A Brain Gone Bad
February 8, 2016 - accent chair
The initial thing Patient 53 saw as he walked in was a red football helmet. A plaint rattled by his vending-machine-sized frame. “The final thing we wish to see,” he said, “is a football helmet..”
It was a complicated cosmetic various from his personification days, in a 1980s, as an descent lineman in a National Football League, one of 4 helmets lined adult on a front table of a Center for a Study of Traumatic Encephalopathy. Tucked into a seventh building of a Boston University School of Medicine, a core had welcomed 52 late football players like him over a past 6 months, any racked by a singular question: Had their smarts left bad?
Two years before, when he entered his mid-50s, Patient 53 fell into a fog, and he hadn’t come behind since. He was drunken and sleepy and frazzled. He’d visited some-more than a dozen doctors. None helped much. He’d seen a news, seen former teammates struggle. The suicides. He knew doctors had found a degenerative mind disease—chronic dire encephalopathy, or CTE, as it’s known—in a series of defunct former football players. But zero could contend if he had it. There was no approach to know; it could be diagnosed customarily by slicing a mind open, they told him.
So when Patient 53 listened that these Boston researchers, a same pioneers who had found a illness in those upheld pros, were recruiting former players to assistance them diagnose CTE in a living, he sealed adult immediately. So did several hundred of his peers.
This is a problem you’ve listened about. Over a past decade, CTE, a illness once suspicion singular to a few boxers and labeled dismissively as “punch-drunk syndrome,” has blown adult as a medical and informative phenomenon. 60 Minutes investigated it. Prime-time courtroom dramas have filmed scripts on it. Worry is widespread: Is it a hazard customarily to a thousands of stream and former NFL players? What about a some-more than 60,000 active players in college football? The 1.1 million children personification in high school? The dual million veterans of a wars in Iraq and Afghanistan?
Concerned relatives inundate a five-year-old BU core with questions; given a symptoms—anxiety, depression, confusion—are widespread, and distant from exclusive, it’s easy to burst to self-diagnosis. “Everybody wants to know if they have this disease,” one researcher told me. “Then everybody wants a treatment.” What they don’t wish to know is how small a scientists know.
“We don’t have any idea about a rest of a disease—the hows, a whys. Anything unequivocally about it, solely what it looks like,” says Robert A. Stern, a BU neurology highbrow heading a showing study, that began final year and is a initial such investigate financed by a National Institutes of Health. CTE is closely associated to Alzheimer’s disease. (Only in a past year have many scientists ostensible it as a apart condition.) Do genetics play a role? Can lifestyle assistance means it? “Is it specific to a form and frequencies of hits, or a volume of rest between hits?” Stern asks. “When they start, when they stop? The sum duration? We don’t know any of that.”
To answer any of those questions—to figure out given some football players get CTE and some don’t, or even how prevalent it is—they initial need to be means to diagnose it.
“All we know is that one non-static seems to make it occur in some people,” Stern says.
It’s a unequivocally elementary variable: being hit, repeatedly.
Patient 53 has had that variable. A lot of that variable. On a condition of anonymity, he concluded that we could shade him by his tests. And now he was here, around 8 in a morning, greeted by Stern. Balding and bubbly, a professor, who also leads clinical investigate during BU’s Alzheimer’s Disease Center, is an generous football fan, and he warmed adult Patient 53 with some speak about a former player’s bad back. That’s a form of repairs 53 had famous to design when he played. But not a mind stuff. Is that what was wrong with him?
“Now we wish we had never played. Well, some we do, some we don’t,” 53 told Stern. “I’m anticipating we can help.”
“That’s given we’re so blissful you’re here,” Stern said. “We’re a people who know a most. And we’re hopeful.”
Dressed in loose, aged blue jeans and a teal pullover zipped to a throat, Patient 53 loomed over Stern and Christine Baugh, a study’s investigate coordinator, who would beam him by a subsequent dual days. They would make a excellent investigate in contrasts: 53 was large, his brave patchy, nose thick, respirating heavy. Just a few years out of Harvard University, where she complicated a story of neuroscience, Baugh was unequivocally many a former rower—tall, thin. Her father had played veteran football for a integrate of years, so she has a vested seductiveness in a illness and an easy approach of articulate with former pros. She’s sharp, too, that was good, given as they staid into a discussion room opposite a hallway, 53 would uncover that he’d mislaid small wit to his mental fog.
Baugh was explaining a study’s spinal tap. It’s a normal indicate of anxiety, a reason they’ve had a tough time removing subjects for a control group. (They desperately need volunteers: former veteran or college athletes in sports like ball or rowing who haven’t been strike in a head. When we visited, in March, customarily 3 such volunteers had left by a study.) The same liquid in a spine also surrounds a brain, she explained. In CTE, a protein called tau congregates in sinewy tangles inside a brain’s neurons. It’s one of a mechanisms seen in other degenerative mind diseases, like Alzheimer’s, for that spinal taps have recently valid earnest in diagnosis. They competence find identical spinal biomarkers for CTE, nonetheless that’s distant from certain.
But there are probable side effects, she noted. “The other thing that can occur is what’s called a spinal headache,” she said. “We do a integrate things to try and minimize that. We use a special needle, and we also have we lay down afterward, both of that have indeed been shown to help.”
“What did we call it?” Patient 53 said. “The what headache?”
“I know. We unequivocally try to minimize a headaches. We know we guys have all too many of those.”
They went by permissions—53 donning his steel-framed eyeglasses to review a documents—and descriptions of a rest of a tests: physical, blood sample, neurological exam, EEG, psychiatric interview, medical history, cognitive test, and, on Day 2, a integrate of hours in an MRI machine. A turn of white-plastic smarts hung on a wall, a settlement suggestive of a imagining labyrinth. Don’t worry, Baugh positive Patient 53, if anything health-related arises, they’d let him know right away. But many of this work won’t produce any evidence formula until a investigate is done, she said.
“When do we expect all will be done?” he asked.
“Everybody should be entirely by a investigate in about a year’s time.”
Christine Baugh and Patient 53 eased their approach adult a moody of stairs—given his ongoing behind injuries, he doesn’t travel so many as grind—to a center’s clinical-research unit, a still building mocked adult like a customary hospital, nurse’s hire and all. Patient 53 would spend many of his day here in a drab beige room, paintings of white and blue potted flowers on a wall, attended by a expel of fit caretakers.
First came a dark-haired, prime nurse—a genuine pro in blue scrubs and white coat, with a Boston accent—to take blood and vitals. She indispensable 3 tablespoons of blood, some to see if a spinal daub could go forward, and a rest for genetic tests. The researchers posit that a many common genetic risk means for Alzheimer’s could play a identical purpose in CTE. If it does, it wouldn’t be a means of CTE nonetheless another denote that genes play a purpose in given a formula of mind repairs change so much.
Between tests, Patient 53 encompassed a gray padded chair, his arms swinging tighten to a floor. He gay over a day’s bizarre vocab, a “Johnny top” sanatorium gown, and a scale branded Detecto. Then a neurologist, Samuel Frank, an associate professor, swept in, young-featured and wearing olive pants and a blue-and-white-checked shirt.
Before a spinal tap, he ran 53 by earthy tests: tracking Frank’s fingers, clenching hands, drumming toes. “Do we get many sleep?” he asked during one point. “I don’t nap much,” 53 said. “Not unequivocally well.” Then there was a drunk-driving test, putting one feet in front of a other. “Can we take a few stairs approach adult on your tiptoes?” Frank asked. 53 grimaced. “My calves don’t work,” he said. Long, still pauses punctuated a review as Frank tapped annals into a black tablet. Eventually he started poking 53’s feet with a reserve pin, to small response. 53 had suffered bad frostbite during one game, he explained. His feet were gray for months.
The neurological tests finished with 53 station on a four-inch-thick blue mat, balancing on one foot. Baugh timed him with an iPhone. He hardly had his feet off a building before he sloping forward. “This is depressing,” 53 said.
“This is tough for anybody,” Baugh fast protested.
“You did fine,” Frank said.
“No, we didn’t,” 53 pronounced with a unhappy laugh. “But that’s OK.”
Frank and a helper readied him for a spinal tap. He was a tallest studious they had tested, nonetheless not a heaviest; he hadn’t shrunk like some of his post-steroid peers—53 never took steroids, he said—and carried his tummy well. Still, Frank said, they should start with a prolonged needle. 53 sat on a side of a bed, disposition facedown on dual pillows built on a rollaway food tray. “You should have a documentary Spinal Tap personification when we do this,” he said, his voice muffled. He paused: “The mockumentary.”
Frank streaked red-brown iodine on 53’s spine and pulpy a needle, thin, about a half-inch long, into 53’s back, acid for a track between dual vertebrae. In Alzheimer’s patients, a researchers have seen a vast boost of tau in a spinal fluid, presumably given of haughtiness destruction. They wanted to see if a same hold for CTE—far from a given—and how it competence be rescued early on. The needle resembled a dipstick, a interior shifting out to uncover either Frank had tapped a spinal fluid.
“You in there yet?” 53 asked, after some time had passed. Not yet. “We have a small bit some-more hankie to go by than normal,” Frank said.
As Frank continued to explore, there was a hit on a door, and Robert Stern, a study’s leader, appeared. “Perfect timing,” Frank said.
“No matter what my report is, we travel in just as he’s doing this!” Stern said. “How’s it going?” he asked Patient 53.
“You always ask that customarily as we’re doing this,” Frank said. “What are they ostensible to say? ‘Oh, it’s great’?”
“Are we entrance out a other side or what?” 53 asked, in good humor. They had to try a opposite spot, it incited out; Frank couldn’t get between a bones. Stern chatted with 53 about Lou Gehrig’s disease; one various of it seems associated to CTE, caused by repeated blows to a head.
“It’s nasty,” 53 said.
“It’s unequivocally nasty, unequivocally nasty,” Stern said.
Frank started again. Soon adequate he struck fluid.
“I’ve got maple syrup entrance out of me,” 53 said.
“This is many reduction viscous,” Frank said. “It’s utterly literally like water. Water with a few additional proteins. That’s what we’re looking for.”
The helper walked around a bed to uncover 53 his fluid, now in vials.
“That’s what your mind floats around in,” Baugh said.
“I theory it’s good it’s clear, right?” 53 said.
Patient 53’s day was distant from over. After Frank, Stern, and a helper left, Baugh had him distortion down. She scrubbed his face, afterwards stranded on round white electrodes for a electroencephalogram, that would magnitude a electrical activity of his mind in a resting state. The room was still, nonetheless 53 fidgeted, drawn to discuss with Baugh. She dimmed a lights. The time ticked, ticked again.
He got no spinal headache, thankfully, and a late breakfast shortly arrived: sausage, eggs, banana, apple. “I had never had a spinal tap, so we was a small shaken about that,” 53 said. “But that wasn’t bad.” His behind is such a problem, he continued. He was due for medicine soon, a three-tiered fusion. “I’m not indispensably in pain. But walking is unequivocally uncomfortable. It’s like removing stabbed.”
Patient 53 started personification hit football when he was 14 years old. His father didn’t concede him to play tackle before then. “Smart man,” he said. He was a parsimonious finish in high school, personification basketball (center, of course) and heaving a shot put. His distance and smarts finished him an descent lineman by college, a rugged nonetheless flexible players obliged for fortifying a quarterback and opening holes for a using back. It’s an unheralded position—one that can record thousands of light blows to a head. And blows that are not so light.
We were still in a examination room. Patient 53 had spent a integrate of hours vocalization confidentially with a psychiatrist. Then Baugh returned to learn about his past: sports, injuries, medical history, drug use. He’d taken off his pullover and absently twisted his left palm into a fist, wrapped underneath his beige T-shirt.
“Next I’m going to ask we some questions about concussions.”
“What?” 53 said.
“Next I’m going to ask we some questions about—”
He laughed. “It’s a bad joke.”
53 believes he suffered 30 to 50 concussions during his personification career. A lot of dings. A lot of stars. “Man, that’s a lot of football, isn’t it?” he said. Only once did he black out. (It’s a myth that concussions need a detriment of consciousness.) “I remember putting my pads on, and we remember a helper waking me up,” he said. “With a bad headache.” That was in college, and would have been in practice, he said. He frequency left games after his other concussions; there were smelling salts, after all. More than once he approached a wrong huddle, customarily to have his teammates drag him behind opposite a field.
He incited and looked during me. “Stupid (expletive) sport,” he said.
Though Baugh was seeking about concussions, ongoing dire encephalopathy is not tied customarily to concussions. This is a indicate of far-reaching and distinct confusion; until recently, Stern and his group suspicion it was all about concussions. Now they know that a illness is associated to a hundreds of “subconcussive” blows a mind suffers, a common scrapes and bruises it takes from a skull. “It’s somehow a sum bucket of attack your head,” Stern told me earlier. “Something about that in some people puts into fit this cascade of events in a mind that eventually leads to this altogether illness course.”
The mechanisms aren’t known. The researchers consider that tau spreads in a approach identical to Creutzfeldt-Jakob illness and associated disorders, in that poor proteins, called prions, breed some-more poor proteins. There’s also a neuroinflammation hypothesis, nonetheless zero a researchers are prepared to unveil. The core has found CTE in a smarts of 34 of a 35 defunct players it’s examined, nonetheless that’s a rarely resourceful sample, given that many of those donated smarts came from players famous to have had a disease’s symptoms. Stern has also recently remarkable that CTE has dual stages: one that causes changes in function and mood, and a other, after in life, that causes cognitive problems and leads to dementia. (That paper is not nonetheless published.) Why does that happen? He doesn’t know.
Patient 53 had a lot of story to go over. He’d finished his share of merrymaking in his day. Lots of beer, lots of pot, some cocaine, all of it social. Big nights on a town, customarily after a diversion and during Thursday dinners. The trainers would things them with aspirin, and with other pills in unlabeled white envelopes. He took speed, too, in his final integrate of seasons, when he was slowing. He still hates his aged coach. He’s wrestled with basin given his retirement, mislaid desired ones in what has turn an removed life. He has mood swings. But currently was a flattering good day. A young, intelligent lady was meddlesome in what he had to say. Everyone laughed during his jokes.
Near a finish of a history-taking, Stern seemed again. Another examination still loomed today, a cognitive examination that we couldn’t watch, given an spectator could simply interrupt a results. Tomorrow, 53 would go for his mind scans.
“I’ve seen each alloy there is. Been by each kind of test,” he said.
“We customarily need a right one, then,” Stern said.
“Well, we don’t know. we wish we can find one.”
“We will. We will.”
The second day was a bad day.
Patient 53 had woken tired from a prolonged day during BU and a smoothness cooking of bad Chinese food. He hadn’t slept well. We were in a groundwork of Brigham and Women’s Hospital, not distant from Fenway Park, as he prepared for a dual hours he would spend in a MRI machine. A print of a Eiffel Tower during dusk, a low gaslight in a foreground, hung on a wall. “I customarily don’t feel unequivocally good,” 53 said. Today wasn’t unusual. “This is what we understanding with.”
Hovering nearby, dressed in a colourless suit, was Alexander Lin, a clinical spectroscopist during a hospital. A lead questioner in a CTE study’s MRI work, along with Martha Shenton, executive of a psychoanalysis neuroimaging lab during Harvard Medical School, Lin had primarily worked some-more on serious mind trauma—the kind of repairs that formula in comas—but became meddlesome in amiable mind repairs when he saw one patient, a 14-year-old girl, who had suffered a concussion in soccer and couldn’t lapse to propagandize for months. He met Shenton and Stern during a meeting, and their partnership took off from there.
Lin escorted 53 to an eggshell-blue Siemens MRI machine, a extra-wide gimlet typically used for profound women. 53 eased onto a bed, ginger about his behind and disturbed about his heart arrhythmia. He hold a highlight ball: Squeeze it, Lin told him, and a trigger would have them rush in. 53 had asked for balmy song to be played; Ravel’s “Pavane flow une infante défunte” jockeyed with a MRI’s whine. Lin lowered an enhancing curl on 53’s face. It looked like a charge trooper’s mask.
“This is called a football helmet,” Lin said.
“Yeah, that’s an irony, isn’t it?” 53 said.
Lin hustled into a control room, where resounding slices of 53’s mind popped onto a multiplex of monitors. Lin’s partner flipped by a images with a mouse’s corkscrew wheel. A protein like tau is invisible in these images; a mind carrying a tangles will demeanour customarily like any other. But Lin and Shenton wish that their modernized techniques can start to reveal, somehow, either a mind is pang from CTE.
Lin’s scans came first. He’s an consultant in MR spectroscopy, a fortify that focuses not on a brain’s structure nonetheless on a chemical signatures. “People can hardly pronounce it, let alone spell it,” he said. “So we call it a practical biopsy.” After determining for all a H2O in a brain—”shimming,” they call it—Lin can magnitude how much, say, glutamate, a neurotransmitter, or N-acetylaspartate, a proton found in adult neurons, is found in a brain, in harmed and healthy populations. Such comparisons can be diagnostic: They can envision if a studious will come out of a coma, and Lin suspects that an boost in glutamate could be endangered in CTE’s origins.
53’s scans lasted during slightest 10 mins during a time; intermittently Lin called by a intercom, checking in, to understanding groans in response. (“Next indicate will be 12 minutes. You’re doing great!”) The practical biopsy was targeting a posterior cingulate, a neural clump nearby a brain’s back. In total, a group would demeanour during a contentment of 20 molecules. After a minute, a colorful bar draft popped up. “There’s a spectrum,” Lin said.
Halfway through, 53 took a break, walking to a outpatient locker room. He was groggy, his voice quiet. Did he nap during a scan? “In and out,” he said. “It was loud.” “This partial is going to be a small louder,” warned a investigate partner walking with him. They returned to a MRI’s bed, and he got behind in.
Martha Shenton’s indicate used a technique called freeing tensor imaging—an commanding term, unless we consider of ink and paper. Drip black ink on a paper though fibers, and it spreads in a ideal circle; season a same on sinewy paper, and a ink follows those channels. Looking during a figure of a ink’s widespread can tell we about those fibers. The same is loyal for H2O and a brain’s haughtiness fibers, called axons, along with some of a other structures. But formulating a conditions for freeing calls for a pulsing captivating margin from a MRI machine. A shrill pulsing captivating field.
It was a day’s toughest scan, durability 18 minutes. As a magnet got going, it warbled like a house-sized songbird. “The table’s jolt in there,” one technician said. “This is hard-core,” Lin said. The exemplary song was drowned out.
The intercom crackled.
“It’s like one of those hotel massage beds,” 53 said.
Lin, Shenton, and Stern wish that 53’s MRI scans will shortly be rendered, in some ways, obsolete. Over a past year, dual investigate groups have finally grown a proton that will pass by to a mind and connect to tau, permitting a protein to be seen in PET scans, rather than merely inferred, as it competence be from a MRI.
“This is substantially a many sparkling thing in a whole field,” Stern told me progressing that week. “Not customarily in CTE nonetheless in a whole of neurodegenerative diseases.” One of those investigate groups, afterwards formed during Siemens (and now owned by Eli Lilly and Company), reported a successful use of a tracer in tellurian beings this year, to small fanfare, in a Journal of Alzheimer’s Disease. The group’s extend offer to use a tracer is tentative with a Defense Department, that is endangered about a bequest of subconcussive blows for former soldiers. “This is going to be worse than Agent Orange,” Shenton told me that morning.
But for now, there are customarily a MRI scans, that for 53 went on for somewhat over dual hours. When they were done, he walked behind to a locker room to change. It had been a severe dual days. It took all he had. He was blissful to do a tests, he said, even if it incited out he didn’t have CTE.
The subsequent week, Stern would go by his total annals and give him a call to speak about his ubiquitous health. But there would be no diagnosis of CTE. Not yet. Like a 52 patients before him, and a 47 after, he won’t know for years, nonetheless Stern, a study’s leader, is hopeful—if they can get some-more volunteers for controls. He had told me that with adequate resources, an accurate diagnosis was 5 years away. A cure? Decades.
A transparent diagnosis couldn’t come shortly enough.
“It’s not fun,” 53 pronounced as he shrugged on his pullover. “Whatever it is that’s going on, it’s not fun.”
Back in travel clothes, Patient 53 found Christine Baugh, who had been in a watchful room all day, drumming on a laptop. She greeted him, a accessible face from a improved day, and they ambled down a hospital’s far-reaching white hallway, toward a elevators, a airport, and a pale day beyond.
Paul Voosen is a comparison contributor during The Chronicle.