Individuals with spinal cord injury (SCI) face a disproportionate burden of obesity and cardiometabolic disease, however, evidence to guide pharmacologic treatment is minimal. Mainstay diet and exercise recommendations often yield modest, unsustainable results for those with SCI. In the general population, glucagon-like peptide-1 receptor agonists and dual agonists (GLP-1s) have emerged as potent therapies for obesity and related cardiometabolic disorders. Initially developed for type 2 diabetes mellitus, GLP-1s improve glycemic control, promote substantial weight loss, and reduce other cardiometabolic risk factors. Although robust data from the general population show weight-dependent and independent benefits, evidence specific to SCI is limited to case presentations. These reports suggest the potential for significant reductions in body fat and improvements in cardiometabolic risk. However, concerns remain regarding potential complications, including worsened gastrointestinal dysfunction, reduced muscle mass with a proclivity to develop pressure injuries, and further compromises in bone density. This special communication draws on evidence from the general population and limited SCI-specific evidence to examine the relevance of GLP-1s for individuals with SCI and provides commentary on key clinical considerations for navigating their use in this population.

Objective To evaluate the feasibility and potential efficacy of percutaneous spinal stimulation (epidural stimulation, ES) combined with task-specific training to reduce spasticity and improve gait and balance in individuals with progressive multiple sclerosis (MS). Methods Two men with progressive MS (EDSS 6.5) underwent ES lead implantation targeting the lower spinal cord, followed by one month of rehabilitation involving 12 ES-assisted training sessions. Assessments included instrumented gait analysis, Modified Ashworth Scale (MAS), pendulum test, and static balance testing performed at baseline, and at end of the study with ES-Off and ES-On conditions. Results Participant 1, with spastic hemiparetic gait, demonstrated improved lower extremity joint kinematics and muscle activation during gait, reduced knee extensor spasticity, and enhanced functional movement patterns with ES-On. Participant 2, with significant paraparesis and minimal spasticity, showed limited gait changes but experienced marked improvements in static balance, particularly under eyes-closed conditions. No adverse events were reported. Conclusion This pilot study demonstrates the feasibility and tolerability of ES paired with task-specific training in progressive MS. Participant-specific responses were observed, including improvements in gait kinematics, neuromuscular activation, spasticity, or balance; however, spatiotemporal gait parameters did not improve. These preliminary findings highlight response heterogeneity and the need for individualized ES parameter tuning. Trial registry name and URL: https://clinicaltrials.gov/study/NCT06019611

Between 1940 and 2010, life expectancy doubled for people with spinal cord injury (SCI). In response to this survival trend, literature emerged examining how people grow older with SCI. While some authors posited that people with SCI age prematurely, others focused on the incidence of coexisting conditions over the course of an injury. These latter data are important in that they can help individuals with SCI, their care partners, and clinicians anticipate medical needs, but they fail to capture the subjective experience of aging with SCI. To date, no work has examined the complex health-related challenges that may attend longer standing injuries or whether and how the presentation and management of coexisting conditions change over time. Given this dearth of knowledge around the real-world experiences of aging with SCI, the authors hosted a community-focused, peer-led, Zoom-based conference addressing medical challenges specific to growing older with SCI. Focusing on bone health, chronic pain, blood pressure management, and neurogenic bladder, invited speakers presented cases and a moderator facilitated discussions between attendees. In this report, we summarize the concerns and questions that arose during the conference and propose topics for future investigation.

Spinal cord injury (SCI) results in permanent impairment of sensory, motor and autonomic function. Epidural electrical stimulation (EES) applied below the lesion can restore voluntary movement, autonomic function and locomotion following chronic SCI. However, impaired sensation below the SCI does not improve during the application of sublesional EES. Here we present first-in-human results demonstrating simultaneous lower extremity motor activation and somatosensory feedback in three participants with motor complete, chronic SCI enabled by perilesional EES. We determined motor- and sensory-specific EES parameters by leveraging modern deep learning methods and participant-directed control of stimulation. Supralesional EES evoked sensations were synchronized with leg movement, enabling participants to accurately report leg position. We then applied simultaneous supralesional and sublesional EES, enabling intentional control over leg movements and somatosensory feedback during functional tasks. Overall, we demonstrate a perilesional EES framework to modulate sensorimotor function that may improve quality of life in individuals with SCI.

Study objective: To characterize physiologic autonomic dysfunction in humans after chronic spinal cord injury (SCI) relative to uninjured controls and to identify autonomic correlates to neuroimmune deficits. Hypothesis: Individuals with greater autonomic dysfunction after SCI will have more pronounced immune dysfunction, which will be further influenced by sympathetically mediated increases in catecholamine levels. Methodology: Both uninjured controls and individuals with SCI completed a battery of autonomic physiology tests aimed at characterizing preservation of supralesional/sublesional sympathetic activation and global sympathetic inhibition. The autonomic testing battery included 3-minute hand and foot cold pressor tests, 3 Valsalva maneuvers with goal expiratory pressure of 30 mmHg, a novel bladder pressor test (5 minutes of sustained bladder pressure at 35 cmH20 with room temperature sterile water infusion), paced breathing at 0.25 Hz for heart rate/blood pressure variability, and successive doses of bolus intravenous phenylephrine (Oxford technique). A subset of individuals in both cohorts had baseline and cold pressor stressed levels of catecholamines/cortisol drawn and immunologic assessments. Peripheral blood mononuclear cells were extracted from this baseline sample and assessed with flow cytometry for cellular exhaustion markers (CD69, PD-1, TIGIT, TIM-3). Antigen recall response, with/without primed exposure of catecholamines was also completed to identify how sympathetic activation variably impacted functional immune performance with exposure to viral peptides. Data: n=35 uninjured controls; n=29 individuals with SCI Summary of Results: When compared to uninjured controls, individuals with SCI demonstrated significant autonomic dysfunction in all three domains, with decreased supralesional sympathetic activation (Valsalva pressure recovery time, p< 0.0001), abnormal sublesional sympathetic activation (increased bradycardia, p< 0.0001), and impaired sympathetic inhibition (larger dose/body-weight adjusted increase in mean arterial pressure, p=0.0006). As expected, autonomic dysfunction in those with SCI existed on a continuum, with some having largely normal autonomic regulation and others exhibiting profound deficits. Principal component analysis confirmed these three domains as the primary drivers of variability. Cellular exhaustion markers were increased in those with SCI, with positive correlation (R2=0.42) between degree of global autonomic dysfunction (Z-score over 2.0) and CD3+ CD8+ T-cell TIM-3 immunologic exhaustion markers. Antigen recall response was impaired in those with SCI and autonomic dysfunction on physiologic testing, with pronounced decrement in response when catecholamines were added (mean 57% of response lost in CD69 T-cells to Epstein-Barr virus antigen exposure, 53% lost to Flu antigen). Conclusions: In humans with SCI, early evidence supports that individuals have greater autonomic dysfunction and that this is correlated to increased immunologic deficits. Funding Sources: NIH K23HD102663, R01NS115126 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

OBJECTIVE:This study aimed to evaluate the off-target effects of motor-optimized SCS-enabled task-specific training (SCS-TST) on lower urinary tract function through self-reported data from individuals with chronic spinal cord injury (SCI), using the Neurogenic Bladder Symptom Score (NBSS). A secondary objective was to explore whether participant characteristics or bladder treatments were associated with changes in NBSS outcomes. DESIGN:Datasets from two prospective pilot trials using percutaneous spinal cord stimulation (SCS) to enable motor function were analyzed and reported. SETTING:Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota. PARTICIPANTS:Adults ≥ 1-year post traumatic SCI. INTERVENTIONS:Participants received either 12 days of epidural stimulation (ES) or 10 days of ES and dorsal root ganglion stimulation (ESDRS), each coupled with 6-8 SCS-TST sessions. OUTCOME MEASURES:NBSS was administered pre- and post-intervention. RESULTS:Analysis of 23 participants (ES, n = 3; ESDRS, n = 20) showed no significant group-level changes in total NBSS (p = 0.49) or functional domains (p = 0.56-0.85). Individually, 83% demonstrated no clinically meaningful change, while 9% improved and 9% worsened. Exploratory analyses identified that symptom change was associated with neurological level of injury (p = 0.017), age (p = 0.026), and marginally associated with injury severity (p = 0.055). Oxybutynin use was associated with lower symptom variability, without statistical significance (p = 0.074). CONCLUSIONS:Motor-optimized SCS-TST did not lead to significant group-level changes in patient-reported urinary symptoms. However, a subset of individuals experienced improvement or worsening, suggesting that injury characteristics and medication use may influence urinary outcomes. These preliminary findings warrant confirmation in larger, adequately powered trials.Trial Registration: ClinicalTrials.gov identifiers: NCT05095454, NCT04736849.

The expanding application of spinal stimulation therapies in spinal cord injury (SCI) rehabilitation necessitates a critical reexamination of cardiovascular (CV) responses to these interventions. A key question arises: How should blood pressure (BP) responses to stimulation be interpreted, and does the conventional definition of autonomic dysreflexia (AD) adequately capture these phenomena? Researchers remain divided-some classify BP elevations during stimulation as AD, while others attribute them to intentional neuromodulation targeting sympathetic preganglionic neurons. This review scrutinizes the various AD definitions in the literature, including the conventional threshold (systolic BP increase >20 mmHg), revealing substantial limitations in research contexts. While symptomatic AD occurs in only 4-7% of stimulation study participants, asymptomatic BP increases are considerably more frequent. This established threshold lacks robust physiological rationale and creates significant interpretive challenges, particularly when evaluating interventions designed to modulate BP responses. The current limitations of guideline-based definitions of AD challenge research interpretation and clinical translation. Although several publications describe AD as "unregulated" or "uncontrolled," it has not yet been incorporated into formal guideline definitions. This review underscores the need for a collaborative effort to refine AD definitions in research, particularly in the context of spinal stimulation. Future consensus development should address whether uniform thresholds should apply across different contexts, how to integrate heart rate dynamics and absolute BP values alongside symptomatic status, and how to meaningfully distinguish therapeutic BP modulation from adverse autonomic responses. This is essential for standardizing research approaches, optimizing stimulation parameters, and ensuring efficacy and safety as spinal stimulation technologies advance clinically.

BACKGROUND: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 evaluate the relationship between baroreflex and blood vessel sensitivity with AD 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 = .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. CONCLUSIONS:Although 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.

Background: Emerging neuromodulation approaches, including epidural electrical stimulation (EES), offer hope for restoration of function following chronic spinal cord injury (SCI). However, integrating neuromodulation therapies into clinical procedures is challenging due to the unique needs of the SCI population. Objectives: The purpose of this study was to understand the experiences of participants during a first-in-human trial of perilesional EES aimed at restoring sensorimotor function. Methods: We report participants' experiences by describing their clinical care, experiences during experimental neuromodulation sessions, and perspectives on the utility of a perilesional EES system. Three participants with chronic thoracic SCI participated in semistructured interviews after completing a 14-day inpatient experimental protocol, which included stimulation mapping, lower extremity motor control experiments, and treadmill stepping. Interview data were analyzed using an applied thematic analysis approach. Nine key themes addressed 4 major topic areas: clinical experiences, experiences during laboratory experiments, experiences as a research participant, and perceived value of perilesional EES. Results: All participants noted the potential for EES to enhance functional recovery, though their postoperative experiences related to clinical care, postoperative pain, and disruptions to routine care differed. Insights gained from qualitative analyses highlighted challenges and opportunities for improving postsurgical care and refining application of EES technology. Further, these results inform recommendations for neuromodulation trials in the SCI community to help mitigate postoperative complications and improve study participant experiences. Conclusion: Key recommendations include being proactive regarding potential postsurgical complications, educating clinical staff regarding common SCI comorbidities, and customizing experimental protocols to align with the priorities and clinical needs of each participant

BACKGROUND:Individuals with spinal cord injury (SCI) are known to have high rates of cardiovascular disease that have traditionally been attributed to inability to engage in adequate intensity exercise. However, individuals with SCI also commonly experience instability in blood pressure. Blood pressure fluctuations are known to contribute to cardiovascular disease in other conditions, though this relationship in SCI is unknown. OBJECTIVE:To evaluate correlations between a clinical history of symptomatic blood pressure instability and objective evidence of vascular endothelial dysfunction in individuals with SCI. DESIGN:Case control. SETTING:Academic medical center. PARTICIPANTS:Twenty-four individuals with SCI, 14 uninjured controls of matched age, gender, and body mass index. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Symptomatic blood pressure instability was measured by the Autonomic Dysfunction Following SCI (ADFSCI) survey. Vascular endothelial dysfunction was quantified by ultrasound recordings of brachial flow mediated dilation following 5 minutes of forearm arterial occlusion. RESULTS:Total ADFSCI scores were significantly higher in individuals with SCI compared to controls (41.0 vs. 9.0, p = .002). Both percentage of brachial flow mediated dilation and consensus recommended allometrically scaled percentage of flow mediated dilation were significantly less in individuals with SCI (p < .001 for both), demonstrating greater vascular dysfunction. More symptoms of blood pressure instability on the ADFSCI survey were correlated with more objective evidence of vascular dysfunction (R2 = 0.24, p = .03) for individuals with SCI. This relationship was not seen in uninjured controls. CONCLUSIONS:In individuals with SCI, more severe symptoms of blood pressure instability are significantly correlated with more severe vascular endothelial dysfunction, making management of orthostatic hypotension and autonomic dysreflexia both high potential, modifiable risk factors for individuals with SCI to mitigate cardiovascular disease.

BACKGROUND:After high-level spinal cord injury (SCI), motor recovery of wrist extensors has significant functional consequences as it can facilitate grasp through tenodesis. A small seminal study from 1993 established widely used prognostic rules for wrist extensor recovery, though these have not been replicated with larger, real-world samples since inception. OBJECTIVE:To determine the prognostic value of initial C5 sharp-dull discrimination, C5 motor strength, and C6 motor strength on predicting 1-year ipsilateral wrist extensor motor recovery for patients with SCI with neurological level of C4 or C5. DESIGN:Retrospective cohort replication study. SETTING:SCI Model Systems. PARTICIPANTS:35,675 total individuals with acute traumatic SCI with 219 cases of initial wrist extensor weakness (0/5-2/5) meeting inclusion criteria. INTERVENTION:Not applicable. MAIN OUTCOME MEASURE:Recovery of wrist extensor strength to ≥3/5 at 1 year. RESULTS:The positive predictive and negative predictive values were 57% (95% CI, 47.4%-66.1%) and 66% (56.0%-75.1%) if initial C5 sharp-dull discrimination was present, 61% (52.7%-69.3%) and 82% (71.4%-89.7%) if initial C5 myotome strength was at least antigravity, and 74% (63.7%-82.5%) and 74% (65.5%-81.4%) if initial C6 myotome strength was at least a 1/5 or 2/5. Synthesizing these three rules, an updated branched nomogram for functional wrist extensor recovery prediction was created. CONCLUSIONS:In isolation, none of the previously established wrist extensor motor recovery predictive rules had as high of a prognostic value when using a larger dataset. As such, singular reliance on these prediction rules to identify who will gain 1-year antigravity wrist extension should be approached with decreased certainty. The best positive and negative predictors were trace C6 strength and absent C5 strength, respectively. An updated nomogram provides more nuanced prognostic information to guide clinical care following acute SCI.

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.

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. 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. 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

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.

Abstract Study Design: Secondary outcome measures analysis of a randomized, controlled study. Objectives: To assess the effects of hybrid-functional electrical stimulation (FES) rowing, arms only (AO) rowing and waitlist (WL) controls on pain, pain interference, and depression in individuals with spinal cord injury (SCI). Setting: Outpatient rehabilitation networks Methods: 44 participants were randomly assigned to FES (n = 19), AO (n= 12) or WL (n=13). The FES group completed 6 months of rowing scheduled 3 times per week. Individuals in the AO and WL groups were allowed to cross over to FES rowing after 6 months and were included in subsequent analyses of the effects of FES rowing. Rowing distance and intensity was logged, and maximal oxygen consumption (VO2max) measures were obtained before and after the intervention. Changes in the Patient-Reported Outcomes Measurement Information System (PROMIS-56) derived pain interference, pain, and depression scores were analyzed. Results: FES-rowing led to modest improvements in depression, AO led to modest improvements in pain intensity, and WL did not improve pain nor depression. After incorporating individuals who crossed over to FES rowing, we observed modest but significant improvement in depression scores but not in pain. Among the participants who benefited from the FES intervention, the reduction in depression was correlated to the average weekly rowing distance (r2=0.79 p=0.0001). Conclusions: 6 months of FES rowing spent in a supportive environment can help persons with spinal cord injuries alleviate moderate depression in a dose-dependent manner.

Leveraging genetics to optimize rehabilitation outcomes after spinal cord injury: contemporary challenges and future opportunities

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.

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.