Heart Rate Variability-Based Prediction of Autonomic Dysreflexia After Spinal Cord Injury.

Autonomic dysreflexia (AD) is a common autonomic complication of spinal cord injury (SCI) characterized by a sudden increase is blood pressure triggered by peripheral stimulation, such as bladder distention. Iatrogenic AD events often occur during various medical procedures including urodynamic assessments (UDSs) used to evaluate lower urinary tract (LUT) function in individuals with SCI. To date, there are no established clinical practices that would allow early detection of the development of episodes of AD. Heart rate variability (HRV) is a reliable and non-invasive metric for evaluating autonomic regulation of the cardiovascular system, with demonstrated utility in people with SCI during UDSs. We aim to provide a comprehensive evaluation of cardiovascular function during UDS-induced AD using ultra-short-term HRV analysis and identify changes in cardiovascular dynamics to predict the onset of AD. We assessed cardiovascular data in a total of 24 participants with sensorimotor complete SCI above T6 (17 males, 7 females, median age = 43 [36-50] years) who experienced AD during UDS. We used continuous electrocardiographic recordings to evaluate HRV in 60 sec overlapping windows during filling cystometry. The mean of "normal-to-normal" heartbeats (meanNN), its standard deviation (SDNN), and the root mean square of successive differences (RMSSD) were calculated and used in all subsequent analyses. We found that SDNN and RMSSD diminished during the early phase of bladder filling and sharply increased during AD. Using the lowest point of statistical variability in heart rate (i.e., SDNN), we were able to predict AD events within 240 sec (percentile 25-percentile 75: 172-339 sec) before the first systolic blood pressure peak after AD onset (sensitivity = 0.667; specificity = 0.875). Our results indicated a temporary increase in sympathetic activity during the early phase of bladder filling, which is followed by an increase in parasympathetic outflow to the heart when AD occurs. These findings have significant clinical implications that extend beyond the context of UDS and demonstrate the importance of identifying early changes in HRV in order to accurately predict AD episodes in people living with SCI.

Fesoterodine Ameliorates Autonomic Dysreflexia While Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals With Spinal Cord Injury: A Prospective Phase IIa Study.

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Compared with baseline, fesoterodine improved lower urinary tract (LUT) function, that is, increased cystometric capacity (205 vs. 475 mL, p = 0.002) and decreased maximum detrusor pressure (44 vs. 12 cm H2O, p = 0.009). NDO was eliminated in seven (58%) participants. Severity of AD events during urodynamics (40 vs. 27 mm Hg, p = 0.08) and 24-h ABPM (59 vs. 36 mm Hg, p = 0.05) were both reduced, yielding a large effect size (r = -0.58). AD Frequency (14 vs. 3, p = 0.004) during 24-h ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.

May I Have This Dance: A Case-Series on the Acute Cardiometabolic Demand of Wheelchair Dancing in Recreational Dancers with Spinal Cord Injury.

OBJECTIVES: This case-series investigated energy expenditure, cardiovascular responses, and psychosocial outcomes during two wheelchair dancing routines with different tempos. METHODS: Three individuals with chronic, non-traumatic spinal cord injuries [males, mean age 42 (13) years, C3-T12, AIS D, schwannoma=1, poliomyelitis=1, ependymoma=1] performed slow (rumba, 80 bpm) and fast (salsa, 170 bpm) wheelchair dance routines. Physiological [heart rate, blood pressure, relative oxygen consumption (VO2), metabolic task equivalent] and psychosocial parameters [ratings of perceived exertion, enjoyment and Brunel Mood Score] were measured pre, during, and post-dancing. RESULTS: All participants showed an elevation in heart rate and relative VO2 from rest to dancing with a subsequent decrease in these parameters post-dance for both routines. Relative to the slow dance routine, two out of three participants demonstrated greater heart rate, relative VO2, ratings of perceived exertion, and enjoyment during the fast dance routine. For all three participants, metabolic task equivalents ranged from 1.7-2.4 (slow) and 2.1-3.8 (fast), suggesting the intervention was of light to moderate intensity for slow and fast dance routines, respectively. Enjoyment ratings ranged from "quite a bit" to "extremely." No differences in Brunel mood subscales were observed. CONCLUSION: This case-series offers a preliminary understanding of the acute cardiometabolic and psychosocial responses to wheelchair dance routines of differing intensities per¬formed by individuals with spinal cord injury. Responsiveness observed among these participants suggests the potential use of wheelchair dance for promoting physical activity and improving psychological well-being.

Passive leg cycling increases activity of the cardiorespiratory system in people with tetraplegia.

Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this study was to investigate the cardiorespiratory response to passive leg cycling in people with cervical SCI. Beat-by-beat blood pressure, heart rate, and cerebral blood flow were measured before and throughout 10 minutes of cycling in 11 people with SCI. Femoral artery flow-mediated dilation was also assessed before and immediately after passive cycling. Safety was monitored throughout all study visits. Passive cycling elevated systolic blood pressure (5 ± 2 mm Hg), mean arterial pressure (5 ± 3 mm Hg), stroke volume (2.4 ± 0.8 mL), heart rate (2 ± 1 beats/min) and cardiac output (0.3 ± 0.07 L/min; all p < 0.05). Minute ventilation (0.67 ± 0.23 L/min), tidal volume (70 ± 30 mL) and end-tidal PO2 (2.6 ± 1.23 mm Hg) also increased (all p < 0.05). Endothelial function was improved immediately after exercise (1.62 ± 0.13%, p < 0.01). Passive cycling resulted in an incidence of autonomic dysreflexia. Therefore, passive leg cycling increased the activity of the cardiorespiratory system and improved endothelial function, indicating it may be a beneficial exercise intervention for the cardiovascular and respiratory systems in people with cervical SCI. Novelty: Passive leg cycling increases the activity of the cardiorespiratory system and improves markers of cardiovascular health in cervical SCI. Passive leg cycling exercise is an effective, low-cost, practical, alternative exercise modality for people with cervical SCI.

Noninvasive Neuroprosthesis Promotes Cardiovascular Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) leads to severe impairment in cardiovascular control, commonly manifested as a rapid, uncontrolled rise in blood pressure triggered by peripheral stimuli-a condition called autonomic dysreflexia. The objective was to demonstrate the translational potential of noninvasive transcutaneous stimulation (TCS) in mitigating autonomic dysreflexia following SCI, using pre-clinical evidence and a clinical case report. In rats with SCI, we show that TCS not only prevents the instigation of autonomic dysreflexia, but also mitigates its severity when delivered during an already-triggered episode. Furthermore, when TCS was delivered as a multisession therapy for 6 weeks post-SCI, the severity of autonomic dysreflexia was significantly reduced when tested in the absence of concurrent TCS. This treatment effect persisted for at least 1 week after the end of therapy. More importantly, we demonstrate the clinical applicability of TCS in treatment of autonomic dysreflexia in an individual with cervical, motor-complete, chronic SCI. We anticipate that TCS will offer significant therapeutic advantages, such as obviating the need for surgery resulting in reduced risk and medical expenses. Furthermore, this study provides a framework for testing the potential of TCS in improving recovery of other autonomic functions such lower urinary tract, bowel, and sexual dysfunction following SCI.

The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord Injuries: A Systematic Review.

BACKGROUND: People with spinal cord injuries (SCI) commonly experience pain and spasticity; limitations of current treatments have generated interest in cannabis as a possible therapy. OBJECTIVES: We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use in people with SCI. METHODS: PubMed, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature databases were queried for keywords related to SCI and cannabinoids. RESULTS: 7,232 studies were screened, and 34 were included in this systematic review. Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity. The most common method of use was smoking. Relief of pain, spasticity and recreation were the most common reasons for use. A statistically significant reduction of pain and spasticity was observed with cannabinoid use in 83% and 100% of experimental studies, respectively. However, on examination of randomized control trials (RCTs) alone, effect sizes ranged from - 0.82 to 0.83 for pain and -0.95 to 0.09 for spasticity. Cannabinoid use was associated with fatigue and cognitive deficits. CONCLUSION: Current evidence suggests that cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance are unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Long-term, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understand the effects of cannabinoid use in people with SCI.

Long-term neurogenic lower urinary tract dysfunction: A case of cardiovascular nightmares.

CONTEXT: Individuals with spinal cord injury (SCI) suffering from autonomic dysreflexia (AD) due to neurogenic detrusor overactivity (NDO) can effectively be treated with intradetrusor onabotulinumtoxinA. We present a complex case to highlight the treatment's potential limitations to ameliorate AD and improve lower urinary tract (LUT) function in this population. FINDINGS: A 46-year old man, who was relying on an indwelling urethral catheter for bladder emptying due to severely impaired hand function following a SCI (C5, AIS B) sustained 30 years ago, underwent intradetrusor onabotulinumtoxinA injections for treatment of refractory NDO and associated AD. Although LUT function slightly improved (i.e. cystometric capacity increased while detrusor pressure was reduced), severe bladder-related AD persisted post-treatment. CONCLUSIONS: This case raises awareness of serious considerations when treating NDO-related AD in individuals with longstanding neurogenic LUT dysfunction and compromised dexterity following SCI. Given the limited improvement in LUT function and persisting bladder-related AD following treatment, urinary diversion as advocated in the wider literature should be considered to protect an individual's urinary tract from further deterioration and thus eliminate bladder-related AD consequences long-term. Early treatment and management of NDO and AD is crucial to minimize complications associated with these two major health risks in this population.

Intradetrusor OnabotulinumtoxinA Injections Ameliorate Autonomic Dysreflexia while Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals with Cervical and Upper Thoracic Spinal Cord Injury.

Pilot data of our phase IV clinical trial (pre/post study design) highlighted a beneficial effect of intradetrusor onabotulinumtoxinA (200 IU) injections to reduce autonomic dysreflexia (AD) in individuals with chronic spinal cord injury (SCI) at T6 or above. After trial completion, we assessed whether our primary expectation (i.e., decrease of AD severity in 50% of participants during urodynamics [UDS]) was met. Secondary outcome measures were reduction of spontaneous AD in daily life as well as amelioration of AD-related and urinary incontinence-related quality of life (QoL). In addition, we conducted injury-level-dependent analysis-i.e., cervical and upper thoracic-to explore group-specific treatment efficacy. Post-treatment, AD severity decreased in 82% (28/34) of all participants during UDS and in 74% (25/34) in daily life assessed with 24-h ambulatory blood pressure monitoring. In addition, urinary incontinence-related QoL was improved, cystometric capacity was increased, and maximum detrusor pressure during storage was reduced (all p < 0.001). Further, the treatment was well tolerated, with only minor complications (grade I [n = 7] and II [n = 7]) in accordance with the Clavien-Dindo classification recorded in 11 individuals (cervical n = 9, upper thoracic n = 2). Injury-level-dependent analysis revealed lower incidence (cervical n = 15/23, upper thoracic n = 6/11) and lesser severity (cervical p = 0.009; upper thoracic p = 0.06 [Pearson r = -0.6, i.e., large effect size]) of AD during UDS. Further, reduced AD severity in daily life, improved urinary incontinence-related QoL, greater cystometric capacity, and lower maximum detrusor pressure during storage (all p < 0.05) were found in both groups post-treatment. Intradetrusor onabotulinumtoxinA injections are an effective and safe second-line treatment option that ameliorates AD while improving lower urinary tract function and urinary incontinence-related QoL in individuals with cervical and upper thoracic SCI.

Medical and surgical management of acute spinal injury during pregnancy: A case series in a third-world country.

BACKGROUND: There is scant literature describing the management of acute spinal injury in pregnant patients. Here, we report our experience with five cases of pregnant patients including three females who suffered acute traumatic spinal cord injuries (SCIs). METHODS: This retrospective study evaluated five pregnant women presenting with traumatic spinal injuries over a 16-month period. All were assessed using the International Standards for Neurological Classification of Spinal Cord Injury Patients and the American Spine Injury Association Impairment Scale (AIS). RESULTS: Three patients sustained SCIs: two cervical spine (C4 AIS-A and C5 AIS-B) and one thoracolumbar junction fracture dislocation (T11 AIS-A). Two patients required surgical stabilization during pregnancy, with one undergoing surgery after delivery. All three patients subsequently delivered healthy newborns. The remaining two patients without neurologic deficits at admission were treated conservatively; one had a healthy child, whereas the other patient aborted the baby due to the initial trauma. CONCLUSIONS: Our study demonstrates that the same surgical principals may be applied to pregnant women as to routine patients with SCIs. Further studies with greater patient data should be performed to better develop significant guidelines for the management of pregnant patients with spinal injuries.

Active-Arm Passive-Leg Exercise Improves Cardiovascular Function in Spinal Cord Injury.

In a 43-yr-old male subject with a chronic T3 AIS A spinal cord injury, the acute cardiorespiratory responses to active upper-extremity exercise alone and combined active-arm passive-leg exercise (AAPLE) were investigated, along with the cardiorespiratory, cardiac, vascular, and body composition responses to a 6-wk AAPLE interval training intervention. AAPLE elicited superior acute maximal cardiorespiratory responses compared with upper-extremity exercise alone. In response to a 6-wk interval training regimen, AAPLE caused a 25% increase in peak oxygen uptake, a 10% increase in resting stroke volume, and a 4-fold increase in brachial artery blood flow. Conversely, there were no changes in femoral arterial function, body composition, or bone mineral density in response to training. As a potential clinical intervention, AAPLE may be advantageous over other forms of currently available exercise, owing to the minimal setup time and cost involved and the nonreliance on specialized equipment that is required for other exercise modalities.

Response to functional electrical stimulation cycling in women with spinal cord injuries using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography: a case series.

BACKGROUND: Loss of bone mass is common after spinal cord injury (SCI). One rehabilitation modality that has shown some promise for maintaining bone health is the functional electrical stimulation (FES) cycle ergometer. Although there has been some research investigating bone health and FES cycle ergometry, few have provided a detailed description of the changes that can occur in bone mass and soft-tissue mass. OBJECTIVE: To use 2 types of bone imaging, peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), to provide a detailed description of bone and soft-tissue response to FES cycle ergometry training in women with SCI. STUDY DESIGN: Case series; a 6-month program of FES cycle ergometry for women with chronic motor complete (n = 2) and incomplete (n = 1) SCI. SETTING: Outpatient rehabilitation center in Canada. METHODS: Three women participated in a thrice weekly 6-month exercise program of FES cycle ergometry. We used DXA (lower extremity) and pQCT at the midshaft (50%) and distal (5%) sites of the tibia to assess bone density and soft-tissue mass before and after the exercise program. RESULTS: There was an increase or maintenance in bone mineral density by DXA and pQCT in the lower extremity for all 3 participants. Muscle mass by DXA increased in the lower extremity in 2 participants. CONCLUSION: In this case series, we note a positive response in bone mass and soft-tissue mass in the lower extremity after a 6-month FES cycle ergometry program.

Hematologic abnormalities within the first week after acute isolated traumatic cervical spinal cord injury: a case-control cohort study.

STUDY DESIGN: Case-control cohort study. OBJECTIVE: To evaluate 1) the hematologic abnormalities within the first week following isolated acute cervical spine trauma or spinal cord injury (SCI); and 2) the influence of age, sex, and severity of SCI on these hematologic abnormalities. SUMMARY OF BACKGROUND DATA: Given that autonomic nervous system has a critical role in the regulation of the hematopoietic system, we sought to evaluate the potential association between hematologic abnormalities within the first week posttrauma and the severity of SCI. METHODS: All consecutive individuals with isolated acute cervical spine trauma admitted to our institution from 1998 to 2000 were reviewed. Exclusion criteria included preexisting medical comorbidities and polytrauma. The study population was divided into a SCI group and a control group (individuals with spine trauma without neurologic impairment). The SCI group was subdivided into patients with motor complete SCI (American Spinal Injury Association [ASIA] Grades A/B) and individuals with motor incomplete SCI (ASIA Grades C/D). RESULTS: There were 21 SCI individuals (15 male, 6 female; ages 17-83 years; mean, 57 years) and 11 controls (6 male, 5 female; ages 18-75 years; mean, 41 years). When controlled for age, SCI individuals showed a significantly higher frequency of reduced hemoglobin concentration (RHC), leukocytosis, lymphopenia, and thrombocytopenia than controls within the first week posttrauma. Blood hemoglobin concentration, lymphocyte, and platelet counts in the SCI group were significant lower than the controls. The SCI group showed a significant higher leukocyte count than the controls. The degree of RHC and lymphopenia was significantly correlated with the severity of SCI. CONCLUSION: Our results indicate that patients with isolated cervical SCI have significantly greater frequency of RHC, leukocytosis, lymphopenia, and thrombocytopenia than controls during the first week posttrauma. The degree of RHC and lymphopenia was significantly associated with the severity of SCI. While the mechanisms underlying these clinically important hematologic consequences of SCI remain undetermined, evidence from the literature suggests that acute autonomic denervation of the hematopoietic system could play a key role.

Multimodality intraoperative monitoring during complex lumbosacral procedures: indications, techniques, and long-term follow-up review of 61 consecutive cases.

OBJECT: The purpose of this study was to examine the neurological outcomes after complex lumbosacral surgery in patients undergoing multimodality neurophysiological monitoring. METHODS: Sixty-one patients were consecutively enrolled in this study. These patients underwent complex intra- and extradural lumbosacral procedures with concomitant intraoperative electromyography (EMG) monitoring of the lower-limb muscles, external anal and urethral sphincters (EAS and EUS), and lower-limb somatosensory evoked potentials (SSEPs). Long-term (minimum 2-year) clinical follow-up data were obtained in all cases. Most patients were treated for spinal/spinal cord tumors (61%) or adult tethered cord syndrome (25%). Recordable lower-extremity SSEPs were reported in 54 patients (89%). New postoperative neurological deficits occurred in only three patients (4.9%), and remained persistent in only one patient (1.6%) at long-term follow-up examination. In only one of these cases was a significant decrease in SSEP amplitude detected. Spontaneous EMG activity was observed in the lower-extremity muscles and/or EAS and EUS in 51 cases (84%). Intraoperatively, EMG demonstrated activity only in the EUS in 5% of patients and only in the EAS in 28%. In seven patients (11%) spontaneous intraoperative EMG activity was observed in both the EAS and the EUS; however, in only three of these cases was EMG activity recorded in both sphincters simultaneously. In addition to spontaneously recorded EMG activity, electrically evoked EMG activity was also used as an intraoperative adjunct. A bipolar stimulating electrode was used to identify functional neural tissue before undertaking microsurgical dissection in 58 individuals (95%). In the majority of these patients, evoked EMG activity occurred either in one (33%) or in two muscles (9%) simultaneously. The presence of electrically evoked EMG activity in structures encountered during microdissection altered the plan of treatment in 24 cases (42%). CONCLUSIONS: The authors conclude that the combined SSEP and EMG monitoring of lower-limb muscles, EAS, and EUS is a practical and reliable method for obtaining optimal electrophysiological feedback during complex neurosurgical procedures involving the conus medullaris and cauda equina. Analysis of the results indicates that these intraoperative adjunctive modalities positively influence decision making with regard to microsurgery and reduce the risk of perioperative neurological complications. Validation of the clinical value of these approaches, however, will require further assessment in a larger prospective cohort of patients.

Real-time continuous intraoperative electromyographic and somatosensory evoked potential recordings in spinal surgery: correlation of clinical and electrophysiologic findings in a prospective, consecutive series of 213 cases.

STUDY DESIGN: Retrospective analysis of a prospectively accrued series of 213 consecutive patients who underwent intraoperative neurophysiologic monitoring with electromyography and somatosensory-evoked potentials during thoracolumbar spine surgery. OBJECTIVES: To study the incidence of significant intraoperative electrophysiologic changes and new postoperative neurologic deficits. SUMMARY OF BACKGROUND DATA: Continuous intraoperative electromyography and somatosensory-evoked potentials are frequently used in spinal surgery to prevent neural injury. However, only limited data are available on the sensitivity, specificity, and predictive values of intraoperative electrophysiologic changes with regard to the occurrence of new postoperative neurologic deficits. METHODS: We examined data on patients who underwent intraoperative monitoring with continuous lower limb electromyography and somatosensory-evoked potentials. The analysis focused on the correlation of intraoperative electrophysiologic changes with the development of new neurologic deficits. RESULTS: A total of 213 patients underwent surgery on a total of 378 levels; 32.4% underwent an instrumented fusion. Significant electromyograph activation was observed in 77.5% of the patients and significant somatosensory-evoked potential changes in 6.6%. Fourteen patients (6.6%) had new postoperative neurologic symptoms. Of those, all had significant electromyograph activation, but only 4 had significant somatosensory-evoked potential changes. Intraoperative electromyograph activation had a sensitivity of 100% and a specificity of 23.7% for the detection of a new postoperative neurologic deficit. Somatosensory-evoked potentials had a sensitivity of 28.6% and specificity of 94.7%. CONCLUSIONS: Intraoperative electromyographic activation has a high sensitivity for the detection of a newpostoperative neurologic deficit but a low specificity. In contrast, somatosensory-evoked potentials have low sensitivity but high specificity. Combined intraoperative neurophysiologic monitoring with electromyography and somatosensory-evoked potentials is helpful for predicting and possibly preventing neurologic injury during thoracolumbar spine surgery.