Project description:ObjectiveTo investigate whether prevalent hospital-acquired pneumonia and wound infection affect the clinical long-term outcome after acute traumatic spinal cord injury (SCI).MethodsThis was a longitudinal cohort study within the prospective multicenter National Spinal Cord Injury Database (Birmingham, Alabama). We screened datasets of 3,834 patients enrolled in 20 trial centers from 1995 to 2005 followed up until 2016. Eligibility criteria were cervical SCI and American Spinal Cord Injury Association impairment scale A, B, and C. Pneumonia or postoperative wound infections (Pn/Wi) acquired during acute medical care/inpatient rehabilitation were analyzed for their association with changes in the motor items of the Functional Independence Measure (FIMmotor) using regression models (primary endpoint 5-year follow-up). Pn/Wi-related mortality was assessed as a secondary endpoint (10-year follow-up).ResultsA total of 1,203 patients met the eligibility criteria. During hospitalization, 564 patients (47%) developed Pn/Wi (pneumonia n = 540; postoperative wound infection n = 11; pneumonia and postoperative wound infection n = 13). Adjusted linear mixed models after multiple imputation revealed that Pn/Wi are significantly associated with lower gain in FIMmotor up to 5 years after SCI (-7.4 points, 95% confidence interval [CI] -11.5 to -3.3). Adjusted Cox regression identified Pn/Wi as a highly significant risk factor for death up to 10 years after SCI (hazard ratio 1.65, 95% CI 1.26 to 2.16).ConclusionHospital-acquired Pn/Wi are predictive of propagated disability and mortality after SCI. Pn/Wi qualify as a potent and targetable outcome-modifying factor. Pn/Wi prevention constitutes a viable strategy to protect functional recovery and reduce mortality. Pn/Wi can be considered as rehabilitation confounders in clinical trials.
Project description:ObjectiveTo investigate the long-term outcome of patients with spinal cord infarct (SCI) and identify prognostic predictors.MethodsWe reviewed 115 patients with SCI treated between 1990 and 2007. Severity of impairment was defined using the American Spinal Injury Association (ASIA) scoring. Functional outcome endpoints were ambulatory status, need for bladder catheterization, and pain.ResultsMean age was 64 years; 72 (62.6%) patients were men. A total of 45% of infarcts were perioperative (69% aortic surgeries). A total of 68% reached maximal deficit within 1 hour (mean = 5 hours). Impairment at nadir was ASIA A 23%, B 26%, C 14%, and D 37%. A total of 75/93 (81%) patients studied with MRI had cord signal abnormality. At nadir, 81% required wheelchair, 86% required catheterization, and 32% had pain. At last follow-up (mean = 3 years), 23% had died. Among survivors, 42% required a wheelchair, 54% required catheterization, and 29% had pain upon last follow-up. Of 74 patients using a wheelchair at hospital dismissal, 41% were walking by final follow-up. Of 83 patients catheterized at dismissal, 33% were catheter-free at last follow-up. Older age (p < 0.0001), increased severity of impairment at nadir (p = 0.02), and peripheral vascular disease (p = 0.003) were independent risk factors for mortality. Severe impairment (ASIA A/B) at nadir predicted wheelchair use (p < 0.0001) and bladder catheterization (p < 0.0001) at last follow-up.ConclusionsGradual improvement in not uncommon after spinal cord infarction and it may continue long after hospital dismissal. While severe impairment at nadir is the strongest predictor of poor functional outcome, meaningful recovery is also possible in a substantial minority of these patients.
Project description:Background and purposeThe natural history of PMAVFs, also known as type IV spinal cord AVFs, is incompletely understood. Both open surgical and endovascular approaches have been described as treatment modalities for this disease. The goal of this study was to evaluate the long-term outcome of patients with PMAVFs treated at a single tertiary care institution.Materials and methodsWe conducted a retrospective study of 32 patients with PMAVFs, evaluated between 1983 and 2009. Data were gathered by reviewing outpatient clinic notes, operative and radiologic reports, and spinal angiograms. The PMAVFs were categorized into 1 of 3 types based on the angiographic imaging criteria. Pretreatment and posttreatment ambulation and micturition symptoms were quantified by using the ALS.ResultsThirty patients underwent corrective procedures, 4 by embolization alone, 11 by surgery alone, and 15 with a combination of the 2. Twenty-eight patients underwent follow-up spinal angiography, with residual shunt noted in 6 patients. The mean follow-up period was 54 months (range, 1-228 months). Analysis of the ALS scores revealed that treatment of PMAVFs, independent of technique, resulted in significant improvement in ambulation but inconsistent changes in micturition. In addition, residual fistula at the time of the follow-up angiogram was associated with worsened neurologic status or lack of improvement. Outcome analysis based on fistula type showed dramatic improvement in ALS ambulation scores (62%) for type 3 fistulas, compared with types 1 and 2 (26% and 27%, respectively).ConclusionsSignificant improvement in ambulation but in not micturition was observed following treatment. Residual fistula on follow-up angiography was associated with progressive worsening or lack of improvement in neurologic function. Patients with type 3 fistulas were shown to benefit most from treatment, with marked improvement in posttreatment ambulation scores. As endovascular and surgical techniques continue to evolve, further studies are warranted.
Project description:Intermittent stimulation of the respiratory system with hypoxia causes persistent increases in respiratory motor output (i.e., long-term facilitation) in animals with spinal cord injury. This paradigm, therefore, has been touted as a potential respiratory rehabilitation strategy.To determine whether acute (daily) exposure to intermittent hypoxia can also evoke long-term facilitation of ventilation after chronic spinal cord injury in humans, and whether repeated daily exposure to intermittent hypoxia enhances the magnitude of this response.Eight individuals with incomplete spinal cord injury (>1 yr; cervical [n = 6], thoracic [n = 2]) were exposed to intermittent hypoxia (eight 2-min intervals of 8% oxygen) for 10 days. During all exposures, end-tidal carbon dioxide levels were maintained, on average, 2 mm Hg above resting values. Minute ventilation, tidal volume, and breathing frequency were measured before (baseline), during, and 30 minutes after intermittent hypoxia. Sham protocols consisted of exposure to room air and were administered to a subset of the participants (n = 4).Minute ventilation increased significantly for 30 minutes after acute exposure to intermittent hypoxia (P < 0.001), but not after sham exposure. However, the magnitude of ventilatory long-term facilitation was not enhanced over 10 days of intermittent hypoxia exposures.Ventilatory long-term facilitation can be evoked by brief periods of hypoxia in humans with chronic spinal cord injury. Thus, intermittent hypoxia may represent a strategy for inducing respiratory neuroplasticity after declines in respiratory function that are related to neurological impairment. Clinical trial registered with www.clinicaltrials.gov (NCT01272011).
Project description:Background: Chronic spinal cord injury (SCI) portends a low probability of recovery, especially in the most severe subset of motor-complete injuries. Active spinal cord stimulation with or without intensive locomotor training has been reported to restore movement after traumatic SCI. Only three cases have been reported where participants developed restored volitional movement with active stimulation turned off after a period of chronic stimulation and only after intensive rehabilitation with locomotor training. It is unknown whether restoration of movement without stimulation is possible after stimulation alone. Objective: We describe the development of spontaneous volitional movement (SVM) without active stimulation in a subset of participants in the Epidural Stimulation After Neurologic Damage (ESTAND) trial, in which locomotor training is not prescribed as part of the study protocol, and subject's rehabilitation therapies are not modified. Methods: Volitional movement was evaluated with the Brain Motor Control Assessment using sEMG recordings and visual examination at baseline and at follow-up visits with and without stimulation. Additional functional assessment with a motor-assisted bicycle exercise at follow-up with and without stimulation identified generated work with and without effort. Results: The first seven participants had ASIA Impairment Scale (AIS) A or B thoracic SCI, a mean age of 42 years, and 7.7 years post-injury on average. Four patients developed evidence of sustained volitional movement, even in the absence of active stimulation after undergoing chronic epidural spinal cord stimulation (eSCS). Significant increases in volitional power were found between those observed to spontaneously move without stimulation and those unable (p < 0.0005). The likelihood of recovery of spontaneous volitional control was correlated with spasticity scores prior to the start of eSCS therapy (p = 0.048). Volitional power progressively improved over time (p = 0.016). Additionally, cycling was possible without stimulation (p < 0.005). Conclusion: While some SVM after eSCS has been reported in the literature, this study demonstrates sustained restoration without active stimulation after long-term eSCS stimulation in chronic and complete SCI in a subset of participants. This finding supports previous studies suggesting that "complete" SCI is likely not as common as previously believed, if it exists at all in the absence of transection and that preserved pathways are substrates for eSCS-mediated recovery in clinically motor-complete SCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03026816.
Project description:We investigated whether imatinib (Gleevec®, Novartis), a tyrosine kinase inhibitor, could improve functional outcome in experimental spinal cord injury. Rats subjected to contusion spinal cord injury were treated orally with imatinib for 5 days beginning 30 minutes after injury. We found that imatinib significantly enhanced blood-spinal cord-barrier integrity, hindlimb locomotor function, sensorimotor integration, and bladder function, as well as attenuated astrogliosis and deposition of chondroitin sulfate proteoglycans, and increased tissue preservation. These improvements were associated with enhanced vascular integrity and reduced inflammation. Our results show that imatinib improves recovery in spinal cord injury by preserving axons and other spinal cord tissue components. The rapid time course of these beneficial effects suggests that the effects of imatinib are neuroprotective rather than neurorestorative. The positive effects on experimental spinal cord injury, obtained by oral delivery of a clinically used drug, makes imatinib an interesting candidate drug for clinical trials in spinal cord injury.
Project description:To improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ? 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score >50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families.
Project description:ObjectiveThe objective of this study was to evaluate the impact of urinary tract infections (UTIs) acquired during acute inpatient traumatic Spinal Cord Injury (tSCI) rehabilitation on Functional Independence Measure (FIM) gains.DesignRetrospective chart review of consecutive patients with tSCI admitted to an acute rehabilitation facility from 2007-2012. The primary outcome was FIM scores and the association with UTI.ResultsThe sample included 110 patients and 70 acquired UTIs. No demographic differences were observed between groups with and without UTI. Those with UTIs had significantly lower FIM motor scores, on admission, discharge, and gain, as well as lower FIM efficiency and longer lengths of stay compared to those without a UTI. Recurrence of UTI was associated with increased length of stay, but did not impact FIM motor gains.ConclusionsThere was a statistically significant correlation between acquired UTIs and lower FIM motor scores on admission, gain, and discharge in tSCI rehabilitation. The correlation of UTI and decreased FIM gains are similar to other neurorehabilitation populations with UTI occurrence. UTIs are an important negative variable when measuring functional outcomes in rehabilitation. Further prospective studies should be performed to investigate this correlation.
Project description:Spinal cord injury (SCI)-induced bone loss represents the most severe osteoporosis with no effective treatment. Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae, and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography (µCT), micro-finite element, histology, and serum biochemical analyses. At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.