Brain Enzyme May Help to Flag Severity of Traumatic Injuries

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 said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

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, she explained.

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.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. 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 after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels 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. “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, she said.

“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 said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA

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 said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

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, she explained.

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.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. 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 after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels 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. “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, she said.

“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 said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA

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 said at the annual meeting of the Society for Academic Emergency Medicine.

“We know that biomarkers can provide diagnostic and prognostic information, give us insight into the pathophysiology of the brain injury, and guide therapy in both the emergency department and intensive care unit,” said Dr. Papa, director of academic clinical research at Orlando (Fla.) Regional Medical Center.

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, she explained.

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.

The primary outcome was severity of injury as measured by postresuscitation and 24-hour dichotomized GCS score. Secondary outcome included the presence of evolving lesions on CT scan at 24 and 72 hours post injury. Over 16 months, 41 patients with severe TBI were enrolled. 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 after TBI and was measured by enzyme-linked immunosorbent assay for UCH-L1 levels.

The control group consisted of uninjured patients who required CSF drainage for other reasons. Mean 12-hour UCH-L1 levels 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. “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, she said.

“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 said, adding that these data suggest that UCH-L1 is a potential TBI biomarker. Dr. Papa said more than 5 million Americans live with TBI disabilities, and the hospital and fatality costs related to TBI exceed $48 billion annually.

'Patients with evolving lesions had significantly higher levels of the biomarker' after 48 hours. DR. PAPA