Biomarkers may hold key to better brain injury treatments

Objective measures will guide more accurate outcome predictions.

Asked to pinpoint the best way to increase understanding and decrease the impact of traumatic brain injuries (TBIs), Christopher Giza, MD, professor of pediatrics and neurosurgery and pediatric neurology division chief, UCLA Mattel Children’s Hospital, took only a split second before answering, “through research.”

Part of a UCLA research group participating in multiple national and international head injury consortia, Dr. Giza and his team study head injuries in both adults and children.

“Most people don’t realize the toll of pediatric neurological illnesses. We focus on all ages, including childhood and young adulthood when the brain is changing rapidly,” says Dr. Giza. “We also are examining long-term sequelae of head injuries in aging people who played sports and got injured when they were teenagers. Now they’re over 60 and they’re worried about dementia or cognitive decline.”

Participating in one of the largest NIH-funded studies of persisting post-concussion symptoms (PPCS), Dr. Giza hopes to identify biological mechanisms, which restrict some concussed patients from recovering.

“Many get better, but 10 to 30% do not, and we don’t know why. And since over 5-7 million children in the U.S. alone suffer TBI annually, 10-30% of a big number is still a big number (500,00 to 2,000,000 who develop PPCS). Until we understand the biology happening in those people, it’s hard to treat them. So, we’re capturing biomarkers in children with concussions and following them as they go through their recovery, in order to discover things we can treat. We also are studying people who don’t recover right away and trying to pinpoint exactly what their unique biology is.  It is efforts like this that will allow us to offer ‘precision medicine’ for these patients in the future.”

The study is still in the recruitment phase, so findings are at least a year off.

“However, we already know, from smaller studies, that one of the most common predictors of slow recovery from concussion is other brain conditions like migraines, anxiety, physical deconditioning and sleep disturbances,” Dr. Giza explains. “We’re trying to identify how head trauma affects these conditions.  We can duplicate this biology in the lab and can start to treat these conditions in animal models.

“In humans, we’re looking at MRIs of the brain, molecules in the blood and the autonomic nervous system’s response to injury. So, how is variability of the heart rate, blood pressure and pupillary reaction, etc., affected by TBI? What will that tell us that so that we can design future studies to treat TBI?”

Dr. Giza believes the first “deliverable” from ongoing research will be objective biomarkers from brain injury in adolescents that will improve clinicians’ ability to predict outcomes.

“Right now, somebody with a mild head injury may be directed to get a CT scan. Then they’re told they may have symptoms, and not to ‘overdo it until symptoms subside,’” Dr. Giza says.

“In the future, when someone comes in, we’ll have objective measures we can assess, whether related to heart rate, molecules in the blood or things we can see on an MRI. We’ll be able to tell people within the first week or two after an injury, ‘This is what we think is going to happen. And this is the best treatment for you.’ Biomarkers and an algorithm will help us predict [outcomes] and guide us in designing treatment trials.”


Dr. Christopher Giza stresses importance of safeguarding brain development

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