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Old 08-17-2012, 09:23 AM   #3
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Default Re: The Woman Who Would Save Football

This is a charge Cantu adamantly rejects: "She is a scientist first, not an activist first."

McKee sighs. "You get enemies in this business." She must tread a not-so-fine line between SLI's advocacy mission and the publishing protocols of medical research. "This was discussed from the day we started working together," Nowinski says. "She recognized she would be criticized in academic circles for talking about [some of] the work before academic publication. A lot of the blame — pushing for some of the information to get out comes from me."

Hovda, whose research into the neurobiology of concussions demonstrated the vulnerability of the brain to second insults, says McKee's science is rigorous, significant, and does not overinterpret the available data, which is inherently limited by the facts of neuropathology — you only get to diagnose people who are already dead.

The bull's-eye on her back is likely to remain there as long as postmortem exam remains the only way to diagnose CTE. Progress toward identifying the disease in the living has been rapid — compared to the agonizingly slow pace of Alzheimer's disease research. Blood tests for tau, diffusion tensor imaging, functional MRI, and biomarkers that will allow doctors to image the disease are all in development. Already, Hovda says, researchers at UCLA can image tau and beta-amyloid deposits in laboratory animals, and may be able to do so in humans within the year. "I'd love to put her out of this business," he says. "And I bet Ann would love me to put her out of business."

McKee says: "I'll keep this up as long as it takes."

Longevity runs in her family.

She never expected to get inside the head of the NFL. She thought she would become an internist and turned to neurology and neuropathology not to get away from people but to get closer to what makes them uniquely themselves. "They entrust me with their privacy, really," she says. "What a person's tissues look like, what struggles they were going through during life, and then what disease they have at death is a very private matter. That's as naked as you could possibly be. It's revealing yourself and revealing your internal structure."

For 25 years she studied tau in perfect anonymity, trying to understand its pivotal role in aging and Alzheimer's disease.

"Why tau?" I asked.

"Because it's pretty," was the artist/pathologist's reply.

The tau protein, named for the 19th letter of the Greek alphabet, is a naturally occurring substance in brain cells. Its job is to hold together microtubules, which are rigid, hollow rods like beach reeds that serve as conduits between brain cells. Tau provides "the scaffolding to support its shape and also to help transport molecules, nutrients, back and forth," McKee says. "Without tau the cell would collapse and the transport functions would be critically impaired."

With repeated head trauma tau turns insurgent, a guerrilla force occupying and killing more and more of the brain. "It falls off the microtubules, and so they fall apart too," McKee says.

Each concussive blow to the head — a right cross, a body check into the boards, a helmet-to-helmet collision in the open field, a header inside the goalie's circle — becomes a potential IED, a bomb hidden on a neural pathway. Think of it this way, she says: "This transport function of the cell is just like a road. And the road just fell apart."

Dementia pugilistica — punch drunkenness — first appeared in the medical literature in 1928. In 2002, Bennet Omalu, then a neuropathologist at the University of Pittsburgh, diagnosed the first known case of CTE in former Pittsburgh Steeler Mike Webster. He joined forces with Chris Nowinski, who procured three more donations, including former Eagle Andre Waters. All showed evidence of CTE.

In 2003, McKee performed an autopsy on a 72-year-old veteran who had been diagnosed with Alzheimer's disease 15 years earlier. She found toxic tangles of tau common to Alzheimer's and CTE, but they appeared in a totally unfamiliar pattern. And there was no evidence of the beta-amyloid plaques also present in Alzheimer's patients.

After the autopsy, she learned he had been a world-champion boxer. "That was the aha moment," she says. "I kept asking my colleagues if they had another boxing brain. I couldn't get it out of my mind."

McKee's laboratory does the neuropathology work for the Framingham Heart Study, the landmark multi-generational investigation into causes of heart disease. "I went back and stained all the Framingham heart disease cases we had, looking for a pattern of change that looked anything like this. I have drawers and drawers and drawers of these slides, and nothing looked like it.

"Then [in 2005] we got another through the Alzheimer's Center. There wasn't any history of head trauma. I went through all the medical records and nothing, so I got the name of the family. And I called the daughter, and she said, 'Well, he did box professionally in his 20s.' So, that was like, 'Okaaay.'"

In Stage 3, the medial temporal lobe atrophies. The hippocampus, essential for learning and memory, is attacked. The amygdala, which governs aggressiveness and rage, is assaulted. Symptoms multiply and intensify: headaches, depression, insomnia, anxiety; loss of impulse control, executive function, and emotional regulation; tremors, vertigo, slurred speech and a staggered gait; and finally dementia.

In 2008 Nowinski came calling. He had parted ways with Omalu. He was also suffering the consequences of his WWE career, when he was known as Chris Harvard. Four wrestling concussions and two others on the gridiron had left him with severe headaches and impaired short-term memory — although he hasn't forgotten the taste of blood in the back of his throat that accompanied hits he took as a defensive tackle for the Crimson. (Thanks to a recent pickup basketball game, the count is now seven.)

He consulted Cantu about his symptoms. The doctor-patient relationship evolved into a professional alliance. They created SLI and later partnered with Robert Stern, director of Boston University's Alzheimer's Disease Clinical & Research Program, to create the Center for the Study of Traumatic Encephalopathy with the goal of acquiring and examining brains of deceased athletes exhibiting symptoms of premature dementia. All they needed was someone to do the autopsies. "Have I got the neuropathologist for you!" said Stern.

McKee sounds a lot like a football coach when she talks about her team at the Brain Bank, except, she says, her people give 400 percent. Over the course of three or four painstaking months, McKee's staff will cut half the brain into slices the thickness of white bread. They will use a high-tech deli slicer called a Microtome to shave 50-micron slivers of tissue — 0.001968 inches — which will shrink to less than half that size and be stained, fixed to slides, and magnified, perhaps 100 times, under the microscope.

"Handwork," she calls it.

Unstained, tau is unidentifiable. Staining makes the texture and the damage palpable. Some pathologists use a blood-red color to dramatize areas of disease. McKee favors brown, the color of dried blood.

On the day I visited, she spoke about the woman who prepared her slides for the last decade and whose devotion to her craft, despite failing health, was that of a mother hoping to find a way to protect her son. "An artisan," McKee calls her. "Like a person who makes a mosaic out of a million little pieces. It can take three or four hours just to lay the tissue out on the slide" — not including cutting and staining — "because you get it when it's wet and you have to manually smooth down every single teeny-tiny wrinkle."

John Grimsley, a linebacker who suffered three concussions in college and eight in the NFL, was the first NFL player whose tissue they examined. What McKee saw was so unprecedented in her experience that she twice asked Dan Perl to come look at the slides. It was a case of: Do you see what I see? He did. "When you look at the tangles, you say, 'Wow,'" Perl says.

While McKee and her staff dissect and preserve tissue, Stern, who oversees the CSTE registry, interviews family members to develop a case history: number of years and position played and in what decade, number of concussions suffered and symptoms noted. The most frightening finding is that "the biggest problem isn't the concussions, actually," McKee says. "It's the sub-concussive hits that mount up every single time these guys line up."

It's been estimated that there are 1,000 to 1,500 of those kinds of hits per season per person in the NFL. "A big job liability," she says.

In November, Stern received a $1.5 million grant from the National Institutes of Health to study 100 former players between ages 40 and 69 with symptoms consistent with CTE who played positions at the greatest exposure for getting hit in the head — defensive linemen, linebackers, offensive linemen, and defensive backs. The goal is to establish risk factors for the disease and genetic predisposition. "If we can figure out the genetic risk, we could be much smarter about informing individuals who are considering playing these sports what their relative risks are," McKee says.

Despite new NFL rules limiting the number of padded practices, and protecting defenseless receivers, the cumulative effect of violent collision remains dire. McKee believes there is "a window of reversibility" of perhaps one year before the disease has had "a chance to gain speed [and] cause the cells to die."

Stern: "With each brain that comes in, especially the younger ones, and especially the ones without any known significant history of concussions, but a whole lot of sub-concussive blows, that's where she gets really scared. That's where we all get really scared."

Posters hanging in the conference room show the sickening march of the disease — an 18-year-old who looked like he had cigarette holes burned in his brain; Owen Thomas, a junior and co-captain of the University of Pennsylvania football team who never suffered a concussion; Dave Duerson, who played 11 years in the NFL.

McKee has developed a four-tier system for staging the disease that first invades the front cortex — the province of judgment, insight, inhibition, and concentration — and then begins to "work its way inward, penetrating the essence of a person."

All generalizations are dangerous.
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