As for Emily, she is now a happy and healthy six-year-old. She is much more certain than the usual child her age when asked what she wants to be when she grows up—a doctor. “She plays with her doctor kit,” says Peter, “and tells me I can be her nurse and work for her when she’s the doctor.”
And one other thing, she never drinks apple cider.
part two
The External Environment
6 Two Ticks from Jersey
“When I first saw her, she was nontoxic looking, did not have a fever and was very interactive, but she couldn’t speak properly; the words were slurred,” recalls Dr. Fred Henretig, a pediatric emergency physician and toxicologist at Children’s Hospital of Philadelphia (CHOP). His patient was Annie (as I’ll call her), a five-year-old girl who had been transferred to the emergency department at CHOP for evaluation of a baffling and frightening constellation of symptoms. Little Annie had been a perfectly normal and healthy child until the day before her visit with Dr. Henretig in May 2003.
After day care that day, Annie began to squint because, she said, she couldn’t see right. That evening, the brown-haired girl began to complain to her parents that she was seeing double and could see well only with one eye closed. She looked fine, however, and there were no obvious problems, so off to bed she went. But at 4 AM she woke up, crying that she couldn’t see anything because she was seeing two of everything, and she was clenching her hands repeatedly. Her mother, a veterinarian, noticed that Annie’s speech was slurred and she couldn’t sit up or walk. Naturally, her mother was alarmed and rushed her daughter off to the emergency department at their local hospital.
The emergency physician working that shift at the hospital in Burlington County in southern New Jersey was equally alarmed. He was confronted with a little girl who had a highly abnormal neurological examination. His little patient was weak, could not speak properly, and had double vision. Her eyes could not move in tandem. In addition, she was ataxic, meaning she could not walk properly. This combination of symptoms—double vision and abnormal gait—suggests a problem with the back, or posterior, portion of the brain and demands a rapid and thorough evaluation.
Unlike chameleons, whose two eyes can move independently, humans are endowed with eyes that track objects only as a paired unit. Although there may be times when a human wishes for a lizard-like view of the environment, in fact the hard wiring in the brain that lets our eyes move together is dazzling. Three separate nerves control eye movements on each side. The nuclei that control each of these nerves lie in different parts of the brain; consequently, another set of electrical cables attach the three nuclei together. So the three nerves, three of the twelve cranial nerves, act in tight unison, yoked together. These cranial nerves (numbers three, four, and six of the twelve) in turn travel from the brain to the sets of ocular muscles that surround the eyes and control the direction that they move.
No matter how fast we move our heads, or how fast an object darts across our visual field, we see only one of it. We take this for granted. But when considering what is happening in the brain, the cranial nerves, and the ocular muscles, it is really quite remarkable. When we track an object moving from right to left, various electrical impulses race to the control centers and tell the eyes what to do. The left eye has to start out looking laterally while the right eye starts out looking medially, and then both eyes track toward the right as the object moves. One cranial nerve nucleus controls the lateral movement of the left eye, and a different one controls the medial movement of the right eye. As the object crosses the midline (our nose), this sequence reverses. If there is a vertical component to the movement, other nerves are involved.
Were it not for this yoking system, a catcher could not catch a pitched ball and each pass in basketball would be an accident waiting to happen. When this system collapses, we see two of everything.
Double vision—or diplopia, as the doctors call it—is a very disconcerting symptom to patients; it’s not the way we’re used to seeing the world and it is frightening when it happens. For doctors too, this symptom is a worrisome one, because the list of conditions that cause diplopia is relatively short, and for the most part consists of serious medical conditions.
A problem anywhere along the neurological pathway can result in double vision. A stroke or a multiple sclerosis plaque placed near the nucleus of the command centers can lead to double vision. Any problem that hits the nerve along its course to the ocular muscles can have the same effect. Potential problems include tumors, an aneurysm in the arteries around the brain that physically compress the nerve, and inflammation of the nerves. Because each one of these is such a serious problem, double vision is a symptom that demands a rapid and thorough evaluation.
So the physician at the local hospital initiated a workup that included a wide array of blood and urine tests. The basic blood work—red and white blood cell counts, routine chemistries like blood sugar and sodium—all came back normal. As one might predict from the list of potential causes of double vision, these basic tests did not result in any diagnosis.
So the emergency physician next ordered sophisticated brain scans, including an MRI (magnetic resonance imaging) and an MRA (magnetic resonance angiography). When the radiologist looked at the MRI, he thought there was diminished flow to one of the arteries at the back of the brain. Translation: Annie might be having a stroke, an odd problem for a five-year-old.
Stroke is a common problem in adults; in fact, it is the third leading cause of death and the leading cause of disability. But it’s distinctly uncommon in children. So the emergency physician did what any prudent doctor would do; he transferred his patient to a tertiary care facility, in this case CHOP, where world-class experts in pediatric neurology could lend their expertise to the case.
And this is where our story opened, sometime in the late afternoon as Annie was ushered into the emergency department at CHOP with an armful of diagnostic studies and a diagnosis of “presumed stroke.” Dr. Henretig’s observation that his little patient looked well is an important one. How sick or well a patient looks to a doctor often dictates the pace that an evaluation will take place, whether that patient is admitted or discharged, and whether medications are started or not, and if they are, whether it is by mouth or intravenously. But although first impressions are important, Dr. Henretig was well aware that despite the fact that she looked well, Annie’s neurological condition was precarious, and determining the cause for her symptoms was the first step toward fixing it. So he was reassured by her overall appearance, but Dr. Henretig took careful stock of the puzzling array of signs and symptoms that he was confronted with.
As is common in emergency medicine, Dr. Henretig started pursuing multiple tasks simultaneously. He wanted his own radiology staff to review the films done at the outside hospital. And he ordered a consultation with neurologists to get their input. But while arranging for these things to be accomplished, he carefully examined Annie.
Her vital signs were essentially normal, with the exception of a slightly rapid pulse rate. But there was no fever, no problems with her ability to breathe and get oxygen into her blood. Her blood pressure was normal. The specialist pediatric neuroradiologists reviewed the MR scans from the original hospital and thought that they were normal. The diagnosis of stroke became much less likely.
But there were obvious and disturbing abnormalities in her neurological function. Her eye movements (the sixth cranial nerve in this particular case) were clearly abnormal; neither eye could look outward from the midline. This finding accounted for her double vision. And Annie’s face was twisted to one side due to facial paralysis. This is known commonly as a Bell’s, or facial nerve, palsy, an indication that her seventh cranial nerve was also not working properly. The difficulty in walking that the doctor in the first emergency department had noticed was because she was so profoundly weak. Not only could she not walk properly, she could barely sit up by herself. Dr. Henretig’s leading diagnosis was Guillain-Barré syndrome.<
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Guillain-Barré syndrome is a condition whereby the peripheral nerve roots, as they exit from the spinal cord, cease to function normally. It is an unusual problem; the nerve roots are thought to become inflamed following some other trouble in the body, such as a trivial upper respiratory infection, a bout of gastroenteritis, or sometimes an immunization.
Guillain-Barré syndrome was first reported in 1859 by a French physician, Jean-Baptiste-Octave Landry de Thézillat. He reported ten cases, half of whom he personally attended. Of those five, two died from respiratory failure. One of the fatal cases was a thirty-four-year-old paver who, on June 1, 1859, walked into the hospital complaining of some weakness and funny sensations in his feet. By the third week his limbs were paralyzed, and he developed difficulty breathing, chewing, and swallowing. Shortly thereafter, he died. The disease became known as ascending paralysis of Landry, and his original description remains accurate to this day.
He wrote: “The main problem is usually a motor disorder characterized by a gradual diminution of muscular strength and flaccid limbs and without contractures, convulsions or reflex movements of any kind. In almost all cases, micturition and defecation remain normal. One does not observe any symptoms referable to the central nervous system. . . . The intellectual faculties are preserved until the end. The onset of paralysis can be preceded by a general feeling of weakness, pins and needles, and even slight cramps. . . . The weakness spreads rapidly from the lower to the upper parts of the body with a universal tendency to become generalized. . . . When the paralysis reaches its maximum intensity the danger of asphyxia is always imminent. However in eight out of ten cases, death was avoided, either by skillful professional intervention or a spontaneous remission of this phase of the illness.”
Decades later, in 1916, three other French physicians (George Guillain, Jean-Alexandre Barré, and André Strohl) described two more cases of what seemed to be the same problem. Guillain and Barré were medical students together who ended up as military doctors. They described two soldiers who became paralyzed for no apparent reason. The patients’ symptoms were similar to those described by Landry—muscle weakness, loss of reflexes, and a gradual progression from the lower extremities to the upper—but both of them recovered. When the doctors did a spinal tap (which had not yet been developed when Landry was practicing), they found an elevated protein level but no white blood cells in the spinal fluid. The absence of cells was important, since two conditions that were common at the time and that could cause similar symptoms, tuberculosis and syphilis, were associated with cells in the spinal fluid.
Over the following years, they described additional cases. Although some coined the moniker Landry-Guillain-Barré syndrome, Guillain was angered by the addition of Landry’s name and argued that Landry’s cases were not really the same condition, in part because their spinal fluid was not tested and in part because some of Landry’s patients died. Over time, Landry’s name was dropped. And somehow the name of Strohl, who never really got much billing, suffered the same fate. So today, doctors commonly refer to this form of ascending paralysis as Guillain-Barré syndrome.
The syndrome often follows an acute infection, often of the gastrointestinal or upper respiratory tract, and sometimes it follows a vaccination. In the 1970s, Guillain-Barré flashed into the headlines after an excess in cases was found in the wake of the swine-flu immunization campaign. Patients experience weakness, usually starting with the lower extremities and then ascending to the arms and to the respiratory muscles, including the diaphragm. When the diaphragm stops working, the patient can no longer breathe, and without prompt intervention will die.
Before the advent of modern intensive care units, approximately 20 – 30 percent of patients with Guillain-Barré died. In a ten-year review of cases from Ethiopia published in 2005, investigators found a mortality rate of 26 percent, a dismal statistic that they ascribed to poor access to intensive care in that country. In developed countries, the mortality rate is closer to 2– 4 percent, because with modern ICU-level supportive care, patients can be kept alive on a breathing machine until the nerve damage improves. Today, treatment of Guillain-Barré is by plasma exchange or intravenous immunoglobulin. Neither is a benign therapy. Before treatment can be initiated, however, the correct diagnosis must be established. Other diseases can mimic Guillain-Barré syndrome, and these other problems have completely different treatments.
Weakness, for example, could be from a tumor, blood clot, or abscess that is compressing the spinal cord. The treatments for these problems might involve surgery to remove a clot or tumor, or powerful antibiotics to treat an infection. Other times, the spinal cord itself might be inflamed. This could be from diseases as diverse as multiple sclerosis, Lyme disease, or even schistosomiasis, caused by a parasite from the Nile that can affect the spine.
But five-year-old Annie had not been to any such exotic locations. So Dr. Henretig’s leading diagnosis was a type of Guillain-Barré syndrome called the Miller-Fisher variant, named for a Canadian neurologist, Charles Miller Fisher, who first described it in 1956. In this syndrome, there is prominent involvement with the cranial nerves. The diagnostic test that Dr. Henretig wanted to perform was a spinal tap, or lumbar puncture. In this procedure, after cleaning the skin of the back with a potent antiseptic solution and numbing the area with a local anesthetic, the physician places a needle into the space between two adjacent bones of the spine. The needle pierces the outer covering of the spinal cord to the area where the spinal fluid lies. The exact location of the needle is a couple of inches lower than the bottom end of the actual spinal cord. Through the needle, he draws out a small quantity of cerebrospinal fluid, which acts as a shock absorber and nutrient source for the brain and spinal cord. This fluid is normally crystal clear and looks like water. The pressure is measured, and the fluid is sent to the hospital laboratory to be tested for protein levels and cell counts. The microbiology lab will determine if there is an infection. The major clue to the diagnosis of Guillain-Barré syndrome is the dual findings of elevated protein level with a normal cell count, as described back in 1916.
To do this procedure in children, physicians will sometimes administer a combination of medications through an intravenous line, to ease the pain and allay the anxiety and fear that a patient will feel when having a spinal tap. This is called intravenous procedural sedation. Dr. Henretig’s associate Dr. Jill Posner and her staff sedated Annie and performed the spinal tap. As it usually does, the procedure went smoothly, and the fluid was sent off to the lab.
One of the other pediatric emergency specialists who was taking care of Annie was Dr. Reza Daugherty. He remembers: “We talked to the neurologists. They came down in a team with like six people: the attending, the fellow, a resident, and some medical students. Annie was areflexic at that point. Because she had lost her reflexes, and given the clinical scenario, we all thought that the Miller-Fisher variant of GuillainBarré was the most likely diagnosis.” Annie was starting to have respiratory problems by this point. The doctors tested her lung function by measuring what is called a negative inspiratory force, to see how well the respiratory muscles are working. Annie’s showed some signs of deterioration.
“She was going to go to pediatric ICU to get plasmapheresis,” recalls Daugherty, “and she was likely going to need to be put on a ventilator. The mother started getting nervous when they talked about the large lines necessary for the plasmapheresis.” The treatment of plasmapheresis involves placing a large intravenous line into a central vein of the body. There are potential complications, both from inserting the large line and from the treatment itself. Plasmapheresis is in some ways similar to hemodialysis, used for patients with kidney failure. Several treatments are done over a week or ten days, during which large volumes of blood plasma are drawn off into a machine, where various proteins and antibodies are removed before the plasma is returned to the patient. The precise mechanism of how this treatment works is unknown, but it clearly improves the outcomes for m
any patients.
The results of Annie’s spinal fluid analysis returned: there were no cells, but the protein level was also normal. However, the normal findings did not definitively exclude a diagnosis of Guillain-Barré; in fact, many times early in the progression, the spinal fluid is normal, and Annie had been sick for less than twenty-four hours.
Dr. Posner recalls: “Even with the procedural sedation, she was very fretful and unhappy during the spinal tap. Afterward, she was rolled up in her mom’s lap. And her mother started to caress her hair to comfort her. At some point, the mother thought she felt something abnormal just behind one ear, and parted her hair.” The “something,” Annie’s mother quickly realized, was a fully engorged tick. She called to the nurse and doctor. Since the mother was a veterinarian, she removed the tick.
The significance of the tick cannot be overstated, and it threw a curve ball into the whole analysis. Lyme disease is an extremely common affliction in southern New Jersey. And Lyme disease can sometimes cause transverse myelitis—an inflammation of the spinal cord that can be confused with Guillain-Barré syndrome. Lyme disease can also cause the cranial nerve problems that Annie had. And the time of year was also right. Late spring and early summer are the peak season for Lyme disease. However, neurological symptoms from Lyme disease follow the tick bite by weeks to months, and are never found while the tick is still attached. Finally, this tick wasn’t right for that. Lyme disease is caused by bacteria spread by the bite of an infected Ixodes tick, usually referred to as the deer tick. These ticks are very small, even when fully engorged. The tick that was removed from Annie’s scalp was not a deer tick; it was a Dermacentor, or common dog tick—not the kind that causes Lyme at all.
The Deadly Dinner Party: and Other Medical Detective Stories Page 10
