More and more players in the NFL are succumbing to symptoms of memory loss, inability to concentrate and changes in personality that they attribute to repeated blows to the head during play. But as their numbers grow, researchers are struggling to keep up with understanding the brain injuries that concussions can cause. Now, for the first time, scientists are classifying the brain injury from head trauma into four distinct stages.
Most agree that repeated mild trauma to the brain in the form of concussions can result in chronic traumatic encephalopathy (CTE), or a gradual buildup of a brain protein called tau. Just as with Alzheimer’s patients, where accumulation of plaques and tau tangles can space out healthy brain tissue and let nerve connections wither away, damage caused by concussions can trigger the accumulation of tau in CTE cases, eventually forming deposits large enough to interfere with key functions such as learning, planning and organization.
In the latest study, published in the journal Brain, scientists led by Dr. Ann McKee studied the brains of 68 deceased patients with CTE in order to find patterns in the way the disease develops. McKee, a professor of neurology and pathology at VA Boston Healthcare System and Boston University School of Medicine, spent more than two decades researching Alzheimer’s disease. She decided to apply the same order in staging brains that she had become accustomed to in her Alzheimer’s work. The number of CTE brains she and her team studied is the largest to date, and allowed them to see patterns in the way the disease progressed. The patients included football players, hockey players, boxers and veterans (many of whom were athletes) and one who engaged in self-inflicted head-banging behavior.
In order to generate the least biased analysis possible, McKee and her pathology team conducted the autopsy analysis of the brain tissue, while another group led by Robert Stern, a neurologist and neurosurgeon at Boston University School of Medicine, carried out detailed interviews with the deceased patients’ families about the patients’ lives, behaviors and symptoms.
In her first pass at the data, McKee was able to discern a distinct pattern of where and how CTE progressed. She and her team found focal points where the injury to the brain seemed to start. These were concentrated in the frontal lobe, deep in the valleys of the convoluted cerebral cortex. Cortex tissue resembles a crumbled piece of paper with folds that create peaks and valleys, and the lesions of CTE seemed to start in the valleys where small blood vessels also congregate. “There is a fairly stereotyped lesion; where the gray matter dives in to create a valley in the brain is where we see the greatest damage,” says McKee. “We also see over and over in all of these cases that there is a strong tendency of the disease to start around blood vessels, which means the blood vessel is damaged with the injury.”
While it’s not clear what triggers the damage, McKee suspects that the junction of the elastic blood vessels butting up against the more gelatinous cortex tissue may be particularly vulnerable to the shearing forces from an impact.
Once the damage is done, however, it’s difficult to stop. Even after the physical blows no longer occur, a destructive chain of events is already in motion. From these seed points in the frontal lobes, damage to nerves and brain tissue radiates to other parts of the brain, until it eventually engulfs most of the organ, impairing many cognitive functions. “Even if a person doesn’t get additional trauma, the disease progresses, like a lit fire,” says McKee. “The fire takes hold and continues to affect the brain with more lesions the longer the person lives.”
Because the study included the brains of patients who died at a range of ages, between 17 and 98, McKee could see the growing buildup of tau in the brain among the older cases. She could also see distinct stages of the disease, from lesser signs of lesions and tau to greater depositions. She could then correlate later stages of damage to longer play for the football players, and therefore likely more concussions.
While the findings confirm, and perhaps even reinforce how damaging concussions can be, McKee says they could also lead to better treatments for CTE. For one, recognizing that the disease begins with small lesions in the blood vessels could lead to helmets or other equipment that better protect the most vulnerable parts of the brain.
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In addition, it could help scientists develop higher-resolution brain scans to detect these early signs of the disease. Current technology is not able to find such small abnormalities, but researchers are testing a tracer that could detect the tiniest deposits of tau protein that would alert doctors to the potential for CTE. Patients could then be warned to avoid repeated head trauma like those that might occur on the football field.
Understanding that the damage occurs in the blood vessels could also lead to ways of protecting those vessels and preventing the damage from spreading to the rest of the brain. It’s not clear yet what is causing the initial lesions to seed damage to other parts of the brain, but if the damage causes leakage of agents that are toxic to nerve cells, for example, drugs or other interventions may block the added injury these lesions can cause.
The insights from CTE could also help researchers develop better treatments for other neurodegenerative conditions as well. “I’m optimistic that this disease gives us lots of insights into other diseases like Alzheimer’s,” says McKee. “If we could reduce tau somehow or wall off the early stages of the disease, we can prevent the degenerative part from developing.” Avoiding head trauma may not always be possible, but stopping the damage it can cause may one day be more realistic.