title: Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.
abstract: 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.
authors.affiliation: 1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .|2 International Collaboration on Repair Discoveries , Vancouver, British Columbia, Canada .
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
authors.affiliation: 2 International Collaboration on Repair Discoveries , Vancouver, British Columbia, Canada .
authors.forename: Femke
authors.initials: F
authors.lastname: Streijger
authors.affiliation: 3 Rick Hansen Institute , Vancouver, British Columbia, Canada .|4 Department of Medicine, University of British Columbia Vancouver , British Columbia, Canada .
authors.forename: Nader
authors.initials: N
authors.lastname: Fallah
authors.affiliation: 1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .|3 Rick Hansen Institute , Vancouver, British Columbia, Canada .
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Noonan
authors.affiliation: 5 Vancouver Spine Program, Vancouver General Hospital , Vancouver, British Columbia, Canada .
authors.forename: Lise M
authors.initials: LM
authors.lastname: Bélanger
authors.affiliation: 5 Vancouver Spine Program, Vancouver General Hospital , Vancouver, British Columbia, Canada .
authors.forename: Leanna
authors.initials: L
authors.lastname: Ritchie
authors.affiliation: 6 Department of Surgery, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Paquette
authors.affiliation: 6 Department of Surgery, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: Tamir
authors.initials: T
authors.lastname: Ailon
authors.affiliation: 6 Department of Surgery, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: Michael C
authors.initials: MC
authors.lastname: Boyd
authors.affiliation: 1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: John
authors.initials: J
authors.lastname: Street
authors.affiliation: 1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: Charles G
authors.initials: CG
authors.lastname: Fisher
authors.affiliation: 1 Department of Orthopedics, Vancouver Spine Surgery Institute , Vancouver, British Columbia, Canada .
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Dvorak
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002574:Cervical Vertebrae; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid*; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D013904:Thoracic Vertebrae; D015599:Trauma Severity Indices; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: biomarkers; cerebrospinal fluid; injury severity; neurological recovery; spinal cord injury