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Authors: Sanjay Gupta

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To understand these remarkable recoveries, you have to shift your focus from individual brain cells, or neurons, to the way
those neurons are organized in the brain. It still holds true that individual neurons don’t regenerate that well, but what
we underestimated was the extent to which a brain could rewire itself using the cells that are already there. Traditional
neuroscience teaches that by the time Terry Wallis was a teenager, he had established certain pathways in his brain, allowing
him to speak, think, and move. Once the brain cells were destroyed in the truck accident and by the subsequent swelling of
his brain, those pathways should have been lost. Perhaps they were, but as we see—quite dramatically, in the raw evidence
of the patient talking—new pathways took their place. Wallis’ brain simply built a detour around the area that was damaged.

Individual neurons are much more versatile than they were once thought to be, and the same goes for specific brain regions.
While neurosurgeons still throw around phrases like “the speech region” or “the visual processing region,” experiments have
shown that depending on the circumstances, different parts of the brain can take on the same duties. These circumstances could
be carefully controlled therapy—like a stroke patient tying down his right hand to force the brain to send signals to a paralyzed
left hand—or something entirely different, like the ravaged brain tissue of an accident victim like Wallis.

This phenomenon, called neuroplasticity, has been used to explain recoveries from stroke and from spinal cord injury; it forms
the basis of many physical therapies, as practiced by rehab physicians like Mark Ragucci. Neuroplasticity even provides a
theoretical framework for cognitive behavioral treatment in psychiatry, where patients are taught to practice helpful thoughts
and behaviors and to avoid damaging or painful ones. What’s remarkable about the Wallis case is that we actually have brain
scans showing the new connections.
15

“How rare is it to have a spontaneous recovery after twenty years? Rare enough to end up on the front page of the
New York Times
[which ran a story]. But for other patients to have the same capacity, we don’t know the answer,” Schiff told me. But, he
says, no one can argue anymore that such recoveries aren’t possible. “[It’s] a knockdown, drag-out counterexample. And the
facts of his case should make us think that it could be a lot less rare than we’ve thought.”

Schiff is busy trying to get a large, multicenter study of coma funded and off the ground. He says, “We need to move away
from just looking at what these patients can do and then looking at the calendar to see how much time has passed.” To be clear,
Schiff doesn’t think we need to sit around waiting twenty years with every coma patient to see if they recover. Rather, he
says, we should be able to develop diagnostic tools to tell us after a reasonable period of time—say, three or six months—which
patients maintain the
capacity
to get better. To do that, he says, we need to figure out how consciousness really works, how neurons function together and
how the brain works to mend itself.

That’s a tall order. Up to now, we just haven’t looked at enough patients. We know more about peering inside the brain than
we did just a few years ago, but Schiff says there are many more questions to be answered: “fMRI, PET scans, EEG—all these
tools are enormously important, but in isolation, individual cases don’t get at the real mysterious question of what is happening
in the brain during coma.”

Aside from Terry Wallis, we know another person who can speak from experience. Mark Ragucci says his conscious mind was working
during his hospital ordeal, even at the time when doctors and even his wife described him as vegetative, with the lowest possible
score on the coma scale. It’s frankly hard to comprehend. Not only was his brain badly injured by lack of oxygen, for much
of that time, Ragucci lay in a medically induced coma that was meant to shut off nearly all brain activity. This is pretty
remarkable. When a medical resident poked him with a small metal tool much like a dentist’s pick, Ragucci didn’t flinch. When
his eyelids were pulled open, he didn’t blink and his pupils didn’t shrink. You could rub a cotton wisp across his cornea
without any response. When questions were shouted in his ear, his expression didn’t change. Yet Ragucci insists that the time
was not a blank slate. From my perspective as a neurosurgeon, where I examine and treat patients like Ragucci all the time,
what he said next was chilling.

“I remember there were voices I could hear around me. I can remember verbatim what they were saying, when I supposedly was
in a deep coma at the time. I subsequently could provide descriptions of the people who were walking around my bed—and this
is when I was in a pretty bad sort of way,” he says. Remember, his doctors had diagnosed him as nearly brain-dead.

A handful of doctors are testing ways to speed up the growth of new brain circuits. Some are looking at stem cells to try
and spark the growth of new neurons. Another promising approach is called deep brain stimulation, or DBS. Neurologists implant
electrodes in the brain and connect them to a pacemaker battery in the chest. They then use electrical current to try and
cajole the growth of new connections in certain parts of the brain.

For years, the leading proponent of deep brain stimulation was a doctor named Edwin Cooper.
16
I was recently shown his patent for the first DBS device back in 1975. Cooper had a few strikes against him from the start:
he was a nonacademic, and he wasn’t even a neurologist; he was trained as an orthopedic surgeon. For years, he struggled to
get researchers to take him seriously and only recently has his theory hit the mainstream. In 2006, Schiff and Dr. Ali Rezai,
a neurosurgeon at the Cleveland Clinic, reported on a man they had treated with deep brain stimulation after he had lain in
a minimally conscious state for six years (he had been injured during a violent robbery). The man showed dramatic improvement.
Before the treatment, he had been hooked to a feeding tube and was only intermittently aware of his surroundings. After just
one session of DBS, he was able to make movements to feed himself and was able to recite sixteen words of the Pledge of Allegiance.
17
Considering where he’d been, the progress was incredible.

R
AGUCCI TOLD ME
, “One of the reasons I didn’t do neurology is because of the fact that a neurologist will tell you what’s wrong, but can’t
tell you what to do about it.” This is conventional wisdom in teaching hospitals.

Mayer hears it all the time. “We’re trying to smash that concept,” he said. “What we’re doing is taking the patients who up
until very recently were assumed to be beyond hope, unsalvageable, and we’re taking an extremely aggressive approach to resuscitating
these people with severe brain injuries—hemorrhages, brain trauma, and the like.”

Decades ago, modern medicine came close to perfecting the ability to keep a patient alive on the most basic level. A breathing
tube and a feeding tube can keep a patient breathing—technically alive—almost indefinitely. The brain, on the other hand,
was out of reach. Mayer admits readily that neither he nor anyone else truly understands what triggers the healing process
in some patients, but not others. What medicine can do—neurocritical care in particular—is to provide an environment where
that healing process, whatever it is, can take place.

I can tell you there’s a lot of watching and waiting. Much of it wouldn’t be possible without careful monitoring of the brain,
something that barely existed when Mark Ragucci landed on Mayer’s doorstep. “We’re putting probes and monitors in that directly
monitor oxygen levels in the brain,” says Mayer. “We can measure the neurochemistry of the injured brain.” I tell my residents,
it’s like rolling a video camera on the damaged brain as opposed to just getting intermittent snapshots.

At New York-Presbyterian Hospital/Columbia University Medical Center, every patient who enters the unit is hooked up to an
EEG monitor to watch for seizures, and most are connected to a system that takes constant readings of oxygen. By monitoring
even subtle changes inside the brain, the team is able to intervene early—for example, by giving vasopressors to raise blood
pressure before it drops to a dangerous level or by giving sedatives to prevent damaging seizures that wouldn’t have otherwise
been spotted by the naked eye.

“When I started in this field thirteen years ago, this was really science fiction. It’s like going into the black box. An
analogy would be: you’re fumbling around in the dark, and then all of a sudden the light goes on, and you’re able to see this
incredible, complex, in some ways beautiful landscape,” says Mayer. “When I think back to what we used to be doing, it was
like flying a plane in the dark, and you could just crash into a mountain. There could be some huge problem: a physiologic
storm, seizures, or a brain injury, and we wouldn’t really know until the plane crashed.”

The thing is, there’s no flight manual, not yet. That means neurointensivists like Mayer have to feel their way along. A good
example appeared on the first day of our visit. A woman who came to the unit three days earlier has started to show an alarming
pattern of brain activity. It’s a slow but steady electrical rhythm known by the unwieldy name of periodic lateralized epileptiform
discharges—PLEDs, for short. Less dramatic than classic seizures, they’re basically invisible to the naked eye. The most you
can see is a trembling of the eyelids. Without the constant monitoring, you wouldn’t even know the seizures are taking place—but
subtle as it is, PLEDs can be a virtual death sentence.

In any case, conventional neurology teaches that there’s nothing to do for a patient with PLEDs, other than hope it goes away.
But we see Mayer attempt something new—a cocktail of medications to try and drive the patient into an even deeper stupor.
He’ll flatten the brain waves into total silence. In three days, he’ll bring her back, let the sedatives wash out of her system
and see if there’s improvement. Think of it sort of like rebooting her brain. “The conventional wisdom has been PLEDs aren’t
seizures, and trying to stop them doesn’t help,” Mayer said. “But we’ve seen the natural history enough, and it’s terrible.
And we’re not satisfied with the status quo. I told the team, ‘Let’s just try this approach for now, for this particular problem,
and if nobody gets better, then at least we’ll know that it’s not going to work and we’ll come up with something else.”

In this case, it didn’t work, not really. A year and a half later, the patient was in a nursing home with severe disabilities—unable
to speak or even feed herself. Her daughter said she doesn’t regret trying “everything,” but doubts she would do it again
if she somehow had the chance.
18
Still, it’s likely that patients do better when they have an aggressive advocate, like Mark Ragucci’s family. There’s clinical
research to suggest that a poor prognosis does, in fact, lead to indifferent care. A 2001 paper published in the journal
Neurology
said that physicians tend to be overly pessimistic in early stroke assessment and warned that the dire assessment could become
a “self-fulfilling prophecy.”
19

A much larger study was published in 2004 in the journal
Stroke.
That paper examined the fate of 8,233 hemorrhagic stroke patients in California hospitals where do not resuscitate orders,
or DNRs, are commonplace and in other California hospitals where DNR orders are less common. There was a lot of variation;
in some hospitals none of the patients were tagged with DNRs, while in others the rate was 70 percent. Make no mistake, even
when researchers accounted for age, gender, severity of symptoms and other details, they still found that patients in the
hospitals where DNRs were rare had a better survival rate.
20
They couldn’t say what caused it, but it’s fair to guess that hospitals that treat patients more aggressively are more likely
to save their lives.

The authors of the California paper write, “Decisions to limit care are often predicated on the assumption that treating physicians
are able to accurately predict outcome in the specific case at hand.” Left unsaid is that those assumptions may be wrong.
Joseph Fins says that aside from a few academic centers, like New York-Presbyterian Hospital/Columbia University Medical Center
and his own New York-Presbyterian Hospital/Weill Cornell Medical Center, most hospitals give up on patients way too soon.
“Overwhelmingly, these patients are still susceptible to undertreatment. I think this susceptibility is not so much in the
first few weeks [after falling into a coma], but in the subacute and chronic phase, when there is pervasive neglect of these
patients.”

You might be surprised to hear that aggressive treatment is not always a good idea. One critic is Dr. Justin Zivin, vice-chairman
of neuroscience at the University of California in San Diego. He says that with patients who suffer severe strokes—or any
injury due to lack of oxygen in the brain—a good neurologist can make a prognosis with near-complete certainty. Someone who
has lost their most basic brain functions, says Zivin, is highly unlikely to make more than a token recovery. “The majority
who recover even a degree of function still have significant deficits. Their quality of life is terrible. When you give people
like that too much hope, it leads to enormous expense and bad outcomes.”
21

Mayer is unapologetic, especially when he’s talking about Mark Ragucci. “All signs pointed to hopelessness and neurological
futility,” says Mayer. “Decisions are made every day in this country to withdraw and remove people from life support without
really giving them a chance. That’s really what the neurointensive care movement is all about. It’s about giving people a
real chance.” Early in his career, Mayer was on the opposite side of the spectrum. A decade ago, he often talked about how
hard it was to push families to give up—to spare themselves the torment of hope, in a hopeless case. Since then, he’s made
a 180 degree turn, and says it was Ragucci who tipped the scales for him.

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