic spinal descending MEP to TMS and ascending somatosensory (SEP) to posterior tibial nerve stimulation across the thoracic cord were recorded in 12 cynomolgus monkeys. Through a small Tn~Tu laminotomy, an insulated stainless steel electrode was inserted into the epidural thoracic space. The potentials were analyzed under 50 vol% NO in 02 with methohexital (0.1-0.2 mg kg~1 min~1). A well-defined periodic TMS-MEPs and PTN-SEPs were recorded with high reproducibility and consistency in repeated trials under N20-methohexital anesthesia. MEP tracing consisted of an initial peak (direct (D) wave), occurring at 2.43 (±0.28) msec followed by subsequent five positive (indirect (I) waves). Spinal SEPs-MEPs were clearly defined, morphologically stable, and consistent over time under N20-methohexitone anesthesia. The present primate study may set a model to monitor both modalities in anesthetized neurosurgical patients.[Neurol Res 1999; 21: 359-367]     

Megnetic motor evoked potentials (MEP) in diseases of the spinal cord

Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic method particularly suited to investigation of the long motor tracts. The clinical value of this method in many cortical and subcortical diseases has been well established, but comparable studies for most spinal cord diseases have still to be made. Forty patients in whom spinal cord disease was established by clinical examination, cerebrospinal fluid examination, and magnetic resonance imaging (MRI) were studied by means of somatosensory evoked potentials (SEP, median and tibial nerve stimulation) and magnetic motor evoked potentials (MEP, first dorsal interosseus and tibialis anterior muscle recordings after transcranial and spinal stimulation). The underlying pathology was neoplastic (n= 16), inflammatory (n= 15) or ischemic (n = 9). Clinical signs and symptoms ranged from slight sensory disturbances to complete paraplegia and had developed within minutes (ischemia) or over many years (benign neoplastic disease). The overall frequency of pathological SEP was slightly higher than that of MEP (78% vs 68%) which was statistically not significant (p > 0.05). This was also true for the subgroups, except for pure motor disorders, which gave the same yield for both methods. Decreased amplitudes or absence of MEP were more frequent in neoplastic than in inflammatory lesions (75% vs 33%, p < 0.05). In the latter, however, MEP more often occurred with increased latencies (40% vs 31%, p > 0.05, n. s.). Pathological SEP were found in 75% of patients presenting with pure motor abnormalities, while pathological MEP were found in 30% of patients with pure sensory disturbances. We conclude, in common with the SEP, the MEP are helpful in the examination of spinal cord diseases, even in subclinical disturbances, although the SEP would seem to yield a larger percentage of pathological results.     

Normal postexercise facilitation and depression of motor evoked potentials in postpolio patients

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation in healthy subjects and postpolio patients. Subjects performed repeated sets of isometric exercise until the muscle fatigued. In both groups, the mean MEP amplitude immediately after each exercise set was approximately twice that of the baseline amplitude, indicating similar postexercise facilitation, and after fatigue was approximately half that of the baseline amplitude, indicating similar postexercise depression. We conclude that the intracortical component of central fatigue is normal in postpolio patients. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:948–950, 1998.     

Monitoring somatosensory evoked potentials in spinal cord ischemia-reperfusion injury

It remains unclear whether spinal cord ischemia-reperfusion injury caused by ischemia and other non-mechanical factors can be monitored by somatosensory evoked potentials. Therefore, we monitored spinal cord ischemia-reperfusion injury in rabbits using somatosensory evoked potential detection technology. The results showed that the somatosensory evoked potential latency was significantly prolonged and the amplitude significantly reduced until it disappeared during the period of spinal cord ischemia. After reperfusion for 30-180 minutes, the amplitude and latency began to gradually recover; at 360 minutes of reperfusion, the latency showed no significant difference compared with the pre-ischemic value, while the somatosensory evoked potential amplitude in- creased, and severe hindlimb motor dysfunctions were detected. Experimental findings suggest that changes in somatosensory evoked potentia~ ~atency can reflect the degree of spinat cord ischemic injury, while the amplitude variations are indicators of the late spinal cord reperfusion injury, which provide evidence for the assessment of limb motor function and avoid iatrogenic spinal cord injury.     

Postexercise facilitation of motor evoked potentials following transcranial magnetic stimulation: a study in normal subjects

The size of the motor evoked potential (MEP) elicited by transcranial magnetic stimulation increases soon after a nonexhaustive voluntary contraction of the target muscle (postexercise facilitation). Our aim was to determine whether the duration or intensity of voluntary muscle contraction influenced postexercise facilitation in normal subjects. We recorded the MEP from the thenar muscles following contractions of different durations (5, 15, and 30 s) and intensities (10%, 25%, and 50% of maximal voluntary contraction). We found that every combination of the tested intensities and durations of physical effort could induce postexercise MEP facilitation. Although the degree of postexercise MEP facilitation was comparable across the different durations and intensities, the maximal facilitation was observed with the shortest and strongest muscle contraction. Our study thus defines the optimal setting to study postexercise facilitation for clinical purposes.     

Time-dependent effects of dantrolene on motor evoked potentials in experimental spinal cord injuries

ABSTRACT

Objectives:Traumatic spinal cord injury (SCI) is a significant clinical problem with numerous secondary complications and perpetual deficits. No potent treatment is currently available to fully repair motor and other neurological functions. We studied the effects of dantrolene (DNT) at different time points, on the motor-evoked potentials (MEPs) and the apoptosis response in spinal cord injury.

Methods:The study was conducted on a total of 38 rabbits divided into five main groups.These were group 1 (sham): only laminectomy (n = 6), group 2 (SCI): laminectomy and traumatic SCI (n = 8), group 3 (DNT 0h): just after the SCI, DNT 10 mg/kg I.P. (n = 8), group 4 (DNT 1h): 1 h after the SCI, DNT 10 mg/kg I.P. (n = 8), and group 5 (DNT 4h): 4 h after the SCI, DNT 10 mg/kg I.P. (n = 8).

Results: DNT, which was administered as the treatment, had a therapeutic effect on the motor function. This effect was observed by recording neural transmission obtained via the Tarlov test and a transcranial magnetic stimulator by using the values of the MEPs. A significant decrease was histopathologically observed in the apoptotic cell count.

Discussion: The electrophysiological efficacy of our model of trauma as SCI has been complemented with the significant differences between the control group and the SCI group. This creates a need for electrophysiological studies to be conducted in the future because effects, even at a minimum level, may play an important role in finding an applicable medicine for SCI.     

重复经颅磁刺激对急性脊髓损伤大鼠运动功能的影响

目的 探讨重复经颅磁刺激对急性脊髓损伤大鼠运动功能的影响. 方法 24只SD大鼠按照随机数字表法分为正常组、脊髓损伤对照组(对照组)、脊髓损伤高频磁刺激组(高频组)、脊髓损伤低频磁刺激组(低频组),每组6只.利用重物撞击法制作T10脊髓损伤模型.磁刺激组于手术后24 h开始给予刺激,高频组频率为10Hz,低频组频率为1 Hz,均为阈值刺激.500个脉冲,每天1次,连续4周,脊髓损伤对照组给予假刺激.各组大鼠分别于术后1 d、3d、7d、11 d、14d、21 d、28 d进行BBB行为学评分,于14、28 d时检测运动诱发电位(MEP),应用HE染色观察脊髓组织形态学变化,并应用免疫组织化学法检测神经丝蛋白(NF-200)表达变化. 结果 高频组、低频组大鼠BBB评分明显高于对照组,高频组BBB评分明显高于低频组,差异均有统计学意义(P<0.05).高频组、低频组运动诱发电位潜伏期较短,与对照组、正常组相比差异均有统计学意义(P<0.05);其中高频组较低频组短,差异有统计学意义(P<0.05).高频组、低频组NF-200表达较对照组明显升高,差异均有统计学意义(P<0.05);其中高频组较低频组高,差异有统计学意义(P<0.05).结论 重复经颅磁刺激可以促进脊髓损伤大鼠运动功能的恢复,其机制可能与促进轴突再生有关.高频组较低频组效果明显可能与调节大脑皮层兴奋性有关.     

Facilitation of motor evoked potentials: Timing of jendrassik maneuver effects

Remote voluntary contraction, such as the classical Jendrassik maneuver (JM), is a procedure routinely used to increase the amplitude of tendon reflexes in the lower limb. In 8 healthy subjects we studied the effects of JM on the motor evoked potentials (MEP) recorded from tibialis anterior muscle, produced by transcranial magnetic stimulation (stimulus output of 5–10% over motor threshold). In this study, JM consisted here of a bilateral violent handgrip, preceding magnetic stimulation from 100 to 50 ms (steps of 100 ms). Compared to the control test, latencies remained unchanged. MEP amplitudes were greatly enhanced with a JM test interval from 200 to 400 ms (170% of control amplitude at 300 ms). We also studied 6 patients with severe alterations of MEPs from tibialis anterior muscle. In each case, JM preceding magnetic stimulation (stimulus output 100%) from 300 ms induced reappearance of response or marked enhancement of amplitude, allowing calculation of central conduction time. Such a technique, which is easy to perform, may be useful in clinical practice to calculate central motor conduction time, where it would otherwise be difficult or impossible. © 1995 John Wiley & Sons, Inc.     

Mechanisms underlying reversal of motor unit activation order in electrically evoked contractions after spinal cord injury

Extracellular stimulation normally activates larger-diameter axons, innervating motor units producing higher force, at lower stimulation intensities than required to activate small-diameter axons innervating motor units producing low force. However, activation of weaker thenar motor units at lower stimulation intensities than required to activate strong motor units has been reported during extracellular stimulation of the median nerve in persons with chronic cervical spinal cord injury. We used a computational model that reproduced this experiment to identify the potential mechanisms for the observed reversal of the inverse recruitment order, including preferential death of large motoneurons, demyelination and remyelination, and denervation and reinnervation of muscle fibers. Five sets of simulations assessed these mechanisms with seven simulated subjects. Preferential reinnervation, with small-diameter axons reinnervating more abandoned muscle fibers than larger-diameter axons, accounted for the apparent reversal of the inverse recruitment order observed previously. Preferential death of larger axons enhanced the reversal, but alone could not account for the observed reversal. Further, demyelination and remyelination, even in an extreme case and when combined with preferential death of large motoneurons, could not reproduce the reversal of inverse recruitment order. Thus, the apparent reversal of the inverse recruitment order was not a reversal of activation order across different diameter nerve fibers, but rather was a consequence of the redistributed force-generating capacity of the motor units resulting from denervation and reinnervation.     

Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury

ObjectiveThe importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans.MethodsUlnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants.ResultsPotentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones.ConclusionsDescending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation.SignificanceEvaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..     

Repetitive magnetic stimulation affects the microenvironment of nerve regeneration and evoked potentials after spinal cord injury

Repetitive magnetic stimulation has been shown to alter local blood flow of the brain, excite the corticospinal tract and muscle, and induce motor function recovery. We established a rat model of acute spinal cord injury using the modiifed Allen’s method. After 4 hours of injury, rat models received repetitive magnetic stimulation, with a stimulus intensity of 35% maximum output intensity, 5-Hz frequency, 5 seconds for each sequence, and an interval of 2 minutes. This was repeated for a total of 10 sequences, once a day, 5 days in a week, for 2 consecutive weeks. After repetitive magnetic stimulation, the number of apoptotic cells decreased, matrix metalloproteinase 9/2 gene and protein expression decreased, nestin expression increased, somatosensory and motor-evoked potentials recovered, and motor function recovered in the injured spinal cord. These ifndings conifrm that repetitive magnetic stimulation of the spinal cord improved the microen-vironment of neural regeneration, reduced neuronal apoptosis, and induced neuroprotective and repair effects on the injured spinal cord.     

Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

A large body of evidence shows that spinal circuits are significantly affected by training,and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection.However,after incomplete lesions,the effect of treadmill training has been debated,which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects.In this study,rats with moderate spinal cord contusion were subjected to either step training on a treadmill or used in the model(control) group.The treadmill training began at day 7 post-injury and lasted 20 ± 10 minutes per day,5 days per week for 10 weeks.The speed of the treadmill was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat.After 3 weeks of step training,the step training group exhibited a significantly greater improvement in the Basso,Beattie and Bresnahan score than the model group.The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury,while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups.These results suggest that treadmill training significantly improves functional recovery and neural plasticity after incomplete spinal cord injury.     

Postexercise facilitation appears durable in normal subjects

Transcranial magnetic stimulation (TMS) was used to study the postexercise facilitation of 11 normal subjects on eight occasions. Between individuals, there was almost a sixfold difference in facilitation. The greatest positive percentage change for any individual was 61%, and the greatest negative percentage change was 51%. The results suggest that facilitation is a durable individual characteristic of normal subjects. Serial studies may therefore be indicated in monitoring individuals suffering relapsing conditions.     

Spectral analysis of corticomotor evoked potentials in spinal cord injury. Part 1. Acute studies

Abstract

A model of graded spinal cord injury using ischaemia has been developed by using balloon occlusion of the abdominal aorta in rabbits. This model has been used to test pharmacological agents thought to provide protection against spinal cord injury based on changes in corticomotor evoked potentials (CMEPs). These highly reproducible signals are percutaneously recorded from the spinal cord in response to cortical stimulation and accurately reflect the degree of residual spinal cord function. The present study focused on the power spectra of CMEPs to clarify alterations in post-injury signals. This added dimension of previously unreported CMEP analysis will augmentfuture applications of the current model. [Neurol Res 1993; 15: 367-372]     

4-Aminopyridine enhances motor evoked potentials following graded spinal cord compression injury in rats

Although several experimental and clinical studies have demonstrated the ability of 4-aminopyridine (4-AP) to restore electrophysiological and/or behavioral function following chronic spinal cord injury, the mechanism by which this occurs remains unclear. Demonstration of efficacy in rat spinal cord injury has not been reported, evidently because even relatively mild spinal cord contusions that produce only minor permanent locomotor disturbances abolish hind limb myoelectric motor evoked potentials (mMEPs). In this study, mMEPs were recorded acutely 25 days following graded thoracic spinal cord compression in rats. mMEP amplitudes were significantly enhanced by a single, 2 mg/kg i.v. dose of 4-AP. mMEPs were increased in all rats showing some evoked responses initially, and also in some animals which had no responses prior to treatment. 4-AP was further found to increase the maximum following frequency of mMEPs in both normal and injured rats from about 0.1 Hz to between 1 and 10 Hz. These data suggest that 4-AP might act by enhancing synaptic efficacy, as well as enhancing conduction in spinal axons whose myelination has been rendered dysfunctional by trauma.     

Spectral analysis of corticomotor evoked potentials in spinal cord injury. Part 2. Chronic studies

Abstract

Corticomotor evoked potentials (CMEPs) have been suggested to accurately reflect neurological function, particularly with regard to the integrity of the spinal cord. However, the utility of these potentials to evaluate gradedchronic injury has received little attention. Frequency analysis has been suggested by the authors to be a method of simplifying interpretation of these complex signals. Ischaemic spinal cord injuries were produced in rabbits causing mild, moderate, or severe neurological deficits. CMEPs were recorded before, during, immediately following, and three days after injury. Alterations in the features of the power spectra reflected the degree of neurological injury. CMEP power spectra may predict neurological outcome and augment currently used electrodiagnostic tests. [Neurol Res 1993; 15: 373-378]     

人参皂甙对损伤脊髓诱发电位的影响

目的　研究猫急性脊髓损伤 (SCI)后脊髓诱发电位 (SCEP)的变化规律及人参皂甙 (GS)对其的影响 ,探讨 GS对 SCI的作用 ,旨在寻求治疗 SCI的新方法。方法　采用改良 Allen氏重量打击法制作猫急性脊髓损伤模型 ,动物随机分组 ,通过电生理及病理学方法 ,研究 SCEP的变化规律及 GS对其的影响 ,脊髓形态学的改变作为进一步的佐证。结果　 (1)损伤组伤后 SCEP辐值随时间延长逐渐变小 ,潜伏期逐渐延长 ;治疗组波形则逐渐恢复 ,6 h全部恢复 ,差异显著。(2 )光镜下两组均有水肿、中心性出血 ,神经元空泡变性 ,核溶解或固缩 ,尼氏小体消失 ,部分神经纤维脱髓鞘或断裂 ,损伤组最重 ,治疗组均有不同程度的恢复。结论　 GS对 SCI有治疗作用。     

Estimate of motor conduction in human spinal cord: slowed conduction in spinal cord injury

By using motor evoked potential (MEP) created by transcranial electric stimulation over the motor cortex and F-wave measurement from the peripheral nerve stimulation, it is possible to estimate the spinal cord motor conduction velocity (SCMCV) in the diseased state. Twenty-four patients with spinal cord injury (SCI) between T1 and T11 neurological levels participated in this study. MEP in leg muscle was absent in all neurologically complete paraplegics. In 16 patients with neurologically incomplete SCI, MEP was obtained in 13 patients. The SCMCV estimated from C7 to T12 spinal levels was 32.1 (SD = 9.4) m/s. This was significantly slower than 63.3 (SD = 8.6) m/s in 40 normal controls. This noninvasive, indirect method is measurable, and can provide valuable electrophysiological data in the assessment of motor function in patients with SCI.     

Fatigue-induced motor cortex excitability changes in subjects with spinal cord injury

To further investigate the mechanisms of exercise-induced cortical plasticity after spinal cord injury (SCI), the cortical silent period (CoSP) evoked by transcranial magnetic stimulation (TMS) during a fatiguing muscle contraction was evaluated in 5 patients with incomplete cervical SCI and in 5 healthy subjects.The physiological lengthening of CoSP end latency during fatigue was not observed in the SCI patients.This reduced intracortical inhibition, probably secondary to decreased activity of the GABAergic inhibitory interneurons that modulate the corticomotoneuronal output, could represent a ‘positive’ neuroplastic response in an attempt to compensate for the loss of corticospinal axons.The investigation of motor cortex excitability during fatiguing exercise may shed light on the role of exercise therapy in promoting brain reorganization and functional recovery in humans.