Predictors of muscle hypertrophy responsiveness to electrically evoked resistance training after spinal cord injury.

The purpose of the study was to identify potential predictors of muscle hypertrophy responsiveness following neuromuscular electrical stimulation resistance training (NMES-RT) in persons with chronic spinal cord injury (SCI). Data for twenty individuals with motor complete SCI who completed twice weekly NMES-RT lasting 12-16 weeks as part of their participation in one of two separate clinical trials were pooled and retrospectively analyzed. Magnetic resonance imaging (MRI) was used to measure muscle cross-sectional area (CSA) of the whole thigh and knee extensor muscle before and after NMES-RT. Muscle biopsies and fasting biomarkers were also measured. Following the completion of the respective NMES-RT trials, participants were classified into either high-responders (n = 8; muscle CSA > 20%) or low-responders (n = 12; muscle CSA < 20%) based on whole thigh muscle CSA hypertrophy. Whole thigh muscle and knee extensors CSAs were significantly greater (P < 0.0001) in high-responders (29 ± 7% and 47 ± 15%, respectively) compared to low-responders (12 ± 3% and 19 ± 6%, respectively). There were no differences in total caloric intake or macronutrient intake between groups. Extensor spasticity was lower in the high-responders compared to the low-responders as was the dosage of baclofen. Prior to the intervention, the high-responders had greater body mass compared to the low-responders with SCI (87.8 ± 13.7 vs. 70.4 ± 15.8 kg; P = 0.012), body mass index (BMI: 27.6 ± 2.7 vs. 22.9 ± 6.0 kg/m2; P = 0.04), as well as greater percentage in whole body and regional fat mass (P < 0.05). Furthermore, high-responders had a 69% greater increase (P = 0.086) in total Akt protein expression than low-responders. High-responders also exhibited reduced circulating IGF-1 with a concomitant increase in IGFBP-3. Exploratory analyses revealed upregulation of mRNAs for muscle hypertrophy markers [IRS-1, Akt, mTOR] and downregulation of protein degradation markers [myostatin, MurF-1, and PDK4] in the high-responders compared to low-responders. The findings indicate that body composition, spasticity, baclofen usage, and multiple signaling pathways (anabolic and catabolic) are involved in the differential muscle hypertrophy response to NMES-RT in persons with chronic SCI.

Denervation impacts muscle quality and knee bone mineral density after spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare muscle size, body composition, bone mineral density (BMD), and metabolic profiles in denervated versus innervated individuals with spinal cord injury (SCI). SETTING: Hunter Holmes McGuire Veterans Affairs (VA) Medical Center. METHODS: Body composition, bone mineral density (BMD), muscle size, and metabolic parameters were collected in 16 persons with chronic SCI (n = 8 denervated, n = 8 innervated) using dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and fasting blood samples. BMR was measured by indirect calorimetry. RESULTS: Percent differences of the whole thigh muscle cross-sectional area (CSA; 38%), knee extensor CSA (49%), vasti CSA (49%), and rectus femoris CSA (61%) were smaller in the denervated group (p < 0.05). Leg lean mass was also lower (28%) in the denervated group (p < 0.05). Whole muscle intramuscular fat (IMF%; 15.5%), knee extensor IMF% (22%), and % fat mass (10.9%) were significantly greater in the denervated group (p < 0.05). Knee distal femur and proximal tibia BMD were lower in the denervated group, 18-22% and 17-23%; p < 0.05. Certain indices of metabolic profile were more favorable in the denervated group though were not significant. CONCLUSIONS: SCI results in skeletal muscle atrophy and dramatic changes in body composition. Lower motor neuron (LMN) injury results in denervation of the lower extremity muscles which exacerbates atrophy. Denervated participants exhibited lower leg lean mass and muscle CSA, greater muscle IMF, and reduced knee BMD compared to innervated participants. Future research is needed to explore therapeutic treatments for the denervated muscles after SCI.

The interaction of macronutrients and body composition among individuals with chronic spinal cord injury.

Changes in body composition and dietary intake occur following spinal cord injury (SCI). The Geometric Framework for Nutrition (GFN) is a tool that allows the examination of the complex relationships between multiple nutrition factors and health parameters within a single model. This study aimed to utilize the GFN to examine the associations between self-reported macronutrient intakes and body composition in persons with chronic SCI. Forty-eight individuals with chronic SCI were recruited. Participants completed and returned 3- or 5-day self-reported dietary recall sheets. Dietary intake of macronutrients (fats, proteins, and carbohydrates) were analysed. Anthropometric measures (circumferences), dual-energy x-ray absorptiometry (DXA), and magnetic resonance imaging (MRI) were used to assess whlole-body composition. Associations between all circumference measures and carbohydrates were observed. Among MRI measures, only significant associations between subcutaneous adipose tissue and protein x carbohydrate as well as carbohydrates alone were identified. Carbohydrates were negatively associated with several measures of fat mass as measured by DXA. Overall, carbohydrates appear to play an important role in body composition among individuals with SCI. Higher carbohydrate intake was associated with lower fat mass. Additional research is needed to determine how carbohydrate intake influences body composition and cardiometabolic health after SCI.

A secondary analysis of testosterone and electrically evoked resistance training versus testosterone only (TEREX-SCI) on untrained muscles after spinal cord injury: a pilot randomized clinical trial.

STUDY DESIGN: Secondary analysis of a clinical trial. OBJECTIVES: To perform a secondary analysis on the effects of neuromuscular electrical stimulation resistance training (RT) combined with testosterone replacement therapy (TRT) compared with TRT on the untrained muscles after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Twenty-two men with chronic motor complete SCI were randomized into TRT + RT group (n = 11) or TRT group (n = 11). Both groups received 16 weeks of TRT (2-6 mg/day) via testosterone patches. The TRT + RT group received twice weekly progressive RT of the knee extensor muscles using electrical stimulation and ankle weights. Magnetic resonance images were captured to measure cross-sectional areas (CSAs) of trunk, glutei, and leg muscles. RESULTS: Total and absolute gluteus maximus m. (14%, P = 0.003 and 16%, P = 0.001), gluteus medius m. (10%; P = 0.008 and 14%; P = 0.02), and total glutei m. (8%, P = 0.01 and 11%, P = 0.005) CSAs increased overtime for the TRT + RT group. Mean between-group differences of 2.86 (95% CI: 0.30, 5.4), 1.89 (95% CI: 0.23, 3.58) and 5.27 (95% CI: 0.90, 9.69) cm2 were noted for absolute gluteus maximus, total gluteus medius and total glutei CSAs, respectively (P < 0.05). Trunk muscle CSAs showed a trend towards an interaction between groups. CONCLUSIONS: RT combined with low-dose TRT results in significant hypertrophy compared with TRT only on the adjacent untrained glutei muscles. Trunk muscles may require direct stimulation to evoke hypertrophy. These exploratory findings may be of clinical relevance in the reduction of incidence and severity of pelvic pressure injuries.

Frequency of Dietary Recalls, Nutritional Assessment, and Body Composition Assessment in Men With Chronic Spinal Cord Injury.

OBJECTIVES: To assess different frequencies of dietary recalls while evaluating caloric intake and the percentage of macronutrients in men with spinal cord injury (SCI) and to examine the relations between caloric intake or percentage of macronutrients and assessment of whole and regional body composition using dual-energy x-ray absorptiometry. DESIGN: Cross-sectional and longitudinal. SETTING: Laboratory and hospital. PARTICIPANTS: Men with chronic (>1 y postinjury) motor complete SCI (N=16). INTERVENTIONS: Participants were asked to turn in a 5-day dietary recall on a weekly basis for 4 weeks. The averages of 5-, 3-, and 1-day dietary recalls for caloric intake and percentage of macronutrients (carbohydrates, fat, protein) were calculated. Body composition was evaluated using whole-body dual-energy x-ray absorptiometry. After overnight fast, basal metabolic rate (BMR) was evaluated using indirect calorimetry and total energy expenditure (TEE) was estimated. MAIN OUTCOME MEASURES: Caloric intake, percentage of macronutrients, BMR, and body composition. RESULTS: Caloric intake and percentage of macronutrients were not different after using 5-, 3-, and 1-day dietary recalls (P>.05). Caloric intake was significantly lower than TEE (P<.05). The percentage of fat accounted for 29% to 34% of the whole and regional body fat mass (P=.037 and P=.022). The percentage of carbohydrates was positively related to the percentage of whole-body lean mass (r=.54; P=.037) and negatively related to the percentage of fat mass. CONCLUSIONS: The frequency of dietary recalls does not vary while evaluating caloric intake and macronutrients. Total caloric intake was significantly lower than the measured BMR and TEE. Percentages of dietary fat and carbohydrates are related to changes in body composition after SCI.

Neuromuscular electrical stimulation training increases intermuscular fascial length but not tendon cross-sectional area after spinal cord injury.

OBJECTIVE: To determine the effects of 12 weeks of neuromuscular electrical stimulation (NMES) training with ankle weights on intermuscular fascial length and patellar tendon cross-sectional area (CSA) in persons with spinal cord injury (SCI). METHODS: This study was a pre-post intervention. Seven men with motor complete SCI were randomly assigned to a resistance training plus diet (RT + diet) group (n = 4) or a diet control group (n = 3). Participants in the RT + diet group were enrolled in a 12-week leg extension weight-lifting program via surface NMES of the knee extensor muscle group. The length of mid-thigh intermuscular fascia and the patellar tendon CSA were measured using MRI. RESULTS: In the RT + diet group, a nonsignificant 8% increase in the CSA of the patellar tendon (P = .14) was noted. The length of the mid-thigh intermuscular fascia increased by 19% and 23% in the right (P = .029) and left (P = .015) legs, respectively, with no changes in the diet control group. Positive relationships were noted between skeletal muscle CSAs of the whole thigh (r = 0.77, P = .041) and knee extensors (r = 0.76, P = .048) and intermuscular fascial length. CONCLUSION: The preliminary results suggest that noncontractile connective tissue structures of the knee extensors respond differently to NMES training after SCI. Skeletal muscle hypertrophy is associated with an increase in the intermuscular fascial length.

Effects of two different paradigms of electrical stimulation exercise on cardio-metabolic risk factors after spinal cord injury. A randomized clinical trial.

Objective: To examine the combined effects of neuromuscular electrical stimulation-resistance training (NMES-RT) and functional electrical stimulation-lower extremity cycling (FES-LEC) compared to passive movement training (PMT) and FES-LEC in adults with SCI on (1) oxygen uptake (VO2), insulin sensitivity and glucose disposal in adults with SCI; (2) Metabolic and inflammatory biomarkers; (3) skeletal muscle, intramuscular fat (IMF) and visceral adipose tissue (VAT) cross-sectional areas (CSAs). Materials and methods: Thirty-three participants with chronic SCI (AIS A-C) were randomized to 24 weeks of NMES-RT + FES or PMT + FES. The NMES-RT + FES group underwent 12 weeks of evoked surface NMES-RT using ankle weights followed by an additional 12 weeks of progressive FES-LEC. The control group, PMT + FES performed 12 weeks of passive leg extension movements followed by an additional 12 weeks of FES-LEC. Measurements were performed at baseline (BL; week 0), post-intervention 1 (P1; week 13) and post-intervention 2 (P2; week 25) and included FES-VO2 measurements, insulin sensitivity and glucose effectiveness using the intravenous glucose tolerance test; anthropometrics and whole and regional body composition assessment using dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging to measure muscle, IMF and VAT CSAs. Results: Twenty-seven participants completed both phases of the study. NMES-RT + FES group showed a trend of a greater VO2 peak in P1 [p = 0.08; but not in P2 (p = 0.25)] compared to PMT + FES. There was a time effect of both groups in leg VO2 peak. Neither intervention elicited significant changes in insulin, glucose, or inflammatory biomarkers. There were modest changes in leg lean mass following PMT + FES group. Robust hypertrophy of whole thigh muscle CSA, absolute thigh muscle CSA and knee extensor CSA were noted in the NMES-RT + FES group compared to PMT + FES at P1. PMT + FES resulted in muscle hypertrophy at P2. NMES-RT + FES resulted in a decrease in total VAT CSA at P1. Conclusion: NMES-RT yielded a greater peak leg VO2 and decrease in total VAT compared to PMT. The addition of 12 weeks of FES-LEC in both groups modestly impacted leg VO2 peak. The addition of FES-LEC to NMES-RT did not yield additional increases in muscle CSA, suggesting a ceiling effect on signaling pathways following NMES-RT. Clinical trial registration: identifier NCT02660073.

Employment of Neuromuscular Electrical Stimulation to Examine Muscle and Bone Qualities after Spinal Cord Injury.

(1) Background: Resource intensive imaging tools have been employed to examine muscle and bone qualities after spinal cord injury (SCI). We tested the hypothesis that surface neuromuscular electrical stimulation (NMES) amplitude can be used to examine knee extensor muscle quality, distal femur and proximal tibia bone mineral density (BMD) in persons with SCI. (2) Methods: Seventeen persons (2 women) with chronic SCI participated in three weeks of NMES-resistance training twice weekly of 4 sets of 10 repetitions. Participants were classified according to the current amplitude (>100 mA) and the number of repetitions (>70 reps) of leg extension into greater (n = 8; 1 woman; group A) and lower (n = 9; 1 woman; group B) musculoskeletal qualities. Magnetic resonance imaging, dual energy x-ray absorptiometry, isometric peak torque, Modified Ashworth and Penn spasm frequency scales were conducted. (3) Results: In between group comparisons, current amplitude was lower (38−46%) in group A. Whole (27−32%; p = 0.02), absolute (26−33%, p = 0.02) thigh muscle and absolute knee extensor muscle cross-sectional areas (22−33%, p = 0.04) were greater in group A. Right distal femur (24%; p = 0.08) and proximal tibia (29%; p = 0.03) BMDs were lower in group B, and peak isometric torque (p < 0.01), extensor spasticity scorers (p = 0.04) and muscle spasm scores (p = 0.002) were significantly higher in group A. Regression models revealed that amplitude of current, repetitions and body weight can accurately predict musculoskeletal qualities in persons with SCI. (4) Conclusions: Surface NMES amplitude and repetitions of leg extension differentiated between SCI survivors with greater versus lower musculoskeletal qualities. The study may shed the light on the interplay between muscle and bone in persons with SCI.

Leisure-time physical activity, anthropometrics, and body composition as predictors of quality of life domains after spinal cord injury: an exploratory cross-sectional study.

The objective of the current work was to examine the relationships between quality of life (QOL) domains in persons with spinal cord injury (SCI) and their levels of weekly leisure-time physical activity (LTPA), anthropometric variables, and body composition variables. This exploratory cross-sectional study consisted of baseline data collected as part of a randomized clinical trial at a VA Medical Center and SCI center. A convenience sample of 36 community-dwelling persons with SCI participated in the current study. Outcome measures included the World Health Organization Quality of Life Short Form (WHOQOL-BREF), Leisure-Time Physical Activity Questionnaire for People with Spinal Cord Injury (LTPAQ-SCI), anthropomorphic measures (waist, hip, and abdominal circumference), and dual-energy x-ray absorptiometry (DXA) to quantify regional and total body composition. Multiple regression models suggested that engagement in LTPA accounted for 35.7% of the variance in physical health QOL, 33.5% in psychological QOL, 14.2% in social relationships QOL, and 38.2% in environmental QOL. Anthropometric measures accounted for 11.3%, 3.1%, 12.0%, and 6.7% of the variance in these QOL indices, respectively, and DXA indices accounted for 18.7%, 17.5%, 27.4%, and 21.9%. Within these models, the number of minutes of heavy LTPA per day uniquely predicted physical health QOL, the number of mild LTPA days per week uniquely predicted psychological QOL, and the amount of mild LTPA per day uniquely predicted environmental QOL. Bivariate analyses also suggested that android and trunk fat, as well as supine waist and abdominal circumferences, were positively associated with social relationships QOL. Encouraging individuals with SCI to engage in LTPA may robustly enhance multiple aspects of QOL while reducing the risk for cardiovascular and metabolic morbidities associated with SCI. Moreover, this may lead to a further understanding of how QOL may impact longitudinal intervention trials. The study protocol and procedures were reviewed and approved by the McGuire VA Research Institutional Review Board (IRB# 02152, approval date August 9, 2015; IRB# 02375, approval date May 2, 2018).

Testosterone and long pulse width stimulation (TLPS) for denervated muscles after spinal cord injury: a study protocol of randomised clinical trial.

INTRODUCTION: Long pulse width stimulation (LPWS; 120-150 ms) has the potential to stimulate denervated muscles and to restore muscle size in denervated people with spinal cord injury (SCI). We will determine if testosterone treatment (TT)+LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in persons with SCI with denervation. We hypothesise that the 1-year TT+LPWS will upregulate protein synthesis pathways, downregulate protein degradation pathways and increase overall mitochondrial health. METHODS AND ANALYSIS: Twenty-four male participants (aged 18-70 years with chronic SCI) with denervation of both knee extensor muscles and tolerance to the LPWS paradigm will be randomised into either TT+neuromuscular electrical stimulation via telehealth or TT+LPWS. The training sessions will be twice weekly for 1 year. Measurements will be conducted 1 week prior training (baseline; week 0), 6 months following training (postintervention 1) and 1 week after the end of 1 year of training (postintervention 2). Measurements will include body composition assessment using anthropometry, dual X-ray absorptiometry and MRI to measure size of different muscle groups. Metabolic profile will include measuring of basal metabolic rate, followed by blood drawn to measure fasting biomarkers similar to hemoglobin A1c, lipid panels, C reactive protein, interleukin-6 and free fatty acids and then intravenous glucose tolerance test to test for insulin sensitivity and glucose effectiveness. Finally, muscle biopsy will be captured to measure protein expression and intracellular signalling; and mitochondrial electron transport chain function. The participants will fill out 3 days dietary record to monitor their energy intake on a weekly basis. ETHICS AND DISSEMINATION: The study was approved by Institutional Review Board of the McGuire Research Institute (ID # 02189). Dissemination plans will include the Veteran Health Administration and its practitioners, the national SCI/D services office, the general healthcare community and the veteran population, as well as the entire SCI community via submitting quarterly letters or peer-review articles. TRIAL REGISTRATION NUMBER: NCT03345576.

Effects of dose de-escalation following testosterone treatment and evoked resistance exercise on body composition, metabolic profile, and neuromuscular parameters in persons with spinal cord injury.

The dose de-escalation (DD) effects of testosterone and evoked resistance training (RT) on body composition, cardiometabolic, and neuromuscular variables were investigated. Thirteen men with chronic complete spinal cord injury (SCI) were followed for additional 16 weeks after receiving either testosterone treatment only (TT) or TT+RT. During the 16-week DD period, the TT+RT group underwent a program of once weekly electrical stimulation with gradually decreasing ankle weights and testosterone patches of 2 mg day-1 (TT+RT group). The TT only group did not receive any intervention throughout the detraining period (no-TT group). Body composition was tested using anthropometrics, dual energy X-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, inflammatory biomarkers, glucose effectiveness, and insulin sensitivity were measured. Finally, peak isometric and isokinetic torques were measured only in the TT+RT group. All measurements were conducted at the beginning and at the end of DD. Absolute thigh muscle cross-sectional areas (CSAs) demonstrated interaction effects (p < 0.05) between the TT+RT (-8.15%, -6.5%) and no-TT (2.3%, 4.4%) groups. Similarly, absolute knee extensor muscle CSA demonstrated interaction effects (p < 0.05) between the TT+RT (-11%, -7.0%) and no-TT (2.6%, 3.8%) groups. There was a trend (p = 0.07) of increasing visceral adipose tissue (VAT) CSAs in the TT+RT (18%) and in the no-TT (16% cm2 ) groups. There was an interaction (p = 0.005) between TT+RT (decreased by 3.7%) and no-TT groups (increased by 9.0%) in BMR. No interactions were evident between groups over time for biomarkers related to carbohydrate, lipid metabolism, or inflammation. Finally, there were no changes (p > 0.05) in peak isometric or isokinetic torques and rise time following 16 weeks of the DD period in the TT+RT group. TT+RT during 16 weeks of DD was minimally effective at preventing detraining relative to no-TT on muscle size, BMR, and VAT. However, neuromuscular gains were successfully maintained.

Neuromuscular electrical stimulation resistance training enhances oxygen uptake and ventilatory efficiency independent of mitochondrial complexes after spinal cord injury: a randomized clinical trial.

The purpose of the study was to determine whether neuromuscular electrical stimulation resistance training (NMES-RT)-evoked muscle hypertrophy is accompanied by increased V̇o2 peak, ventilatory efficiency, and mitochondrial respiration in individuals with chronic spinal cord injury (SCI). Thirty-three men and women with chronic, predominantly traumatic SCI were randomized to either NMES-RT (n = 20) or passive movement training (PMT; n = 13). Functional electrical stimulation-lower extremity cycling (FES-LEC) was used to test the leg V̇o2 peak, V̇E/V̇co2 ratio, and substrate utilization pre- and postintervention. Magnetic resonance imaging was used to measure muscle cross-sectional area (CSA). Finally, muscle biopsy was performed to measure mitochondrial complexes and respiration. The NMES-RT group showed a significant increase in postintervention V̇o2 peak compared with baseline (ΔV̇o2 = 14%, P < 0.01) with no changes in the PMT group (ΔV̇o2 = 1.6%, P = 0.47). Similarly, thigh (ΔCSAthigh = 19%) and knee extensor (ΔCSAknee = 30.4%, P < 0.01) CSAs increased following NMES-RT but not after PMT. The changes in thigh and knee extensor muscle CSAs were positively related with the change in V̇o2 peak. Neither NMES-RT nor PMT changed mitochondrial complex tissue levels; however, changes in peak V̇o2 were related to complex I. In conclusion, in persons with SCI, NMES-RT-induced skeletal muscle hypertrophy was accompanied by increased peak V̇o2 consumption which may partially be explained by enhanced activity of mitochondrial complex I.NEW & NOTEWORTHY Leg oxygen uptake (V̇o2) and ventilatory efficiency (V̇E/V̇co2 ratio) were measured during functional electrical stimulation cycling testing following 12-16 wk of either electrically evoked resistance training or passive movement training, and the respiration of mitochondrial complexes. Resistance training increased thigh muscle area and leg V̇o2 peak but decreased V̇E/V̇co2 ratio without changes in mitochondrial complex levels. Leg V̇o2 peak was associated with muscle hypertrophy and mitochondrial respiration of complex I following training.

Attenuation of autonomic dysreflexia during functional electrical stimulation cycling by neuromuscular electrical stimulation training: case reports.

INTRODUCTION: Spinal cord injury (SCI) may cause impairments of the motor, sensory, and autonomic nervous systems, which result in adverse changes in body composition and cardiovascular health. Functional electrical stimulation (FES) cycling may provide an effective alternative approach to perform exercise and improve cardiovascular health after SCI. Persons with an injury at or above T6 level are at high risk of developing a life-threatening complication of autonomic dysreflexia (AD). CASE PRESENTATION: Two participants with motor-complete C6 SCI completed either 12 weeks of passive range of motion or surface neuromuscular electrical stimulation (NMES) resistance training, followed by 12 weeks of functional electrical stimulation (FES) lower extremity cycling for both participants. Systolic and diastolic blood pressure (BP) were measured to determine the effects of NMES-resistance training and FES-lower extremity cycling during rest and exercise. DISCUSSION: The difference between mean value of BP during FES-lower extremity cycling exercise and resting BP averaged for 24 sessions was smaller for participant A (31.25 mmHg for systolic BP and 10.44 mmHg for diastolic BP), who received NMES-resistance training, as compared with participant B (58.62 mmHg for systolic BP and 35.07 mmHg for diastolic BP). The results of these case reports suggest that 12 weeks of NMES-resistance training preceding FES-lower extremity cycling may attenuate the development of AD after SCI. Risk of AD, triggered by noxious stimuli, may be dampened with FES-lower extremity cycling training in persons with SCI.

Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report.

BACKGROUND: Severe spasticity may negatively impact functionality and quality of life after spinal cord injury (SCI). Intrathecal baclofen treatment (IBT) is effectively used to manage severe spasticity and reduce comorbidities. However, long-term IBT may have a negative effect on bone mineral content (BMC), bone mineral density (BMD) and body composition (such as percentage fat mass and lean body mass). We demonstrated the negative effects of long-term IBT use in a single case compared with two non-IBT users. CASE SUMMARY: A 46-year old Caucasian male Veteran (case) with a 21 year history of complete tetraplegia (complete C6 SCI) was implanted with IBT for 20 years. The case was matched to two participants with different time since injuries [2 (match 1) and 13 (match 2) years] without IBT. Knee BMC and BMD at the epiphysis and metaphysis of the distal femur and proximal tibia were evaluated using dual knee and the dual femur modules of GE Lunar iDXA software. Total and leg body composition assessments were also conducted for the three participants. Potential effect of long-term IBT was demonstrated by changes in BMD, consistent with bone demineralization, at the distal femur and proximal tibia and changes in percentage fat mass and lean mass of legs. The case showed 113% lower BMD at the distal femur, and 78.1% lower at the proximal tibia compared to match 1, moreover the case showed 45% lower BMD at the distal femur, and no observed changes at the proximal tibia compared to match 2. The case had 27.1% and 16.5% greater leg %fat mass compared to match 1 and match 2, respectively. Furthermore, the case had 17.4% and 11.8% lower % leg lean mass compared to match 1 and match 2, respectively. CONCLUSION: Long-term IBT may impact bone health and body composition parameters in persons with complete SCI. It may be prudent to encourage regular screening of individuals on long-term IBT considering the prevalence of osteoporosis related fractures, cardiovascular diseases, and metabolic disorders in this population.

Low-Dose Testosterone and Evoked Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial.

The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18-50 years) were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2-6 mg/day). Body composition was tested using anthropometrics, dual energy x-ray absorptiometry, and magnetic resonance imaging. After an overnight fast, basal metabolic rate (BMR), lipid panel, serum testosterone, adiponectin, inflammatory and anabolic biomarkers (insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 [IGFBP-3]), glucose effectiveness (Sg), and insulin sensitivity (Si) were measured. Total body lean mass (LM; 2.7 kg, p < 0.0001), whole muscle (p < 0.0001), and whole muscle knee extensor cross-sectional areas (CSAs; p < 0.0001) increased in the TRT+RT group, with no changes in the TRT group. Visceral adiposity decreased (p = 0.049) in the TRT group, with a trend in the TRT+RT (p = 0.07) group. There was a trend (p = 0.050) of a 14-17% increase in BMR following TRT+RT. Sg showed a trend (p = 0.07) to improvement by 28.5-31.5% following both interventions. IGFBP-3 increased (p = 0.0001) while IL-6 decreased (p = 0.039) following both interventions, and TRT+RT suppressed adiponectin (p = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.

Skeletal muscle hypertrophy and attenuation of cardio-metabolic risk factors (SHARC) using functional electrical stimulation-lower extremity cycling in persons with spinal cord injury: study protocol for a randomized clinical trial.

BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.

Gender Dimorphism in Central Adiposity May Explain Metabolic Dysfunction After Spinal Cord Injury.

BACKGROUND: Increase in visceral adipose tissue (VAT) is an independent risk for mortality and other health-related comorbidities. OBJECTIVE: To examine the gender differences in VAT and subcutaneous adipose tissue (SAT) cross-sectional areas (CSA) between men and women with chronic spinal cord injury (SCI). The differences in the distribution of central adiposity were used to determine the association of VAT and SAT to metabolic dysfunction after SCI. DESIGN: Cross-sectional design. SETTING: Hospital-based study. PARTICIPANTS: Sixteen individuals (8 men and 8 women) with motor complete SCI were matched based on age, time since injury, and level of injury. METHODS: Anthropometrics, dual x-ray absorptiometry (DXA), and magnetic resonance imaging were captured to measure lean mass, fat mass (FM), percentage FM, VAT, and SAT CSAs. Basal metabolic rate was measured, and intravenous glucose tolerance test and lipid panel were performed. MAIN OUTCOME MEASUREMENTS: VAT, SAT, and metabolic profile. RESULTS: SAT CSA was 1.6 -1.75 times greater in the upper and lower trunks in women compared to men with SCI (P < .05). VAT CSA was 1.8-2.6 times greater in the upper and lower trunks in men compared to women with SCI (P < .05). VAT adjusted to body weight was greater in men compared to women with SCI. High-density lipoprotein cholesterol (HDL-C) was positively related to SAT and negatively related to VAT. Glucose effectiveness was negatively related to lower trunk SAT (r = -0.60, P = .02). HDL-C ratio and triglycerides were positively related to upper VAT, lower VAT, and VAT:SAT ratio. CONCLUSION: Magnetic resonance imaging demonstrated that there is a gender dimorphism in central adiposity in persons with chronic SCI. This gender dimorphism in central adipose tissue distribution may explain the higher prevalence of metabolic dysfunction in men with SCI, especially, the decrease in the HDL-C profile. LEVEL OF EVIDENCE: IV.

Paradigms of Lower Extremity Electrical Stimulation Training After Spinal Cord Injury.

Skeletal muscle atrophy, increased adiposity and reduced physical activity are key changes observed after spinal cord injury (SCI) and are associated with numerous cardiometabolic health consequences. These changes are likely to increase the risk of developing chronic secondary conditions and impact the quality of life in persons with SCI. Surface neuromuscular electrical stimulation evoked resistance training (NMES-RT) was developed as a strategy to attenuate the process of skeletal muscle atrophy, decrease ectopic adiposity, improve insulin sensitivity and enhance mitochondrial capacity. However, NMES-RT is limited to only a single muscle group. Involving multiple muscle groups of the lower extremities may maximize the health benefits of training. Functional electrical stimulation-lower extremity cycling (FES-LEC) allows for the activation of 6 muscle groups, which is likely to evoke greater metabolic and cardiovascular adaptation. Appropriate knowledge of the stimulation parameters is key to maximizing the outcomes of electrical stimulation training in persons with SCI. Adopting strategies for long-term use of NMES-RT and FES-LEC during rehabilitation may maintain the integrity of the musculoskeletal system, a pre-requisite for clinical trials aiming to restore walking after injury. The current manuscript presents a combined protocol using NMES-RT prior to FES-LEC. We hypothesize that muscles conditioned for 12 weeks prior to cycling will be capable of generating greater power, cycle against higher resistance and result in greater adaptation in persons with SCI.

Exoskeleton Training May Improve Level of Physical Activity After Spinal Cord Injury: A Case Series.

Objectives: To determine whether the use of a powered exoskeleton can improve parameters of physical activity as determined by walking time, stand up time, and number of steps in persons with spinal cord injury (SCI). Methods: Three men with complete (1 C5 AIS A and 2 T4 AIS A) and one man with incomplete (C5 AIS D) SCI participated in a clinical rehabilitation program. In the training program, the participants walked once weekly using a powered exoskeleton (Ekso) for approximately 1 hour over the course of 10 to 15 weeks. Walking time, stand up time, ratio of walking to stand up time, and number of steps were determined. Oxygen uptake (L/min), energy expenditure, and body composition were measured in one participant after training. Results: Over the course of 10 to 15 weeks, the maximum walking time increased from 12 to 57 minutes and the number of steps increased from 59 to 2,284 steps. At the end of the training, the 4 participants were able to exercise for 26 to 59 minutes. For one participant, oxygen uptake increased from 0.27 L/min during rest to 0.55 L/min during walking. Maximum walking speed was 0.24 m/s, and delta energy expenditure increased by 1.4 kcal/min during walking. Body composition showed a modest decrease in absolute fat mass in one participant. Conclusion: Exoskeleton training may improve parameters of physical activity after SCI by increasing the number of steps and walking time. Other benefits may include increasing energy expenditure and improving the profile of body composition.

MRI analysis and clinical significance of lower extremity muscle cross-sectional area after spinal cord injury.

Shortly after spinal cord injury (SCI), the musculoskeletal system undergoes detrimental changes in size and composition, predominantly below the level of injury. The loss of muscle size and strength, along with increased immobility, predisposes persons with SCI to rapid and severe loss in bone mineral density and other health related consequences. Previous studies have highlighted the significance of measuring thigh muscle cross-sectional area, however, measuring the size and composition of muscles of the lower leg may provide insights on how to decrease the risk of various comorbidities. The purpose of the current review was to summarize the methodological approach to manually trace and measure the muscles of the lower leg in individuals with SCI, using magnetic resonance imaging. We also intend to highlight the significance of analyzing lower leg muscle cross-sectional area and its relationship to musculoskeletal and vascular systems in persons with SCI.