Siavash S. Haghighi

Physiological analysis of motor reorganization following lower limb amputation

It is now known that amputation results in reorganization of central motor pathways, but the mechanism for the changes is unclear. One possibility is alteration of the excitability of the alpha motoneurons. We studied motor reorganization and excitability of alpha motoneurons to Ia input in 6 subjects with unilateral lower limb amputation. A Cadwell MES-10 stimulator was used to deliver transcranial magnetic stimuli through a circular coil centered on the sagittal axis 4 cm anterior to Cz and through an 8-shaped coil positioned over scalp locations 1 cm apart along the coronal axis. Surface EMG was recorded bilaterally from quadriceps femoris, the first muscle immediately proximal to the site of amputation. Excitability of the spinal alpha motoneuron pool to Ia afferents was assessed by determining the ratio of the maximal H reflex to the maximal M response (H/M ratio) elicited in the quadriceps femoris. Stimuli of equal intensity delivered to optimal scalp positions recruited a larger percentage of the alpha motoneuron pool in muscles ipsilateral to the stump than in those contralateral to the stump (P less than 0.01). Mean onset latencies of motor evoked potentials were shorter in ipsilateral muscles than in contralateral muscles (P less than 0.01). Muscles ipsilateral to the stump showed a trend toward activation from a larger number of scalp positions than those contralateral to the stump (P = 0.06). There was no difference in the quadriceps H/M ratios (7.2% ipsilateral vs. 10.9% contralateral). The absence of changes in the excitability of the alpha motoneuron pool in the presence of motor reorganization targeting muscles proximal to the stump suggests that reorganization occurs proximal to the alpha motoneuron level.

Backfiring in spinal cord monitoring. High thoracic spinal cord stimulation evokes sciatic response by antidromic sensory pathway conduction, not motor tract conduction.

Spinal cord stimulation has been advocated as an alternative to motor cortex stimulation for motor tract activation. To test this theory, evoked responses were recorded from lumbar spinal cord (L2; n = 14), spinal roots (L4-L7; n = 112), peripheral nerves (sciatics; n = 28), and hind limb muscles (n = 28) after epidural stimulation of the T1-T2 segment of the spinal cord in dogs (n - 12), cats (n = 2), and monkeys (n = 2), The spinal response evoked by spinal cord stimulation was resistant to a dorsal hemisectioning (depth, 7–8 mm) of the midthoracic spinal cord. A minimal attenuation of atency and amplitude occurred with dorsal hemlsactioning, suggesting signal transmission through descending or ascending pathways in the ventrolateral and ventral quadrants of the spinal cord. The sciatic nerve response was abolished by a dorsal column transection (depth, 3–4 mm) or ipsilateral lumbar dorsal rhizotomy (four dorsal roots). This shows that the evoked response recorded from the sciatic nerve in our animals was not travelling, as we expected, through the ventral roots, but rather was conducted antidromically through sensory fibers in dorsal roots.

Suppression of motor evoked potentials by inhalation anesthetics.

Summary The purpose of this study was to record evoked action potentials from forearm muscles in response to single-shock supramaximal electrical stimulation of motor cortex in room air and under different concentrations (0.5–1.5%) of isoflurane, enflurane, and halothane anesthesia in rats. Anesthesia was induced with a mixture of fentanyl and droperiodol, which was then followed by 10-min inhalation of each gas anesthetic under controlled ventilation. Increasing concentrations of isoflurane (n = 12) caused a progressive increase in onset latency and a decrease in peak-to-peak amplitude and duration. Similar increases in latency and decreases in amplitude and duration occurred under enflurane (n = 10) and halothane (n = 10) anesthesia. The three anesthetics caused a significant latency increase over baseline (room air) values for concentrations from 0.5 to 1.5% (p < 0.01). The amplitude and duration of muscle responses under all three volatile anesthetics at 0.5–1.5% concentrations were significantly lower than baseline (p < 0.01). Isoflurane, enflurane, and halothane anesthesia significantly altered the muscle response evoked by motor cortex stimulation in experimental animals.

Effects of altering core body temperature on somatosensory and motor evoked potentials in rats

The effects of core temperature on three potentials - so matosensory spinal evoked potential, somatosensory cortical evoked potential, and spinal motor evoked potential were studied in rats. Hyperthermia reduced the latency and increased the conduction velocity of all three potentials. Somatosensory spinal evoked potential amplitude was unchanged, whereas somatosensory cortical and spinal motor evoked potentials deteriorated above 42 C. Hypothermia increased latency and decreased conduction velocity in all three potentials. The amplitude of the spinal motor evoked potential decreased, and the somatosensory cortical and spinal motor evoked potentials disappeared below 28 C. Hyperthermia and hypothermia caused significant changes in the latency of all three potentials. The latency change of all three potentials became significant at 2–2.5 C above or below baseline, suggesting a range within which evoked potential studies should be performed.

Monitoring of motor tracts with spinal cord stimulation.

Study Design Sensory- and motor-evoked potentials were recorded after high thoracic (T2) epidural electrical stimulation of the spinal cord. Under general anesthesia, 22 cats underwent single or repetitive spinal cord stimulation. Objectives Sensory-evoked potentials were recorded after antidromic activation of the posterior column sensory fibers at lower electrical intensities (<5 V). Motor tract activation was accomplished by recording the ventral root and muscle action potential using single pulse stimulation (>50 V). Methods Sensory-evoked potentials were recorded from the lumbar spinal cord (n = 20), dorsal root (n = 80), and peroneal nerve (n = 40). Motor-evoked potentials were recorded from the ventral root (n = 40) and the hindlimb musculature (n = 10). Results The lumbar spinal-evoked response resisted lesioning and showed a minimal change after a spinal cord hemisection. Dorsal rhizotomy abolished the ipsilateral peroneal nerve action potential, indicating antidromic activation of afferent fibers. Motor responses did not change after the dorsal rhizotomy, suggesting involvement of nonsensory pathways. Conclusions These findings indicate that spinal cord stimulation activates sensory and motor tracts that can be recorded at various sites along the central or the peripheral nervous system.

The effects of taxol, methylprednisolone, and 4-aminopyridine in compressive spinal cord injury: a qualitative experimental study.

BACKGROUND Taxol is a diterpene alkaloid that stimulates tubulin production in cells. It may be effective in preserving the cytoskeleton of spinal cord axons after injury. METHODS Thirty-nine rats were submitted to spinal cord compression. The animals were divided into three groups that received taxol (18.75 mg/m2), methylprednisolone (30 mg/kg), or 4-aminopyridine (1 mg/kg). Taxol was administered as one dose immediately after injury and two additional doses on days 14 and 21. Methylprednisolone was given as a single injection immediately postinjury. Four-aminopyridine was administered on days 25, 26, and 27. A group of nine injured animals served as a control without any treatment. Evoked potentials were recorded before, during, and 4 weeks postinjury. Behavioral tests were measured to evaluate recovery of motor function. RESULTS The taxol and methylprednisolone-treated animals demonstrated a significant improvement in comparison with the control group. No functional improvement was found at 1 mg/kg treatment of 4-aminopyridine in rats. CONCLUSIONS We conclude that taxol and methylprednisolone given shortly after the compression injury improve functional outcome after an incomplete spinal cord injury.

Effect of desflurane anesthesia on transcortical motor evoked potentials.

The effect of the volatile anesthetic desflurane on motor evoked potentials was examined in male rats. Animals underwent cortical stimulation using small platinum ball stimulating electrodes secured on the motor cortex. To record evoked compound muscle action potentials (CMAPs), single-shock electrical stimulation was delivered to the forelimb representation of the motor cortex. Muscle responses were readily obtained in the contralateral extensor muscles. The effect of desflurane was examined at various concentrations ranging from 0.7 to 11.4%. With increasing concentrations of desflurane, there was a progressive decrease in the CMAP amplitude and systemic blood pressure over the baseline values. This decrease became statistically significant (p = 0.0078) at 5.7% [1 maximum alveolar concentration (MAC)] concentration of desflurane. Although there was a decrease in heart rate, the results were not statistically significant (p = 0.03). No significant difference in the onset latency or the duration of the CMAP was noted at different concentrations of the anesthetic. We conclude that desflurane anesthesia significantly alters the amplitude of the muscle response evoked by motor cortex stimulation in experimental animals.

Evaluation of the calcium channel antagonist nimodipine after experimental spinal cord injury.

The cortical somatosensory evoked potentials (CSEPs) were recorded to determine if the administration of nimodipine improves axonal function after spinal cord injury. Animals receiving a 52 g compression injury (a moderately severe injury) for 5 minutes were randomly allocated to one of five treatment groups. Each group was given an infusion of one of the following nimodipine regiments over 2 hours, commencing 1 hour before compression: placebo (n = 20), 0.5 micrograms/kg (n = 10), 0.25 micrograms/kg (n = 20), 0.125 micrograms/kg (n = 10), and 0.25 micrograms/kg + Hetstarch (n = 10). In the control group, 65% of animals lost the CSEPs immediately after the injury with almost all (95%) of these regaining the CSEPs within 15 minutes after decompression of the spinal cord. In the treated groups, the rate of the CSEP loss was highest in the 0.5 micrograms/kg group. This group also had the lowest CSEP recovery. The proportion of the CSEP loss was essentially the same for the other nimodipine-treated groups, although it seemed that there was an increasing number of nonresponses with increasing the nimodipine dose. Our data indicate lack of any beneficial effects of nimodipine on axonal function as measured by evoked activities in experimental spinal cord injury.

Effects of Hypovolemic Hypotensive Shock on Somatosensory and Motor Evoked Potentials

The utility of evoked potentials in monitoring spinal cord and cerebral function in various neurosurgical and orthopedic operations has now been established. To study the effects of graded hypotension upon spinal and cortical somatosensory evoked potentials (SMEPs), and spinal motor evoked potentials (SMEPs), 12 anesthetized cats were subjected to graded hypotension ranging from a mean arterial blood pressure of 100 mmHg to 30 mmHg or less. Hypotension causes a progressive increase in onset latency and a decrease in amplitude and conduction velocity of SEPs and SMEPs. Cortical SEPs and SMEPs were sensitive to profound hypotension (MAP less than 30 mmHg). Spinal SEPs showed more resistance and disappeared at lower levels of hypotension. Immediate blood transfusion caused resumption of cortical SEPs and SMEPs within 30 minutes after infusion; however, the latency and amplitude of responses did not reach the baseline values within 1 hour after transfusion. The sequential recovery of evoked responses was dependent upon the length of hypotension. When 15 minutes elapsed between loss of responses and transfusion, cortical SEPs and SMEPs did not resume within 1 hour after infusion. No return of signals occurred if 30 minutes elapsed between the loss of evoked responses and blood reperfusion. These findings suggest that ischemia associated with profound systemic hypotension can alter or obliterate evoked responses.

Effect of 4-aminopyridine in acute spinal cord injury

BACKGROUND The demyelination process has been proven to be an important factor contributing to long-term sensory and motor impairments after spinal cord injury (SCI). The loss of myelin promotes exposure of K+ channels in internodal region of the damaged myelinated axons leading to K+ efflux into the neurons with subsequent blockage of action potentials. The potassium channel blocker 4-aminopyridine (4-AP) has been effective in restoring some sensory and motor impairment in incomplete SCI patients. The effect of this compound given immediately after an acute injury is not known. The objective of this study was to determine if blockage of K+ ions efflux immediately after an acute SCI would improve neuronal conduction in this model of injury. METHODS Cortical somatosensory evoked potentials (SSEPs) were recorded before and after a weight-induced compression injury of 120 grams, and were monitored up to 5 hours postinjury. A randomized treatment was initiated with administration of either vehicle or 4-AP. All 4-AP treatments were given as intravenous bolus injections of 1.0, 0.5, and 0.3 mg/kg at 1, 2, and 3 hours after the trauma. RESULTS The SSEPs were abolished immediately after the injury in all control and treated animals. Both groups showed spontaneous recovery of the SSEPs at the rate of 44.5% for the 4-AP treated and nontreated groups at the second hour postinjury. This recovery rate remained the same for both groups at the end of the experiments. CONCLUSIONS Based on the recovery of the SSEPs, our data indicate that early administration of 4-AP lacks any beneficial effect on axonal function during acute stage of spinal cord injury.