Somatosensory evoked potentials in man: differentiation of spinal pathways responsible for conduction from the forelimb vs hindlimb.

This review suggests that a previously unrecognized spinal cord pathway may be of major importance in the conduction of the somatosensory evoked potential (SEP) from the lower limb in Man. The nerve fiber type activated by a "typical" peripheral nerve stimulus used in studying the SEP will activate the posterior tibial nerve or median nerve predominantly at group I threshold. Group I fibers subserve limb proprioception. Therefore the spinal cord pathways subserving limb position sense will be the same pathways activated by a peripheral nerve stimulus used to evoke an SEP. A relatively newly recognized pathway involved with limb position sense from the lower limb is located in the dorsal portion of the lateral funiculus of the spinal cord whereas pathways subserving limb position sense in forelimb involve predominantly the dorsal column pathways. It is suggested that the dorsal columns play no major role in limb position sense from the lower limb in Man and therefore, the dorsal columns play no major role in the conduction of activity from the lower limb involved with the generation of an SEP.

A method for in vitro enzymatic dissociation of nerve roots and peripheral nerves from adult mammals.

Preparations yielding a high percentage of undamaged axons from fresh peripheral nerve or nerve root were made using an enzymatic dissociation regimen. The nerve was placed in a temperature-controlled chamber mounted over an inverted phase-contrast microscope. An oxygenated solution (Brimijoins) or modified Hank's solution was pumped through the chamber, first in a calcium-free form and then containing enzymes. The enzymes for dissociation were collagenase and trypsin, alternated. Enzymatic dissociation of the epineurium, perineurium and extracellular matrix was achieved. We supplemented the gentle agitation of a 10-roller peristaltic pump by periodically raising and lowering the fluid level in the chamber to provide a controlled mechanical agitation that promoted dissociation. A large percentage of the axons can be dissociated from the nerve, varying from approximately one-quarter to occasional complete dissociation. Action potentials were still conducted through dissociated axons, and axon transport was also still present, as documented by direct visualization using an AVEC-DIC type of microscope system. The axons had a better morphological appearance and displayed better transport than comparison preparations prepared by the usual mechanical teasing method, in our hands. The enzymatic method allows study of axons in an adult or developing mammal with regard to their electrical conduction and axon transport mechanisms. It should help to avoid a selection process for more hardy axons which may be imposed by traditional mechanical teasing methods. Mechanical stress was observed to cause widened Schmidt-Lanterman clefts, widened nodes, myelin bubbles, and other abnormal morphology as evidence of damage.

Review of descending motor pathways involved with transcranial stimulation.

The anatomical basis of the pyramidal tract is reviewed with respect to its proposed role in the conduction of the motor evoked potential. The fiber diameter profiles are discussed in relation to the measured conduction velocities of the corticospinal tract in humans. Stimulus parameters utilized to obtain the motor evoked potential are reviewed in relation to the laterality of response, response threshold, and properties of spatial and temporal summation. A discussion of the major descending tracts involved with walking as opposed to fine distal use of the digits is undertaken in the context of the possible prognostic capabilities of the motor evoked potential.

Evoked potentials from the motor tracts in humans.

Spinal cord monitoring during operation is of increasing importance in the prevention of injury. However, there is no direct monitor of the motor tracts available. We have reported a system using direct stimulation of the area overlying the motor tract between the intermediolateral sulcus and the dentate ligament in cats. This produces a 100-m/second signal with later components, which is abolished by section of the motor area, but not by section of the dorsal columns or the anterior quadrant of the spinal cord. Such stimulation also produces motor movement when the correct frequency is used. We now report the first application of this technique in humans, in whom we found the same 100-m/second signal, as well as slower components. We were able to elicit distal limb motor movement with stimulation of the motor tract area, but not with stimulation of the dorsal column area. This technique can be used either in open surgical cases or percutaneously and should provide an additional valuable technique for assessing spinal cord function.

Caloric stimulation-induced augmentation of H-reflexes in normal subjects, but not in spinal cord-injured patients.

This study examined the effects of ice water caloric stimulation on H-reflex amplitude in normal subjects and three complete spinal cord-injured patients. H-reflexes were obtained by stimulating the tibial nerve at the popliteal fossa and recording the H-response from the gastrocnemius muscle. All normal subjects who experienced nystagmus or vertigo demonstrated significant augmentation in H-reflex amplitude with ice water irrigation of the ear canal. In the three spinal cord-injured patients, there was no significant change of H-reflex with the ice water stimulus. The results suggest that descending tracts in the anterior spinal cord must be functional to demonstrate caloric augmentation of H-reflexes. In patients with spinal cord injury, it may be possible to predict the recovery of motor function using this test together with other clinical signs of neurological function.

Nonpyramidal motor activation produced by stimulation of the cerebellum, direct or transcranial: a cerebellar evoked potential.

There is a need to monitor the functional status of the motor pathways well enough to predict the state of that function during operations and in injured or diseased patients. We previously reported that a motor evoked potential (MEP) can be produced by direct or transcranial stimulation of the motor cortex in both cats and humans. This signal descends through both the dorsolateral and ventral spinal cord and is primarily localized in the pyramidal tracts, producing a peripheral nerve signal and an electromyogram (EMG) response. It is more sensitive to injury than the somatosensory evoked potential (SEP). We report here that one can stimulate the cerebellar cortex, either directly or transcranially, and produce a descending signal in the spinal cord that has different characteristics from the MEP. The cerebellar evoked potential (CEP), located in the dorsolateral and the ventral cord, has an earlier latency and a faster conduction velocity than the MEP. It is predominantly ipsilateral with some contralateral components and also produces EMG responses. In the peripheral nerves, the CEP often produces a pattern of several waves that is different from the one or two predominant contralateral waves of the MEP. The CEP is not diminished by pyramidotomy. It arises from two sites on the cerebellar cortex, medial and lateral. The pathways activated may be the vestibulospinal, rubrospinal, reticulospinal, and fastigiospinal systems. This test seems to offer a monitor of selected motor pathways in the spinal cord largely separate from and complementary to the MEP. The ventral pathways activated probably include those demonstrated to be most essential to basic ambulation after spinal cord injury in primates. Also of importance, one type of evoked potential can facilitate another, which provides additional diagnostic tests. The CEP should be of investigative and clinical value.

Model for the study of individual mammalian axons in vivo, with anatomical continuity and function maintained.

Methods for the study of axons involve whole nerve preparations, teased preparations of axons that are excised from their proximal and distal connections, and tissue culture models. As a complement to these, it would be advantageous to study separated, isolated axons in vivo, still in continuity with the end organ distally and the spinal cord central nervous system neuron proximally. This would allow the study of axon function, normal or pathological, in a close relationship to its biological environment. To achieve this, we have passed the surgically isolated sciatic nerve of a rat through a chamber specially designed for enzymatic dissociation. This was based on principles derived from a prior in vitro method for dissociating nerve into axons. The chamber has controlled temperature and flow and is on an inverted microscope stage, allowing observation of the process. We perfused the chamber with a calcium-free solution followed by a series of enzymes: collagenase, trypsin, and hyaluronidase. This dissociates that part of the extracellular matrix external to the Schwann cells, leaving free, myelinated axons with their Schwann cells. In this acute preparation, the axons continue to conduct action potentials for at least 8 hours. Furthermore, an in vitro study of the axon after the in vivo dissociation demonstrated that axonal transport was maintained in over 90% of the axons, directly visualized on an AVEC-DIC type of microscope system. Properties of axonal transport or active spike propagation can thus be studied individually in an in vivo axon preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor evoked potentials from transcranial stimulation of the motor cortex in cats.

Electrical testing of central nervous system pathways is assuming increasing importance in clinical medicine. However, there is no direct monitor of the motor system. We previously reported using a motor evoked potential created by direct excitation of the spinal cord, placing a stimulating electrode over the corticospinal tract area. To produce a less invasive test, we now use direct transcranial stimulation of the motor cortex through the scalp or direct stimulation of the motor cortex itself during operation. A descending signal can be recorded over the spinal cord and in the peripheral nerves where no retrograde sensory signals should be able to descend. This motor cortex stimulation produces contralateral limb movements and selective activation of the peripheral nerves of a limb. The characteristics of this signal are similar to those described in the neurophysiological literature for a descending motor signal. With a depth electrode, it was found that the signal was strongest in the spinal cord near the corticospinal tracts and in the anterior horn cell area. A set of lesioning studies showed that most of the signal travels in the area of the corticospinal tract, with some traveling in the ventral portion of the spinal cord, perhaps in the anterior corticospinal tract. Section of the pyramid essentially abolishes the signal, but lesioning of the red nucleus does not. This test offers an electrical assessment of the motor system that can be useful in experimental work on spinal cord and brain function. It has potential clinical applicability in humans.

Motor evoked potentials from transcranial stimulation of the motor cortex in humans.

Electrical monitoring of the motor system offers the potential for the detection of injury, the diagnosis of disease, the evaluation of treatment, and the prediction of recovery from damage. Existing evoked potentials monitor one or another sensory modality, but no generally usable motor monitor exists. We have reported a motor evoked potential using direct stimulation of the spinal cord over the motor tracts in cats and in humans. To achieve a less invasive monitor, we used transcranial stimulation over the motor cortex in the cat, thus stimulating the motor cortex. We report here the initial application of this method to humans. A plate electrode over the motor cortex on the scalp and a second electrode on the palate direct a mild current through the motor cortex which will activate the motor pathways. This signal can be recorded over the spinal cord. It can elicit contralateral peripheral nerve and electromyographic signals in the limbs or movements when the appropriate stimulation parameters are used. In clinical use to date, this has been more reliable than the somatosensory evoked potential in predicting motor function in patients where the two tests differed. It offers a number of possibilities for the development of valuable brain and spinal cord monitoring techniques, but requires further animal studies and clinical experience. Studies to date have not demonstrated adverse effects, but evaluation is continuing.

Somatosensory evoked potentials evaluated in normal subjects and spinal cord-injured patients.

Somatosensory evoked cortical potentials (SSEP's) were recorded in 27 healthy subjects using tibial and peroneal nerve stimulation with cephalic and non-cephalic references. Four major peaks were present in all recordings. Analysis of these components showed that SSEP's collected after tibial nerve stimulation with non-cephalic reference (linked earlobes) produced the most consistent clearly defined component peaks. Average latency, amplitude, and interpeak latency differences are presented for these SSEP's. Significant correlations were obtained between the height of the individual and the P1, N2, P2, and N3 latencies, and the N3-P1 interpeak latency. These results suggest that reproducible SSEP's can be obtained from tibial nerve stimulation in normal subjects using minimal numbers of stimulus presentations (28 to 64). The SSEP's from 34 patients with varying degrees of spinal cord trauma were compared with the SSEP's from normal subjects. These comparisons involved the P1, N2, P2, and N3 latencies and the interpeak latency values, as well as the amplitude values. Patients with normal sensory and motor neurological examinations could be distinguished from patients showing decreased sensory and motor findings or clinically complete lesions on the basis of peak latency and interpeak latency values. The latter two groups could not be distinguished from one another. In general, all patient groups had SSEP's of lower amplitude than did normal individuals, but the groups could not be distinguished from one another. These results indicate that SSEP's can be a useful clinical tool for differentiation of complete from incomplete spinal cord lesions, but do not invariably predict recovery of function.

Relationship between visual evoked potentials and intracranial pressure.

The relationship between intracranial pressure (ICP) and latency of visual evoked potentials (VEP) was investigated in hydrocephalic patients with severe head trauma. A positive correlation of increase in latency of wave N2 (normal latency 71 +/- 9.2 msec) of the VEP with elevations in ICP was observed. A potential role for VEP in both the assessment of shunt function and the monitoring of patients with severe head injury is suggested by these findings.

Routine, direct measurement of aortic pressure in the conscious rabbit.

A method for preparation and application of an indwelling catheter for measurement of aortic pressure in conscious rabbits is described. The catheter is generally reliable for periods longer than one month and requires little interference with the normal circulation. The system utilizes coiled polyethylene tubing which has a tapered tip covered with silicone rubber tubing and, at its exterior end, a Velcro matrix for skin healing. The catheter tip is pulled into the abdominal aorta with a trocar, directed caudally. The exterior end is run subcutaneously to the nape of the neck. In 19 rabbits prepared by this method, mean pressure was determined to be 68 +/- 2 mm Hg and pulse pressure was 29 +/- 1 mm Hg two weeks after implantation. The catheters remained patent in 17 rabbits at the time of sacrifice, 12 to 120 days later. In an in vitro sweep-frequency test, maximal resonance of the catheter system was found to lie between 12-14 Hz, at which point the measured pressure amplitude exceeded control by 12.5%.

Effects of chronic intraventricular administration of angiotensin II on drinking behavior and blood pressure.

Angiotensin II was continuously infused into the lateral cerebral ventricle of rats, and the effects on daily food and water consumption, urine volume, and aortic blood pressure were studied. All was infused at a rate of 10 ng/hr for seven days, using subcutaneously implanted osmotic minipumps. An intraventricular (IVT) control group was infused with only the saline vehicle, while a third group received AII subcutaneously. IVT AII rats showed a four-fold increase in water consumption, to a mean of 171 ml/day during Days 2-4 of infusion, whereas water intake of the other groups did not change from preinfusion levels. Urine volume showed a similar pattern to water intake, increasing five-fold in the IVT AII group during Days 2-4. These measures declined during the final three days of AII infusion, but significant tolerance was not observed. Food intake decreased markedly in both saline and IVT AII groups after implantation of the pumps, but the latter resumed normal food intake more slowly than the former, and body weight remained below preinfusion levels throughout the AII period. Aortic blood pressure of the IVT AII rats showed a slight, but progressive, rise during the infusion period, but it did not significantly exceed that of the saline rats. These results indicate that continuous, low-level, intraventricular infusion of AII may markedly increase water intake without significantly increasing fluid retention or blood pressure.

Identification of spinal cord pathways responsible for the peroneal-evoked response in the dog.

The question of whether the dorsal columns were primarily responsible for the conduction of the peroneal-evoked cortical somatosensory response was studied by making staged scalpel transections of the spinal cord at T6 in the anesthetized dog. Control evoked potentials were followed by sequential lesioning of the spinal cord, followed by 30 minutes of evaluation to determine the effect of the lesion. Although slight shifts in latency may have occurred following a particular cut, these were usually transient and recovered to control values, regardless of the order in which various quadrants were sectioned. To alter the peroneal-evoked cortical potential in the dog, at least three quadrants of the spinal cord must be damaged to cause consistent increases in latency or loss of potentials. These findings agree with other investigators' observations in the cat, monkey and human.

Response variability of somatosensory evoked potentials during scoliosis surgery.

Somatosensory evoked potentials (SSEP) were recorded from the scalp for intraoperative monitoring of patients undergoing surgical correction of spine deformities or spine fractures. Alterations in the SSEP with distraction, spine manipulation, anesthesia, hypotension, and other intraoperative variables are described. When loss of the SSEP occurred and a waiting period was undertaken until it returned, all patients with an SSEP present upon closing, which was within +/- 2 SD of their anesthetized control values, had no neurologic complications. Alterations in SSEP consisting of increases in latency of 15% and decreases in amplitude of 50% were not associated with any postoperative neurologic deficits.

Utilization of somatosensory evoked cortical potentials in spinal cord injury. Prognostic limitations.

The prognostic value of somatosensory evoked cortical potentials (SECP) for clinical recovery was studied in 71 patients with complete (28) and incomplete (43) spinal injuries. While the absence of an SECP was associated with no clinical recovery, the presence of an SECP was of little value in predicting the clinical state at the time of examination or the potential for recovery.

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.

Dissociation of somatosensory and motor evoked potentials in a patient with an intramedullary spinal tumor.

We describe a patient with an intramedullary spinal tumor who demonstrated postoperative improvement of motor and sensory function despite the lack of somatosensory evoked potentials (SSEPs) before and after intraoperative monitoring. The motor system was evaluated by direct spinal cord stimulation across the tumor bed. The resultant evoked compound muscle action potentials and compound nerve activities were normal. Although there is sufficient clinical evidence that SSEPs are sensitive to posterior and posterolateral ischemic insults of the spinal cord, the technique should be employed with an awareness of its limitations in monitoring the descending tracts which have a different blood supply and occupy more anterior locations in the spinal cord.