Burns, Kathryn

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.