BOSTON – The biomarker glial fibrillary acidic protein accurately distinguished between mild and moderate traumatic brain injury, between mild traumatic injury and controls, and between patients with and without intracranial lesions on CT in a prospective cohort study of emergency department patients with head injuries.
Glial fibrillary acidic protein (GFAP) is found in glial cells and is specific to the central nervous system. Found in both gray and white brain matter, it has recently been identified in serum, which makes it an attractive candidate as a clinical biomarker. Currently, the Glasgow Coma Scale (GCS) is the primary measure used to assess patients with head injury, but it can be influenced by intoxicants, medication, other injuries, or hypoperfusion and was not actually intended as an emergency department tool. "Really what we’d like is to develop some kind of biomarker that can be [measured] quickly and accurately, just like we do troponin for ischemia, or creatinine or bilirubin. Some type of blood test for the brain is our ultimate goal," said Dr. Linda Papa, director of academic clinical research, graduate medical education, Orlando Health, and an attending emergency physician at Orlando (Fla.) Regional Medical Center.
Dr. Linda Papa
The study enrolled adult patients at three level 1 trauma centers who presented with mild or moderate blunt traumatic brain injury (TBI) and loss of consciousness or change in sensorium. Patients were enrolled from the ED and had blood samples collected within 4 hours of injury. All received CT scans. Control groups included patients with orthopedic trauma or motor vehicle trauma without head injury, and normal healthy people recruited from an ad. One aim of the study was to collect a large amount of normative data, she noted at the annual meeting of the Society for Academic Emergency Medicine.
A total of 307 patients were enrolled in the study, of whom 108 had a TBI. The TBI patients had a mean age of 39 years (range 18-89), and 65% were men. A total of 97 had GCS scores of 13-15 (mild), and 11 had GCS scores of 9-12 (moderate). Of the 97 with GCS 13-15, 24 (25%) had CT scans positive for intracranial lesions, and of the 11 patients with GCS scores 9-12, 8 (73%) had positive CTs. Controls included 176 normal individuals, 16 with non–head injury motor vehicle accidents, and 7 with orthopedic injuries.
Blood samples were drawn within a mean of 2.7 hours after injury. The GFAP biomarker first appeared in the serum within an hour (among those who had blood drawn that soon), increased until 3-4 hours, then leveled off. "It’s very interesting that so early in the course of injury, you can see a marker appearing in the blood," Dr. Papa commented.
Early GFAP levels were able to distinguish TBI patients from uninjured controls with an area under the curve (AUC) of 0.90 (1.0 is perfect), and differentiated those with mild TBI (GCS 15) from all controls with an AUC of 0.88. Mean GFAP levels in patients with negative CT scans versus those with positive CT scans were 0.335 ng/mL and 2.168 ng/mL, a highly significant difference with an AUC of 0.79.
The findings, if validated, suggest that early elevations of GFAP can be a potentially useful clinical tool in determining whether to image patients who are intoxicated or sedated, to admit or discharge patients from the ED, to assess severity of brain injury in a multiple trauma victim, to seek neurosurgical consultation and/or transfer to a neurosurgical facility, and to assess whether the patient can return to play or duty, she said.
Dr. Papa disclosed that she is a scientific consultant for Banyan Biomarkers, the company that is developing GFAP. However, she does not own stock or hold patents with the company. This study was funded by a grant from the Department of Defense and the National Institute of Neurological Disorders and Stroke.