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Find video protocols related to scientific articles indexed in Pubmed.
The Association of Preoperative Cervical Spine Alignment with Spinal Cord Magnetic Resonance Imaging Hyperintensity and Myelopathy Severity: Analysis of a Series of 124 Cases.
Spine
PUBLISHED: 10-25-2014
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Study Design. This is an ambispective analysis of a prospectively-followed cohort of cervical spondylotic myelopathy (CSM) patients.Objective. The goal of this study was to evaluate the impact of sagittal alignment on magnetic resonance imaging (MRI) abnormalities in the cervical spinal cord as well as myelopathy severity in a prospective series of surgical patients.Summary of Background Data. There is emerging evidence that sagittal alignment of the cervical spine in patients with CSM may be associated with disease severity. The impact on actual spinal cord pathology is unclear, with suspected mechanisms including focal static ventral compression, repeated dynamic injury, and increased cord intramedullary tension. The relationship between sagittal imbalance and disease severity remains undefined.Methods. An ambispective analysis of prospectively collected data was performed of surgical patients with CSM at a single tertiary-care neurosurgical centre. Demographic data and measures of neurological disability were collected and analyzed for dependency on cervical spine alignment parameters including qualitative (kyphotic vs. lordotic) and quantitative (sagittal Cobb angle (C2-7) and sagittal vertical axis (SVA, C2-C7)). MRI cord signal hyperintensity at the most pathological level was also evaluated for dependency on the same alignment metrics. Multiple logistic regression analysis was utilized at the 0.05 level of significance with correction for multiple comparisons.Results. Among 124 CSM patients, kyphotic alignment was seen in 34% of patients and hyperintense T2 MRI signal was observed in 55% of patients. No difference in MRI signal or myelopathy severity was observed in univariate analysis on global alignment. Among kyphotic patients, quantitative MRI parameters and myelopathy severity were both correlated with increasing SVA, an observation not seen among lordotic patients.Conclusion. Global sagittal alignment and SVA interactively associate with quantitative MRI spinal cord signal abnormalities and worse CSM-related disability. The reciprocal relationships of SVA effect in kyphotic and lordotic patients may reflect an optimal spinal alignment to achieve during surgical management.
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The Influence of Time from Injury to Surgery on Motor Recovery and Length of Hospital Stay in Acute Traumatic Spinal Cord Injury: An Observational Canadian Cohort Study.
J. Neurotrauma
PUBLISHED: 10-22-2014
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Abstract To determine the influence of time from injury to surgery on neurological recovery and length of stay (LOS) in an observational cohort of individuals with traumatic spinal cord injury (tSCI), we analyzed the baseline and follow-up motor scores of participants in the Rick Hansen Spinal Cord Injury Registry to specifically assess the effect of an early (less than 24?h from injury) surgical procedure on motor recovery and on LOS. One thousand four hundred and ten patients who sustained acute tSCIs with baseline American Spinal Injury Association Impairment Scale (AIS) grades A, B, C, or D and were treated surgically were analyzed to determine the effect of the timing of surgery (24, 48, or 72?h from injury) on motor recovery and LOS. Depending on the distribution of data, we used different types of generalized linear models, including multiple linear regression, gamma regression, and negative binomial regression. Persons with incomplete AIS B, C, and D injuries from C2 to L2 demonstrated motor recovery improvement of an additional 6.3 motor points (SE=2.8 p<0.03) when they underwent surgical treatment within 24?h from the time of injury, compared with those who had surgery later than 24?h post-injury. This beneficial effect of early surgery on motor recovery was not seen in the patients with AIS A complete SCI. AIS A and B patients who received early surgery experienced shorter hospital LOS. While the issues of when to perform surgery and what specific operation to perform remain controversial, this work provides evidence that for an incomplete acute tSCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24?h from injury improves motor neurological recovery. Early surgery also reduces LOS.
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Views of people with traumatic spinal cord injury about the components of self-management programs and program delivery: a Canadian pilot study.
BMC Neurol
PUBLISHED: 10-10-2014
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Given the increasing emphasis on the community management of spinal cord injury (SCI), strategies that could be developed and implemented in order to empower and engage individuals with SCI in promoting their health and minimizing the risk of health conditions are required. A self-management program could be one approach to address these complex needs, including secondary complications. Thus, the objective of this study was to determine the importance attributed to the components of a self-management program by individuals with traumatic SCI and explore their views/opinions about the delivery of such a program.
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Reliability of the spinal instability neoplastic scale among radiologists: an assessment of instability secondary to spinal metastases.
AJR Am J Roentgenol
PUBLISHED: 09-24-2014
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The spinal instability neoplastic scale (SINS) is a new classification system for tumor-related spinal instability. The SINS may prove to be a valuable tool for radiologists to communicate with oncologists and surgeons in a standardized evidence-based manner. The objective of this study was to determine the inter- and intraobserver reliability and validity of the SINS among radiologists.
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Transplantation of Neural Stem Cells Clonally Derived from Embryonic Stem Cells Promotes Recovery After Murine Spinal Cord Injury.
Stem Cells Dev.
PUBLISHED: 09-22-2014
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The pathology of spinal cord injury (SCI) makes it appropriate for cell-based therapies. Treatments using neural stem cells (NSCs) in animal models of SCI have shown positive outcomes, although uncertainty remains regarding the optimal cell source. Pluripotent cell sources such as embryonic stem cells (ESCs) provide a limitless supply of therapeutic cells. NSCs derived using embryoid bodies (EB) from ESCs have shown tumorigenic potential. Clonal neurosphere generation is an alternative method to generate safer and more clinically relevant NSCs without the use of an EB stage for use in cell-based therapies. We generated clonally derived definitive NSCs (dNSCs) from ESC. These cells were transplanted into a mouse thoracic SCI model. Embryonic stem cell-derived definitive neural stem cell (ES-dNSC)-transplanted mice were compared with controls using behavioral measures and histopathological analysis of tissue. In addition, the role of remyelination in injury recovery was investigated using transmission electron microscopy. The SCI group that received ES-dNSC transplantation showed significant improvements in locomotor function compared with controls in open field and gait analysis. The cell treatment group had a significant enhancement of spared neural tissue. Immunohistological assessments showed that dNSCs differentiated primarily to oligodendrocytes. These cells were shown to express myelin basic protein, associate with axons, and support nodal architecture as well as display proper compact, multilayer myelination in electron microscopic analysis. This study provides strong evidence that dNSCs clonally derived from pluripotent cells using the default pathway of neuralization improve motor function after SCI and enhance sparing of neural tissue, while remaining safe and clinically relevant.
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Outcome of the upper limb in cervical spinal cord injury: Profiles of recovery and insights for clinical studies.
J Spinal Cord Med
PUBLISHED: 09-18-2014
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Background Improved appreciation of recovery profiles of sensory and motor function as well as complex motor functions (prehension) after cervical spinal cord injury (SCI) will be essential to inform clinical studies to consider primary and secondary outcome measures for interventions and the optimization of dosing and timing of therapies in acute and chronic SCI. Objectives (1) To define the sensory, motor, and prehension recovery profiles of the upper limb and hand in acute cervical SCI and (2) to confirm the impact of AIS severity and conversion on upper limb sensorimotor recovery. Methods An observational longitudinal cohort study consisting of serial testing of 53 patients with acute cervical SCI was conducted. International Standards of Neurological Classification of Spinal Cord Injury, Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP), Capabilities of Upper Extremity (CUE-Q) Questionnaire, and Spinal Cord Independence Measure III (SCIM-III) were administered at 0-10 days, 1, 3, 6, and 12 months. Analysis Change over time was plotted using mean and standard deviation of the total and subgroups of the sample. Results Individuals with traumatic tetraplegia show distinct patterns of recovery. Factors that distinguish homogeneous subgroups of the sample are: severity of injury (level of injury, completeness) at baseline and conversion from a complete to an incomplete injury. Conclusions In cervical SCI, clinical recovery can be assessed using standardized measures that distinguish levels of activity and impairment. Specific recovery profiles of the upper limb over the 1-year timecourse provide new insights and opportunity for combined analysis of recovery profiles for different clinical assessment tools of upper limb function which are meaningful to inform the design of study protocols.
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Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury.
J. Neurotrauma
PUBLISHED: 09-12-2014
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Abstract Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore- and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.
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An evidence-based medicine model for rare and often neglected neoplastic conditions.
J Neurosurg Spine
PUBLISHED: 09-05-2014
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Object The National Institutes of Health recommends strategies to obtain evidence for the treatment of rare conditions such as primary tumors of the spine (PTSs). These tumors have a low incidence and are pathologically heterogeneous, and treatment approaches are diverse. Appropriate evidence-based care is imperative. Failure to follow validated oncological principles may lead to unnecessary mortality and profound morbidity. This paper outlines a scientific model that provides significant evidence guiding the treatment of PTSs. Methods A four-stage approach was used: 1) planning: data from large-volume centers were reviewed to provide insight; 2) recruitment: centers were enrolled and provided the necessary infrastructure; 3) retrospective stage: existing medical records were reviewed and completed with survival data; and 4) prospective stage: prospective data collection has been implemented. The AOSpine Knowledge Forum Tumor designed six modules: demographic, clinical, diagnostic, therapeutic, local recurrence, survival, and perioperative morbidity data fields and provided funding. Results It took 18 months to implement Stages 1-3, while Stage 4 is ongoing. A total of 1495 tumor cases were captured and diagnosed as one of 18 PTS histotypes. In addition, a PTS biobank network has been created to link clinical data with tumor pathology and molecular analysis. Conclusions This scientific model has not only aggregated a large amount of PTS data, but has also established an international collaborative network of spine oncology centers. Access to large volumes of data will generate further research to guide and enhance PTS clinical management. This model could be applied to other rare neoplastic conditions. Clinical trial registration no.: NCT01643174 ( ClinicalTrials.gov ).
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Very high resolution ultrasound imaging for real-time quantitative visualization of vascular disruption after spinal cord injury.
J. Neurotrauma
PUBLISHED: 09-04-2014
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Abstract Spinal cord injury (SCI) is characterized by vascular disruption with intramedullary hemorrhage, alterations in blood-spinal cord barrier integrity, and perilesional ischemia. A safe and easily applied imaging technique to quantify evolving intraspinal vascular changes after SCI is lacking. We evaluated the utility of very high resolution ultrasound (VHRUS) imaging to assess SCI-induced vascular disruption in a clinically relevant rodent model. The spinal cords of Wistar rats were lesioned at the 11th thoracic vertebra (Th11) by a 35?g 1-minute clip compression. Three-dimensional quantification of intraspinal hemorrhage using VHRUS (at an acute 90-min and subacute 24-h time point post-SCI) was compared with lesional hemoglobin and extravasated Evans blue dye measured spectrophotometrically. The anatomy of hemorrhage was comparatively assessed using VHRUS and histology. Time-lapse videos demonstrated the evolution of parenchymal hemorrhage. VHRUS accurately depicted the structural (gray and white matter) and vascular anatomy of the spinal cord (after laminectomy) and was safely repeated in the same animal. After SCI, a hyperechoic signal extended from the lesion epicenter. Significant correlations were found between VHRUS signal and hemorrhage in the acute (r=0.88, p<0.0001) and subacute (r=0.85, p<0.0001) phases and extravasated Evans blue (a measure of vascular disruption) in the subacute phase (r=0.94, p<0.0001). Time-lapse videos demonstrated that the expanding parenchymal hemorrhage is preceded by new perilesional hemorrhagic foci. VHRUS enables real-time quantitative live anatomical imaging of acute and subacute vascular disruption after SCI in rats. This technique has important scientific and clinical translational applications.
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Spine stereotactic body radiotherapy for renal cell cancer spinal metastases: analysis of outcomes and risk of vertebral compression fracture.
J Neurosurg Spine
PUBLISHED: 08-29-2014
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Object The aim of this study was to evaluate local control (LC) and the risk of vertebral compression fracture (VCF) after stereotactic body radiotherapy (SBRT) in patients with renal cell cancer spinal metastases. Methods Prospectively collected data on 71 spinal segments treated with SBRT in 37 patients were reviewed. The median follow-up was 12.3 months (range 1.2-55.4 months). The LC rate was assessed based on each spinal segment treated and overall survival (OS) according to each patient treated. Sixty of 71 segments (85%) were radiation naive, 11 of 71 (15%) were previously irradiated, and 10 of 71 (14%) were treated with postoperative SBRT. The median SBRT total dose and number of fractions were 24 Gy and 2, respectively. The VCF analysis also included evaluation of the Spinal Instability Neoplastic Score criteria. Results The 1-year OS and LC rates were 64% and 83%, respectively. Multivariate analysis identified oligometastatic disease (13 of 37 patients) as a positive prognostic factor (p = 0.018) for OS. Of 61 non-postoperative spinal segments treated, 10 (16%) developed VCFs; 3 of 10 were de novo VCFs and 7 of 10 occurred as progression of an existing VCF. The 1-year VCF-free probability rate was 82%. Multivariate analysis identified single-fraction SBRT and baseline VCF as significant predictors of SBRT-induced VCF (p = 0.028 and p = 0.012, respectively). Conclusions Spine SBRT yields high rates of local tumor control in patients with renal cell cancer. Baseline VCF and 18-24 Gy delivered in a single fraction were predictive of further collapse. Patients with oligometastatic disease may benefit most from such aggressive local therapy, given the prolonged survival observed.
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Neurological outcomes of animal models of uterine artery ligation and relevance to human intrauterine growth restriction: a systematic review.
Dev Med Child Neurol
PUBLISHED: 08-18-2014
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This review explores the molecular, neurological, and behavioural outcomes in animal models of uterine artery ligation. We analyse the relevance of this type of model to the pathological and functional phenotypes that are consistent with cerebral palsy and its developmental comorbidities in humans.
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Community engagement and knowledge translation: progress and challenge in autism research.
Autism
PUBLISHED: 08-15-2014
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The last decade has seen significant growth in scientific understanding and public awareness of autism. There is still a long road ahead before this awareness can be matched with parallel improvements in evidence-based practice. The process of translating evidence into community care has been hampered by the seeming disconnect between the mainstream scientific research agenda and the immediate priorities of many communities. The need for community engagement in the process of translating knowledge into impact has been recognized. However, there remains little consensus or empirical data regarding the process of such engagement and how to measure its impact. We shed light on a number of engagement models and tools, previously advocated in health research, as they apply to autism research. Furthermore, we illustrate the utility of such tools in supporting identification of knowledge gaps and priorities, using two community-based case studies. The case studies illustrate that information generated from research is indeed relevant and critical for knowledge users in the community. Simple and systematic methods can support the translation and uptake of knowledge in diverse communities, therefore enhancing engagement with research and bridging research findings with immediate community needs.
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Neural precursor cell transplantation enhances functional recovery and reduces astrogliosis in bilateral compressive/contusive cervical spinal cord injury.
Stem Cells Transl Med
PUBLISHED: 08-08-2014
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Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation.
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Changes in gap junction expression and function following ischemic injury of spinal cord white matter.
J. Neurophysiol.
PUBLISHED: 07-30-2014
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Gap junctions are widely present in spinal cord white matter; however, their role in modulating the dynamics of axonal dysfunction remains largely unexplored. We hypothesized that inhibition of gap junctions reduces the loss of axonal function during oxygen and glucose deprivation (OGD). The functional role of gap junctions was assessed by electrophysiological recordings of compound action potentials (CAPs) in Wistar rat spinal cord slices with the sucrose gap technique. The in vitro slices were subjected to 30-min OGD. Gap junction connexin (Cx) mRNA expression was determined by qPCR and normalized to ?-actin. A 30-min OGD resulted in reduction of CAPs to 14.8 ± 4.6% of their pre-OGD amplitude (n = 5). In the presence of gap junction blockers carbenoxolone (Cbx; 100 ?M) and 1-octanol (Oct; 300 ?M), the CAP reduction in OGD was to only 35.7 ± 5.7% of pre-OGD amplitude in Cbx (n = 9) and to 37.4 ± 8.9% of pre-OGD amplitude in Oct (n = 10). Both drugs also noticeably prolonged the half-decline time of CAP amplitudes in OGD from 6.0 min in no-drug conditions to 9.6 min in the presence of Cbx and to 7.7 min in the presence of Oct, suggesting that blocking gap junctions reduces conduction loss during OGD. With application of Cbx and Oct in the setting of OGD, expression of Cx30 and Cx43 mRNA was downregulated. Our data provide new insights into the role of gap junctions in white matter ischemia and reveal the necessity of a cautious approach in determining detrimental or beneficial effects of gap junction blockade in white matter ischemia.
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Minimizing errors in acute traumatic spinal cord injury trials by acknowledging the heterogeneity of spinal cord anatomy and injury severity: an observational Canadian cohort analysis.
J. Neurotrauma
PUBLISHED: 07-08-2014
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Clinical trials of therapies for acute traumatic spinal cord injury (tSCI) have failed to convincingly demonstrate efficacy in improving neurologic function. Failing to acknowledge the heterogeneity of these injuries and under-appreciating the impact of the most important baseline prognostic variables likely contributes to this translational failure. Our hypothesis was that neurological level and severity of initial injury (measured by the American Spinal Injury Association Impairment Scale [AIS]) act jointly and are the major determinants of motor recovery. Our objective was to quantify the influence of these variables when considered together on early motor score recovery following acute tSCI. Eight hundred thirty-six participants from the Rick Hansen Spinal Cord Injury Registry were analyzed for motor score improvement from baseline to follow-up. In AIS A, B, and C patients, cervical and thoracic injuries displayed significantly different motor score recovery. AIS A patients with thoracic (T2-T10) and thoracolumbar (T11-L2) injuries had significantly different motor improvement. High (C1-C4) and low (C5-T1) cervical injuries demonstrated differences in upper extremity motor recovery in AIS B, C, and D. A hypothetical clinical trial example demonstrated the benefits of stratifying on neurological level and severity of injury. Clinically meaningful motor score recovery is predictably related to the neurological level of injury and the severity of the baseline neurological impairment. Stratifying clinical trial cohorts using a joint distribution of these two variables will enhance a study's chance of identifying a true treatment effect and minimize the risk of misattributed treatment effects. Clinical studies should stratify participants based on these factors and record the number of participants and their mean baseline motor scores for each category of this joint distribution as part of the reporting of participant characteristics. Improved clinical trial design is a high priority as new therapies and interventions for tSCI emerge.
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Operative and nonoperative adverse events in the management of traumatic fractures of the thoracolumbar spine: a systematic review.
Neurosurg Focus
PUBLISHED: 07-02-2014
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Thoracolumbar spine injuries are commonly encountered in patients with trauma, accounting for almost 90% of all spinal fractures. Thoracolumbar burst fractures comprise a high percentage of these traumatic fractures (45%), and approximately half of the patients with this injury pattern are neurologically intact. However, a debate over complication rates associated with operative versus nonoperative management of various thoracolumbar fracture morphologies is ongoing, particularly concerning those patients presenting without a neurological deficit.
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Timing of surgery in thoracolumbar trauma: is early intervention safe?
Neurosurg Focus
PUBLISHED: 07-02-2014
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The understanding of the optimal surgical timing for stabilization in thoracolumbar fractures is severely limited. Thoracolumbar spine fractures can be devastating injuries and are often associated with significant morbidity and mortality. The role of early surgical stabilization (within 48-72 hours of injury) as a vehicle to improve outcomes in these patients has generated significant interest. Goals of early stabilization include improved neurological recovery, faster pulmonary recovery, improved pain control, and decreased health care costs. Opponents cite the potential for increased bleeding, hypotension, and the risk of further cord injury as a few factors that weigh against early stabilization. The concept of spinal cord injury and its relationship to surgical timing remains in question. However, when neurological outcomes are eliminated from the equation, certain measures have shown positive influences from prompt surgical fixation. Early fixation of thoracolumbar spine fractures can significantly decrease the duration of hospital stay and the number of days in the intensive care unit. Additionally, prompt stabilization can reduce rates of pulmonary complications. This includes decreased rates of pneumonia and fewer days on ventilator support. Cost analysis revealed as much as $80,000 in savings per patient with early stabilization. All of these benefits come without an increase in morbidity or evidence of increased mortality. In addition, there is no evidence that early stabilization has any ill effect on the injured or uninjured spinal cord. Based on the existing data, early fixation of thoracolumbar fractures has been linked with positive outcomes without clear evidence of negative impacts on the patient's neurological status, associated morbidities, or mortality. These procedures can be viewed as "damage control" and may consist of simple posterior instrumentation or open reductions with internal fixation as indicated. Based on the current literature it is advisable to proceed with early surgical stabilization of thoracolumbar fractures in a well-resuscitated patient, unless extenuating medical conditions would prevent it.
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Tumor extravasation following a cement augmentation procedure for vertebral compression fracture in metastatic spinal disease.
J Neurosurg Spine
PUBLISHED: 06-06-2014
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Balloon kyphoplasty (BKP) has been proven to be safe and effective in the management of pathological vertebral compression fracture (VCF) due to metastatic spinal disease. The most common serious complications related to BKP include cement extravasation and new fractures at adjacent levels. Although the potential for "tumor extravasation" has been discussed as a potential iatrogenic complication, it has yet to be confirmed. The authors report on 2 cases of tumor extravasation following BKP, which they base on an observed unusual rapid tumor spread pattern into the adjacent tissues. They postulate that by increasing the vertebral body internal pressure and disrupting the tissues during balloon inflation and cement application, a soft-tissue tumor can be forced beyond the vertebral bony boundaries through pathological cortical defects. This phenomenon can manifest radiologically as subligamentous spread and/or extension into venous sinusoids, resulting in epidural venous plexus involvement, with subsequent tumor migration into the adjacent vertebral segments. Accordingly, the authors advise caution in using BKP when significant epidural tumor is present. The complication they encountered has caused them to modify their preference such that they now first use radiosurgery and subsequently BKP to ensure the target is appropriately treated, and they are currently developing possible modifications of procedural technique to reduce the risk.
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Improving access to emergent spinal care through knowledge translation: an ethnographic study.
BMC Health Serv Res
PUBLISHED: 04-04-2014
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For patients and family members, access to timely specialty medical care for emergent spinal conditions is a significant stressor to an already serious condition. Timing to surgical care for emergent spinal conditions such as spinal trauma is an important predictor of outcome. However, few studies have explored ethnographically the views of surgeons and other key stakeholders on issues related to patient access and care for emergent spine conditions. The primary study objective was to determine the challenges to the provision of timely care as well as to identify areas of opportunities to enhance care delivery.
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Treatment of spinal cord injury with intravenous immunoglobulin G: preliminary evidence and future perspectives.
J. Clin. Immunol.
PUBLISHED: 03-07-2014
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Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease, with a good safety profile. Thus, it is a promising treatment candidate for SCI. Indeed, IVIg has been shown by our team to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J Neuroinflammation 9:224, 2012). Here we review published data in the context of relevant mechanisms of action that have been proposed for IVIg in other conditions. We hope that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation.
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Perceived facilitators and barriers to self-management in individuals with traumatic spinal cord injury: a qualitative descriptive study.
BMC Neurol
PUBLISHED: 03-05-2014
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Current evidence has suggested the need for increased self-management support efforts in spinal cord injury (SCI) to reduce secondary complications. However, current self-management programs may not be suitable for the unique needs of individuals with SCI, including reduced mobility and the importance of attendant care. There is a need for greater understanding of the self-management strategies adopted by individuals with SCI and the potential need for a tailored self-management program. Thus, the purpose of the current study was to understand the perceived facilitators and barriers to self-management to prevent secondary complications.
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Pathobiology of cervical spondylotic myelopathy.
Eur Spine J
PUBLISHED: 02-20-2014
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In this narrative review, we aim to outline what is currently known about the pathophysiology of cervical spondylotic myelopathy (CSM), the most common cause of spinal cord dysfunction. In particular, we note the unique factors that distinguish it from acute spinal cord injury. Despite its common occurrence, the reasons why some patients develop severe symptomatology while others have few or no symptoms despite radiographic evidence confirming similar degrees of compression is poorly understood. Neither is there a clear understanding of why certain patients have a stable clinical myelopathy and others present with only mild myelopathy. Moreover, the precise molecular mechanisms which contribute to the pathogenesis of the disease are incompletely understood. The current treatment method is decompression of the spinal cord but a lack of clinically relevant models of CSM have hindered the understanding of the full pathophysiology which would aid the development of new therapeutic avenues of investigation. Further elucidation of the role of ischemia, currently a source of debate, as well as the complex cascade of biomolecular events as a result of the unique pathophysiology in this disease will pave the way for further neuroprotective strategies to be developed to attenuate the physiological consequences of surgical decompression and augment its benefits.
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Examination of the Combined Effects of Chondroitinase ABC, Growth Factors and Locomotor Training following Compressive Spinal Cord Injury on Neuroanatomical Plasticity and Kinematics.
PLoS ONE
PUBLISHED: 01-01-2014
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While several cellular and pharmacological treatments have been evaluated following spinal cord injury (SCI) in animal models, it is increasingly recognized that approaches to address the glial scar, including the use of chondroitinase ABC (ChABC), can facilitate neuroanatomical plasticity. Moreover, increasing evidence suggests that combinatorial strategies are key to unlocking the plasticity that is enabled by ChABC. Given this, we evaluated the anatomical and functional consequences of ChABC in a combinatorial approach that also included growth factor (EGF, FGF2 and PDGF-AA) treatments and daily treadmill training on the recovery of hindlimb locomotion in rats with mid thoracic clip compression SCI. Using quantitative neuroanatomical and kinematic assessments, we demonstrate that the combined therapy significantly enhanced the neuroanatomical plasticity of major descending spinal tracts such as corticospinal and serotonergic-spinal pathways. Additionally, the pharmacological treatment attenuated chronic astrogliosis and inflammation at and adjacent to the lesion with the modest synergistic effects of treadmill training. We also observed a trend for earlier recovery of locomotion accompanied by an improvement of the overall angular excursions in rats treated with ChABC and growth factors in the first 4 weeks after SCI. At the end of the 7-week recovery period, rats from all groups exhibited an impressive spontaneous recovery of the kinematic parameters during locomotion on treadmill. However, although the combinatorial treatment led to clear chronic neuroanatomical plasticity, these structural changes did not translate to an additional long-term improvement of locomotor parameters studied including hindlimb-forelimb coupling. These findings demonstrate the beneficial effects of combined ChABC, growth factors and locomotor training on the plasticity of the injured spinal cord and the potential to induce earlier neurobehavioral recovery. However, additional approaches such as stem cell therapies or a more adapted treadmill training protocol may be required to optimize this repair strategy in order to induce sustained functional locomotor improvement.
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Global prevalence and incidence of traumatic spinal cord injury.
Clin Epidemiol
PUBLISHED: 01-01-2014
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Spinal cord injury (SCI) is a traumatic event that impacts a patient's physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI.
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Delayed administration of a bio-engineered zinc-finger VEGF-A gene therapy is neuroprotective and attenuates allodynia following traumatic spinal cord injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Following spinal cord injury (SCI) there are drastic changes that occur in the spinal microvasculature, including ischemia, hemorrhage, endothelial cell death and blood-spinal cord barrier disruption. Vascular endothelial growth factor-A (VEGF-A) is a pleiotropic factor recognized for its pro-angiogenic properties; however, VEGF has recently been shown to provide neuroprotection. We hypothesized that delivery of AdV-ZFP-VEGF--an adenovirally delivered bio-engineered zinc-finger transcription factor that promotes endogenous VEGF-A expression--would result in angiogenesis, neuroprotection and functional recovery following SCI. This novel VEGF gene therapy induces the endogenous production of multiple VEGF-A isoforms; a critical factor for proper vascular development and repair. Briefly, female Wistar rats--under cyclosporin immunosuppression--received a 35 g clip-compression injury and were administered AdV-ZFP-VEGF or AdV-eGFP at 24 hours post-SCI. qRT-PCR and Western Blot analysis of VEGF-A mRNA and protein, showed significant increases in VEGF-A expression in AdV-ZFP-VEGF treated animals (p<0.001 and p<0.05, respectively). Analysis of NF200, TUNEL, and RECA-1 indicated that AdV-ZFP-VEGF increased axonal preservation (p<0.05), reduced cell death (p<0.01), and increased blood vessels (p<0.01), respectively. Moreover, AdV-ZFP-VEGF resulted in a 10% increase in blood vessel proliferation (p<0.001). Catwalk™ analysis showed AdV-ZFP-VEGF treatment dramatically improves hindlimb weight support (p<0.05) and increases hindlimb swing speed (p<0.02) when compared to control animals. Finally, AdV-ZFP-VEGF administration provided a significant reduction in allodynia (p<0.01). Overall, the results of this study indicate that AdV-ZFP-VEGF administration can be delivered in a clinically relevant time-window following SCI (24 hours) and provide significant molecular and functional benefits.
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Hypoxic locomotor rehabilitation for incomplete spinal cord injury: Not an oxymoron.
Neurology
PUBLISHED: 11-27-2013
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Neurorehabilitation is experiencing a paradigm shift toward treatments that are both effective and efficient, driven by increasing demands upon clinical practice and the staggering burden of health care expenditures. The impetus is toward finding ways to maximize the potential for recovery by targeting networks spared by the lesion. Residual networks can undergo reorganization with recovery, involving plasticity or improved efficiency at the level of preexisting synapses and sprouting from surviving fibers for creation of new circuits.(1) Capitalizing on the potential for plasticity and employing methods that can augment this potential are the 2 driving themes in current rehabilitation research. In this issue of Neurology®, Hayes et al.(2) present a study that sought to address both.
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Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 10-17-2013
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Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in KLK expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. Kallikrein 9 showed the most marked changes and remained chronically elevated. Importantly, a subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI cases examined. Together, these findings demonstrate that elevated levels of a significant subset of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and, therefore, represent new potential targets for the development of neuroprotective strategies.
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A Prospective, Multicenter, Phase I Matched-Comparison Group Trial of Safety, Pharmacokinetics, and Preliminary Efficacy of Riluzole in Patients with Traumatic Spinal Cord Injury.
J. Neurotrauma
PUBLISHED: 10-11-2013
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Abstract A prospective, multicenter phase I trial was undertaken by the North American Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety of, as well as obtain pilot data on, the effects of riluzole on neurological outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites between April 2010 and June 2011. Patients received 50?mg of riluzole PO/NG twice-daily, within 12?h of SCI, for 14 days. Peak and trough plasma concentrations were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic exposure to riluzole varied significantly between patients. On the same dose basis, Cmax did not reach levels comparable to those in patients with amyotrophic lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than on day 14, resulting from a lower clearance and a smaller volume of distribution on day 3. Rates of medical complications, adverse events, and progression of neurological status were evaluated by comparison with matched patients in the NACTN SCI Registry. Medical complications in riluzole-treated patients occurred with incidences similar to those in patients in the comparison group. Mild-to-moderate increase in liver enzyme and bilirubin levels were found in 14-70% of patients for different enzymes. Three patients had borderline severe elevations of enzymes. No patient had elevated bilirubin on day 14 of administration of riluzole. There were no serious adverse events related to riluzole and no deaths. The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2 points from admission to 90 days, compared to 15.7 points for 26 registry patients, a 15.5-point difference (p=0.021). Patients with cervical injuries treated with riluzole had more-robust conversions of impairment grades to higher grades than the comparison group.
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Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy.
Neurobiol. Dis.
PUBLISHED: 10-04-2013
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Cervical spondylotic myelopathy (CSM) is the commonest cause of spinal cord impairment worldwide and despite surgical treatment, it is commonly associated with chronic neuropathic pain and neurological impairment. Based on data suggesting a key role of sodium and glutamate mediated cellular injury in models of spinal cord compression, we examined whether riluzole, a sodium channel/glutamate blocker, could improve neurobehavioral outcomes in a rat model of CSM. To produce chronic progressive compression of the cervical spinal cord, we used an established model of graded mechanical cord compromise developed in our laboratory. The chronic (8weeks) mechanical compression of the cervical spinal cord resulted in persistent mechanical allodynia and thermal hyperalgesia at 8weeks. Moreover, we found increased expression of phosphorylated NR1 and NR2B in the dorsal horns as well as astrogliosis and increased microglia expression in the dorsal horns after mechanical compression. Following daily systemic administration for 7weeks after the induction of compression, riluzole (8mg/kg) significantly attenuated forelimb and hindlimb mechanical allodynia and alleviated thermal hyperalgesia in the tail. Importantly, riluzole led to a decrease in swing phase duration, an increase in hind leg swing speed and an increase paw intensity in gait analysis. Riluzole also decreased the number of phosphorylated NR1 and phosphorylated NR2B positive cells in the dorsal horns and the microglia activation in the dorsal horns. Together, our results indicate that systemic riluzole administration during chronic cervical spinal cord compression is effective at protecting spinal cord tissue, preserving neurobehavioral function and alleviating neuropathic pain, possibly by decreasing NMDA receptor phosphorylation in astrocytes and by eliminating microglia activation. As such, riluzole represents a promising clinical treatment for CSM.
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The SCIentinel study - prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS) - study protocol and interim feasibility data.
BMC Neurol
PUBLISHED: 09-24-2013
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Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome ("disease modifying factor"). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is neurogenic including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury.Methods/design: SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i) <31 hours, ii) 31--55 hours, iii) 7 days, iv) 14 days, and v) 10 weeks post-trauma. Assessment includes infections, concomitant injury, medication and neurological classification using American Spinal Injury Association impairment scale (AIS) and neurological level. Laboratory analyses comprise haematological profiling, immunophenotyping, including HLA-DR expression on monocytes, cytokines and gene expression of immune modulators. We provide an administrative interim analysis of the recruitment schedule of the trial.
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Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy.
Neuro-oncology
PUBLISHED: 09-24-2013
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Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival.
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A clinical prediction model to determine outcomes in patients with cervical spondylotic myelopathy undergoing surgical treatment: data from the prospective, multi-center AOSpine North America study.
J Bone Joint Surg Am
PUBLISHED: 09-20-2013
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Cervical spondylotic myelopathy is a progressive spine disease and the most common cause of spinal cord dysfunction worldwide. The objective of this study was to develop a prediction model, based on data from a prospective multi-center study, relating a combination of clinical and imaging variables to surgical outcome in patients with cervical spondylotic myelopathy.
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Efficacy and safety of surgical decompression in patients with cervical spondylotic myelopathy: results of the AOSpine North America prospective multi-center study.
J Bone Joint Surg Am
PUBLISHED: 09-20-2013
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Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction worldwide. The objective of this study was to evaluate the impact of surgical decompression on functional, quality-of-life, and disability outcomes at one year after surgery in a large cohort of patients with this condition.
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Spinal cord injury: Visualizing plasticity and repair in the injured CNS.
Nat Rev Neurol
PUBLISHED: 09-10-2013
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The heterogeneity of traumatic spinal cord injury necessitates large clinical trials to differentiate natural improvements from enhanced recovery due to therapeutic intervention. Recent development of an imaging biomarker to visualize changes in the corticospinal motor system could offer the opportunity to directly visualize anatomical evidence of repair, regeneration and plasticity.
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Meeting the privacy requirements for the development of a multi-centre patient registry in Canada: the Rick Hansen Spinal Cord Injury Registry.
Healthc Policy
PUBLISHED: 08-24-2013
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Privacy legislation addresses concerns regarding the privacy of personal information; however, its interpretation by research ethics boards has resulted in significant challenges to the collection, management, use and disclosure of personal health information for multi-centre research studies. This paper describes the strategy used to develop the national Rick Hansen Spinal Cord Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked against best practices. An analysis of the regional and national privacy legislation was conducted to determine the requirements for each of the 31 local RHSCIR sites and the national RHSCIR office. A national privacy and security framework was created for RHSCIR that includes a governance structure, standard operating procedures, training processes, physical and technical security and privacy impact assessments. The framework meets a high-water mark in ensuring privacy and security of personal health information nationally and may assist in the development of other national or international research initiatives.
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Myelopathy and spinal deformity: relevance of spinal alignment in planning surgical intervention for degenerative cervical myelopathy.
Spine
PUBLISHED: 08-22-2013
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Surgical management of degenerative cervical myelopathy requires careful pathoanatomic consideration to select between various surgical options from both anterior and posterior approach. Hitherto, unexplored is the relevance of cervical deformity to the pathophysiology of such neurological disability, and whether correction of that deformity should be a surgical objective when planning for reconstruction after spinal cord decompression. Such correction could address both the static cord compression and the dynamic repetitive cord injury, while also restoring more normal biomechanics to the cervical spine. The articles in this focus issues section on cervical spinal deformity reveal that cervical sagittal alignment is geometrically related to thoracolumbar spinal pelvic alignment and to T1 slope, and that it is further clinically correlated to regional disability and general health scores and to myelopathy severity. These conclusions are based on narrative reviews and a selection of primary research data, reflecting the nascency of this field. They further recommend for preoperative assessment of spinal alignment when significant deformity is suspected, and that correction of cervical kyphosis should be an objective when surgery is planned.
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Surgical management of degenerative cervical myelopathy: a consensus statement.
Spine
PUBLISHED: 08-22-2013
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Degenerative cervical myelopathy (DCM), including cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament, presents a heterogeneous set of variables reflecting its complex nature. Multiple studies in the past have attempted to elucidate an ideal surgical algorithm that surgeons may use when treating these patients, unfortunately all studies to date, including the rigorous systematic review used in this focus issue, have fallen short in identifying a superior approach when addressing DCM. Likely because of a superior approach being nonexistent because there are multiple pathoanatomical considerations. In addition to the multitude of variables that spine surgeons face when deciding the treatment options for patients with DCM, the previous studies that have been published, unfortunately, lack in consistent outcome and complication reporting. Therefore, synthesizing a treatment algorithm remains difficult, however, the articles in this focus issue use the GRADE system to assess the overall quality (strength) of available evidence and, where appropriate, formulate evidence-based recommendations. Factors that should be included in surgical decision making are the sagittal alignment, anatomical location of the compressive pathology, number of levels of compression, presence of absence or instability or subluxation, the type compressive pathology (e.g., spondylosis vs. ossification of the posterior longitudinal ligament), neck anatomy, bone quality, and surgeon experience or preference. Fortunately, as reviewed in the accompanying articles, a number of excellent surgical options exist that can be selected on the basis of the aforementioned pathoanatomical considerations.
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Symptomatic progression of cervical myelopathy and the role of nonsurgical management: a consensus statement.
Spine
PUBLISHED: 08-22-2013
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This section of the cervical spondylotic myelopathy Spine focus issue collates the existing evidence related to natural history and nonoperative management. In the case of patients with symptomatic cervical spondylotic myelopathy treated nonoperatively, while 20% to 62% will deteriorate at 3 to 6 years of follow-up, no specific patient or disease characteristics have been shown to predict this change reliably. For patients without myelopathy with spondylotic cord compression, the rate of myelopathy development is approximately 8% at 1 year and approximately 23% at 4 years of follow-up. Clinical and/or electrophysiological evidence of cervical radiculopathy has been shown to predict such progression and should prompt strong consideration of surgical decompression. With respect to nonoperative care, in the case of mild myelopathy, there is low evidence that such treatment may have a role; for moderate and severe myelopathy, this treatment results in outcomes inferior to those of surgery and is not recommended. Given the unpredictably progressive nature of cervical myelopathy, the indications for nonoperative management are ostensibly limited. Finally, the preclinical rationale and clinical translation of a putative neuroprotective drug, which may one day serve to augment the effects of surgery in the treatment of cervical spondylotic myelopathy, is presented and discussed.
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Diagnosis, heritability, and outcome assessment in cervical myelopathy: a consensus statement.
Spine
PUBLISHED: 08-22-2013
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This section of the cervical spondylotic myelopathy (CSM) Spine focus issue collates evidence related to diagnosis, outcome assessment, and genetics. Given that a variety of different disease states can present similarly, a guide for diagnosing and differentiating CSM from other neurological conditions is initially presented. Although the value of magnetic resonance imaging in diagnosing CSM is cemented, its value as a tool to predict future outcome is less well established. To this end, the existing evidence suggests that although increased T2 cord signal is of limited value, the pairing of high T2 signal with low T1 signal, or a high T2 to T1 signal ratio, is associated with a reduced potential for neurological recovery at follow-up. Outcome assessment in CSM is of paramount importance when monitoring patients clinical course or measuring the efficacy of therapeutic interventions. Here, the main outcome measures that have been used to assess patients with CSM are reviewed. At present, we recommend that clinicians acquire the modified Japanese Orthopaedic Association scale score and the Neck Disability Index on all patients with CSM at presentation and follow-up. Finally, in regard to genetics, the existing evidence seems to support the principle of an inherited predisposition to both CSM and ossification of the posterior longitudinal ligament. Although several genetic polymorphisms have been consistently associated with ossification of the posterior longitudinal ligament, no specific polymorphisms were consistently associated with CSM.
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Pathophysiology and natural history of cervical spondylotic myelopathy.
Spine
PUBLISHED: 08-22-2013
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This study is a combination of narrative and systematic review.
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Cervical spondylotic myelopathy: current state of the art and future directions.
Spine
PUBLISHED: 08-22-2013
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Narrative overview of the focus issue on cervical spondylotic myelopathy (CSM).
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Vertebral compression fracture after spine stereotactic body radiotherapy: a multi-institutional analysis with a focus on radiation dose and the spinal instability neoplastic score.
J. Clin. Oncol.
PUBLISHED: 08-19-2013
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Vertebral compression fracture (VCF) is increasingly recognized as an adverse event after spine stereotactic body radiotherapy (SBRT). We report a multi-institutional study aimed at clarifying the risk and predictive factors associated with VCF.
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The potential for stem cells in cerebral palsy--piecing together the puzzle.
Semin Pediatr Neurol
PUBLISHED: 08-17-2013
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The substantial socioeconomic burden of a diagnosis of cerebral palsy, coupled with a positive anecdotal and media spin on stem cell treatments, drives many affected families to seek information and treatment outside of the current clinical and scientific realm. Preclinical studies using several types of stem and adult cells--including mesenchymal stem cells, neural precursor cells, olfactory ensheathing glia and Schwann cells--have demonstrated some regenerative and functional efficacy in neurologic paradigms. This paper describes the most common cell types investigated for transplant in vivo and summarizes the current state of early-phase clinical trials. It investigates the most relevant and promising coadministered therapies, including rehabilitation, drug targeting, magnetic stimulation, and bioengineering approaches. We highlight the need for adjunctive combinatorial strategies to successfully transfer stem cell treatments from bench to bedside.
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Adult-Derived Pluripotent Stem Cells.
World Neurosurg
PUBLISHED: 08-07-2013
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The global incidence of spinal cord injury (SCI) is 15-40 cases per million people, with the socioeconomic and healthcare costs amounting to nearly $10 billion per annum in the USA alone. Despite substantial advances in medical care and surgical technology, many patients with SCI still experience significant long-term neurologic disability. Cellular transplantation offers a promising therapy to address the multifactorial nature of SCI in both the subacute and chronic phase of the injury to promote central nervous system repair and regeneration and to augment existing therapies. Adult-derived stem cells are the least ethically challenging stem cells but, until recently, a major hurdle has been inducing pluripotency to generate the required neural lineages. Improved generation and transfection techniques, combined with positive experimental outcomes in SCI models, suggest that adult-derived induced pluripotent stem cells could be a genuine alternative to embryonic stem cells for clinical treatments. For translation from bench to bedside, the efficacy of induced pluripotent stem cell-derived neural stem and progenitor cells in suitable SCI models needs to be validated further and backed up with rigorous early-stage clinical trials.
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A summary of assessment tools for patients suffering from cervical spondylotic myelopathy: a systematic review on validity, reliability and responsiveness.
Eur Spine J
PUBLISHED: 07-28-2013
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One of the objectives of this review is to summarize the important features of a good scale. A second aim is to conduct a systematic review to identify scales that can detect the presence of cervical myelopathy and to determine their psychometric properties including validity, reliability and responsiveness.
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Effects of adult neural precursor-derived myelination on axonal function in the perinatal congenitally dysmyelinated brain: optimizing time of intervention, developing accurate prediction models, and enhancing performance.
J. Neurosci.
PUBLISHED: 07-19-2013
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Stem cell repair shows substantial translational potential for neurological injury, but the mechanisms of action remain unclear. This study aimed to investigate whether transplanted stem cells could induce comprehensive functional remyelination. Subventricular zone (SVZ)-derived adult neural precursor cells (aNPCs) were injected bilaterally into major cerebral white matter tracts of myelin-deficient shiverer mice on postnatal day (P) 0, P7, and P21. Tripotential NPCs, when transplanted in vivo, integrated anatomically and functionally into local white matter and preferentially became Olig2+, Myelin Associated Glycoprotein-positive, Myelin Basic Protein-positive oligodendrocytes, rather than Glial Fibrillary Acidic Protein-positive astrocytes or Neurofiliment 200-positive neurons. Processes interacted with axons and transmission electron microscopy showed multilamellar axonal ensheathment. Nodal architecture was restored and by quantifying these anatomical parameters a computer model was generated that accurately predicted action potential velocity, determined by ex vivo slice recordings. Although there was no obvious phenotypic improvement in transplanted shi/shis, myelinated axons exhibited faster conduction, lower activation threshold, less refractoriness, and improved response to high-frequency stimulation than dysmyelinated counterparts. Furthermore, they showed improved resilience to ischemic insult, a promising finding in the context of perinatal brain injury. This study describes, for the first time mechanistically, the functional characteristics and anatomical integration of nonimmortalized donor SVZ-derived murine aNPCs in the dysmyelinated brain at key developmental time points.
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Defining age-related differences in outcome after traumatic spinal cord injury: analysis of a combined, multicenter dataset.
Spine J
PUBLISHED: 07-15-2013
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The existing evidence suggests that, although older spinal cord injury (SCI) patients experience a similar degree of neurologic recovery to younger patients, older patients experience diminished functional outcomes at follow-up. However, all studies have assumed that the impact of age on functional outcome is the same across the spectrum of injury severity.
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Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases.
Lancet Oncol.
PUBLISHED: 07-03-2013
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The use of stereotactic body radiotherapy for metastatic spinal tumours is increasing. Serious adverse events for this treatment include vertebral compression fracture (VCF) and radiation myelopathy. Although VCF is a fairly low-risk adverse event (approximately 5% risk) after conventional radiotherapy, crude risk estimates for VCF after spinal SBRT range from 11% to 39%. In this Review, we summarise the evidence and predictive factors for VCF induced by spinal SBRT, review the pathophysiology of VCF in the metastatic spine, and discuss strategies used to prevent and manage this potentially disabling complication.
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Do omega-3 polyunsaturated fatty acids ameliorate spinal cord injury?: Commentary on: Lim et al., Improved outcome after spinal cord compression injury in mice treated with docosahexaeonic acid. Exp. Neurol. Jan; 239:13-27.
Exp. Neurol.
PUBLISHED: 06-24-2013
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Long chain polyunsaturated fatty acid, docosahexaenoic acid (DHA) treatment is emerging as a potential treatment for spinal cord injury. Spinal cord injury, which mainly affects young adults, leads to devastating consequences for the afflicted person with very few treatment options available. In addition to the initial neuronal and glial cell loss, secondary injuries such as excitotoxicity, oxidative stress and inflammation magnify the initial damage. Current strategies involve surgical stabilization and decompression and post-injury rehabilitation but these result in only limited improvements. Therefore, there is still a need for pharmacological interventions to limit the secondary injury processes and improve functional recovery. Research in the past decade has implicated n-3 polyunsaturated fatty acids (PUFAs) as a neuroprotective agent capable of limiting post-injury excitotoxic events. This commentary examines the recent findings suggesting a neuroprotective and anti-inflammatory role for the PUFA, docosahexaenoic acid (DHA), in a mouse model of SCI. These findings on DHA are addressed in relation to previous data on DHA and various other promising treatment options being investigated for SCI. Finally, the research involved in the translation of DHA therapy for SCI patients is explored.
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Defining the role of sensation, strength, and prehension for upper limb function in cervical spinal cord injury.
Neurorehabil Neural Repair
PUBLISHED: 06-18-2013
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. Upper limb function plays a significant role in enhancing independence for individuals with tetraplegia. However, there is limited knowledge about the specific input of sensorimotor deficits on upper limb function. Thus the theoretical framework designed to develop the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) was used as a hypothetical model to analyze the impact of impairment on function.
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Predictors of Outcome in Patients with Cervical Spondylotic Myelopathy undergoing Surgical Treatment: A Survey of Members from AOSpine International.
World Neurosurg
PUBLISHED: 06-03-2013
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To conduct a survey of the AOSpine community to determine international perceptions of key predictors of outcome in patients with cervical spondylotic myelopathy. This knowledge will guide the development of clinical prediction models, allowing the alignment of clinical perceptions with evidence-based reality.
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A self-assembling peptide reduces glial scarring, attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury.
Acta Biomater
PUBLISHED: 05-23-2013
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The pathophysiology of spinal cord injury (SCI) involves post-traumatic inflammation and glial scarring which interfere with repair and recovery. Self-assembling peptides (SAPs) are molecules designed for tissue engineering. Here, we tested the performance of K2(QL)6K2 (QL6), a SAP that attenuates inflammation and glial scarring, and facilitates functional recovery. We injected QL6 into the spinal cord tissue of rats 24 h after clip compression SCI. QL6 led to a significant reduction in post-traumatic apoptosis, inflammation and astrogliosis. It also resulted in significant tissue preservation as determined by quantitative histomorphometry. Furthermore, QL6 promoted axonal preservation/regeneration, demonstrated by BDA anterograde and Fluorogold retrograde tracing. In vitro experiments found that a QL6 scaffold enhanced neuronal differentiation and suppressed astrocytic development. The electrophysiology confirmed that QL6 led to significant functional improvement of axons, including increased conduction velocity, reduced refractoriness and enhanced high-frequency conduction. These neuroanatomical and electrophysiological improvements were associated with significant neurobehavioral recovery as assessed by the Basso-Beattie-Bresnahan technique. As the first detailed examination of the pathophysiological properties of QL6 in SCI, this work reveals the therapeutic potential of SAPs, and may suggest an approach for the reconstruction of the injured spinal cord.
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Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model.
BMC Genomics
PUBLISHED: 03-27-2013
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The aneurysm clip impact-compression model of spinal cord injury (SCI) is a standard injury model in animals that closely mimics the primary mechanism of most human injuries: acute impact and persisting compression. Its histo-pathological and behavioural outcomes are extensively similar to human SCI. To understand the distinct molecular events underlying this injury model we analyzed global mRNA abundance changes during the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord.
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Mild diabetes is not a contraindication for surgical decompression in cervical spondylotic myelopathy: results of the AOSpine North America multicenter prospective study (CSM).
Spine J
PUBLISHED: 03-08-2013
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Cervical spondylotic myelopathy (CSM) is a chronic spinal cord disease and can lead to progressive or stepwise neurologic decline. Several factors may influence this process, including extent of spinal cord compression, duration of symptoms, and medical comorbidities. Diabetes is a systemic disease that can impact multiple organ systems, including the central and peripheral nervous systems. There has been little information regarding the effect of diabetes on patients with coexistent CSM.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.