Degenerative cervical myelopathy delays responses to lateral balance perturbations regardless of predictability.

The aim of this study was to quantify balance impairments in standing in people with degenerative cervical myelopathy (PwDCM) in response to external perturbations. PwDCM have damage to their spinal cord due to degeneration of the cervical vertebral column, but little is known about balance. Balance was quantified by capturing kinetics, kinematic, and electromyographic data during standing in response to lateral waist pulls. Participants received pulls during predictable and unpredictable contexts in three stance widths at two magnitudes. In response to lateral waist pulls, PwDCM had larger center of mass excursion (P < 0.001) and delayed gluteus medius electromyography onset (P < 0.001) and peak (P < 0.001) timing. These main effects of history of myelopathy were consistent across predictability, stance width, and magnitude. A multilinear regression determined that gluteus medius peak timing + tibialis anterior peak timing most strongly predicted center of mass excursion (R2 = 0.50, P < 0.001). These data suggest that PwDCM have delays in generating voluntary and reactive motor commands, contributing to balance impairments. Future rehabilitation strategies should focus on generating rapid muscular contractions. Additionally, frontal plane postural control is regulated by the gluteus medius and the tibialis anterior, whereas other muscles (e.g. gluteus minimus, ankle invertors/evertors) not studied here may also contribute.NEW & NOTEWORTHY Frontal plane reactive postural control is impaired in persons with degenerative cervical myelopathy because of delayed muscle responses. Additionally, postural control varies across stance width, predictability, and perturbation magnitude.

Diffusion tensor imaging and tractography in Brown-Sequard syndrome.

STUDY DESIGN: Case report. OBJECTIVE: To demonstrate the utility of diffusion tensor imaging and tractography in two patients with Brown-Sequard syndrome after penetrating cervical cord injury. SETTING: Milwaukee, WI, USA. METHODS: Two patients, who presented with features of Brown-Sequard syndrome after sustaining stab wounds to the neck, underwent DTI and tractography of the cervical cord within a week of the injury. DTI metrics were measured within the left and right hemicord around the level of injury. Diffusion tensor tractography was performed to visualize the site of injury and injured fiber tracts. RESULTS: Axial fractional anisotropy maps at the site of injury showed unilateral damage to the cord structure, and FA was significantly reduced within the injured hemicord in both patients. Tractography allowed for visualization of the injured fiber tracts around the level of injury. Both DTI metrics and tractography showed an asymmetry that corresponded to the neurological deficits exhibited by the patients. CONCLUSION: This report illustrates the utility of DTI and DTT in delineating regions of cord injury in two patients with traumatic Brown-Sequard syndrome. Our results indicate that DTI provides clinically relevant information that supplements conventional MR imaging for patients with acute SCI.

Diffusion tensor MR imaging in chronic spinal cord injury.

BACKGROUND AND PURPOSE: Diffusion tensor MR imaging is emerging as an important tool for displaying anatomic changes in the brain after injury or disease but has been less widely applied to disorders of the spinal cord. The aim of this study was to characterize the diffusion properties of the entire human spinal cord in vivo during the chronic stages of spinal cord injury (SCI). These data provide insight into the structural changes that occur as a result of long-term recovery from spinal trauma. MATERIALS AND METHODS: Thirteen neurologically intact subjects and 10 subjects with chronic SCI (>4 years postinjury) were enrolled in this study. A single-shot twice-refocused spin-echo diffusion-weighted echo-planar imaging pulse sequence was used to obtain axial images throughout the entire spinal cord (C1-L1) in <60 minutes. RESULTS: Despite heterogeneity in SCI lesion severity and location, diffusion characteristics of the chronic lesion were significantly elevated compared with those of uninjured controls. Fractional anisotropy was significantly lower at the chronic lesion and appeared dependent on the completeness of the injury. Conversely, mean diffusivity measurements in the upper cervical spinal cord in subjects with SCI were significantly lower than those in controls. These trends suggest that the entire neuraxis may be affected by long-term recovery from spinal trauma. CONCLUSION: These results suggest that diffusion tensor imaging may be useful in the assessment of SCI recovery.

Diffusion tensor MR imaging of the neurologically intact human spinal cord.

BACKGROUND AND PURPOSE: The aim of this study was to characterize the diffusion properties of the entire human spinal cord in vivo. These data are essential for comparisons to pathologic conditions as well as for comparisons of different pulse sequence design parameters aimed to reduce scan time and more accurately determine diffusion coefficients. MATERIALS AND METHODS: A total of 13 neurologically intact subjects were enrolled in this study. A single-shot, twice-refocused, spin-echo, diffusion-weighted, echo-planar imaging (EPI) pulse sequence was used to obtain axial images throughout the entire spinal cord (C1-L1) in 45 minutes. RESULTS: Diffusion images indicated slight geometric distortions; however, gray and white matter contrast was observed. All measurements varied across the length of the cord. Whole cord diffusion coefficients averaged 0.5-1.3 x 10(-3) mm(2)/s depending on orientation, mean diffusivity (MD) averaged 0.83 +/- 0.06 x 10(-3) mm(2)/s, fractional anisotropy (FA) averaged 0.49 +/- 0.05, and volume ratio (VR) averaged 0.73 +/- 0.05. CONCLUSION: This study provided normative diffusion values for the entire spinal cord for use in comparisons with pathologic conditions as well as improvements in pulse sequence design.

Contribution of muscle afferents to prolonged flexion withdrawal reflexes in human spinal cord injury.

The contribution of force-sensitive muscular afferents to prolonged flexion withdrawal reflexes, or flexor spasms, after human spinal cord injury (SCI) was investigated. In three separate experimental conditions, flexion reflexes were triggered in subjects with SCI using trains of electrocutaneous stimuli delivered at the foot and lower leg and compared with reflexes elicited via intramuscular (i.m.) electrical stimuli. In the first experiment, flexion reflexes were elicited using i.m. stimuli to the tibialis anterior (TA) in the majority of subjects tested. The ratio of peak isometric ankle to hip torques during i.m.-triggered reflexes were proportionally similar to those evoked by electrocutaneous foot or shank stimulation, although the latency to onset and peak flexion torques were significantly longer with i.m. stimulation. In the second experiments, the amplitude and frequency of i.m. TA stimulation were varied to alter the stimulus-induced muscle torque. Peak ankle and hip torques generated during the flexion reflex responses were correlated to a greater extent with stimulus-induced muscle torques as compared with the modulated stimulus parameters. In the third experimental series, i.m. stimuli delivered to the gastrocnemius (GS) elicited flexion reflexes in approximately half of the subjects tested. The combined data indicate a potentially prominent role of the stimulus-induced muscle contraction to the magnitude and latency of flexor reflex behaviors after i.m. TA stimulation. Results after i.m. GS stimulation indicate multi-joint flexion reflexes can also be elicited, although to a lesser extent than i.m. TA stimulation.

Quantification of morphological changes in the spinal cord in chronic spinal cord injury using magnetic resonance imaging.

Following spinal cord injury (SCI), morphological changes in the spinal cord are observed at the clinically diagnosed level of injury, as well as at segmental levels above and below the injury site due to axonal degeneration. In order to quantify the extent of morphological changes, a three dimensional segmentation of the spinal cord was constructed using magnetic resonance images (MRI) of the cervical spinal cord. Six neurologically intact (NI) and five spinal cord injured (SCI) subjects were scanned using an axial, T2 weighted fluid-attenuated inversion recovery (FLAIR) sequence. The boundaries of the spinal cord volume were then identified using a three-dimensional, seeded region growing technique. The area of 4 slices approximating the C3 segment were measured and the mean area was calculated for each subject. In NI subjects the mean C3 cord area was 75.2 +/- 11 mm(2). In contrast, SC subjects had a mean C3 cord area of 60.4 +/- 7.3 mm(2). This 20% decrease in area for the SCI subjects, compared to the NI subjects, was statistically significant (t-test, p<0.05). These results show that the narrowing of the spinal cord after SCI is measurable using MRI.

Windup of flexion reflexes in chronic human spinal cord injury: a marker for neuronal plateau potentials?

The physiological basis of flexion spasms in individuals after spinal cord injury (SCI) may involve alterations in the properties of spinal neurons in the flexion reflex pathways. We hypothesize that these changes would be manifested as progressive increases in reflex response with repetitive stimulus application (i.e., "windup") of the flexion reflexes. We investigated the windup of flexion reflex responses in 12 individuals with complete chronic SCI. Flexion reflexes were triggered using trains of electrical stimulation of plantar skin at variable intensities and inter-stimulus intervals. For threshold and suprathreshold stimulation, windup of both peak ankle and hip flexion torques and of integrated tibialis anterior electromyographic activity was observed consistently in all patients at inter-stimulus intervals < or =3 s. For subthreshold stimuli, facilitation of reflexes occurred only at intervals < or =1 s. Similarly, the latency of flexion reflexes decreased significantly at intervals < or =1 s. Patients that were receiving anti-spasticity medications (e.g., baclofen) had surprisingly larger windup of reflex responses than those who did not take such medications, although this difference may be related to differences of spasm frequency between the groups of subjects. The results indicate that the increase in spinal neuronal excitability following a train of electrical stimuli lasts for < or =3 s, similar to previous studies of nociceptive processing. Such long-lasting increases in flexion reflex responses suggest that cellular mechanisms such as plateau potentials in spinal motoneurons, interneurons, or both, may partially mediate spinal cord hyperexcitability in the absence of descending modulatory input.

Identification of static and dynamic components of reflex sensitivity in spastic elbow flexors using a muscle activation model.

Static and dynamic components of the stretch reflex were studied in elbow flexors of 13 hemiparetic brain-injured individuals. Constant-velocity joint rotations were applied to the elbow, and the resulting stretch reflex torque and electromyographic responses were recorded in the biceps brachii and brachioradialis muscles. Ten elbow extension velocities between 6 and 150 deg s(-1) were applied in random order. The resulting reflex torque response was plotted as a function of elbow angle and fitted with a mathematical model designed to depict elbow flexor activation. We found that four of the six model parameters were essentially independent of test velocity. Conversely, 73% (19/26) of cases involving the other two model parameters were dependent on velocity of joint extension (p<0.05). We conclude from these results that four of the model parameters reflect the static reflex response while the two remaining velocity-dependent parameters reflect the dynamic reflex response. To describe overall velocity dependence of stretch reflexes in spastic elbow muscles, the two dynamic reflex parameters were fitted to a fractional exponential function of velocity, similar to a model previously used to describe spindle firing rate in the cat hindlimb. We found that the mean velocity exponent of the dynamic reflex parameters was 0.24 + 0.17 (s.d.) (N = 13), a value similar to that for muscle spindle velocity sensitivity in reduced animal preparations. We conclude that both static and dynamic reflex sensitivities can be measured by examining different aspects of the torque/angle relation associated with the reflex response to a large-amplitude ramp stretch of the elbow.

Effect of muscle biomechanics on the quantification of spasticity.

The impact of muscle biomechanics on spasticity was assessed by comparison of the reflex responses of the elbow and metacarpophalangeal (MCP) flexor muscles in individuals with chronic spastic hemiplegia following stroke. Specifically, methods were developed to quantify reflex responses and to normalize these responses for comparison across different muscle groups. Stretch reflexes were elicited in the muscles of interest by constant velocity ramp-and-hold stretches at the corresponding joint. The muscles were initially passive, with the joint placed in a midrange position. Estimates of biomechanical parameters were used to convert measured reflex joint torque and joint angle into composite flexor muscle stress and stretch. We found that the stretch reflex response for the MCP muscle group had a 74% greater mean stiffness modulus than that for the elbow muscle group, and that the reflex threshold was initiated at an 80% shorter mean muscle stretch. However, we determined that initial normalized fiber length was significantly greater for the experiments involving the MCP muscles than for those involving the elbow muscles. Increasing the initial composite fiber length of the elbow flexors produced significant reduction of the reflex threshold (p<0.001), while decreasing the initial length of the MCP flexors significantly reduced their measured reflex stiffness (p<0.001). Thus, biomechanical parameters of muscle do appear to have an important effect on the stretch reflex in individuals with impairment following stroke, and this effect should be accounted for when attempting to quantify spasticity.

Mechanical measures of spasticity in stroke.

Mechanical measurements of stretch reflexes show promise for the quantification of spasticity after stroke. Mechanical measurements can increase the objectivity, repeatability, and precision of spasticity quantification and provide additional insight into the neuropathology that is not available with current clinical measurements. Several techniques are reviewed and the advantages and disadvantages of quantification of spasticity using mechanical measurements are considered. Although mechanical measures of spasticity offer many advantages, much research needs to be done to establish a standard measurement of spasticity that can be easily implemented in the clinic.

Flexor reflexes in chronic spinal cord injury triggered by imposed ankle rotation.

Hypersensitivity of the flexor reflexes to input from force-sensitive muscle afferents may contribute to the prevalence and severity of muscle spasms in patients with spinal cord injuries. In the present study, we triggered flexor reflexes with constant-velocity ankle movements into end-range dorsiflexion and plantarflexion positions in 8 individuals with spinal cord injuries. We found that all 8 subjects had coordinated increases in flexion torque at the hip and ankle following externally imposed plantarflexion movements at the ankle. In addition, end-range dorsiflexion movements also triggered flexor reflexes in 3 subjects, although greater loads were required to trigger such reflexes using dorsiflexion movements (compared to plantarflexion movements). These three-joint reflex torque patterns triggered by ankle movement were broadly comparable to flexion withdrawal responses elicited by electrocutaneous stimuli applied to a toe, although the amplitude of the torque response was generally lower. We conclude that excitation of muscle and joint-related afferents induced by end-range movements may be responsible for exaggerated flexion reflex responses in spinal cord injury.

Stretch reflex adaptation in elbow flexors during repeated passive movements in unilateral brain-injured patients.

OBJECTIVE: To evaluate the effects of repeated, externally imposed, flexion-extension movements of the elbow on the resulting stretch reflex response in hemiparetic spastic brain-injured patients. These effects were compared within a recording session and across sessions for the same subject to determine the impact of movement history on the quantification of spastic hypertonia using the stretch reflex response. DESIGN: Twenty to 30 sequential, constant velocity flexion-extension movements were applied to the impaired elbow of our cohort, with a 10-second hold interposed between flexion and extension. Movements were applied regularly at 1-minute intervals. Changes in stretch reflex responses were monitored during the applied movements. PARTICIPANTS: We examined a convenience sample of seven hemiparetic brain-injured subjects between the ages of 26 and 60 yrs, with moderate-to-severe spastic hypertonia of elbow muscles (Ashworth score 2-4/4). Subjects participated in 2 to 9 sessions. MEASURES: Elbow torque, position, velocity, and electromyograms of the biceps, brachioradialis, and triceps muscles were recorded for each flexion and extension movement. Stretch reflex torque was calculated by subtracting passive torque from total elbow torque, recorded over large amplitude movements. A linear regression analysis quantified both the initial torque response of the stretch reflex and the ensuing adaptation of the stretch reflex during sequential movements. Intersession variability was characterized both for spastic hypertonia measures and for stretch reflex adaptation. RESULTS: Repeated, externally imposed, sequential flexion-extension movements of the elbow decreased the elbow flexor stretch reflex in six of seven subjects. The mean reduction in reflex torque after 30 movements was 50% of the initial torque values (p = .001, t test vs. 0% change). Intersession stretch reflex responses for each subject were found to vary greatly (SDs of reflex torque ranged from 0.1 to 4.0 Nm), and there were also significant variations in the degree of adaptation between subjects. CONCLUSIONS: Stretch reflex adaptation must be taken into consideration when spastic hypertonia is quantified using repeated joint motion, as is often the case. The magnitude of intersession variation in spastic hypertonia measures suggests that ideally, such measurements should be made across multiple sessions before conclusions are made regarding the efficacy of spastic hypertonia interventions. This study provides quantitative evidence that repeated joint movements may have a significant short-term beneficial effect on spastic hypertonia.

Understanding and treating arm movement impairment after chronic brain injury: progress with the ARM guide.

Significant potential exists for enhancing physical rehabilitation following neurologic injury through the use of robotic and mechatronic devices (or "rehabilitators"). We review the development of a rehabilitator (the "ARM Guide") to diagnose and treat arm movement impairment following stroke and other brain injuries. As a diagnostic tool, the ARM Guide provides a basis for evaluation of several key motor impairments, including abnormal tone, incoordination, and weakness. As a therapeutic tool, the device provides a means to implement and evaluate active assist therapy for the arm. Initial results with three stroke subjects demonstrate that such therapy can produce quantifiable benefits in the chronic hemiparetic arm. Directions for future research regarding the efficacy and practicality of rehabilitators are discussed.

The effects of epimysial electrode location on phrenic nerve recruitment and the relation between tidal volume and interpulse interval.

Electrode location is of vital importance to diaphragm pacing devices using electrodes implanted on the diaphragm. Complete phrenic nerve recruitment with a single epimysial electrode implanted on the abdominal surface of the diaphragm required placement within 1 cm of the motor point. Recruitment could be increased further using multiple electrodes, provided the electrodes were implanted on opposite sides of the phrenic nerve motor point. The location of the implanted electrode relative to the phrenic nerve motor point also affected the relation between the stimulus interpulse interval (IPI) and the measured tidal volume. Specifically, we found that electrodes implanted lateral to the phrenic nerve motor point had different tidal volume--IPI relations than electrodes placed anterior or posterior to the motor point. We concluded that properly placed epimysial electrodes are required to obtain adequate phrenic nerve recruitment for full time ventilation and knowledge of the relative location of the electrode with respect to motor point is necessary to predict the tidal volume produced by a specific IPI.

An implantable impedance pneumograph monitor for detection of diaphragm contraction and airway obstruction during diaphragm pacing.

Impedance pneumography signals were characterised during diaphragm pacing using stimulating and recording electrodes placed on the abdominal surface of the diaphragm. These measurements were useful for the detection of muscle contraction without confounding effects from stimulus artifacts. Impedance pneumography signals were measured using 23 epimysial electrodes implanted in seven dogs with 1-5 experiments on each electrode. The polarity of the change in impedance associated with diaphragm pacing differed for each recording electrode and its configuration. Thirty-four of 57 cases produced increased impedance, 11 produced decreased impedance and the remaining 12 depended on the level of diaphragm activation. Impedance pneumography signals were useful for detecting complete airway obstruction. The mean difference between the impedance measured during open and obstructed airway conditions was 80% of the open airway impedance signal. The difference between open and obstructed airway impedance measurements was a mean of 2.3 times larger with a recording electrode on the same hemidiaphragm as the stimulating electrode, compared to an electrode placed on the opposite hemidiaphragm (p < 0.05, paired t test, four dogs). In addition, the differences between open and completely obstructed airways were a mean of 2.8 times larger when the second recording electrode was placed on the thorax at the fifth intercostal space, compared to the ninth intercostal space (p < 0.05, two-factor ANOVA, one dog, two replicates). It was concluded that impedance pneumograph circuitry could be incorporated into an existing diaphragm pacer using electrodes placed on the diaphragm to provide valuable measurements of the function of the device.

Assessment of active and passive restraint during guided reaching after chronic brain injury.

We report the use of a mechatronic device for assessing arm movement impairment after chronic brain injury. The device, called the "Assisted Rehabilitation and Measurement Guide," is designed to guide reaching movements across the workspace, to measure movement and force generation, and to apply controlled forces to the arm along linear reaching paths. We performed a series of experiments using the device in order to identify the contribution of active muscle and passive tissue restraint to decreased active range of motion of guided reaching (i.e., "workspace deficits") in a group of five chronic, spastic hemiparetic, brain-injured subjects. Our findings were that passive tissue restraint was increased in the spastic arms, as compared to the contralateral, nonparetic arms. Active muscle restraint, on the other hand, was typically comparable in the two arms, as quantified by measurements of active arm stiffness at the workspace boundary during reaching. In all subjects, there was evidence of movement-generated weakness, consistent with a small contribution of spasticity to workspace deficits. These results demonstrate the feasibility of mechatronic assessment of the causes of decreased functional movement, and could provide a basis for enhanced treatment planning and monitoring following brain injury.

Reflex torque response to movement of the spastic elbow: theoretical analyses and implications for quantification of spasticity.

A parametric model of the human reflex torque response to a large-amplitude, constant angular velocity elbow extension was developed in order to help quantify spasticity in hemiparetic stroke patients, and to better understand its pathophysiology. The model accounted for the routinely observed leveling of torque (i.e., a plateau) at a mean angular increment of 51 degrees +/- 10 degrees s.d. (n = 98) after the initial rise. This torque "plateau" was observed in all eight subjects, and in 98 of 125 trials across 25 experimental sessions. The occurrence of this plateau cannot be explained by decreases in elbow flexor moment arms during elbow extension. Rather, the plateau is attributable to a consistent leveling in muscle activation as confirmed both qualitatively from recordings of rectified, smoothed electromyograph (EMG) activity, and quantitatively using an EMG coefficient model. A parametric model was developed in which the pattern of muscle activation in the stretch reflex response of elbow flexors was described as a cumulative normal distribution with respect to joint angle. Two activation functions, one related to biceps and the other to brachioradialis/brachialis, were incorporated into the model in order to account for observations of a bimodal angular stiffness profile. The resulting model yielded biologically plausible parameters of the stretch reflex response which may prove useful for quantifying spasticity. In addition, the model parameters had clear pathophysiological analogs, which may help us understand the nature of the stretch reflex response in spastic muscles.

Mechatronic assessment of arm impairment after chronic brain injury.

Significant potential exists for mechatronic devices to improve assessment and treatment of individuals with a movement disability following stroke, traumatic brain injury, or cerebral palsy. We report the use of a mechatronic device for evaluation of the arm after chronic brain injury. We performed a series of experiments with the device in order to identify the relative contribution of three different motor impairments to decreased active range of motion of reaching in five brain-injured subjects. Our findings were that passive tissue restraint and agonist weakness, rather than antagonist restraint, were the most common contributors to decreased active range of motion. These results demonstrate the feasibility of objective assessment of functional movement using a mechatronic device, and could provide the basis for improved, individualized treatment planning and monitoring following brain injury.

Laparoscopic placement of electrodes for diaphragm pacing using stimulation to locate the phrenic nerve motor points.

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.

The tissue response to epimysial electrodes for diaphragm pacing in dogs.

Epimysial electrodes stapled to the abdominal surface of the diaphragm produced a chronic inflammatory response that appeared to be mediated by mechanical stresses placed on the encapsulation tissue by periodic diaphragm contraction. The tissue response surrounding 34 epimysial electrodes implanted in 11 dogs was studied three months post implant. The tissue response was characterized by a capsule having a mean thickness of 1.24 mm between the electrode and the muscle, while having only a very thin capsule on the back, or abdominal side of the electrode. The tissue response between the electrode and the muscle was comprised of two tissue layers: a layer of granulation tissue and a layer of collagen. The granulation tissue layer contained evidence of acute inflammatory processes including the presence of polymorphonuclear leukocytes in 68% of the samples. Granulation layer thickness was inversely correlated with back encapsulation indicating a reduction in granulation tissue for mechanically stabilized electrodes. In addition, encapsulation tissue surrounding the granulation layer was comprised of collagen fibers with an oblique orientation and an extraperitoneal locale suggesting mechanical load transfers between the electrode and the surrounding tissue. As a result, the histological response to epimysial electrodes implanted on the diaphragm suggests that mechanical loading, induced by movement associated with the contraction of adjacent muscle, must be a consideration for devices that employ epimysial electrodes.