“I turned to the parents and started asking questions. Mr. Matthews said that, other than some ear infections as a toddler, Shawn had always been in excellent health and seemed entirely well until shortly after breakfast, when he began complaining of a headache behind his left eye and blurred vision. When he told his parents, they noticed the dilated pupil and promptly brought him to the emergency room. There was no history of eye injury or trauma, medications, use of eye drops, or any past or family history of eye problems. He had no fever, stiff neck, and so on.”
Next, Setnik questioned Shawn directly. The boy told him that the headache was constant and dull, and located directly behind the abnormal eye. Shawn had no problem speaking, chewing, swallowing, or walking, and no difficulty with balance. He had been playing in his room when the headache began, but nothing unusual had occurred.
Before examining Shawn, Setnik began to consider what lay ahead. “I wondered if he was going to need other, sophisticated tests and the expertise of a pediatric neurosurgeon. The mind of an emergency physician is always moving two or three steps ahead, time being of the essence. One thing that distinguishes emergency medicine from many other specialties is that time is such a major component in the management of the patient. I was already thinking, will I need to transfer this boy to a hospital with a pediatric neurosurgeon? Would he require an ambulance or would I let the parents drive him in the family car? Initially, I had two possible concerns. The first possible cause of Shawn’s symptoms was eye trauma, but there was no history of that. The other possibility that came to mind, and the one that I was most concerned about, was could this be an aneurysm of a cerebral artery.”
The eye is one of the body’s great marvels, and the iris is a wonder in itself. The pupil of the eye is the dark central area that is surrounded by the colored part, the iris. The iris is actually the business portion of the apparatus that continually adjusts the size of the pupil, which is essentially just a hole in the iris. Although we usually take this mechanism for granted, imagine stepping out of a darkened movie theater into bright sunshine. The importance of the iris’s never-ending task becomes instantly apparent. In the dim light of the theater, dilator muscles in the iris contract, dilating the pupil and allowing more light to strike the retina, so that we can see better in the darkness. This mechanism operates on the same principle as the aperture setting of a camera. As you walk out of the darkened theater, the sunlight floods the retina with too much light for your dilated pupils. You automatically squint and raise your hand to shade your eyes. But within seconds, the sphincter muscles of the iris constrict, making the pupil smaller and allowing less light into the eye.
The pupil continually adjusts and readjusts, depending on both the brightness and the distance of the object that you’re looking at. Generally, both pupils are the same size, but in up to 25 percent of normal individuals, small differences in pupillary size may occur intermittently and occasionally even switch sides from one to the other.
The nervous system, just as it does for all the muscles in the body, controls the iris. And, as with all of the body’s involuntary muscles, those responsible for bodily functions that we do not consciously think about (like the heart or intestine or diaphragm), it is the autonomic nervous system that regulates the size of the pupils. The autonomic nervous system consists of two parts—the sympathetic and the parasympathetic components. These are like the yin and yang of the body. The sympathetic system gears the body for action—accelerated heartbeat, increased rate of breathing, diminished intestinal activity and salivary secretions—known as the fight-or-flight response. The parasympathetic system does the opposite. It increases salivary secretions, augments intestinal activity, and slows the heart and respiratory rates. As for pupil size, the sympathetic nervous system dilates and the parasympathetic constricts. Like yin and yang, these two components of the autonomic nervous system are continually establishing balance with each other and setting the right tone for any given situation.
There are other differences in the way that the sympathetics and parasympathetics affect the eye; one of those differences is the route taken by the nerve fibers to get to the eye. The sympathetic fibers originate in the thoracic portion of the spinal cord, regroup in a ganglion in the neck, and then hitch a ride along blood vessels to find their way to the iris. The parasympathetic fibers come from deep in the midbrain, a primitive part of the brainstem, then exit the brain as part of the third cranial nerve. This nerve, which includes other fibers that control eye movements, courses along the floor of the skull to find its way to the orbit. As it exits the brain, it enters what is known as the subarachnoid space, the area where the cerebrospinal fluid resides. This clear fluid supplies nutrients to the brain and spinal cord and acts as a shock absorber as well. As the third cranial nerve traverses this fluid-filled space, it is vulnerable to compression by other structures in the region. One of those structures is the posterior communicating artery, a blood vessel that links up the arterial supply in the front of the brain with that of the back (posterior) part. If something were to press on the nerve in this location, then the yin and yang would be thrown out of balance. In this case, the mass could push on the parasympathetic fibers, and diminish their function. The sympathetics, because of their different path to the eye, would remain active and unopposed, resulting in a dilated pupil.
With knowledge of this anatomy in mind, and noting normal findings on Shawn’s throat, neck, heart, lung, and abdominal examination, Setnik turned his attention to the boy’s nervous system. He checked Shawn’s sensation, strength, balance, and reflexes. He listened over his skull for bruits (French for noises)—whooshing sounds caused by a tangle of abnormal cerebral blood vessels. He inspected the retina with an ophthalmoscope, looking for signs of brain swelling or bleeding. He checked Shawn’s neck for stiffness, an indicator of inflammation in the subarachnoid space.
“I very carefully checked the movements of his eyes, because the same nerve that controls the pupils also controls some eye motions. His eyes moved completely normally,” recalls Setnik. “I checked all of the twelve cranial nerves and I did a detailed pupil exam. When you shine a light in one pupil, both of them will constrict; that’s called the consensual reaction. The dilated pupil did not react. The pupil will also constrict when a person switches from looking at an object in the distance to looking at a near object; that’s called the accommodation reflex. His dilated pupil did not constrict to near objects either.” But except for the dilated pupil, Shawn seemed to be perfectly healthy.
It didn’t add up.
“At the end of that examination, I sat back and I remember putting my fingers to my bearded chin and just thinking. I was struck by how well he looked. It was just my gut feeling that he wasn’t sick. You develop this instinct as an emergency physician; it’s not very scientific but you get pretty good at it. There are times when you don’t act reflexively but you just sit down and give yourself space to think. I was confronted now by a most unusual situation. It was becoming less conceivable to me that the likeliest diagnosis—bleeding or pressure on a nerve—was really the problem. Bottom line is that Shawn just didn’t look sick to me. Also, his eye movements were normal, and I thought that it would be unusual for the pupil to be dilated from a nerve lesion without any effect on the muscles that move the eyes.”
Setnik knew all too well that a relatively common mass that can compress the third cranial nerve is an aneurysm of the posterior communicating artery. Aneurysms are outpouchings in a weak spot of an artery. Like a weak spot in a tire that balloons out from the pressure of the air within, aneurysms can balloon out from an artery under the pressure of blood. They can occur in any artery of the body. Aneurysms in and around the brain are surprisingly common; they occur in up to 2 percent of people. In most cases, they never cause symptoms and are never detected. But for reasons that are not completely understood, in some patients they begin to grow. Sometimes, when they grow large enough, they will rupture. When they do, patients usuall
y have an excruciating pain, the worst headache of their life. Because these aneurysms are almost always in the subarachnoid space, this bleeding is known as a subarachnoid hemorrhage. It is usually diagnosed with a CT scan or by a lumbar puncture, or spinal tap.
After experiencing a subarachnoid hemorrhage, patients must be treated very quickly. In the late 1980s, when this case occurred, the primary treatment was open brain surgery. The first step would be to carry out an angiogram to identify an aneurysm and then rapidly perform a procedure to isolate it from the circulation and protect the patient from further bleeding. At the time Setnik saw Shawn Matthews, the angiogram itself had some risk. A doctor would insert a catheter into the femoral artery in the groin and snake it up the aorta and into the major arteries of the brain. The patient would be injected with a small amount of dye, and then x-rays would be taken. The dye would show the outlines of the arteries in the brain, and if there was an aneurysm, it would appear in the x-ray. Once the aneurysm was defined, a specially trained neurosurgeon would drill holes into the skull and remove a flap of bone to expose the brain. The surgeon would carefully retract portions of the brain to expose the major blood vessel that includes the aneurysm. The surgeon would place a metal clamp across the base of the aneurysm, thus excluding it from the rest of the circulation and preventing any subsequent rupture.
Nowadays, there are much less invasive aneurysm treatments called endovascular therapy. A physician with special training will place a platinum coil inside the aneurysm via a catheter similar to the one used for the angiogram. The coils induce the blood in the aneurysm to clot, which functionally excludes the aneurysm from the circulation the same as surgery.
Aneurysms don’t always present with a subarachnoid hemorrhage, however. Sometimes they expand but do not rupture. If the aneurysm happens to be on the posterior communicating artery, it often presses on the third cranial nerve. When it does, the pupil dilates and there is often a mild headache. If Setnik’s worst fears were true, Shawn might need to be transported to a specialized pediatric neurosurgical center for an angiogram and brain surgery.
“At that point, I recalled another patient I had seen about five years previously. He was a Harvard grad student who had been working in a chemistry lab and came in with a dilated pupil too. The chemical he was working with was atropine, which is a potent stimulus for pupillary dilation. That man had accidentally gotten some on his finger, then causally rubbed his eye. Somehow, the two cases linked up in my mind.”
Atropine has a long and checkered past. It is an alkaloid, extracted from an herb native to Europe and Asia that produces sweet black berries. Botanists call it Atropa belladonna; its common name is deadly nightshade or devil’s cherries. The plant is widely distributed and can be found across large parts of central and southern Europe, southwestern Asia, Algeria, and North America. A bushy plant that grows several feet high, it prefers the shade beneath large trees. The leaves are a dull dark green of various sizes between three and ten inches in length. The dull purple flowers appear in June and July, and bloom through September, at which time they form a black berry about the size of a small cherry. These berries contain a dark, inky juice that is seductively sweet.
The herb belongs to the Solanacea family, a very large group of plants that contains some members that are quite edible and others that are incredibly toxic to humans. Such important staples of the human food supply as tomatoes, eggplants, chili and Tabasco peppers, and potatoes belong to the Solanacea family. So does the petunia. And so does the tobacco plant, from which the alkaloid nicotine is derived. Nicotine has many effects on humans—some toxic, others physiologic.
As entrenched in the human food chain as the potato is now, it was not always so. The potato probably originated in the Chilean Andes thirteen thousand years ago and was not cultivated in the area until five thousand years later. When the Spanish encountered the potato in the late sixteenth century, they did not welcome it at all. One reason was that the potato was a plant without standard growing seasons that the Europeans were accustomed to. The other reason was that Europeans thought the potato plant too closely resembled other plants that Western society had feared for millennia.
Consider the henbane plant. This herb is indigenous to many parts of Europe and Asia and has been imported to the New World. Its leaves, which are of medicinal value, have been harvested for over two thousand years. Its two major alkaloids, hyoscyamine and scopolamine, have important pharmacologic effects on humans. Henbane will commonly induce hallucinations, dilated pupils, restlessness, and flushed skin. The Egyptian queen Cleopatra is rumored to have used an extract of the plant to kill her enemies, although when she decided to end her own life she settled on a bite from an asp. She also recognized that a much more dilute solution, when placed in the eyes, would dilate her pupils to make her more alluring. Henbane’s effects were also known to the ancient Greeks and Romans. The priestess of Apollo allegedly used it to help increase the accuracy of her pronouncements. In the Middle Ages, criminals used an extract of henbane as a poison. It was also used in traditional German pilsner beers until 1516, when the Bavarian Purity Law abolished its use in favor of a brew made from pure hops.
Another poisonous plant from the Solanacea group is the datura. This foul-smelling plant originated in India but has spread all over the world. Some believe that it first reached North America at Jamestown, Virginia, because records suggest that sailors in the original settlement were poisoned by it. After eating it like spinach, they nearly died. This led to the name Jamestown weed, which at some point became contracted to simply jimsonweed. During the Middle Ages, Italian professional killers devised a brew from the datura plant that not only would kill those who drank it, but had the advantage (to the criminal) of dulling the victims’ senses before they died. Extracts from this plant have a decided psychogenic effect. Hindu prostitutes in the sixteenth century used it to dope their clients, and white slavers were reputed to use it as an aphrodisiac.
The major plant in this group, and the one with the most significance for humans, is the deadly nightshade, Atropa belladonna, a plant with a double-edged history as both a poison and a medication. The genus name, Atropa, derives from Atropos, the oldest of the three fates, and the one that was responsible for snipping the thread of life. So, as the name implies, atropine is deadly. Eating a single berry can be fatal.
The plant has influenced several military campaigns. Belladonna was allegedly the poison that weakened Marc Antony’s troops during the Parthian Wars. According to Plutarch, “Those who sought for herbs obtained few that they had been accustomed to eat, and in tasting unknown herbs, they found one that brought on madness and death. He that had eaten of it immediately lost all memory and knowledge, but at the same time would busy himself in turning and moving every stone he met with, as if he was upon some very important pursuit. The camp was full of unhappy men, bending to the ground and thus digging up and removing stones, till at last they were carried off by a bilious vomiting, when wine, the only remedy, was not to be found.”
The Scottish army under Macbeth used belladonna to poison the Danish troops during a “truce.” The Scots supplied the Danes with liquor that had been infused with a root that was likely belladonna. This escapade finds its way into Shakespeare’s Macbeth, when Banquo says, “Or have we eaten of the insane root that takes the reason prisoner?”
It’s more than a poison, though. Women in Renaissance Italy learned what Cleopatra had known about henbane. If they applied a very dilute drop of the plant’s juice to their eyes, it would make the pupils dilate, thus enhancing the user’s beauty. Hence, the species name—belladonna, Italian for “beautiful lady.”
The berries appear similar enough to those of edible species that people sometimes eat them by mistake. The Lancet in 1846 chronicled the case of an herbalist who was hawking his wares in the Whitechapel Road area. A woman bought a pint of so-called nettleberries for three pence and made a pie. The journal reported: “Her husband ate more heartil
y of the pie than she did. Before the remains of the dinner were removed, a customer came in to pay some money, and was accompanied by a child, named Samuel Jones. The little boy looked very anxiously at the tart, and she gave him some, little thinking at that time that the berries were poisonous. A few minutes after her husband had finished his dinner, he said he was very drowsy, and went into the bar-parlour. His lethargy soon increased, his countenance changed colour, and the pupils of his eyes became dilated. He said he had a very strange coppery taste in his mouth, and that he would go up stairs and lie down upon the bed. As he went up stairs he staggered, and upon entering his bedroom fell upon the floor, and became insensible.” By the next morning, both the man and the little boy were dead, and several others who had eaten the berries had fallen seriously ill.
There were also medical uses for belladonna. As of 1803, it was still used to treat febrile illnesses such as plague, apoplexy, whooping cough, rabies, depression, and mania. Nineteenth-century practitioners were aware of the toxic properties and recommended gradually increasing the dose from day to day, until the patient developed “tension in the throat,” a sign of toxicity.
In the mid-nineteenth century, medicinal chemistry was becoming a well-developed science, and chemists from France, Germany, and Britain were all busy in their labs trying to uncover the secrets of the human nervous system and the various plants that had been used for centuries. In 1831, a German apothecary was the first to isolate atropine from the roots of the belladonna plant. These discoveries helped physiologists unravel the components of the autonomic nervous system.
Atropine, sometimes marketed as belladonna on the label, was used for neuralgia, back pain and joint complaints, tuberculosis, and a variety of other conditions. It was incorporated into bandages to help heal skin lesions. So even though the science was evolving, the use of atropine was anything but scientific. In part because of this, atropine poisoning was a regular occurrence as the nineteenth century became the twentieth.
The Deadly Dinner Party: and Other Medical Detective Stories Page 15