Doctors who work in neurological intensive care units are managers of the brain in crisis. In Back from the Brink, journalism professor Edward J. Sylvester presents the world of the “neuro ICU” through the stories of patients at the Johns Hopkins Medical Centers, Baltimore, where neurointensive care was pioneered, and Columbia’s New York Presbyterian Medical Center, New York. Although neuro ICUs are springing up at medical centers around the world, there are still relatively few, and, writes Sylvester, their new breed of specialists—neurointensivists—“aim to establish themselves as the ﬁrst-line rescuers of the brain...”
Sylvester describes the ICU as “at once an island of peace, a clean well-lighted place, and a harbinger of dread, the next-to-last place you ever hope to be. The last place, of course, is the situation that brought you through these doors.” Because the concept of the neuro ICU was “hammered out of the wreckage of failed responses to brain trauma,” its patients are of all ages—many in the prime of life. Stroke, a traumatic accident or violence, or the ﬁrestorm of uncontrolled epilepsy may strike and in a ﬂash the healthy young adult may become comatose, the person on his daily rounds may drop in his tracks. When this occurs,“Time is brain,” and intensive care often starts in the ambulance bound for the hospital and the neuro ICU.
Chapter 5 of Back from the Brink tells the story of two patients (coincidentally both from Long Island) who are treated in Columbia’s New York Presbyterian Neurological Intensive Care Unit, one of just a few of the highest level “neuro centers” in its part of the country. In the excerpt that follows, Sylvester recounts the story of Gail Beck, who, with her husband, Joe, and two small boys, lives in the town of Huntington and works as a technical editor for the American Institute of Physics. The Becks are both in their thirties when the story begins.
Excerpted from Back from the Brink: How Crises Spur Doctors to New Discoveries about the Brain by Edward J. Sylvester. © 2004 by Edward J. Sylvester. Published by Dana Press.
MULTIPLE LIGHTNING STORMS IN THE BRAIN
On this Saturday, June 22, the day after school closed, the Becks had been headed for the American Institute of Physics annual picnic, but Gail didn’t feel very well. She had been ﬁghting what seemed like ﬂu all week and ﬁnally decided she wasn’t up to the picnic. Her legs felt like iron. She lay down on the living-room couch and slept most of the day. Joe spent the afternoon at the computer, writing. About four o’clock he heard Gail moan, then nothing. As he rushed into the living room, she moaned loudly again, then began thrashing, then nothing again.
Joe later wrote the next thing he remembers:
“Gail, Gail!” The paramedic repeated my wife’s name as she worked over her in the ambulance. We were on our way to Huntington Hospital after she had had a major convulsive seizure ...
[The paramedic] shined a light in her eyes. “Gail!” she repeated. “Can you hear me?” She moaned...
A string of questions: Prior seizures? Illegal drug use? Smoker?
“No.” I bent down to hold her hand. “Look, can we just get to the hospital?” Fear and anger welled up in me and my eyes were moist.
“We’re doing the best we can, sir. We’ll be there in about six minutes.” So they were, and [Gail’s parents] the Domroes joined them minutes later. Gail’s seizures increased in severity and duration. She did not regain consciousness. The antiseizure drugs she was given dampened but would not quell the seizures, even the powerful barbiturate phenobarbital. Finally, staff neurologist Barbara Allis told them what the doctors knew. Gail was having intractable seizures, “intractable” meaning nothing seemed to relieve them for more than a short period. Seizures had progressed from focal—localized within a particular region— to become generalized throughout her cortex. And instead of slowing under the powerful drugs that dampen neurons’ ﬁring out of control, the seizures were worsening.
If we could spread the six-layer sheet of the neuronal cortex out and actually see the ﬂashes of seizures as thunderbolts, we would see multiple lightning storms searing its critical regions, more streaks of lightning surging back and forth, seemingly random in their patterns. And like lightning, these seizures would destroy.
What was happening? If we could spread the six-layer sheet of the neuronal cortex out and actually see the ﬂashes of seizures as thunderbolts, we would see multiple lightning storms searing its critical regions, more streaks of lightning surging back and forth, seemingly random in their patterns. And like lightning, these seizures would destroy. There would be no ﬂame, but the constant ﬁring eventually would burn out the neurons. The unrelenting bursts would lead to excitotoxicity, whose synergy would combine single harmful effects into lethal combinations just as Gail’s single seizures had spread outward.
Day after day, the storms played out. Yet every test over the next ﬁve days would prove frustratingly normal. Blood proteins normal. Spinal ﬂuid told that the brain’s health appeared normal. Temperature. Blood pressure. No matter what the test, normal—frustrating because seizures broke through every powerful drug, and something causes seizures that is not at all normal.
Gail, who had had several seizures on Saturday, was in full status epilepticus, the seizures coming so frequently that they were for all intents and purposes constant, and life threatening. Some epilepsy patients suffer multiple daily seizures yet have no brain damage years later. Why is status so deadly? Because neurons do not have time to recover, to rebuild their energy stores, between ﬁrings. David Treiman, one of the leading investigators of status epilepticus, believes that even two seizures should be considered status if they are close enough together to prevent the ﬁring brain cell from recovering.
Allis recommended transferring Gail to Columbia’s NICU. As the neurologist and Joe Beck clambered into the ambulance behind Gail’s gurney for the journey down the Long Island Expressway to Columbia, there seemed little if any hope for something like recovery. But there was hope for life, for some kind of life that would have to be invented. That would have to do, Joe decided. Anything would be better than losing Gail. Thank God he had the summer off. They were insured, but how much beyond their coverage would this carry them? The boys were with the Kinsellas now, but he would have to get home soon for them. Gail would not be working. Joe knows this trip on the LIE as any Long Islander would, making a run to the city. There was too much time to think and too few facts to stoke the thinking, so the questions just jumped and danced.
They were in the city now, ﬁnally pulling in to the ambulance entrance of Columbia’s New York Presbyterian Hospital on Fort Washington Avenue, the George Washington Bridge looming to the north. Finally they’d reached the fourth ﬂoor: Neurological Intensive Care Unit.
“A PATTERN INDISTINGUISHABLE FROM BRAIN DEATH”
Stephan Mayer led afternoon rounds on Thursday, June 27. The year was 1996. This is how he saw Gail Beck just hours after her admission:
Diagnoses: 1. Status epilepticus, 2. Idiopathic encephalopathy possibly secondary to encephalitis ... Chief Complaint: 31-year-old woman with status epilepticus ... Her brain is practically on ﬁre, Mayer saw, so convulsed in the horriﬁc, non-stop, global brain seizures of status. He had never seen such unremitting, intense seizures, even in status. “Everything in my training, in medicine, neurology, said this woman is a goner. There’s nothing to be done,” he recalls. Only his readings and experience as an intensivist suggested that extreme treatments might work in the carefully monitored and controlled environment of the NICU. The aggressive approach to status epilepticus championed by Treiman and others was just taking hold in these elite environments. Only a year earlier a case study in the journal Critical Care Medicine had described a patient pulled out of status epilepticus after 53 days in “burst suppression,” or barbiturate coma. The authors: Marek A. Mirski, Michael A. Williams, Daniel F. Hanley. But few outcomes were as good as theirs, even when patients survived.
The familiar EEG portrays waves dancing in regular patterns throughout the living brain, the music of hundreds of billions of brain cells ﬁring in synchronies so complex that neuroscientists are just beginning to understand them, and they may never do so fully. The patterns displayed on the EEG screen may be modulating bursts ﬁred like timing signals by certain neurons in thousands of networks, to keep the brain in tune, to bind into a single moment dozens of network activities that are occurring in parallel.
But many, if not most, of the ﬁring patterns represent activity that is counterintuitive.
The brain in deep sleep is at its most synchronized. Rhythmic pulsings from deep within during sleep appear to block transmission of the bursts that communicate sensation and other messages throughout the alert, conscious brain. It’s a perfect example of signal jamming.
During a seizure, something crashes chaotically through the harmonies of the brain; however, just as in sleep, this is a well-organized kind of havoc. A wave of lightning replaces the thousands of steady thrums of interconnected networks, and the victim may thrash about wildly or pass out.
During a seizure, something crashes chaotically through the harmonies of the brain; however, just as in sleep, this is a well-organized kind of havoc. A wave of lightning replaces the thousands of steady thrums of interconnected networks, and the victim may thrash about wildly or pass out. Another lightning wave may strike, then another. If seizures are not controlled, kindling can occur, just as in a wildﬁre. In a distant part of the brain, blown as though on the wind by neuronal ﬁrings, another local seizure-blaze can break out, and elsewhere another. The metaphors for what happens are vivid, but they remain metaphors: kindling, recruitment, entrainment. But the critical fact about the pathways of seizure is that, unlike an electrical short circuit, neuronal ﬁrings are not “jumping their networks.” The spread of seizures from local to general follows normal pathways, ampliﬁed out of bounds, repeating out of control.
In the worst cases, the separate seizure-ﬁres grow into one ﬁrestorm throughout the entire brain, when virtually all the neurons can become involved. That is a generalized seizure, but generalized seizures are usually brief. Any seizures that repeat rapidly represent status epilepticus, and the most serious level of status is generalized. Gail Beck’s was the worst case Mayer had ever seen. If he could not stop the ﬁrestorm, her brain would burn out—if it had not already—in the metaphorical sense of fatally exhausting itself.
Medications on transfer from Huntington: the anticonvulsant Dilantin and a powerful intravenous drip of the sedative Ativan. But they had failed to stem the explosions. Not even phenobarbital had stopped them. One possibility remained, risky enough that few neurologists outside a neurointensive setting would try it, and that was the barbiturate pentobarbital. A very low dose of sodium pentobarbital provides the so-called truth serum that is a staple of melodrama; a higher dose yields a common general anesthetic. But large doses of the barbiturate hammer the brain’s neurons into silence, and, equally dangerously, they drag down the electrical signals that keep the heart beating and can even halt them permanently.
Mayer gave Gail Beck a megadose, suppressing her brain’s electrical activity into ﬂatline. The waves vanished from the EEG so it now showed a pattern indistinguishable from that of brain death. The idea was to smother the ﬁrings, then slowly bring her back.
After several days Mayer lifted the “barbs.” His patient now was in so profound a coma that she registered 3 on the Glasgow Coma Scale, the worldwide quick test of brain function. She could have scored a maximum of 5 in each of three series of tests of responsiveness, for a total GCS of 15. But there is no zero score; 1 is the lowest in each series, a limit brain doctors say is there to remind them that no simple test can be certain. Thus, a cadaver scores 3 on the GCS. As the grim joke goes, on this test you get three points just for showing up. There she was.
Yet even at that level, as Mayer relieved the grip of pentobarbital, the ﬁrestorm in Gail’s brain resumed, and he pushed her down again. And again. Over days and then weeks she remained in ﬂatline, a state from which many physicians said she could not return. Not at all, never mind to anywhere near “baseline”—that prosaic term for all the rich complexity of life in the moment before.
Idiopathic: occurring without known cause. Another meaning, even stranger and best not dwelt on: self-originating. How can you make science out of that? Making science out of epilepsy has been one of the great challenges of neurology.
THE MANY MYSTERIES OF SEIZURE
Encephalitis was the culprit, Mayer was certain, inﬂammation of the brain that causes swelling and often leads to seizures. The several varieties of encephalitis are caused by viruses, in the United States most commonly carried by mosquitos. Three years later, a new and even deadlier variety would turn up in New York under the name West Nile Virus. Was this, in fact, West Nile itself, years ahead of its emergence? Could have been, but the point is moot. No sign of the cause of Gail’s encephalitis had been found, nor would it ever be, and there was never even a conﬁrming test that encephalitis was present.
No proof. Idiopathic: occurring without known cause. Another meaning, even stranger and best not dwelt on: self-originating. How can you make science out of that? Making science out of epilepsy has been one of the great challenges of neurology. To get a sense of this, draw back, as though hovering over it as an island, matching brain structures and actions with names of explorers and investigators. It is surprising how many people’s paths cross. It is equally surprising how many “good roads” go nowhere.
At one level, epilepsy seems simple— chronic seizures, sometimes with consciousness altered or lost, sometimes with consciousness not affected at all. It has been known by this name for thousands of years. Yet the study of epilepsy, the attempts to grasp the many causes that funnel down into variations on a theme, is so complex and difﬁcult that the physicians who treat it form one of only two board-certiﬁed subspecialties in neurology. The ﬁrst is child neurology; children’s developing brains are different enough in their plasticity and function that treating them requires a different ﬁnish to residency. Epileptologists’ branch is formally known as neurophysiology. Say anatomy and we rightly think of a map, for no matter how complex in the relationships of parts, anatomy is structure, still photos. Physiology is the study of dynamics, the parts in motion and communication, if such terms are precise enough for the welter within the body. Motion there is, of many kinds. The speed of ﬂowing blood can be measured by the same means as the speed of galaxies or submarines. And the moving images on the EEG, the thrashing motions of seizure, all clearly suggest the result of electrical discharge, like grabbing a hot wire.
But nowhere else, even in the brain, are appearances at one level so difﬁcult to relate to the underlying events that cause them as they are in neural electricity. Robert Fisher’s name comes up often as you travel the tight, small network of epileptologists who balance the worlds of research and patient care—clinician-investigators. Fisher has spent his life studying the electrochemistry of the brain and is “a real dynamic force in our ﬁeld,” one Columbia epileptologist says. Fisher has studied epilepsy in the laboratory and traced it through the often-difﬁcult lives of patients in his clinic and in the neurointensive care units where status epilepticus brings those it has stricken.
“Be careful not to speak of epilepsy as though it were an electrical disease, or a disease of the brain’s electrical functions,” he cautions in his Stanford ofﬁce. “It’s so much more complicated than that.”
As though electricity were simple. More than 200 years after electric current was generated by a battery and “seen” jerking the leg of a dead frog, establishing its neural presence, you can only get a feel for the physical reality of electricity from specialists, be they quantum physicists, biochemists, electrical engineers, or epileptologists. Each will deﬁne electricity in terms of its manifestations in their own realm, and, in theory, the laws describing electricity’s causes and effects are as translatable as currencies. But what is it, other than a way of speaking of particular causes and effects? A ﬂow of charge is the most common denominator, and it appears to work here, in the ﬁring of one neuron. But the actual communication between neurons that sets up the “waves” of the EEG is via neurotransmitter molecules that lock into receptors, like keys slipping into and turning locks. Hence the chemistry of electrochemistry. In this respect, to speak of the brain as “electric” is like calling the Long Island Railroad an electrical network, rather than a network of steel trains powered by electricity.
Seizures represent out-of-control ﬁring—measurable electrical pulsing—of masses of neurons, but the neurons are only out of normal controls. In fact, the problem is that they are under some other controls.
Fisher’s point is that the convenient electrical analogies break down when you try to employ them in healing the brain. Seizures represent out-of-control ﬁring— measurable electrical pulsing—of masses of neurons, but the neurons are only out of normal controls. In fact, the problem is that they are under some other controls. The spiking neurons are very much in alignment, as coordinated as an army marching in perfect step. They are entrained, lined up, but inappropriately. It is difﬁcult to know whether they get that way because their ﬁring mechanisms are too energized or because the inhibitions—the “Don’t ﬁre!” signals—are lost. But most investigators these days believe that focal seizures are caused by loss of inhibition. That loss allows normal ﬁring patterns to form a closed loop, as noise can feed back from a bandstand speaker through a microphone and ampliﬁer, then out through the speaker into the mike, leading to an ear-splitting screech. That screech is limited by the power of the components, and in what seems a perfect analogy, most seizures are self-limiting. But there—Fisher’s point again—the analogy breaks down. It is now believed that seizures don’t stop because the neurons are exhausted of supplies. Exhaustion of supplies leads to brain damage—excitotoxicity—not to the termination of seizures.
Generalized seizures are something else again, and their causes are linked both to structures deep in the brain and to the exquisitely sensitive membrane-skin of neurons.
What causes epilepsy in some people and not in others? Genetics plays a clear role in some childhood epilepsies that run in families, and very recently a faulty gene was found in one of the inherited forms. The inﬂammation of brain cells through infection, the apparent cause in Gail Beck’s case, or because those delicate outer membranes have been bathed in blood, as in a hemorrhage, are other known ways that ﬁring inhibition can be lost and the entrainment can begin in which, like too many soldiers marching in step across a bridge, a destructive rhythm begins and ampliﬁes itself.
Maybe we’re all susceptible to seizures, some people only more so. “If we all live long enough, maybe we’ll all have a seizure,” Fisher hypothesizes. “One person’s mean time between seizures is two weeks, maybe mine is 150 years.”
Finally, though, to someone who has stared as long and hard at the many faces of epilepsy as Fisher has, another answer suggests itself: Maybe we’re all susceptible to seizures, some people only more so. “If we all live long enough, maybe we’ll all have a seizure,” Fisher hypothesizes. “One person’s mean time between seizures is two weeks, maybe mine is 150 years. At some later age, I have one single seizure—not so unusual for anyone, especially as we get older—and I never have another one. I had the ﬁrst one earlier than my 150 years but won’t live long enough for another.”
Fisher points out that many of history’s leading ﬁgures suffered from epilepsy, and it was frequently associated with a possession, holy or demonic. Socrates and St. Paul, Julius Caesar and Joan of Arc, Dostoyevsky, Tchaikovsky, Alexander and Napoleon, James Madison, Vincent Van Gogh—all had epilepsy. Did they have anything else in common? Not apparently. So different are the expressions of epilepsy—it is, after all, a chronic set of symptoms called seizure, with any number of potential underlying causes— that it has taken until the last few decades for specialists to come up with an internationally agreed upon terminology for its many modes.
Does the person lose or change consciousness? If not, it is a simple seizure; if so, it is complex. Does the seizure occur in only one place, emanating from one small spot, its spread limited to a tight, local network of cells? Then it is focal. Does it spread from that single focus to a few other tight, local networks, maybe to its complementary networks on the other side of the brain? Then it is multifocal. On the other hand, if a seizure begins in one place and then spreads throughout the entire cortex, it is termed secondarily generalized. But what if it begins virtually everywhere at once, across most of the vast territory of the cortex? Then it is general—primary generalized.
Interestingly, as noted, those seizures that begin in one place then spread to many, or even become secondarily generalized, follow the paths of normal cortex networks. That is, they don’t represent the kind of short circuit in which ﬁring spreads randomly. So far, so good. But the spread throughout cortical pathways doesn’t hold for so-called primary generalized seizures. They begin everywhere at once.
How can a seizure literally begin all over the brain at the same moment? Here is yet another doorway into the deepest unknowns of brain function: by emanating from a structure deep within the brain, a structure that sends its ﬁring axons everywhere within the cortex, modulating, relaying, perhaps helping bind sensation, thought, motive, and movement into one.
How can a seizure literally begin all over the brain at the same moment? Here is yet another doorway into the deepest unknowns of brain function: by emanating from a structure deep within the brain, a structure that sends its ﬁring axons everywhere within the cortex, modulating, relaying, perhaps helping bind sensation, thought, motive, and movement into one.
Most of the neurons—the “thinking cells” of the brain—interweave their tendrils among the six layers of the cortex, the deep-folded surface of the brain. But deeper in the brain are other neuronal structures that in lower animals may constitute most of what they’ve got for a brain. If all the lights in a skyscraper began ﬂickering at once, you would look for a single damaged input source. When ﬁring begins all over the brain at once, you look for someplace like the thalamus. Thalamus and hypothalamus compose the diencephalon, sitting like a metropolis on the giant trade routes between the brain stem—sensation in, action out, rudimentary controls—and the upper brain, the domain of “I.” As we’ll see, the thalamus has two opposing sets of behaviors that point to it as a major player in those most serious seizures.
In contrast, what would be a likely source for purely local out-of-control ﬁring? That is, what parts of the brain normally have to be ﬁring a lot, just to keep us going? Loss of control in these areas, loss of inhibition, would hit harder and faster. The structure twinned in the left and right sides of the brain, called the hippocampus, is the crucial site for laying down new memories— that is, learning—and for recalling what we’ve learned, or remembering. Long term, the memories are stored throughout our brains. Getting them there requires action within the hippocampus. For all our lives— as long as we can learn a new phone number, remember a new name, see something we’ve never seen before and embrace or ﬂee from it, then call it all back later on—the hippocampus is a tightly controlled storm of activity. It is the most common site of seizures. Both hippocampi can be damaged by repeated seizures, loss of oxygen in a heart attack, cardiac arrest or near drowning, or through the inﬂammation of encephalitis. The most common casualties of the damage are learning and memory. The hippocampus is nested within the temporal lobe, which also contains a region involved in language understanding, another hotspot of brain activity. Damage the hippocampus, especially on the left side for most people, and problems in understanding language can occur.
How does brain trauma bring on seizure, even if no hemorrhage is involved? In trauma, neurons are often destroyed, their connections lost, Fisher points out. Even if few new neurons are grown in adults, new connections are made constantly. That is how stroke survivors often regain lost abilities as different structures take over the roles of the missing by forming new pathways. That means, again, furious activity among surrounding neurons, like plants sending roots and spreading into a weeded patch. A frenzy of new growth to a good end—re-learning—but leaving the network more vulnerable to lost control, which the trauma may also engender.
None of this, of course, is status epilepticus. Some years ago, Robert Fisher stood at the bedside of a young woman who had suffered status through a long, painful period. He had brought her out of it with complete success. She lived “two wonderful years,” her mother said, and now she had relapsed with no hope of a meaningful recovery. That was at Barrow Neurological Institute in Phoenix, where Fisher was head of neurology and had ﬁrst call in the Neuro ICU for cases like these. He left Barrow for the endowed professorship he now holds at Stanford. The girl had told her family she wanted meaningful life or none at all, and the family made the decision to follow her wishes and let her go. Fisher did so. Status is special, Fisher says, and perhaps the leading authority on the subject is David Treiman, who coincidentally has just taken over as head of epilepsy at the Barrow Neurological Institute. There, on a dark winter evening when he gets free of his schedule, Treiman elaborates on this mysterious killer. Status epilepticus is called by some a caricature of epilepsy, as though it represented an exaggeration of each of the features that are epilepsy’s hallmarks. Epilepsy is common— as many as 1 or even 2 percent of the world’s people suffer from it—but status is rare. It can be deadly when generalized, and that is its most common form.
Treiman argues that status epilepticus can be any series of seizures—from the simplest to the most complex, focal or general— marked by lack of recovery of the brain between seizures. That’s what causes the damage. The historical ﬁgures mentioned suffered epilepsy throughout their lives with no loss of brain function. The damage wrought by status epilepticus, Treiman believes, results from the inability of the neurons to recover before they ﬁre again. That leads to excitotoxicity, but now glutamate, the excitatory neurotransmitter, does not appear to be the major culprit. In status, “there is an alteration in the physiology of the brain such that the normal mechanisms of shutdown fail,” Treiman says. Shutdown means inhibition.
And that introduces the most common neurotransmitter in the mammalian brain— gamma-aminobutyric acid, mercifully shortened to GABA. Unlike glutamate, it is inhibitory, and that in itself sheds light on how the brain works. Inhibition is the key to controlled action. By far most of the neurotransmitters latching onto a neuron’s inputs tell it, “Don’t ﬁre.” It’s as though all the neurons in the brain had their ﬁring hammers set, and just the right bursts to initiate a complex and precise action—a tiger springing, a composer humming—are brought about by blocking the circuits not wanted more than by tripping those needed to make it so. The analogy recalls Michelangelo’s description of sculpting as cutting away stone to bring out forms within in the rock. GABA is the sculptor. But something happens to GABA or its receptor, Treiman says, that allows one circuit or all of them to ﬁre without end. And the latter, the ﬁring of all circuits, is the generalized status epilepticus Gail Beck suffered, the worst killer.
Treiman’s published research asserts that generalized status epilepticus kills 50 percent of its victims unless they can be brought out of it quickly. Many survivors are vegetative, others left with little that could be called a meaningful quality of life.
Thinking of these ominous facts brings back a profoundly cautionary comment by Jeffrey Frank, the neurointensivist in charge of the University of Chicago NICU, on the power of modern medicine: “Sometimes we can enable our patients to survive with a disability beyond their worst nightmare.”
Ever more haggard, he took Mayer’s answers down carefully. But the neurointensivist didn’t have much to tell, other than to caution him that his wife’s odds were looking worse. It was only after 14 days that he was able to bring Gail out of coma without her seizures recurring. But there was little sign of recovery.
Each day as Mayer led the team on rounds, there was Joe Beck, distraught but determined, with a thick notebook in hand and a dozen new questions. Ever more haggard, he took Mayer’s answers down carefully. But the neurointensivist didn’t have much to tell, other than to caution him that his wife’s odds were looking worse. It was only after 14 days that he was able to bring Gail out of coma without her seizures recurring. But there was little sign of recovery. He had to let Joe know that there was a very real possibility Gail would glide into the death-inlife of the persistent vegetative state. Joe was in living hell.
From there Gail developed pneumonia and was pumped full of antibiotics, including antiviral acyclovir for the still-unconﬁrmed encephalitis. Her ventilator face mask was replaced with tracheostomy, a permanent air tube in her throat. IV feeding yielded to a PEG, a permanent feeding tube inserted through her stomach wall. Permanent is an ominous term in the ICU. Each of these decisions is a landmark one hopes not to reach.
Rashes indicated allergic reaction to one or more of her powerhouse drugs. Other drugs were mixed and matched to control it.
The seizures returned.
Mid-July: Seizures controlled for a time.
July 23: Up through the tight web of anticonvulsants burst new, “breakthrough seizures.”
August 8: The NICU team had done all it could. Gail Beck was no longer in status; epilepsy is a chronic condition, and it was unclear what other aspects of her desperate condition were chronic. She was sent to Mount Sinai Rehabilitation Center.
August 8, same day: Back to Columbia Neuro ICU with uninterrupted seizing. On and on, up and down, lightning storms damping only to rekindle, without betraying a cause. This, Mayer told Joe, was the waiting game.
Joe was now looking back on summer with little more to recall than the NICU and the Long Island Expressway. Sixty-four round trips on the LIE, sometimes alone, sometimes with one or more of the family.
LIVING WITH THE DAMAGED BRAIN
Jump to the end of the dramatic phase of the waiting game. Gail did not die, nor did she sink into a persistent vegetative state. On Wednesday, September 4, the ﬁrst day of the new school year, Joe made the ﬁnal trip to the NICU, to bring Gail “home,” to the St. Charles Rehabilitation Center, two miles down the road in Melville. She had no muscle strength or energy so she could hardly walk, even with a walker. But she was going home. Her mother carried Ian in to reunite them. Gail looked up, burst into a grin. “What a beautiful baby!” she cried. “Whose is it?”
No memory. No bad memory of the summer, no good memory of the years behind, her long-term memory shot; perhaps she would have to begin again, laying down short term memories one by one. But there was something more, which many would consider the worst. She suffered from “ﬂat affect,” a common outcome of severe epilepsy when recognition does not bring along rich, layered feelings.
No memory. No bad memory of the summer, no good memory of the years behind, her long-term memory shot; perhaps she would have to begin again, laying down short term memories one by one. But there was something more, which many would consider the worst. She suffered from “ﬂat affect,” a common outcome of severe epilepsy when recognition does not bring along rich, layered feelings. Emotions are somehow tied into memory and perception in the region surrounding the hippocampus, and deep down in the hypothalamus, and perhaps deeper still in the adjoining thalamus, and it was not clear that she would ever regain them. Often she was in despair, and that represents feeling, but not necessarily feelings tagged onto the words and thoughts, faces, sounds that draw meaningful human life out of raw experience. She was alive and home again. Joe got his wish. Now what?
Possible outcomes of the waiting game: in addition to memory deﬁcits there were language problems, called aphasias, of an astonishing variety, each a window into a part of the brain. Damage to Broca’s area in the frontal lobe, in a region of the motor cortex across the valley from the temporal lobe, can leave the inability to speak, even though words are understood. Damage to a rear sector of the temporal lobe, called Wernicke’s area and appropriately near the auditory cortex, can produce an inability to understand language. For most of us, these language areas are on the left side. But Johns Hopkins neurologist Argye Hillis points out that the right hemisphere, which we associate with global apprehending, gestalt, intuition rather than serial thinking, also has a language link. Those suffering right-brain damage often do not get the meaning of what is said. They may fail to understand emotional intonations, even though the sentences make perfect sense since their left brains are intact. For example, they may fail to get jokes. In a visual analog, they may not recognize emotion in facial expression. Hillis said one of her patients could perfectly describe a drawing on which she was tested. It showed a woman cooking at a stove, a nearby kitchen sink, a pot on the edge of the sink, and water ﬂowing into and out of it. She could not apprehend the single thing the rest of us would spot at ﬁrst glance: the pot is overﬂowing, ﬂooding the kitchen ﬂoor. She got everything but the import.
Possible outcomes of the waiting game: in addition to memory deﬁcits there were language problems, called aphasias, of an astonishing variety, each a window into a part of the brain.
It is four summers later, 2000, when Stephan Mayer plops down the thick folder with Gail Beck’s name on it and recounts her story. His colleague Stanley Resor has been Gail’s epileptologist in all the years since, and Stephan only knows it’s been some roller coaster for her. He hasn’t seen her, has no idea how she is, how the Becks are doing. It’s the nature of the job of the intensivist—the rescuer—to be left with little or no idea of the fate of patients unless they write or visit, and, since the patients usually remember little of their time in the NICU, that is rare. There was only a letter from Joe Beck in 1998 that began, “This is the saddest letter I have ever had to write...” and went on to detail the family’s grinding ﬁnancial straits and Gail’s condition.
How could one measure her current condition? Mayer is particularly critical of the category-coded language of patient follow-ups that are written up in all branches of medicine. “The patient says, ‘I feel ﬁne, just like before, never better,’” Mayer says. “You talk to the wife alone and she says, ‘He used to play with the kids, he worked like crazy, he loved sports. Now he just sits around the house all day watching whatever comes on TV.’ But based on the guy’s report, you could write him up as complete recovery. That’s not what I call a good outcome.”...
It’s always rush hour on the Long Island Expressway, and the feeder highway off of it is also heavy with trafﬁc, leading right to the door of the Becks’ duplex across the street from a pocket shopping center. Gail answers the door, apologizes for the tumble of boxes and housewares, toys scattered in the living room. They are moving in two weeks. She is, on ﬁrst meeting, a “regular person.” There is nothing in her speech or manner that suggests she has survived a devastating illness. Joe gives a hearty greeting and handshake, and it’s clear from his tone, his words, that he feels they are delivered. Gail is less sure, quick to be annoyed with herself. “I used to love Hamlet,” she says. “I can’t concentrate anymore. I’m trying to get through The Godfather now, and that’s tough enough.”
“It’s a start!” Joe counters, encouragingly.
The boys shyly say hello. Gail says they’ve been terriﬁc about her recurrent seizures. “I’ll be sitting on the couch and slump over, and they know to call my sister and not to worry,” she says. “The seizures aren’t bad. I usually just fade out, like falling asleep for a few minutes. Every now and then I have a worse one and wake up on the ﬂoor. Usually, I can get to the couch. But I guess what gets to me most is my memory. Sometimes it seems I can’t remember anything.”
Her frustrations seem small by comparison with what her prospects had been, but they are sharp all the same. “I know this will sound crazy to most women, but I just wish I could do my own shopping. I would love to drive again.”
Her frustrations seem small by comparison with what her prospects had been, but they are sharp all the same. “I know this will sound crazy to most women, but I just wish I could do my own shopping. I would love to drive again. I could drive the boys around; I could shop by myself.”
At this, or at any hint of pessimism, Joe looks heavenward, shakes his head. Deliverance. He is teaching English at nearby Plainview High School. He has written a play, and in its depiction of an elderly husband’s efforts to cope with his wife’s Alzheimer’s, it’s clear he is exorcizing the early years of recovery when Gail’s memory really was shot, when everything looked dark.
They’ve been seeing epileptologist Stanley Resor at Columbia for four years now. First this medication, now that one; a new combination. Two years ago they went to the Mayo Clinic in Rochester, Minnesota, as long a trip as Gail has ever taken. Ups, downs. She tries not to get discouraged. “I try to take it a little bit at a time,” she says. True, as you listen to her, there is a slow, measured texture to her speech that suggests someone on tranquilizers. But someone all there, for sure.
Ups, downs. She tries not to get discouraged. “I try to take it a little bit at a time,” she says. True, as you listen to her, there is a slow, measured texture to her speech that suggests someone on tranquilizers. But someone all there, for sure.
In his Columbia ofﬁce, Resor ﬂips the pages of Gail’s life, as measured in dosages of medications with arcane, tongue-twisting names. Gail’s seizures, he is sure, had a multifocal onset, then became generalized and progressed to status epilepticus. Reﬂecting on the fact that she cried out as she ﬁrst seized, he says it is common for a seizure to strike the motor cortex region controlling the diaphragm or the throat’s glottis, yielding an involuntary cry or loud moan. She has auras, premonitions of a seizure coming, also a sign of focal rather than generalized seizure at the start. “Primary generalized seizures are usually genetic” in origin, he says. Still, Gail’s auras are not well focused. Some patients have auras so clear, with such precise timing, that they can drive, knowing they will be prompted by the clockwork aura minutes before a seizure to pull off the road.
Tall and lanky, Resor slouches in his chair, seven o’clock on a Friday night and the last patient just gone. “Phenobarbital at ﬁrst, but that’s a barbiturate, so it’s addictive,” he says as he reads from Gail’s ﬁle. “If you withdraw it suddenly, you can give a seizure to someone who’s never had one.” He carefully picks his way through the ﬁeld of possibilities, many discovered serendipitously. “Valproic acid is a solvent. In the early sixties it was used to dissolve seizure-inducing drugs being given to test animals. None of them had seizures. Someone ﬁgured out it was the solvent.” That’s now called Depakote, one of the major antiseizure drugs. He doesn’t like Depakote compared with others, not long term, so he works to get his patients off it if he can. Balancing this panoply of drugs and doses underscores what skills are needed to be an epileptologist, other than correctly interpreting a seemingly impenetrable EEG printout.
“Phenobarbital makes the body get rid of Depakote quickly,” he says. “So you have to give a bigger dose of Depakote if it’s in combination.” A pause. “But Depakote makes it harder for the body to get rid of phenobarbital, so if you’re not careful you wind up with too big a dose of phenobarbital.”
A bit of this, a jolt of that. This is the high-art end of the medical spectrum, empirical to the core. True, a new drug protocol may emerge from clinical trials as “evidence-based medicine,” but it takes far more than formulas and error bars to make it all work.
A bit of this, a jolt of that. This is the high-art end of the medical spectrum, empirical to the core. True, a new drug protocol may emerge from clinical trials as “evidence-based medicine,” but it takes far more than formulas and error bars to make it all work. Resor points out that only two seizure medications were developed from scratch—that is, with their mechanisms of action known from the start. The others were developed for other purposes, such as sedation. Their effects suggested a beneﬁt in seizure control, and trials conﬁrmed it.
Even so, the preferences of epileptologists vary more radically than, say, favoring mannitol over salt solution in the NICU. Resor dislikes one of the hot new drugs on the market because “it makes people stupid.” On the other hand, he likes Lamictal, which “scared off lots of U.S. doctors” after it was introduced from Great Britain. It gave some patients severe rashes of the epithelium, the lining of the mouth and throat, of blood vessels, and of such inner organs as the liver and kidneys. The kidney rashes proved fatal in some cases. But Resor says such side effects can be completely prevented. “You start slower, monitor very closely, and look for signs of oral rash.” Gail has been doing well on Lamictal, which has fewer side effects than many other drugs.
Phenobarbital reduces the effectiveness of Lamictal, so once Resor was able to get Gail off phenobarbital, the Lamictal’s effectiveness increased. “But when I stop the Depakote, that will make Lamictal levels drop, so I’ll have to increase it.” And on through the maze.
A year has gone by since the Becks loaded up all those boxes and moved a few miles away to their new home, in a quiet neighborhood of Bethpage. Long gone is The Godfather, but Gail is not yet ready for Hamlet. Gone, too, is the ﬂat, emotionless voice that had marked her as she left Columbia and whose traces remained even a year ago. She laughs a lot. Her sense of humor is keen. She plays on words.
She still has seizures. “Not as bad as before,” she says. “And the boys are great about it.” Her big leap forward: she must still be driven to the store, but she can take care of all the shopping herself, preparing the list, remembering where to ﬁnd everything. She loves the new house, really loves the neighborhood. Her next goal is to stencil borders atop the dining room walls. Her mother doesn’t want her to do it alone, afraid she will fall off the ladder, but Gail is certain enough of her auras not to be worried. Lately, she has never failed to make it to the couch when she felt a seizure coming on.
“Part of my frustration is that I’m very competitive,” she says. “I can’t stand to lose.” But now she is losing at chess, not the simple board games of a year ago. At ﬁrst, playing with 11-year-old Andrew—who is, she admits, a very good chess player and as competitive as she is—Gail was losing consistently. Now she beats him often enough. A big roll of the eyes from Joe.
Sometimes she feels those auras, a sense of fading, while she is playing chess and thinking about the many possible moves ahead, hopping in her mind among alternatives. Sometimes it’s in big family gatherings, like Thanksgiving, when many people are talking in cross-conversation and she is trying to thread her way among them. “I just pull back a while. I’ll go take it easy, by myself, for a few minutes, and it goes away.”
Her memory may skip a few beats now and then, but never her will and self-direction. Here she is walking Ian to the school bus for his ﬁrst day of kindergarten. One minute, there they are. The next, she’s looking at the sky as the gurney is being loaded into an ambulance. “I’m telling them, ‘Stop, I’m okay. Just leave me, I’m ﬁne.’ But, no, they had to take me.” She is determined that, with her prodding, anyone who knows her will, like Andrew and Ian, not worry if she fades out for a few moments.
Time heals. Medicine heals. Neither works all the time. Which is the tonic for Gail Beck? Hard to tell, say Mayer and Resor. Only the outcome is clear.
Time heals. Medicine heals. Neither works all the time. Which is the tonic for Gail Beck? Hard to tell, say Mayer and Resor. Only the outcome is clear. A few weeks after Mayer had brought out her thick, years’ old ﬁle in his ofﬁce, Gail and Joe walked into the NICU for the ﬁrst time since she had gone home. Nurses ﬂocked toward her, weeping with joy. Gail, who was meeting them for the ﬁrst time, couldn’t help but join in....