Reaching Down the Rabbit Hole: Extraordinary Journeys into the Human Brain

by Allan H. Ropper

Her blood pressure was so low that Tony couldn’t find a distended vein to put in an IV. I started to do a cut down on her ankle, once a very popular and macho thing to do. There’s one big vein in the medial ankle, and if you can find it and slip your finger under it, it will fill with blood and you can stick whatever you want into it.

neosynephrine

Neosynephrine is a drug that further constricts the peripheral blood vessels in order to ramp up the blood pressure. You sacrifice perfusion to the limbs in order to keep the brain, the heart, the viscera, and the lungs getting adequate blood.

At that time toxic shock syndrome was just being recognized. It was named in 1978, but we had been seeing cases for a few years before that, and at first had called it staph sepsis. Several of our clinicians were already onto the idea that it was due to an infection caused by tampons, and that’s what this looked like at first. She had a rash, which fit, and I said,

Seconal

Often, it was a cocktail of drugs that produced mental depression, excitation, and psychosis all together, as if everybody was in a rush to finish an advanced psych course and meet their maker at the same time.

“Look at her pupils! Sheesh!” Nobody had noticed. Her state of shock and the neosynephrine had given her enlarged pupils down in the ER, but now, almost two hours into it, I could see her tiny pinpoint pupils. We gave her some Narcan and she woke up almost immediately. She and her roommate had both been doing heroin.

Narcan, or naxolone, is an antidote for an opiate overdose. It competes with narcotics to bind to the brain’s opiate receptors, and kicks them off so that they lose their effect. We infused it, and she woke up in thirty seconds.

“Basilar artery thrombosis.”

Eventually they did the angiogram, and—what do you know?—she had a thrombosis in the basilar artery: a stroke.

Think about it: There are more diseases of the muscle, just the muscle, which is a tiny sliver of neurology, than there are all diseases of the lungs. There are more diseases of the spinal cord than there are of all diseases of the heart. There are more diseases of the white matter, not the whole brain, but just the white matter, than there are of all the rheumatologic and joint diseases. Neurology has more diseases and more complexity and more need for exquisite clinical analysis than any other branch of medicine. Take one little piece of neurology: there is more to it than in the totality of any other medical specialty. And yet lung disease and heart disease dominate our collective fears. Dermatology is the only field that has more diseases than neurology. There are a billion skin diseases, but only ten of them occur with any regularity. Whereas in neurology people may say, “Oh, it’s just a stroke,” well, strokes are a big proportion of neurological cases, but there’s so much else to it: What kind of stroke? Where did it occur? What caused it? To master all that is a lifetime effort. So if you really want to be challenged instead of being bored in seven years, when you know all there is to know in your specialty, you may wish to consider neurology.

axial dystonia.

her examination, I took Nancy aside and said, “She has a glioma in her thalamus,” in other words, a brain tumor.

hepatolenticular degeneration.

how the thalamus—a small, central switchboard for the sensory system—works, and how it could produce this pain.

Fasciculations—the fluttering of small parts of a muscle, or what used to be called live flesh—are almost always benign. Virtually everyone has had the experience: small contractions around the eyes or the mouth, in the calf or the forearm. It happens when people are tired or they’ve had too much coffee or alcohol. Tending as they do to come in clusters over several days, these muscle flutters can reflect a patient’s self-involvement or their fear of illness.

Benign fasciculations can lead to a cramp, but are unassociated with muscle weakness. They go away. The bad twitches, such as the one I saw in Mrs. Nagle’s hand, result from the dying of nerve cells in the spinal cord. They occur when a group of muscle fibers loses the connection to its controlling nerve cell—the dying cell—and an adjacent surviving cell then takes over control of those fibers. This new, larger, motor unit cannot easily be sustained by the single nerve cell, and becomes very unstable, producing the spontaneous contractions in the remolded motor unit.

Hobson’s choice.

Air hunger is one of the most uncomfortable symptoms known to man or woman. Struggling to breathe, the awareness of breathing, contemplating the difficulty of each breath—something that a healthy, resting person never has to think about—is the feeling of dying. It probably contributes to the imminent sense of death (angor animi) of a panic attack.

George reminds me often that our role is to give Sophie balloons, not anchors.

Dejerine-Roussy syndrome, a debilitating combination of aching, burning, jabbing pain that is so life-altering that it frequently leads to depression and psychiatric problems.

I think life is too serious to be taken entirely too seriously.”

Happiness is a decision. What other people think of me is not my business. Live and try.

Michael J. Fox was first diagnosed with the disease in 1991, at the age of thirty-one, at a high point in his career. By the time he went public about his condition five years later he was starring in one of the top-rated shows on television (Spin City), had a string of post–Back to the Future movie hits under his belt, and was one of the most popular and widely recognized celebrities in America. That he happened to show up in my office before the public knew of his condition was a fluke. At the time, he was working in New York with Woody Allen on a television movie, a remake of the 1969 film Don’t Drink the Water. His condition was still a tightly guarded secret, one that was becoming increasingly difficult to keep hidden.

Sinemet

Artane

Ever since the name of the surgeon of Hoxton Square was attached to the disease over a century ago, there have been precious few breakthroughs in the treatment of Parkinson’s—two to be exact, each one a game changer. The first was the accidental discovery that the surgical destruction of a structure known as the globus pallidus could short-circuit the signals that caused Parkinsonian tremor and rigidity. Irving Cooper, a young neurosurgeon toiling in semi-obscurity in the Bronx, perfected the technique—called a pallidotomy—in the early 1950s. His results were so dramatic and unexpected that he was accused of faking his data, and was nearly drummed out of the profession. But by the mid-1950s, the pallidotomy became the standard of care. Over the next decade, Dr. Cooper and a few other neurosurgeons experimented with alternative lesioning techniques, notably the thalamotomy—the destruction of a pea-sized portion of the thalamus, another deep-brain structure—that also proved effective in eliminating tremors. Then one morning in the fall of 1968, after having performed over six thousand of these procedures, as many as six per day, Dr. Cooper walked into his clinic and announced that all such surgeries would stop, effective immediately. The reason was the arrival of a nonsurgical alternative: the drug called L-dopa, the secret ingredient of Sinemet.

Sinemet is in many ways a wonder drug. Its origins go back to 1967, when a Harvard-trained physician named George Cotzias found that administration of the chemical L-dopa in carefully timed doses relieved most Parkinson symptoms. L-dopa, or levodopa, crosses the blood-brain barrier and is converted into dopamine, the neurotransmitter whose curtailed production is a signature feature of Parkinson’s. Over the next decade, a series of hybrid drugs that combined L-dopa with a targeted delivery agent hit the market. One of these was Sinemet. Although it had only a modest effect on tremor, it became the drug of choice for most other Parkinson’s symptoms. With surgery no longer considered optimal, or even advisable, the question for neurologists boiled down to this: for any given patient, which of the L-dopa drugs should be chosen, how big should the doses be, and how frequently should they be given? To figure that out, I sometimes had to dabble in a little field research.

dyskinesias.

The drug provides an inverted arc of an effect: a big shot of L-dopa knocks out the symptoms, affording a twenty-minute window of fluidity and fluency. If too much is taken, the dose will overshoot the mark, producing the wild gesticulations and head twists. When the L-dopa begins to wear off, the descent is even quicker: a rapid reentry into a state of torpor marked by a frozen affect, the opposite of Michael’s on-screen persona.

At that time, neurosurgeons in Europe were experimenting with an extension of the Cooper procedure in which, instead of merely making a hole in the thalamus or globus pallidus, they placed an electrode at the site, and ran wires from the electrode through the skull to a small stimulator, essentially a pacemaker, implanted under the collar bone. It was called deep brain stimulation, or DBS. At that time, the technique and the equipment were primitive by today’s standards, and not yet approved by the FDA. The procedure offered little in the way of customization, and Michael was adamant that he did not want wires coming out of his head. But he was still a good candidate for the old Cooper procedure—the lesion without the implant—and this made sense given his unique needs and the time frame. He was still dealing mostly with tremor, something a thalamotomy could handle very well.

Lewy-body dementia.

Guillain-Barré syndrome,

made it impossible for him to stand, accompanied by loss of reflexes—pointed to a problem in the peripheral nervous system, most likely the result of Guillain-Barré syndrome, a treatable form of paralysis due to an inflammation of the nerves. It can cause a rapidly progressive weakness, and the disease is right in my wheelhouse: serious but manageable if caught in time.

By the dictates of the scientific method, we are obliged to seek evidence to disprove our assumptions rather than verify them. If you have a theory, you are not supposed to fixate only on the evidence supporting it.

Babinski signs, a toe reflex which is probably the most typical feature of compression of the spinal cord.

Deductive reasoning, as opposed to inductive reasoning, is what detectives and diagnosticians should be doing. Deduction works from general facts toward specific conclusions. If the “facts” really are facts, the conclusions have to be true. But induction—a quicker and much more practical method of reasoning that everyone uses every day—can lead to errors. That’s because an inductive process infers a conclusion, but doesn’t prove it. If the nerve conduction tests are normal, for example, the patient cannot have Guillain-Barré. But the inverse of that statement—that an abnormal test (like Harry’s) must be Guillain-Barré—does not logically follow.

The acute pain, while not typical, could possibly fit with Guillain-Barré. I know because I had written the paper on it. It’s called the coup de poignard, or stroke of the dagger.

(Most people don’t understand that the spinal cord doesn’t go all the way down the spinal column, but stops in the upper back.)

Because one of the results of an acute transection of a spinal cord that high up is an inability to sustain blood pressure, the decision was not about removing him from life support. All we had to do was stop raising the intravenous pressors, the medication that was keeping his blood pressure up. We wouldn’t withdraw anything. When his blood pressure started to decline, we wouldn’t raise it as we had before. Harry understood that. So we watched as his BP declined more and more. Two hours later, he died.

subdural is short for a subdural hematoma, a brain hemorrhage typical of traumatic brain injuries, caused in this case when the skull hit the sidewalk and the brain caromed off the inside of the skull, in the process tearing veins that run across its surface.

“He was intubated in the field with a GCS of five,” Trey dourly pronounced, as if that would capture everything about the case. It rarely does. The Glasgow Coma Scale was devised as an assessment of consciousness, especially for the use of first responders in cases of head trauma. It runs from a high value of 15 for a normal person, down to 3, indicating deep coma.

Imagine two scenarios. In one, the viewer, perhaps yourself, sees a dog being hit by a car, being thrown thirty feet to the side of the road, where it lies motionless, probably dead. In the other, you watch a fly land on a countertop, where it is swatted and effectively crushed. Most definitely dead. Why do we agonize over the dog but not the fly? The philosopher says, “Because the dog is conscious and the fly is not.” How do we know? Because the dog has eyes that look at you. The secret to consciousness is in the eyes. If the creature has humanoid eyes and it looks at you, then it is conscious. And if it doesn’t, it isn’t. The compound eyes of the fly do not convey any feeling to us of consciousness. Same with the worm. Philosophers and neurologists have come to the same conclusion with regard to consciousness, and that is that the secret to consciousness is in the eyes. If you understand the eyes, you will understand a lot about consciousness. In fact if you know a lot about the eyes—in great detail—then you’re practically a neurologist. This is not chance.

Remember, an overdose of barbiturates will make you look absolutely dead—no pupils, no eye movement, no vestibular ocular reflex, no calorics, no EEG, nothing—until you crawl out of the grave. So until you know with reasonable certainty that there are no drugs, that there has not been any severe hypothermia, and the criteria are fulfilled, don’t pronounce anyone dead.

Don’t let yourself be forced to pronounce death by brain criteria until you’re ready, no matter what they try to do. The neurology service is put in the middle here, in the Emergency Department and the Intensive Care Units, for various reasons, some of which have to do with organ transplantation, some of them with family pressure, some with the anxiety of caregivers (that is, other doctors).

I was mad at myself for not doing a better exam in the ED to see if our guy was truly brain dead. That diagnosis is transformative. The same warm body from ten seconds ago undergoes a state change, much like the transition of a liquid into a solid, and once pronounced officially dead, is entitled to all the rights and privileges thereof, which is to say, none whatsoever. When you are dead you cease to be a person, and you become an object. You no longer have possessions, a future, even a present, only a past. But Mike was not dead yet, not legally, not biologically, not until we said he was. He was still warm, still breathing (with assistance), still digesting his last meal.

The cranial nerves are key because they come out of the brain stem segmentally, and the big question is: is the brain stem involved? That’s why we begin with the eyes. The eyes are the secret to unconsciousness. We can’t test smell in these patients because that requires cooperation. Remember that smelling salts do not test smell; they test pain, the fifth cranial nerve. You can test everything else, but do you? You don’t have to. The eyes include cranial nerves 2, 3, 4, and 6, so you can go from 2 to 6 just by looking at the eyes. Whether the person gags or swallows when you move the tube depends on the level of anesthetic and many other functions.

What I noticed, and what I’m sure the others occupied in the dance did not, was the complete lack of a cough, a grunt, or even a quickening of breath coming from the patient. Sliding a tube up and down the trachea is one of the most noxious stimuli that can be applied to any live body, so noxious that it stimulates certain obligatory reactions. Awake but paralyzed persons tear profusely. Comatose people flinch and cough weakly. The dead are dead to it, and our guy hadn’t even flinched.

Once we had him situated in the bed, it was time for a curious piece of neurology: the brain death exam. This involves a sequence of tests designed to confirm a suspicion that the brain is not working on any level. There are five features that confirm a diagnosis of death by brain criteria, a few surrogate features that accomplish the same task, and a few that exclude the diagnosis. If you get a perfect score on the brain-death examination—five yeses—you can officially pronounce the patient as dead as Jacob Marley: as dead as a doornail. There is no other neurologic situation in which you would push a body to the extremes that these tests require, in particular, shutting off the ventilator to see whether someone can breathe on their own. It could kill someone who wasn’t already dead.

We don’t call it “brain death.” We call it “death by brain criteria.” To use the term “brain dead” confuses the public because they ask the question: “If it’s only brain death, what is alive? Are the kidneys alive?” I don’t use the term alive with regard to the kidneys or the skin. The person is in the brain, and virtually everybody in every culture agrees with that. It’...