Concussion Pathologist Played by Will Smith Tells His Story

NASHVILLE, Tennessee — Movie trailers about Bennet Omalu have already hit theatres promoting the film Concussion. And Dr Omalu will be in the spotlight again this weekend at the College of American Pathologists 2015 Meeting, when he recounts the winding road that took him from a coroner's office, to the discovery of a new neuropathology, and on to Hollywood.

The attention and bright lights are new to Dr Omalu, who remembers a solitary Saturday alone in the Allegheny County medical examiner's office where his journey began.

Fresh out of his fellowship training in neuropathology, Dr Omalu found himself looking down at the body of former Pittsburgh Steelers center Mike Webster.

It was 2002 and Dr Omalu knew the basics of the trajectory that had led Webster to where he was. An autopsy begins with a profile of a person's life, he explained to Medscape Medical News.

Webster had played professional football for 17 years. After he retired, he fell into a depression, struggled with drug abuse, and attempted suicide. By the age of 50, he was dead of vascular disease.

Dr Omalu was expecting to see this hard life reflected in Webster's autopsy, particularly in his brain. "But to my utter amazement, when I opened his skull, Webster's brain looked completely normal — there wasn't even any evidence of bleeding — and this in somebody who had received over 200,000 blows to his head playing football and in practice," he said.

Puzzled, even unsettled, by the lack of obvious pathology, Dr Omalu decided that he would fix the brain in formalin rather than cut into it so that he could study the specimen more closely.

This was the beginning of a journey that would lead him to identify a new neuropathology, which became known as chronic traumatic encephalopathy (CTE).

After about 6 months of "spending time with Webster's brain," as he put it, Dr Omalu noticed patterns of diffuse amyloid — this in a man with no history of Alzheimer's disease in his family.

There were also sparse neurofibrillary tangles and tau-positive neuritic threads in the neocortical areas of Webster's brain, although there was no evidence of either Lewy bodies or classic Alzheimer's disease.

Not finding any disease to which he could reasonably match the observed histomorphology, Dr Omalu went to the literature and then to his fellowship mentor, Ronald Hamilton, MD, from the University of Pittsburgh.

"I showed him the specimen and told him who it was, and Dr Hamilton said it was unusual, but he didn't know what it was either," Dr Omalu recalled.

Together, they consulted with neurologist Steven DeKosky, MD, then also at the University of Pittsburgh, who confirmed the findings were real, but not recognizable as belonging to a known disease.

Dr Omalu decided to report this unusual pathology as a sentinel case.

Three years later — journal reviewers proved to be a skeptical bunch, said Dr Omalu — a report appeared in Neurosurgery (2005;57:128-134), in which Dr Omalu and fellow authors described what looked to them like possible long-term neurodegenerative outcomes in retired professional NFL players subjected to repeated brain injury, as Mike Webster had so obviously been.

Dr Omalu then set out to gather evidence that others like Webster had been similarly afflicted.

"This is not about football; it's not even about sports," he told Medscape Medical News. "It's about any human activity that exposes people to repeated blows to the head."

Traumatic Brain Injury

The medical community has long understood that repeated blows to the head can cause brain damage. As literature reports indicate, concussion or mild traumatic brain injury account for about 90% of all brain injuries. In athletes who compete in high-impact contact sports, like football, hockey, and boxing, blows to the head are almost a daily occurrence.

The pathologic mechanisms leading to delayed post-traumatic changes may be multiple, but it is thought that some of these changes are brought about by biochemical cascades that are induced by the cumulative effects of repeated low-grade concussive brain injury.

"It has been suggested that repeated axonal injury, vascular injury, and ischemia trigger a cascade of molecular events involving derangement of neuronal cytoskeletal metabolism and accumulation of abnormal cytoskeletal proteins," Dr Omalu and his colleagues write in their seminal 2005 publication.

There is also increased expression of amyloid precursor protein and a subsequent increase in beta-amyloid fragment, which is deposited in amyloid plaques.

A recent study, reported in a documentary that aired on Frontline September 18, found that all but four of 91 former NFL players who donated their brains for research were diagnosed with CTE.

According to a PBS news release, 40% of those who tested positive for CTE in this study were offensive and defensive linemen who came into contact with one another on every play of a game.

Dr Omalu was also the first to identify CTE in the brains of returning war veterans who had initially been diagnosed with post-traumatic stress disorder and who had committed suicide on their return from active duty.

It is now believed that CTE identified in the military veterans might be due to what is being called a blast-variant of CTE caused by the explosions and energy jolts common in warfare.

Diagnosing CTE

So far, only findings on autopsy can confirm or rule out the presence of CTE; however, Dr Omalu and others are exploring the value of a new tracer,¹⁸F-FDDNP, that interacts with amyloid and tau in the brain. The tracer could allow researchers to identify CTE in living individuals with the help of PET imaging.

A study evaluating FDDNP-PET demonstrated that FDDNP signals are higher in NFL players with histories of mood and cognitive symptoms in all subcortical regions and in the amygdala — areas that produce tau deposits after trauma — than in control subjects (Am J Geriatr Pyschiatry. 2013;21:138-144).

Dr Omalu has been working closely with writers, producers, and editors on the film version of the book Concussion. The movie, starring Will Smith, will be released December 25.

"This all started with a promise I made to Mike Webster. I said to him: 'Mike, if you help me, we shall vindicate you'," Dr Omalu explained.

"I think players and their families are now being vindicated," he added, "because we are finally beginning to understand the problems they have had and the issues they have had to face."

Dr Omalu holds a patent license on behalf of Taumark, a company that owns the rights to an experimental imaging probe currently used in research with neurodegenerative disease patients.

College of American Pathologists (CAP) 2015 Meeting. Presented October 4, 2015.

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Cite this: Concussion Pathologist Played by Will Smith Tells His Story - Medscape - Oct 04, 2015.