Last year, the National Institutes of Health, with funds provided by the NFL, held what it optimistically called a consensus workshop, at which McKee and other specialists hammered out a definition. According to the criteria, CTE progresses in stages and can be distinguished from other neurodegenerative disorders by the location of NFTs. Specifically, the NFTs accumulate within cells near the blood vessels at the bottom of the sulci, the folded portions, of the cortex. There are other abnormalities supporting the case definition, but without tau in the cortical sulci, the other elements aren’t specific to CTE.
Teasing Out a Diagnosis
Is there consensus? Not yet. Critics of the Boston University team, most of whom are not associated with the NFL, have grudgingly gone along with the tau-based definition while raising a rash of other questions. Their core objection is that the post-mortem signs of the pathology are only vaguely correlated with concussions and clinical symptoms in vivo: what players actually go through during life.
Rudy Castellani, a neuropathologist at the University of Maryland, has been the lead author on several skeptical reviews of CTE. “In neuropathology we can’t say what a concussion is,” Castellani says. “Then, to use tau data to say there have been concussions upstream [earlier in time] and then downstream effects like suicide — I think relating suicide to tau is absurd. From a neuropathological standpoint we have enough difficulty, during life, diagnosing dementia and Alzheimer’s in patients.”
Why do the great majority of players who suffer repetitive concussions never develop the cognitive and psychological problems associated with CTE?
McKee’s Boston University colleague Robert Stern has a study underway to classify the symptoms and identify real-time biological markers of CTE in athletes. At UCLA, researchers have tested PET (positron-emission) scans as a diagnostic tool. But other uncertainties will be even harder to resolve. Why do the great majority of players who suffer repetitive concussions never develop the cognitive and psychological problems associated with CTE? Is there a quantifiable risk for the disease? That is, if concussions are comparable to a toxic exposure, what is the dose-response — the number and severity of impacts that drive the progression of the condition? What are the genetic factors and lifestyle factors, especially drug and alcohol abuse, that may aggravate or dampen the hazard? And since the clinical symptoms ascribed to CTE strongly overlap with the symptoms of depression and Alzheimer’s disease, to name just two confounders, how can related conditions be teased apart? Proponents acknowledge that CTE and Alzheimer’s can affect a single brain at the same time. This wrangling is only over diagnosis, which pushes questions about prevention and treatment further into the future.
“As the research goes forward, it will get more precise,” says McKee. A recent study applied the McKee criteria to a repository of brain tissue in Florida having nothing to do with professional football. CTE was detectable in about a third of the men who’d said they played contact sports, but it did not show up in matched controls, the men whose histories didn’t refer to activities where concussion was a risk. The gold standard is to track athletes and non-athletes forward through their lives and compare what happens to their behavior, cognition and brains. That research has begun, too.
The watchword is patience, often in short supply in a football stadium. McKee and her associates have been quick to publish a CTE finding when they diagnose it in a prominent ex-athlete. She does so, she says, because of the “urgent nature of this research. We need more funding and attention to the public health issue.”
But feelings of urgency can prompt mistakes. Take Todd Ewen’s story. Ewen, a 49-year-old former professional hockey player, a brawler on the ice, killed himself last fall. He was terrified of CTE, said his wife, and was sure he had it. An autopsy showed he didn’t. Something else was tormenting his brain.
[This article originally appeared in print as "Ahead of the Hit."]