Cardiometabolic risk factor clustering in persons with spinal cord injury: A principal component analysis approach.

CONTEXT/OBJECTIVE: To identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals. APPROACH: A cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation. Total and central adiposity [total body fat (TBF) percent and visceral adipose tissue (VAT) percent, respectively] were obtained by dual x-ray absorptiometry (DXA). A PCA was used to identify the CM outcome measurements that cluster to confer CVD risk in SCI and non-SCI cohorts. RESULTS: Using PCA, six factor-components (FC) were extracted, explaining 77% and 82% of the total variance in the SCI and non-SCI cohorts, respectively. In both groups, FC-1 was primarily composed of lipoprotein particle concentration variables. TBF and VAT were included in FC-2 in the SCI group, but not the non-SCI group. In the SCI cohort, logistic regression analysis results revealed that for every unit increase in the FC-1 standardized score generated from the statistical software during the PCA, there is a 216% increased risk of MetS (P = 0.001), a 209% increased risk of a 10-yr. FRS ≥ 10% (P = 0.001), and a 92% increase in the risk of HOMA2-IR ≥ 2.05 (P = 0.01). CONCLUSION: Application of PCA identified 6-FC models for the SCI and non-SCI groups. The clustering of variables into the respective models varied considerably between the cohorts, indicating that CM outcomes may play a differential role on their conferring CVD-risk in individuals with chronic SCI.

Preliminary observations on the administration of a glucagon-like peptide-1 receptor agonist on body weight and select carbohydrate endpoints in persons with spinal cord injury: A controlled case series.

CONTEXT/OBJECTIVE: To describe the effect of semaglutide, a glucagon-like peptide-1 (GLP-1) agonist, to reduce body weight and improve glycemic control in overweight or obese individuals with spinal cord injury (SCI). DESIGN: Open-label, randomized drug intervention case series. SETTING: This study was performed at James J. Peters VA Medical Center (JJP VAMC) and Kessler Institute for Rehabilitation (KIR). PARTICIPANTS: Five individuals with chronic SCI meeting criteria for obesity and abnormal carbohydrate metabolism. INTERVENTION: Administration of semaglutide (subcutaneously once per week) versus no treatment (control) for 26 weeks. OUTCOME MEASURES: Change in total body weight (TBW), fat tissue mass (FTM), total body fat percent (TBF%), and visceral adipose tissue volume (VATvol) was determined at baseline and after 26 weeks using Dual energy X-ray absorptiometry; fasting plasma glucose (FPG) concentration and serum glycated hemoglobin (HbA1C) values were obtained at the same two time points. RESULTS: In 3 participants, after 26 weeks of semaglutide administration, TBW, FTM, TBF%, and VATvol decreased, on average, by 6, 4.4 kg, 1.7%, and 674 cm3, respectively. In addition, values for FPG and HbA1c decreased by 17 mg/dl and 0.2%, respectively. After 26 weeks of observation in the 2 control participants, TBW, FTM, TBF% and VATvol increased on average by 3.3 , 4.5 kg, 2.5%, and 991 cm3, respectively. The average values for FPG and HbA1c also increased by 11 mg/dl and 0.3%, respectively. CONCLUSIONS: Administration of semaglutide for 26 weeks resulted in favorable changes in body composition and glycemic control, suggesting a reduced risk for the development of cardiometabolic disease in obese individuals with SCI.Trial registration: ClinicalTrials.gov identifier: NCT03292315.

Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.

Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization. OBJECTIVE: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year. METHODS: Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry. RESULTS: The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05). CONCLUSIONS: In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.

Concussion History and Heart Rate Variability During Bouts of Acute Stress.

CONTEXT: After a sport-related concussion, many athletes experience persisting neurophysiological alterations. These alterations may be absent at rest but emerge during moments of physiological stress. Unnoticed and untreated neurophysiological dysfunction may negatively affect long-term neurologic health in adolescent athletes, as they are at a critical point in development. OBJECTIVE: To assess cardio-autonomic functioning in athletes with and those without a history of concussion by quantifying measures of heart rate variability (HRV) during times of physical and mental exertion. DESIGN: Case-control study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-four male Hockey Quebec Midget-AAA hockey players were separated into those with (n = 16; age = 16.06 ± 0.73 years, body mass index = 23.29 ± 1.79) and those without (n = 18; age = 15.98 ± 0.62 years, body mass index = 23.60 ± 2.49) a history of concussion. INTERVENTION(S): All athletes underwent a series of HRV recording sessions (1) at rest, (2) while completing a cognitive task at rest, and (3) while completing a cognitive task after a bout of submaximal aerobic exercise. MAIN OUTCOME MEASURE(S): Time-domain measures of HRV, including mean NN intervals, SD of NN intervals, and root mean square of successive NN interval differences, were quantified for each assessment. RESULTS: No differences in characteristics were evident between groups. No between-groups differences in HRV at rest were observed. However, during the cognitive task at rest and after aerobic exercise, athletes with a history of concussion demonstrated a higher SD of NN intervals (78.1 ± 4.3 versus 63.2 ± 4.1 milliseconds and 71.2 ± 4.3 versus 65.2 ± 3.8 milliseconds, respectively; F1,31 = 4.31, P = .046) and root mean square of successive NN interval differences (75.8 ± 6.0 versus 59.0 ± 5.6 milliseconds and 74.0 ± 5.5 versus 59.0 ± 5.2 milliseconds, respectively; F1,31 = 4.88, P = .04) than athletes without a history of concussion. CONCLUSIONS: Concussive injuries may result in long-term cardio-autonomic dysfunction. These deficits may not be present at rest but may be triggered by physiological stress.

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

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

Generation of a Reference Dataset to Permit the Calculation of T-scores at the Distal Femur and Proximal Tibia in Persons with Spinal Cord Injury.

Persons with traumatic spinal cord injury (SCI) have severe bone loss below the level of lesion with the distal femur (DF) and proximal tibia (PT) being the skeletal regions having the highest risk of fracture. While a reference areal bone mineral density (aBMD) database is available at the total hip (TH) using the combined National Health and Nutrition Examination Survey (NHANES) III study and General Electric (GE) combined (GE/NHANES) to calculate T-score (T-scoreGE/NHANES), no such reference database exists for aBMD of the DF, and PT. The primary objectives of this study were (1) to create a reference dataset of young-healthy able-bodied (YHAB) persons to calculate T-score (T-scoreYHAB) values at the DF and PT, (2) to explore the impact of time since injury (TSI) on relative bone loss in the DF and PT regions using the two computation models to determine T-score values, and (3) to determine agreement between T-score values for a cohort of persons with SCI using the (T-scoreYHAB) and (T-scoreGE/NHANES) reference datasets. A cross-sectional prospective data collection study. A Department of Veterans Affairs Medical Center and a Private Rehabilitation Hospital. A normative reference aBMD database at the DF and PT was collected in 32 male and 32 female Caucasian YHAB participants (n=64) and then applied to calculate T-score values at the DF and PT in 105 SCI participants from a historical cohort. The SCI participants were then grouped based on TSI epochs (E-I: TSI < 1y, E-II: TSI 1-5y, E-III: TSI 6-10y, E-IV: TSI 11-20y, E-V: TSI > 20y). N/A. The knee and hip aBMD values were obtained by dual energy X-ray absorptiometry (GE Lunar iDXA) using standard clinical software for proximal femur orthopedic knee software applications. There were no significant differences in mean aBMD values across the four YHAB age subgroups (21-25, 26-30, 31-35, and 36-40 yr of age) at the TH, DF, and PT; mean aBMD values were higher in men compared to the women at all skeletal regions of interest. Using the mean YHAB aBMD values to calculate T-score values at each TSI epoch for persons with SCI, T-score values decreased as a function of TSI, and they continued to decline for 11-20 yr. Moderate kappa agreement was noted between the YHAB and the GE/NHANES reference datasets for the T-score cutoff criteria accepted to diagnose osteoporosis (i.e., SD <-2.5). A homogeneous reference dataset of YHAB aBMD values at the DF and PT was applied to calculate T-score values in persons with chronic SCI. There was a moderate level of agreement at the TH between the YHAB and GE/NHANES reference datasets when applying the conventional T-score cutoff value for the diagnosis of osteoporosis.

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

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

Predicting Cardiometabolic Risk From Visceral Abdominal Adiposity in Persons With Chronic Spinal Cord Injury.

Persons with spinal cord injury (SCI) have increased adiposity that may predispose to cardiovascular disease compared to those who are able-bodied (AB). The purpose of this study was to determine the relationships between dual energy X-ray absorptiometry (DXA)-derived visceral adipose tissue (VAT) and biomarkers of lipid metabolism and insulin resistance in persons with chronic SCI. A prospective observational study in participants with chronic SCI and age- and gender-matched AB controls. The study was conducted at a Department of Veterans Affairs Medical Center and Private Rehabilitation Hospital. The quantification of DXA-derived VAT volume (VATvol) and blood-derived markers of lipid and carbohydrate metabolism were determined in 100 SCI and 51 AB men. The VATvol was acquired from a total body DXA scan and analyzed using iDXA enCore CoreScan software (GE Lunar). Blood samples were collected for the serum lipid profile and plasma and glucose concentrations, with the latter two values used to calculate a measure of insulin resistance. In the SCI and AB groups, VAT% was significantly correlated with most cardiometabolic biomarkers. The results of the binary logistic regression analysis revealed that participants who had a VATvol above the cutoff value of 1630 cm3 were 3.1-, 4.8-, 5.6-, 19.2-, and 16.7-times more likely to have high serum triglycerides (R2N= 0.09, p = 0.014), low serum high density lipoprotein cholesterol (R2N = 0.16, p < 0.001), HOMA2-IR (R2N = 0.18, p < 0.001), metabolic syndrome (R2N = 0.25, p < 0.001), and a 10-yr Framingham Risk Score ≥ 10% (R2N = 0.16, p = 0.001), respectively, when compared to participants below this VATvol cutoff value. Our findings reveal that persons with chronic SCI have a higher VATvol than that of AB controls, and VATvol correlates directly with biomarkers of lipid and carbohydrate metabolism that are strong predictors of cardiometabolic disorders.

Long-Term Influence of Concussion on Cardio-Autonomic Function in Adolescent Hockey Players.

CONTEXT: Concussion may negatively influence cardiovascular function and the autonomic nervous system, defined by alteration in heart rate variability (HRV). Differences in HRV most commonly emerge during a physical challenge, such as the final steps of the return-to-sport progression. OBJECTIVE: To assess the effect of concussion history on aspects of cardio-autonomic function during recovery from a bout of submaximal exercise in adolescent male hockey athletes. DESIGN: Case-control study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-three male athletes participating in Midget-AAA hockey were divided into those with (n = 15; age = 16 ± 1 years, height = 1.78 ± 0.06 m, mass = 73.9 ± 7.4 kg, 10.5 ± 1.6 years of sport experience, 25.2 ± 18.3 months since last injury) or without (n = 18; age = 16 ± 1 years, height = 1.78 ± 0.05 m, mass = 74.8 ± 7.6 kg, 10.6 ± 1.9 years of sport experience) a concussion history. Those with a concussion history were binned on total count: 1 concussion or 2 or more concussions. INTERVENTION(S): All athletes underwent 5 minutes of resting HRV assessment, followed by 20 minutes of aerobic exercise at 60% to 70% of their maximal target heart rate and a 9-minute, postexercise HRV assessment. MAIN OUTCOME MEASURE(S): Heart rate variability measures of mean NN interval, root mean square of successive differences, and standard deviation of NN interval (SDNN). RESULTS: Group demographic characteristics were not different. When the control and concussed groups were compared, group and time main effects for heart rate recovery, root mean square of successive differences, and SDNN (P values < .01), and an interaction effect for SDNN (P < .05) were demonstrated. Recovery trends for each group indicated that a history of 2 or more concussions may negatively affect cardio-autonomic recovery postexercise. CONCLUSIONS: Our findings suggest that those with more than 1 previous concussion may be associated with a greater risk for long-term dysautonomia. Future use of HRV may provide clinicians with objective guidelines for concussion-management and safe return-to-participation protocols.

Administration of Denosumab Preserves Bone Mineral Density at the Knee in Persons With Subacute Spinal Cord Injury: Findings From a Randomized Clinical Trial.

Persons with neurologically motor-complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor-κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty-six SCI participants with subacute motor-complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x-ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p < 0.001); distal femoral epiphysis = mean aBMD 1.557; 95% CI, 1.437 to 1.675 and mean aBMD 1.570; 95% CI, 1.440 to 1.700 versus mean aBMD 1.565; 95% CI, 1.434 to 1.696 and mean aBMD 1.103; 95% CI, 0.898 to 1.309, respectively (p = 0.002); and proximal tibial epiphysis = mean aBMD 1.071; 95% CI, 0.957 to 1.186 and mean aBMD 1.050; 95% CI, 0.932 to 1.168 versus mean aBMD 0.994; 95% CI, 0.879 to 1.109 and mean aBMD 0.760; 95% CI, 0.601 to 0.919, respectively (p < 0.001). Analysis of pQCT imaging revealed a continued trend toward significantly greater loss in total volumetric BMD (vBMD) and trabecular vBMD at the 4% distal tibia region, with a significant percent loss for total bone mineral content. Thus, at 18 months after acute SCI, our findings show that denosumab maintained aBMD at the knee region, the site of greatest clinical relevance in the SCI population. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Fenofibrate therapy to lower serum triglyceride concentrations in persons with spinal cord injury: A preliminary analysis of its safety profile.

Context: Fenofibrate is used to treat elevated serum triglyceride (TG) concentrations (e.g. ≥150 mg/dl). The lipoprotein profile of most individuals with spinal cord injury (SCI) would not satisfy conventional criteria to initiate lipid-lowering therapies. Serum TG concentrations of 115 and 137 mg/dl were recently identified as potential intervention thresholds for persons with a SCI proximal to the 4th and below the 5th thoracic vertebrae, respectively. Fenofibrate therapy has not been tested for safety in persons with SCI. Methods: An open-label trial was performed in 15 persons with SCI to determine the safety profile of 4 months of once-daily fenofibrate (145 mg tablet) treatment when initiated using modified intervention thresholds. Fasting blood tests and a review of systems were performed monthly to determine changes in liver and kidney function, as well as overall health status. Results: Fifteen subjects participated and 4 had an adverse event (e.g. 2 with gastrointestinal distress; 2 with elevated liver enzymes). Three subjects discontinued the trial within the first month and one participant remained in the trial with no further adverse events. Two participants were discontinued from fenofibrate after 2 months after not responding to treatment, as per protocol, and 10 participants completed the 4-month trial without experiencing an adverse event. Conclusion: In persons with SCI, 4 months of fenofibrate therapy initiated at lower threshold serum TG concentrations did not result in an increased incidence of adverse events compared to that reported in the general population. Fenofibrate therapy appears to be well tolerated in persons with SCI.

Relationships between T-scores at the hip and bone mineral density at the distal femur and proximal tibia in persons with spinal cord injury.

Objective: To identify T-score values at the total hip (TH) and femoral neck (FN) that correspond to the cutoff value of <0.60 g/cm2 for heightened risk of fracture at the distal femur (DF) and proximal tibia (PT).Design: Retrospective analysis of data in a research center's database. Setting: Community-based individuals with spinal cord injury (SCI). Participants: 105 unique individuals with SCI. Outcome Measurements: DXA derived areal BMD (aBMD) and T-score of the DF, PT, TH, and FN. Results: The aBMD at the DF and PT regions were predictors of T-scores at the TH (R2 = 0.63, P < 0.001 and R2 = 0.65, P < 0.001) and FN (R2 = 0.55, P < 0.001 and R2 = 0.58, P < 0.001). Using the DF and PT aBMD of 0.60 g/cm2 as a value below which fractures were more likely to occur, the predicted T-score was -3.1 and -3.5 at the TH and -2.6 and -2.9 at the FN, respectively. However, when the predicted and observed T-score values disagree outside the 95% limit of agreement, the predicted T-score values are lower than the measured T-score values, overestimating the measured values between -2.0 and -4.0 SD. Conclusion: The DF and PT cutoff value for aBMD of 0.60 g/cm2 was a moderate predictor of T-score values at the TH and FN, with considerable inaccuracies outside the clinically acceptable limits of agreement. As such, the direct measurement of knee aBMD in persons with SCI should be performed, whenever possible, prior to prescribing weight bearing upright activities, such as robotic exoskeletal-assisted walking.

A Four Month Randomized Controlled Trial on the Efficacy of Once-daily Fenofibrate Monotherapy in Persons with Spinal Cord Injury.

An open-label, randomized clinical trial of once-daily fenofibrate monotherapy administered for 2- (Mo2) and 4- (Mo4) months using modified intervention thresholds for triglyceride (TG) was performed in persons with chronic spinal cord injury (SCI). Fenofibrate (145 mg tablet) was self-administered daily in 10 persons with SCI for 4 months with monthly blood testing to quantify the lipoprotein profile (e.g., serum TG, LDL-C, and HDL-C concentrations). Eight SCI participants were control subjects. In comparison to the control group, the treatment group at Mo2 had a 40% (±12%; p < 0.05) reduction in serum TG concentration, a 28% (±21%; p < 0.05) increase in HDL-C and 14% (±20%; p < 0.05) decline in LDL-C. In the same comparison at Mo4, the treatment group maintained a 40% (±20%; p < 0.05) reduction in serum TG concentration, had an 18% in reduction in LDL-C (±12%; p < 0.05) and a 23% (±23%; p < 0.05) increase in HDL-C. Fenofibrate monotherapy for Mo2 and Mo4 initiated in persons with SCI resulted in a robust and favorable change in the serum lipoprotein profile and ratios, suggesting reduced risk for cardiovascular disease.

Preliminary Evidence for a Window of Increased Vulnerability to Sustain a Concussion in Females: A Brief Report.

A difference exists between sexes for the incidence of concussion injuries and severity of post-injury outcomes with females having a higher incidence rate (in comparable sports) and experience more robust symptoms than males. The basis for this disparity has remained largely unresolved. Recent findings point to a potential biological mechanism that may be related to the menstrual cycle as an arbiter of post-injury outcomes. What has not been addressed, is whether the phase of menstrual cycle (inferred fluctuations of ovarian hormones) contributes to an increased vulnerability to sustain a concussion injury. This prospective, observational study sought to determine if concussions occurred at different frequencies throughout the phase of the menstrual cycle. Female athletes who sustained a concussion injury were queried three times over the 7-day study (e.g., within 48 h of injury, and 4 and 7 days after injury) to recall the number of days that have elapsed since the beginning of their most recent menstruation. Twenty female athletes enrolled after sustaining a concussion; 18 were eumenorrheic and 2 amenorrheic. Among eumenorrheic participants at the time of injury, 2 were in the follicular phase, 4 were in the early luteal phase and 9 were in the late luteal phase. Two athletes were injured on the first and 1 was injured on the second day of menstruation. The greatest number of concussions were sustained during the late luteal phase and during the first 2 days of menstruation. This 9-day window accounted for 2/3rd of the sustained concussions in our study.

Attenuation of Spontaneous Baroreceptor Sensitivity after Concussion.

INTRODUCTION: Cardiovascular autonomic nervous system (CV-ANS) function is negatively impacted after concussion. The arterial baroreflex buffers pressor and depressor challenges through efferent modulation of cardiac chronotropism and inotropism, and peripheral vascular tone. Baroreceptor sensitivity (BRS) reflects the capacity of the CV-ANS to accommodate dynamic metabolic demands in the periphery. The impact of concussion on BRS has yet to be defined. METHODS: Cardiovascular autonomic nervous system assessment (e.g., electrocardiogram and beat-to-beat systolic blood pressure [SBP]) was performed the seated upright position at rest within 48 h (V1) of concussion and 1 wk later (V2) in 10 intercollegiate male athletes with concussion and 10 noninjured male athletes. Changes in HR, SBP, high- and low-frequency HR variabilities (HF-HRV and LF-HRV, respectively), LF-SBP variability and BRS for increasing (BRSn-Up) and decreasing (BRSn-Dn) SBP excursions, and overall BRS (BRSn-Avg) were assessed for differences at V1 and V2. RESULTS: The concussion (age, 20 ± 1 yr; height, 1.79 ± 0.14 m; weight, 83 ± 10 kg) and control (age, 20 ± 1 yr; height, 1.78 ± 0.10 m; weight, 79 ± 13 kg) groups were matched for demographics. Concussed athletes had a significantly reduced BRSn-Up, BRSn-Dn, and BRSn-Avg compared with controls at V1 or V2; these changes occurred without differences in conventional markers of CV-ANS function (e.g., HF-HRV, LF-HRV, LF-SBP), HR, or SBP at either visit. CONCLUSIONS: Reduced BRS is a postconcussive consequence of CV-ANS dysfunction during the first postinjury week. Because SBP was similar between groups, it may be speculated that reduced BRS was not afferent in origin, but represents a postinjury consequence of the central nervous system after injury.

Progressive Sublesional Bone Loss Extends into the Second Decade After Spinal Cord Injury.

OBJECTIVE: The rate of areal bone mineral density (aBMD) loss at the knee (distal femur (DF) and proximal tibia ) and hip (femoral neck (FN) and total hip (TH)) was determined in persons with traumatic spinal cord injury (SCI) who were stratified into subgroups based on time since injury (TSI). DESIGN: Cross-sectional retrospective review. SETTING: Department of Veterans Affairs Medical Center and Private Rehabilitation Hospital. PARTICIPANTS: Data on 105 individuals with SCI (TSI ≤12 months, n = 19; TSI 1-5 years, n = 35; 6-10 years, n = 19; TSI 11-20 years, n = 16; TSI >20 years, n = 15) and 17 able-bodied reference (ABref) controls. INTERVENTIONS: NA Main Outcome Measures: The knee and hip aBMD values were obtained by dual energy X-ray absorptiometry (GE Lunar iDXA) using standard clinical software for the proximal femur employed in conjunction with proprietary research orthopedic knee software applications. Young-normal (T-score) and age-matched (Z-scores) standardized scores for the FN and TH were obtained using the combined GE Lunar/National Health and Nutrition Examination Survey (NHANES III) combined reference database. RESULTS: When groups were stratified and compared as epochs of TSI, significantly lower mean aBMD and reference scores were observed as TSI increased, despite similar mean ages of participants among the majority of TSI epoch subgroups. Loss in aBMD occurred at the distal femur (DF), proximal tibia (PT), FN, and TH with 46%, 49%, 32%, and 43% of the variance in loss, respectively, described by the exponential decay curves with a time to steady state (tss) occurring at 14.6, 11.3, 14, and 6.2 years, respectively, after SCI. CONCLUSIONS: Sublesional bone loss after SCI was marked and occurred as an inverse function of TSI. For aBMD at the hip and knee, tss extended into the second decade after SCI.

Establishing a threshold to predict risk of cardiovascular disease from the serum triglyceride and high-density lipoprotein concentrations in persons with spinal cord injury.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: This report identified the serum triglyceride (TG) concentrations in persons with spinal cord injury (SCI) and able-bodied (AB) individuals that the serum high-density lipoprotein cholesterol (HDL-C) equaled 40 mg/dl, a concentration below which is an independent risk factor for coronary artery disease. METHODS: Retrospective analysis was performed on 578 participants: 223 with SCI at or proximal to the 4th thoracic vertebrae (↑T4), 178 with SCI at or distal to the 5th thoracic vertebrae (↓T5), and 177 AB. Different statistical modeling approaches identified the intersecting serum TG concentration with a serum HDL-C concentration equal to 40 mg/dl. Participants were dichotomized into subgroups by TG concentration exceeding (supra) or falling below (sub) the intersecting value and the TG/HDL-C ratios were compared. RESULTS: Linear regression analysis revealed that the serum TG concentration that intersects with serum HDL-C concentration at 40 mg/dl was 121 mg/dl in SCI ↑T4 and 137 mg/dl in SCI ↓T5 group. A ROC curve identified the optimal TG concentration as 115 mg/dl in SCI ↑T4 and 137 mg/dl in SCI ↓T5 group with the latter concentration being similar to the AB group (e.g., 137 mg/dl). The TG/HDL-C ratios in the respective ↑T4, ↓T5, and AB supra and subgroups were similar within each group. CONCLUSIONS: A lower TG concentration appears to be associated with dyslipidemia in persons with SCI than AB individuals. These findings should prompt clinicians to screen for and consider instituting lifestyle or pharmacological interventions at lower TG concentrations to reduce risk of CVD.

A call to reevaluate cardiac autonomic assessment after spinal cord injury.

This "Perspectives" article puts forward the notion that measuring heart rate variability, or other forms of cardiac autonomic regulation, after spinal cord injury must be performed during a test of autonomic stress. Resting values of heart rate variability are often similar to those obtained from able-bodied individuals, which may therefore be falsely interpreted as normal or healthy autonomic regulation. However, evidence shows that despite normal resting values, cardiac autonomic control is impaired when individual with spinal cord injury are subjected to a cold face test, head-up tilt, or recovery from exercise. Accordingly, examination of cardiac autonomic function must be performed during an autonomic challenge, as resting measures do not accurately reflect the state of cardiovascular regulation after spinal cord injury and can provide false information.

An anatomical and physiological basis for the cardiovascular autonomic nervous system consequences of sport-related brain injury.

Concussion is defined as a complex pathophysiological process affecting the brain that is induced by the application or transmission of traumatic biomechanical forces to the head. The result of the impact is the onset of transient symptoms that may be experienced for approximately 2weeks in most individuals. However, in some individuals, symptoms may not resolve and persist for a protracted period and a chronic injury ensues. Concussion symptoms are generally characterized by their emergence through changes in affect, cognition, or multi-sensory processes including the visual and vestibular systems. An emerging consequence of concussion is the presence of cardiovascular autonomic nervous system dysfunction that is most apparent through hemodynamic perturbations and provocations. Further interrogation of data that are derived from continuous digital electrocardiograms and/or beat-to-beat blood pressure monitoring often reveal an imbalance of parasympathetic or sympathetic nervous system activity during a provocation after an injury. The disturbance is often greatest early after injury and a resolution of the dysfunction occurs in parallel with other symptoms. The possibility exists that the disturbance may remain if the concussion does not resolve. Unfortunately, there is little evidence in humans to support the etiology for the emergence of this post-injury dysfunction. As such, evidence from experimental models of traumatic brain injury and casual observations from human studies of concussion implicate a transient abnormality of the anatomical structures and functions of the cardiovascular autonomic nervous system. The purpose of this review article is to provide a mechanistic narrative of multi-disciplinary evidence to support the anatomical and physiological basis of cardiovascular autonomic nervous system dysfunction after concussion. The review article will identify the anatomical structures of the autonomic nervous system and propose a theoretical framework to demonstrate the potential effects of concussive head trauma on corresponding outcome measurements. Evidence from experimental models will be used to describe abnormal cellular functions and provide a hypothetical mechanistic basis for the respective responses of the anatomical structures to concussive head trauma. When available, example observations from the human concussion literature will be presented to demonstrate the effects of concussive head trauma that may be related to anomalous activity in the respective anatomical structures of the autonomic nervous system.