CHAPTER 1
Andrea
Andrea was 27 years old, a beauty queen from Virginia, and a graduate of Harvard Law School. Brilliant, energetic, kind-hearted, and ambitious, she wanted to make a difference, so she chose government service, responding no thank you to the big law firms and their promises of early partnerships and seven-figure salaries. She believed in the power of policy and the law to make a positive impact in people’s lives; after all, that was why she went to law school in the first place.
She was a rising star, a supernova. Although she was just a few years out of school, her career had already taken off, fueled by a large dose of talent and a dollop of good luck. She had a position in the White House in the early, heady days of the Carter administration. Wonder Woman.
Exactly when the wheels went off the tracks was uncertain, but it was probably no longer than six weeks before we met. It began with changes in behavior that were entirely out of character; she became chatty, seductive, and socially inappropriate. She showed terrible judgment at work. Word soon spread among her colleagues that something was wrong with Andrea. She was seen by a psychiatrist, who suspected a mental disorder, but when counseling failed to reveal a cause and medications didn’t help, her family was advised to hospitalize her. But first, the psychiatrist counseled, just to be sure that this wasn’t a neurologic problem, maybe Andrea should see a neurologist. Her behavior was so completely out of character, and psychiatric disorders usually don’t explode on the scene in this way.
Her frightened parents arranged for Andrea to fly to the Massachusetts General Hospital for a consultation with the renowned neurologist Charles Miller Fisher. Later that day, Fisher told me her story.
“One of the most remarkable cases I’ve ever seen. Quite astonishing. I heard that she’d be arriving from Washington and told my secretary to have her wait in my office until we finished morning rounds. When I walked in, she was stretched out across the top of my desk, reclining on an elbow, smiling, naked, and dangling a cluster of grapes in her hand. I think that she was reenacting a Roman bacchanal. I spoke to her in a stern voice. ‘Please,’ I said, ‘immediately get off my desk and dress. I’ll leave, return in a few minutes, and then let’s start again as if this never happened.’”
An injured brain can sometimes direct the body to act inappropriately. Fisher taught us to recognize such changes as a reflection of underlying neurologic disease. Similar to paralysis or loss of speech, abnormal behavior can also help localize where a disease is in the nervous system. The best approach in these situations, he’d say, was to strongly encourage better behavior and hope that less damaged areas of the brain could replace the lost function.
“When I returned, she seemed quite normal, but lacked any awareness that her behavior was odd or that anything was amiss. I couldn’t find much else wrong on examination. She was completely oriented, with excellent memory and full command of most facts, and her strength, sensation, coordination, and vision were perfectly normal. I thought that she could safely return to Virginia for close observation until we could learn what was wrong. The cause of her problem would reveal itself over time.”
So Andrea was hospitalized in a psychiatric facility in rural Virginia, close to her family’s home. Little progress was made. And then, two weeks later, the sky fell in. The medical team was making its morning rounds. When they greeted her, she responded with slurred, mumbled, incoherent vocalizations. She had lost the ability to speak.
Psychiatric diseases sometimes produce speech disturbances. Patients can seem mute; they will use nonsense words, rhyming words, clicking words, or develop a sing-song cadence, but they don’t slur or mumble. There was now no doubt that Andrea was suffering from a brain disease, and a terrible one at that.
We carried beepers in those days, little square boxes clipped to our belts that would alert us each time we were needed, telling us to locate a phone and receive a message from the bank of switchboard operators on the top floor of the old hospital building. A late beep usually meant little sleep that night, but no matter, for we were residents, still trainees, and immensely proud to be part of the grand tradition of the august Massachusetts General Hospital. We’d never admit to being tired, or hurried, or sick ourselves. Dedication was taught by example, and our highest goal was to someday practice with the skill of the great ones who taught us. But the beep that brought Andrea into my life was different. It arrived at eight o’clock one morning and came from Dr. Fisher, who never paged me at such an early hour.
“Hello, Steve. Dr. Fisher here,” he said. “I need to admit Andrea, the young woman I told you about last month. She seems to have taken a sudden turn for the worse. She’s now on her way from Washington and should be here within the hour. Could you see her as soon as she arrives and let me know what you think?”
“Of course,” I replied.
When the beeper next went off, it was the message that she’d arrived.
I quickly assigned a few remaining tasks to medical students and interns on our service and ran down to the emergency ward. There, in a small corner room separated from the hallway by only the thinnest of translucent curtains, I saw Andrea for the first time. In a baggy hospital gown, head of bed raised 45 degrees, this young woman, whose life had seemed so full of promise just a few weeks ago, was now bedbound, helpless.
As I pulled the curtains aside and entered the room, she tracked my movements, hyperalert, staring silently. A look of bewilderment was etched on her face. I imagined what she was thinking.
What is happening to me? How can this be possible?
A single tear slowly made its way down her cheek.
Her parents stood helpless at her bedside, overwhelmed, her father’s forced smile unable to conceal his agony, her mother gently clasping her hand.
Why her, of all people? Is this somehow our fault?
Nature did not intend it to be this way. Daughter should be tending to parent, not the other way around. They stared at me with a surprised and quizzical look, as if they were wondering about me.
This doctor is no older than our daughter! We flew here, leased a plane, to see Dr. C. Miller Fisher, the great Harvard neurologist, and instead this young resident is taking care of our Andrea. Maybe we should call the head of the hospital. Well, at least he looks professional. Clean white coat, starched button-down shirt, crisply knotted tie, buffed wingtips.
We always looked professional at Massachusetts General Hospital. And what Andrea’s parents didn’t know was that if you were ill, really ill, a young top-of-game resident with fast reflexes, high octane, and lots of recent experience was your best bet … by far.
I began my assessment. The right side of her mouth drooped slightly, and saliva pooled there. Clear signs that the muscles of Andrea’s face were no longer receiving proper instructions from the left side of her brain.
Soon, she’ll be weaker, I thought, but of more urgent concern was the risk that she’d choke on her secretions or aspirate food into her lungs. She’s critically ill and could suddenly worsen at any time.
“Hello,” I began. “My name is Dr. Steve Hauser. I work with Dr. Fisher.”
I reached out to touch her forearm gently, then introduced myself to her folks, shaking hands as we did in those pre-pandemic days. Touching is sometimes the most important thing that a physician can do. A soft touch and a calm voice.
“How are you feeling?”
“Aaar … ga.”
She tried to sit up to greet me but fell back, torso shaking. My first impression was correct; she had a right hemiparesis (weakness) with ataxia (incoordination). This could be caused by damage at only one discrete place, on the left side of the upper brain stem, just behind the nose. The brain stem is a small area of the brain that connects the overlying cerebral hemispheres with nerve pathways traveling out to the body.
“Is it OK,” I asked her, “if your parents stay here with us and I speak with them so that they can help me understand what is happening to you?”
“Ya,” she answered, nodding yes.
She understood language, a positive sign. But then an exaggerated yawn, and a burst of explosive laughter. Pseudobulbar palsy, another mark of something wrong at the stem of the brain. A false or inappropriate emotion was a particularly bad sign that signified extensive damage to the emotional circuitry, disconnecting facial expressions from cognitive intent. The face laughs while the brain cries.
I quickly reviewed the records from the psychiatric hospital. The previous evening’s report noted that she was unchanged, but her parents told me that her speech had been slurred for at least two days and that yesterday she had difficulty walking, falling over unless she had someone to lean on. Not unusual for medical records to be misleading. So, I knew now that this new problem had come on over a couple of days, on top of the behavioral problem that had first brought her to us.
Andrea’s march of symptoms over time wasn’t like that of a sudden stroke or a slowly growing brain tumor. She had no fever, and there was no report of headache, ruling out most brain infections. And the damage was asymmetric, more on the right side of the body, so a toxin or a metabolic problem was unlikely since these cause symmetric disturbances. Inflammation was by far the most likely culprit, I thought, but this still could be an unusual virus.
“May I call you Andrea?”
“Ya.”
Her speech was limited to a few grunts, and she followed commands poorly. She seemed to be choking.
I turned to her parents.
“Has Andrea ever experienced other neurologic problems,” I asked, “either in the distant past or more recently?”
“Yes,” her father replied. “A few months ago, she complained of blurred vision on the right.”
I looked into her right eye with an ophthalmoscope, a special magnifying lens to peer through the pupil and visualize the retina at the back of the eye. It was clearly swollen. She had inflammation of the nerve that carries visual information and connects the back of the eye to the brain. So, she had damage to at least two places in her nervous system, one on the left side of the upper brain stem and a second in the right optic nerve. Multiple lesions.
This was the key to her problem. Two attacks, separated in time and place, meant that she almost certainly had multiple sclerosis (MS).
Just then, she experienced a brief paroxysm of intense coughing and turned blue, her limbs shaking spasmodically. Her life was in danger, and we needed to move fast.
“Andrea,” I said to her, “I think that we should move you to another part of the hospital where we can monitor you more closely, just for a few days. Do you understand what I’m saying? And do you have any questions for me?”
A look of fear, another tear, and a silent shake of her head signifying “no.” I glanced at her parents who nodded their assent.
I enlisted the help of two nurses, and after an advance call to the ICU, we transferred her to a stretcher loaded with resuscitation supplies in case of disaster during the transport and raced to the intensive care unit. Here we could manage her ABCs—airway, breathing, and circulation—and because she was young and otherwise healthy, I was hopeful that, once stabilized, she might improve from this catastrophic attack, which had disabled critical life support centers in the brain stem.
“Can you excuse us for a moment and wait in the visitors’ room?” I asked her parents, who had followed us to the ICU. They didn’t need to see what would happen next.
As soon as they left, I inserted a breathing tube to protect her airway, then a nasogastric tube from her nose to her stomach so she could be fed. There was also an intravenous line for fluids and medications. Several blood tests were needed, mostly to exclude other causes of this catastrophic illness. But by far, the most important diagnostic test would be to examine the cerebrospinal fluid, liquid from the fluid-filled sac that encircles the brain and spinal cord.
For this, I needed to do a spinal tap. I rolled her gently onto her side and, with a nurse’s assistance, bent her legs into a fetal position. Then, explaining each step as I went along, not knowing whether she understood me, I sterilized her lower back, carefully inserted the long spinal needle, measured the pressure of the fluid, and withdrew the clear liquid for study.
I hurried down the hall to examine the fluid with a small microscope located in the residents’ sleeping quarters. No sign of infection, but numerous white blood cells, clear evidence of inflammation. Results from the key test—measurement of specific immune molecules called oligoclonal bands—wouldn’t be available for several days. Oligoclonal bands are abnormal antibodies made by a subset of white blood cells called B lymphocytes, or B cells. Their presence would indicate MS. At the time, we believed that these antibodies were simply markers of the disease and had nothing whatsoever to do with its cause. Overturning this concept would become a central focus of my professional life.
When Andrea’s test came back, it was overwhelmingly positive. Her spinal fluid was packed with antibodies, a tsunami of oligoclonal bands, pouring out of angry B cells that had traveled from her bloodstream to her brain.
MS usually arrives softly, a lamb, not a lion. Nagging numbness in a leg, a touch of blurred vision, or a dizzy spell. Explosions are unusual, but this is what befell Andrea. And for MS to begin with a change in behavior was even rarer. Young people with MS often recover from the first few episodes, but as attacks pile up over months and years, brain damage accumulates, recovery falters, and permanent disability takes hold. At the time, the outlook for most patients was a wheelchair by midlife, and for some, a helpless bedbound state. Andrea’s prognosis was not even that good. She had a ferocious case, the likes of which I’d never seen.
She’d need to recover mostly on her own, healed by her body’s natural capacity for repair, by her brain’s resilience, but she would never regain her former level of function. There was little that we could do for her MS. No treatments existed then except for steroids, and these barely worked.
I returned to her bedside frequently that night, checking on her breathing, sitting by her side for a few minutes each time. ICU policies restricted visitors to short 15-minute stays during daytime hours only, but the nursing staff made an exception for Andrea, rolling in a reclining chair-bed so that one of her parents could be with her, speak to her, touch her shoulder, throughout the night. Sometimes rules are meant to be broken. Each time I checked in on Andrea, I’d also speak with her parents, comfort them as best I could, answer questions, and let them know what to expect in the coming days. Her mom’s quiet sobbing and dad’s look of total devastation remain etched in my memory.
Andrea seemed unable to understand anything that was said by that point, but I always assume that all patients, even those in deep coma, might comprehend more than we think, so what is said at the bedside should always be encouraging and never frightening. Young clinicians must be taught this simple but profoundly important rule, an axiom of the Hippocratic oath to “first of all, do no harm.”
The next morning, I met Dr. Fisher in the intensive care unit, and we stepped away to review my findings and plan the next steps. Andrea’s mom brought me coffee and a donut.
“You’ve been up all night; you must be exhausted and hungry,” she said.
I also met Andrea’s boyfriend, her high school sweetheart who’d just arrived from Virginia, a lanky and clean-cut young man who radiated goodwill and confidence that all would be well. Youth is courageous, but also clueless. Happily, though, his presence buoyed everyone’s spirits.
But love and prayers would be no match for Andrea’s illness. Faced with what would prove to be one of the most aggressive forms of MS, Andrea declined rapidly. Loss of speech and ability to swallow, cough, and breathe was followed by total paralysis on the right side of her body, and then weakness on the left. Simple tasks that we take for granted, like brushing our teeth or holding a book, were now impossible. She couldn’t even sit unless strapped to a chair or bed. Within a few days, it became clear that surgery would be needed to create openings in her throat and stomach for insertion of permanent breathing and feeding tubes.
Copyright © 2023 by Stephen L. Hauser
