The University of Rochester Medical Center received $1.5 million to develop a blood test for concussions by isolating proteins that can predict memory loss, chronic headaches or other neurological problems.
At least one million Americans seek treatment for head injuries each year. However, many people initially assume their injury is mild and do not visit a doctor until after they experience cognitive difficulties. Having a rapid test that could be administered on sports fields, at the scene of automobile accidents or in combat situations would give medical personnel a head start, and offer clues about the extent of the brain injury.
“We are discovering that concussions are not benign, even if you only have one in a lifetime and it's relatively mild,” said principal investigator Jeffrey J. Bazarian, M.D., M.P.H., associate professor of Emergency Medicine and Neurology. “The latest research shows that mild or moderate head injuries might be a risk factor for early-onset dementia or Alzheimer's disease. This makes proper, timely diagnosis very important.”
A blood test would help doctors diagnose axonal injury, a type of brain injury that often occurs after a concussion but does not show up on a CT scan of the brain. In fact, a CT scan can appear normal in patients who suffer from lasting neurological defects due to axonal injuries, Bazarian said.
Diagnosis of axonal injury is difficult because CT scans are designed to detect bleeding in the brain, and not more subtle injury to neurons, the cells responsible for cognitive functioning. Axons make up the bulk of the neuron's structure. Axons travel in clusters, providing a connection to different areas of the brain through delicate, spaghetti-like strands. When axon fibers are stretched or strained, they stop working and the entire cell dies. Blows to the head, falls, or sudden deceleration from motor vehicle accidents can cause axonal injuries.
In a pilot study, Bazarian investigated whether a new type of brain scan called Diffusion Tensor Imaging (DTI), a dynamic form of the well-known MRI, could detect axonal damage from a minor injury. He studied the DTI scans of six people with mild concussions, and compared them to six scans of non-injured brains. Indeed, the DTI showed subtle axon swelling, which is known to occur when the axons are over-stretched. The axonal swelling correlated with the patients who were having trouble processing information or remembering things as well as before the injury.
Now, with the latest funding from the National Institutes of Health, Bazarian will use DTI technology to aid in a search for biomarkers that indicate axonal damage.
Researchers will conduct a clinical study by enrolling 37 adults, ages 18 to 65, who seek emergency treatment for head injuries. A control group will consist of 37 patients who seek treatment for orthopedic injuries such as sprained ankles or broken wrists. All patients will undergo a DTI brain scan and provide blood samples.
Researchers expect to screen about 15,000 proteins from the blood samples, and search for the small number of proteins that are different among the head injury group. Further analysis will include a study of the serum markers one week and one month after the head injury, to determine how cells change as the brain heals, Bazarian said.
“Mild traumatic brain injury is an important public health problem for which there is currently no objective diagnostic aid and no treatment,” Bazarian said. “Not only does it affect many people who are injured in their homes, on sports fields and in car accidents, but it frequently harms U.S. soldiers and public safety officers. Development of a rapid blood test is an essential first step to coming up with a treatment.”
For several years Bazarian has been studying head injuries on two paths: one toward the public-health goal of prevention, and the other in the laboratory to improve diagnosis. Previous NIH funding allowed him to start the nation's first Emergency Department-based traumatic brain injury registry, to understand how and where most people get injured. In addition, in 2006 he was awarded New York state funding to develop a finger-stick blood test that would quickly tell doctors whether a patient needed a brain scan to rule out internal bleeding.
Co-investigators from the University of Rochester are: Brian Blyth, M.D., Jianhui Zhong, Ph.D., Laura Cushman, Ph.D., Gerald Hoehn, Ph.D.