Effects of a Low-Carbohydrate, High-Protein Diet on Gut Microbiome Composition in Insulin-Resistant Individuals With Chronic Spinal Cord Injury: Preliminary Results From a Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of a low-carbohydrate, high-protein (LC/HP) diet that includes healthy dietary components (eg, lean meat, whole grains, fruits and vegetables, fiber, etc) on the gut microbiome composition in individuals with chronic spinal cord injury (SCI). DESIGN: A single-center randomized parallel controlled trial. SETTING: Research University. PARTICIPANTS: Adult participants with chronic SCI (N=19, 3 years or more after the injury, C2-L2, American Spinal Injury Association Impairment Scale A-D). Participants were insulin resistant and had not received antibiotics within 4 weeks before enrolling in the study. INTERVENTIONS: Participants were randomized to the LC/HP diet group (40% energy from carbohydrates, 30% energy from protein, and 30% energy from fat and met dietary guideline recommendations) or the control group for 8 weeks. Participants assigned to the LC/HP group were provided with all meals delivered weekly to their homes. Participants assigned to the control group were asked to continue their usual diet. MAIN OUTCOME MEASURES: Stool samples were collected at baseline and the end of week 8. The gut microbiome 16S ribosomal RNA V4 region was sequenced, and gut microbiome diversity and taxonomical abundance were computed using the QIIME2 suite. RESULTS: Participants in the LC/HP group had significant changes in alpha-diversity (reduced operational taxonomic unit and Faith's phylogenetic diversity) and beta-diversity (unweighted UniFrac), while no significant differences were observed among participants in the control group after the intervention. Moreover, several taxa changed differently over time between groups, including increased Bacteroides thetaiotaomicron, Coprococcus 3, Fusicatenibacter, Tannerellaceae, and decreased Tyzzerella, Phascolarctobacterium, Romboutsia, Clostridium sensu stricto 1, Hungatella, Ruminococcus gauvreauii, family XI, and Bacillales among participants in the diet group, while these taxa did not change in the control group. CONCLUSIONS: An LC/HP diet with healthy dietary components improved gut microbiome composition in individuals with SCI, including increased bacteria implicated in fiber metabolism and reduced bacteria communities linked to cardiometabolic disorders.

Gut Microbiome Composition and Serum Metabolome Profile Among Individuals With Spinal Cord Injury and Normal Glucose Tolerance or Prediabetes/Type 2 Diabetes.

OBJECTIVE: To compare the gut microbiome composition and serum metabolome profile among individuals with spinal cord injury (SCI) and normal glucose tolerance (NGT) or prediabetes/type 2 diabetes (preDM/T2D). DESIGN: Cross-sectional design. SETTING: Research university. PARTICIPANTS: A total of 25 adults (N=25) with SCI were included in the analysis and categorized as NGT (n=16) or preDM/T2D (n=9) based on their glucose concentration at minute 120 during a 75-g oral glucose tolerance test. The American Diabetes Association diagnosis guideline was used for grouping participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A stool sample was collected and used to assess the gut microbiome composition (alpha and beta diversity, microbial abundance) via the 16s ribosomal RNA sequencing technique. A fasting serum sample was used for liquid chromatography-mass spectrometry-based untargeted metabolomics analysis, the results from which reflect the relative quantity of metabolites detected and identified. Gut microbiome and metabolomics data were analyzed by the Quantitative Insights into Microbial Ecology 2 and Metaboanalyst platforms, respectively. RESULTS: Gut microbiome alpha diversity (Pielou's evenness index, Shannon's index) and beta diversity (weighted UniFrac distances) differed between groups. Compared with participants with NGT, participants with preDM/T2D had less evenness in microbial communities. In particular, those with preDM/T2D had a lower abundance of the Clostridiales order and higher abundance of the Akkermansia genus, as well as higher serum levels of gut-derived metabolites, including indoxyl sulfate and phenylacetylglutamine (P < .05 for all). CONCLUSIONS: Our results provide evidence for altered gut microbiome composition and dysregulation of gut-derived metabolites in participants with SCI and preDM/T2D. Both indoxyl sulfate and phenylacetylglutamine have been implicated in the development of cardiovascular diseases in the able-bodied population. These findings may inform future investigations in the field of SCI and cardiometabolic health.

Differences in Glucose Metabolism Among Women With Spinal Cord Injury May Not Be Fully Explained by Variations in Body Composition.

OBJECTIVE: To investigate the differences in glucose metabolism among women with paraplegic, and tetraplegic spinal cord injury (SCI) in comparison to their able-bodied (AB) counterparts after adjusting for differences in body composition. DESIGN: Cross-sectional study. After an overnight fast, each participant consumed a 75-g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C-peptide concentrations were analyzed before and 30, 60, 90, and 120 minutes after ingesting glucose solution. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and total body lean mass (TBLM) were estimated using data from dual-energy x-ray absorptiometry. Visceral fat (VF) was quantified using computed tomography. Outcome measures were compared among groups using analysis of covariance with %FM (or VF) and TBLM as covariates. SETTING: Research university. PARTICIPANTS: Women (N=42) with SCI (tetraplegia: n=8; paraplegia: n=14) and their race-, body mass index-, and age-matched AB counterparts (n=20). INTERVENTIONS: Not applicable. RESULTS: At fasting, there was no difference in glucose homeostasis (glucose, insulin, C-peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C-peptide concentrations at minute 120 during OGTT were higher in women with tetraplegia versus women with paraplegia and AB women (P<.05, adjusted for TBLM and %FM). In addition, women with tetraplegia had lower ISI (P<.05, adjusted for TBLM and %FM) versus AB women. These differences remained after adjusting for VF and TBLM. CONCLUSION: Our study confirms that impaired glucose metabolism among women with tetraplegia may not be fully explained by changes in their body composition. Future studies exploring additional factors involved in glucose metabolism are warranted.

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.

Mechanosensitivity may be enhanced in skeletal muscles of spinal cord-injured versus able-bodied men.

We investigated the effects of an acute bout of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) on intracellular signaling pathways involved in translation initiation and mechanical loading-induced muscle hypertrophy in spinal cord-injured (SCI) versus able-bodied (AB) individuals. AB and SCI individuals completed 90 isometric knee extension contractions at 30% of maximum voluntary or evoked contraction, respectively. Muscle biopsies were collected before, and 10 and 60 min after NMES-RE. Protein levels of α7- and ß1-integrin, phosphorylated and total GSK-3α/ß, S6K1, RPS6, 4EBP1, and FAK were assessed by immunoblotting. SCI muscle appears to be highly sensitive to muscle contraction even several years after the injury, and in fact it may be more sensitive to mechanical stress than AB muscle. Heightened signaling associated with muscle mechanosensitivity and translation initiation in SCI muscle may be an attempted compensatory response to offset elevated protein degradation in atrophied SCI muscle. .

Pregnancy, labor, and delivery outcomes of women with and without spinal cord injury.

Objectives: Compare outcomes in pregnant women with and without Spinal Cord Injury (SCI).Design: Case study and inception cohort comparison.Setting: Community, primary care/referral center and university practice.Participants: Twenty-eight pregnant women (12 with SCI ( = PW-SCI) and 16 without SCI ( = PW-AB)) were enrolled. Six PW-SCI left study and six completed data collection and were matched, by age, parity, and race, with 12 PW-AB (1:2 ratio, respectively). Final analysis included 18 (78%) subjects.Interventions: Not applicable.Main Outcome Measures: Utilizing standardized, templated medical records (published by NIH/NICHHD and DHHS) and self-report, prospective, longitudinal and retrospective details of pregnancy, labor and delivery experiences/complications were recorded for all women and their neonates. Data collection included vital signs, urinalysis, pregnancy-related conditions/complications (i.e. UTIs, hyperglycemia), and labor, delivery, fetal outcomes. For PW-SCI, demographics, occurrences of autonomic dysreflexia (AD), pressure sores, worsening SCI conditions (i.e. spasticity, bladder spasms, lost independence) were recorded.Results: PW-SCI had statistically greater (P < .05) UTIs than PW-AB (three (50%) to 0 (0%), respectively). One PW-SCI (17%) reported pressure sores and one AD. Three (50%) PW-SCI and 4 (33%) PW-AB experienced a complication at delivery. Newborn mean birth weight (2854 g vs 3578 g; P = 0.12), and length (49.3 vs 45.8 cm; P = 0.32) were lower for PW-SCI than PW-AB. Head circumference was significantly less for PW-SCI than PW-AB (30.3 vs 34.5 cm; P = 0.04).Conclusions: Women with SCI tend to have more complicated courses of pregnancy, labor and delivery and smaller newborns than non-SCI peers. Neonatal head circumference is significantly smaller.

Effects of a low-carbohydrate/high-protein diet on metabolic health in individuals with chronic spinal cord injury: An exploratory analysis of results from a randomized controlled trial.

We explored the impact of a low-carbohydrate/high-protein diet (LC/HP, ~30% energy from protein, 40% energy from carbohydrate) on indices of metabolic function and body composition in individuals with chronic spinal cord injury (SCI). Adults with SCI (≥3 years post-injury, C4-L2, AIS A-D) and insulin resistance or pre-diabetes were randomly assigned to an 8-week iso-caloric LC/HP diet group (n = 11) or control group (n = 14). All LC/HP meals were delivered weekly to participants' homes, and participants in the control group consumed their habitual diet. Each participant underwent an oral glucose tolerance test (OGTT) to assess glucose tolerance, insulin, area under the curve (AUC) for glucose and insulin, Matsuda Index, glucose-stimulated insulin secretion (GSIS), disposition index, and hepatic insulin extraction (HIE). Fasting blood lipid and inflammation were assessed, and body composition was estimated using dual-energy x-ray absorptiometry. A linear mixed model was used to evaluate the main effect of diet, time, and their interaction. Compared to the control group, participants in the LC/HP group had reduced total body fat mass (LC/HP: -5.9%, Control: 0.7%), visceral fat mass (LC/HP: -16.2%, Control: 5.2%), total- (LC/HP: -20.1, Control: 3.7 mg/dl), and LDL-cholesterol (LC/HP: -13.9, Control: 3.1 mg/dl) (pdiet*time < 0.05 for all). Regardless of group, AUCinsulin and peak insulin during the OGTT decreased, and HIE increased over time (ptime < 0.05). A trend for diet*time interaction was observed for glucoseOGTT120min (LC/HP: -20.7, Control: 3.0 mg/dl, pdiet*time  = 0.09) and peak C-peptide (LC/HP: -2.1, Control: 0.0 ng/ml, pdiet*time  = 0.07). HDL-cholesterol, lean body mass, Matsuda Index, fasting glucose, insulin, insulinOGTT120min , AUCglucose , pancreatic beta cell function (GSIS, disposition index), and inflammation (C-reactive protein, IL-6, IL-8, IL-10, TNF-α) did not change over time. In conclusion, our results suggest that individuals with SCI and insulin resistance may adopt an LC/HP diet to improve body composition and lipid profiles. Its impact on glucose metabolism and inflammation remains inconclusive and warrants future investigations.

Comparison of the gut microbiome composition among individuals with acute or long-standing spinal cord injury vs. able-bodied controls.

Objective: Compare the gut microbiome composition among individuals with acute spinal cord injury (A-SCI), long-standing SCI (L-SCI), vs. able-bodied (AB) controls.Design: Cross-sectional study.Setting: The University of Alabama at Birmingham.Participants: Seven adults with A-SCI (36 ± 12 years, 2F/5M, C4-T10, and American Spinal Injury Association Impairment Scale [AIS] A-D), 25 with L-SCI (46 ± 13 years, 6F/19M, C4-L1, and AIS A-D), and 25 AB controls (42 ± 13 years, 9F/16M).Methods: Stool samples were collected after a median of 7 days and 18 years after injury in the A-SCI and L-SCI groups, respectively. Gut microbiome composition was analyzed using the 16S rRNA sequencing technique and QIIME software. The abundances of bacteria communities among groups were compared using the Kruskal-Wallis test adjusted for age.Results: Several alpha diversity indices were different among groups (Chao1, Observed species, and Phylogenetic Diversity), but not others (Shannon and Simpson). Beta diversity differed among each pair of groups (P < 0.05). A number of microbial communities were differentially abundant among the groups (P < 0.05).Conclusion: Our results revealed differences in the gut microbiome composition among groups. Compared to the AB controls, the SCI groups demonstrated microbiome profiles that shared features linked to metabolic syndrome, inflammation-related bowel disorders, depressive disorders, or antibiotics use, whereas the L-SCI group's microbiome included features linked to reduced physical activity compared to the A-SCI and AB controls. Our results provided preliminary data and a scientific foundation for future studies investigating the impact of the gut microbiome composition on long-term health in individuals with SCI.

A qualitative interview study on successful pregnancies in women with spina bifida.

BACKGROUND: Improvements in antenatal medicine and surgical management for conditions associated with spina bifida such as hydrocephalus have extended the lifespan for individuals with spina bifida (SB) into adulthood. Decisions and education regarding reproductive care and pregnancies for patients with spina bifida are increasingly important. Pregnancy in these patients can be particularly challenging due to physical limitations, previous abdominal surgery for urinary or bowel management and presence of a ventriculoperitoneal shunt. To date, little research has examined the unique challenges that women with spina bifida face during pregnancy. OBJECTIVE: The purpose of this descriptive study is to characterize the successful pregnancy histories of SB women and describe how pregnancy affected their mobility as well as bladder and bowel management. STUDY DESIGN: We conducted semi-structured interviews with women followed in our adult multidisciplinary SB clinic who previously had successful pregnancies. Questions regarding perinatal issues, obstetrical complications, urinary tract infections (UTI) and neurological changes were asked. Baseline mobility, bladder and bowel management were compared with changes during and after pregnancy. RESULTS: 121 women of childbearing age were followed per year by our adult multidisciplinary spina bifida clinic between 2009 and 2016. We identified 6 women who successfully carried 8 pregnancies to term. There were no miscarriages. Four women had ventriculoperitoneal (VP) shunts. No children were born with neural tube defects. Mean age at first pregnancy was 23.5 years. Average gestational age at delivery was 37 weeks. 50% of the women had a spontaneous vaginal delivery. Five of six women intended to get pregnant; only one patient consumed folic acid regularly prior to pregnancy. Two of six women had bladder augmentation surgery, one of whom had urologic changes during pregnancy that persisted after childbirth. The other patient had a concomitant bladder neck sling procedure and did not have urologic issues during pregnancy. 50% of the patients experienced bladder-bowel dysfunction during their pregnancy. While 67% patients had full baseline ambulatory function, 4 patients had decreased mobility and required additional assistance during pregnancy. All returned to their baseline functionality afterwards. CONCLUSION: Six of our patients had eight successful pregnancies, with no children born with neural tube defects. New changes to mobility, bladder and bowel management were experienced by over half of the women during their pregnancies. Future studies should focus on the role of multidisciplinary teams in reproductive health education and perinatal management of changes to activities of daily living during pregnancy in this population.

Limited Association between the Total Healthy Eating Index-2015 Score and Cardiovascular Risk Factors in Individuals with Long-Standing Spinal Cord Injury: An Exploratory Study: An Exploratory Study.

BACKGROUND: The healthy eating index-2015 (HEI-2015) reflects diet quality in reference to the 2015-2020 Dietary Guidelines for Americans (DGA). Little is known regarding its application in individuals with chronic spinal cord injury (SCI). OBJECTIVE: To explore the relationship between diet quality as assessed by the HEI-2015 and cardiovascular risk factors among individuals with chronic SCI. DESIGN: This is a cross-sectional analysis of baseline data collected from August 2017 through November 2019 for an interventional study that evaluates the effects of a high-protein/low-carbohydrate diet on cardiovascular risk factors in individuals with chronic SCI at the University of Alabama at Birmingham. PARTICIPANTS/SETTING: Twenty-four free-living adults with SCI (mean age, 45 ± 12 y; 8F/16M, level of injury: nine cervical, 15 thoracic; mean duration of injury: 20 ± 13 y) were included. MAIN OUTCOME MEASURES: Participants underwent a 2-hour oral glucose tolerance test (OGTT) and a dual-energy x-ray absorptiometry scan. Dietary intake was assessed by three, 24-hour multiple-pass dietary recalls to calculate the HEI-2015 using the simple HEI scoring algorithm method. DATA ANALYSIS: Multiple linear regression analyses were performed to predict indices of lipid metabolism and glucose homeostasis and C-reactive protein (CRP) from the HEI-2015. Principal component analysis was used to reduce the number of covariates (level of injury, sex, and body fat percentage). RESULTS: On average, participants' diets were of low quality (HEI-2015, 47.2 ± 10.8). The regression models for fasting glucose (FG), cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and CRP had moderate to large effect sizes (adjusted R2 ≥ 13%), suggesting good explanatory abilities of the predictors. Small or limited effect sizes were observed for glucose tolerance, fasting insulin, triglycerides, and Matsuda index (adjusted R2 < 13%). The HEI-2015 accounted for a moderate amount of variation in FG (partial omega-squared, ωP2 = 13%). Each 10-point HEI-2015 score increase was associated with a 3.3-mg/dL decrease in FG concentrations. The HEI-2015 accounted for a limited amount of variation in other indices (ωP2 < 5%). CONCLUSIONS: Among participants with SCI, higher conformance to the 2015-2020 DGA was 1) moderately associated with better FG homeostasis; and 2) trivially associated with other cardiovascular risk factors. Because of the small sample size, these conclusions cannot be extrapolated beyond the study sample. Future larger studies are warranted to better understand the relationship between diet quality and cardiovascular disease risks in this population.

Assessing the ability of the Sacral Autonomic Standards to document bladder and bowel function based upon the Asia Impairment Scale.

Study design: Retrospective review of data. Objective: To determine if there is a relationship between the Asia Impairment Scale (AIS) and the bladder and bowel components of the International Standards to Document Remaining Autonomic Function after SCI (ISAFSCI). Setting: University-Based Academic Rehabilitation Program. Methods: Retrospective cross-sectional study assessing International Standards for Neurologic Classification After SCI (ISNCSCI) examination along with bladder and bowel components of the ISAFSCI. Results: Subjects with AIS A injuries were statistically less likely to have history of bladder control and bowel control per investigator determination and bladder sensation via self-report versus patients categorized with AIS B injuries. Self-reported history of bowel sensation and control of voiding were more likely in subjects with C, D, or E injuries than with B injuries. Bowel and bladder control as determined by investigator and bladder and bowel sensation and control as self-reported were all statistically less likely in persons with AIS A injuries versus CDE. Conclusions: This retrospective study provides initial data regarding components of the bladder and bowel sections of the sacral ISAFSCI and AIS. Further prospective research is needed to further characterize the relationship between retention of bladder and bowel sensation and function and the AIS. We suggest that incorporation of the sacral components of the ISAFSCI into the ISNCSCI may be beneficial to obtain further information about retention of sacral function with specific patterns of injury.

Utilizing a low-carbohydrate/high-protein diet to improve metabolic health in individuals with spinal cord injury (DISH): study protocol for a randomized controlled trial.

BACKGROUND: Metabolic disorders (e.g., impaired glucose tolerance, insulin resistance, and type 2 diabetes) are more prevalent in people with spinal cord injury (SCI) than able-bodied individuals. Dietary modification is a more cost-effective treatment option than pharmacological therapies for reducing the risk of metabolic dysfunction. Lowering carbohydrate, increasing protein, and maintaining a proper dietary fat intake are expected to induce favorable adaptations in glucose control, body fat distribution, and the composition of the gut microbiome. However, dietary modification has not been rigorously investigated in people with SCI. The purpose of this study is to determine if an 8-week low-carbohydrate/high-protein (LC/HP) dietary intervention will show improvements in clinically important metrics of metabolic function, body composition, the composition of gut bacteria, and quality of life. METHODS/DESIGN: We intend to recruit 100 participants with chronic traumatic SCI (3 years postinjury, C5-L2, American Spinal Injury Association impairment scale A-D, and aged 18-65 years) and insulin resistance, impaired glucose tolerance or untreated type 2 diabetes and randomly assign them to an 8-week LC/HP dietary intervention group or a control group. The daily LC/HP dietary intervention includes ~ 30% total energy as protein (1.6 g/kg per day) with a carbohydrate-to-protein ratio < 1.5 and fat intake set at ~ 30% of the total energy intake. The control group does not receive any dietary intervention and are continuing with their regular daily diets. Glucose tolerance, insulin sensitivity, ß-cell function, body composition, gut microbiome composition, and quality of life measures are assessed at week 1, before starting the LC/HP dietary intervention, and at week 8, after completion of the LC/HP dietary intervention. DISCUSSION: New information derived from this project will result in the development of a low-cost, simple, self-administered LC/HP dietary intervention for improving metabolic function in individuals with chronic SCI, improved understanding of the composition of gut bacteria in SCI, and how a LC/HP dietary intervention alters gut bacteria composition. In addition, this project will improve our understanding of the relationship between metabolic function and quality of life in individuals with long-standing SCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03207841. Registered on 5 June 2017.

Paralytic and nonparalytic muscle adaptations to exercise training versus high-protein diet in individuals with long-standing spinal cord injury.

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85-90%, V̇o2peak) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o2peak, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.

A high-protein diet or combination exercise training to improve metabolic health in individuals with long-standing spinal cord injury: a pilot randomized study.

We compared the effects of an 8-week iso-caloric high-protein (HP) diet versus a combined exercise regimen (Comb-Ex) in individuals with long-standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT-4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb-Ex: n = 6; 46 ± 8 years; C5-T12 levels; American Spinal Injury Association Impairment Scale A or B). The Comb-Ex regimen included upper body resistance training (RT) and neuromuscular electrical stimulation-induced-RT for paralytic quadriceps muscles, interspersed with high-intensity (80-90% VO2 peak) arm cranking exercises 3 days/week. The HP diet included ~30% total energy as protein (carbohydrate to protein ratio <1.5, ~30% energy from fat). Oral glucose tolerance tests and muscle biopsies of the vastus lateralis (VL) and deltoid muscles were performed before and after the trial. Fasting plasma glucose levels decreased in the Comb-Ex (P < 0.05) group compared to the HP-diet group. A decrease in areas under the curve for insulin and TNF-α concentrations was observed for all participants regardless of group assignment (time effect, P < 0.05). Although both groups exhibited a quantitative increase in insulin sensitivity as measured by the Matsuda Index, the change was clinically meaningful only in the HP diet group (HP diet: pre, 4.6; post, 11.6 vs. Comb-Ex: pre, 3.3; post, 4.6). No changes were observed in proteins associated with GLUT-4 translocation in VL or deltoid muscles. Our results suggest that the HP-diet and Comb-Ex regimen may improve insulin sensitivity and decrease TNF-α concentrations in individuals with SCI.

The development of a lifetime care model in comprehensive spina bifida care.

PURPOSE: To describe the development and implementation of the Children's of Alabama (COA) Spina Bifida (SB) Lifetime-Care-Model, including standardized care protocols and transition plan. METHODS: In 2010, members of the pediatric team at COA began to evaluate limitations in access to care for patients with SB at various stages of life. Through clinic surveys, observations, and caregiver report, a Lifetime-Care-Model was developed and implemented. Partnerships were made with adult medicine colleagues to create an interdisciplinary model at each stage. Since developing this program, it has evolved to include standardized care protocols. RESULTS: Since 2011, there have been 42 prenatal clinics; 114 families received counseling and prenatal care. Of these, 106 have delivered at our center and established care in our pediatric clinic. There are currently 474 patients in the pediatric and 218 in the adult clinics. CONCLUSIONS: Our institutional experience suggests that patients with SB benefit from continuity of care throughout their lifetime. This article describes early failures which led to an evolution in approach and implementation of a Lifetime-Care-Model which results in a smooth transition between all phases of life. We hope that other institutions may adapt and build upon it to create programs unique to their specific patient needs.

Women's Sexual Health and Reproductive Function After SCI.

Sexual function and to a lesser extent reproduction are often disrupted in women with spinal cord injuries (SCI), who must be educated to better understand their sexual and reproductive health. Women with SCI are sexually active; they can use psychogenic or reflexogenic stimulation to obtain sexual pleasure and orgasm. Treatment should consider a holistic approach using autonomic standards to describe remaining sexual function and to assess both genital function and psychosocial factors. Assessment of genital function should include thoracolumbar dermatomes, vulvar sensitivity (touch, pressure, vibration), and sacral reflexes. Self-exploration should include not only clitoral stimulation, but also stimulation of the vagina (G spot), cervix, and nipples conveyed by different innervation sources. Treatments may consider PDE5 inhibitors and flibanserin on an individual basis, and secondary consequences of SCI should address concerns with spasticity, pain, incontinence, and side effects of medications. Psychosocial issues must be addressed as possible contributors to sexual dysfunctions (eg, lower self-esteem, past sexual history, depression, dating habits). Pregnancy is possible for women with SCI; younger age at the time of injury and at the time of pregnancy being significant predictors of successful pregnancy, along with marital status, motor score, mobility, and occupational scores. Pregnancy may decrease the level of functioning (eg, self-care, ambulation, upper-extremity tasks), may involve complications (eg, decubitus ulcers, weight gain, urological complications), and must be monitored for postural hypotension and autonomic dysreflexia. Taking into consideration the physical and psychosocial determinants of sexuality and childbearing allows women with SCI to achieve positive sexual and reproductive health.

Upper extremity motor training of a subject with initially motor complete chronic high tetraplegia using constraint-induced biofeedback therapy.

INTRODUCTION: The purpose of this case study was to determine if a subject with chronic high tetraplegia (C3 AIS A) could learn to use an initially paralyzed upper extremity on the basis of training procedures alone. CASE PRESENTATION: Initially, an AIS examination revealed no purposive movement below the neck other than minimal shoulder movement. Training was carried out weekly over 39 months. Training began based on electromyographic biofeedback; the electrical activity of a muscle (biceps or triceps) was displayed visually on a computer monitor and the subject was encouraged to progressively increase the magnitude of the response in small increments on a trial-by-trial basis (i.e., shaping). When small, overt movements began to appear; these were, in turn, shaped so that their excursion progressively increased. Training then progressed to enable lifting the arm with the aid of the counterweight of a Swedish Help Arm. Mean movement excursions in the best session were: internal rotation 52.5 cm; external rotation 26.9 cm; shoulder extension 22.1 cm; shoulder flexion 15.2 cm; pronation/supination 120°; extension of index finger (D2) 2.5 cm. Movements were initially saltatory, becoming smoother over time. With the Swedish Help Arm, the subject was able to lift her hand an average of 24.3 cm in the best session with 0.7 kg counterweight acting at the wrist (1.9 J of work). DISCUSSION: Results suggest in preliminary fashion the effectiveness of this approach for improving upper extremity function after motor complete high tetraplegia. Thus, future studies are warranted. Possible mechanisms are discussed.

Predictors of permanent disability among adults with spinal dysraphism.

OBJECTIVE Predictors of permanent disability among individuals with spinal dysraphism are not well established. In this study, the authors examined potential risk factors for self-reported permanent disability among adults with spinal dysraphism. METHODS A total of 188 consecutive individuals undergoing follow-up in an adult spinal dysraphism clinic completed a standardized National Spina Bifida Patient Registry survey. Chi-square tests and logistic regression were used to assess bivariate relationships, while multivariate logistic regression was used to identify factors independently associated with self-identification as "permanently disabled." RESULTS A total of 106 (56.4%) adults with spina bifida identified themselves as permanently disabled. On multivariate analysis, relative to completion of primary and/or secondary school, completion of technical school (OR 0.01, 95% CI 0-0.40; p = 0.021), some college (OR 0.22, 95% CI 0.08-0.53; p < 0.001), college degree (OR 0.06, 95% CI 0.003-0.66; p = 0.019), and holding an advanced degree (OR 0.12, 95% CI 0.03-0.45; p = 0.002) were negatively associated with permanent disability. Relative to open myelomeningocele, diagnosis of closed spinal dysraphism was also negatively associated with permanent disability (OR 0.20, 95% CI 0.04-0.90; p = 0.036). Additionally, relative to no stool incontinence, stool incontinence occurring at least daily (OR 6.41, 95% CI 1.56-32.90; p = 0.009) or more than weekly (OR 3.43, 95% CI 1.10-11.89; p = 0.033) were both positively associated with permanent disability. There was a suggestion of a dose-response relationship with respect to the influence of educational achievement and frequency of stool incontinence on the likelihood of permanent disability. CONCLUSIONS The authors' findings suggest that level of education and degree of stool incontinence are the strongest predictors of permanent disability among adults with spinal dysraphism. These findings will be the basis of efforts to improve community engagement and to improve readiness for transition to adult care in a multidisciplinary pediatric spina bifida clinic.

Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity.

The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.