Proprioceptive neuropathy affects normalization of the H-reflex by exercise after spinal cord injury

The H-reflex habituates at relatively low frequency (10 Hz) stimulation in the intact spinal cord, but loss of descending inhibition resulting from spinal cord transection reduces this habituation. There is a return towards a normal pattern of low-frequency habituation in the reflex activity with cycling exercise of the affected hind limbs. This implies that repetitive passive stretching of the muscles in spinalized animals and the accompanying stimulation of large (Group I and II) proprioceptive fibers has modulatory effects on spinal cord reflexes after injury. To test this hypothesis, we induced pyridoxine neurotoxicity that preferentially affects large dorsal root ganglia neurons in intact and spinalized rats. Pyridoxine or saline injections were given twice daily (IP) for 6 weeks and half of the spinalized animals were subjected to cycling exercise during that period. After 6 weeks, the tibial nerve was stimulated electrically and recordings of M and H waves were made from interosseous muscles of the hind paw. Results show that pyridoxine treatment completely eliminated the H-reflex in spinal intact animals. In contrast, transection paired with pyridoxine treatment resulted in a reduction of the frequency-dependent habituation of the H-reflex that was not affected by exercise. These results indicate that normal Group I and II afferent input is critical to achieve exercise-based reversal of hyper-reflexia of the H-reflex after spinal cord injury.     

Neuropeptides are selectivemarkers of spinal cord autonomic pathways

The view that various neuropeptides are preferentially present in central autonomic pathways in the mammalian spinal cord is gaining credence. A good example is the vasoactive intestinal polypeptide (VIP)-containing system concentrated in the sacral spinal cord of man¹ and cat^2,3,4, which selectively marks pelvic nerve afferent fibres. Although the functional role of neuropeptides in spinal cord pathways is unknown, their selective appearance provides neurobiologists and pathologists with a new key to understanding the autonomic nervous system.     

Reorganization of corticospinal pathways following spinal cord injury

To assess changes in the relationship between cortical motor representation areas and their target muscles following spinal cord lesions, we studied motor evoked potentials (MEPs) to transcranial magnetic stimulation in six patients with complete spinal cord injuries at low thoracic levels and eight healthy subjects. Magnetic stimulation at rest activated a larger fraction of the motoneuron pool and evoked MEPs with shorter latencies from a larger number of scalp positions in muscles immediately rostral to the level of a spinal cord injury than in corresponding muscles in controls. The MEPs associated with maximal voluntary activation were not significantly different in the two groups. These results suggest enhanced excitability of motor pathways targeting muscles rostral to the level of a spinal transection, reflecting reorganization of motor pathways either within cortical motor representation areas or at the level of the spinal cord. The data do not allow the determination of the contribution of spinal or cortical mechanisms. However, they support the notion of a limited flexible relationship between primary motor cortex and its target muscles following alterations of normal input-output patterns.     

Assessing the integrity of sympathetic pathways in spinal cord injury

STUDY DESIGN: Measurement of cutaneous sympathetic reflexes and hemodynamic responses to brief electrical stimuli applied above (forehead) and below (abdominal wall) a spinal lesion. OBJECTIVE: To assess the validity of using cutaneous vasoconstriction as a sensitive indicator of increases in sympathetic activity in spinal cord injury. SETTING: Prince of Wales Medical Research Institute, Australia. SUBJECTS: Twenty spinal cord injured subjects with injuries ranging from C3-T11 and nine able-bodied controls. METHOD: Cutaneous electrical stimulation was applied to the forehead and abdominal wall to subjects at unexpected times. Sudomotor and vasomotor responses, as well as continuous arterial pressure, heart rate and respiration were monitored. RESULTS: Sudomotor (electrodermal) responses to forehead stimulation were scarce in spinal cord injured subjects, whereas cutaneous vasoconstrictor responses (photoelectric pulse plethysmography) provided a sensitive indicator of any remaining central control of sympathetic function below the lesion. Electrical stimulation applied to the abdominal wall evoked vasoconstrictor reflexes below the lesion in the majority of spinal cord injured subjects, whereas only a limited number of electrodermal responses were observed. That these cutaneous vasoconstrictor responses could reflect parallel increases in muscle and splanchnic vasoconstrictor activity was indicated by the increases in blood pressure; patients lacking vasoconstrictor responses rarely showed stimulus-induced blood pressure increases. CONCLUSION: Our findings show that skin vasomotor responses to somatosensory stimulation provide a more sensitive tool than electrodermal responses for evaluation of sympathetic function below a spinal cord lesion. STATEMENT OF ETHICS: We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research, and all experiments were conducted with the understanding and consent of each subject.     

Neurophysiological assessment of the motor and sensory spinal pathways in chronic spinal cord injury

Introduction of transcranial magnetic stimulation (TMS) has provided means to study non-invasively corticospinal functions in humans. The purpose of the present study was to obtain an objective evaluation of spinal cord functions in spinal cord injury (SCI) subjects using TMS, multichannel surface EMG and somatosensory-evoked potentials (SSEP). Multichannel surface EMG recording was performed during reinforcement manoeuvres and during vibratory tonic reflex. Twenty-five post-traumatic clinically incomplete (ambulatory, AMB, and non-ambulatory, nAMB) SCI subjects were studied and compared to a control group of seven subjects. After preliminary analysis of neurophysiological studies they were divided into four groups according to presence or absence of motor-evoked potentials (MEP) in response to TMS in muscles below the level of the lesion and according to their ability to ambulate. TMS was delivered at vertex at 100% intensity and recorded from the large muscles of the upper and lower limbs. Surface EMG was recorded during reinforcement manoeuvres (RM) in the leg muscles and EMG activity was scored. SSEP were recorded at T12, L2, L4 and SI spinous processes and at Cz' on the scalp following tibial nerve stimulation at popliteal fossa. The prevalence of EMG responses during RM was higher in group with present MEPs (AMB/MEP+ and nAMB/MEP+) than in the group without MEPs. The group with present MEPs also showed better preserved functions of the ascending tracts compared to subjects without MEPs. Groups with present MEPs had 5/10 normal, 2/10 abnormal and 3/10 absent cortical SSEPs, whereas groups without MEPs showed 1/11 normal, 4/11 abnormal and 6/11 absent cortical SSEPs. Sustained function of ascending tracts was also positively correlated with preserved ability to ambulate. It was concluded that TMS in combination with multichannel surface EMG monitoring and sensory evoked potentials may prove feasible in assessing the functional capacity of the spinal cord after spinal cord lesion.     

Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers.

Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris-leucoagglutinin (PHA-L) in intact and brainstem-operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pons. Some fibers crossover under the fourth ventricle. The locus ceruleus and the Barrington's nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network here, and loop rostralward to innervate the entire NTS. A midsagittal knife-cut through the NTS eliminated paraventricular-fibers on the contralateral side. Synaptic contacts between PHA-L-labeled boutons and tyrozine hydroxilase-positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover.     

Schistosomiasis of the spinal cord.

Four cases of spinal cord schistosomiasis were characterized by paraparesis, sensory loss, and sphincter disturbances progressing over hours to days. One patient showed deterioration over months and remission after laminectomy, followed by the typical, rapidly progressive deficits. Biopsies on two patients showed granulomatous and necrotizing myelitis. Spontaneous improvement and unremitting deterioration, despite chemotherapy, make evaluation of treatment difficult. A survey of all previously reported cases provided no consistent pattern of response to any treatment modalities. Laminectomy for decompression and diagnosis, administration of antischistosomal medications, and high-dose oral prednisone early in the illness are recommended.     

Termination of supraspinal descending pathways in the spinal cord of the tegu lizard, Tupinambis nigropunctatus.

Descending fiber projections to the lizard spinal cord were studied using anterograde axonal degeneration. Following hemisection of the cord at the first spinal segment, degeneration was found in the white and gray matter as far down as the 31st (caudal) segment. Degenerating fibers in the white matter were confined to the ipsilateral side and were found in the medial longitudinal fasiculus and the outer half ot the lateral and ventral funiculi. Degeneration was more intense in the dorsolateral and ventromedial funiculi than in the ventrolateral funiculus. In the gray matter, REXED's criteria were applied to Nissl-stained material to delimit boundaries of ten laminae. Degeneration of suprospinal axons was most intense in the medial part of VII, dorsal and ventral commissures to ramify contralaterally in the medial part of VII, in VII, and in medial IX. No degeneration was present in the lateral part of the spinal gray on the contralateral side. In Golgi-stained material, dendrites of lateral IX cells were seen to extend into lamina VII, the dorsolateral part of VII, and the lateral funiculus. Thus, fibers of the ventromedial supraspinal pathway may make axodendritic contact with motoneurons of lateral IX as well as medial IX, ipsilaterally. In addition, there is a possibility of a crossed connection to contralateral motoneurons.     

The action of plantar pressure on flexion reflex pathways in the isolated human spinal cord.

OBJECTIVE: To investigate the conditioning effects of plantar pressure on flexion reflex excitability in patients with motor complete spinal cord injury (SCI). METHODS: In five motor complete SCI subjects, the non-nociceptive flexion reflex was evoked via electrical stimulation of the right sural nerve and was recorded from the ipsilateral tibialis anterior muscle. Pressure ranging from 25 to 80kPa was applied to the metatarsal heads through an adjustable platform incorporated into a foot rest and a comparison of the reflex size made between control conditions and during pressure application. RESULTS: In all subjects, a significant depression of the long latency flexion reflex was observed when pressure was applied to the foot sole. The short latency flexion reflex appearing at latencies less than 100ms was absent in all patients. CONCLUSIONS: The results demonstrate that flexion reflex excitability in the isolated human spinal cord can be modulated by adequate activation of plantar mechanoreceptors. SIGNIFICANCE: Activation of plantar mechanoreceptors is a feature of normal standing and walking. Rehabilitation for standing and walking in SCI commonly uses body weight support based protocols. The strong inhibitory actions of plantar pressure on reflex pathways in the isolated human spinal cord suggest that sensory feedback from the foot sole may be an important factor in successful rehabilitation of standing and stepping in SCI patients.     

Descending supraspinal pathways in amphibians. II. Distribution and origin of the catecholaminergic innervation of the spinal cord

Immunohistochemical studies with antibodies against tyrosine hydroxylase, dopamine, and noradrenaline have revealed that the spinal cord of anuran, urodele, and gymnophionan (apodan) amphibians is abundantly innervated by catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur in all three orders of amphibians CA, it is unclear to what extent the CA innervation of the spinal cord is of supraspinal origin. In a previous study, we showed that many cell groups throughout the forebrain and brainstem project to the spinal cord of two anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), a urodele (the Iberian ribbed newt, Pleurodeles waltl), and a gymnophionan (the Mexican caecilian, Dermophis mexicanus). To determine the exact site of origin of the supraspinal CA innervation of the amphibian spinal cord, retrograde tracing techniques were combined with immunohistochemistry for tyrosine hydroxylase in the same sections. The double-labeling experiments demonstrated that four brain centers provide CA innervation to the amphibian spinal cord: 1.) the ventrolateral component of the posterior tubercle in the mammillary region, 2.) the periventricular nucleus of the zona incerta in the ventral thalamus, 3.) the locus coeruleus, and 4.) the nucleus of the solitary tract. This pattern holds for all three orders of amphibians, except for the CA projection from the nucleus of the solitary tract in gymnophionans. There are differences in the strength of the projections (based on the number of double-labeled cells), but in general, spinal functions in amphibians are controlled by CA innervation from brain centers that can easily be compared with their counterparts in amniotes. The organization of the CA input to the spinal cord of amphibians is largely similar to that described for mammals. Nevertheless, by using a segmental approach of the CNS, a remarkable difference was observed with respect to the diencephalic CA projections.     

The origin of spinocerebellar pathways. I. The nucleus cervicalis centralis of the cranial cervical spinal cord.

The origin of spinocerebellar projections from the cranial cervi cal spinal cord was studied in neonatal dogs following cerebellar ablations or the injection of horseradish peroxidase (HRP) into the cerebellum. Cerebellar ablations produced distinct retrograde changes of three types: type I response or cen tral chromatolysis; type II response or ghost cells; and type 111 response or neu ronal loss and gliosis. These ablation-induced changes were evident in the cells of the nucleus cervicalis centralis. The results of hemicerebellectomy, unilateral cer ebellar pedunculotomy, and cordotomy established that the cells of this nucleus project contralaterally to the cerebellum. Cytoarchitectonic study revealed that this nucleus is composed of clustered medium-sized, multipolar, chromatophilic neurons located in the zona intermedia of the C₁-C₄ segments. The retrograde la beling of central cervical neurons following cerebellar injections of HRP con firmed the results obtained with the axonal reaction. Anterograde fiber degeneration was present in the central cervical nucleus following dorsal rhizotomy in the dog and cat. These experiments demonstrated dorsal root fibers among the somata of central cervical neurons rendered chromatolytic following cerebellectomy in the dog. Electron microscopic evidence is presented for the presence of degenerated dorsal root terminals upon the dendrites and somata of central cervical neurons. The nucleus cervicalis centralis forms a direct link between neck afferents and the cerebellum by way of a crossed cervicospinocerebellar pathway. Evidence could not be found for the presence of a spinocerebellar projection originating in the nucleus ceruicalis lateralis.     

Long-term reorganization of respiratory pathways after partial cervical spinal cord injury

High cervical spinal cord injury (SCI) interrupts bulbospinal respiratory pathways innervating phrenic motoneurons, and induces an inactivation of phrenic nerves (PN) and diaphragm. We have previously shown that the ipsilateral (ipsi) PN was inactivated following a lateral C2 SCI, but was spontaneously partially reactivated 7 days post - SCI. This phrenic reactivation depended on contralateral (contra) descending pathways, located laterally, that cross the spinal midline. We analysed here whether long-term post-lesional changes may occur in the respiratory network. We showed that ipsi PN reactivation was greater at 3 months compared with 7 days post-SCI, and that it was enhanced after acute contra phrenicotomy (Phx), which also induced a substantial reactivation of the ipsi diaphragm (not detected at 7 days post-SCI). At 3 months post-SCI (compared with 7 days post-SCI), ipsi PN activity was only moderately affected by ipsi Phx or by gallamine treatment, a nicotinic neuromuscular blocking agent, indicating that it was less dependent on ipsi sensory phrenic afferents. After an additional acute contra SCI (C1) performed laterally, ipsi PN activity was abolished in rats 7 days post-SCI, but persisted in rats 3 months post-SCI. This activity thus depended on new functional descending pathways located medially rather than laterally. These may not involve newly recruited neurons as retrograde labelling showed that ipsi phrenic motoneurons were innervated by a similar number of medullary respiratory neurons after a short and long post-lesional time. These results show that after a long post-lesional time, phrenic reactivation is reinforced by an anatomo-functional reorganization of spinal respiratory pathways.