CHICAGO — An enzyme found in brain cells may become the first bedside biomarker for assessing the severity of traumatic brain injury, according to Dr. Linda Papa.
In a multicenter trial, levels of the enzyme ubiquitin C-terminal hydrolase (UCH-L1) rose significantly in severely injured brains, an increase that paralleled the rise in cerebral spinal fluid and correlated with the Glasgow Coma Scale (GCS) score, Dr. Papa told the annual meeting of the Society for Academic Emergency Medicine.
If further study confirms the value of UCH-L1 as the first clinical biomarker in traumatic brain injury (TBI), physicians will be better able to identify targets for drug therapy and guide the timing of treatment with such agents as tissue plasminogen activator, explained Dr. Papa, director of academic clinical research at Orlando Regional Medical Center.
This prospective case-control study enrolled consecutive adult patients presenting to two tertiary care teaching hospitals following severe TBIs, defined by a GCS score of less than 8 and requiring invasive intracerebral monitoring. Fourteen patients with severe TBI were enrolled over 16 months. Their mean age was 38 years, and four-fifths were men. Patients were excluded if they did not have ventriculostomy, which is necessary to obtain cerebrospinal fluid (CSF). Ventricular CSF was drained from each patient at 6, 12, 24, 48, 72, and 96 hours following TBI, and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.
Mean 12-hour UCH-L1 levels in the control group of uninjured patients with other indications for CSF drainage were 145 ng/mL for patients with GCS scores of 3–5, and 38.5 ng/mL in those with GCS scores of 6–8. Similarly, 24-hour levels were 76 and 36 ng/mL for those with GCS scores of 3–5 and 6–8, respectively. The largest increase in the experimental biomarker occurred during the first 48 hours after injury, Dr. Papa said, noting: “Then we found that patients with evolving lesions had significantly higher levels of the biomarker” than did patients with nonevolving lesions at both 48 and 72 hours.”
“There is a significant increase in CSF UCH-L1 following severe human TBI compared to uninjured controls, and there is a significant association with severity of injury as measured by GCS and the presence of evolving lesions on CT,” Dr. Papa concluded, adding that these data suggest that UCH-L1 is a potential TBI biomarker.
Levels of the enzyme in the CSF corresponded to severity of injury and to CT evidence of evolving lesions. DR. PAPA