PUBLICATIONS
PUBLICATION SNAPSHOT
This study was a prospective randomized clinical trial in acute SCI patients in which lumbar intrathecal drains were inserted and the patients were then randomized to CSF drainage versus no drainage. We reported surprising (and potentially deleterious) changes in CSF pressure that occurred around the injured spinal cord after surgery. The recognition of these previously undetected changes may improve standard protocols for the hemodynamic management of acute SCI in patients. This paper set the stage for the follow-on CAMPER clinical trial to evaluate CSF pressure and spinal cord perfusion pressure in acute SCI.
This paper describes the outcome of our CAMPER clinical trial and revealed that spinal cord perfusion pressure (SCPP) was more meaningful than MAP for the prognostication of outcome after acute SCI. This paper is important because it reveals a potential role for routinely installing intrathecal catheters in acute SCI patients and monitoring (and potentially managing) SCPP. This publication led a number of institutions to begin instituting lumbar catheters as part of the standard hemodynamic management protocols for acute SCI (e.g. Univ. Pittsburgh and UCSF). This study has led to the initiation of the CASPER clinical trial which is being done in multiple centers across North America, in which we will actively manage SCPP by draining cerebrospinal fluid.
From our clinical trial of CSF drainage, we also obtained CSF samples for biochemical analyses in the lab. We characterized the temporal pattern of expression of inflammatory cytokines after human SCI from the CSF samples, and identified a series of proteins (IL-6, IL-8, MCP-1, GFAP, tau, S100b) as potential biomarkers of injury severity and predictors of outcome. The characterization of inflammatory changes after human SCI will help to focus the scientific community on changes that are clinically relevant. The identification of biomarkers of injury severity leads to the potential that biological measures could be used to stratify injury severity and predict neurologic outcome, instead of relying solely on functional measures.
This paper is important because it and the previous Journal of Neurosurgery paper published in 2009 prompted the launch of the $2.5M nation-wide multi-centre study called CAMPER (the Canadian Multicenter CSF Pressure and Biomarker Study). In CAMPER, a team of collaborators in Montreal, London, Toronto, Halifax, and San Francisco participated by enrolling acute SCI patients and installing lumbar intrathecal catheters. The goal was to establish new hemodynamic management guidelines for acute SCI patients, and to validate our previously identified biomarkers.
This was a large survey of opinion of researchers within the SCI community to address the question of “what preclinical evidence in scientific studies is needed to justify translating a potential SCI therapy into human clinical trials?”. This question is important because the clinical trials are extremely expensive and time-consuming to conduct, and hence, we cannot squander valuable resources to test therapies that have little preclinical substantiation. We obtained responses from over 300 individuals, and this, for the first time, provided a broad perspective from the clinical and scientific research community on these issues. This initiative to characterize how the research community feels about how these decisions are made will provide rational guidance to our field, and potentially prevent us from squandering valuable resources to test treatments that lack preclinical robustness.
This paper establishes a ‘bench to bedside’ and ‘bedside back to bench’ translational resource and has been employed in a number of our research studies. It also led to a number of further initiatives to characterize a rational roadmap for preclinical translation of SCI therapies. This paper has led to the publication of a number of additional manuscripts which engage both researchers and SCI patients to guide the process of translation in our field. These include:
This paper describes our work to develop a large animal model of spinal cord injury using the Yucatan mini-pig. Our work which surveyed the SCI research community (Kwon BK et al, Translational research in spinal cord injury: a survey of opinion from the SCI community. Journal of Neurotrauma. 2010 Jan;27(1):21-33) revealed that the majority of researchers strongly advocate for validating novel therapeutics in large animal models of SCI – and yet, such well characterized models are not readily available. Here, we set out to develop such a model. We outline the systematic testing of over 40 Yucatan mini-pigs (approx. 22-25 kg) in which a thoracic SCI was induced using a custom-made weight drop device and recovery was monitored over 3 months. This paper describes the refinement of the injury technique, a new locomotor recovery scale (PTIBS, or Porcine Thoracic Injury Behavioural Score), and resultant histologic damage within the cord.
This paper is important as it establishes a ‘bench to bedside’ and ‘bedside back to bench’ translational resource and has been employed in a number of our research studies.