“The ominous events in the early morning hours of August 12, 1997 led to a tragedy in Lloydminster, Saskatchewan….”– from a Saskatchewan Court of Queen’s Bench ruling issued in 1998.
There was a small band playing at the Dr. Cooke Extended Care Centre’s annual Christmas party this year, and tables laden with shortbread and popcorn curls and Christmas cookies. On one side of the room sat Jeffrey Tremblay and his father, Paul. Jeff has lived at the Lloydminster facility since he was 19 years old. He turns 41 this week.
Jeff can’t move or speak. He has to be tube-fed through his stomach. He’s aware of what’s going on, Paul says, which is remarkable given doctors wrote Jeff off as being trapped in a vegetative state for 16 years. Only Jeff wasn’t vegetative. Roughly 20 per cent of people like Jeff who are assumed to be totally unconscious — no idea of who they are or where they are, unable to exhibit any “willful behaviour” — are actually aware, lingering undetected somewhere in a state between life and nothingness.
New guidelines could help in the search to find them.
It’s not clear how much Jeff knows about the role he’s playing in what some are calling a revolution in the treatment of the catastrophically brain injured. A senseless attack sent Jeff into the unknowable world he now inhabits.
Jeffrey Tremblay and his father Paul in October 2018.
Courtesy of the Tremblay family
The assault happened after a night out at a bar with friends. Jeff, the kid with the heart of gold and a smile that could light up a room, was beaten into a coma in a fit of jealousy over a girl. His assailant, then 19, six-feet-two-inches tall and weighing 250 pounds, kicked skinny, wiry, 130-pound Jeff in the chest with enough force to propel a football 25 yards. Jeff’s heart went into arrhythmia, starving his brain of oxygen. When he arrived in emergency by ambulance, he had no pulse, no blood pressure, no “respiratory effort,” no movement. His pupils were fixed and dilated. The blow to his chest “at the critical time of the cardiac electrical cycle,” Saskatchewan Court of Queen’s Bench justice Robert Hrabinsky would write, led to “no effective circulation for many minutes.”
Jeff remained comatose for three weeks, until one day Paul, camped out around the clock in Jeff’s hospital room, looked up from his crossword puzzle and saw his son’s wide-open eyes and that great big smile, and thought, ‘Geez, he’s going to be fine.’”
He wasn’t. Jeff was awake, but doctors said his brain injury, his neurological loss, was so extensive, so diffuse he likely had no awareness whatsoever. “It’s tough to hear when a doctor says that. They want you to pull the plug,” Paul said. “I wasn’t prepared to do that.”
Paul didn’t know much about the brain back then but one day he found a story about a neuroscientist named Adrian Owen, a British-born researcher who for years had been using brain scans to reach inside the minds of people considered all but gone, unable to speak or move or signal to the outside world, “I can hear you. I’m in here.”
They want you to pull the plug
Sixteen years after his beating, Jeff was flown to London, where he was slid inside a functional magnetic resonance imaging scanner, or fMRI, which measures brain activity by detecting changes in blood oxygenation and flow, and shown a short Alfred Hitchcock movie — Bang! You’re Dead! Jeff’s brain fired off the same peaks and dips in electrical activity in the frontal and parietal regions of the brain at critical points of the movie that were uncannily identical to healthy volunteers shown the same eight-minute clip. Before then, Jeff had shown no “higher-order” signs of awareness, Owen and his team wrote in the journal PNAS in 2014, no communication in any form. The experiment suggested he was exhibiting executive processing, that he was able to engage in “complex thoughts about real-world events unfolding over time.”
Owen not only reached Jeff. The Western University scientist has used fMRI to help people once diagnosed “vegetative” follow commands, acknowledge where they are and with whom, and answer questions like, “are you in pain,” by decoding their brain activity.
Now, tests that can detect covert consciousness, not just expensive, bulky fMRI, but bedside EEG machines that use small discs on the scalp to measure brain activity, are moving a step closer to routine use. New guidelines from the American Academy of Neurology and other bodies recommend that, where there is any ambiguity or “inconclusive” findings, brain imaging should be used to hunt for emerging signs of consciousness in the brain injured who have no recourse to speech or action — a “milestone” development in the history of brain science, Owen and colleagues wrote in a paper, “Alive Inside,” in the journal Bioethics.
“The problem up until now has been that we develop these techniques, we put them out there, we tell people how to do them and the only patients that benefit are the people who make it into other research institutions,” Owen says. “It hasn’t been incorporated into guidelines for how one treats these patients. And that has now changed.”
Neuroscientist Adrian Owen.
Paul Mayne
Owen is pushing for the tests to be adopted even more widely, used not just months or years out from a brain injury, but at the front end in the first hours after a traumatic brain injury to help predict which patients might recover from a vegetative state, which ones might benefit from rehabilitation. Most decisions to remove life support — to pull the proverbial “plug” — occur within the first 72 hours after injury. If we can improve prognosis in that group, if we can better understand who might make some recovery, “we can perhaps save some of those lives,” Owen says.
“Maybe a different decision is right for some of those patients.”
Most remarkably, others are testing deep brain stimulation and other interventions to “re-awaken” or hasten awareness in people in minimally conscious states, even years out from their injury.
But the rapidly evolving field is also raising serious ethical challenges, about how we think about consciousness; about false hope and about the existential risks of making people more aware of an existence many would consider a living nightmare.
If someone can modulate their neural activity — communicate via signals from his or her brain — is that a sufficient, or even reliable proxy for speech? And if we find a way to communicate, what, then, do we ask them? Is there anything we can do to make you more comfortable? Is there anything you’d prefer to watch on TV? Do you wish to continue living?
“What is most tantalizing about this prospect is that it would allow a seriously brain-injured patient to express their current wishes, which may well have changed radically in the interval (sometimes decades) before they expressed any premorbid opinion,” Owen wrote this year in the journal Neuron.
“Ultimately, the morally challenging question of whether theirs is a life that is ‘worth living’ is one that could be answered by the patient using fMRI,” he said.
A PET-fMRI machine at the Brain Imaging Centre in Ottawa.
Ashley Fraser/Postmedia
Sophisticated neuroimaging is already being used to involve some “covertly aware” patients in their daily care. But fMRI is expensive, bulky and nowhere near every hospital has one. However, 20 years from now brain-computer interfaces that use electrical signals from the brain to say, manipulate a computer, or move a robotic arm, could be as common as smartphones, Owen wrote.
But this is where things get dicey, says Dr. Judy Illes, Canada Research Chair in neuroethics at the University of British Columbia.
“How reliable is the signal? How do we make sure that it’s the intent of the person, that it hasn’t been hacked and that it is reproducible?” Illes wonders.
When it comes to communicating hunger or pain, it might matter less if the signal is noisy. “It’s not good to overmedicate someone but it’s much worse to under-medicate,” Illes says.
But could the signals be used in a courtroom as a form of testimony? To redirect an inheritance from the children who don’t visit anymore, to a nurse? Enable a person to request a medically assisted death?
Individuals who we thought were in a persistent vegetative state may not be and, in some cases, certainly are not
And what good is the information that a loved one appears to have some conscious processing, if there’s little available to help them? “I think that’s where I get stuck,” Illes says.
This much is true. “The technology has advanced to the point that we must attend to the fact that individuals who we thought were in a persistent vegetative state may not be and, in some cases, certainly are not. And those numbers are bigger than we ever thought,” she says.
Today, the standard way of checking for any “residual” or preserved awareness or cognitive function in brains damaged by a stroke, cardiac arrest or bash to the head are bedside scales that use response and command-following tasks — look this way or that, squeeze my hand, move a foot, follow the tennis ball with your eyes.
However, people diagnosed as being in a vegetative state, or the much larger group known as the minimally conscious, simply can’t marshal the resources to, say, blink an eye, or move a foot on command. It’s not a muscular problem. They aren’t paralyzed. Rather, there’s a central nervous system problem, a disconnection that’s preventing them from executing any movement at all, Owen says. But their thoughts, their mental process could be intact.
These people do spontaneously move. They often grunt; they’ll open their eyes or move a hand. The problem is knowing whether that’s a conscious response or merely chance.
Except in circumstances such as complete brain death, relying on neurological exams at the beside is, in many cases, “hopelessly unreliable,” Owen says.
Images of “healthy” vs. “vegetative brains.”
Courtesy of Adrian Owen
Brain imaging takes behaviour out of the equation.
In a ground-breaking Science paper published in 2006, Owen and colleagues reported that an apparently vegetative woman showed distinct patterns of brain activity when asked, while lying inside a fMRI, to imagine herself playing tennis, or walking through the rooms of her house. The pattern of her brain activity was indistinguishable from what is seen in healthy volunteers. Owen believes she was entirely aware during the scanning procedure.
Next, working with Steven Laureys from the University of Liege, Owen showed that, of 54 patients in a vegetative or minimally conscious state, five 5 were able to “willfully modulate” their brain activity. One was able to answer yes or no to questions during functional MRI even though it remained impossible to establish any form of communication at the bedside. Then, in an experiment that made worldwide headlines, the team slid a man named Scott Routley inside an fMRI scanner and asked if he was in pain. The Sarnia, Ont. man had remained in what doctors were convinced was a vegetative state for 12 years after a police cruiser rushing to the scene of a crime slammed into his car in December 1999. Lying inside the scanner, Scott was told to imagine walking around his house if the answer was “yes” or playing tennis if the answer was “no.” “Do any parts of your body hurt right now,” Owen asked Routley. The answer was, no.
Images of “healthy” vs. “vegetative brains.”
Courtesy of Adrian Owen
Since then, Owen and his team have used imaging to ask patients if they prefer the temperature lower or higher, whether they still like watching hockey. “One of the sad truths is that they get exposed to an awful lot of whatever it is they used to like before they had a brain injury,” Owen says. “If you were a great lover of Celine Dion 20 years ago when you had your brain injury, maybe you don’t want to listen to that anymore. We can return a little autonomy to patients.”
Ironically, they’re often relatively healthy. They breathe on their own. Their hearts beat on their own. They’re not being kept alive, except, like Jeff Tremblay, they have to be fed and hydrated. There’s no “plug’ to pull. They can only die by withdrawing nutrition and hydration.
The better their responses in the fMRI scanner, the more likely they are to recover, Owen believes. And there have been some spectacular cases of recovery, including Juan Torres, to whom Owen devotes an entire chapter of his book, Into the Gray Zone. The Toronto-area man suffered a catastrophic brain injury when he was 19 years old. Today, six years out, he has re-enrolled in school. “He’s intellectually right back to where he was before,” Owen says.
But Juan is truly the exception. “People often think these people go from being in a vegetative state to being back on the golf course. That almost never happens,’ Owen says.
We’ve got patients who we know are on the edge of being able to establish communication
However, he and others are starting to think about interventions that might accelerate their return to consciousness, even a normal life. “Twenty years ago, people would say to me, ‘isn’t there some sort of surgery you could do to fix these patients?
“Well, maybe, but we didn’t know where to start. You need the basic imaging and you need to understand what’s causing the problem before you can solve the problem of how to fix people. And I think we’re getting there. We’re just at the tipping point right now,” Owen says.
Researchers are testing different drug therapies, including anti-virals as well as a sleeping pill called zolpidem that famously and transiently roused Louis Viljoen, of Johannesburg, from a vegetative state in 2006. Twenty minutes after his first dose, he opened his eyes, looked at his mother and said, “Hello mummy.” More recently, in October, British scientists floated the idea of using the psychedelic psilocybin, the active substance in magic mushrooms, the idea being the hallucinogen might increase brain complexity and brain plasticity — the brain’s ability to rewire itself, and grow new neurons.
The biggest hope, however, may rest with deep-brain stimulation, or DBS. Dr. Nicholas Schiff is a neuroscientist at Weill Cornell Medicine in New York City. Schiff was also the lead author of a breakthrough study published in Nature in 2007 involving a 38-year-old man who had spent more than five years in a minimally conscious state who can now communicate with his family, thanks to pulses of electric current to his brain.
By stimulating the central thalamus, which relays motor and sensory signals to the cerebral cortex, the part of the brain involved in consciousness, Schiff’s team was able to help the man name objects, make hand gestures and eat without a feeding tube — suggesting DBS “can promote significant late functional recovery from severe traumatic brain injury” even years after the injury occurred.
“We’ve got patients who we know are on the edge of being able to establish communication, but we don’t really know what to do for them yet,” says Schiff, adding that it’s a population of patients that has been horribly neglected for years.
“Just because we identify consciousness and awareness, it’s not enough. It’s terrible to know we can make these measurements, identify awareness and not be doing what needs to be done, which is to build a medical infrastructure to support these people.”
But how quickly should we be moving? And is there a risk of overestimating what fMRI mental imagery really means? The fact this area is so fraught with ethical challenges is precisely because we don’t know what it’s like to be in such a state, or whether a person’s mental processes are functioning at full capacity. A signal is one thing. But what does it mean?
“I’ve always imagined a clinician entering a room and saying, ‘I have wonderful news! John is aware! We know this because he’s volitionally modulating his brain activity,” Andrew Peterson, an assistant professor at George Mason University, who works with Owen’s lab, wrote in an email.
“My gut tells me that families might not know what to do with this information. What they will want to know is whether their loved one can hear their voices, feel their touch, or if he or she is experiencing pain.” However, the tests aren’t pitch perfect. Accuracy rates range from 60 to 80 per cent.
The Tremblay family in October 2018.
Courtesy of the Tremblay family
What’s more, to truly tap into a person’s state of mind requires a rich, two-way conversation, and the current technology, whether fMRI or less cumbersome, bedside EEG machines, prevents that, Peterson said. Such deeply profound decisions as “do you wish to stop being fed or hydrated” couldn’t be handled, legally or ethically, as if it were a “yes” or “no” game of 20 Questions.
A more likely scenario is how brain imaging might influence legal fights around decisions to withdraw life support.
Consider this example, Peterson says: A person’s advance directive states, “I don’t want to live if I’m in a vegetative state.” But then brain imaging detects covert consciousness. “One family member thinks that this clearly shows that the patient is not in a vegetative state and they shouldn’t withdraw care,” Peterson said. Other family members insist any detection of “covert” consciousness is irrelevant because their son or daughter or spouse could remain in that brain state for the rest of his or her life.
And it’s mostly young people who are most likely to end up with disorders of consciousness. Young people are resilient, Peterson says. They don’t die from the initial injury. Instead, they’re left in that grey zone between consciousness and unconsciousness.
And it’s impossible to know what their interior lives might be like. Some people might be relieved to learn their loved one can hear, can process speech, that they are fully aware of everything that is going on around them. Others will be horrified, and left with gut-wrenching questions about quality of life.
My gut tells me that families might not know what to do with this information
Still, the harms associated with undetected consciousness, whether it’s unnecessary pain or prematurely withdrawing care, is just too great not to starting moving the research into practice, Peterson said. “At the very least, it seems that clinicians have an ethical duty to discuss this option with families” in appropriate cases.
Before he took his son to Owen’s London lab, “everything was a dark hole,” Paul Tremblay says. “Everything was negative, negative, negative.”
“But the more you read about it, it’s just not true.”
Jeff can’t communicate. But Paul reads his eyes, to see if he’s listening or not. He smiles when he’s happy, grimaces when he’s sad, groans when he’s in pain. When he’s really tired, like most of us Jeff doesn’t listen very much. Paul takes his son to the movies once a week. He remains in touch with Owen’s lab.
“It might not help Jeff, in the long run,” Paul said. “But I think Jeff is helping the research.”
In 1998, Jeff Tremblay’s attacker was convicted of aggravated assault.
He served eight months of a three-year prison sentence.
MILWAUKEE (AP) — Whooping cough is at its highest level in a decade for this time of year, U.S. health officials reported Thursday.
There have been 18,506 cases of whooping cough reported so far, the Centers for Disease Control and Prevention said. That’s the most at this point in the year since 2014, when cases topped 21,800.
The increase is not unexpected — whooping cough peaks every three to five years, health experts said. And the numbers indicate a return to levels before the coronavirus pandemic, when whooping cough and other contagious illnesses plummeted.
Still, the tally has some state health officials concerned, including those in Wisconsin, where there have been about 1,000 cases so far this year, compared to a total of 51 last year.
Nationwide, CDC has reported that kindergarten vaccination rates dipped last year and vaccine exemptions are at an all-time high. Thursday, it released state figures, showing that about 86% of kindergartners in Wisconsin got the whooping cough vaccine, compared to more than 92% nationally.
Whooping cough, also called pertussis, usually starts out like a cold, with a runny nose and other common symptoms, before turning into a prolonged cough. It is treated with antibiotics. Whooping cough used to be very common until a vaccine was introduced in the 1950s, which is now part of routine childhood vaccinations. It is in a shot along with tetanus and diphtheria vaccines. The combo shot is recommended for adults every 10 years.
“They used to call it the 100-day cough because it literally lasts for 100 days,” said Joyce Knestrick, a family nurse practitioner in Wheeling, West Virginia.
Whooping cough is usually seen mostly in infants and young children, who can develop serious complications. That’s why the vaccine is recommended during pregnancy, to pass along protection to the newborn, and for those who spend a lot of time with infants.
But public health workers say outbreaks this year are hitting older kids and teens. In Pennsylvania, most outbreaks have been in middle school, high school and college settings, an official said. Nearly all the cases in Douglas County, Nebraska, are schoolkids and teens, said Justin Frederick, deputy director of the health department.
That includes his own teenage daughter.
“It’s a horrible disease. She still wakes up — after being treated with her antibiotics — in a panic because she’s coughing so much she can’t breathe,” he said.
It’s important to get tested and treated with antibiotics early, said Dr. Kris Bryant, who specializes in pediatric infectious diseases at Norton Children’s in Louisville, Kentucky. People exposed to the bacteria can also take antibiotics to stop the spread.
“Pertussis is worth preventing,” Bryant said. “The good news is that we have safe and effective vaccines.”
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AP data journalist Kasturi Pananjady contributed to this report.
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The Associated Press Health and Science Department receives support from the Robert Wood Johnson Foundation. The AP is solely responsible for all content.
How a sperm and egg fuse together has long been a mystery.
New research by scientists in Austria provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people.
“We discovered this mechanism that’s really fundamental across all vertebrates as far as we can tell,” said co-author Andrea Pauli at the Research Institute of Molecular Pathology in Vienna.
The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published Thursday in the journal Cell.
Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg’s membrane. Working with international collaborators, Pauli’s lab used Google DeepMind’s artificial intelligence tool AlphaFold — whose developers were awarded a Nobel Prize earlier this month — to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.
It wasn’t previously known how the proteins “worked together as a team in order to allow sperm and egg to recognize each other,” Pauli said.
Scientists still don’t know how the sperm actually gets inside the egg after it attaches and hope to delve into that next.
Eventually, Pauli said, such work could help other scientists understand infertility better or develop new birth control methods.
The work provides targets for the development of male contraceptives in particular, said David Greenstein, a genetics and cell biology expert at the University of Minnesota who was not involved in the study.
The latest study “also underscores the importance of this year’s Nobel Prize in chemistry,” he said in an email.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.
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