John J. Oro

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.

Phenotypic definition of chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15

Chiari type I malformation (CMI; OMIM 118420) is narrowly defined when the tonsils of the cerebellum extend below the foramen magnum, leading to a variety of neurological symptoms. It is widely thought that a small posterior fossa (PF) volume, relative to the total cranial volume leads to a cramped cerebellum and herniation of the tonsils into the top of the spinal column. In a collection of magnetic resonance imagings (MRIs) from affected individuals and their family members, we measured correlations between ten cranial morphologies and estimated their heritability in these families. Correlations between bones delineating the PF and significant heritability of PF volume (0.955, P = 0.003) support the cramped PF theory and a genetic basis for this condition. In a collection of 23 families with 71 affected individuals, we performed a genome wide linkage screen of over 10,000 SNPs across the genome to identify regions of linkage to CMI. Two‐point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1‐22.3). This region contains a biologically plausible gene for CMI, fibrillin‐1, which is a major gene in Marfan syndrome and has been linked to Shprintzen–Goldberg syndrome, of which CMI is a distinguishing characteristic. Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33‐33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. This linkage evidence supports a genetic role in Chiari malformation and justifies further exploration with fine mapping and investigation of candidate genes in these regions.

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.

Determination of Death by Neurological Criteria

Until 1968, when an ad hoc Harvard Medical School Committee published a landmark paper calling for determination of death using neurological rather than cardio-vascular criteria, death was considered to have occurred when the heart irreversibly ceased beating. Since that time, every jurisdiction in the country has come to accept through law or court decision neurological criteria to define death. The authors review the issue of death by neurological criteria in light of current guidelines and recent advances.

Prospective Analysis of Presenting Symptoms Among 265 Patients With Radiographie Evidence of Chiari Malformation Type I With or Without Syringomyelia

Objective To characterize the presenting symptoms among persons with radiographic evidence of Chiari malformation (CM) type I in an effort to help the primary care provider determine accurate diagnosis and treatment. Methods The symptoms of CM can often be vague and ambiguous, leading to misdiagnosis. Patients who had radiographic evidence of CM with or without syringomyelia were prospectively studied. The detailed symptom data were collected from patient reports at initial examination to determine if there was a pattern of symptoms typically attributable to the CM. Results Analysis of presenting symptoms among 265 patients demonstrated a distinct pattern of symptom constellation. This study reports a prospective analysis of presenting symptoms among 265 patients with radiographic evidence of CM with or without syringomyelia and defines a common presentation pattern. Recognition of typical symptoms attributable to CM can result in appropriate diagnostic workup, accurate diagnosis, and timely treatment, leading to improved patient outcomes.

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.

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.