Treatment of orthostatic hypotension during acute inpatient rehabilitation after spinal cord injury: usual care versus anti-hypotensive therapy.

BACKGROUND: To compare pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). METHODS: Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5) and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?". Study participants and therapists were unaware of group assignment. RESULTS: A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT and 17 in the UC group. There was an average of 81±51 therapy sessions/participant in the TXT and 60±27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9±8 sessions/participant in the TXT group and 10±12 sessions/participant in the UC group. Neither the total number of therapy sessions (p=0.16) nor group assignment (p=0.83) significantly predicted the number of sessions affected by low BP. CONCLUSIONS: These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to usual care treatment of symptomatic hypotension and OH in newly injured patients with SCI.

The effects of sustained, low- and high-intensity isometric tasks on performance fatigability and the perceived responses that contributed to task termination.

PURPOSE: The present study examined the effects of sustained, isometric low- versus high-intensity tasks on time to task failure (TTF), performance fatigability (PF), ratings of perceived exertion (RPE), and the perceived causes of task termination from a post-test questionnaire (PTQ). METHODS: Ten men (mean ± SD: age = 21.1 ± 2.3 years; height = 180.2 ± 5.7 cm; body mass = 79.5 ± 8.8 kg) performed maximal voluntary isometric contractions (MVICs) before and after fatiguing, isometric forearm flexion tasks anchored to the torque corresponding to RPE values of 2 (TRQ2FT = 23.8 ± 7.1 N·m) and 8 (TRQ8FT = 60.9 ± 11.4 N·m). In addition, the subjects completed a PTQ which surveyed whether the perceived sensations of fatigue or pain, and/or the psychological factors of loss of focus and motivation contributed to the decision to terminate the task. Repeated measures ANOVAs, Wilcoxon-Signed Rank tests, and Spearman's Rank-Order Correlations were used to analyze the data. RESULTS: Across the fatiguing tasks, there were similar decreases in MVIC torque (95.2 ± 20.3 vs. 68.9 ± 15.6 N·m; p < 0.001) and RPE values (p = 0.122) at task failure for TRQ2FT (7.4 ± 2.7) and TRQ8FT (8.9 ± 1.0), but a longer (p = 0.005) TTF for the TRQ2FT (245.0 ± 177.0 s) than TRQ8FT (36.8 ± 11.1 s). CONCLUSIONS: Despite reaching task failure, the subjects were able to perform MVICs that were 100-300% greater than the target torque values within seconds of terminating the tasks. Thus, we hypothesized that task failure was not caused by an inability to produce sufficient torque to sustain the tasks, but rather an unwillingness to continue the task.

Transcutaneous Spinal Cord Stimulation to Stabilize Seated Systolic Blood Pressure in Persons With Chronic Spinal Cord Injury: Protocol Development.

Transcutaneous spinal cord stimulation (tSCS) is an emerging therapeutic strategy to target spinal autonomic circuitry to normalize and stabilize blood pressure (BP) in hypotensive persons living with chronic spinal cord injury (SCI). Our aim is to describe our current methodological approach to identify individual tSCS parameters that result in the maintenance of seated systolic blood pressure (SBP) within a pre-defined target range. The parent study is a prospective, randomized clinical trial in which eligible participants will undergo multiple mapping sessions to optimize tSCS parameter settings to promote stable SBP within a target range of 110-120 mm Hg for males and 100-120 mm Hg for females. Parameter mapping includes cathode electrode placement site (T7/8, T9/10, T11/12, and L1/2), stimulation frequency (30, 60 Hz), current amplitudes (0-120 mA), waveform (mono- and biphasic), pulse width (1000 µs), and use of carrier frequency (0, 10 kHz). Each participant will undergo up to 10 mapping sessions involving different electrode placement sites and parameter settings. BP will be continuously monitored throughout each mapping session. Stimulation amplitude (mA) will be increased at intervals of between 2 and 10 mA until one of the following occurs: 1) seated SBP reaches the target range; 2) tSCS intensity reaches 120 mA; or 3) the participant requests to stop. Secondary outcomes recorded include 1) symptoms related to autonomic dysreflexia and orthostatic hypotension, 2) Likert pain scale, and 3) skin appearance after removal of the tSCS electrode. Clinical Trials Registration: NCT05180227.

Unilaterally Induced Quadriceps Fatigue during Sustained Submaximal Isometric Exercise Does Not Alter Contralateral Leg Extensor Performance.

This study investigated the effects of fatiguing unilateral exercise on the ipsilateral, exercised, and contralateral, non-exercised limb's post-exercise performance in males and females. Ten males and ten females performed a fatiguing, unilateral isometric leg extension at 50% maximal voluntary isometric contraction (MVIC) force. Prior to and immediately after the fatiguing tasks, MVICs were performed for the exercised and non-exercised limb, with surface electromyographic (sEMG) and mechanomyography (sMMG) amplitude (AMP) and mean power frequency (MPF) recorded from each limb's vastus lateralis. There were no fatigue-induced, sex-dependent, differences in time to task failure (p = 0.265) or ipsilateral performance fatigability (p = 0.437). However, there was a limb by time interaction (p < 0.001) which indicated decreases in MVIC force of the ipsilateral, exercised (p < 0.001), but not the contralateral, non-exercised limb (p = 0.962). There were no sex-dependent, fatigue-induced differences in neurophysiological outcomes between the limbs (p > 0.05), but there was a fatigue-induced difference in sEMG MPF (p = 0.005). To summarize, there were no differences in fatigability between males and females. Moreover, there was insufficient evidence to support the presence of a general crossover effect following submaximal unilateral isometric exercise. However, independent of sex, the neurophysiological outcomes suggested that competing inputs from the nervous system may influence the performance of both limbs following unilateral fatigue.

Sex differences in NIRS-derived values of reactive hyperemia persist after experimentally controlling for the ischemic vasodilatory stimulus.

Men and women exhibit different near-infrared spectroscopy (NIRS) outcomes in response to vascular occlusion tests (VOT), which may be due to phenotypic characteristics or different degrees of desaturation during ischemia. The minimum skeletal muscle tissue oxygenation (StO2min) observed during a VOT may be the primary determinant of reactive hyperemic (RH) responses. Our purpose was to determine the contribution StO2min and participant characteristics including adipose tissue thickness (ATT), lean body mass (LBM), muscular strength, and limb circumference to NIRS-derived indexes of RH. Also, we aimed to determine if matching StO2min would eliminate NIRS-VOT sex differences. Thirty-one young adults completed one or two VOTs during which the vastus lateralis was continuously assessed for StO2. The men and women each completed a standard VOT with a 5-min ischemic phase. The men completed a second VOT with a shortened ischemic phase to produce a matching StO2min to the minimum of the women observed during the standard VOT. Mean sex differences were determined with t tests, and relative contributions were assessed with multiple regression and model comparison approaches. During the 5-min ischemic phase, the men exhibited greater upslopes (1.97 ± 0.66 vs. 1.23 ± 0.59%·s-1) and greater StO2max than the women (80.3 ± 4.17 vs. 76.2 ± 2.86%). Analysis revealed StO2min was a greater contributor to upslope than sex and/or ATT. For StO2max, sex was the only significant predictor (r2 = 0.26, men ∼4.09% > women). Experimentally matching StO2min did not eliminate the sex differences in upslope or StO2max, suggesting that characteristics other than the degree of desaturation primarily provoke sex differences in RH.NEW & NOTEWORTHY Men exhibit greater values of reactive hyperemia than women even when controlling for the magnitude of desaturation during transient ischemia. Factors other than the ischemic vasodilatory stimulus, such as skeletal muscle mass and quality, likely provoke the commonly reported sex differences in reactive hyperemia measured by near-infrared spectroscopy.

Autonomic Cardiovascular Control, Psychological Well-Being, and Cognitive Performance in People With Spinal Cord Injury.

PURPOSE: To examine associations between parameters of psychological well-being, injury characteristics, cardiovascular autonomic nervous system (ANS) control, and cognitive performance in persons with spinal cord injury (SCI) compared with age-matched uninjured controls. This is an observational, cross-sectional study including a total of 94 participants (52 with SCI and 42 uninjured controls: UIC). Cardiovascular ANS responses were continuously monitored at rest and during administration of the Paced Auditory Serial Addition Test (PASAT). Self-report scores on the SCI-Quality of Life questionnaires are reported for depression, anxiety, fatigue, resilience, and positive affect. Participants with SCI performed significantly more poorly on the PASAT compared with the uninjured controls. Although not statistically significant, participants with SCI tended to report more psychological distress and less well-being than the uninjured controls. In addition, when compared with uninjured controls, the cardiovascular ANS responses to testing were significantly altered in participants with SCI; however, these responses to testing did not predict PASAT performance. Self-reported levels of anxiety were significantly related to PASAT score in the SCI group, but there was no significant relationship between PASAT and the other indices of SCI-Quality of Life. Future investigations should more closely examine the relationship among cardiovascular ANS impairments, psychological disorders, and cognitive dysfunction to better elucidate the underpinnings of these deficits and to guide interventions aimed at improving physiological, psychological, and cognitive health after SCI. Tetraplegia, paraplegia, blood pressure variability, cognitive, mood.

Clinical trial of home blood pressure monitoring following midodrine administration in hypotensive individuals with spinal cord injury.

BACKGROUND: Individuals with spinal cord injury (SCI) above thoracic level-6 (T6) experience impaired descending cortical control of the autonomic nervous system which predisposes them to blood pressure (BP) instability, including includes hypotension, orthostatic hypotension (OH), and autonomic dysreflexia (AD). However, many individuals do not report symptoms of these BP disorders, and because there are few treatment options that have been proven safe and effective for use in the SCI population, most individuals remain untreated. OBJECTIVE: The primary aim of this investigation was to determine the effects of midodrine (10 mg) prescribed TID or BID in the home environment, compared to placebo, on 30-day BP, study withdrawals, and symptom reporting associated with OH and AD in hypotensive individuals with SCI. DESIGN/METHODS: Participants were randomly assigned to received midodrine/placebo or placebo/midodrine, with a 2-weeks washout period in between, and both the participants and investigators were blinded to randomization order. Study medication was taken 2 or 3 times/day, depending on their sleep/wake schedule, BP, and any related symptoms were recorded before and 1 h after each dosage and periodically throughout the day. RESULTS: Nineteen individuals with SCI were recruited; however, 9 withdrew prior to completion of the full protocol. A total of 1892 BP recordings (75 ± 48 recordings/participant/30-day period) were collected in the 19 participants over the two 30-day monitoring periods. Average 30-day systolic BP was significantly increased with midodrine compared to placebo (114 ± 14 vs. 96 ± 11 mmHg, respectively; P = 0.004), and midodrine significantly reduced the number of hypotensive BP recordings compared to placebo (38.7 ± 41.9 vs. 73.3 ± 40.6, respectively; P = 0.01). However, compared to placebo, midodrine increased fluctuations in BP, did not improve symptoms of OH, but did significantly worsen the intensity of symptoms associated with AD (P = 0.03). CONCLUSION: Midodrine (10 mg) administered in the home environment effectively increases BP and reduces the incidence of hypotension; however these beneficial effects come at the expense of worsened BP instability and AD symptom intensity.

Evaluation of raw segmental bioelectrical impedance variables throughout anterior cruciate ligament reconstruction rehabilitation.

Background.Raw bioelectrical impedance analysis (BIA) variables are related to physical function in healthy and diseased populations. Therefore, BIA may be an insightful, noninvasive method of assessment to track following anterior cruciate ligament reconstruction (ACLR).Objectives.Evaluate phase angle, reactance and impedance at 50 kHz (PhA50, Xc50, andZ50, respectively) in the operative (OP) and non-operative (NOP) limbs during ACLR rehabilitation.Approach.Seventeen patient (12 M, 5 F; 18.8 ± 4.8 years) clinic reports were evaluated prior to ACLR (PRE), two- (2 W), six- (6 W), and twelve-weeks (12 W) post-ACLR and at return to sport testing (RTS).Setting.All observations occurred during the participant's physical therapy visits.Measurements.A multi-frequency BIA device measured segmental PhA, Xc, andZ. Linear mixed effects models were used to assess any leg and time interaction and changes over leg and time, independently. Any interactions or main effects were considered significant atp< 0.05.Main results.Significant legxtime interactions were observed for each variable. PhA50and Xc50of NOP were higher (p< 0.001) than OP at each time point by an average of by 0.9° and 4.9 Ω, respectively. In OP, PhA50and Xc50decreased from PRE to 2 W and increased from 6 to 12 W and 12 W to RTS (p< 0.01, for all). At RTS, PhA50and Xc50were similar to PRE in OP (p> 0.05). ForZ50, the OP leg did not change over time (p> 0.05).Z50was greater in NOP at 2 and 6 W (p< 0.01, for both). There were differences in PhA50in NOP between PRE and 6 W and from 6 W to RTS (p< 0.05 for both). Xc50did not change (p> 0.05), andZ50PRE was lower than at 2 W (p< 0.05).Significance.A multi-frequency BIA device can detect changes in segmental BIA variables following ACLR.

Observations from a prospective small cohort study suggest that CGRP genes contribute to acute posttraumatic headache burden after concussion.

Introduction: Post-traumatic headache (PTH) is commonly reported after concussion. Calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of migraine. We explored how single nucleotide polymorphisms (SNPs) from CGRP-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) related to headache burden during the first week after concussion. Methods: A prospective study was performed in 34 collegiate athletes who sustained a concussion. Participants completed the symptom evaluation checklist from the SCAT3 within 48 h of injury (V1), and again 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0-6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were reported and summed to calculate the headache burden. A saliva sample was obtained and genotyped for CALCA (rs3781719) and RAMP1 (rs10185142). RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) were dichotomized (A+, A- and T+, T-, respectively), and concatenated (T+A+, T+A-, T-A+, T-A-) for analyses. Results: Headache Burden at Visit 1 was greatest in T+A+ compared to T-A+, and trended toward a significant difference with T+A-. Repeated-measures ANOVA revealed the presence of significant visit main effects (p < 0.001, η2 = 0.404), but the group (p = 0.055) and interaction effects only trended (p = 0.094). Pearson's χ2-tests revealed that 88% of those with return-to play (RTP) exclusions ≥15 days had PTH with multi-sensory symptoms (PTH+SENS) as compared to 35% in those with RTP < 14 day. Conclusion: Knowledge of RAMP1 and CALCA genotypes appear to improve an understanding the presenting features and magnitude of headache burden after concussion injury.

Evaluation of Cardiovascular Autonomic Function during Inpatient Rehabilitation following Traumatic Spinal Cord Injury.

Assessment of the degree of impaired autonomic nervous system (ANS) function is not part of routine clinical practice during inpatient rehabilitation following traumatic spinal cord injury (SCI). The goal of this investigation was to determine the utility of the International Standards for Neurologic Classification of SCI (ISNCSCI) and the recently revised International Standards to document remaining Autonomic Function after SCI (ISAFSCI) in documenting cardiovascular ANS impairment during inpatient rehabilitation following traumatic SCI. Beat-to-beat recording of supine heart rate (HR) and blood pressure (BP) were collected at the bedside for estimation of total cardiovascular ISAFSCI score, cardio-vagal modulation (i.e., high frequency HR variability [HFHRV]) and sympathetic vasomotor regulation (i.e., Mayer wave component of systolic BP [SBPmayer]). A total of 41 participants completed baseline testing, which was conducted 11 ± 5 days from the admission ISNCSCI examination. There were no differences in supine HR or BP based on the ISNCSCI or ISAFSCI assessments. The HFHRV was generally lower with more distal lesions (r2 = 0.15; p = 0.01), and SBPmayer was significantly lower in those with American Spinal Injury Association Impairment Scale (AIS) A compared with AIS B, C, D (Cohen's d = -1.4; p < 0.001). There were no significant differences in HFHRV or SBPmayer in patients with or without ISAFSCI evidence of cardiovascular ANS impairment. These preliminary data suggest that neither the ISNCSCI nor the ISAFSCI are sensitive to changes in ANS cardiovascular function following traumatic SCI. Bedside assessment of HR and BP variabilities may provide insight, but are not readily available in the clinical setting. Further research is required to evaluate methods that accurately assess the degree of ANS impairment following traumatic SCI.

Orthostatic systemic and cerebral hemodynamics in newly injured patients with spinal cord injury.

BACKGROUND: Low blood pressure (BP) may lead to reduced cerebral blood flow velocity (CBFv) during an orthostatic challenge in newly injured patients with traumatic spinal cord injury (SCI), which, may relate to the neurological level of injury (NLI) as documented on the International Standards for the Neurologic Classification of SCI (ISNCSCI), or to evidence of cardiovascular autonomic impairment as determined by the International Standards to document remaining Autonomic Function after SCI (ISAFSCI). OBJECTIVE: To examine the influence of patient demographics, ISNCSCI and ISAFSCI scores on hemodynamic responses to a bedside sit-up test in newly injured patients with SCI. DESIGN: Cross-sectional, prospective analysis. METHODS: A modified sit-up test was conducted at the bedside with the hips at an angle between 45° and 90° and the legs horizontal, level with the hips. Heart rate, BP, and CBFv were recorded for 10 min in the supine and seated positions. RESULTS: Fifty-three newly injured patients (median 39.5 days post-injury) with traumatic SCI were enrolled. Overall, 28 (53%) patients met ISAFSCI criteria, and the number of criteria met (total score) was significantly related to orthostatic changes in CBFv. Change in SBP and change in CBFv were not significantly related, but NLI and total sensory score from the ISNCSCI were significant predictors of the change in CBFv. CONCLUSIONS: Total ISAFSCI score, NLI and sensory scores were positively associated with orthostatic changes in CBFv. Long term follow-up should be considered to determine the consequences of diminished CBFv on cognitive function and quality of life following SCI.

Effects of continuous cycling training on motor unit firing rates, input excitation, and myosin heavy chain of the vastus lateralis in sedentary females.

This study examined the effects of continuous endurance training on motor unit (MU) mean firing rates (MFR), percent myosin heavy chain (%MHC) isoforms, and muscle cross-sectional area (mCSA) of the vastus lateralis (VL). Twelve females completed 5-weeks of continuous cycling-training (CYC), while 8 females were controls (CON). Participants performed maximal voluntary contractions (MVCs) and 40% MVCs of the knee extensors before (PRE) and after the 5-week treatment period at the same absolute pre-treatment submaximal torque (POSTABS) and relative to post-treatment MVCs (POSTREL). Surface electromyographic (EMG) signals were decomposed with the Precision Decomposition III algorithm. MU firing times and waveforms were validated with reconstruct-and-test and spike trigger average procedures. MFRs at steady torque, recruitment thresholds (RT), and normalized EMG amplitude (N-EMGRMS) were analyzed. Y-intercepts and slopes were calculated for the MFR vs. RT relationships. MHC isoforms and mCSA were determined with muscle biopsies and ultrasonography. CYC decreased MVCs and type IIX %MHC isoform without changes in mCSA. The slopes for the MFR vs. RT relationships decreased for CYC during POSTREL and POSTABS while N-EMGRMS increased for POSTABS with no differences between PRE and POSTREL. Type I %MHC isoform was correlated with the slope for the MFR vs. RT relationship during POSTABS and POSTREL for CYC. This study provides evidence that decreases in the MFRs of higher threshold MUs post-CYC is likely a function of changes in input excitation (POSTABS) and the firing frequency-excitation relationships (POSTREL). Evidence is provided that MHC isoforms influence the firing rate scheme of the muscle following short-term training.

Change in measures of moral function following acute bouts of Marine Corps Martial Arts Training.

The Marine Corps Martial Arts Program (MCMAP) was developed to prepare Marines for complex battlefield situations that include hand-to-hand combat and ethical decision making. The objective of this study was to quantify changes in ethical decision-making following MCMAP training. Fifty-five, active duty, newly enlisted U.S. Marines (Males: n = 37; age = 19 ± 1 years; height = 176 ± 7 cm; mass = 74 ± 7 kg; Females: n = 18; age = 20 ± 2 years; height = 164 ± 6 cm; mass = 61 ± 6 kg) volunteered for this investigation and were assessed three times over 6 weeks, with 3 weeks between each visit, using serial blood samples for cortisol, norepinephrine, and epinephrine collected before training and during recovery [Immediate Post (IP), 15, 30, 45 and 60 min]. The Moral Functioning Continuum was used to quantify moral function before training, IP, 30, and 60 min post. Moral intention exhibited an acute response to training with significantly impaired decision making immediately post training. Moreover, both moral intention and moral judgement worsened over the visits suggesting a chronic impairment related to time in training suggesting a functional change in ethical decision-making following acute bouts of MCMAP.

Use of Mayer wave activity to demonstrate aberrant cardiovascular autonomic control following sports concussion injury.

Dysregulation of cardiovascular autonomic control is gaining recognition as a prevailing consequence of concussion injury. Characterizing the presence of autonomic dysfunction in concussed persons is inconsistent and conventional metrics of autonomic function cannot differentiate the presence/absence of injury. Mayer wave (MW) activity originates through baroreflex adjustments to blood pressure (BP) oscillations that appear in the low-frequency (LF: 0.04-0.15 Hz) band of the BP and heart rate (HR) power spectrum after a fast Fourier transform. We prospectively explored MW activity (∼0.1 Hz) in 19 concussed and 19 noninjured athletes for 5 min while seated at rest within 48 h and 1 week of injury. MW activity was derived from the LF band of continuous digital electrocardiogram and beat-to-beat BP signals (LFHR, LF-SBP, MWHR, and MW-SBP, respectively); a proportion between MWBP and MWHR was computed (cMW). At 48 h, the concussion group had a significantly lower MWBP and cMW than controls; these differences were gone by 1 week. MWHR, LFHR, and LF-SBP were not different between groups at either visit. Attenuated sympathetic vasomotor tone was present and the central autonomic mechanisms regulating MW activity to the heart and peripheral vasculature became transiently discordant early after concussion with apparent resolution by 1 week.

Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation.

Transcutaneous spinal cord stimulation (TSCS) has demonstrated potential to beneficially modulate spinal cord motor and autonomic circuitry. We are interested in pairing cervical TSCS with other forms of nervous system stimulation to enhance synaptic plasticity in circuits serving hand function. We use a novel configuration for cervical TSCS in which the anode is placed anteriorly over ~C4-C5 and the cathode posteriorly over ~T2-T4. We measured the effects of single pulses of TSCS paired with single pulses of motor cortex or median nerve stimulation timed to arrive at the cervical spinal cord at varying intervals. In 13 participants with and 15 participants without chronic cervical spinal cord injury, we observed that subthreshold TSCS facilitates hand muscle responses to motor cortex stimulation, with a tendency toward greater facilitation when TSCS is timed to arrive at cervical synapses simultaneously or up to 10 milliseconds after cortical stimulus arrival. Single pulses of subthreshold TSCS had no effect on the amplitudes of median H-reflex responses or F-wave responses. These findings support a model in which TSCS paired with appropriately timed cortical stimulation has the potential to facilitate convergent transmission between descending motor circuits, segmental afferents, and spinal motor neurons serving the hand. Studies with larger numbers of participants and repetitively paired cortical and spinal stimulation are needed.

Effects of Transspinal Direct Current Stimulation on Cycling Perception of Effort and Time to Exhaustion.

ABSTRACT: Ciccone, AB, Fry, AC, Emerson, DM, Gallagher, PM, Herda, TJ, and Weir, JP. Effects of transspinal direct current stimulation on cycling perception of effort and time to exhaustion. J Strength Cond Res 35(2): 347-352, 2021-In the past decade, researchers have investigated the efficacy of transspinal direct current stimulation (tsDCS) on the central nervous system and afferent neuron function in humans. Recently, data have suggested it may be possible for such tsDCS-induced changes in neuromuscular function to enhance performance. This study used noninvasive thoracic spine tsDCS to determine if cycling performance and perception of effort could be modulated by tsDCS. In 3 different stimulation conditions, anodal, cathodal, and sham, subjects cycled at 80% of their maximal aerobic capacity until exhaustion and reported their rating of perceived exertion (RPE) every minute. From this period, we compared the RPE responses over the first 3 minutes and time to exhaustion. There was no significant difference in time to exhaustion between anodal (408 ± 121 seconds), cathodal (413 ± 168 seconds), and sham (440 ± 189 seconds) conditions (p = 0.58). There was no significant difference in RPE from minutes 1-3 (collapsed across time) between anodal (12.9 ± 2.4 arbitrary units (AUs)), cathodal (13.3 ± 2.2 AUs), and sham (12.9 ± 2.1 AUs) conditions (p = 0.51). These data suggest tsDCS condition did not influence cycling performance or perception of effort during high-intensity cycling. Therefore, thoracic spine and lower abdominal montage delivering a current density of 0.071 mA·cm-2 for 20 minutes likely does not substantially improve high-intensity cycling work capacity. Therefore, more research is needed to investigate the efficacy of tsDCS and which stimulation methods may and may not enhance human performance.

Increased pulse wave velocity in persons with spinal cord injury: the effect of the renin-angiotensin-aldosterone system.

Increased pulse wave velocity (PWV), a marker of cardiovascular disease (CVD), has been reported in otherwise healthy individuals with spinal cord injury (SCI) compared with age-matched uninjured controls. Due to decentralized descending sympathetic vascular control, individuals with injuries above T6 are prone to orthostatic hypotension and, as a result, depend on the renin-angiotensin-aldosterone system (RAAS) to maintain orthostatic blood pressure (BP). The purpose of this study was to determine resting PWV, a noninvasive surrogate of central arterial stiffness, in individuals with cervical (C4-T1; n = 11) and thoracic (T6-T12; n = 11) SCI, compared with age-matched controls (controls; n = 11). Next, our aim was to describe group differences in BP, plasma norepinephrine (NE), and renin response to head-up tilt (HUT). Finally, we sought to determine the relationship between PWV and the orthostatic change in BP, NE, and the plasma renin during HUT among the groups. PWV was significantly increased in both cervical (8.81 ± 1.91 m/s) and thoracic (7.36 ± 1.58 m/s) SCI compared with the controls (5.53 ± 0.95 m/s; P < 0.05). The change from supine to 60° HUT in BP and NE was significantly reduced and change in plasma renin was significantly increased in the cervical group compared with the thoracic and control groups. Group affiliation and change in plasma renin were significant predictors of PWV (R2 = 0.63, P = 0.001). These data suggest that dependency on the RAAS for orthostatic BP maintenance may be associated with increased PWV and risk of CVD in the SCI population.NEW & NOTEWORTHY Our novel findings suggest that increased arterial stiffness in individuals with SCI may be due to greater dependency on the RAAS to maintain hemodynamic stability during an orthostatic challenge. Asymptomatic orthostatic hypotension can occur in persons with SCI during transition from the supine to the seated position and during other upright activities of daily living; however, it is seldom addressed by clinicians.

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI.

STUDY DESIGN: Clinical trial. OBJECTIVES: Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system, which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared with placebo, to increase and normalize systolic blood pressure (SBP) between 110 and 120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function. SETTING: United States clinical research laboratory. METHODS: Forty-one healthy hypotensive individuals with chronic (≥1-year post injury) SCI participated in this 2-day study. Seated SBP, CBFv, and cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. RESULTS: Compared with placebo, midodrine increased SBP (4 ± 13 vs. 18 ± 24 mmHg, respectively; p < 0.05); however, responses varied widely with midodrine (-15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared with placebo. Although higher SBP was associated with higher CBFv (p = 0.02), global cognitive function was not improved with midodrine. CONCLUSIONS: The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggests careful monitoring of patients following administration. CLINICAL TRIALS REGISTRATION: NCT02307565.

Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots.

OBJECTIVE: We aim to non-invasively facilitate activation of spared neural circuits after cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). We developed and tested a novel configuration for cervical transcutaneous spinal stimulation (cTSS). METHODS: cTSS was delivered via electrodes placed over the midline at ~T2-T4 levels posteriorly and ~C4-C5 levels anteriorly. Electromyographic responses were measured in arm and hand muscles across a range of stimulus intensities. Double-pulse experiments were performed to assess homosynaptic post-activation depression (PAD). Safety was closely monitored. RESULTS: More than 170 cTSS sessions were conducted without major safety or tolerability issues. A cathode-posterior, 2 ms biphasic waveform provided optimal stimulation characteristics. Bilateral upper extremity muscle responses were easily obtained in subjects with SCI and ALS. Resting motor threshold at the abductor pollicis brevis muscle ranged from 5.5 to 51.0 mA. As stimulus intensity increased, response latencies to all muscles decreased. PAD was incomplete at lower stimulus intensities, and decreased at higher stimulus intensities. CONCLUSIONS: Posteroanterior cTSS has the capability to target motor neurons both trans-synaptically via large-diameter afferents and non-synaptically via efferent motor axons. SIGNIFICANCE: Posteroanterior cTSS is well tolerated and easily activates upper extremity muscles in individuals with SCI and ALS.

Blood Pressure Instability in Persons With SCI: Evidence From a 30-Day Home Monitoring Observation.

BACKGROUND: To determine the degree of blood pressure instability over a 30-day home observation in participants with spinal cord injury grouped by level of injury pertaining to cardiovascular autonomic regulation. METHODS: This is an observational study completed at the Kessler Foundation and James J. Peters Veterans Medical Center. Seventy-two participants with tetraplegia (C1-T1), 13 with high thoracic (T2-T4), and 28 with low thoracic (T5-T12) injury participated in this study. Participants were asked to record their blood pressure using an ambulatory blood pressure monitor three times a day for 30 days. RESULTS: The number of blood pressure fluctuations was significantly increased in the tetraplegia group compared with the paraplegia groups. Age and duration of injury contributed to an increase in the observation of 30-day blood pressure instability; however, completeness of injury did not. CONCLUSION: The data indicate significant blood pressure instability that may not be exclusive to persons with tetraplegia; in fact, individuals with low thoracic injuries demonstrated severe blood pressure fluctuations. The use of a monitor at home for an extended period may help document dangerous and extreme fluctuations in blood pressure and should be considered an important adjunctive clinical practice for tracking of the secondary consequences in the spinal cord injury population.