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.

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.

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.

Surveillance for Pressure Injuries on Admission to Inpatient Rehabilitation Hospitals During the COVID-19 Pandemic.

OBJECTIVE: To determine if the incidence of pressure injuries (PIs) on admission to an inpatient rehabilitation hospital (IRH) system of care was increased during the early coronavirus disease 2019 (COVID-19) pandemic period. DESIGN: Retrospective survey chart review of consecutive cohorts. Admissions to 4 acute IRHs within 1 system of care over the first consecutive 6-week period of admitting patients positive for COVID-19 during the initial peak of the COVID-19 pandemic, April 1-May 9, 2020. A comparison was made with the pre-COVID-19 period, January 1-February 19, 2020. SETTING: Four acute IRHs with admissions on a referral basis from acute care hospitals. PARTICIPANTS: A consecutive sample (N=1125) of pre-COVID-19 admissions (n=768) and COVID-19 period admissions (n=357), including persons who were COVID-19-positive (n=161) and COVID-19-negative (n=196). MAIN OUTCOME MEASURES: Incidence of PIs on admission to IRH. RESULTS: Prevalence of PIs on admission during the COVID-19 pandemic was increased when compared with the pre-COVID-19 period by 14.9% (P<.001). There was no difference in the prevalence of PIs in the COVID-19 period between patients who were COVID-19-positive and COVID-19-negative (35.4% vs 35.7%). The severity of PIs, measured by the wound stage of the most severe PI the patient presented with, worsened during the COVID-19 period compared with pre-COVID-19 (χ2 32.04%, P<.001). The length of stay in the acute care hospital before transfer to the IRH during COVID-19 was greater than pre-COVID-19 by 10.9% (P<.001). CONCLUSIONS: During the early part of the COVID-19 pandemic time frame, there was an increase in the prevalence and severity of PIs noted on admission to our IRHs. This may represent the significant burden placed on the health care system by the pandemic, affecting all patients regardless of COVID-19 status. This information is important to help all facilities remain vigilant to prevent PIs as the pandemic continues and potential future pandemics that place strain on medical resources.

Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management.

Spinal cord injury (SCI) disrupts autonomic circuits and impairs synchronistic functioning of the autonomic nervous system, leading to inadequate cardiovascular regulation. Individuals with SCI, particularly at or above the sixth thoracic vertebral level (T6), often have impaired regulation of sympathetic vasoconstriction of the peripheral vasculature and the splanchnic circulation, and diminished control of heart rate and cardiac output. In addition, impaired descending sympathetic control results in changes in circulating levels of plasma catecholamines, which can have a profound effect on cardiovascular function. Although individuals with lesions below T6 often have normal resting blood pressures, there is evidence of increases in resting heart rate and inadequate cardiovascular response to autonomic provocations such as the head-up tilt and cold face tests. This manuscript reviews the prevalence of cardiovascular disorders given the level, duration and severity of SCI, the clinical presentation, diagnostic workup, short- and long-term consequences, and empirical evidence supporting management strategies to treat cardiovascular dysfunction following a SCI.

Measurement of Visceral Adipose Tissue in Persons With Spinal Cord Injury by Magnetic Resonance Imaging and Dual X-Ray Absorptiometry: Generation and Application of a Predictive Equation.

PURPOSE: Dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) permits quantification of visceral adipose tissue (VAT). However, DXA has not been validated against MRI in persons with chronic spinal cord injury (SCI). A predictive equation was generated from the measurement of VAT by MRI, a "gold" standard to quantitate VAT, compared to that of DXA, a method with several practical advantages. METHOD: DXA and MRI scans were performed in 27 participants with SCI. MRI multiaxial images were captured for VAT analysis. DXA-VAT was quantified at the android region (DXA-VATANDROID-VOL) using enCore software. Android regions of DXA and MRI were matched using android height. Volumes of multiaxial MRI-VAT and subcutaneous adipose tissue (SAT) were quantified for the android region (MRI-VATANDROID-VOL, MRI-SATANDROID-VOL) and total trunk (MRI-VATANDROID-VOL). Linear regression analysis was used to establish the proposed predication equations. The prediction equations were then applied to an independent sample that consisted of 98 participants with SCI. Bland-Altman analysis was used to determine the limits of agreement. RESULTS: DXA-VATANDROID-VOL predicted 92% of the variance in MRI-VATANDROID-VOL (SEE = 252.5, p < 0.0005) and 85% of the variance in MRI-VATTRUNK-VOL (SEE = 1526.9, p < 0.0005). DXA-SATANDROID-VOL predicted 81.5% of the variance in MRI-SATANDROID-VOL (SEE = 458.2, p < 0.0005). Bland-Altman analysis revealed a high level of agreement between MRI-VATANDROID-VOL and DXA-VATANDROID-VOL (mean bias = 58.45 cm3). A predicted mean DXA-VATANDROID-VOL of 995.2 cm3 was estimated as the population-specific cut-off point for high levels of VAT. CONCLUSION: DXA-VATANDROID-VOL may accurately predict MRI-VATANDROID-VOL in persons with SCI. The ability of DXA to detect VAT changes in longitudinal studies in persons with SCI should be performed.

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

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

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.

Charcot Spine following chronic spinal cord injury: an analysis of 201 published cases.

STUDY DESIGN: Analysis of published cases OBJECTIVES: To identify and describe symptoms, radiologic findings, treatment strategies, and reoccurrence of Charcot spine in individuals with spinal cord injury (SCI). METHODS: This analysis included all English articles published prior to October 2017, describing Charcot spine after SCI as identified by multiple reviewers. Articles were excluded if Charcot spine was attributed to alternative conditions. Individual level data were available for 94% of reported cases. Outcomes included demographic factors, injury characteristics, clinical presentation, radiologic findings, management, and reoccurrence. RESULTS: Fifty included papers described 201 individuals with SCI who developed Charcot spine. 86% of individuals had paraplegia and 93% of individuals had a neurologically complete injury. Mean length of initial spinal fusion spanned 7.7 vertebral bodies (SD = 3.9). The most common presenting symptoms were back pain (56%), spinal deformity (48%), and crepitus (34%). Vertebral body destruction (83%), osteophytes (61%), and endplate destruction (57%) were commonly reported on radiographs. Reoccurrence of Charcot spine was described in 19% of cases after initial treatment. CONCLUSION: Charcot spine after SCI commonly presents with low back pain and radiologic evidence of vertebral body destruction. Cases have been described more often in individuals with paraplegia and neurologically complete injuries. Surgical management is often pursued. A high rate of reoccurrence of Charcot spine in individuals with SCI after initial treatment has been reported.

Administration of increasing doses of gonadotropin-releasing hormone in men with spinal cord injury to investigate dysfunction of the hypothalamic-pituitary-gonadal axis.

STUDY DESIGN: Prospective. OBJECTIVES: To determine the optimum gonadotropin-releasing hormone (GnRH) dose to identify dysfunction of the hypothalamic-pituitary-gonadal axis in men with spinal cord injury (SCI). SETTING: Metropolitan Area Hospitals, New York and New Jersey, USA. METHODS: SCI men (16 hypogonadal (HG = serum testosterone <12.1 nmol/l) and 14 eugonadal (EG)) and able-bodied (AB) men (27 HG and 11 EG) were studied. GnRH (10, 50, and 100 µg) was randomly administered intravenously on three separate visits. Blood samples were collected post-GnRH for serum-luteinizing hormone (LH) and follicular-stimulating hormone (FSH). RESULTS: HG and EG men had a similar proportion of clinically acceptable gonadotropin responses to all three GnRH doses. The incremental gonadotropin responses to GnRH were not significantly different across the groups. However, in the SCI-HG group, GnRH of 100 µg resulted in the greatest integrated FSH response, and in the SCI-EG group, GnRH of 50 µg resulted in the greatest integrated LH response compared with the AB groups. A consistent, but not significant, absolute increase in gonadotropin release was observed in the SCI groups at all GnRH doses. CONCLUSIONS: Lower doses of GnRH did not improve the ability to identify the clinical dysfunction of the hypothalamic-pituitary-gonadal axis. However, the absolutely higher SCI-HG FSH response to GnRH of 100 µg and a higher SCI-EG LH response to GnRH of 50 µg, along with a higher gonadotropin release at all GnRH doses, albeit not significant, suggests a hypothalamic-pituitary dysfunction in persons with 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.

Patterns of Sacral Sparing Components on Neurologic Recovery in Newly Injured Persons With Traumatic Spinal Cord Injury.

OBJECTIVE: To assess the patterns of sacral sparing and recovery in newly injured persons with traumatic spinal cord injury (SCI). DESIGN: Retrospective analysis of data from the national Spinal Cord Injury Model Systems (SCIMS) database for patients enrolled from January 2011 to February 2015. SETTING: SCIMS centers. PARTICIPANTS: Individuals (N=1738; age ≥16y) with traumatic SCI admitted to rehabilitation within 30 days after injury with follow-up at discharge, at 1 year, or both. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: International Standards for Neurological Classification of Spinal Cord Injury examination results at admission and follow-up (discharge or 1y, or both). RESULTS: Conversion from an initial American Spinal Injury Association Impairment Scale (AIS) grade A to incomplete status was 20% at rehabilitation discharge and 27.8% at 1 year, and was greater in cervical and low paraplegia levels (T10 and below) than in high paraplegia level injuries (T1-9). Conversion from AIS B to motor incomplete was 33.9% at discharge and 53.6% at 1 year, and the initial sparing of all sacral sensory components was correlated with the greatest conversion to motor incomplete status at discharge and at 1 year. For patients with initial AIS C, the presence of voluntary anal contraction (VAC) in association with other sacral sparing was most frequently observed to improve to AIS D status at discharge. However, the presence of VAC alone as the initial sacral sparing component had the poorest prognosis for recovery to AIS D status. At follow-up, regaining sacral sparing components correlated with improvement in conversion for patients with initial AIS B and C. CONCLUSIONS: The components of initial and follow-up sacral sparing indicated differential patterns of neurologic outcome in persons with traumatic SCI. The more sacral components initially spared, the greater the potential for recovery; and the more sacral components gained, the greater the chance of motor recovery. Consideration of whether VAC should remain a diagnostic criterion sufficient for motor incomplete classification in the absence of other qualifying sublesional motor sparing is recommended.

Reliability and Validity of S3 Pressure Sensation as an Alternative to Deep Anal Pressure in Neurologic Classification of Persons With Spinal Cord Injury.

OBJECTIVE: To determine whether pressure sensation at the S3 dermatome (a new test) could be used in place of deep anal pressure (DAP) to determine completeness of injury as part of the International Standards for Neurological Classification of Spinal Cord Injury. DESIGN: Prospective, multicenter observational study. SETTING: U.S. Spinal Cord Injury Model Systems. PARTICIPANTS: Persons (N=125) with acute traumatic spinal cord injury (SCI), neurologic levels T12 and above, were serially examined at 1 month (baseline), 3, 6, and 12 months postinjury. There were 80 subjects with tetraplegia and 45 with paraplegia. INTERVENTIONS: S3 pressure sensation at all time points, with a retest at the 1-month time point. MAIN OUTCOME MEASURES: Test-retest reliability and agreement (κ), sensitivity, specificity, positive and negative predictive values. RESULTS: Test-retest reliability of S3 pressure at 1 month was almost perfect (κ=.98). Agreement of S3 pressure with DAP was substantial both at 1 month (κ=.73) and for all time points combined (κ=.76). The positive predictive value of S3 pressure for DAP was 89.3% at baseline and 90.3% for all time points. No pattern in outcomes was seen in those cases where S3 pressure and DAP differed at 1 month. CONCLUSIONS: S3 pressure sensation is reliable and has substantial agreement with DAP in persons with SCI at least 1 month postinjury. We suggest S3 pressure as an alternative test of sensory sacral sparing for supraconus SCI, at least in cases where DAP cannot be tested. Further research is needed to determine whether S3 pressure could replace DAP for classification of SCI.

Zoledronic acid administration failed to prevent bone loss at the knee in persons with acute spinal cord injury: an observational cohort study.

After acute spinal cord injury (SCI), rapid depletion of the sublesional skeleton occurs, particularly at the distal femur and proximal tibia. Subsequently, fragility fractures of the knee may occur. We determined the efficacy of zoledronic acid to prevent sublesional bone mineral density (BMD) loss at 6 and 12 months after acute SCI. Thirteen subjects with acute motor-complete SCI were prospectively studied: 6 patients received zoledronic acid (5 mg) and 7 subjects did not receive the drug (controls). Zoledronic acid was administered intravenously within 16 weeks of acute injury. Areal BMD was performed by dual energy X-ray absorptiometry at baseline, 6, and 12 months after administration of drug. The treatment group demonstrated sparing of BMD at the total hip at month 6 (p < 0.0006) and at month 12 (p < 0.01). In contrast to the findings at the hip, the treatment group had a greater loss of BMD compared to the control group at the distal femur and proximal tibia at month 6 (-7.9% ± 3.4 vs.-2.7% ± 5.0, respectively, p = 0.054; and -10.5% ± 6.4 vs. -4.8% ± 6.8, respectively, p = NS) and at month 12 (-18.5% ± 3.9 vs. -8.4% ± 7.2, respectively, p = 0.01; and -20.4% ± 8.8 vs.-7.9% ± 12.3, respectively, p = 0.06). A single dose of zoledronic acid administered soon after acute SCI reduced the %BMD loss at the hip, but appeared to have no effect to prevent %BMD loss at the knee, the site where fracture risk is greatest in persons with SCI.

Orthostatic responses to anticholinesterase inhibition in spinal cord injury.

INTRODUCTION: Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP). OBJECTIVES: The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). METHODS: Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded. RESULTS: Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. CONCLUSIONS: These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.

Lipoprotein heterogeneity in persons with Spinal Cord Injury: a model of prolonged sitting and restricted physical activity.

BACKGROUND: Persons with spinal cord injury (SCI) often have low levels of physical activity, which predispose to increased adiposity and decreased high density lipoprotein cholesterol (HDL-C) concentrations, and, generally, normal low density lipoprotein cholesterol (LDL-C) concentrations. In spite of the mixed lipoprotein profile, the SCI population has been reported to have an elevated risk of cardiovascular-related morbidity and mortality. Nuclear magnetic resonance spectroscopy may permit a more precise quantification of lipoprotein particle (P) species, enabling a more accurate inference of risk for cardiovascular disease (CVD) in the SCI population. METHODS: Fasting blood samples were obtained on 83 persons with chronic SCI and 62 able-bodied (AB) subjects. Fasting plasma insulin (FPI), triglycerides (TG), and P number and size of VLDL (very low density lipoprotein), LDL, and HDL subclasses were determined. AB and SCI subjects were stratified based on HDL-C (i.e., Low <40 and Normal ≥ 40 mg/dl): AB-Normal (n = 48), AB-Low (n = 14), SCI-Normal (n = 49), and SCI-Low (n = 34). Factorial analyses of variance were performed to identify group differences in lipoprotein measurements. Pearson correlations were performed between the number of P by lipoprotein subclass, size, FPI, and TG. RESULTS: The SCI-Normal group was not significantly different from the AB-Normal group for body composition, FPI, TG or LP-IR and had negligible differences in the lipoprotein P profile, except for fewer number and smaller size of HDL-P. The SCI-Low group had a similar lipoprotein profile to that of the AB-Low group, but with a lipid P composition associated with a heightened atherogenic risk and greater tendency toward insulin resistance by the Lipoprotein-Insulin Resistance (LP-IR) score. In the SCI-Low group, the decreased number and reduced size of lipoprotein P were more prevalent and may be associated with increased waist circumference (i.e., abdominal adiposity), relatively elevated TG values (compared to the other subgroups), and an underlying subclinical state of insulin resistance. CONCLUSIONS: Prolonged sitting and restricted physical activity in individuals with SCI had the most profound effect on the HDL-C and its lipoprotein P subclasses, but not on LDL-C, however its P subclasses were also unfavorably affected but not to the same degree. The quantification of lipoprotein P characteristics may be a potent tool for the determination of risk for CVD in persons with SCI.

Development and psychometric characteristics of the SCI-QOL Pressure Ulcers scale and short form.

OBJECTIVE: To develop a self-reported measure of the subjective impact of pressure ulcers on health-related quality of life (HRQOL) in individuals with spinal cord injury (SCI) as part of the SCI quality of life (SCI-QOL) measurement system. DESIGN: Grounded-theory based qualitative item development methods, large-scale item calibration testing, confirmatory factor analysis (CFA), and item response theory-based psychometric analysis. SETTING: Five SCI Model System centers and one Department of Veterans Affairs medical center in the United States. PARTICIPANTS: Adults with traumatic SCI. MAIN OUTCOME MEASURES: SCI-QOL Pressure Ulcers scale. RESULTS: 189 individuals with traumatic SCI who experienced a pressure ulcer within the past 7 days completed 30 items related to pressure ulcers. CFA confirmed a unidimensional pool of items. IRT analyses were conducted. A constrained Graded Response Model with a constant slope parameter was used to estimate item thresholds for the 12 retained items. CONCLUSIONS: The 12-item SCI-QOL Pressure Ulcers scale is unique in that it is specifically targeted to individuals with spinal cord injury and at every stage of development has included input from individuals with SCI. Furthermore, use of CFA and IRT methods provide flexibility and precision of measurement. The scale may be administered in its entirety or as a 7-item "short form" and is available for both research and clinical practice.

Development and psychometric characteristics of the SCI-QOL Bladder Management Difficulties and Bowel Management Difficulties item banks and short forms and the SCI-QOL Bladder Complications scale.

OBJECTIVE: To describe the development and psychometric properties of the Spinal Cord Injury--Quality of Life (SCI-QOL) Bladder Management Difficulties and Bowel Management Difficulties item banks and Bladder Complications scale. DESIGN: Using a mixed-methods design, a pool of items assessing bladder and bowel-related concerns were developed using focus groups with individuals with spinal cord injury (SCI) and SCI clinicians, cognitive interviews, and item response theory (IRT) analytic approaches, including tests of model fit and differential item functioning. SETTING: Thirty-eight bladder items and 52 bowel items were tested at the University of Michigan, Kessler Foundation Research Center, the Rehabilitation Institute of Chicago, the University of Washington, Craig Hospital, and the James J. Peters VA Medical Center, Bronx, NY. PARTICIPANTS: Seven hundred fifty-seven adults with traumatic SCI. RESULTS: The final item banks demonstrated unidimensionality (Bladder Management Difficulties CFI=0.965; RMSEA=0.093; Bowel Management Difficulties CFI=0.955; RMSEA=0.078) and acceptable fit to a graded response IRT model. The final calibrated Bladder Management Difficulties bank includes 15 items, and the final Bowel Management Difficulties item bank consists of 26 items. Additionally, 5 items related to urinary tract infections (UTI) did not fit with the larger Bladder Management Difficulties item bank but performed relatively well independently (CFI=0.992, RMSEA=0.050) and were thus retained as a separate scale. CONCLUSION: The SCI-QOL Bladder Management Difficulties and Bowel Management Difficulties item banks are psychometrically robust and are available as computer adaptive tests or short forms. The SCI-QOL Bladder Complications scale is a brief, fixed-length outcomes instrument for individuals with a UTI.

A survey of protective cushion usage in individuals with spinal cord injury while traveling in a motor vehicle and on a commercial airliner.

OBJECTIVE: While there are specific recommendations for pressure relieving cushions when seated in a wheelchair, there is a paucity of information regarding prescribed wheelchair cushions for persons with spinal cord injury (SCI) when traveling and not in their wheelchair seat. A questionnaire was designed to ascertain if individuals with SCI who are primarily wheelchair users utilize a prescribed wheelchair cushion when traveling in a motor vehicle (MV) or on a commercial airliner, as not utilizing one may be a causative factor in developing pressure ulcers. DESIGN AND SETTING: Survey design in an outpatient SCI rehabilitation setting. PARTICIPANTS: Full-time wheelchair users, with chronic (>1 year) SCI. RESULTS: Forty-two participants completed the survey, with a mean age of 39 years old and time post-injury of 10.4 years. All subjects used a prescribed wheelchair cushion when seated in their wheelchair. Twenty-seven subjects reported transferring to a MV seat (59.5% of sample), with 25 (92.6%) reporting not using a prescribed wheelchair cushion when sitting directly on the MV seat. For subjects who traveled on an airplane (n = 23-54.8%), 19 (82.6%) reported that they do not sit on a prescribed specialty cushion. CONCLUSION: Persons with chronic SCI, who are primary wheelchair users, utilize prescribed wheelchair cushions when sitting in their wheelchair, but most do not utilize a prescribed wheelchair cushion when seated in a MV (if they transfer out of their chair) or on a airplane seat. Studies to determine the pressures over the bony prominences on their travel surfaces may need to be undertaken to see whether the pressures are appropriate, as they may be a source of skin breakdown.

The relationship between the postprandial lipemic response and lipid composition in persons with spinal cord injury.

OBJECTIVE: To determine the influence of lipid concentration, lipid particle size, and total abdominal fat (TAF) on postprandial lipemic response (PPLr) in persons with spinal cord injury (SCI). METHODS: Thirty-five persons with SCI (17 paraplegia, 18 tetraplegia) and 18 able-bodied (AB) individuals participated. Following a 10-hour fast, blood was drawn for lipids, apolipoprotein (apo) A1 and B concentrations, and low-density (LSP) and high-density (HSP) lipoprotein particle sizes. A high-fat milkshake was consumed (∼1.3 g fat/kg). Blood was drawn at 2, 4, and 6 hours to determine PPLr, (triglyceride (TG) area under the curve). TAF and visceral (VF) fat were measured by ultrasonography; total body fat (TBF) by dual-energy X-ray absorptiometry. Differences between the groups were determined by independent sample t-tests. Pearson correlation coefficients determined the relationship among PPLr and lipids, and TAF. RESULTS: There were no significant differences in fasting TG, low-density lipoprotein (LDL), apoB, TAF, or PPLr values between the groups. In SCI, PPLr significantly correlated with: apoB (r = 0.63, P < 0.01, LSP (r = 0.57, P < 0.01), and TAF (r = 0.36, P < 0.01). After controlling for age and duration of injury, PPLr significantly correlated with apoB (r = 0.66, P = 0.001), TBF (r = 0.45, P = 0.03), VF (r = 0.66, P = 0.02), and TAF (r = 0.56, P = 0.007). CONCLUSIONS: Although concentrations of LDL cholesterol and apoB were not different between SCI and AB groups, LSP, apoB, and TAF correlated with PPLr in persons with SCI. ApoB was associated with a greater PPLr in those with motor complete SCI, after controlling for age and duration of injury.