Schouten R.,University of British Columbia |
Albert T.,Thomas Jefferson University |
Kwon B.K.,Blusson Spinal Cord Center
Journal of the American Academy of Orthopaedic Surgeons | Year: 2012
Failure to recognize spinal column or spinal cord injuries, or improper treatment of them, can have catastrophic and often irreversible neurologic consequences. Although the initial assessment is often shared with emergency care personnel, an orthopaedic surgeon's perspective can elevate the priority of spinal care to the level that is warranted. An accurate early appraisal, including complete neurologic assessment, is critical. All aspects of emergent care, including optimal immobilization precautions, resuscitation, and choice of imaging modalities, should be systematically reviewed, and practice guidelines should be adopted by each institution. Increased vigilance is required in patients with underlying ankylosing spinal conditions. The use of CT in the symptomatic patient is established, but the use of cervical MRI in the obtunded individual is contentious. By informing decisions around appropriate preliminary treatment, particularly for persons with neurologic deficits or those at high risk for developing neurologic impairment, long-term outcomes can be optimized.
Plemel J.R.,University of British Columbia |
Plemel J.R.,University of Calgary |
Plemel J.R.,Blusson Spinal Cord Center |
Plemel J.R.,3330 Hospital Drive Nw |
And 11 more authors.
Progress in Neurobiology | Year: 2014
After spinal cord injury (SCI) there is prolonged and dispersed oligodendrocyte cell death that is responsible for widespread demyelination. To regenerate this lost myelin, many investigators have transplanted myelin-producing cells as a treatment for contusive SCI. There are several documented examples of cellular transplantation improving function after injury, with the degree of myelin regeneration correlating with functional recovery. On the basis of these findings, remyelination is hypothesized to be a beneficial strategy to promote recovery after injury. As cellular transplantation is now entering clinical trials for treatment of SCI, it is important to dissect carefully whether accelerating remyelination after SCI is a valid clinical target. In this review we will discuss the consequences of demyelination and the potential benefits of remyelination as it relates to injury. Prolonged demyelination is hypothesized to enhance axonal vulnerability to degeneration, and is thereby thought to contribute to the axonal degeneration that underlies the permanent functional losses associated with SCI. Currently, strategies to promote remyelination after SCI are largely limited to cellular transplantation. This review discusses those strategies as well as new, and largely untested, modes of therapy that aim to coax endogenous cells residing adjacent to the injury site to differentiate in order to replace lost myelin. © 2014 Elsevier Ltd.
Kwon B.K.,Blusson Spinal Cord Center |
Kwon B.K.,University of British Columbia |
Okon E.B.,University of British Columbia |
Plunet W.,University of British Columbia |
And 6 more authors.
Journal of Neurotrauma | Year: 2011
An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications or are available in a form that could be administered to humans. These included: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in vivo animal model was utilized to assess the efficacy of the therapy in a traumatic spinal cord injury paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the preclinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation. © 2011 Mary Ann Liebert, Inc.
Heinemann A.W.,Northwestern University |
Steeves J.D.,Blusson Spinal Cord Center |
Boninger M.,University of Pittsburgh |
Boninger M.,Human Engineering Research Laboratories |
And 2 more authors.
Spinal Cord | Year: 2012
Study design: This manuscript summarizes recommendations from the State of the Science Conference in Spinal Cord Injury Rehabilitation 2011. Objectives: To develop an agenda for spinal cord injury (SCI) rehabilitation research in the next decade. Setting: Participants scheduled planning meetings and then gathered at the 2011 joint meeting of the American Spinal Injury Association and International Spinal Cord Society in Washington DC. Methods: Recommendations were made by an international, multidisciplinary team that met in large plenary sessions and breakout groups during the meeting.Results:Recommendations are organized by conference track, including neurological and functional recovery; technology issues; aging with spinal cord injury; and employment, psychosocial and quality of life issues. Conclusion: A number of themes emerged across the conference tracks, including the need for improved measures of process and outcome constructs, application of qualitative and quantitative research designs, and use of contemporary statistical analytic approaches. Participants emphasized the value of collaborative research that uses the latest methods, techniques and information. © 2012 International Spinal Cord Society. All rights reserved.
Charest-Morin R.,University of Québec |
Dea N.,Université de Sherbrooke |
Fisher C.G.,Blusson Spinal Cord Center
Current Treatment Options in Oncology | Year: 2016
Treatment of primary bone tumours (PBT) of the spine is complex, often involving numerous surgical and oncology disciplines. Surgical en bloc resection with oncologically appropriate margins is the modality of choice when treating malignant PBT. En bloc resection with wide or marginal margins appears to offer better local and systemic control of the disease. This type of surgical resection can also be considered when treating benign aggressive tumours such as aneurysmal bone cyst, giant cell tumour and osteoblastoma. Although these surgeries respect oncologic principles, significant morbidity and mortality are associated. Adverse event collection is highly variable in the literature and mostly from retrospective studies. Wound complication, neurologic deficit and significant blood loss are encountered with surgical resection of PBT of the mobile spine and especially, the sacrum. The adverse event profile of these surgeries is high even in experienced quaternary referral centres. Therefore, primary spinal tumour resection is best performed in experienced centre with adequate multidisciplinary support. Furthermore, prospective and systematic adverse event data collection should be developed to ensure accurate data. The impact of such extensive and potentially impairment producing procedures on health-related quality of life (HRQOL) is another critically valuable piece of information in the era of shared treatment decision making. At the present time, there is paucity of published data regarding HRQOL following these surgeries. Nonetheless, in theory, it seems that health-related quality of life after surgery for PBT is acceptable given the curative intent of the treatment. However, a decision-making process should be tailored to each patient and his or her expectations. Comprehensive discussions should be held preoperatively with the patient, family and other related allied health professionals if the informed consent and decision-making process is to be optimal. © 2016, Springer Science+Business Media New York.
Lam C.J.,University of British Columbia |
Lam C.J.,Blusson Spinal Cord Center |
Assinck P.,Blusson Spinal Cord Center |
Assinck P.,University of British Columbia |
And 5 more authors.
Journal of Neurotrauma | Year: 2014
Spinal cord injury (SCI) biomechanics suggest that the mechanical factors of impact depth and speed affect the severity of contusion injury, but their interaction is not well understood. The primary aim of this work was to examine both the individual and combined effects of impact depth and speed in contusion SCI on the cervical spinal cord. Spinal cord contusions between C5 and C6 were produced in anesthetized rats at impact speeds of 8, 80, or 800mm/s with displacements of 0.9 or 1.5mm (n=8/group). After 7 days postinjury, rats were assessed for open-field behavior, euthanized, and spinal cords were harvested. Spinal cord tissue sections were stained for demyelination (myelin-based protein) and tissue sparing (Luxol fast blue). In parallel, a finite element model of rat spinal cord was used to examine the resulting maximum principal strain in the spinal cord during impact. Increasing impact depth from 0.9 to 1.5mm reduced open-field scores (p<0.01) above 80mm/s, reduced gray (GM) and white matter (WM) sparing (p<0.01), and increased the amount of demyelination (p<0.01). Increasing impact speed showed similar results at the 1.5-mm impact depth, but not the 0.9-mm impact depth. Linear correlation analysis with finite element analysis strain showed correlations (p<0.001) with nerve fiber damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with WM (R2=0.90) and GM (R2=0.76) sparing. The results demonstrate that impact depth is more important in determining the severity of SCI and that threshold interactions exist between impact depth and speed. © Mary Ann Liebert, Inc. 2014.
Moore G.R.W.,University of British Columbia |
Moore G.R.W.,Vancouver General Hospital |
Moore G.R.W.,Blusson Spinal Cord Center |
Laule C.,University of British Columbia
Journal of Neuropathology and Experimental Neurology | Year: 2012
The advent of magnetic resonance imaging (MRI) has revolutionized concepts of the pathogenesis of multiple sclerosis (MS). Magnetic resonance imaging provides the ability to delineate the evolution of the disease process over time; captured static snapshots can then be used in pathologic correlations studies. Certain patterns in the 2-or 3-dimensional MRI sphere correlate very well with similarpatterns of histopathology. A multimodality approach that makes use of numerous MRI techniques can lead to significant insights into the nature of the changes in the CNS. MRI-pathology correlation studies in MS are being performed using newer MRI techniques as they become available. Such correlations and basic histopathologic studies have shown abnormalities in MS far beyond the well-documented changes in the plaque and have brought into question the dogma that MS is an initially inflammatory nondegenerative disease. This review briefly outlines technical considerations in MRI-pathology correlativestudies and describes the past and current status of our ability to correlate focal and diffuse changes on the MRI with neuropathologic findings in MS patients. Copyright © 2012 by the American Association of Neuropathologists, Inc.
Streijger F.,Blusson Spinal Cord Center |
Beernink T.M.J.,Blusson Spinal Cord Center |
Lee J.H.T.,Blusson Spinal Cord Center |
Bhatnagar T.,Blusson Spinal Cord Center |
And 7 more authors.
Journal of Neurotrauma | Year: 2013
The majority of clinical spinal cord injuries (SCIs) are contusive and occur at the cervical level of the spinal cord. Most scientists and clinicians agree that the preclinical evaluation of novel candidate treatments should include testing in a cervical SCI contusion model. Because mice are increasingly used because of the availability of genetically engineered lines, we characterized a novel cervical hemicontusion injury in mice using the Infinite Horizon Spinal Cord Impactor (Precisions Systems & Instrumentation, Lexington, KY). In the current study, C57BL/6 mice received a hemicontusion injury of 75 kilodynes with or without dwell time in an attempt to elicit a sustained moderate-to-severe motor deficit. Hemicontusion injuries without dwell time resulted in sustained deficits of the affected forepaw, as revealed by a 3-fold decrease in usage during rearing, a ~50% reduction in grooming scores, and retrieval of significantly fewer pellets on the Montoya staircase test. Only minor transient deficits were observed in grasping force. CatWalk analysis revealed reduced paw-print size and swing speed of the affected forelimb. Added dwell time of 15 or 30 sec significantly worsened behavioral outcome, and mice demonstrated minimal ability of grasping, paw usage, and overground locomotion. Besides worsening of behavioral deficits, added dwell time also reduced residual white and gray matter at the epicenter and rostral-caudal to the injury, including on the contralateral side of the spinal cord. Taken together, we developed and characterized a new hemicontusion SCI model in mice that produces sufficient and sustained impairments in gross and skilled forelimb function and produced primarily unilateral functional deficits. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
Scott A.L.M.,Blusson Spinal Cord Center |
Ramer M.S.,Blusson Spinal Cord Center
Brain | Year: 2010
Schwann cells are attractive candidates for repair of the injured spinal cord. Transplanted Schwann cells are permissive to regeneration, but their ability to promote regeneration into distal spinal cord remains weak despite their production of growth-promoting neurotrophins. Schwann cell activation such as that which accompanies peripheral nerve injury results in massive upregulation of the p75NTR pan-neurotrophin-receptor. Here we test the hypothesis that this p75NTR upregulation following dorsal root injury limits availability of endogenous neurotrophin to axons and restricts regeneration of injured axons into the spinal cord. We injured dorsal roots (fourth cervical to second thoracic) in mice lacking the neurotrophin-binding domain of p75NTR and in wild-type littermates. Axonal regeneration was assessed by selective tracing of neurotrophin-responsive and non-responsive dorsal root ganglion neurons. Functional reinnervation of the spinal cord was assessed in behavioural experiments and via Fos immunohistochemistry following formalin injection into the forepaw. We also measured levels of nerve growth factor and neurotrophin-3 following nerve injury in knockout and wild-type mice, and used Trk-Fc receptor chimeras to block nerve growth factor and neurotrophin-3 signalling in dorsal root ganglion/Schwann cell co-cultures and following dorsal root injury in vivo. The roles of neuronal and glial p75 NTR were assessed in transplant experiments in vivo and in co-cultures. We found that nerve growth factor and neurotrophin-3-responsive axons regenerated into the spinal cord of p75NTR knockout mice where they made functional connections with dorsal horn neurons. Despite equivalent levels of nerve growth factor and neurotrophin-3 in wild-type and knockout mice, successful regeneration in knockouts was neurotrophin-dependent. Transplantation of p75-/- neurons into a wild-type environment, p75-/- peripheral nerve grafts into the injured p75+/+ spinal cord, and dissociated sensory neuron/Schwann cell co-cultures showed that the absence of p75NTR from glia, not from neurons, promotes regeneration. These findings indicate that Schwann cell p75NTR restricts neurotrophin availability to the extent that it prevents spontaneous sensory axon regeneration into the spinal cord. The implication is that inactivating p75NTR in Schwann (or olfactory ensheathing) cells may enable axons to grow beyond transplants, improving the outcome of spinal cord injury.
Scott A.L.M.,Blusson Spinal Cord Center |
Ramer M.S.,Blusson Spinal Cord Center
Brain Research | Year: 2010
Spontaneous and/or treatment-evoked re-modeling of the CNS following spinal cord injury is a prerequisite for functional recovery. While there has been considerable interest in the role of endogenous neurotrophins in spontaneous plasticity of several populations of spinal axons, the same cannot be said for morphological changes to dendrites. Here, we examined the responses of dendrites in the mouse lateral spinal nucleus (LSN, a site of sensory integration in the dorsolateral white matter) to exogenous and endogenous neurotrophins. We performed a septuple dorsal rhizotomy, which permanently eliminates sensory input to the spinal cord, and stimulates sprouting of spinal axons. While dendrites showed no change in density following injury alone, they sprouted vigorously (a two-fold increase in density) upon addition of exogenous brain-derived neurotrophic factor (BDNF). On the other hand, endogenous nerve growth factor (NGF) severely restricted dendritic sprouting, as TrkA-Fc treatment also roughly doubled the density of dendritic processes in the LSN. Spontaneous, BDNF- and TrkA-Fc mediated sprouting was unaffected by the absence of p75NTR. Importantly, TrkA-Fc treatment markedly reduced expression of the truncated BDNF receptor TrkBT1 in both p75+/+ and p75-/- mice, which was robustly-upregulated by deafferentation in both genotypes. We propose that the upregulation of TrkBT1 by NGF results in a reduced availability of endogenous BDNF to dendrites. Accordingly, sprouting of serotonergic axons, a BDNF-dependent consequence of dorsal root injury, was significantly enhanced in TrkA-Fc-treated animals. These results suggest that NGF and BDNF signaling differentially regulates dendritic plasticity in the deafferented spinal cord. © 2010 Elsevier B.V. All rights reserved.