Biomarkers Combined Differentiate Between TBI and Non-TBI Patients

A study in the Journal of Neurotrauma hypothesized that two specific biomarkers reflect the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are the most scientifically accepted biomarkers that relate to brain injury. They also presumed that measurement of both of these biomarkers together would be superior to measurement of these individually.

Serum levels of GFAP and UCH-L1 were measured in a group of 206 patients participating in the multicenter study. Each biomarker by itself had sensitivity for determining the difference between patients with TBI and healthy controls. When combined, better sensitivity and specificity for determining TBI patients was obtained.

Sensitivity is the degree to which a test might rule in a problem. For example, a test for memory might rule in those with brain injury and Alzheimer’s. Specificity is the degree to which those who are ruled in actually have the specific condition which is being test for versus something else. A test might be sensitive for memory impairments but not able to tell whether the memory impairments were caused by TBI or aging.  Often times, external factors (like age or medical condition) can be used to make an otherwise non-specific test, useful for diagnosis. For example if you see significant memory deficits in someone who is under 60, age related dementia is not the likely cause.

Both biomarkers determined the difference between those with intracranial lesions on a CT scan and those without. GFAP measures were more sensitive and specific. For outcome after three months, neither biomarker had adequate sensitivity or specificity. However, the research still does support multiple biomarkers in TBI research.

One goal of the study was to see if knowledge of biomarkers would make it easier to predict what patients would have long-term effects from a brain injury, whether it be mild or severe. It would also aid in deciding what kind of pharmacological interventions should be taken. UCH-L1 is found in nerves and is involved in the degradation of protein cells. GFAP is a protein induced by neural injury and released on decay of the cytoskeleton of a star-shaped glial cell of the nervous system, called an astrocyte. In other words, these proteins are released in the acute period of TBI.

The study’s subjects were involved in a clinical trial. The researchers had the opportunity to collect their blood. Anyone who had a traumatic brain injury that required admission to the hospital was included. This included people who were in comas from severe TBI. Mild cases who were sent home from the hospital were not included.

Dr. Ramon Diaz-Arrastia was the lead researcher at the Uniformed Services University’s Center for Neuroscience and Regenerative Medicine in Bethesda, Maryland. “The main purpose of the study is to help people recover from brain injury,” he said in our interview with him. “Biomarkers can be assessed in an acute period.”

He also explained that the research could be pharmacodynamic, or able to measure the effectiveness of treatment. “Until we have these biomarkers, it’s going to be very difficult to find treatment,” he said.

So far, researchers have relied on animal models to find the proper dose and timing of treatments. “We need biomarkers in human TBI,” he said.

With the biomarkers, doctors could identify who should be treated with the optimal dose and timing. “Until we know these things, it’s going to be very hard to develop a neuroprotective therapy,” he said.

While we hail the research for biomarkers of TBI, we also caution that much of the impetus for such work is so that the TBI Drug can be developed. A shortcoming in such research thus far has been that theory that there can be a simple drug to treat something as complex as even a single neuron, more or less the human brain. The pharmaceutical industry is hoping they can follow the model of research into heart ailments, to find the cure for neurological disorders. The heart is essentially a muscular pump. The brain is more complex than the most sophisticated computer. This research is a good start, but nuts and bolts rehabilitation, a commitment to a lifetime of recovery, is the only realistic horizon for brain injury survivors.

Attorney Gordon Johnson


Gordon Johnson

Attorney Gordon Johnson is one of the nations leading brain injury advocates. He is Past-Chair of the TBILG, a national group of more than 150 brain injury advocates. He has spoken at numerous brain injury seminars and is the author of some of the most read brain injury web pages on the internet.

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