Concussion study may 'change the game'

Researchers have identified evidence of early chronic traumatic encephalopathy (CTE) brain pathology after head impact -- even in the absence of signs of concussion. Early indicators of CTE pathology not only persisted long after injury but also spread through the brain, providing the best evidence to date that head impact, not concussion, causes CTE.

The findings, published online in the journal Brain, help to explain why approximately 20 percent of athletes with CTE never suffered a diagnosed concussion. The findings were based on analysis of human brains from teenagers with recent head injury, animal experiments that recreate sports-related head impact and military-related blast exposure, and computational models of the skull and brain during these injuries.

CTE is a neurodegenerative disease characterized by abnormal accumulation of tau protein around small blood vessels in the brain. CTE causes brain cell death, cognitive deficits and dementia. CTE pathology has been observed in brains of teenagers and adults with exposure to repeated head injury. However, the mechanisms that cause CTE and their relationship to concussion, subconcussive injury and traumatic brain injuries (TBI) like CTE remain poorly understood.

"Concussion appears to be distinct from CTE," said William Moss, LLNL physicist and co-author on the paper. "This could be game changing. It means that we may need more than a concussion protocol to protect athletes."

CTE has been observed in the brains of teenagers and adults with exposure to repeated head injury, both concussive and subconcussive episodes. A recent study published in the Journal of the American Medical Association by other co-authors of this paper found signs of the neurodegenerative disease in 99 percent of the brains donated by families of former NFL players, in 91 percent of college football players and 21 percent of high school players.

Moss and computational engineer Andy Anderson joined a team of more than 40 researchers led by Dr. Lee Goldstein, Boston University School of Medicine. The Livermore team used computational modeling to understand why both impact and blast triggered CTE but only impact resulted in concussion. This surprising result uncoupled concussion and CTE and suggested different mechanisms leading to each.

Surprising observation and a eureka moment

Researchers began by examining four postmortem brains from teenage athletes who had sustained head-impact injuries just prior to death and comparing these brains to age-matched control brains. Analysis showed a spectrum of post-traumatic pathology, including one case of early-stage CTE and two cases with abnormal accumulation of tau protein. Brains from the control group did not show these pathological changes.

Then they tested the effects of a blast versus impact in animal experiments designed to produce identical motions of the head. Both loading mechanisms showed strong causal evidence linking head acceleration to TBI and early CTE, but there was one striking difference: Impact caused concussion but blast didn’t. These observations suggested that concussion and CTE might be unrelated.

"That result was very surprising," Anderson said. "So, Willy [Moss] and I turned to supercomputer simulations to take a closer look."

Moss has spent nearly a decade simulating how blast and impact interact with the skull and brain. Before partnering with Goldstein, his research focused on helmet pads, comparing the effectiveness of combat and football pads in protecting the brain from the effects of impact.

While it was impossible for Goldstein to design an experiment that could explain the surprising observation, the Livermore computational simulations provided Moss and Anderson a glimpse into why impact caused concussion while blast didn’t.

"We first looked at pressure fields and didn’t see anything surprising going on," Moss said. "Then we looked at shear stress and saw a clear difference. We suspected we were on to something important. When I shared the results with Lee, he had a eureka moment: ‘Willy, I think you may have uncovered the cause of concussion.’"

In a blast, the pressure wave flows fairly uniform around the head. In an impact, the pressure is loaded through a more focused point. Even with a low magnitude impact, one that wouldn’t rip or tear brain tissue, shearing can disrupt small blood vessels, nerve fibers and chemical channels in the brain.

"All this takes place in less than a millisecond," Moss said. "The concussion occurs before there is any significant head motion."

The simulations were completely consistent with the experimental data, and the result proved crucial for the research team, helping them conclude that the force-loading mechanism (impact versus blast) at the time of injury shapes the effect on the brain, and confirming that the mechanisms that cause concussion are distinct from those that lead to CTE.

These findings have direct relevance for athletes and military veterans. This study provides the best evidence to date that the neurodegenerative disease is triggered by repeated neurotrauma, not concussion.

"Our findings provide strong causal evidence linking head impact to TBI and early CTE, independent of concussion," Goldstein said. "To prevent the disease, you have to prevent head impact – it’s hits to the head that cause CTE."