Motor and autonomic concomitant health improvements with neuromodulation and exercise (MACHINE) training: a randomised controlled trial in individuals with spinal cord injury.

INTRODUCTION: Motor and autonomic dysfunctions are widespread among people with spinal cord injury (SCI), leading to poor health and reduced quality of life. Exercise interventions, such as locomotor training (LT), can promote sensorimotor and autonomic recovery post SCI. Recently, breakthroughs in SCI research have reported beneficial effects of electrical spinal cord stimulation (SCS) on motor and autonomic functions. Despite literature supporting the independent benefits of transcutaneous SCS (TSCS) and LT, the effect of pairing TSCS with LT is unknown. These therapies are non-invasive, customisable and have the potential to simultaneously benefit both sensorimotor and autonomic functions. The aim of this study is to assess the effects of LT paired with TSCS in people with chronic SCI on outcomes of sensorimotor and autonomic function. METHODS AND ANALYSIS: Twelve eligible participants with chronic (>1 year) motor-complete SCI, at or above the sixth thoracic segment, will be enrolled in this single-blinded, randomised sham-controlled trial. Participants will undergo mapping for optimisation of stimulation parameters and baseline assessments of motor and autonomic functions. Participants will then be randomly assigned to either LT+TSCS or LT+Sham stimulation for 12 weeks, after which postintervention assessments will be performed to determine the effect of TSCS on motor and autonomic functions. The primary outcome of interest is attempted voluntary muscle activation using surface electromyography. The secondary outcomes relate to sensorimotor function, cardiovascular function, pelvic organ function and health-related quality of life. Statistical analysis will be performed using two-way repeated measures Analysis of variance (ANOVAs) or Kruskal-Wallis and Cohen's effect sizes. ETHICS AND DISSEMINATION: This study has been approved after full ethical review by the University of British Columbia's Research Ethics Board. The stimulator used in this trial has received Investigation Testing Authorisation from Health Canada. Trial results will be disseminated through peer-reviewed publications, conference presentations and seminars. TRIAL REGISTRATION NUMBER: NCT04726059.

Influence of traumatic lower-limb amputation on physical activity, body composition, and cardiometabolic risks: A descriptive preliminary study.

BACKGROUND: Following traumatic lower-limb amputation (LLA), humans are predisposed to numerous unfavorable changes in health, including the development of secondary chronic health conditions such as metabolic disorders and cardiovascular disease. OBJECTIVE: To determine within and between group differences in cardiometabolic component risks, body composition, and physical activity (PA) in individuals with traumatic unilateral and bilateral LLA, compared to noninjured controls. DESIGN: Prospective observational cohort study. SETTING: A military complex trauma rehabilitation center. PARTICIPANTS: Sixteen males with traumatic LLA (8 unilateral, mean age 30 ± 5 years and 8 bilateral, mean age 29 ± 3 years). Thirteen active age-matched males with no LLA (28 ± 5 years) acted as controls and performed habitual activities of daily living. INTERVENTION: Participants with LLA attended two 4-week periods of inpatient rehabilitation, separated by two 6-week periods of home-based recovery. MAIN OUTCOME MEASURES: Venous blood samples were taken prior to and following a 75 g oral glucose load, for determination of biomarkers, including insulin and glucose, at baseline and 20 weeks. Body composition (dual X-ray absorptiometry) was measured at baseline, 10 weeks, and 20 weeks. Daily PA was recorded using a triaxial accelerometer for 7 days during inpatient rehabilitation and while at home. Energy expenditure was estimated using population-specific equations. RESULTS: Individuals with bilateral LLA demonstrated more unfavorable mean body composition values, lower PA, and increased cardiometabolic health risk compared to controls. Cardiometabolic syndrome was identified in 63% of individuals with bilateral LLA. No statistically significant differences in cardiometabolic component risk factors, body composition, and estimated daily PA were reported between unilateral LLA and control groups (p > .05). While at home, mean PA counts.day-1 reduced by 17% (p = .018) and 42% (p = .001) in the unilateral and bilateral LLA groups, respectively. CONCLUSIONS: Despite extensive inpatient rehabilitation, cardiometabolic component risks are elevated in individuals with bilateral LLA but are comparable between unilateral LLA and active noninjured control groups. Innovative strategies that improve/support the long-term PA and cardiometabolic health of severely injured individuals with bilateral LLA are warranted.

Cannabis health survey on usage in women with spinal cord injury and knowledge among physicians: A cross-sectional study.

OBJECTIVE: Individuals with spinal cord injury (SCI) report using cannabis to self-manage chronic pain and spasticity. However, its safety and efficacy are not well understood. As more women with SCI are pursuing motherhood, clinicians must consider the possibility of maternal cannabis use and its impact on fetal development. Moreover, due to the lack of current evidence for cannabis, it is important to characterize the perceptions and knowledge of physicians towards both recreational and synthetic cannabinoids. DESIGN: Two anonymous surveys (10-items each) were conducted. SETTING AND PARTICIPANTS: Women with SCI (n = 20) completed an anonymous, online survey regarding cannabis use. Physicians at a Canadian SCI rehabilitation center (n = 15) completed a survey on their knowledge of recreational and synthetic cannabinoids among individuals with SCI. OUTCOME MEASURES: Survey 1 evaluated cannabis use patterns and perceptions before/after SCI in women, including during pregnancy and breastfeeding. The aim of Survey 2 was to understand the perception and current knowledge of physicians regarding recreational cannabis and synthetic cannabinoid use by patients with SCI. RESULTS: At the time of survey, 7 women with SCI reported use of cannabis, only 4 of them used prior to injury. Managing tone/spasticity (n = 5) was the major reported benefit of cannabis use. Women used cannabis during pregnancy and/or breastfeeding as a sleep aid or relief for morning sickness (n = 1 pregnancy, n = 1 breastfeeding, n = 1 both). The most-reported challenge with cannabis use was difficulty obtaining consistent, desirable effects (n = 5). Almost all physicians (n = 13) described their knowledge on recreational cannabis products as "none, very little or poor", with greater overall comfort and knowledge of synthetic cannabinoids. CONCLUSION: Due to the reported use of cannabis during pregnancy/breastfeeding and current impoverishment of physicians' knowledge (particularly regarding recreational cannabis products), it is imperative to further investigate the safety and efficacy of cannabis use in women with SCI.

Fesoterodine Ameliorates Autonomic Dysreflexia While Improving Lower Urinary Tract Function and Urinary Incontinence-Related Quality of Life in Individuals With Spinal Cord Injury: A Prospective Phase IIa Study.

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. Compared with baseline, fesoterodine improved lower urinary tract (LUT) function, that is, increased cystometric capacity (205 vs. 475 mL, p = 0.002) and decreased maximum detrusor pressure (44 vs. 12 cm H2O, p = 0.009). NDO was eliminated in seven (58%) participants. Severity of AD events during urodynamics (40 vs. 27 mm Hg, p = 0.08) and 24-h ABPM (59 vs. 36 mm Hg, p = 0.05) were both reduced, yielding a large effect size (r = -0.58). AD Frequency (14 vs. 3, p = 0.004) during 24-h ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.

When the whole is greater than the sum of its parts: a scoping review of activity-based therapy paired with spinal cord stimulation following spinal cord injury.

Spinal cord injury (SCI) results in both motor and autonomic impairments, which can negatively affect independence and quality of life and increase morbidity and mortality. Despite emerging evidence supporting the benefits of activity-based training and spinal cord stimulation as two distinct interventions for sensorimotor and autonomic recovery, the combined effects of these modalities are currently uncertain. This scoping review evaluated the effectiveness of paired interventions (exercise + spinal neuromodulation) for improving sensorimotor and autonomic functions in individuals with SCI. Four electronic databases were searched for peer-reviewed manuscripts (Medline, Embase, CINAHL, and EI-compedex Engineering Village) and data were independently extracted by two reviewers using pre-established extraction tables. A total of 15 studies representing 79 participants were included in the review, of which 73% were conducted within the past 5 years. Only two of the studies were randomized controlled studies, while the other 13 studies were case or case-series designs. Compared with activity-based training alone, spinal cord stimulation combined with activity-based training improved walking and voluntary muscle activation, and augmented improvements in lower urinary tract, bowel, resting metabolic rate, peak oxygen consumption, and thermoregulatory function. Spinal neuromodulation in combination with use-dependent therapies may provide greater neurorecovery and induce long-term benefits for both motor and autonomic function beyond the capacity of traditional activity-based therapies. However, evidence for combinational approaches is limited and there is no consensus for outcome measures or optimal protocol parameters, including stimulation settings. Future large-scale randomized trials into paired interventions are warranted to further investigate these preliminary findings.

The safety of epidural spinal cord stimulation to restore function after spinal cord injury: post-surgical complications and incidence of cardiovascular events.

STUDY DESIGN: Cohort prospective study. OBJECTIVES: Epidural spinal cord stimulation (eSCS) improves volitional motor and autonomic function after spinal cord injury (SCI). While eSCS has an established history of safety for chronic pain, it remains unclear if eSCS in the SCI population presents the same risk profile. We aimed to assess safety and autonomic monitoring data for the first 14 participants in the E-STAND trial. SETTING: Hennepin County Medical Center, Minneapolis and Minneapolis Veterans Affairs Medical Center, Minnesota, USA. METHODS: Monthly follow-up visits assessed surgical and medical device-related safety outcomes as well as stimulation usage. Beat-by-beat blood pressure (BP) and continuous electrocardiogram data were collected during head-up tilt-table testing with and without eSCS. RESULTS: All participants had a motor-complete SCI. Mean (SD) age and time since injury were 38 (10) and 7 (5) years, respectively. There were no surgical complications but one device malfunction 4 months post implantation. Stimulation was applied for up to 23 h/day, across a broad range of parameters: frequency (18-700 Hz), pulse width (100-600 µs), and amplitude (0.4-17 mA), with no adverse events reported. Tilt-table testing with eSCS demonstrated no significant increases in the incidence of elevated systolic BP or a greater frequency of arrhythmias. CONCLUSIONS: eSCS to restore autonomic and volitional motor function following SCI has a similar safety profile as when used to treat chronic pain, despite the prevalence of significant comorbidities and the wide variety of stimulation parameters tested.

Can Magnetic Resonance Imaging Reveal Lower Motor Neuron Damage after Traumatic Spinal Cord Injury? A Scoping Review.

Restoring muscle function to patients with spinal cord injuries (SCIs) will invariably require a functioning lower motor neuron (LMN). As techniques such as nerve transfer surgery emerge, characterizing the extent of LMN damage associated with SCIs becomes clinically important. Current methods of LMN diagnosis have inherent limitations that could potentially be overcome by the development of magnetic resonance imaging (MRI) biomarkers: specific features on MRI that are indicative of LMN integrity. To identify research on MRI biomarkers of LMN damage in the acute phase after SCI, we searched PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for articles published from inception to April 27, 2021. Overall, 2 of 58 unique articles screened met our inclusion criteria, both of which were small studies. We therefore identify MRI biomarkers of LMN damage overlying SCI as a notable gap in the literature. Because of the lack of existing literature on this specific problem, we further our discussion by examining concepts explored in research characterizing MRI biomarkers of spinal cord and neuronal damage in different contexts that may provide value in future work to identify a biomarker for LMN damage in SCI. We conclude that MRI biomarkers of LMN damage in SCI is an underexplored, but promising, area of research as emerging, function-restoring therapies requiring this information continue to advance.

Effect of Exercise on Cardiometabolic Risk Factors in Adults With Chronic Spinal Cord Injury: A Systematic Review.

OBJECTIVE: To determine the effects of exercise on individual cardiometabolic syndrome (CMS) risk factors in adults with chronic spinal cord injury (SCI). DATA SOURCES: English language searches of PubMed, Web of Science, EMBASE, and Scopus (January 1, 1970, to July 31, 2019). STUDY SELECTION: Articles were included if they met the following criteria: (1) original articles with statistical analysis, (2) participants were adults with a SCI sustained ≥1 year ago, (3) exercise intervention duration ≥2 weeks, and (4) included any CMS risk factor as an outcome. DATA EXTRACTION: The methodological quality of articles was assessed using the Downs and Black score. DATA SYNTHESIS: Sixty-five studies were included for the final analysis, including 9 studies classified as high quality (≥66.7%), 35 studies classified as fair quality (50%-66.6%), and 21 studies classified as low quality (<50%). Improvements in waist circumference (4/6 studies) and markers of hepatic insulin sensitivity (4/5 studies) were reported following upper body aerobic exercise training, but no improvements in fasting glucose (8/8 studies), lipid profile (6/8 studies), systolic blood pressure (8/9 studies), or diastolic blood pressure (9/9 studies) were observed. Improvements in markers of peripheral insulin sensitivity (5/6 studies) were observed following functional electrical stimulation (FES) cycling. Improvements in lipid profile (4/5 studies) were observed following upper body resistance training (RT) (with or without aerobic exercise). No consistent improvements in CMS risk factors were observed following assisted ambulation, FES hybrid, FES rowing, and FES RT. CONCLUSIONS: Upper body aerobic exercise training (>75% maximum heart rate) appears to improve waist circumference and hepatic insulin sensitivity but appears insufficient for improving fasting glucose, lipid profile, or resting blood pressure. The addition of RT to upper body aerobic exercise may elicit favorable changes in the lipid profile. More high-quality studies are needed to confirm if FES cycling is effective at improving peripheral insulin sensitivity.

Anthropometric cutoffs and associations with visceral adiposity and metabolic biomarkers after spinal cord injury.

BACKGROUND/OBJECTIVES: To examine associations of different anthropometric measurements of central adiposity to visceral adipose tissue (measured via multi-axial magnetic resonance imaging; MRI) and cardiometabolic disease risk factors in men with spinal cord injury (SCI). Additionally, to determine population-specific seated/supine waist and abdominal circumference cutoffs, which may identify men at increased risk of cardiometabolic disease. PARTICIPANTS/METHODS: Twenty-two men with chronic SCI underwent MRI scans, anthropometric measurements along with assessments of various cardiometabolic risk biomarkers. Pearson/part (accounting for age as a covariate) correlation coefficients were calculated to determine the associations between study variables. Abdominal and waist circumference cutoffs were extrapolated using the slope of linear regression equations. RESULTS: Seated/supine abdominal and waist circumferences were (P < 0.01) associated with MRI visceral fat cross-sectional area (VATCSA), VAT volume and CSA:TotalCSA. Low density lipoprotein, non-high-density lipoprotein and total cholesterol were positively associated with seated/supine abdominal and waist circumferences after controlling for age; r = 0.50-0.61, r = 0.46-0.58, r = 0.52-0.58, P < 0.05, respectively. Tumor necrosis factor alpha was associated with seated/supine abdominal and waist circumferences after accounting for age; r = 0.49-0.51 and r = 0.48-0.56, P < 0.05 respectively. The population-specific cutoffs were 86.5cm and 88.3cm for supine waist and abdominal circumferences, respectively, as well as 89cm and 101cm for seated waist and abdominal circumferences, respectively. After dichotomizing VATCSA (< or ≥ 100cm2), peak oxygen uptake, triglycerides, insulin sensitivity and glycated hemoglobin were different (P < 0.05) between groups. After dichotomizing (< or ≥ 86.5cm) supine waist circumference, VATCSA, triglycerides and insulin sensitivity were different (P < 0.05) between groups. CONCLUSIONS: Seated/supine circumferences are associated with both central adiposity and biomarkers of cardiometabolic disease risk in persons with SCI. Population-specific cutoffs are proposed herein to identify central adiposity and potential cardiometabolic disease risk after SCI.

Assessment of laboratory and daily energy expenditure estimates from consumer multi-sensor physical activity monitors.

Wearable physical activity monitors are growing in popularity and provide the opportunity for large numbers of the public to self-monitor physical activity behaviours. The latest generation of these devices feature multiple sensors, ostensibly similar or even superior to advanced research instruments. However, little is known about the accuracy of their energy expenditure estimates. Here, we assessed their performance against criterion measurements in both controlled laboratory conditions (simulated activities of daily living and structured exercise) and over a 24 hour period in free-living conditions. Thirty men (n = 15) and women (n = 15) wore three multi-sensor consumer monitors (Microsoft Band, Apple Watch and Fitbit Charge HR), an accelerometry-only device as a comparison (Jawbone UP24) and validated research-grade multi-sensor devices (BodyMedia Core and individually calibrated Actiheart™). During discrete laboratory activities when compared against indirect calorimetry, the Apple Watch performed similarly to criterion measures. The Fitbit Charge HR was less consistent at measurement of discrete activities, but produced similar free-living estimates to the Apple Watch. Both these devices underestimated free-living energy expenditure (-394 kcal/d and -405 kcal/d, respectively; P<0.01). The multi-sensor Microsoft Band and accelerometry-only Jawbone UP24 devices underestimated most laboratory activities and substantially underestimated free-living expenditure (-1128 kcal/d and -998 kcal/d, respectively; P<0.01). None of the consumer devices were deemed equivalent to the reference method for daily energy expenditure. For all devices, there was a tendency for negative bias with greater daily energy expenditure. No consumer monitors performed as well as the research-grade devices although in some (but not all) cases, estimates were close to criterion measurements. Thus, whilst industry-led innovation has improved the accuracy of consumer monitors, these devices are not yet equivalent to the best research-grade devices or indeed equivalent to each other. We propose independent quality standards and/or accuracy ratings for consumer devices are required.