1. Characterization of Cerebrospinal Fluid Ubiquitin C-Terminal Hydrolase L1 as a Biomarker of Human Acute Traumatic Spinal Cord Injury.
- Author
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Stukas S, Gill J, Cooper J, Belanger L, Ritchie L, Tsang A, Dong K, Streijger F, Street J, Paquette S, Ailon T, Dea N, Charest-Morin R, Fisher CG, Dhall S, Mac-Thiong JM, Wilson JR, Bailey C, Christie S, Dvorak MF, Wellington C, and Kwon BK
- Subjects
- Adolescent, Adult, Aged, Biomarkers blood, Biomarkers cerebrospinal fluid, Canada, Case-Control Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Motor Activity, Pilot Projects, Predictive Value of Tests, Prospective Studies, Recovery of Function, Spinal Cord Injuries physiopathology, Time Factors, Trauma Severity Indices, Young Adult, Spinal Cord Injuries blood, Spinal Cord Injuries cerebrospinal fluid, Ubiquitin Thiolesterase blood, Ubiquitin Thiolesterase cerebrospinal fluid
- Abstract
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.
- Published
- 2021
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