Modulation of spinal reflex by assisted locomotion in humans with chronic complete spinal cord injury

Objective

In healthy subjects, spinal reflexes (SR) evoked by non-noxious tibial nerve stimulation consist of an early (60–120 ms latency) and an occasional late-appearing (120–450 ms latency) component in the ipsilateral tibialis anterior. In chronic (>1 year) complete spinal cord injured (cSCI) subjects early components are small or lacking while late components are dominant. Here we report on the modulation of SR by assisted locomotion in healthy and chronic motor cSCI subjects.

Methods

SR was evoked by tibial nerve stimulation at the terminal stance phase during assisted locomotion and was compared to SR recorded during upright stance.

Results

In chronic cSCI subjects only a late SR component was consistently present during upright stance. However during assisted locomotion, an early SR component appeared, while amplitude of the late SR component became small. In contrast, in healthy subjects the early SR component dominated in all conditions, but a small late component appeared during assisted locomotion.

Conclusion

A more balanced activity of early and late SR components occurred in both subject groups if an appropriate proprioceptive input was provided.

Significance

Early and late SR components are assumed to reflect the activity of separate neuronal circuits, which are associated with the locomotor circuitry possibly by shaping the pattern.     

Gentamicin disposition kinetics in humans with spinal cord injury

The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers. The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects. The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours. The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown. The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man. The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population.     

Electromyography detects mechanically-induced suprasegmental spinal motor tract injury: Review of decompression at spinal cord level

ObjectiveHerein, we report use of electromyography (EMG) to anticipate corticospinal conduction block, as defined by muscle-derived transcranial electrical motor evoked potential (TCE MEP) loss, during extradural spinal cord decompression.MethodsOne hundred and eighty-four patients underwent cervical (173) or thoracic (11) decompression. The same derivations were recorded for EMG and TCE MEP neuromonitoring. When highly repetitive, complex, and prolonged EMG discharges were identified in myotomes below the operated level (severe suprasegmentally-generated EMG discharges = severe SEDs), a report of possible spinal cord impact was made and a TCE MEP obtained. TCE MEP loss (with or without antecedent SEDs) was defined as >90% amplitude reduction compared to baseline recordings.ResultsSevere SEDs, seen in 15 cases, anticipated TCE MEP loss in 7/15. In 13/15 severe SED cases, manipulations near dura were the proximate cause. Interventions after TCE MEP loss included changed instrumentation, re-positioning, increased blood pressure, wake-up test, and surgical pause.ConclusionsSEDs can be identified during extradural spinal cord decompression. Severe SED occurrence is associated with a ∼50% risk of subsequent corticospinal conduction block.SignificanceAlthough SED occurrence does not provide specific information for lesions of the fast neurons of the corticospinal tract, SED surveillance during decompression at spinal cord level can supplement TCE MEP recording.     

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs.     

Expansion of nociceptive withdrawal reflex receptive fields in spinal cord injured humans

OBJECTIVE: In spinal cord injured (SCI) subjects, exaggerated withdrawal reflexes associated with a dominant flexor pattern irrespective of stimulation site have been reported. In the present study, withdrawal reflex receptive field (RRF) was determined in complete SCI subjects (N=9). METHODS: Distributed electrical stimulation was applied to the sole of the foot, and reflexes in tibialis anterior, soleus, biceps femoris, and vastus lateralis muscles were recorded together with knee and ankle movement trajectories. A group of spinally intact subjects (N=10) were included as controls. With the subjects in supine position, stimulation was applied to 10 different sites on the foot sole. Based on the tibialis anterior reflex threshold for stimulation on the mid foot sole, two stimulus intensities (1.1 times the reflex threshold and 1.4 times the reflex threshold) were used for all 10 sites. RESULTS: In SCI subjects, dorsi-flexion dominated independent of stimulus site and the tibialis anterior RRF covered the entire foot sole in contrast to a well-defined tibialis anterior receptive field at the medial, distal foot sole in the spinally intact subjects. Further, the soleus RRF also covered the entire sole in the SCI subjects. The reflexes in biceps femoris and vastus lateralis muscles were small and associated with weak knee flexion at all 10 sites in the SCI subjects and in the controls. CONCLUSIONS: The RRF of the ankle flexor and the ankle extensor muscles both covered the entire sole of the foot indicating an expansion of the RRFs following spinal cord injury. The expansion is most likely due to lack of descending inhibitory control and/or increased sensitivity of the spinal reflex loop in the SCI subjects. SIGNIFICANCE: The study improves the understanding of spinal reflex control in spinal intact and spinal cord injured subjects.     

Central sensitization in spinal cord injured humans assessed by reflex receptive fields

ObjectiveTo investigate the effects of central sensitization, elicited by intramuscular injection of capsaicin, by comparing the reflex receptive fields (RRF) of spinally-intact volunteers and spinal cord injured volunteers that present presensitized spinal nociceptive mechanisms.MethodsFifteen volunteers with complete spinal cord injury (SCI) and fourteen non-injured (NI) volunteers participated in the experiment. Repeated electrical stimulation was applied on eight sites on the foot sole to elicit the nociceptive withdrawal reflex (NWR). RRF were assessed before, 1 min after and 60 min after an intramuscular injection of capsaicin in the foot sole in order to induce central sensitization.ResultsBoth groups presented RRF expansion and lowered NWR thresholds immediately after capsaicin injection, reflected by the enlargement of RRF sensitivity areas and RRF probability areas. Moreover, the topography of the RRF sensitivity and probability areas were significantly different in SCI volunteers compared to NI volunteers in terms of size and shape.ConclusionsSCI volunteers can develop central sensitization, despite adaptive/maladaptive changes in synaptic plasticity and lack of supraspinal control.SignificanceProtective plastic mechanisms may still be functional in SCI volunteers.     

Hip-phase-dependent flexion reflex modulation and expression of spasms in patients with spinal cord injury

The flexion reflex in human spinal cord injury (SCI) is believed to incorporate interneuronal circuits that consist elements of the stepping generator while ample evidence suggest that hip proprioceptive input is a controlling signal of locomotor output. In this study, we examined the expression of the non-nociceptive flexion reflex in response to imposed sinusoidal passive movements of the ipsilateral hip in human SCI. The flexion reflex was elicited by low-intensity stimulation (300 Hz, 30 ms pulse train) of the right sural nerve at the lateral malleolus, and recorded from the tibialis anterior (TA) muscle. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by a Biodex system while subjects were supine. The effects of leg movement on five leg muscles along with hip, knee, and ankle joint torques were established simultaneously with the modulation pattern of the flexion reflex during hip oscillations. Phase-dependent modulation of the flexion reflex was present during hip movement, with the reflex to be significantly facilitated during hip extension and suppressed during hip flexion. The phase-dependent flexion reflex modulation coincided with no changes in TA pre- and post-stimulus background ongoing activity during hip extension and flexion. Reflexive muscle and joint torque responses, induced by the hip movement and substantiated by excitation of flexion reflex afferents, were entrained to specific phases of hip movement. Joint torque responses were consistent with multi-joint spasmodic muscle activity, which was present mostly during the transition phase of the hip from flexion to extension and from mid- to peak extension. Our findings provide further evidence on the interaction of hip proprioceptors with spinal interneuronal circuits engaged in locomotor pathways, and such interaction should be considered in rehabilitation protocols employed to restore sensorimotor function in people with SCI.     

Voluntary supraspinal suppression of spinal reflex activity in paralyzed muscles of spinal cord injury patients

Having previously demonstrated that residual facilitatory brain influence on segmental structures occurs in paralyzed spinal cord injury patients, we sought evidence of suprasegmental suppression in such patients. By recording EMG activity from leg muscles, we studied changes in segmental excitability of the plantar reflex elicited by cutaneous stimulation of the plantar surface. Using surface EMG recordings, 50 paralyzed spinal cord injury patients were examined for their ability to volitionally suppress the plantar reflex on three repeated trials after three baseline trials. The patients, who had no voluntary EMG activity in the monitored muscles, were able to volitionally suppress the plantar reflex responses by 45% in the tibialis anterior, hamstring, and triceps surae muscles and to suppress the quadriceps response by 72%. In this patient group, 73 of 100 tibialis anterior muscle groups showed suppression of more than 20% compared with the control response. On reexamination, these findings were consistent during a period of 2 years in six patients. We conclude that suprasegmental suppression of segmental activity does occur in paralyzed spinal cord injury patients, and that in clinically complete patients, neurological evaluation should include assessment of the degree of preservation of suprasegmental neurocontrol on segmental activity below the lesion.     

Behavior of the H-reflex in humans following mechanical perturbation or injury to rostral spinal cord

In humans, H-reflexes are suppressed during early spinal shock. In animals, rostral cord injury results in loss of segmental reflexes within seconds. If H-reflexes persist under general anesthesia, can they be used to monitor the integrity of the rostral cord? In part I of this study, we recorded H-reflexes intraoperatively in 25 patients to elucidate general anesthesia effect. In 23 subjects, H-reflexes were consistently elicited, and within ±13% of the normalized group mean amplitude. In part II, we recorded H-reflexes in 31 patients during spinal cord surgery to elucidate H-reflex behavior immediately following rostral spinal cord injury. In 6, abrupt suppression of the H-reflex coincided with cord injury. In 4 of 6, suppression was transient and less than 50% of baseline; none of these patients developed neurological deficits. In 2, suppression exceeded 90% and persisted throughout surgery; both patients developed profound deficits. We conclude that (1) the H-reflex can be consistently elicited under general anesthesia in most patients, (2) rostral cord injury rapidly suppresses the H-reflex, and (3) the degree and duration of H-reflex suppression reflects the severity of the injury. © 1996 John Wiley & Sons, Inc.     

Predictive model of muscle fatigue after spinal cord injury in humans

The fatigability of paralyzed muscle limits its ability to deliver physiological loads to paralyzed extremities during repetitive electrical stimulation. The purposes of this study were to determine the reliability of measuring paralyzed muscle fatigue and to develop a model to predict the temporal changes in muscle fatigue that occur after spinal cord injury (SCI). Thirty-four subjects underwent soleus fatigue testing with a modified Burke electrical stimulation fatigue protocol. The between-day reliability of this protocol was high (intraclass correlation, 0.96). We fit the fatigue index (FI) data to a quadratic-linear segmental polynomial model. FI declined rapidly (0.3854 per year) for the first 1.7 years, and more slowly (0.01 per year) thereafter. The rapid decline of FI immediately after SCI implies that a "window of opportunity" exists for the clinician if the goal is to prevent these changes. Understanding the timing of change in muscle endurance properties (and, therefore, load-generating capacity) after SCI may assist clinicians when developing therapeutic interventions to maintain musculoskeletal integrity.     

Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerve system of humans

The effects of skin pressure applied to one side of the waist on sudomotor and vasoconstrictor nerve activity were compared with the effects on sweating and cutaneous blood flow in humans. The sweat rate and cutaneous blood flow were measured on left and right dorsal feet. Skin sympathetic nerve activity (SSNA) was recorded by microneurography from a microelectrode inserted in left and right peroneal nerves. Skin pressure was applied in a supine position to the area over the left or right anterior superior iliac spine under warm (T(a): 30-36 degrees C) and cool (T(a): 19-23 degrees C) conditions. Sudomotor and vasoconstrictor bursts were identified for quantitative analysis. The skin pressure increased the contralateral/ipsilateral ratio of the sweat rate. It also increased the contralateral/ipsilateral ratio of the cutaneous blood flow and the contralateral/ipsilateral ratio of the sudomotor burst amplitude. However, skin pressure did not induce any significant changes in the contralateral/ipsilateral ratio of the vasoconstrictor burst amplitude. The results indicate that an asymmetrical reflex effect of skin pressure on vasoconstrictor nerve activity was absent, suggesting that, whereas the ipsilateral suppression of sweating elicited by skin pressure was mediated by the sudomotor nerve system, the ipsilateral suppression of cutaneous blood flow was not mediated by the vasoconstrictor nerve system. Thus, the occurrence of the spinal reflex due to skin pressure is not uniform between the sudomotor and the vasoconstrictor nerve systems, which represent different organizations at the level of spinal cord.     

Flexor reflex decreases during sympathetic stimulation in chronic human spinal cord injury

A better understanding of autonomic influence on motor reflex pathways in spinal cord injury is important to the clinical management of autonomic dysreflexia and spasticity in spinal cord injured patients. The purpose of this study was to examine the modulation of flexor reflex windup during episodes of induced sympathetic activity in chronic human spinal cord injury (SCI). We simultaneously measured peripheral vascular conductance and the windup of the flexor reflex in response to conditioning stimuli of electrocutaneous stimulation to the opposite leg and bladder percussion. Flexor reflexes were quantified using torque measurements of the response to a noxious electrical stimulus applied to the skin of the medial arch of the foot. Both bladder percussion and skin conditioning stimuli produced a reduction (43–67%) in the ankle and hip flexor torques (p < 0.05) of the flexor reflex. This reduction was accompanied by a simultaneous reduction in vascular conductance, measured using venous plethysmography, with a time course that matched the flexor reflex depression. While there was an overall attenuation of the flexor reflex, windup of the flexor reflex to repeated stimuli was maintained during periods of increased sympathetic activity. This paradoxical depression of flexor reflexes and minimal effect on windup is consistent with inhibition of afferent feedback within the superficial dorsal horn. The results of this study bring attention to the possible interaction of motor and sympathetic reflexes in SCI above and below the T5 spinal level, and have implications for clinicians in spasticity management and for researchers investigating motor reflexes post SCI.     

Electrodiagnostic investigation of motor neuron and spinal reflex arch (H-reflex) in spinal cord injury

Twenty patients with spinal cord injury underwent serial electromyographic examinations. Fibrillation potentials and positive waves were noted in six patients in the spinal shock phase. In another subject, these potentials were found 27 months after injury. Our finding of significant slowing in the NCV of both nerves, indicates that lower motor neurons are indeed affected by upper motor neuron lesions. The H-reflex studies showed an increase in the mean H/M ratio. This may indicate an increase of reflex motor neuron excitability. No clear correlation was found between this increase and the degree of clinical spasticity. With repeat investigations, after a period of physical activity, a trend to reduction of the H/M ratio was noted with no clinical confirmation of reduction in spasticity. These findings emphasise the need for not assigning diagnostic terms to EMC abnormalities, but rather identifying them as neurophysiological changes which must be interpreted in the light of the clinical picture.     

Impaired immune responses following spinal cord injury lead to reduced ability to control viral infection

Spinal cord injuries disrupt central autonomic pathways that regulate immune function, and increasing evidence suggests that this may cause deficiencies in immune responses in people with spinal cord injuries. Here we analyze the consequences of spinal cord injury (SCI) on immune responses following experimental viral infection of mice. Female C57BL/6 mice received complete crush injuries at either thoracic level 3 (T3) or 9 (T9), and 1 week post-injury, injured mice and un-injured controls were infected with different dosages of mouse hepatitis virus (MHV, a positive-strand RNA virus). Following MHV infection, T3- and T9-injured mice exhibited increased mortality in comparison to un-injured and laminectomy controls. Infection at all dosages resulted in significantly higher viral titer in both T3- and T9-injured mice compared to un-injured controls. Investigation of anti-viral immune responses revealed impairment of cellular infiltration and effector functions in mice with SCI. Specifically, cell-mediated responses were diminished in T3-injured mice, as seen by reduction in virus-specific CD4⁺ T lymphocyte proliferation and IFN-γ production and decreased numbers of activated antigen presenting cells compared to infected un-injured mice. Collectively, these data indicate that the inability to control viral replication following SCI is not level dependent and that increased susceptibility to infection is due to suppression of both innate and adaptive immune responses.     

Limb segment vibration modulates spinal reflex excitability and muscle mRNA expression after spinal cord injury

ObjectiveWe investigated the effect of various doses of vertical oscillation (vibration) on soleus H-reflex amplitude and post-activation depression in individuals with and without SCI. We also explored the acute effect of short-term limb vibration on skeletal muscle mRNA expression of genes associated with spinal plasticity.MethodsSix healthy adults and five chronic complete SCI subjects received vibratory stimulation of their tibia over three different gravitational accelerations (0.3g, 0.6g, and 1.2g) at a fixed frequency (30 Hz). Soleus H-reflexes were measured before, during, and after vibration. Two additional chronic complete SCI subjects had soleus muscle biopsies 3 h following a single bout of vibration.ResultsH-reflex amplitude was depressed over 83% in both groups during vibration. This vibratory-induced inhibition lasted over 2 min in the control group, but not in the SCI group. Post-activation depression was modulated during the long-lasting vibratory inhibition. A single bout of mechanical oscillation altered mRNA expression from selected genes associated with synaptic plasticity.ConclusionsVibration of the lower leg inhibits the H-reflex amplitude, influences post-activation depression, and alters skeletal muscle mRNA expression of genes associated with synaptic plasticity.SignificanceLimb segment vibration may offer a long term method to reduce spinal reflex excitability after SCI.