Prevalence of autonomic dysreflexia during spinal cord stimulation after spinal cord injury.

Over the past decade, clinical trials have shown that spinal cord stimulation can restore motor functions that were thought to be permanently impaired in persons with spinal cord injury. However, the off-target effects of delivering electrical impulses to intertwined spinal networks remain largely unknown. This generates safety concerns for this otherwise fast-progressing technology. Herein, we present the prevalence of autonomic dysreflexia (AD) that occurred during implanted spinal cord stimulation testing for motor activation of the lower extremities. Eleven participants with spinal cord injury underwent implantation of temporary percutaneous epidural and dorsal root ganglia stimulation leads. Participants completed two days of parameter testing at baseline, then six days of motor rehabilitation sessions, and two days of parameter testing at end of study. The goal of parameter testing was to determine electrode configuration(s), pulse amplitudes, and frequencies that activated lumbosacral spinal sensorimotor networks that generate lower extremity functions. During all parameter testing sessions, continuous blood pressure and heart rate monitoring recordings were collected. Evidence of autonomic dysreflexia was found in 22% of all parameter tests with participants at rest. Most of these episodes (97%) were asymptomatic. These episodes occurred more frequently when using epidural stimulation, at or near amplitudes that elicited whole leg muscle activation and using a wide-field electrode configuration. Although monitoring occurred during passive testing, motor rehabilitation sessions use stimulation for longer periods, at higher frequencies and amplitudes. These sessions may carry additional risks of autonomic dysreflexia. Investigation of these concerns should continue as spinal cord stimulation progresses toward clinical translation.NEW & NOTEWORTHY Spinal cord stimulation for motor recovery after spinal cord injury is a popular research intervention, though off-target effects are a concern. Using continual blood pressure and heart rate recordings during passive spinal cord stimulation parameter testing, we identified frequent episodes of autonomic dysreflexia that were rarely associated with symptoms. This presents a previously unrecognized risk of spinal cord stimulation and appropriate vigilance in targeted monitoring is urged to maintain participant safety.

Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. Although recent findings postulate that spinal cord stimulation improves autonomic regulation, limited scope of past methods have tested only above level sympathetic activation, leaving significant uncertainty. To identify whether transcutaneous spinal cord stimulation improves cardiovascular autonomic regulation, two pairs of well-matched individuals with and without high thoracic, complete SCI were recruited. Baseline autonomic regulation was characterized with multiple tests of sympathoinhibition and above/below injury level sympathoexcitation. At three subsequent visits, testing was repeated with the addition submotor threshold transcutaneous spinal cord stimulation at three previously advocated frequencies. Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. As expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared with baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in cardiovascular autonomic regulation. Collectively, transcutaneous spinal cord stimulation demonstrates no improvements in autonomic regulation after SCI, and instead likely generates tonic sympathoexcitation which may lower the threshold for dangerous autonomic dysreflexia.NEW & NOTEWORTHY Spinal cord stimulation increases blood pressure after spinal cord injury, though it is unclear if this restores natural autonomic regulation or induces a potentially dangerous pathological reflex. We performed comprehensive autonomic testing batteries, with and without transcutaneous spinal cord stimulation at multiple frequencies. Across 96 independent tests, stimulation did not change uninjured control responses, though all frequencies facilitated pathological reflexes without improved autonomic regulation for those with spinal cord injuries.

Valsalva maneuver pressure recovery time is prolonged following spinal cord injury with correlations to autonomically-influenced secondary complications.

PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications. METHODS: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden. RESULTS: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk. CONCLUSIONS: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.

Autonomic impairment is not explained by neurological level of injury or motor-sensory completeness.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine how well common clinical assessments of level and completeness of injury are correlated with symptoms of autonomic blood pressure instability and secondary medical complications after spinal cord injury (SCI). SETTING: Academic medical center, United States. METHODS: Eighty-two individuals with (n = 48) and without (n = 34) SCI had symptoms of autonomic blood pressure instability quantified with the Autonomic Dysfunction Following SCI (ADFSCI) survey. Health histories quantified the secondary medical complications through number of urinary tract infections and hospitalizations in the past year, time to complete bowel program, and lifetime pressure injuries. Regression models were completed to identify strengths of associated correlations. RESULTS: ADFSCI scores were significantly higher in individuals with SCI than controls. Neurological level of injury and ASIA impairment scale were both minimally correlated to symptoms of autonomic blood pressure instability, accounting for only 11.5% of variability in regression models. Secondary medical complications had similar, minimal correlations to level and motor/sensory completeness of SCI (R2 = 0.07 and R2 = 0.03 respectively). Contrasting this, symptoms of blood pressure instability on ADFSCI far outperformed the common clinical motor/sensory bedside exam, with moderately strong correlations to the ranked number of secondary medical complications after SCI (R2 = 0.31). CONCLUSION: Neurological level of injury and motor/sensory completeness provided limited insights into which individuals with SCI would have blood pressure instability or secondary medical complications. Interestingly, symptoms of blood pressure instability outperform the clinical motor/sensory bedside exam, with higher correlations to secondary medical complications after SCI.

Patient Perceptions and Clinical Assessments of Cardiometabolic Disease After Subacute Spinal Cord Injury.

OBJECTIVES: To investigate the effectiveness of health care team communication regarding cardiometabolic disease (CMD) risk factors with patients with subacute spinal cord injury (SCI). DESIGN: Multi-site prospective cross-sectional study. SETTING: Five National Institute on Disability, Independent Living, and Rehabilitation Research Model SCI Rehabilitation Centers. PARTICIPANTS: Ninety-six patients with subacute SCI, aged 18-70 years, with SCI (neurologic levels of injury C2-L2, American Spinal Injury Association Impairment Scale grades A-D), and enrolled within 2 months of initial rehabilitation discharge (N=96). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Objective risk factors of CMD (body mass index, fasting glucose, insulin, high-density lipoprotein cholesterol, triglyceride levels, and resting blood pressure). Patient reported recall of these present risk factors being shared with them by their health care team. Medications prescribed to patients to address these present risk factors were checked against guideline- assessed risk factors. RESULTS: Objective evidence of 197 CMD risk factors was identified, with patients recalling less than 12% of these (P<.0001) being shared with them by their health care team. Thirty-one individuals (32%) met criteria for a diagnosis of CMD, with only 1 of these patients (3.2%) recalling that this was shared by their health care team (P<.0001). Pharmacologic management was prescribed to address these risk factors only 7.2% of the time. CONCLUSIONS: Despite high prevalence of CMD risk factors after acute SCI, patients routinely do not recall being told of their present risk factors. Multifaceted education and professionals' engagement efforts are needed to optimize treatment for these individuals.

Acute Spinal Cord Injury Is Associated With Prevalent Cardiometabolic Risk Factors.

OBJECTIVES: To (1) describe the prevalence of cardiometabolic disease (CMD) at spinal cord injury (SCI) rehabilitation discharge; (2) compare this with controls without SCI; and (3) identify factors associated with increased CMD. DESIGN: Multicenter, prospective observational study. SETTING: Five National Institute on Disability, Independent Living, and Rehabilitation Research Model SCI Rehabilitation Centers. PARTICIPANTS: SCI (n=95): patients aged 18-70 years, with SCI (neurologic levels of injury C2-L2, American Spinal Injury Association Impairment Scale grades A-D), and enrolled within 2 months of initial rehabilitation discharge. Control group (n=1609): age/sex/body mass index-matched entries in the National Health and Nutrition Examination Education Survey (2016-2019) (N=1704). INTERVENTIONS: None MAIN OUTCOME MEASURES: Percentage of participants with SCI with CMD diagnosis, prevalence of CMD determinants within 2 months of rehabilitation discharge, and other significant early risk associations were analyzed using age, sex, body mass index, insulin resistance (IR) by fasting glucose and Homeostasis Model Assessment (v.2), fasting triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol, total cholesterol, and resting blood pressure (systolic and diastolic). RESULTS: Participants with SCI had significantly higher diastolic blood pressure and triglycerides than those without SCI, with lower fasting glucose and HDL-C. A total of 74.0% of participants with SCI vs 38.5% of those without SCI were obese when applying population-specific criteria (P<.05). Low HDL-C was measured in 54.2% of participants with SCI vs 15.4% of those without (P<.05). IR was not significantly different between groups. A total of 31.6% of participants with SCI had ≥3 CMD determinants, which was 40.7% higher than those without SCI (P<.05). Interplay of lipids and lipoproteins (ie, total cholesterol:HDL-C ratio and triglyceride:HDL-C ratio) were associated with elevated risk in participants with SCI for myocardial infarction and stroke. The only significant variable associated with CMD was age (P<.05). CONCLUSIONS: Individuals with SCI have an increased CMD risk compared with the general population; obesity, IR, and low HDL-C are the most common CMD risk determinants; age is significantly associated with early CMD.

The effect of heart rate variability on blood pressure is augmented in spinal cord injury and is unaltered by exercise training.

PURPOSE: To define differences in heart rate and blood pressure variability (HRV/BPV) after spinal cord injury (SCI) compared with uninjured controls, and to determine whether variabilities are impacted by whole-body exercise after SCI. METHODS: Individuals with SCI (n = 40), aged 18-40, and uninjured age/sex-matched controls (n = 22) had HRV and BPV determined during supine paced (0.25 Hz) breathing. Spectral and cross-spectral values were derived for fluctuations at low (LF 0.05-0.15 Hz) and high (HF 0.20-0.30 Hz) frequencies. Thirty-two individuals with SCI further underwent either 6 months of whole-body exercise training (n = 17) or a control intervention (n = 15). RESULTS: Individuals with SCI had injuries graded A-C in severity, neurological levels of injury C1-T10. LF and HF HRV and LF BPV were significantly lower in individuals with SCI (p = 0.008-0.002), though HF BPV was similar. The LF cross-spectrum demonstrated similar phase and gain relationships between groups. The HF phase relationship between pressure and heart rate differed markedly: individuals with SCI demonstrated a -11.7 ± 3.4° phase lag (241 ± 70 ms feedback mechanism of pressure into heart rate), whereas uninjured controls demonstrated a +21.5 ± 10.8° phase lead (443 ± 224 ms feedforward mechanism of heart rate into pressure, p = 0.007). Whole-body exercise increased mean VO2peak by 2.09 ml/kg, whereas HRV, BPV, and their cross-spectral relationships were not significantly altered relative to the control intervention after SCI. CONCLUSION: After SCI, marked frequency-specific differences exist in the relationship between heart rate and blood pressure variabilities. The high-frequency cross-spectral relationship indicates that a feedback mechanism of blood pressure into heart rate may predominate in this range.

Buspirone for functional improvement after acute traumatic spinal cord injury: a propensity score-matched cohort study.

STUDY DESIGN: Retrospective analysis of treated inpatients compared to expected neurorecovery from a propensity score-matched national database cohort. OBJECTIVE: Evaluate the effectiveness of buspirone on clinical neurorecovery following traumatic SCI when started during acute inpatient rehabilitation. SETTING: University-based hospital in Boston, USA. METHODS: Chart review yielded thirty-one individuals with acute, traumatic SCI treated with buspirone during inpatient rehabilitation from 2011-2017. Propensity score matching to a cohort of individuals from the spinal cord injury model systems (SCIMS) national database was completed. Changes in upper extremity motor score (UEMS), lower extremity motor score (LEMS), American Spinal Injury Association Impairment Scale (AIS), neurological level of injury (NLI), and functional impairment measure (FIM) from admission to discharge and discharge to 1 year were computed and compared between matched pairs (buspirone and mean national SCIMs cohort). A local control cohort not treated with buspirone was similarly compared to a matched mean national SCIMs group to identify location-specific effects. RESULTS: From admission to discharge from inpatient rehabilitation, 95% confidence intervals of changes in UEMS (-2.43 to +2.78), LEMS (-1.02 to +6.02), AIS (-0.04 to +0.35), NLI (-0.42 to +1.08), and FIM (-4.42 to +6.40) were not significantly different between those individuals who received buspirone and their propensity-matched SCIMS cohort. Similarly, changes in these metrics were not significantly different at 1-year follow up. Buspirone group individuals with initial clinically complete SCI demonstrated a higher 1-year conversion rate to incomplete injury (6 out of 14; 42.9%) compared to the matched national SCIMS cohort (14 out of 70; 21.2%, p = 0.047) though this was not significantly different from non-buspirone local controls (p = 0.25). CONCLUSIONS: Retrospective analysis shows no statistically significant difference in gross markers of neurorecovery following acute traumatic SCI when buspirone is initiated indiscriminately during acute inpatient rehabilitation. In individuals with clinically complete SCI, findings suggest possible increased rates of 1-year conversion to incomplete injury.

Onset of the action of intravesical lidocaine after spinal cord injury.

AIMS: To obtain objective evidence for the time to onset of action for intravesical lidocaine utilizing exaggerated sympathetic blood-pressure responsiveness in patients with spinal cord injuries (SCI). METHODS: This prospective observational cohort study analyzed blood pressure responses in individuals with SCI at or above T6 who did (lidocaine-instillation group) or did not (control group) receive 10 ml of 2% lidocaine gel instilled through their catheters before routine suprapubic catheter change. Care was taken to minimize any potentially confounding position change or catheter manipulation. Given the potential for C-fiber mediated systolic blood pressure (SBP) increases after SCI, the time to lidocaine's onset of action for blocking these C-fibers (as seen by the decrease in SBP more than and equal to 10 mm Hg) was assessed with serial blood pressures for 4 to 6 minutes. RESULTS: Blood pressures were evaluated in 32 individuals with SCI (lidocaine-instillation group n = 22, control group n = 10). In the lidocaine-instillation group, 45% individuals demonstrated a sustained decrease in SBP more than and equal to 10 mm Hg, which occurred at a mean of 98.1 seconds (SD 59 seconds) after lidocaine instillation. Despite up to 6 minutes of serial monitoring, the remainder of the lidocaine-instillation group and the entire control group had SBP fluctuations less than 10 mm Hg. The serial mean SBPs of those who responded to lidocaine were significantly less than the remaining groups (P < .001 for both comparisons). CONCLUSION: Utilizing lidocaine's properties to decrease sympathetic-inducing afferents after SCI, the time to onset of action for intravesical lidocaine was found to be approximately 90 seconds. This relatively rapid initial onset on action is especially pertinent when managing autonomic dysreflexia.

Effects of hybrid-functional electrical stimulation (FES) rowing whole-body exercise on neurologic improvement in subacute spinal cord injury: secondary outcomes analysis of a randomized controlled trial.

STUDY DESIGN: Secondary outcome measures analysis of a randomized, controlled study. OBJECTIVE: To assess the effects of hybrid-functional electrical stimulation (FES) rowing on motor and sensory recovery in individuals with spinal cord injury (SCI) 6-18 months post injury. SETTING: Outpatient rehabilitation network. METHODS: 25 participants 6-12 months after SCI were randomly assigned to hybrid-FES rowing (n = 10) or standard of care (n = 15) groups. The hybrid-FES rowing group completed 6 months of rowing scheduled 3 times per week for 26 weeks at an exercise intensity of 70-85% of maximal heart rate. The standard of care group either participated in an arm ergometer exercise program (n = 6) or a waitlist without an explicit exercise program (n = 9). Changes in motor score and combined sensory score of the International Standards for Neurological Classification of SCI (ISNCSCI) were analyzed. RESULTS: Both groups demonstrated increases in motor and combined sensory scores, but no significant differences were noted between intervention groups (motor difference mean ↑1.3 (95% CI, -1.9 to 4.4), combined sensory difference mean ↓10 (-30 to 18)). There was an average of 63% adherence to the hybrid-FES rowing protocol, with no significant correlation in changes in motor or combined sensory score in the hybrid-FES rowing group with total distance or time rowed. CONCLUSIONS: No significant effects to neurologic improvement were found with hybrid-FES rowing when compared with standard of care interventions in individuals with SCI 6-18 months post injury.

Charcot Spine following chronic spinal cord injury: an analysis of 201 published cases.

STUDY DESIGN: Analysis of published cases OBJECTIVES: To identify and describe symptoms, radiologic findings, treatment strategies, and reoccurrence of Charcot spine in individuals with spinal cord injury (SCI). METHODS: This analysis included all English articles published prior to October 2017, describing Charcot spine after SCI as identified by multiple reviewers. Articles were excluded if Charcot spine was attributed to alternative conditions. Individual level data were available for 94% of reported cases. Outcomes included demographic factors, injury characteristics, clinical presentation, radiologic findings, management, and reoccurrence. RESULTS: Fifty included papers described 201 individuals with SCI who developed Charcot spine. 86% of individuals had paraplegia and 93% of individuals had a neurologically complete injury. Mean length of initial spinal fusion spanned 7.7 vertebral bodies (SD = 3.9). The most common presenting symptoms were back pain (56%), spinal deformity (48%), and crepitus (34%). Vertebral body destruction (83%), osteophytes (61%), and endplate destruction (57%) were commonly reported on radiographs. Reoccurrence of Charcot spine was described in 19% of cases after initial treatment. CONCLUSION: Charcot spine after SCI commonly presents with low back pain and radiologic evidence of vertebral body destruction. Cases have been described more often in individuals with paraplegia and neurologically complete injuries. Surgical management is often pursued. A high rate of reoccurrence of Charcot spine in individuals with SCI after initial treatment has been reported.

Why do different people with Spinal Cord Injury have differing severity of symptoms with Autonomic Dysreflexia? Exploring relationships of vascular alpha-1 adrenoreceptor and baroreflex sensitivity after SCI.

Introduction: Individuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness. Objective: To evalate relationship between baroreflex and blood vessel sensitivity with autonomic dysreflexia symptoms. Design: Case control. Setting: Tertiary academic center. Patients: 14 individuals with SCI, 17 matched uninjured controls. Interventions: All participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)-AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15-40 mmHg. Continuous heart rate (R-R interval, ECG), beat-to-beat blood pressures (finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated. Main outcome measures: Baroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2-minute area under the curve and change in vascular resistance. Results: SCI and control cohorts were well-matched with mean age 31.9 and 29.6 years (p=0.41), 21.4% and 17.6% female respectively. Baseline MAP (p=0.83) and R-R interval (p=0.39) were similar. ADFSCI-AD scores were higher following SCI (27.9+/-22.9 vs 4.2+/-2.9 in controls, p=0.002).To quantify SBP response, MAP area under the curve was normalized to dose/bodyweight. Individuals with SCI had significantly larger responses (0.26+/-0.19 mmHg*s/kg*ug) than controls (0.06+/-0.06 mmHg*s/kg*ug, p=0.002). Similarly, leg vascular resistance increased after SCI (24% vs 6% to a normalized dose, p=0.007). Baroreflex sensitivity was significantly lower after SCI (15.0+/-8.3 vs 23.7+/-9.3 ms/mmHg, p=0.01). ADFSCI-AD subscore had no meaningful correlation with vascular responsiveness (R2=0.008) or baroreflex sensitivity (R2=0.092) after SCI. Conclusions: While this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms to explain why some individuals with SCI develop symptoms is needed.

Characterizing preserved autonomic regulation following spinal cord injury: Methods of a novel concerted testing battery and illustrative examples of a new translationally focused data representation.

Autonomic dysfunction is common after spinal cord injury, though differing from motor and sensory function, there are currently no established batteries of tests to comprehensively characterize these deficits. Further, while individual established autonomic tests have a long history and sound scientific background, translating these autonomic testing results to inform clinical understanding is a major barrier. Herein, we outline a battery of six laboratory autonomic tests which were carefully curated to collectively describe the ability of individuals with spinal cord injury to inhibit and recruit sympathetic activity through the injured spinal cord. Presenting normative control data in 23 uninjured individuals completing this testing battery, we further demonstrate the utility of extracting three key testing metrics for each test, comparing these control results to 11 individuals with spinal cord injury. Results demonstrate strong normality of data with testing psychometrics suggesting reliable reproducibility on repeat testing. Further, even in this preliminary sample of individuals with spinal cord injuries, clear differences begin to emerge. This illustrates the ability of this collective testing battery to characterize autonomic regulation after spinal cord injury. To aid in clinical translation, we further present a graphical representation, an autonomic phenotype, which serves as a snapshot of how normal or abnormal sympathetic inhibition and recruitment of activation may be after spinal cord injury. Utilizing these autonomic phenotypes, three example cases of individuals with spinal cord injury highlight evidence of varied degrees of autonomically complete spinal cord injury. Together, this represents a key advancement in our understanding of autonomic function after spinal cord injury.

Autonomic dysreflexia: Current pharmacologic management.

BACKGROUND: Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition are unknown. Correspondingly, it is unclear if national differences in practice patterns exist. OBJECTIVE: To determine trends in current pharmacologic management of AD throughout the Americas. DESIGN: International survey of current physician practice patterns. SETTING: Academic medical center. PARTICIPANTS: Sixty physicians managing patients with SCI and prescribing medications to manage AD. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Presence of a formal pharmacologic AD management protocol, first- and second-line medications, patient characteristics influencing pharmacologic management. RESULTS: The majority of physicians (69%) had a formal AD management protocol for inpatient care, with nitroglycerin ointment (82%) being the most common first-line medication. Strong national differences existed regarding the use of nitroglycerin ointment, with 98% of U.S.-based physicians using this as first-line medication and 0% of physicians in Canada or Latin America using this due to recent lack of medication availability. Only 67% of physicians had a preferred second-line medication, with preferences split between hydralazine (48%) and nifedipine (28%). A systolic blood pressure threshold for pharmacologic management was used by 56% of physicians, wheres 26% considered neurological level of injury in decisions to use medications for AD. Heart rate was used by only 5% of physicians in their decision to manage AD with medications. CONCLUSIONS: As of 2023, U.S.-based physicians caring for individuals with SCI largely have formal inpatient protocols in place for medication management of AD, with nearly all relying on nitroglycerin ointment as their first-line medication. In areas outside of the United States where nitroglycerin ointment is unavailable, pharmacologic practice patterns significantly differ.

Comparing the role of renal ultrasound vs MAG3 renal scans for evaluation of neurogenic bladder after spinal cord injury.

OBJECTIVE: Compare ability of renal ultrasound and Tc-99m mercaptoacetyltriglycine (MAG3) renal scan to identify upper urinary tract stasis. DESIGN: Retrospective chart review. SETTING: Outpatient Neuro-urology clinic serving a large SCI population. PARTICIPANTS: One hundred and sixty-five individuals with spinal cord injury, presenting for annual evaluation. INTERVENTIONS: Renal ultrasound, MAG3 renal scan. OUTCOME MEASURES: Radiologic evidence of upper urinary tract stasis as reviewed by independent radiologist. For renal ultrasounds, this included: mild hydronephrosis, dilation of collecting systems, pelviectasis, or caliectasis. For MAG3 renal scans, this included evidence of slow drainage of radioisotope, dilation of collecting systems, or reverse peristalsis. RESULTS: Forty-five individuals with spinal cord injury demonstrated upper tract stasis, with 12 identified by renal ultrasound and 43 identified by MAG3 renal scan. There was a strong relative correlation between test results (Yule's Q = 0.90), though MAG3 renal scan identified a significantly higher rate of upper tract stasis within the same patients (P < 0.0001). The odds ratio of improved identification using MAG3 renal scan was 16.5 (95% CI 3.96-68.76). CONCLUSIONS: While renal ultrasound is more effective at evaluating renal anatomy, MAG3 renal scan identifies significantly more upper urinary tract stasis than renal ultrasound and should be considered for SCI individuals with risk factors of upper tract injury.

Diagnosis and management of cardiometabolic disease after spinal cord injury: Identifying gaps in physician training and practices.

CONTEXT: Cardiometabolic disease (CMD) frequently occurs in individuals with spinal cord injury (SCI), with growing awareness surrounding the expansive scope of this problem. As CMD has significant morbidity and mortality, early guidelines-based screening and management have been established. However, the extent to which these guidelines have been adopted are unclear. OBJECTIVE: Describe physicians' screening and management pattern for CMD in patients with SCI, as compared to SCI-specific CMD screening guidelines, and elucidate variables linked to screening and management patterns. METHODS: SCI medicine-boarded physicians were surveyed on screening timing for CMD following acute SCI, along with their practice pattern and comfort level managing common CMD risk factors. RESULTS: Of the forty-seven SCI medicine physicians that responded, 62% felt the ideal timing for CMD screening is 6 months after the acute injury. Of these same physicians, few were screening for insulin resistance and lipid dysregulation prior to 6 months after injury. In addition, less than half felt comfortable writing new prescriptions for anti-glycemic and anti-lipid medications. Furthermore, no association was found between the amount of CMD education with screening or management patterns. Finally, VA-based providers were more likely to screen for CMD within 6 months of injury and were more comfortable managing/starting anti-glycemic medications and statins. CONCLUSIONS: Despite the presence of SCI-specific CMD guidelines, gaps in screening and management practices still exist, most notably with insulin resistance and lipid dysregulation. VA-based providers generally screen and manage CMD risk factors more effectively, and further CMD education could consider emulating VA training modules.

The Impact of Transcutaneous Spinal Cord Stimulation on Autonomic Regulation after Spinal Cord Injury: A randomized crossover trial.

Importance: Individuals with spinal cord injury (SCI) have significant autonomic nervous system dysfunction. However, despite recent findings postulated to support that spinal cord stimulation improves dynamic autonomic regulation, limited scope of previous testing means the true effects remain unknown. Objective: To determine whether transcutaneous spinal cord stimulation improves dynamic autonomic regulation after SCI. Design: Single-blinded, randomized crossover trial with matched cohorts. Setting: Academic autonomic physiology laboratory. Participants: Two pairs of well-matched individuals with and without high-thoracic, complete SCI. Interventions: Sub-motor threshold transcutaneous spinal cord stimulation delivered at T10-T11 using 120Hz, 30Hz, and 30Hz with 5kHz carrier frequency at separate autonomic testing sessions. Main Outcomes and Measures: Baseline autonomic regulation was characterized with tests of above injury level sympathoexcitation (Valsalva's maneuver), sympathoinhibition (progressive doses of bolus intravenous phenylephrine), and below level sympathoexcitation (foot cold pressor test). At three subsequent visits, this testing battery was repeated with the addition of spinal cord stimulation at each frequency. Changes in autonomic regulation for each frequency were then analyzed relative to baseline testing for each individual and within matched cohorts. Results: Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. Contrasting this, and as expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared to baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in autonomic regulation. Conclusions and Relevance: Transcutaneous spinal cord stimulation does not improve autonomic regulation after SCI, and instead likely generates tonic, frequency-dependent sympathoexcitation which may lower the threshold for autonomic dysreflexia.

Toward rebalancing blood pressure instability after spinal cord injury with spinal cord electrical stimulation: A mini review and critique of the evolving literature.

High-level spinal cord injury commonly leads to blood pressure instability. This manifests clinically as orthostatic hypotension (OH), where blood pressure can drop to the point of loss of consciousness, and autonomic dysreflexia (AD), where systolic blood pressure can climb to over 300 mmHg in response to an unperceived noxious stimulus. These blood pressure fluctuations can occur multiple times a day, contributing to increased vessel shear stress and heightened risk of cardiovascular disease. The pathophysiology of both of these conditions is rooted in impairments in regulation of spinal cord sympathetic preganglionic neurons, which control blood pressure by mediating vascular resistance and catecholamine release. Recently, spinal cord electrical stimulation has provided evidence that it may modulate these blood pressure imbalances. Early proposed mechanisms suggest activation of spinal cord dorsal horn neurons that ultimately act upon the sympathetic preganglionic neuronal pathways. For OH, spinal cord stimulation likely induces local activation of these neurons to generate baseline sympathetic tone and accompanying vasoconstriction. The mechanisms for spinal stimulation regulating AD are less clear, though some suggest it activates inhibitory circuits to dampen the overactive sympathetic response. While questions remain, spinal cord electrical stimulation is an intriguing new modality that may restore blood pressure regulation following spinal cord injury.

Relationship of cardiometabolic disease risk factors with age and spinal cord injury duration.

CONTEXT/OBJECTIVES: Cardiometabolic disease (CMD) is increased after spinal cord injury (SCI), with an increased number of CMD risk factors that relate to higher mortality. The study objective was to characterize the relationship of age and injury duration with CMD. DESIGN: Retrospective cohort assessment of CMD risks using unbiased recursive partitioning to divide for group comparison: (1) Lowest Risk, (2) Moderate Risk, and (3) Highest Risk based on classification and regression trees predicting CMD diagnosis by age and injury duration. SETTING: Academic rehabilitation center laboratory. PARTICIPANTS: Adults (N = 103; aged 18-75) with traumatic SCI (C4-L2) of 3 months to 42 years duration. INTERVENTIONS: NA. OUTCOME MEASURES: CMD risk factors (obesity, insulin resistance, dyslipidemia, and hypertension) using Paralyzed Veterans of America SCI-specific guidelines. RESULTS: Obesity was prevalent (82%) and co-occurred with most other risk factors present. Age increased odds for CMD diagnosis by 1.05 per year (P = 0.02) and was directly related to elevated body mass index (BMI, ß = 0.42, P < 0.05), fasting glucose (ß = 0.58, P < 0.01), and higher systolic blood pressure (ß = 0.31, P < 0.10). In contrast, time since injury contributed to lower risk factor count (ß = -0.29, P < 0.10) and higher HDL-C (ß = 0.50, P < 0.01), and was not related to odds of CMD diagnosis. CONCLUSION: While SCI is linked to an increased risk of CMD, age is associated with higher CMD risk. Increased SCI duration related to improvement in individual CMD risk factors but did not decrease overall risk for CMD diagnosis. SCI may not uniformly increase CMD risks and highlight a necessary focus on weight management for risk prevention.

Methodologic implications for rehabilitation research: Differences in heart rate variability introduced by respiration.

BACKGROUND: Heart rate variability is a measure of autonomic activity that is growing in popularity as a research outcome. However, despite its increased use, the known effects of respiration on heart rate variability measures are rarely accounted for in rehabilitation medicine research, leading to potential misinterpretation. OBJECTIVE: To describe the effect that unpaced and paced breathing introduces to heart rate variability measures in a rehabilitation medicine relevant example of individuals with spinal cord injury. DESIGN: Cross-sectional comparison of heart rate variability during unpaced and paced breathing (0.25 Hz, 15 breaths per minute) within the same individuals during the same lab session. SETTING: Academic autonomic physiology laboratory. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mean low frequency (LF) and high frequency (HF) heart rate variability power, percentage of total power derived from the LF spectrum, LF:HF ratio. RESULTS: Fifty-nine individuals with spinal cord injury completed laboratory assessments using standardized protocols (NCT02139436). In repeated measures within individuals, mean LF power was significantly higher in unpaced breathing compared to paced breathing (1292 vs. 573 ms2 , p < .001). A Bland-Altman plot demonstrated significant positive proportional bias for LF power when comparing unpaced and paced breathing conditions (R2  = 0.39). Mean HF power was similar between unpaced and paced breathing conditions, although there were wide positive and negative differences between measures, leading to notable uncertainty when respiratory confounders were not accounted for. The percentages of total power derived from the LF spectrum and the mean LF:HF ratio were both significantly higher for unpaced breathing compared to paced breathing (64 vs. 42%, p < .001; and 3.2 vs. 1.1, p < .001, respectively). CONCLUSION: Respiration has a significant effect on heart rate variability following spinal cord injury, and not accounting for this has serious consequences for accurate interpretation of unpaced data. Future studies of heart rate variability in rehabilitation medicine should accordingly consider paced breathing.