Carlos G. Tun

A prospective assessment of mortality in chronic spinal cord injury

Study design:Prospective mortality study.Objective:To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI).Setting:Boston, MA, USA.Methods:Between 1994 and 2000, 361 males ⩾1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33–74.4 months) through 12/31/2000 using the National Death Index.Results:At entry, mean (±SD) age was 50.6±15.0 years (range 23–87) and years since injury was 17.5±12.8 years (range 1.0–56.5). Mortality was elevated (observed/expected deaths=37/25.1; SMR=1.47; 95% CI=1.04–2.03) compared to US rates. Risk factors for death were diabetes (RR=2.62; 95% CI=1.19–5.77), heart disease (RR=3.66; 95% CI=1.77–7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390–459) in 40%, and of the respiratory system in 24% (ICD-9 460-519).Conclusions:These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.

Prevalence of chronic pain, posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF veterans: polytrauma clinical triad.

This study examines the prevalence and coprevalence with which returning Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans were reporting symptoms consistent with chronic pain, posttraumatic stress disorder (PTSD), and persistent postconcussive symptoms (PPCS). The medical records of 340 OIF/OEF veterans seen at a Department of Veterans Affairs Polytrauma Network Site were comprehensively reviewed. Analyses indicated a high prevalence of all three conditions in this population, with chronic pain, PTSD, and PPCS present in 81.5%, 68.2%, and 66.8%, respectively. Only 12 of the veterans (3.5%) had no chronic pain, PTSD, or PPCS. The frequency at which these three conditions were present in isolation (10.3%, 2.9%, and 5.3%, respectively) was significantly lower than the frequency at which they were present in combination with one another, with 42.1% of the sample being diagnosed with all three conditions simultaneously. The most common chronic pain locations were the back (58%) and head (55%). These results underscore the complexity of the presenting complaints in OIF/OEF veterans and support the importance of a multidisciplinary team approach to assessment and treatment.

Chronic postconcussion symptoms and functional outcomes in OEF/OIF veterans with self-report of blast exposure.

Postconcussion symptoms (PCS) and functional outcomes were evaluated in 91 OEF/OIF outpatient veterans with reported histories of blast-exposure, with the goal of evaluating (1) the association between these outcomes and a clinical diagnosis of mild traumatic brain injury (mTBI) with or without loss of consciousness (LOC); and (2) the influence of post-traumatic stress disorder (PTSD) and depression on PCS reporting and perceived functional limitations. Individuals who reported mTBI with LOC had greater PCS complaints than individuals who reported mTBI without LOC or individuals without mTBI. However, after adjusting for severity of PTSD and depression symptoms, this group difference disappeared. Functional limitations were particularly prominent in the psychosocial domain. Again, PTSD was significantly associated with functional outcomes, but the mTBI with LOC group had greater psychosocial limitations than the other two groups, even when PTSD and depression symptoms were taken into account. These findings highlight the role of mental health in both outcomes, but additionally point to the impact of mTBI with LOC on long-term psychosocial adjustment.

Association between sclerostin and bone density in chronic spinal cord injury.

Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short‐term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long‐term, chronic paraplegia. This is in contrast to the acute sclerostin‐mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short‐term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI‐induced osteoporosis.

Factors Associated with Health-Related Quality of Life in Chronic Spinal Cord Injury

Jain NB, Sullivan M, Kazis LE, Tun CG, Garshick E: Factors associated with health-related quality of life in chronic spinal cord injury. Am J Phys Med Rehabil 2007;86:387–396. Objective:An important goal of rehabilitation and treatment after spinal cord injury (SCI) is to improve function and enhance health-related quality of life (HRQoL). However, previous assessments are limited by use of HRQoL instruments not specific to SCI. Although respiratory dysfunction is common in SCI, it has not been possible to assess the association of comorbid medical conditions, including respiratory symptoms and pulmonary function, to HRQoL. Therefore, we assessed whether these factors were associated with HRQoL in SCI using an SCI-specific HRQoL questionnaire. Design:In our cross-sectional study, 356 participants ≥1 yr post-SCI completed a 23-item SCI-specific HRQoL questionnaire and a detailed health questionnaire, and underwent pulmonary function testing and a neurological exam at VA Boston between 1998 and June 2003. Results:In a multivariate regression model, age, employment status, motor level and completeness of injury, and ambulatory mode (use of hand-propelled or motorized wheelchair, use of crutches or canes, or walking independently) were independently associated with HRQoL. After adjusting for these factors, chronic cough, chronic phlegm, persistent wheeze, dyspnea with activities of daily living, and lower forced expiratory volume in 1 sec and forced vital capacity were each associated with a lower HRQoL. Conclusions:These results provide evidence for the clinical validity of our SCI-specific HRQoL instrument. We also identify potentially modifiable factors that, if addressed, may lead to HRQoL improvement in SCI.

Spirometry--acceptability and reproducibility in spinal cord injured subjects.

The American Thoracic Society (ATS) has formulated guidelines for spirometry. We hypothesized that individuals with SCI (SCI), as a result of weak respiratory muscles, would exhibit poor test acceptability and reproducibility. Seventy-eight SCI subjects (39 with complete SCI) answered a respiratory questionnaire and performed spirometry. Of those with complete SCI, the proportion of subjects which met ATS criteria decreased with higher levels of injury. Poor test performance was not associated with age, respiratory symptoms or muscle fatigue. The most common reason for failing to meet ATS criteria for acceptability was excessive back extrapolated volumes (EBEV). Individuals with efforts that were acceptable except for EBEV and/or for exhalation of less than six seconds had values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) that were reproducible. If ATS criteria for acceptable spirometry were used in studying subjects with SCI, individuals producing otherwise reproducible values for FVC and FEV1 would be excluded. We found reproducibility similar to what has been reported in other cohorts and conclude that longitudinal study of respiratory function in SCI is feasible.

Longitudinal Change in FEV1 and FVC in Chronic Spinal Cord Injury

RATIONALE Although respiratory dysfunction is common in chronic spinal cord injury (SCI), determinants of longitudinal change in FEV(1) and FVC have not been assessed. OBJECTIVES Determine factors that influence longitudinal lung function decline in SCI. METHODS A total of 174 male participants (mean age of 49 and 17 yr after injury) completed a respiratory questionnaire and underwent spirometry over an average follow-up of 7.5 years (range, 4-14 yr). MEASUREMENTS AND MAIN RESULTS In multivariate models, longitudinal decline in FEV(1) was significantly related to continued smoking, persistent wheeze, an increase in body mass index, and respiratory muscle strength. Aging was associated with an accelerated decline in FEV(1) (for ages <40, 40-60, >60 yr: -27, -37, and -71 ml/yr, respectively). Similar effects were observed for FVC. CONCLUSIONS Longitudinal change in FEV(1) and FVC was not directly related to level and severity of SCI, but was attributable to potentially modifiable factors in addition to age. These results suggest that weight control, smoking cessation, trials directed at the recognition and treatment of wheeze, and efforts to improve respiratory muscle strength may slow lung function decline after SCI.

Association Between Mobility Mode and C-Reactive Protein Levels in Men With Chronic Spinal Cord Injury

OBJECTIVE To assess clinical determinants of systemic inflammation in persons with chronic spinal cord injury (SCI). DESIGN Cross-sectional survey. SETTING Veterans Affairs medical center. PARTICIPANTS As part of an epidemiologic study assessing SCI-related health conditions, 63 men with chronic SCI provided a blood sample and information regarding locomotive mode and personal habits. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURE Plasma high-sensitivity C-reactive protein (CRP). RESULTS The mean +/- standard deviation age was 56+/-14y, and participants were assessed 21+/-13y after injury. Adjusting for heart disease, hypertension, and body mass index (BMI), the mean CRP in 12 motorized wheelchair users (5.11mg/L) was not significantly greater than 23 participants who used a manual wheelchair (2.19mg/L) (P=.085) but was significantly greater than the 17 who walked with an assistive device (1.41mg/L) (P=.005) and the 12 who walked independently (1.63mg/L) (P=.027). CRP was significantly greater in participants with obesity but was not related to age, smoking, or SCI level and severity. CRP was elevated in participants reporting a urinary tract infection (UTI) or pressure ulcer within a year, but adjustment for this did not account for the elevated CRP in motorized wheelchair users. CONCLUSIONS These results suggest that CRP in chronic SCI is independently related to locomotive mode, BMI, and a history of pressure ulcers and UTI. It is suggested that future studies in SCI investigate whether modifying these factors influence systemic inflammation and cardiovascular health.

Sclerostin: a candidate biomarker of SCI-induced osteoporosis

SummaryWe assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker.IntroductionSpinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI.MethodsWe assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI.ResultsAfter adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p = 0.0002−0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p = 0.18−0.99).ConclusionThese findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI.

Breathlessness in spinal cord injury depends on injury level.

Little is known about the prevalence and predictors of breathlessness in individuals with neurologically complete chronic spinal cord injury (SCI). Between December 1992 and September 1993, we mailed a respiratory questionnaire to 1,147 community-based individuals with chronic SCI. The questionnaire included four questions about the presence of breathlessness during activities related to moving about. Of the 485 who replied (42 percent response rate), analysis was limited to adult males with neurologically complete motor injuries who reported using a hand-propelled wheelchair more than 50 percent of the time to get around. Of 130 subjects (33 tetraplegics, 53 high thoracic SCI, 44 lower injury levels), the patients with tetraplegia reported breathlessness more frequently (range for the four questions, 21-33%) than those with high thoracic (range, 9-15%) or lower injury levels (range, 2-11%). For each of the four questions there was a significant trend (p < 0.05) for subjects with higher levels of injury to report the greatest prevalence of breathlessness (tetraplegia > high thoracic > lower). The frequency of breathlessness was greatest in those with neurologically complete cervical injuries, an effect that was independent of obesity, smoking, age, and years since SCI. The mechanisms of breathlessness in SCI are unclear but elucidation might lead to strategies for providing relief.