Recovery of Locomotion in Monkeys With Spinal Cord Lesions.

This study reanalyzes kinematically (via film) the pre- and postoperative locomotor behavior of 4 of the 10 monkeys with partial spinal cord lesions (T8) briefly described by Eidelberg, Walden, and Nguyen (1981). The behavior of the remaining 6 monkeys is qualitatively described. The analysis reveals that 5 of the animals initially exhibited unilateral hind limb stepping. Hind and forelimb cycle durations often differed postoperatively; the hind limbs commonly showed increased values, whereas forelimb cycle durations were reduced: ipsilateral interlimb phase values were usually inconsistent. A review of prior studies of primate spinal cord lesions indicates that sparing of the ventrolateral quadrant may not be essential for locomotor recovery (cf. Eidelberg, Walden, & Nguyen, 1981). Furthermore, this review as well as the kinematic analysis indicates that primates with very significant spinal lesions can stilI exhibit locomotor movements. Thus, although the primate's spinal cord seems less able than other mammals' to readily organize locomotor movements (Eidelberg, Walden, & Nguyen, 1981), the total absence of stepping in primates with completely transected cords is unexpected and warrants further research.

Cauda equina syndrome of long-standing ankylosing spondylitis. Case report and review of the literature.

Cauda equina syndrome as a neurological complication of long-standing ankylosing spondylitis was first reported in 1961. The syndrome is relatively uncommon and its pathophysiology is still poorly understood. Based on their experience with such a case, the authors review the clinical, electrographic, histological, and radiographic features of the syndrome, including the findings of magnetic resonance (MR) imaging. The addition of MR imaging to the evaluation of patients with ankylosing spondylitis and the cauda equina syndrome not only aids in the diagnosis of the syndrome but may also provide valuable insight into the pathophysiology of this condition.

Transsynaptic degeneration of motoneurones caudal to spinal cord lesions.

We studied the effects of complete transversal section of the spinal cord, at T8-10, in adult rats, upon the number and morphology of identified motoneurones in lumbar segments L4 and L5. In observations by light and electron microscopy many lumbar motoneurones had structural abnormalities when the interval between surgery and perfusion ranged between a few hours and one week. We found also that as many as 25% of the motoneurones distal to a cord transection disappeared as a consequence of the lesions. We did not find comparable changes in the spinal cord at C6 after transection at T8-10. Complete removal of the cerebellum did not reduce the lumbar motoneurone counts. Bilateral ablation of the "motor" cortex did cause a reduction of motoneurone counts at L4-5; these animals showed normal or near normal spontaneous locomotor activity beginning a few days after the lesion was placed. Motoneurone counts were significantly reduced after partial cord lesions that spared the dorsal funiculi (where the corticospinal tract travels in the rat), but in this case the rats were paraplegic as a result of the lesion. Cord transection at 7 days of postnatal age resulted in reduced motoneurone counts when the rats reached adulthood. Intraspinal or subarachnoid administration of colchicine led to reduced motoneurone counts. Prolonged infusion of a GABA agonist, muscimol, into the lumbar CSF did not prevent the loss of motoneurones produced by cord transection. Pretreatment of animals with a Ca2+ channel blocker (nimodipine) did not prevent the effects of cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurements of regional glucose metabolism in studies of motor control.

We used the incorporation of tracer quantities of radiolabeled glucose analogues into muscle and CNS tissues to determine, first, whether unilateral dorsal root deafferentation affects hindlimb flexor and extensor muscles of that side equally. For this we compared the incorporation of [3H]fluorodeoxyglucose into selected muscles in the intact and the deafferented side. The muscles were dissected out after exercise on a treadmill, and tracer incorporation was measured by scintillation counting. Second, we used the [14C]2-DG radioautographic method of Sokoloff to seek confirmation of the involvement of certain CNS structures in locomotor control. We found fascinating side to side asymmetries in glucose metabolism, in the cervical spinal cord, motor cortex, and caudate nucleus. There is still debate about the manner in which "neuronal function", regional blood flow, and glucose metabolism, may be coupled (or even on the existence of such coupling). However, these methods can be useful by their anatomical resolution, and the possibility of making multiple regional measurements from a single subject.

Behavioral and biochemical studies in monkeys made hemiparkinsonian by MPTP.

Monkeys were required to press a lever rapidly for food, using either the right or the left hand. After stable baseline performance was established, MPTP (N-methyl-4-phenyl-2,3,5,6-tetrahydropyridine) was injected into the internal carotid of one side via a transfemoral catheter. The onset and time course of clinically severe, Parkinson-like symptoms were paralleled by a significant decrease of bar-pressing activity in the side contralateral to injection, while the forelimb in the unaffected side continued normal pressing. The unilaterality of effects was confirmed biochemically after sacrifice by a 95% drop in striatal dopamine (DA) levels of the injected compared to the uninjected hemisphere. The results show that hemiparkinsonism achieved by carotid injection is very stable; that normal motor behavior is maintained on the unaffected side and that goal-achieving strategies remain active, but that the affected side is unable to execute the task unless extrinsic levodopa is provided.

40 Hz--middle latency auditory evoked response in comatose patients.

Brain-stem auditory evoked response (BAER) and 40 Hz middle latency auditory evoked response (40 Hz AER) were elicited in 12 comatose patients. The concept of a midbrain generator of 40 Hz AER is being discussed.

Asymmetrical regional changes in energy metabolism of the central nervous system during walking.

Cats were injected with 2-deoxy- [14C]glucose (2-DG) while walking on a moving treadmill (experimental group), or sitting down on a stationary one (controls). After a 45-min equilibration period they were anesthetized, and their central nervous system (CNS) was removed rapidly and frozen. The tissue blocks were sectioned serially, and X-ray film exposed to the sections was used for quantitative densitometric analysis by Sokoloff's method. The utilization of glucose in a CNS region (LCMRg) was regarded as a measure of that region's energy metabolic activity and--indirectly--of its functional status. The walking cats exhibited significantly higher LCMRg in many but not all places of the neuraxis, compared to the control group. Also, LCMRg was symmetrical (side to side) in the control group but significantly asymmetrical in certain regions of the CNS in the experimental group. In all but one of these cats the LCMRg was greater in the right side of the gray matter of the cervical spinal cord and in the left visual and motor cortices and caudate nucleus. The finding that the motor cortex and other supraspinal regions become more active during walking suggests they may contribute to the control of locomotion and/or processing of related sensory data. The side to side asymmetry in the spinal cord and hemispheres during walking may be related to the phenomenon of lateral dominance.

Variability and functional recovery in the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism in monkeys.

Fourteen macaque monkeys were injected intravenously with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. All developed the cardinal signs of parkinsonism (akinesia, rigidity, etc.) in varying degrees; some required repeated series of injections of the drug, while others developed the syndrome readily after the first series. Most of the subjects that were kept for longer than 4 weeks after the first dose of the drug showed complete or partial recovery after that time. Measurement, in some of the subjects, of the neostriatal levels of dopamine and dihydroxyphenylacetic acid showed the expected depletion of these substances at the peak of the behavioral action of the drug, but no recovery when the animals had returned to, or near, pre-drug behavioral status. No firm conclusion can be reached at this time as to the reasons for the behavioral recovery or the variability of the effects of the drug across subjects.

Recovery of locomotor function after hemisection of the spinal cord in cats.

Cats were subjected to high lumbar hemisection of the spinal cord, on the right side. The initial paralysis of the right hindlimb became rapidly attenuated, and they walked again in one week or less after surgery. Minor residual deficits in gait remained, that may be permanent. Electrical stimulation of the bulbar reticulospinal formation showed residual crossed connections reaching the right lumbosacral cord via the left hemicord. Recovery from Brown-Séquard's syndrome may be primarily due to the survival of low crossing descending projections to the spinal cord.

Effects of sensory deafferentation on glucose metabolism of muscles during locomotion.

We measured the uptake of a radiolabeled analogue of glucose ([3H]FDG) into muscles during treadmill walking so as to determine whether sensory deafferentation of a limb affects the muscles' metabolic response to the exercise. The muscles on the deafferented side took up less tracer than those in the intact side with exercise, but not at rest. Extensor muscles were more affected than flexors by deafferentation. This agrees with the proposal that "reflex" inputs adjust the level of recruitment of motor units by central pattern generators.

Recovery of locomotor function in cats after localized cerebellar lesions.

Cats were trained to walk on a motorized treadmill, at speeds up to a brisk walk, for food reward. A cerebellar lesion was placed in each animal, either unilateral removal of paravermal cortex, or unilateral coagulation of n. interpositus, or bilateral coagulation of the fastigial nuclei. The effects of these lesions upon locomotor activity were measured by conventional kinematic methods, and were found to be generally in agreement with prior observations. Also in agreement with prior work was the fact that these initial deficits disappeared in a relatively short time. The kinematic data suggest that this recovery of function was genuine in the sense that compensatory alterations in limb motion could not be demonstrated. In disagreement with prior studies, we failed to elicit decompensation (e.g. reinstatement of the original deficits) by subsequent pyramidal tract sections, or ablation of the 'motor' cortex. We conclude that the corticospinal system is probably not essential to the recovery observed, and also that perhaps there are substantial differences in the mechanisms of recovery of 'spontaneous' overground locomotion, compared to walking on a treadmill as a conditioned instrumental response.

Regional metabolic changes in the spinal cord related to spinal shock and later hyperreflexia in monkeys.

The regional metabolic rate for glucose (rMRglu) was studied in macaque monkeys after spinal cord transection at T10, both during spinal shock and after reflexes had returned. The rMRglu was measured in all Rexed layers in cord segments both caudal and rostral to the level of the transection utilizing the quantitative [14C]deoxyglucose technique. The monkeys in spinal shock exhibited a significant increase in rMRglu in Rexed layer I and a significant reduction in layers VI to IX of the lumbosacral cord. In contrast, after reflexes had returned the rMRglu was increased in all Rexed layers of the lumbosacral cord; this increase was significant in layers I, V, and VI.

Phase relations of hippocampal projection cells and interneurons to theta activity in the anesthetized rat.

The correlation between cell firing and hippocampal theta activity was studied with the spike-triggered averaging method in rats anesthetized with urethane. Projection cells in the CA1 region and the dentate gyrus fired with highest probability on the negative phase of the theta waves recorded from the corresponding regions. CA1 interneurons discharged mainly on the positive phase. In the dentate gyrus about half of the interneurons fired on the negative phase, while the remaining half discharged preferentially on the positive phase of the locally derived theta waves. It was suggested that septal theta "pacemaker' cells directly excite hippocampal interneurons which in turn rhythmically inhibit a large number of projection cells.

Convergence of associational and commissural pathways on CA1 pyramidal cells of the rat hippocampus.

The interaction of the commissural and associational systems to the CA1 region of the hippocampus was studied by recording extracellular field potentials and single unit activity in anesthetized rats. Associational fibers were activated by stimulating the stratum oriens of the CA1 region contralateral to recording: this stimulation activated the Schaffer collaterals by antidromically firing the pyramidal cells of the CA3 region on the side of recording. Commissural fibers were stimulated where they emerge from CA3 region. Both pathways excited both the basal and apical dendrites of the CA1 pyramidal cells. Commissural activation in stratum oriens was more efficient than associational path stimulation, while the opposite was seen in stratum radiatum. Responses elicited by associational path activation had their peak negativity 100--150 micrometers deeper in stratum radiatum than commissurally evoked responses. Both pathways were able to discharge pyramidal neurons. Both homonymous and heteronymous double pulse stimulation showed response facilitation. Simultaneous activation of both pathways induced a greater amplitude population spike than predicted by algebraic summation of the independent responses. Over 80% of the responsive CA1 cells could be fired by either pathway. These results show a considerable convergence of the commissural and associational pathways on CA1 pyramidal cells, although their predominant locus of excitation might be different.

Spatial mapping, working memory, and the fimbria-fornix system.

Rats with lesions severing either the subcallosal fornix (Fo) or the medial half of the fimbria (Fi) were used. They were compared with control (Co) animals in a working memory task (serial alternation) and a reference memory task (cue-guided alternation). Neither task required spatial mapping strategy. Damaging the Fi, but not the Fo, caused a severe deficit in the serial alternation task. Analysis of individual performance revealed that Fi rats either adopted a "side strategy, " resulting in worse than chance performance. This active perseveration required intact working memory mechanism. In the cue-guided alternation task, Fo animals proved superior to Co and Fi rats. These findings are inconsistent with notions that the exclusive role of the hippocampus is spatial mapping or storing of recent memories. They indicate also differential involvement of the fimbria and fornix fibers in behavior.

Histochemical evidence for the existence of skeletofusimotor (beta) innervation in the primate.

A total of ten alpha motor axons which innervated the peroneus brevis muscle were isolated in two cynomolgus monkeys. In each experiment, the isolated alpha axons were stimulated collectively to deplete glycogen from their muscle units. The muscle was then frozen quickly , cut serially, and stained for glycogen. Of the 52 muscle spindles that were examined, zones of glycogen depletion were found in the intrafusal fibres of 32 spindles. The glycogen-depleted motor units included both fast-twitch and slow-twitch types. Depleted zones were observed in all three types of intrafusal muscle fibres. It was concluded that skeletofusimotor (beta) efferents were among the stimulated motor axons. This finding constitutes the first anatomical evidence for the existence of beta innervation in the primate.

Extracranial surgical procedures in the management of vertebrobasilar insufficiency.

Vertebrobasilar insufficiency is an important syndrome in the spectrum of cerebrovascular disease. Its clinical importance and the frequency of its clinical manifestations are often underestimated. Our experience with a large population of patients having extensive cerebrovascular disease has led us to recognize two classes of vertebrobasilar insufficiency--simple and complex--and, also, to recognize that vertebrobasilar insufficiency is often associated with disease in multiple extracranial vessels. Until recently, direct approaches to the vertebral artery have been underutilized for these patients. In fact, there has been a tendency either to relegate patients with vertebrobasilar disease to medical follow-up or to surgical procedures upon the carotid system. We believe that the resurgence of neurosurgical interest in the vertebrobasilar system is most appropriate. Furthermore, the active interest that neurosurgeons are now taking in developing procedures for managing extracranial vertebral artery problems is in the best interest of patients with cerebrovascular disease. We believe that careful neurosurgical evaluation of patients with simple and complex vertebrobasilar insufficiency will lead to appropriate selection of candidates for vascular reconstruction of the vertebral system. Finally, we believe that vertebral artery to common carotid artery transposition, and its variations, is a procedure that has an important role in the management of cerebrovascular disease.