Characterization of CSF ubiquitin C-terminal hydrolase L1 (UCH-L1) as a biomarker of human acute traumatic spinal cord injury.

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 hours post-injury from 32 acute SCI patients who were followed prospectively to determine neurologic outcomes at 6 months post-injury. UCH-L1 concentration was measured using the Quanterix Simoa platform and correlated to injury severity, time, and neurologic recovery. We found that CSF UCH-L1 was significantly elevated by 10-100-fold over laminectomy controls in an injury severity and time dependent manner. 24h post-injury CSF UCH-L1 concentrations distinguished between 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 subjects who did not improve their AIS grade at 6-months post-injury were characterized by sustained elevations in CSF UCH-L1 up to 96 hours. Similarly, the failure to gain more than 8 points on the total motor score at 6 months post-injury was associated with higher 24h 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 to predict outcome. Keywords: UCH-L1; biomarker; spinal cord injury; cerebrospinal fluid; prognosis.