Citations

Background: Autonomic dysfunction is common after spinal cord injury (SCI). There are currently limited tools to comprehensively characterize its deficits. 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. Objectives: To assess a strategic battery of autonomic tests to characterize and act as a biomarker of autonomic regulation for individuals with SCI and to develop a novel graphical representation of these data to facilitate understanding of autonomic dysfunction after SCI. Methods: We outline a battery of six laboratory autonomic tests that were curated to collectively describe the ability of individuals with SCI to inhibit and recruit sympathetic activity through the injured spinal cord. Heart rate/blood pressure variability, bolus phenylephrine, hand and foot cold pressor, Valsalva maneuver, and bladder pressor are herein described. Incorporating normative control data for 30 uninjured individuals completing this testing battery, we further demonstrate the utility of a composite biomarker, comparing these control results to 11 individuals with SCI. Results: Results demonstrate strong normality of data with testing psychometrics, suggesting stable reproducibility with repeat testing. Even in this preliminary sample of individuals with SCI, clear differences begin to emerge compared to uninjured norms. This illustrates the ability of this collective testing battery to characterize autonomic regulation after SCI. 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 SCI. Conclusion: Utilizing these autonomic phenotypes, three example cases of individuals with SCI highlight evidence of varied degrees of autonomically complete SCI. Together, this represents a key advancement in our understanding of autonomic function after SCI.

AbstractBackgroundIndividuals 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.ObjectiveTo evaluate the relationship between baroreflex and blood vessel sensitivity with AD symptoms.DesignCase control.SettingTertiary academic center.Patients14 individuals with SCI, 17 matched uninjured controls.InterventionsAll 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 MeasuresBaroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2‐minute area under the curve and change in vascular resistance.ResultsSCI and control cohorts were well matched with mean age 31.9 and 29.6 years (p = .41); 21.4% and 17.6% female, respectively. Baseline MAP (p = .83) and R‐R interval (p = .39) were similar. ADFSCI‐AD scores were higher following SCI (27.9 ± 22.9 vs. 4.2 ± 2.9 in controls, p = .002). To quantify SBP response, MAP area under the curve was normalized to dose/body weight. Individuals with SCI had significantly larger responses (0.26 ± 0.19 mmHg*s/kg*μg) than controls (0.06 ± 0.06 mmHg*s/kg*μg, p = .002). Similarly, leg vascular resistance increased after SCI (24% vs. 6% to a normalized dose, p = .007). Baroreflex sensitivity was significantly lower after SCI (15.0 ± 8.3 vs. 23.7 ± 9.3 ms/mmHg, p = .01). ADFSCI‐AD subscore had no meaningful correlation with vascular responsiveness (R2 = 0.008) or baroreflex sensitivity (R2 = 0.092) after SCI.ConclusionsAlthough this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, contrary to our hypothesis these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms is needed to explain why some individuals with SCI develop symptoms.

Abstract 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 autonomically-mediated secondary medical complications after SCI.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. While 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 sub-motor 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 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 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.