Targeting bladder function with network-specific epidural stimulation after chronic spinal cord injury.

Profound dysfunctional reorganization of spinal networks and extensive loss of functional continuity after spinal cord injury (SCI) has not precluded individuals from achieving coordinated voluntary activity and gaining multi-systemic autonomic control. Bladder function is enhanced by approaches, such as spinal cord epidural stimulation (scES) that modulates and strengthens spared circuitry, even in cases of clinically complete SCI. It is unknown whether scES parameters specifically configured for modulating the activity of the lower urinary tract (LUT) could improve both bladder storage and emptying. Functional bladder mapping studies, conducted during filling cystometry, identified specific scES parameters that improved bladder compliance, while maintaining stable blood pressure, and enabled the initiation of voiding in seven individuals with motor complete SCI. Using high-resolution magnetic resonance imaging and finite element modeling, specific neuroanatomical structures responsible for modulating bladder function were identified and plotted as heat maps. Data from this pilot clinical trial indicate that scES neuromodulation that targets bladder compliance reduces incidences of urinary incontinence and provides a means for mitigating autonomic dysreflexia associated with bladder distention. The ability to initiate voiding with targeted scES is a key step towards regaining volitional control of LUT function, advancing the application and adaptability of scES for autonomic function.

Heart rate and blood pressure response improve the prediction of orthostatic cardiovascular dysregulation in persons with chronic spinal cord injury.

Unstable blood pressure after spinal cord injury (SCI) is not routinely examined but rather predicted by level and completeness of injury (i.e., American Spinal Injury Association Impairment Scale AIS classification). Our aim was to investigate hemodynamic response to a sit-up test in a large cohort of individuals with chronic SCI to better understand cardiovascular function in this population. Continuous blood pressure and ECG were recorded from individuals with SCI (n = 159) and non-injured individuals (n = 48). We found orthostatic hypotension occurred within each level and AIS classification (n = 36). Moreover, 45 individuals with chronic SCI experienced a drop in blood pressure that did not meet the criteria for orthostatic hypotension, but was accompanied by dramatic increases in heart rate, reflecting orthostatic intolerance. A cluster analysis of hemodynamic response to a seated position identified eight distinct patterns of interaction between blood pressure and heart rate during orthostatic stress indicating varied autonomic responses. Algorithmic cluster analysis of heart rate and blood pressure is more sensitive to diagnosing orthostatic cardiovascular dysregulation. This indicates blood pressure instability cannot be predicted by level and completeness of SCI, and the consensus statement definition of orthostatic hypotension is insufficient to characterize the variability of blood pressure and heart rate responses during orthostatic stress. Both blood pressure and heart rate responses are needed to characterize autonomic function after SCI.

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury.

Spinal cord injury (SCI) results in profound neurologic impairment with widespread deficits in sensorimotor and autonomic systems. Voluntary and autonomic control of bladder function is disrupted resulting in possible detrusor overactivity, low compliance, and uncoordinated bladder and external urethral sphincter contractions impairing storage and/or voiding. Conservative treatments managing neurogenic bladder post-injury, such as oral pharmacotherapy and catheterization, are important components of urological surveillance and clinical care. However, as urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments. Several human and animal studies, including our previously published reports, have documented gains in bladder function due to activity-based recovery strategies, such as locomotor training. Furthermore, epidural stimulation of the spinal cord (scES) combined with intense activity-based recovery training has been shown to produce volitional lower extremity movement, standing, as well as improve the regulation of cardiovascular function. In our center, several participants anecdotally reported improvements in bladder function as a result of training with epidural stimulation configured for motor systems. Thus, in this study, the effects of activity-based recovery training in combination with scES were tested on bladder function, resulting in improvements in overall bladder storage parameters relative to a control cohort (no intervention). However, elevated blood pressure elicited during bladder distention, characteristic of autonomic dysreflexia, was not attenuated with training. We then examined, in a separate, large cross-sectional cohort, the interaction between detrusor pressure and blood pressure at maximum capacity, and found that the functional relationship between urinary bladder distention and blood pressure regulation is disrupted. Regardless of one's bladder emptying method (indwelling suprapubic catheter vs. intermittent catheterization), autonomic instability can play a critical role in the ability to improve bladder storage, with SCI enhancing the vesico-vascular reflex. These results support the role of intersystem stimulation, integrating scES for both bladder and cardiovascular function to further improve bladder storage.

Respiratory muscle activation patterns during maximum airway pressure efforts are different in women and men.

Maximum inspiratory and expiratory pressure values (PImax and PEmax) are indirect measures of respiratory muscle strength that, in healthy adults, are known to be significantly lower in women compared to men. In part, sex differences in breathing kinematics, lung size, body composition, muscle mass, and muscle fiber composition are thought to be responsible for these effects. However, it is not known whether respiratory muscle activation during maximum respiratory efforts is also sex-specific. In this study, we addressed whether respiratory multi-muscle activation patterns during PImax and PEmax efforts are different between healthy women and men. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), PImax, PEmax, and surface electromyographic (sEMG) activity recorded from respiratory muscles during these maximum airway pressure efforts were obtained in 13 women and 11 men. Percent predicted values of FVC and FEV1 were not significantly different in these two groups (women vs. men: 112 ± 14 vs. 105 ± 15%, p = 0.29; and 92 ± 12 vs. 93 ± 13, p = 0.82, Mean ± SD, respectively), while PImax and PEmax measures were significantly lower in women compared to men (68 ± 16 vs. 88 ± 19 cmH2O, p = 0.011; and 69 ± 13 vs. 94 ± 17, p = 0.0004, respectively). Using vector-based methodology, by calculating the Similarity Index (SI) as measure of the resemblance between two sEMG patterns and the Magnitude (Mag) representing the overall amount sEMG during motor task, we have found that although the Mag values for both PImax and PEmax tasks were not significantly different in two groups, the SIs revealed significant sex-dependent differences in muscle activation patterns (0.89 ± 0.08 vs. 0.97 ± 0.02, p = 0.016; and 0.77 ± 0.11 vs. 0.92 ± 0.04, p = 0.0006, respectively). During the PImax effort, presented as the percentage of total sEMG amplitude, activity of upper trapezius muscle was significantly larger (p = 0.001) while activation of rectus abdominus, oblique, and lower paraspinal muscles were significantly smaller (p = 0.002, p = 0.040, p = 0.005, respectively) in women when compared to the men (50 ± 21 vs. 22 ± 11%; 2 ± 2 vs. 8 ± 7; 4 ± 3 vs. 9 ± 7, 2 ± 3 vs. 7 ± 6, respectively). During PEmax effort, the percentage of sEMG activity were significantly larger in upper and lower trapezius, and intercostal muscles (p = 0.038, p = 0.049, p = 0.037, respectively) and were significantly smaller in pectoralis, rectus abdominus, and oblique muscles (p = 0.021, p < 0.0001, p = 0.048, respectively) in women compared to men (16 ± 10 vs. 9 ± 4%; 16 ± 9 vs. 8 ± 5; 36 ± 12 vs. 25 ± 9; 6 ± 3 vs. 15 ± 5; 14 ± 5 vs. 20 ± 7, respectively). These findings indicate that respiratory muscle activation patterns during maximum airway pressure efforts in healthy individuals are sex-specific. This information should be considered during respiratory motor control evaluation and treatment planning for people with compromised respiratory motor function.

Muscle Activation Patterns During Movement Attempts in Children With Acquired Spinal Cord Injury: Neurophysiological Assessment of Residual Motor Function Below the Level of Lesion.

Introduction: Characterization of residual neuromotor capacity after spinal cord injury (SCI) is challenging. The current gold standard for measurement of sensorimotor function after SCI, the International Society for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam, seeks to determine isolated intentional muscle activation, however many individuals with SCI exhibit intentional movements and muscle activation patterns which are not confined to specific joint or muscle. Further, isolated muscle activation is a feature of the neuromuscular system that emerges during development, and thus may not be an appropriate measurement standard for children younger than 6. Methods: We utilized neurophysiological assessment methodology, long studied in adult SCI populations, to evaluate residual neuromotor capacity in 24 children with SCI, as well as 19 typically developing (TD) children. Surface electromyography (EMG) signals were recorded from 11 muscles bilaterally, representing spinal motor output from all regions (i.e., cervical, thoracic, and lumbosacral), during standardized movement attempts. EMG records were subjectively analyzed based on spatiotemporal muscle activation characteristics, while the voluntary response index (VRI) was utilized for objective analysis of unilateral leg movement tasks. Results: Evidence of intentional leg muscle activation below the level of lesion was found in 11/24 children with SCI, and was classified based on activation pattern. Trace activation, bilateral (generalized) activation, and unilateral or isolated activation occurred in 32, 49, and 8% of movement tasks, respectively. Similarly, VRI analyses objectively identified significant differences between TD and SCI children in both magnitude (p < 0.01) and similarity index (p < 0.05) for all unilateral leg movement tasks. Activation of the erector spinae muscles, recorded at the T10-T12 vertebral level, was observed in all children with SCI, regardless of injury level or severity. Conclusions: Residual descending influence on spinal motor circuits may be present after SCI in children. Assessment of multi-muscle activation patterns during intentional movement attempts can provide objective evidence of the presence and extent of such residual muscle activation, and may provide an indicator of motor recovery potential following injury. The presence of residual intentional muscle activation has important implications for rehabilitation following pediatric-onset SCI.

Epidural Spinal Cord Stimulation of Lumbosacral Networks Modulates Arterial Blood Pressure in Individuals With Spinal Cord Injury-Induced Cardiovascular Deficits.

Disruption of motor and autonomic pathways induced by spinal cord injury (SCI) often leads to persistent low arterial blood pressure and orthostatic intolerance. Spinal cord epidural stimulation (scES) has been shown to enable independent standing and voluntary movement in individuals with clinically motor complete SCI. In this study, we addressed whether scES configured to activate motor lumbosacral networks can also modulate arterial blood pressure by assessing continuous, beat-by-beat blood pressure and lower extremity electromyography during supine and standing in seven individuals with C5-T4 SCI. In three research participants with arterial hypotension, orthostatic intolerance, and low levels of circulating catecholamines (group 1), scES applied while supine and standing resulted in increased arterial blood pressure. In four research participants without evidence of arterial hypotension or orthostatic intolerance and normative circulating catecholamines (group 2), scES did not induce significant increases in arterial blood pressure. During scES, there were no significant differences in electromyographic (EMG) activity between group 1 and group 2. In group 1, during standing assisted by scES, blood pressure was maintained at 119/72 ± 7/14 mmHg (mean ± SD) compared with 70/45 ± 5/7 mmHg without scES. In group 2 there were no arterial blood pressure changes during standing with or without scES. These findings demonstrate that scES configured to facilitate motor function can acutely increase arterial blood pressure in individuals with SCI-induced cardiovascular deficits.

Respiratory functional and motor control deficits in children with spinal cord injury.

Children with spinal cord injury (SCI) are at high risk for developing complications due to respiratory motor control deficits. However, underlying mechanisms of these abnormalities with respect to age, development, and injury characteristics are unclear. To evaluate the effect of SCI and age on respiratory motor control in children with SCI, we compared pulmonary function and respiratory motor control outcome measures in healthy typically developing (TD) children to age-matched children with chronic SCI. We hypothesized that the deficits in respiratory functional performance in children with SCI are due to the abnormal and age-dependent respiratory muscle activation patterns. Fourteen TD (age 7±2 yrs., Mean±SD) and twelve children with SCI (age 6±1 yrs.) were evaluated by assessing Forced Vital Capacity (FVC); Forced Expiratory Volume in 1sec (FEV1); and respiratory electromyographic activity during maximum inspiratory and maximum expiratory airway pressure measurements (PImax and PEmax). The results indicate a significant reduction (p<.01) of FVC, FEV1 and PEmax values in children with SCI compared to TD controls. During PEmax assessment, children with SCI produced significantly decreased (p<.01) activation of respiratory muscles below the neurological level of injury (rectus abdominous and external oblique muscles). In addition, children with SCI had significantly increased (p<.05) compensatory muscle activation above the level of injury (upper trapezius muscle). In the TD group, age, height, and weight significantly (p<.05) contributed towards increase in FVC and FEV1. In children with SCI, only age was significantly (p<.05) correlated with FVC and FEV1 values. These findings indicate the degree of SCI-induced respiratory functional and motor control deficits in children are age-dependent.

Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury.

OBJECTIVE: To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI). DESIGN: Before-after intervention case-controlled clinical study. SETTING: SCI research center and outpatient rehabilitation unit. PARTICIPANTS: Participants (N=44) consisted of persons with chronic SCI ranging from C2 to T11 who participated in RT (n=24), and untrained control subjects with chronic SCI ranging from C2 to T9 (n=20). INTERVENTIONS: A total of 21±2 RT sessions performed 5 days a week during a 4-week period using a combination of pressure threshold inspiratory and expiratory devices. MAIN OUTCOME MEASURES: Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and beat-to-beat arterial blood pressure and heart rate changes during the 5-second-long maximum expiratory pressure maneuver (5s MEP) and the sit-up orthostatic stress test, acquired before and after the RT program. RESULTS: In contrast to the untrained controls, individuals in the RT group experienced significantly increased FVC and FEV1 (both P<.01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (P<.05) increased during the 5s MEP. During the orthostatic stress test, improved autonomic control over heart rate was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change: P<.01 and P<.05, respectively). CONCLUSIONS: Inspiratory-expiratory pressure threshold RT is a promising technique to positively affect both respiratory and cardiovascular dysregulation observed in persons with chronic SCI.

Baroreceptor reflex during forced expiratory maneuvers in individuals with chronic spinal cord injury.

Pulmonary and cardiovascular dysfunctions are leading causes of morbidity and mortality in patients with chronic Spinal Cord Injury (SCI). Impaired respiratory motor function and decreased Baroreflex Sensitivity (BS) are predictors for the development of cardiopulmonary disease. This observational case-controlled clinical study was undertaken to investigate if respiratory motor control deficits in individuals with SCI affect their ability to perform the Valsalva maneuver, and to determine if a sustained Maximum Expiratory Pressure (MEP) effort can serve as an acceptable maneuver for determination of the BS in the event that the Valsalva maneuver cannot be performed. The BS outcomes (ms/mmHg) were obtained using continuous beat-to-beat arterial blood pressure (BP) and heart rate (HR) recordings during Valsalva or MEP maneuvers in thirty nine individuals with chronic C3-T12 SCI. Twenty one participants (54%) reported signs of intolerance during the Valsalva maneuver and only 15 individuals (39%) were able to complete this task. Cervical level of injury was a significant risk factor (p=0.001) for failing to complete the Valsalva maneuver, and motor-complete injury was a significant risk factor for symptoms of intolerance (p=0.04). Twenty eight participants (72%) were able to perform the MEP maneuver; the other 11 participants failed to exceed the standard airway pressure threshold of 27cm H2O. Neither level nor completeness of injury were significant risk factors for failure of MEP maneuver. When the required airway pressure was sustained, there were no significant differences between BS outcomes obtained during Valsalva and MEP maneuvers. The results of this study indicate that individuals with high-level and motor-complete SCI are at increased risk of not completing the Valsalva maneuver and that baroreflex-mediated responses can be evaluated by using sustained MEP maneuver when the Valsalva maneuver cannot be performed.

Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (p<0.05) overall respiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization.

Respiratory Training Improves Blood Pressure Regulation in Individuals With Chronic Spinal Cord Injury.

OBJECTIVE: To investigate the effects of respiratory motor training (RMT) on pulmonary function and orthostatic stress-mediated cardiovascular and autonomic responses in individuals with chronic spinal cord injury (SCI). DESIGN: Before-after intervention case-controlled clinical study. SETTING: SCI research center and outpatient rehabilitation unit. PARTICIPANTS: A sample of (N=21) individuals with chronic SCI ranging from C3 to T2 diagnosed with orthostatic hypotension (OH) (n=11) and healthy, noninjured controls (n=10). INTERVENTIONS: A total of 21±2 sessions of pressure threshold inspiratory-expiratory RMT performed 5d/wk during a 1-month period. MAIN OUTCOME MEASURES: Standard pulmonary function test: forced vital capacity, forced expiratory volume in one second, maximal inspiratory pressure, maximal expiratory pressure, beat-to-beat arterial blood pressure, heart rate, and respiratory rate were acquired during the orthostatic sit-up stress test before and after the RMT program. RESULTS: Completion of RMT intervention abolished OH in 7 of 11 individuals. Forced vital capacity, low-frequency component of power spectral density of blood pressure and heart rate oscillations, baroreflex effectiveness, and cross-correlations between blood pressure, heart rate, and respiratory rate during the orthostatic challenge were significantly improved, approaching levels observed in noninjured individuals. These findings indicate increased sympathetic activation and baroreflex effectiveness in association with improved respiratory-cardiovascular interactions in response to the sudden decrease in blood pressure. CONCLUSIONS: Respiratory training increases respiratory capacity and improves orthostatic stress-mediated respiratory, cardiovascular, and autonomic responses, suggesting that this intervention can be an efficacious therapy for managing OH after SCI.

Prediction of Maximal Oxygen Consumption from Rating of Perceived Exertion (RPE) using a Modified Total-body Recumbent Stepper.

Exercise training is crucial to improve cardiovascular health and quality of life in people with spinal cord injuries (SCI). A key limitation is the lack of validated submaximal tests to evaluate and predict cardiovascular fitness in this population. The purpose of this study was to validate a submaximal test to predict maximal oxygen consumption for individuals with SCI. Ten able-bodied participants and two individuals with SCI completed a rating of perceived exertion (RPE)-based submaximal oxygen consumption test and a graded maximal oxygen consumption test on a NuStep T4 recumbent stepper. Prediction of VO2max from an RPE-based protocol is feasible and can produce reliable predicted VO2max values in the able bodied population. This study is a proof of concept to the implementation of a submaximal test protocol using a total body recumbent stepper to predict VO2max in able-bodied individuals. Additionally, this study shows evidence of feasibility of performing this test in SCI individuals.

Respiratory motor function in seated and supine positions in individuals with chronic spinal cord injury.

This case-controlled clinical study was undertaken to investigate to what extent pulmonary function in individuals with chronic spinal cord injury (SCI) is affected by posture. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) were obtained from 27 individuals with chronic motor-complete (n=13, complete group) and motor-incomplete (n=14, incomplete group) C2-T12 SCI in both seated and supine positions. Seated-to-supine changes in spirometrical (FVC and FEV1) and airway pressure (PImax and PEmax) outcome measures had different dynamics when compared in complete and incomplete groups. Patients with motor-complete SCI had tendency to increase spirometrical outcomes in supine position showing significant increase in FVC (p=.007), whereas patients in incomplete group exhibited decrease in these values with significant decreases in FEV1 (p=.002). At the same time, the airway pressure values were decreased in supine position in both groups with significant decrease in PEmax (p=.031) in complete group and significant decrease in PImax (p=.042) in incomplete group. In addition, seated-to-supine percent change of PImax was strongly correlated with neurological level of motor-complete SCI (ρ=-.77, p=.002). These results indicate that postural effects on respiratory performance in patients with SCI can depend on severity and neurological level of SCI, and that these effects differ depending on respiratory tasks. Further studies with adequate sample size are needed to investigate these effects in clinically specific groups and to study the mechanisms of such effects on specific respiratory outcome measures.

Evaluation of respiratory muscle activation using respiratory motor control assessment (RMCA) in individuals with chronic spinal cord injury.

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax). These values provide indirect measurements of respiratory muscle performance(6). In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles, known as the voluntary response index (VRI), we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA). This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity. We showed previously that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.

Blood pressure regulation in neurally intact human vs. acutely injured paraplegic and tetraplegic patients during passive tilt.

We investigated autonomic control of cardiovascular function in able-bodied (AB), paraplegic (PARA), and tetraplegic (TETRA) subjects in response to head-up tilt following spinal cord injury. We evaluated spectral power of blood pressure (BP), baroreflex sensitivity (BRS), baroreflex effectiveness index (BEI), occurrence of systolic blood pressure (SBP) ramps, baroreflex sequences, and cross-correlation of SBP with heart rate (HR) in low (0.04-0.15 Hz)- and high (0.15-0.4 Hz)-frequency regions. During tilt, AB and PARA effectively regulated BP and HR, but TETRA did not. The numbers of SBP ramps and percentages of heartbeats involved in SBP ramps and baroreflex sequences increased in AB, were unchanged in PARA, and declined in TETRA. BRS was lowest in PARA and declined with tilt in all groups. BEI was greatest in AB and declined with tilt in all groups. Low-frequency power of BP and the peak of the SBP/HR cross-correlation magnitude were greatest in AB, increased during tilt in AB, remained unchanged in PARA, and declined in TETRA. The peak cross-correlation magnitude in HF decreased with tilt in all groups. Our data indicate that spinal cord injury results in decreased stimulation of arterial baroreceptors and less engagement of feedback control as demonstrated by lower 1) spectral power of BP, 2) number (and percentages) of SBP ramps and barosequences, 3) cross-correlation magnitude of SBP/HR, 4) BEI, and 5) changes in delay between SBP/HR. Diminished vasomotion and impaired baroreflex regulation may be major contributors to decreased orthostatic tolerance following injury.