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 \u3c 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

Parallel Facilitatory Reflex Pathways from the Foot and Hip to Flexors and Extensors in the Injured Human Spinal Cord

Spinal integration of sensory signals associated with hip position, muscle loading, and cutaneous sensation of the foot contributes to movement regulation. The exact interactive effects of these sensory signals under controlled dynamic conditions are unknown. The purpose of the present study was to establish the effects of combined plantar cutaneous afferent excitation and hip movement on the Hoffmann (H) and flexion reflexes in people with a spinal cord injury (SCI). The flexion and H-reflexes were elicited through stimulation of the right sural (at non-nociceptive levels) and posterior tibial nerves respectively. Reflex responses were recorded from the ipsilateral tibialis anterior (TA) (flexion reflex) and soleus (H-reflex) muscles. The plantar cutaneous afferents were stimulated at three times the perceptual threshold (200 Hz, 24-ms pulse train) at conditioning–test intervals that ranged from 3 to 90 ms. Sinusoidal movements were imposed to the right hip joint at 0.2 Hz with subjects supine. Control and conditioned reflexes were recorded as the hip moved in flexion and extension. Leg muscle activity and sagittal-plane joint torques were recorded. We found that excitation of plantar cutaneous afferents facilitated the soleus H-reflex and the long latency flexion reflex during hip extension. In contrast, the short latency flexion reflex was depressed by plantar cutaneous stimulation during hip flexion. Oscillatory joint forces were present during the transition phase of the hip movement from flexion to extension when stimuli were delivered during hip flexion. Hip-mediated input interacts with feedback from the foot sole to facilitate extensor and flexor reflex activity during the extension phase of movement. The interactive effects of these sensory signals may be a feature of impaired gait, but when they are appropriately excited, they may contribute to locomotion recovery in these patients

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

Objective: To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke. Design: Double-blind, randomized, placebo-controlled crossover trial. Setting: Outpatient research setting. Participants: Individuals (N=10; 7 men; mean age ± SD, 57±10y) with poststroke hemiplegia of \u3e1 year duration who completed all assessments. Interventions: Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions. Main Outcome Measures: Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30°/s–120°/s) plantarflexor stretch reflexes under passive conditions, and separately during and after 3 superimposed maximal volitional drive to simulate conditions of increased serotonin release. Secondary measures included clinical measures of lower limb coordination and locomotion. Results: SSRI administration significantly increased stretch reflex torques at higher stretch velocities (eg, 90°/s; P=.03), with reflexes at lower velocities enhanced by superimposed voluntary drive (P=.02). No significant improvements were seen in volitional peak torques or in clinical measures of lower limb function (lowest P=.10). Conclusions: Increases in spasticity but not strength or lower limb function were observed with single-dose SSRI administration in individuals with chronic stroke. Further studies should evaluate whether repeated dosing of SSRIs, or as combined with specific interventions, is required to elicit significant benefit of these agents on lower limb function poststroke

\u3cem\u3eEx Vivo\u3c/em\u3e Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

The aim of this study was to characterize magnetic resonance diffusion tensor imaging (DTI) in proximal regions of the spinal cord following a thoracic spinal cord injury (SCI). Sprague–Dawley rats (n = 40) were administered a control, mild, moderate, or severe contusion injury at the T8 vertebral level. Six direction diffusion weighted images (DWIs) were collected ex vivo along the length of the spinal cord, with an echo/repetition time of 31.6 ms/14 sec and b = 500 sec/mm2. Diffusion metrics were correlated to hindlimb motor function. Significant differences were found for whole cord region of interest (ROI) drawings for fractional anisotropy (FA), mean diffusivity (MD), longitudinal diffusion coefficient (LD), and radial diffusion coefficient (RD) at each of the cervical levels ( p \u3c 0.01). Motor function correlated with MD in the cervical segments of the spinal cord (r2 = 0.80). The diffusivity of water significantly decreased throughout ‘‘uninjured’’ portions of the spinal cord following a contusion injury ( p \u3c 0.05). Diffusivity metrics were found to be altered following SCI in both white and gray matter regions. Injury severity was associated with diffusion changes over the entire length of the cord. This study demonstrates that DTI is sensitive to SCI in regions remote from injury, suggesting that the diffusion metrics may be used as a biomarker for severity of injury

Using Swing Resistance and Assistance to Improve Gait Symmetry in Individuals Post-Stroke

A major characteristic of hemiplegic gait observed in individuals post-stroke is spatial and temporal asymmetry, which may increase energy expenditure and the risk of falls. The purpose of this study was to examine the effects of swing resistance/assistance applied to the affected leg on gait symmetry in individuals post-stroke. We recruited 10 subjects with chronic stroke who demonstrated a shorter step length with their affected leg in comparison to the non-affected leg during walking. They participated in two test sessions for swing resistance and swing assistance, respectively. During the adaptation period, subjects counteracted the step length deviation caused by the applied swing resistance force, resulting in an aftereffect consisting of improved step length symmetry during the post-adaptation period. In contrast, subjects did not counteract step length deviation caused by swing assistance during adaptation period and produced no aftereffect during the post-adaptation period. Locomotor training with swing resistance applied to the affected leg may improve step length symmetry through error-based learning. Swing assistance reduces errors in step length during stepping; however, it is unclear whether this approach would improve step length symmetry. Results from this study may be used to develop training paradigms for improving gait symmetry of stroke survivors

Leg Sympathetic Response to Noxious Skin Stimuli is Similar in High and Low Level Human Spinal Cord Injury

Objective To determine if sympathetically mediated vasoconstriction in the lower extremities is injury level dependent. Although sympathetic responses have been measured in the limbs of people with high and low level SCI using blood flow measurements, including Doppler ultrasound and venous plethysmography, a direct comparison between injury levels has not been made. Methods Volunteers with chronic SCI were grouped according to injury level. Above T6: high level (HL, n = 7), and T6 and below: low level (LL, n = 6). All subjects had complete motor and sensory loss. Leg arterial flows were recorded by venous occlusion plethysmography, and continuous heart rate and mean arterial pressure (MAP) were measured. The conditioning stimulus consisted of transcutaneous stimulation to the arch of the contralateral foot. Results HL and LL subjects demonstrated a significant decrease in arterial conductance during stimulation with no significant difference found between groups. As expected, only group HL demonstrated a significant increase in MAP. Conclusions These results support our hypothesis that local (leg) sympathetic responses are similar for both high and low level SCI. Significance While low level SCI does not typically present with autonomic dysreflexia, bouts of increased reflex sympathetic activity could have ramifications for metabolism as well as renal and motor system functio

Effects of Wrist Tendon Vibration on Targeted Upper-Arm Movements in Poststroke Hemiparesis

Background. Impaired motor control of the upper extremity after stroke may be related to lost sensory, motor, and integrative functions of the brain. Artificial activation of sensory afferents might improve control of movement by adding excitatory drive to sensorimotor control structures. The authors evaluated the effect of wrist tendon vibration (TV) on paretic upper-arm stability during point-to-point planar movements. Methods. TV (70 Hz) was applied to the forearm wrist musculature of 10 hemiparetic stroke patients as they made center-out planar arm movements. End-point stability, muscle activity, and grip pressure were compared as patients stabilized at the target position for trials completed before, during, and after the application of the vibratory stimulus. Results. Prior to vibration, hand position fluctuated as participants attempted to maintain the hand at the target after movement termination. TV improved arm stability, as evidenced by decreased magnitude of hand tangential velocity at the target. Improved stability was accompanied by a decrease in muscle activity throughout the arm as well as a mean decrease in grip pressure. Conclusions. These results suggest that vibratory stimulation of the distal wrist musculature enhances stability of the proximal arm and can be studied further as a mode for improving end-point stability during reaching in hemiparetic patients

Pre- and Post-alpha Motoneuronal Control of the Soleus H-reflex during Sinusoidal Hip Movements in Human Spinal Cord Injury

The aim of this study was to establish the contribution of hip-mediated sensory feedback to spinal interneuronal circuits during dynamic conditions in people with incomplete spinal cord injury (SCI). Specifically, we investigated the effects of synergistic and antagonistic group I afferents on the soleus H-reflex during imposed sinusoidal hip movements. The soleus H-reflex was conditioned by stimulating the common peroneal nerve (CPN) at short (2, 3, and 4 ms) and long (80, 100, and 120 ms) conditioning test (C-T) intervals to assess the reciprocal and pre-synaptic inhibition of the soleus H-reflex, respectively. The soleus H-reflex was also conditioned by medial gastrocnemius (MG) nerve stimulation at C-T intervals ranging from 4 to 7 ms to assess changes in autogenic Ib inhibition during hip movement. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by the Biodex system while subjects were supine. The effects of sinusoidal hip movement on five leg muscles along with hip, knee, and ankle joint torques were also established during sensorimotor conditioning of the reflex. Phase-dependent modulation of antagonistic and synergistic muscle afferents was present during hip movement, with the reciprocal, pre-synaptic, and Ib inhibition to be significantly reduced during hip extension and reinforced during hip flexion. Reflexive muscle and joint torque responses – induced by the hip movement – were entrained to specific phases of hip movement. This study provides evidence that hip-mediated input acts as a controlling signal of pre- and post-alpha motoneuronal control of the soleus H-reflex. The expression of these spinal interneuronal circuits during imposed sinusoidal hip movements is discussed with respect to motor recovery in humans after SCI

White Matter Structural Connectivity is Associated with Sensorimotor Function in Stroke Survivors

Purpose Diffusion tensor imaging (DTI) provides functionally relevant information about white matter structure. Local anatomical connectivity information combined with fractional anisotropy (FA) and mean diffusivity (MD) may predict functional outcomes in stroke survivors. Imaging methods for predicting functional outcomes in stroke survivors are not well established. This work uses DTI to objectively assess the effects of a stroke lesion on white matter structure and sensorimotor function. Methods A voxel-based approach is introduced to assess a stroke lesion\u27s global impact on motor function. Anatomical T1-weighted and diffusion tensor images of the brain were acquired for nineteen subjects (10 post-stroke and 9 age-matched controls). A manually selected volume of interest was used to alleviate the effects of stroke lesions on image registration. Images from all subjects were registered to the images of the control subject that was anatomically closest to Talairach space. Each subject\u27s transformed image was uniformly seeded for DTI tractography. Each seed was inversely transformed into the individual subject space, where DTI tractography was conducted and then the results were transformed back to the reference space. A voxel-wise connectivity matrix was constructed from the fibers, which was then used to calculate the number of directly and indirectly connected neighbors of each voxel. A novel voxel-wise indirect structural connectivity (VISC) index was computed as the average number of direct connections to a voxel\u27s indirect neighbors. Voxel-based analyses (VBA) were performed to compare VISC, FA, and MD for the detection of lesion-induced changes in sensorimotor function. For each voxel, a t-value was computed from the differences between each stroke brain and the 9 controls. A series of linear regressions was performed between Fugl-Meyer (FM) assessment scores of sensorimotor impairment and each DTI metric\u27s log number of voxels that differed from the control group. Results Correlation between the logarithm of the number of significant voxels in the ipsilesional hemisphere and total Fugl-Meyer score was moderate for MD (R2 = 0.512), and greater for VISC (R2 = 0.796) and FA (R2 = 0.674). The slopes of FA (p = 0.0036), VISC (p = 0.0005), and MD (p = 0.0199) versus the total FM score were significant. However, these correlations were driven by the upper extremity motor component of the FM score (VISC: R2 = 0.879) with little influence of the lower extremity motor component (FA: R2 = 0.177). Conclusion The results suggest that a voxel-wise metric based on DTI tractography can predict upper extremity sensorimotor function of stroke survivors, and that supraspinal intraconnectivity may have a less dominant role in lower extremity function

Influence of Visual Feedback On Dynamic Balance Control in Chronic Stroke Survivors

Chronic stroke survivors have an increased incidence of falls during walking, suggesting changes in dynamic balance control post-stroke. Despite this increased incidence of falls during walking, balance control is often studied only in standing. The purpose of this study was to quantify deficits in dynamic balance control during walking, and to evaluate the influence of visual feedback on this control in stroke survivors. Ten individuals with chronic stroke, and ten neurologically intact individuals participated in this study. Walking performance was assessed while participants walked on an instrumented split-belt treadmill with different types of visual feedback. Dynamic balance control was quantified using both the extent of center of mass (COM) movement in the frontal plane over a gait cycle (COM sway), and base of support (step width). Stroke survivors walked with larger COM sway and wider step widths compared to controls. Despite these baseline differences, both groups walked with a similar ratio of step width to COM sway (SW/COM). Providing a stationary target with a laser reference of body movement reduced COM sway only in the stroke group, indicating that visual feedback of sway alters dynamic balance control post-stroke. These results demonstrate that stroke survivors attempt to maintain a similar ratio of step width to COM movement, and visual cues can be used to help control COM movement during walking post-stroke