Diagnosis and Management of Cardiovascular Risk in Individuals With Spinal Cord Injury: A Narrative Review.

More than 16 000 Americans experience spinal cord injury (SCI), resulting in chronic disability and other secondary sequelae, each year. Improvements in acute medical management have increased life expectancy. Cardiovascular disease is a leading cause of death in this population, and seems to occur earlier in individuals with SCI compared with the general population. People with SCI experience a high burden of traditional cardiovascular disease risk factors, including dyslipidemia and diabetes, and demonstrate anatomic, metabolic, and physiologic changes alongside stark reductions in physical activity after injury. They also experience multiple, complex barriers to care relating to disability and, in many cases, compounding effects of intersecting racial and socioeconomic health inequities. Given this combination of risk factors, some investigators have proposed that people with SCI are at increased risk for cardiovascular disease, beyond that associated with traditional risk factors, and SCI could be considered a risk-enhancing factor, analogous to other risk-enhancing factors defined by the 2019 American Heart Association/American College of Cardiology Primary Prevention Guidelines. However, more research is needed in this population to clarify the role of traditional risk factors, novel risk factors, health care access, social determinants of health, and intersectionality of disability, race, and socioeconomic status. There is an urgent need for primary care physicians and cardiologists to have awareness of the importance of timely diagnosis and management of cardiac risk factors for people with SCI.

TLR2 agonist prevents the progression of periapical lesions in mice by reducing osteoclast activity and regulating the frequency of Tregs.

AIM: To evaluate the role of regulatory T lymphocytes (Tregs) in the presence or absence of the synthetic ligand Pam3Cys during the progression of periapical lesion in wild-type (WT) and toll-like receptor 2 knockout (TLR2KO) mice. METHODOLOGY: A total of 130 C57BL/6 male WT and TLR2KO mice were allocated into control (n = 5) and experimental (periapical lesion induction) (n = 10) groups. In specific groups (WT+Pam3cys and TLR2KO+Pam3cys), the synthetic ligand Pam3cys was administered intraperitoneally every 7 days, according to the experimental period (14, 21 and 42 days). At the end of those periods, the animals were euthanized, and the mandible and the spleen were submitted to histotechnical processing. Mandible histological sections were analysed by haematoxylin and eosin, TRAP histoenzymology and immunohistochemistry (FOXP3, RANK, RANKL and OPG). Spleen sections were analysed by immunohistochemistry (FOXP3). RESULTS: The inflammatory infiltrate and bone resorption were more intense in the TLR2KO group compared to the WT group. The animals that received the Pam3cys had smaller periapical lesions when compared to the animals that did not receive the ligand (p < .05). TLR2KO animals showed a significant increase in the number of osteoclasts when compared to TLR2KO+Pam3cys group (p < .05). At 21 days, the WT+Pam3cys group had a lower number of osteoclasts when compared to the WT animals (p = .02). FOXP3 expression was more intense in the WT+Pam3cys groups when compared to the WT animals in the 42 days (p = .03). In the spleen analysis, the WT+Pam3cys group also had a higher expression of FOXP3 when compared to the WT animals at 14 and 42 days (p = .02). Concerning RANKL, there was a reduction in staining in the KOTLR2+Pam3cys groups at 21 and 42 days (p = .03) and a higher binding ratio between RANK/RANKL in animals that did not receive the ligand. CONCLUSION: Administration of the Pam3cys increased the proliferation of Tregs, showed by FOXP3 expression and prevented the progression of the periapical lesion in WT mice. On the other hand, in the TLR2KO animals, Treg expression was lower with larger areas of periapical lesions. Finally, systemic administration of the Pam3cys in KO animals was able to limit the deleterious effects of the absence of the TLR2 receptor.

Comparison of DXA-based versus CT-based indices to predict prevalent fracture history in men with spinal cord injury.

Fracture risk prediction remains challenging in adults with spinal cord injury. Here, we compare the ability of CT- and DXA-derived indices to discriminate between those with and without prevalent osteoporotic fracture. Novel CT-derived indices may offer improved assessment of fragility fracture risk as well as improved monitoring of response to therapies. INTRODUCTION: Individuals with spinal cord injury are particularly susceptible to osteoporosis. As advanced imaging techniques become more readily available clinically, there is limited information on the relative strength of various outcomes for fracture risk prediction. The purpose of this study was to compare the ability of DXA-based versus CT-based indices to predict prevalent fracture history in adults with spinal cord injury. METHODS: Thirty-six men with known SCI underwent dual energy X-ray absorptiometry and computed tomography assessments of the lower extremities. We used age-adjusted area under the curve models to compare the predictive value for each bone parameter to identify prevalent fracture history. RESULTS: CT-based indices outperformed DXA-based indices at all sites. The site with the highest AUC was the trabecular BMD at the proximal tibial epiphysis. CONCLUSIONS: CT imaging may have clinical utility to improve fracture risk prediction in adults with SCI. More work is needed to confirm these findings and to assess the value of CT-based indices to predict incident fracture, monitor longitudinal bone loss, and monitor response to various therapies, both pharmacological and rehabilitation.

Pharmacologic and Nonpharmacologic Treatment Modalities for Bone Loss in SCI - Proposal for Combined Approach.

Increased risk of bone fracture due to bone mineral density (BMD) loss is a serious consequence of spinal cord injury (SCI). Traditionally, pharmaceutical approaches, such as bisphosphonates, have been prescribed to prevent bone loss. However, there is controversy in the literature regarding efficacy of these medications to mitigate the drastic bone loss following SCI. Individuals with SCI are particularly at risk of osteoporosis because of the lack of ambulation and weight bearing activities. In the past two decades, functional electric stimulation (FES) has allowed for another approach to treat bone loss. FES approaches are expanding into various modalities such as cycling and rowing exercises and show promising outcomes with minimal consequences. In addition, these non-pharmacological treatments can elevate overall physical and mental health. This article provides an overview of efficacy of different treatment options for BMD loss for SCI and advocates for a combined approach be pursued in standard of care.

Bone Mineral Loss at the Distal Femur and Proximal Tibia Following Spinal Cord Injury in Men and Women.

PURPOSE: Spinal cord injury (SCI) causes rapid bone loss and increases risk of fragility fractures in the lower extremities. The majority of individuals with SCI are men, and few studies have investigated sex as a biological variable in SCI-induced osteoporosis. This cross-sectional study aimed to quantify sex-specific differences in bone mineral following SCI. METHODS: Quantitative computed tomography (QCT) scans of the distal femur and proximal tibia were obtained at baseline of one of four clinical trials enrolling people who sustained SCI 1 month to 50 years prior to recruitment. Bone volume (BV), bone mineral content (BMC), bone mineral density (BMD), and bending strength index (BSI) were quantified in the integral, trabecular, and cortical bone in the epiphysis, metaphysis and diaphysis. Scans from 106 men and 31 women were analyzed to measure sex-specific effects on bone loss over time post-SCI. RESULTS: BMC and BSI declined exponentially as a function of time post-SCI and were best described by separate decay curves for men and women. Women had BV, BMC, and BSI at 58-77% that of men in the acute and plateau phases, with both sexes showing similar rates of loss as a function of time post-SCI. Trabecular BMD was best described as an exponential decay versus time post-SCI, with no sex-specific differences. CONCLUSIONS: Due to consistently lower BV, BMC, and BSI, women may be more susceptible to fractures after SCI than men.

Changes in essential care in individuals with spinal cord injury during the COVID-19 pandemic.

STUDY DESIGN: Cross-sectional, observational study. OBJECTIVES: To determine whether changes in essential care during the COVID-19 pandemic impacted satisfaction with activities, participation, and relationships among individuals with spinal cord injury (SCI). SETTING: Data were collected online between December 31, 2020 and February 14, 2021 among community dwelling adults with SCI (N = 123). METHODS: The primary outcome variables were satisfaction with the ability to complete activities of daily living (ADLs) (mobility, dressing, feeding, and toileting), as well as satisfaction with participation in household and recreational activities, and satisfaction with relationships among friends, family, and with the status of one's relationship measured with the International Spinal Cord Injury Data Sets Activities and Participation Basic Data Set. Primary predictors were age, gender, time since injury, completeness of injury, injury level, access to mental health, access to medications, access to medical supplies, and access to personal care assistants (PCAs). RESULTS: Impact on access to mental health and impact on access to supplies were the most common factors affecting satisfaction with activities, participation, and relationships for individuals with SCI during the COVID-19 pandemic. Impact on access to PCAs/homecare was also found to impact certain outcomes including feeding and participation in household activities. CONCLUSIONS: Future supply chain disruptions from pandemics or natural disasters could have wide-reaching effects for individuals with SCIs. Thus, further research and advocacy is needed to improve mental health care planning and supply chain access during subsequent natural disasters.

miR-338-5p Levels and Cigarette Smoking are Associated With Neuropathic Pain Severity in Individuals With Spinal Cord Injury: Preliminary Findings From a Genome-Wide microRNA Expression Profiling Screen.

OBJECTIVE: To identify microRNA biomarkers and clinical factors associated with neuropathic pain after spinal cord injury. DESIGN: Cross-sectional, secondary analysis of baseline data collected from ongoing clinical studies. Using a genome-wide microRNA screening approach, we studied differential microRNA expression in serum from 43 adults with spinal cord injury enrolled in ongoing clinical studies. Least squares regression was used to identify associations between microRNA expression, clinical factors, and neuropathic pain severity. SETTING: Community-dwelling individuals with spinal cord injury. PARTICIPANTS: Participants (N=43) were at least 18 years old with spinal cord injury, with 28 reporting neuropathic pain and 15 reporting no neuropathic pain. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain presence, type, and intensity were assessed with the International Spinal Cord Injury Pain Basic Data Set. Serum microRNA normalized deep sequencing counts were quantified from blood samples. Participant demographic factors, injury characteristics, medication use, and health habits were collected via questionnaire. RESULTS: miR-338-5p expression and history of cigarette smoking were associated with and explained 37% of the variance in neuropathic pain severity (R2=0.37, F2,18=5.31, P=.02) independent of other clinical factors. No association was identified between miR-338-5p levels and nociceptive pain severity. CONCLUSIONS: Our findings suggest that miR-338-5p and cigarette smoking may both play a role in the development or maintenance of neuropathic pain after spinal cord injury. While additional work is needed to confirm these findings, validated target analysis suggests a neuroprotective role of miR-338-5p in modulating neuroinflammation and neuronal apoptosis and that its downregulation may result in maladaptive neuroplastic mechanisms contributing to neuropathic pain after spinal cord injury.

Predictors of Postacute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study.

OBJECTIVE: To examine the frequency of postacute sequelae of SARS-CoV-2 (PASC) and the factors associated with rehabilitation utilization in a large adult population with PASC. DESIGN: Retrospective study. SETTING: Midwest hospital health system. PARTICIPANTS: 19,792 patients with COVID-19 from March 10, 2020, to January 17, 2021. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Descriptive analyses were conducted across the entire cohort along with an adult subgroup analysis. A logistic regression was performed to assess factors associated with PASC development and rehabilitation utilization. RESULTS: In an analysis of 19,792 patients, the frequency of PASC was 42.8% in the adult population. Patients with PASC compared with those without had a higher utilization of rehabilitation services (8.6% vs 3.8%, P<.001). Risk factors for rehabilitation utilization in patients with PASC included younger age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-1.00; P=.01). In addition to several comorbidities and demographics factors, risk factors for rehabilitation utilization solely in the inpatient population included male sex (OR, 1.24; 95% CI, 1.02-1.50; P=.03) with patients on angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers 3 months prior to COVID-19 infections having a decreased risk of needing rehabilitation (OR, 0.80; 95% CI, 0.64-0.99; P=.04). CONCLUSIONS: Patients with PASC had higher rehabilitation utilization. We identified several clinical and demographic factors associated with the development of PASC and rehabilitation utilization.

Association between weekly exercise minutes and resting IL-6 in adults with chronic spinal cord injury: findings from the fracture risk after spinal cord injury exercise study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess associations between weekly aerobic exercise minutes and resting interleukin-6 (IL-6), C-reactive protein (CRP), or leptin levels in adults with chronic spinal cord injury (SCI). SETTING: Three hundred and forty-four community-dwelling men and women with SCI duration of > 1 year. METHODS: CRP, IL-6, and leptin levels were quantified by ultra-sensitive enzyme-linked immunoassay. Smoking, medication use, comorbidities, and aerobic exercise minutes per week were assessed by self-reported questionnaire. Body composition was determined by whole-body dual-energy X-ray absorptiometry. Generalized linear models were used to assess associations. RESULTS: In multivariable modeling, resting IL-6 levels were 0.001 pg/mL lower for every 1 min of weekly aerobic exercise. IL-6 levels increased with increasing android-to-gynoid fat ratio, in active/ever smokers compared to never smokers, and in individuals with skin pressure injuries compared to those without. IL-6 levels were lower in active ibuprofen users compared to nonusers. We found no association between weekly exercise minutes and CRP or leptin when designing similar models. CONCLUSIONS: Increasing aerobic exercise minutes is associated with lower IL-6 levels in adults with chronic SCI when considering body composition, smoking, skin pressure injuries, and ibuprofen use. CRP and leptin did not demonstrate an association with exercise when considering the similar variables. The use of these biomarkers in assessing the therapeutic value of future exercise-related interventions will be paramount for meaningful health improvement among those with SCI. Although a large, prospective dataset, this cross-sectional study cannot assign causation. Future prospective studies are needed to confirm these findings.

Resilience and mental health in individuals with spinal cord injury during the COVID-19 pandemic.

STUDY DESIGN: Cross-sectional, observational study. OBJECTIVES: To understand how resilience, access to personal care attendants (PCAs) and medical supplies, and concerns about medical rationing, finances, and social isolation are related to overall and mental health in individuals with spinal cord injury (SCI) in the context of the COVID-19 pandemic. SETTING: Community dwelling adults (N = 187) with SCI. METHODS: Data were collected online between May 1, 2020 and August 31, 2020. Outcomes were overall and mental health, depression and anxiety symptoms, and quality of life (QoL). Predictors were resilience, access to PCAs and medical supplies, and concerns about medical rationing, finances, and social isolation. RESULTS: Incomplete injury, concern about medical rationing, medical supply disruption, and social isolation predicted a greater perceived impact of the pandemic on overall heath. Younger age, decreased resilience, and concern about medical rationing and social isolation predicted greater perceived impact of the pandemic on mental health. Decreased resilience and concern about medical rationing and finances predicted increased anxiety symptoms. Incomplete injury, believing that medical rationing was occurring, decreased resilience, and concern about finances and social isolation predicted increased depressive symptoms. Decreased resilience and concern about finances, medical rationing, and social isolation predicted lower QoL. CONCLUSIONS: The negative effects of the pandemic on the overall and mental health of individuals with SCI may be ameliorated by resilience. In future crises, it may be beneficial to screen individuals for resilience so that those with decreased resilience are offered the appropriate resources to enhance resilience and improve overall wellbeing.

Snx10 and PIKfyve are required for lysosome formation in osteoclasts.

Bone resorption and organelle homeostasis in osteoclasts require specialized intracellular trafficking. Sorting nexin 10 (Snx10) is a member of the sorting nexin family of proteins that plays crucial roles in cargo sorting in the endosomal pathway by its binding to phosphoinositide(3)phosphate (PI3P) localized in early endosomes. We and others have shown previously that the gene encoding sorting Snx10 is required for osteoclast morphogenesis and function, as osteoclasts from humans and mice lacking functional Snx10 are dysfunctional. To better understand the role and mechanisms by which Snx10 regulates vesicular transport, the aim of the present work was to study PIKfyve, another PI3P-binding protein, which phosphorylates PI3P to PI(3,5)P2. PI(3,5)P2 is known to be required for endosome/lysosome maturation, and the inhibition of PIKfyve causes endosome enlargement. Overexpression of Snx10 also induces accumulation of early endosomes suggesting that both Snx10 and PIKfyve are required for normal endosome/lysosome transition. Apilimod is a small molecule with specific, nanomolar inhibitory activity on PIKfyve but only in the presence of key osteoclast factors CLCN7, OSTM1, and Snx10. This observation suggests that apilimod's inhibitory effects are mediated by endosome/lysosome disruption. Here we show that both Snx10 and PIKfyve colocalize to early endosomes in osteoclasts and coimmunoprecipitate in vesicle fractions. Treatment with 10 nM apilimod or genetic deletion of PIKfyve in cells resulted in the accumulation of early endosomes, and in the inhibition of osteoclast differentiation, lysosome formation, and secretion of TRAP from differentiated osteoclasts. Snx10 and PIKfyve also colocalized in gastric zymogenic cells, another cell type impacted by Snx10 mutations. Apilimod-specific inhibition of PIKfyve required Snx10 expression, as it did not inhibit lysosome biogenesis in Snx10-deficient osteoclasts. These findings suggest that Snx10 and PIKfyve are involved in the regulation of endosome/lysosome homeostasis via the synthesis of PI(3,5)P2 and may point to a new strategy to prevent bone loss.

Circulating PAMM, a novel antioxidant and anti-inflammatory protein, is elevated in acute SCI.

BACKGROUND: Peroxiredoxin activated in M-CSF stimulated monocytes (PAMM) is a novel protein produced by adipocytes with putative redox regulatory and anti-inflammatory properties. Because acute spinal cord injury (SCI) is associated with oxidative stress and neuroinflammation and because PAMM can be detected in systemic circulation, we hypothesized that acute neuro-trauma might induce changes in circulating PAMM expression. Specifically, we hypothesized that PAMM levels might vary based on the presence or absence of acute, traumatic SCI. We therefore investigated circulating PAMM levels in adults with and without acute traumatic SCI. METHODS: We studied 105 men and women (54 with SCI and 51 without SCI). Participants with SCI were admitted for acute rehabilitation within 1 month after injury. Serum samples were obtained during hospitalization and stored at - 80 °C until batch analysis. Total PAMM was quantified by ELISA assay (MyBiosource, Cat. No: MBS9327247) with a detection limit of 0.25 ng/ml. Separate multivariate models including age, BMI, and injury severity were assessed to determine significant clinical predictors of change in PAMM levels. RESULTS: When adjusting for BMI, age, and gender, mean change in PAMM levels were greatest in participants with motor complete SCI compared to able-bodied (1.65 ng/ml versus 0.94 ng/ml, p = 0.003). This model explained 26% of the variation in change in circulating PAMM levels. CONCLUSIONS: Our results suggest that PAMM may be a novel biomarker of neurological injury or of native anti-inflammatory responses to neurological injury. More work is needed to establish the role of PAMM and other adipocyte-derived factors in the acute response to neurotrauma.

FKBP12: A partner of Snx10 required for vesicular trafficking in osteoclasts.

Osteoclasts employ highly specialized intracellular trafficking controls for bone resorption and organelle homeostasis. The sorting nexin Snx10 is a (Phosphatidylinositol 3-phosphate) PI3P-binding protein, which localizes to osteoclast early endosomes. Osteoclasts from humans and mice lacking functional Snx10 are severely dysfunctional. They show marked impairments in endocytosis, extracellular acidification, ruffled border formation, and bone resorption, suggesting that Snx10 regulates membrane trafficking. To better understand how SNx10 regulates vesicular formation and trafficking in osteoclasts, we set out on a search for Snx10 partners. We performed a yeast two-hybrid screening and identified FKBP12. FKBP12 is expressed in receptor activator of nuclear factor kB ligand-stimulated RAW264.7 monocytes, coimmunoprecipitates with Snx10, and colocalizes with Snx10 in osteoclasts. We also found that FKBP12, Snx10, and early endosome antigen 1 (EEA1) are present in the same subcellular fractions obtained by centrifugation in sucrose gradients, which confirms localization of FKBP12 to early endosomes. Taken together, these results indicate that Snx10 and FKBP12 are partners and suggest that Snx10 and FKBP12 are involved in the regulation of endosome/lysosome homeostasis via the synthesis. These findings may suggest novel therapeutic approaches to control bone loss by targeting essential steps in osteoclast membrane trafficking.

Bone Mineral Density Testing in Spinal Cord Injury: 2019 ISCD Official Position.

Spinal cord injury (SCI) causes rapid osteoporosis that is most severe below the level of injury. More than half of those with motor complete SCI will experience an osteoporotic fracture at some point following their injury, with most fractures occurring at the distal femur and proximal tibia. These fractures have devastating consequences, including delayed union or nonunion, cellulitis, skin breakdown, lower extremity amputation, and premature death. Maintaining skeletal integrity and preventing fractures is imperative following SCI to fully benefit from future advances in paralysis cure research and robotic-exoskeletons, brain computer interfaces and other evolving technologies. Clinical care has been previously limited by the lack of consensus derived guidelines or standards regarding dual-energy X-ray absorptiometry-based diagnosis of osteoporosis, fracture risk prediction, or monitoring response to therapies. The International Society of Clinical Densitometry convened a task force to establish Official Positions for bone density assessment by dual-energy X-ray absorptiometry in individuals with SCI of traumatic or nontraumatic etiology. This task force conducted a series of systematic reviews to guide the development of evidence-based position statements that were reviewed by an expert panel at the 2019 Position Development Conference in Kuala Lumpur, Malaysia. The resulting the International Society of Clinical Densitometry Official Positions are intended to inform clinical care and guide the diagnosis of osteoporosis as well as fracture risk management of osteoporosis following SCI.

Executive Summary of the 2019 ISCD Position Development Conference on Monitoring Treatment, DXA Cross-calibration and Least Significant Change, Spinal Cord Injury, Peri-prosthetic and Orthopedic Bone Health, Transgender Medicine, and Pediatrics.

To answer important questions in the fields of monitoring with densitometry, dual-energy X-ray absorptiometry machine cross-calibration, monitoring, spinal cord injury, periprosthetic and orthopedic bone health, transgender medicine, and pediatric bone health, the International Society for Clinical Densitometry (ISCD) held a Position Development Conference from March 20 to 23, 2019. Potential topics requiring guidance were solicited from ISCD members in 2017. Following that, a steering committee selected, prioritized, and grouped topics into Task Forces. Chairs for each Task Force were appointed and the members were co-opted from suggestions by the Steering Committee and Task Force Chairs. The Task Forces developed key questions, performed literature searches, and came up with proposed initial positions with substantiating draft publications, with support from the Steering Committee. An invited Panel of Experts first performed a review of draft positions using a modified RAND Appropriateness Method with voting for appropriateness. Draft positions deemed appropriate were further edited and presented at the Position Development Conference meeting in an open forum. A second round of voting occurred after discussions to approve or reject the positions. Finally, a face-to-face closed session with experts and Task Force Chairs, and subsequent electronic follow-up resulted in 34 Official Positions of the ISCD approved by the ISCD Board on May 28, 2019. The Official Positions and the supporting evidence were submitted for publication on July 1, 2019. This paper provides a summary of the all the ISCD Adult and Pediatric Official Positions, with the new 2019 positions highlighted in bold.

Associations Between Insurance Provider and Assistive Technology Use for Computer and Electronic Devices 1 Year After Tetraplegia: Findings From the Spinal Cord Injury Model Systems National Database.

OBJECTIVE: To investigate the association between insurance provider and reported assistive technology (AT) use to access computers and electronic devices 1 year after sustaining tetraplegia. DESIGN: Multicenter cross-sectional study. SETTING: Participants enrolled in the Spinal Cord Injury Model Systems (SCIMS) National Database. INTERVENTIONS: Not applicable. PARTICIPANTS: Men and women with tetraplegia (N=498) enrolled in the SCIMS National Database were included in the analysis. MAIN OUTCOME MEASURES: The primary study outcome was the use of AT when operating a computer or other mobile electronic device. The primary predictor was the subject's principal health insurance provider, which was grouped into the 3 categories: government (Medicare, Medicaid, and other government), private (private insurance, private funds, and other), and workers' compensation. RESULTS: Overall, 34.7% of participants reported using AT to access computers and electronic devices. Results of logistic regression analysis revealed sex, injury level, injury completeness, self-perceived health status, and 12-month history of pressure ulcer were all significantly associated with AT use. After adjusting for these factors, participants with workers' compensation were more likely to report AT use than individuals with either government or private insurance. CONCLUSIONS: Despite significant technological advances, AT is not readily available to the people who might benefit most from its use. Findings from the present study are the first to shed light on AT funding sources and reveal that individuals with workers' compensation are more likely use AT than individuals with either government or private insurance. Additional work focused on AT use and functional outcomes is needed to assess the effect of barriers to use. Collectively, this work may inform insurers of the importance of having AT available for this unique population to potentially improve quality of life and participation.

Factors associated with osteocalcin in men with spinal cord injury: findings from the FRASCI study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the association between clinical and demographic factors, bisphosphonate use, and circulating total osteocalcin levels in men with chronic spinal cord injury. SETTING: Veteran Affairs Medical Center. METHODS: As part of an epidemiological study assessing SCI-related health conditions, 214 men with chronic spinal cord injury underwent a DXA scan and provided a blood sample and information regarding SCI, medication use, and fracture history. General linear models were used to assess clinical/demographic factors of osteocalcin, and if significant, were included in multivariate model. RESULTS: We found that total osteocalcin levels increased 1.0 ng/ml for every kilogram increase in lean mass (p = 0.05) and increased 4.53 ng/ml for every ng/ml increase in C-telopeptide level (p < 0.0001). Osteocalcin levels were greater in people reporting no alcohol consumption compared with drinkers (15.49 ng/ml versus 18.58 ng/ml, p < 0.0002), lower in diabetics compared with nondiabetics (15.23 ng/ml versus 18.92 ng/ml, p = 0.0001), and lower in bisphosphonate users compared with nonusers (15.50 ng/ml versus 18.58 ng/ml, p < 0.03). The association between age and osteocalcin was not significant (p = 0.06). This model explained 58% of the variation in ln osteocalcin levels (model p < 0.0001, r2 = 0.58). CONCLUSIONS: Total osteocalcin levels vary based on health habits, body composition, comorbid illnesses, and bisphosphonate use in men with chronic spinal cord injury.

Perceived injustice after spinal cord injury: evidence for a distinct psychological construct.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To identify unique predictors of perceived injustice compared with depression symptoms within the first year after SCI. SETTING: Inpatient rehabilitation program in a large urban region in the Southwestern United States. METHODS: A sample of 74 participants with median time since injury of 52 days completed measures of perceived injustice, depression symptoms, posttraumatic stress symptoms, expected disability, pain intensity, and anger. RESULTS: Three unique predictors of perceived injustice as compared with depression symptoms were found-time since injury, state anger, and sex. These predictors had significantly different relationships with perceived injustice than with depression symptoms. CONCLUSIONS: Results replicate previous findings that perceived injustice is moderately correlated with depression symptoms. However, findings also reveal factors uniquely associated with perceived injustice than with depression symptoms, providing support that these are two separate constructs. Thus, these findings support development of novel interventions targeting perceptions of injustice.

Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture.

Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist. Acupuncture is a minimally-invasive and conservative therapeutic option, and while rooted in a complex practice ritual, acupuncture overlaps significantly with many conventional peripherally-focused neuromodulatory therapies. However, the neurophysiological mechanisms by which acupuncture impacts accepted subjective/psychological and objective/physiological outcomes are not well understood. Eligible patients (n = 80, 65 female, age: 49.3 ± 8.6 years) were enrolled and randomized into three intervention arms: (i) verum electro-acupuncture 'local' to the more affected hand; (ii) verum electro-acupuncture at 'distal' body sites, near the ankle contralesional to the more affected hand; and (iii) local sham electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome Questionnaire assessed pain and paraesthesia symptoms at baseline, following therapy and at 3-month follow-up. Nerve conduction studies assessing median nerve sensory latency and brain imaging data were acquired at baseline and following therapy. Functional magnetic resonance imaging assessed somatotopy in the primary somatosensory cortex using vibrotactile stimulation over three digits (2, 3 and 5). While all three acupuncture interventions reduced symptom severity, verum (local and distal) acupuncture was superior to sham in producing improvements in neurophysiological outcomes, both local to the wrist (i.e. median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 cortical separation distance). Moreover, greater improvement in second/third interdigit cortical separation distance following verum acupuncture predicted sustained improvements in symptom severity at 3-month follow-up. We further explored potential differential mechanisms of local versus distal acupuncture using diffusion tensor imaging of white matter microstructure adjacent to the primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 49.7 ± 9.9 years old), patients with carpal tunnel syndrome demonstrated increased fractional anisotropy in several regions and, for these regions we found that improvement in median nerve latency was associated with reduction of fractional anisotropy near (i) contralesional hand area following verum, but not sham, acupuncture; (ii) ipsilesional hand area following local, but not distal or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not local or sham, acupuncture. As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex somatotopy can predict long-term clinical outcomes for carpal tunnel syndrome.

Sensitivity of the SCI-FI/AT in Individuals With Traumatic Spinal Cord Injury.

OBJECTIVE: To examine the ability of the Spinal Cord Injury-Functional Index/Assistive Technology (SCI-FI/AT) measure to detect change in persons with spinal cord injury (SCI). DESIGN: Multisite longitudinal (12-mo follow-up) study. SETTING: Nine SCI Model Systems programs. PARTICIPANTS: Adults (N=165) with SCI enrolled in the SCI Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SCI-FI/AT computerized adaptive test (CAT) (Basic Mobility, Self-Care, Fine Motor Function, Wheelchair Mobility, and/or Ambulation domains) completed at discharge from rehabilitation and 12 months after SCI. For each domain, effect size estimates and 95% confidence intervals were calculated for subgroups with paraplegia and tetraplegia. RESULTS: The demographic characteristics of the sample were as follows: 46% (n=76) individuals with paraplegia, 76% (n=125) male participants, 57% (n=94) used a manual wheelchair, 38% (n=63) used a power wheelchair, 30% (n=50) were ambulatory. For individuals with paraplegia, the Basic Mobility, Self-Care, and Ambulation domains of the SCI-FI/AT detected a significantly large amount of change; in contrast, the Fine Motor Function and Wheelchair Mobility domains detected only a small amount of change. For those with tetraplegia, the Basic Mobility, Fine Motor Function, and Self-Care domains detected a small amount of change whereas the Ambulation item domain detected a medium amount of change. The Wheelchair Mobility domain for people with tetraplegia was the only SCI-FI/AT domain that did not detect significant change. CONCLUSIONS: SCI-FI/AT CAT item banks detected an increase in function from discharge to 12 months after SCI. The effect size estimates for the SCI-FI/AT CAT vary by domain and level of lesion. Findings support the use of the SCI-FI/AT CAT in the population with SCI and highlight the importance of multidimensional functional measures.