Publications by authors named "Lise Belanger"

22 Publications

  • Page 1 of 1

Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study.

J Pain 2021 Jul 21. Epub 2021 Jul 21.

International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, British Columbia, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada; Hugill Centre for Anesthesia, Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

There is currently a lack of information regarding neuropathic pain in the very early stages of spinal cord injury (SCI). In the present study, neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) for the patient's worst pain within the first 5 days of injury (i.e., hyperacute) and on follow-up at 3, 6, and 12 months. Within the hyperacute time-frame (i.e., 5 days), at- and below level neuropathic pain were reported as the worst pain in 23% (n=18) and 5% (n=4) of individuals with SCI, respectively. Compared to the neuropathic pain observed in this hyperacute setting, late presenting neuropathic pain was characterized by more intense painful electrical and cold sensations, but less itching sensations. Phenotypic differences between acute and late neuropathic pain support the incorporation of timing into a mechanism-based classification of neuropathic pain after SCI. The diagnosis of acute neuropathic pain after SCI is challenged by the presence of nociceptive and neuropathic pains, with the former potentially masking the latter. This may lead to an underestimation of the incidence of neuropathic pain during the very early, hyperacute time points post-injury. Trial registration: ClinicalTrials.gov (Identifier: NCT01279811) Perspective: This article presents distinct pain phenotypes of hyperacute and late presenting neuropathic pain after spinal cord injury and highlights the challenges of pain assessments in the acute phase after injury. This information may be relevant to clinical trial design and broaden our understanding of neuropathic pain mechanisms after spinal cord injury.
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http://dx.doi.org/10.1016/j.jpain.2021.06.013DOI Listing
July 2021

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Mol Cell Proteomics 2021 Jun 12;20:100096. Epub 2021 Jun 12.

Division of Neurosurgery, University of British Columbia, Vancouver, British Columbia, Canada.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.
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http://dx.doi.org/10.1016/j.mcpro.2021.100096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260874PMC
June 2021

Patient perspective: diagnosis and prognosis of acute spinal cord injuries.

Spinal Cord 2021 Jun 3. Epub 2021 Jun 3.

Combined Neurosurgical and Orthopaedic Spine Program, Blusson Spinal Cord Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Study Design: Qualitative study.

Objectives: The purpose of this study is to understand the patient perspective after diagnosis of an acute traumatic spinal cord injury (tSCI). Discussing the diagnosis and prognosis of a tSCI with a patient can be a challenging experience for both the patient and the physician. As such, this paper attempts to better understand the patient experience to improve communication when discussing this life-altering injury.

Setting: Vancouver General Hospital, Vancouver, British Columbia, Canada.

Methods: This study is a qualitative study utilizing grounded theory and semi-structured interviews. The interview transcripts were manually coded using manifest and latent content analysis. Major and minor codes were identified and discussed.

Results: In total, 17 interviews were conducted, fifteen individuals with tSCI who received acute care at Vancouver General Hospital (VGH) and eleven family members were interviewed. Patient participants were interviewed individually or in a paired interview with a participating family member. Patient participants had varying spinal cord injuries from AIS A-D. Two major themes were identified from the interviews. The first major theme was physician demeanor (general approach and attitude towards patients) and the second major theme was delivery of information (content, timing, and source).

Conclusions: This study summarizes the preferences of patients who sustained a tSCI discussions regarding their diagnosis and prognosis in the acute care setting. The goal of this study is to help guide physician interactions at this difficult and vulnerable time for patients with hopes to improve patient care through effective communication.
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http://dx.doi.org/10.1038/s41393-021-00641-5DOI Listing
June 2021

Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) as a Biomarker of Human Acute Traumatic Spinal Cord Injury.

J Neurotrauma 2021 May 3. Epub 2021 May 3.

International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Center, University of British Columbia, Vancouver, British Columbia, Canada.

A major obstacle for translational research in acute spinal cord injury (SCI) is the lack of biomarkers that can objectively stratify injury severity and predict outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a neuron-specific enzyme that shows promise as a diagnostic biomarker in traumatic brain injury (TBI), but has not been studied in SCI. In this study, cerebrospinal fluid (CSF) and serum samples were collected over the first 72-96 h post-injury from 32 acute SCI patients who were followed prospectively to determine neurological outcomes at 6 months post-injury. UCH-L1 concentration was measured using the Quanterix Simoa platform (Quanterix, Billerica, MA) and correlated to injury severity, time, and neurological recovery. We found that CSF UCH-L1 was significantly elevated by 10- to 100-fold over laminectomy controls in an injury severity- and time-dependent manner. Twenty-four-hour post-injury CSF UCH-L1 concentrations distinguished between American Spinal Injury Association Impairment Scale (AIS) A and AIS B, and AIS A and AIS C patients in the acute setting, and predicted who would remain "motor complete" (AIS A/B) at 6 months with a sensitivity of 100% and a specificity of 86%. AIS A patients who did not improve their AIS grade at 6 months post-injury were characterized by sustained elevations in CSF UCH-L1 up to 96 h. Similarly, the failure to gain >8 points on the total motor score at 6 months post-injury was associated with higher 24-h CSF UCH-L1. Unfortunately, serum UCH-L1 levels were not informative about injury severity or outcome. In conclusion, CSF UCH-L1 in acute SCI shows promise as a biomarker to reflect injury severity and predict outcome.
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http://dx.doi.org/10.1089/neu.2020.7352DOI Listing
May 2021

Effectiveness of silver alloy-coated silicone urinary catheters in patients with acute traumatic cervical spinal cord injury: Results of a quality improvement initiative.

J Clin Neurosci 2020 Aug 11;78:135-138. Epub 2020 Jun 11.

Combined Neurosurgical and Orthopaedic Spine Program, Department of Orthopaedic Surgery, University of British Columbia, Vancouver Spine Surgery Institute, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC V5Z 1M9, Canada. Electronic address:

Patients with acute traumatic cervical spinal cord injury (ATCSCI) have an increased risk of catheter-associated urinary tract infection (CAUTI). The effectiveness of silver alloy-coated silicone urinary catheters (SACC) in preventing CAUTI in ATCSCI is unknown and was the objective of this study. We performed a quality improvement initiative in an attempt to reduce CAUTI in patients undergoing spine surgery at a single quaternary center. Prior to July 2015, all patients received a latex indwelling catheter (LIC). All patients with ATCSCI with limited hand function (AIS A,B, or C) received a SACC. Incidence of CAUTI, microbiology, duration of infection, antibiotic susceptibility, and catheter-associated adverse events were recorded prospectively. We studied 3081 consecutive patients over the three years, of whom 302 (9.8%) had ATCSCI; 63% of ATCSCI patients were ASIA Impairment Scale (AIS) A or B. The overall rate of CAUTI was 19% (585/3081), and was 38% (116/302) in patients with ATCSCI. Of 178 ATCSCI patients with LIC, 100 (56%) developed a CAUTI compared with 28 of 124 (23%) patients with SACC (p < 0.05). Poly-microbial and gram-positive infection was more common in LIC than in SACC (p < 0.05). Median duration of infection was 9 days in SACC group and 12 days in LIC group (p = 0.08). Resistance to trimethoprim (p < 0.001) and ciprofloxacin (p < 0.05) were more common in LIC group. There was no difference in catheter-associated adverse events or length of stay between the groups. This quality improvement initiative illustrates the effectiveness of antiseptic silver alloy-coated silicone urinary catheters in patients with ATCSCI. In our population, the use of SACC reduces the incidence and the complexity of CAUTI.
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http://dx.doi.org/10.1016/j.jocn.2020.05.036DOI Listing
August 2020

Empirical targets for acute hemodynamic management of individuals with spinal cord injury.

Neurology 2019 09 13;93(12):e1205-e1211. Epub 2019 Aug 13.

From the International Collaboration on Repair Discoveries (J.W.S., C.R.W., B.K.K.); MD/PhD Training Program (J.W.S.), School of Kinesiology (C.R.W.), and Department of Orthopaedics (R.C.-M., J.S., T.A., S. Paquette, N.D., C.G.F., M.F.D.), University of British Columbia; Vancouver Spine Program (L.M.B., A.T., L.R.), Vancouver General Hospital, British Columbia; Department of Surgery (J.-M.M.-T., S. Parent), Hôpital du Sacré-Coeur de Montréal, and Chu Sainte-Justine (S.C.), Department of Surgery, Université de Montréal, Quebec; Division of Orthopaedic Surgery (C.B.), London Health Sciences Centre, University of Western Ontario, Canada; Department of Neurological Surgery (S.D.), University of California, San Francisco; Vancouver Spine Surgery Institute (R.C.-M., J.S., T.A., S. Paquette, N.D., C.G.F., M.F.D., B.K.K.); and Division of Neurosurgery (B.K.K.), University of British Columbia, Blusson Spinal Cord Centre, Vancouver, Canada.

Objective: To determine the hemodynamic conditions associated with optimal neurologic improvement in individuals with acute traumatic spinal cord injury (SCI) who had lumbar intrathecal catheters placed to measure CSF pressure (CSFP).

Methods: Ninety-two individuals with acute SCI were enrolled in this multicenter prospective observational clinical trial. We monitored mean arterial pressure (MAP) and CSFP during the first week after injury and assessed neurologic function at baseline and 6 months after injury. We used relative risk iterations to determine transition points at which the likelihood of either improving neurologically or remaining unchanged neurologically was equivalent. These transition points guided our analyses in which we examined the linear relationships between time spent within target hemodynamic ranges (i.e., clinical adherence) and neurologic recovery.

Results: Relative risk transition points for CSFP, MAP, and spinal cord perfusion pressure (SCPP) were linearly associated with neurologic improvement and directed the identification of key hemodynamic target ranges. Clinical adherence to the target ranges was positively and linearly related to improved neurologic outcomes. Adherence to SCPP targets, not MAP targets, was the best indicator of improved neurologic recovery, which occurred with SCPP targets of 60 to 65 mm Hg. Failing to maintain the SCPP within the target ranges was an important detrimental factor in neurologic recovery, particularly if the target range is set lower.

Conclusion: We provide an empirical, data-driven approach to aid institutions in setting hemodynamic management targets that accept the real-life challenges of adherence to specific targets. Our results provide a framework to guide the development of widespread institutional management guidelines for acute traumatic SCI.
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http://dx.doi.org/10.1212/WNL.0000000000008125DOI Listing
September 2019

Predicting Injury Severity and Neurological Recovery after Acute Cervical Spinal Cord Injury: A Comparison of Cerebrospinal Fluid and Magnetic Resonance Imaging Biomarkers.

J Neurotrauma 2018 02 6;35(3):435-445. Epub 2017 Nov 6.

3 International Collaboration on Repair Discoveries (ICORD), University of British Columbia , Blusson Spinal Cord Center, Vancouver, British Columbia, Canada .

Biomarkers of acute human spinal cord injury (SCI) could provide a more objective measure of spinal cord damage and a better predictor of neurological outcome than current standardized neurological assessments. In SCI, there is growing interest in establishing biomarkers from cerebrospinal fluid (CSF) and from magnetic resonance imaging (MRI). Here, we compared the ability of CSF and MRI biomarkers to classify injury severity and predict neurological recovery in a cohort of acute cervical SCI patients. CSF samples and MRI scans from 36 acute cervical SCI patients were examined. From the CSF samples taken 24 h post-injury, the concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, monocyte chemotactic protein-1), and structural proteins (tau, glial fibrillary acidic protein, and S100β) were measured. From the pre-operative MRI scans, we measured intramedullary lesion length, hematoma length, hematoma extent, CSF effacement, cord expansion, and maximal spinal cord compression. Baseline and 6-month post-injury assessments of American Spine Injury Association Impairment Scale (AIS) grade and motor score were conducted. Both MRI measures and CSF biomarker levels were found to correlate with baseline injury grade, and in combination they provided a stronger model for classifying baseline AIS grade than CSF or MRI biomarkers alone. For predicting neurological recovery, the inflammatory CSF biomarkers best predicted AIS grade conversion, whereas structural biomarker levels best predicted motor score improvement. A logistic regression model utilizing CSF biomarkers alone had a 91.2% accuracy at predicting AIS conversion, and was not strengthened by adding MRI features or even knowledge of the baseline AIS grade. In a direct comparison of MRI and CSF biomarkers, the CSF biomarkers discriminate better between different injury severities, and are stronger predictors of neurological recovery in terms of AIS grade and motor score improvement. These findings demonstrate the utility of measuring the acute biological responses to SCI as biomarkers of injury severity and neurological prognosis.
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http://dx.doi.org/10.1089/neu.2017.5357DOI Listing
February 2018

Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury.

Neurology 2017 Oct 15;89(16):1660-1667. Epub 2017 Sep 15.

From the International Collaboration on Repair Discoveries (ICORD) (J.W.S., M.F.D., C.R.W., B.K.K.); MD/PhD Training Program (J.W.S.), Department of Orthopaedics (J.S., C.G.F., M.F.D, B.K.K) and Division of Neurosurgery (T.A., S. Paquette, N.D.), Vancouver Spine Surgery Institute, Blusson Spinal Cord Centre, and School of Kinesiology (C.R.W.), University of British Columbia; Vancouver Spine Program (L.M.B., A.T., L.R.), Vancouver General Hospital; Department of Surgery, Hôpital du Sacré-Coeur de Montréal (J.-M.M.-T., S. Parent), and Chu Sainte-Justine, Department of Surgery (S.C.), Université de Montréal; Division of Orthopaedic Surgery (C.B.), London Health Sciences Centre, University of Western Ontario, Canada; and Department of Neurological Surgery (S.D.), University of California, San Francisco.

Objective: To determine whether spinal cord perfusion pressure (SCPP) as measured with a lumbar intrathecal catheter is a more predictive measure of neurologic outcome than the conventionally measured mean arterial pressure (MAP).

Methods: A total of 92 individuals with acute spinal cord injury were enrolled in this multicenter prospective observational clinical trial. MAP and CSF pressure (CSFP) were monitored during the first week postinjury. Neurologic impairment was assessed at baseline and at 6 months postinjury. We used logistic regression, systematic iterations of relative risk, and Cox proportional hazard models to examine hemodynamic patterns commensurate with neurologic outcome.

Results: We found that SCPP (odds ratio 1.039, = 0.002) is independently associated with positive neurologic recovery. The relative risk for not recovering neurologic function continually increased as individuals were exposed to SCPP below 50 mm Hg. Individuals who improved in neurologic grade dropped below SCPP of 50 mm Hg fewer times than those who did not improve ( = 0.012). This effect was not observed for MAP or CSFP. Those who were exposed to SCPP below 50 mm Hg were less likely to improve from their baseline neurologic impairment grade ( = 0.0056).

Conclusions: We demonstrate that maintaining SCPP above 50 mm Hg is a strong predictor of improved neurologic recovery following spinal cord injury. This suggests that SCPP (the difference between MAP and CSFP) can provide useful information to guide the hemodynamic management of patients with acute spinal cord injury.
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http://dx.doi.org/10.1212/WNL.0000000000004519DOI Listing
October 2017

Evaluation of a Clinical Protocol to Assess and Diagnose Neuropathic Pain During Acute Hospital Admission: Results From Traumatic Spinal Cord Injury.

Clin J Pain 2018 02;34(2):104-112

Departments of Anesthesiology, Pharmacology and Therapeutics.

Objectives: A clinical protocol was developed for clinicians to routinely assess and initiate treatment for patients with neuropathic pain (NP) in an acute care setting. The objectives of this study were to: (1) determine the incidence and onset of NP in patients with traumatic spinal cord injury during acute care and (2) describe how the implementation of a clinical protocol impacts the assessment and diagnosis of NP.

Materials And Methods: The study was a cohort analysis with a pre-post-test utilizing a historical control. Data were retrospectively collected from a patient registry and charts. Participants were randomly selected in cohort 1 (control) and cohort 2 (NP clinical protocol).

Results: The incidence of NP was 56% without significant difference between the cohorts (P=0.3). Onset of NP was 8 days (SD=14) across the study and >85% of the participants with NP were diagnosed within 2 weeks. Participants with incomplete injuries had a significant earlier onset than participants with complete injuries (6.2±12.8, 10.9±15.8 d; P=0.003). The mean number of days from hospital admission to initial assessment decreased with use of the NP clinical protocol (3.7±5.7 d; P=0.02).

Discussion: This study demonstrates a high incidence and early onset of NP in traumatic spinal cord injury during acute hospital care, with an earlier emergence in participants with incomplete injury. The NP clinical protocol ensured continuous assessment and documentation of NP while decreasing the time to an initial screen, but did not impact diagnosis.
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http://dx.doi.org/10.1097/AJP.0000000000000523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768215PMC
February 2018

Methodology of the Access to Care and Timing Simulation Model for Traumatic Spinal Cord Injury Care.

J Neurotrauma 2017 Oct 14;34(20):2843-2847. Epub 2017 Apr 14.

Sauder School of Business, University of British Columbia, Vancouver, British Columbia, Canada.

Despite the relatively low incidence of traumatic spinal cord injury (tSCI), the management and care of persons with tSCI can be resource intensive and complex, spanning multiple phases of care and disciplines. Using a simulation model built with a system level view of the healthcare system allows for prediction of the impact of interventions on patient and system outcomes from injury through to community reintegration after tSCI. As has been previously described, the Access to Care and Timing (ACT) project developed a simulation model for tSCI care using techniques from operations research. The objective of this article is to briefly describe the methodology and the application of the ACT Model, as it was used in several of the articles in this focus issue. The approaches employed in this model provide a framework to look into the complexity of interactions both within and among the different SCI programs, sites, and phases of care.
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http://dx.doi.org/10.1089/neu.2016.4927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652975PMC
October 2017

A Targeted Proteomics Analysis of Cerebrospinal Fluid after Acute Human Spinal Cord Injury.

J Neurotrauma 2017 06 7;34(12):2054-2068. Epub 2017 Apr 7.

1 International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, University of British Columbia , Vancouver, British Columbia, Canada .

Efforts to validate novel therapies in acute clinical trials for spinal cord injury (SCI) are impeded by the lack of objective quantitative measures that reflect injury severity and accurately predict neurological recovery. Therefore, a strong rationale exists for establishing neurochemical biomarkers that objectively quantify injury severity and predict outcome. Here, we conducted a targeted proteomics analysis of cerebrospinal fluid (CSF) samples derived from 29 acute SCI patients (American Spinal Injury Association Impairment Scale [AIS] A, B, or C) acquired at 24, 48, and 72 h post-injury. From a total of 165 proteins, we identified 27 potential biomarkers of injury severity (baseline AIS A, B, or C), with triosephosphate isomerase having the strongest relationship to AIS grade. The majority of affected proteins (24 of 27) were more abundant in samples from AIS A patients than in those from AIS C patients, suggesting that for the most part, these proteins are released into the CSF more readily with more severe trauma to the spinal cord. We then analyzed the relationship between CSF protein abundance and neurological recovery. For AIS grade improvement over 6 months, we identified 34 proteins that were associated with AIS grade conversion (p < 0.05); however, these associations were not statistically significant after adjusting for multiple comparisons. For total motor score (TMS) recovery over 6 months, after adjusting for baseline neurological injury level, we identified 46 proteins with a statistically significant association with TMS recovery. Twenty-two of these proteins were among the 27 proteins that were related to baseline AIS grade, consistent with the notion that protein markers that reflect a more severe injury also appropriately predict a poorer recovery of motor function. In summary, this study provides a description of the CSF proteome changes that occur after acute human SCI, and reveals a number of protein candidates for further validation as potential biomarkers of injury severity.
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http://dx.doi.org/10.1089/neu.2016.4879DOI Listing
June 2017

Mean Arterial Blood Pressure Management of Acute Traumatic Spinal Cord Injured Patients during the Pre-Hospital and Early Admission Period.

J Neurotrauma 2017 03 13;34(6):1271-1277. Epub 2017 Jan 13.

3 Department of Orthopaedics, Vancouver Spine Surgery Institute, University of British Columbia , Blusson Spinal Cord Centre, Vancouver, British Columbia, Canada .

The optimization and maintenance of mean arterial blood pressure (MAP) and the general avoidance of systemic hypotension for the first 5-7 days following acute traumatic spinal cord injury (tSCI) is considered to be important for minimizing secondary spinal cord ischemic damage. The characterization of hemodynamic parameters in the immediate post-injury stage prior to admission to a specialized spine unit has not been previously reported. Here we describe the blood pressure management of 40 acute tSCI patients in the early post-injury phases of care prior to their arrival in a specialized spinal injury high dependency unit (HDU), intensive care unit (ICU), or operating room (OR). This study found that a significant proportion of these patients experience periods of relative hypotension prior to their admission to a specialized spinal unit. In particular, the mean calculated MAP was 78.8 mm Hg, with 52% of MAP measurements <80 mm Hg at primary receiving hospitals. Despite having a mean calculated MAP of 83.3 mm Hg in the emergency room of the tertiary hospital, 40% of the MAP measurements were <80 mm Hg. Although stringent monitoring and management of MAP may be facilitated and adhered to in a spinal HDU, ICU, or OR, it is important to recognize that acute traumatic SCI patients may experience many periods of relative hypotension prior to their arrival in such specialized units. This study highlights the need for education and awareness to optimize the hemodynamic management of acute SCI patients during the immediate post-injury period.
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http://dx.doi.org/10.1089/neu.2016.4689DOI Listing
March 2017

Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.

J Neurotrauma 2017 02 15;34(3):567-580. Epub 2016 Aug 15.

1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .

Neurologic impairment after spinal cord injury (SCI) is currently measured and classified by functional examination. Biological markers that objectively classify injury severity and predict outcome would greatly facilitate efforts to evaluate acute SCI therapies. The purpose of this study was to determine how well inflammatory and structural proteins within the cerebrospinal fluid (CSF) of acute traumatic SCI patients predicted American Spinal Injury Association Impairment Scale (AIS) grade conversion and motor score improvement over 6 months. Fifty acute SCI patients (29 AIS A, 9 AIS B, 12 AIS C; 32 cervical, 18 thoracic) were enrolled and CSF obtained through lumbar intrathecal catheters to analyze interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tau, S100β, and glial fibrillary acidic protein (GFAP) at 24 h post-injury. The levels of IL-6, tau, S100β, and GFAP were significantly different between patients with baseline AIS grades of A, B, or C. The levels of all proteins (IL-6, IL-8, MCP-1, tau, S100β, and GFAP) were significantly different between those who improved an AIS grade over 6 months and those who did not improve. Linear discriminant analysis modeling was 83% accurate in predicting AIS conversion. For AIS A patients, the concentrations of proteins such as IL-6 and S100β correlated with conversion to AIS B or C. Motor score improvement also was strongly correlated with the 24-h post-injury CSF levels of all six biomarkers. The analysis of CSF can provide valuable biological information about injury severity and recovery potential after acute SCI. Such biological markers may be valuable tools for stratifying individuals in acute clinical trials where variability in spontaneous recovery requires large recruitment cohorts for sufficient power.
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http://dx.doi.org/10.1089/neu.2016.4435DOI Listing
February 2017

Modeling the patient journey from injury to community reintegration for persons with acute traumatic spinal cord injury in a Canadian centre.

PLoS One 2013 30;8(8):e72552. Epub 2013 Aug 30.

Rick Hansen Institute, Vancouver, Canada ; Division of Spine, Department of Orthopaedics, University of British Columbia, Vancouver, Canada.

Background: A patient's journey through the health care system is influenced by clinical and system processes across the continuum of care.

Methods: To inform optimized access to care and patient flow for individuals with traumatic spinal cord injury (tSCI), we developed a simulation model that can examine the full impact of therapeutic or systems interventions across the care continuum for patients with traumatic spinal cord injuries. The objective of this paper is to describe the detailed development of this simulation model for a major trauma and a rehabilitation centre in British Columbia (BC), Canada, as part of the Access to Care and Timing (ACT) project and is referred to as the BC ACT Model V1.0.

Findings: To demonstrate the utility of the simulation model in clinical and administrative decision-making we present three typical scenarios that illustrate how an investigator can track the indirect impact(s) of medical and administrative interventions, both upstream and downstream along the continuum of care. For example, the model was used to estimate the theoretical impact of a practice that reduced the incidence of pressure ulcers by 70%. This led to a decrease in acute and rehabilitation length of stay of 4 and 2 days, respectively and a decrease in bed utilization of 9% and 3% in acute and rehabilitation.

Conclusion: The scenario analysis using the BC ACT Model V1.0 demonstrates the flexibility and value of the simulation model as a decision-making tool by providing estimates of the effects of different interventions and allowing them to be objectively compared. Future work will involve developing a generalizable national Canadian ACT Model to examine differences in care delivery and identify the ideal attributes of SCI care delivery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072552PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758357PMC
April 2014

Development and assessment of a community follow-up questionnaire for the Rick Hansen spinal cord injury registry.

Arch Phys Med Rehabil 2013 Sep 22;94(9):1753-65. Epub 2013 Mar 22.

Centre for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec City, Quebec, Canada.

Objective: To develop a comprehensive community follow-up questionnaire for participants enrolled in the Rick Hansen Spinal Cord Injury Registry (RHSCIR).

Design: Development and preliminary assessment of measurement properties (reliability and validity) of instruments used during a community follow-up and aligned with the International Classification of Functioning, Disability and Health (ICF).

Setting: General community setting.

Participants: People with spinal cord injury (N=50) living in the community.

Intervention: Not applicable.

Main Outcome Measures: A comprehensive follow-up questionnaire, referred to as the RHSCIR Community Follow-up Questionnaire Version 2.0 (CFQ-V2.0), includes 8 instruments. Four new instruments were developed, 2 existing instruments were modified, and 2 previously published instruments were included.

Results: Intra- and interrater reliability statistics (Gwet's AC1) support the measurement properties of the new and modified instruments. Correlations between new and existing instruments and between groups based on the severity of injury support the construct validity of the secondary complications and person-perceived participation instruments.

Conclusions: The RHSCIR CFQ-V2.0 is a comprehensive community follow-up questionnaire that aligns to the ICF. Initial study results suggest that it covers all relevant aspects of community living, and the measurement properties are promising.
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http://dx.doi.org/10.1016/j.apmr.2013.03.006DOI Listing
September 2013

The validity of administrative data to classify patients with spinal column and cord injuries.

J Neurotrauma 2013 Feb;30(3):173-80

Rick Hansen Institute, Vancouver, British Columbia, Canada.

International Classification of Diseases (ICD) codes are used to document patient morbidity in administrative databases. Although administrative data are used for research purposes, the validity of the data to accurately describe clinical diagnostic information is uncertain. We compared the clinical diagnoses for spinal cord and column injuries from a longitudinal patient registry, the Rick Hansen Spinal Cord Injury Registry (RHSCIR), to the ICD-10 spinal injury codes from the Discharge Abstract Database (DAD) at one institution. There were 603 RHSCIR participants with data describing the spinal cord injury, and 341 had data on the spinal column injury. The validity of DAD data to describe spinal injuries was evaluated using the sensitivity and positive predictive values of specific ICD-10 codes; 5.3% of the spinal column injuries and 10.9% of the spinal cord injuries documented in RHSCIR were missed in data from the DAD using ICD-10 codes. The most problematic spinal column ICD-10 code was the dislocation of the cervical vertebra (S13.1); only 14.0% of the dislocations of the cervical vertebrae in RHSCIR were correctly coded in the DAD. The most problematic spinal cord injury ICD-10 code was the incomplete lesion of the lumbar spinal cord (S34.1X); 66.7% of incomplete lesions of the lumbar spinal cord in RHSCIR were correctly coded in the DAD. The validity of DAD data to code spinal injuries is variable, and cannot be reliably used to classify all types of spinal injuries. Patient registries, such as RHSCIR, should be used if accurate detailed diagnostic data are required.
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http://dx.doi.org/10.1089/neu.2012.2441DOI Listing
February 2013

Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury.

J Neurotrauma 2010 Apr;27(4):669-82

Department of Orthopaedics, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada.

There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.
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http://dx.doi.org/10.1089/neu.2009.1080DOI Listing
April 2010

Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial.

J Neurosurg Spine 2009 Mar;10(3):181-93

Departments of Orthopaedics, Combined Neurosurgical and Orthopaedic Spine Program, University of British Columbia, Canada.

Object: Ischemia is an important factor in the pathophysiology of secondary damage after traumatic spinal cord injury (SCI) and, in the setting of thoracoabdominal aortic aneurysm repair, can be the primary cause of paralysis. Lowering the intrathecal pressure (ITP) by draining CSF is routinely done in thoracoabdominal aortic aneurysm surgery but has not been evaluated in the setting of acute traumatic SCI. Additionally, while much attention is directed toward maintaining an adequate mean arterial blood pressure (MABP) in the acute postinjury phase, little is known about what is happening to the ITP during this period when spinal cord perfusion pressure (MABP - ITP) is important. The objectives of this study were to: 1) evaluate the safety and feasibility of draining CSF to lower ITP after acute traumatic SCI; 2) evaluate changes in ITP before and after surgical decompression; and 3) measure neurological recovery in relation to the drainage of CSF.

Methods: Twenty-two patients seen within 48 hours of injury were prospectively randomized to a drainage or no-drainage treatment group. In all cases a lumbar intrathecal catheter was inserted for 72 hours. Acute complications of headache/nausea/vomiting, meningitis, or neurological deterioration were carefully monitored. Acute Spinal Cord Injury motor scores were documented at baseline and at 6 months postinjury.

Results: On insertion of the catheter, mean ITP was 13.8 +/- 1.3 mm Hg (+/- SD), and it increased to a mean peak of 21.7 +/- 1.5 mm Hg intraoperatively. The difference between the starting ITP on catheter insertion and the observed peak intrathecal pressure after decompression was, on average, an increase of 7.9 +/- 1.6 mm Hg (p < 0.0001, paired t-test). During the postoperative period, the peak recorded ITP in the patients randomized to the no-drainage group was 30.6 +/- 2.3 mm Hg, which was significantly higher than the peak intraoperative ITP (p = 0.0098). During the same period, the peak recorded ITP in patients randomized to receive drainage was 28.1 +/- 2.8 mm Hg, which was not statistically higher than the peak intraoperative ITP (p = 0.15).

Conclusions: The insertion of lumbar intrathecal catheters and the drainage of CSF were not associated with significant adverse events, although the cohort was small and only a limited amount of CSF was drained. Intraoperative decompression of the spinal cord results in an increase in the ITP measured caudal to the injury site. Increases in intrathecal pressure are additionally observed in the postoperative period. These increases in intrathecal pressure result in reduced spinal cord perfusion that will otherwise go undetected when measuring only the MABP. Characteristic changes in the observed intrathecal pressure waveform occur after surgical decompression, reflecting the restoration of CSF flow across the SCI site. As such, the waveform pattern may be used intraoperatively to determine if adequate decompression of the thecal sac has been accomplished.
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http://dx.doi.org/10.3171/2008.10.SPINE08217DOI Listing
March 2009

In search of the "superior" cervical orthosis: Philadelphia Cervical Orthosis versus Aspen Cervical Orthosis.

SCI Nurs 2004 ;21(3):158-60

Acute Spine Program, Vancouver Coastal Health Authority, British Columbia, USA.

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December 2004

The Vancouver General Hospital acute spine journal club: a success story.

Authors:
Lise Belanger

SCI Nurs 2004 ;21(1):29-30

Acute Spine Program, Vancouver Coastal Health Authority, Vancouver, British Columbia.

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July 2004

Early versus late enteral feeding in patients with acute cervical spinal cord injury: a pilot study.

Spine (Phila Pa 1976) 2004 May;29(9):E175-80

Division of Spine, Department of Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada.

Study Design: A prospective randomized clinical pilot study to compare early versus late enteral feeding in patients with acute cervical spinal cord injury.

Objectives: To compare the incidence of infections in patients with acute cervical spinal cord injury who received early versus late enteral feeding. Secondary objectives included assessing nutritional status, feeding tolerance, the number of ventilator hours, and acute-care hospital length of stay.

Summary Of Background Data: Early nutritional support has been found to be beneficial in critically ill patients. However, the same benefits may not be realized in patients with acute cervical spinal cord injury because of their unique nutritional challenges.

Methods: Eligible patients were randomized to early feeding (initiated before 72 hours after injury) and late (initiated more than 120 hours after injury). Patients were stratified on the basis of their neurologic level. Patients were assessed daily for the first 15 days. After that time, infections (according to Center for Disease Control criteria), ventilator hours, and length of acute-care hospital stay were tracked.

Results: Twenty-three patients met the eligibility criteria, and 17 patients were included in the analysis. There were 7 patients in the early group and 10 in the late group. The early group had a mean of 2.4 +/- 1.5 infections compared with the late group, which had a mean of 1.7 +/- 1.1 infections. Secondary outcomes were not substantially different between the two groups.

Conclusions: This pilot study failed to detect any differences in the incidence of infection, nutritional status, feeding complications, number of ventilator hours, or length of stay between patients receiving early versus late initiation of enteral feeding. These data will assist in the determination of an adequate sample size for future studies.
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http://dx.doi.org/10.1097/00007632-200405010-00020DOI Listing
May 2004

Prospective randomized clinical trial comparing patient-controlled intravenous analgesia with patient-controlled epidural analgesia after lumbar spinal fusion.

Spine (Phila Pa 1976) 2003 Apr;28(8):739-43

Combined Neurosurgical and Orthopaedic Spine Program, Department of Orthopaedics, University of British Columbia, Vancouver Hospital and Health Sciences Centre.

Study Design: A prospective, randomized, double-blind clinical trial was conducted.

Objective: To compare the efficacy of patient-controlled analgesia (PCA) with that of patient-controlled epidural analgesia (PCEA) in terms of overall patient satisfaction with postoperative pain management after lumbar spine fusion.

Summary Of Background Data: In numerous surgical disciplines, PCEA and PCA have proved to be effective methods of postoperative pain control. The literature states that with PCEA, less opioid use is required during the immediate postoperative period to maintain equivalent pain control compared to PCA. Continuous epidural infusion has been assessed in spine fusion patients, but PCEA has not been evaluated. Furthermore, this is the first prospective randomized clinical trial to assess overall patient satisfaction while stratifying patients for both anxiety level and preoperative opioid use.

Methods: For this study, 74 patients were assigned randomly to one of two treatment groups, with PCA and PCEA administered in a double-blind manner for a 3-day postoperative course. All the patients received both PCA and PCEA delivery systems. Assessment was by a blinded, independent observer. Overall patient satisfaction with pain management was assessed by a visual analog scale at the end of postoperative day 3. Secondary measures included: three scales from the Functional Independence Measure instrument; opioid quantity; side effects; and length of hospital stay.

Results: Thirty-eight patients were randomized to PCA, and 36 were randomized to PCEA. No baseline variable differences between the groups were observed. The results showed no difference between the groups on the following measures: overall patient satisfaction with pain management, ambulation, and length of stay. The PCA patients used significantly more opioid than the PCEA patients.

Conclusions: Both postoperative analgesic regimens provided good overall patient satisfaction. The only clinical advantage of PCEA over PCA for spine fusion patients was the lower amount of opioid consumed, although the PCEA group experienced significantly more side effects than the PCA group. There were no other significant differences. Therefore, patient or physician preference could select either postoperative pain management delivery system.
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April 2003
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