The Doric Column
November 24, 1998
It was a decade ago now. My life-long friend, an outstanding family physician who had delivered hundreds of babies, studied the framed photograph hanging on the wall of my home office.
He knew of my interest in his profession, especially medical research. He also knew that my job was closely connected to pathology and that I had witnessed a kidney transplant by pioneering surgeon John Najarian and had written about it.
So maybe I was being unfair by asking him to tell me what he saw.
He continued to study the photograph as if he were back in a pathology lab at the University Medical School: a globular mass of flesh captured as it was being removed from another mass of flesh by hands in surgical gloves, with instruments glistening against the pale-blue backdrop. All in a soft, dream-like focus.
By and by he rendered his verdict. "It looks like an ovarian cyst," he said.
My spine stiffened. "An ovarian cyst!" I exclaimed. "That's my son, you idiot!"
I didn't really say that to my dear friend. But it hurts when one's magnificent offspring is mistaken for a cyst.
It was Robbie in the picture, or about half of his 9 pounds 6 ounces, the top half, bursting forth from his mom's retracted tummy, using her as a launching pad.
Some anxious minutes later (his mother's epidural block had worn off and she needed more anesthesia fast) I got to hold him while a nurse took his footprints. His eyes were open and I looked into them. They were the eyes of a dreamer.
Later I found a biblical passage I liked, pulled it out of context, and put it on the back of the photograph: "Behold, this dreamer cometh." Genesis 37:19.
The first time was a surprise, yet it wasn't.
It all began a couple of years ago. Robbie was 10 years old. One morning at breakfast his mother noticed that his jaw was twitching. She was going to call the doctor, but waited, and after 20 minutes it passed.
A couple months later I saw the twitching myself. Again at breakfast. Uncontrollable spasms, actually more of a rhythmic quaking of his jaw. He seemed confused when I asked him about it. "My jaw is shaky," he said. I could tell he was not quite there. He had trouble finishing his cereal. Something was wrong.
I sent him upstairs for a shower, expecting ... hoping that a shower would relax him and somehow end the inexplicable. I heard the shower start up and went about my work.
The scream, when it came, was a familiar one. I had heard it before when I would sneak up and pour cold water on his feet under the shower curtain. But I was downstairs.
The scream was followed by a thud. A bathtub emits a characteristic sound when someone falls in one, a deep, hollow reverberating sound.
As I raced up the stairs I knew what was happening, even though I had not consciously considered it, perhaps out of fear. I didn't want to know.
Robbie was in full seizure, on his back, the shower streaming into his face. I didn't recognize his face.
Turning him on his side, I reached up with my left hand and turned off the shower. Then I gently held him just as he was, rigid as a board, jerking and hissing, rolling his eyes, emitting gutteral sounds from the depth of his soul, finishing his dream.
The word epilepsy comes from the Greek "epilepsia," meaning "to take hold of" or "to seize."
Hippocrates wrote a famous treatise on epilepsy, "On the Sacred Disease". Yet he believed that the disorder had nothing to do with the world of the spirit and everything to do with the brain. Nearly two millennia passed before that view began to be accepted, in the 19th century.
History is punctuated with famous people who had epilepsy. Julius Caesar had it. So did Peter the Great and Lord Byron and Fydor Dostoevsky. Dostoevsky's description of the seizure of Prince Myshkin in his novel The Idiot is perhaps the most famous account in literature:
Then suddenly some gulf seemed to open before
A "blinding inner light" brought about not by evil spirits but by clusters of brain neurons short-circuiting: bursts of electrochemical energy, an electrical storm beginning in the brain and transmitted instantly via the spinal cord to every neural fiber in the body.
But a storm preceded, it appears, by neurons acting dangerously in concert, as musicians in a symphony orchestra, a pattern that shows up minutes before a seizure. A biological paradox: synchrony begets chaos. The calm before the storm.
Robbie's seizure was the kind most people are familiar with. It used to be called grand mal but today is called tonic clonic: "tonic" is the initial phase when individuals lose consciousness, "clonic" is the phase when they begin to shake rhythmically, turn blue in the face and dribble from their mouths.
Tonic clonic seizures affect about 2 out of every 10,000 people. Some of the causes include congenital defects, metabolic disorders like diabetes, brain injury, tumors, and infections. But many have "idiopathic" causes. That is, no one knows.
Sometimes they are preceded by less severe seizures. When Robbie experienced a quaking jaw and appeared dazed and confused after waking, he was having complex partial seizures. These seizures affect only one part of the brain and usually last for only a few minutes.
Robbie's seizures are associated with the transition from a sleeping to a waking state. According to one theory, people who have this experience have difficulty moving out of the deepest phase of sleep, the rapid eye movement or REM phase. The dream phase.
Robbie, the dreamer.
Sometimes a genetic factor is involved. One of Robbie's uncles had a long bout with seizures during his adolescence and early adulthood. Typically he would have them in the morning, upon waking.
The room where Robbie had his first EEG (electroencephalogram) was set up to induce sleep. The best results are obtained when patients are in the sleeping state, their heads fully wired with multicolor electrodes. Robbie's results showed spikes of seizure activity in his left forebrain.
But a battery of additional tests, including an MRI scan of his brain, showed nothing unusual. The neurologist wanted to take a conservative wait-and-see approach. No medications for now. That was all right with us.
Treatment for epilepsy can demonstrate why medicine is as much an art as a science.
Some months passed. Then one morning, shortly after waking, his jaw began to quake. Off to the emergency room at Children's Hospital in Minneapolis, where he experienced his second tonic clonic seizure, right there on the bed, surrounded by health care professionals.
Dilantin (phenytoin), a drug used for seizures since the 1930s, was prescribed as the first line of defense. It worked well, with few side effects. Later on Tegretol (carbamazeprine) was added. Robbie began to show increased seizure activity, waking up with partial seizures time and time again.
After a series of trips to the emergency room over the course of a couple months, Depakote (valproic acid) was added to the regimen. And the neurologist gave us a prescription for Diastat, a formulation of diazepam, the active ingredient of Valium.
Diastat is a rectal gel developed by University of Minnesota researchers for at-home treatment of people experiencing a pattern of acute seizures. It can eliminate trips to the emergency room.
Jim Cloyd, a professor of pharmacy and head of the Epilepsy Center in the College of Pharmacy, and Robert Kriel, a pediatric neurologist at Hennepin County Medical Center, developed the treatment 10 years ago in partnership with Upsher-Smith Laboratories in Minneapolis.
Cloyd and his colleagues concluded in a study published last June in the New England Journal of Medicine that rectal diazepam gel, administered at home, "is an effective and well-tolerated treatment for acute repetitive seizures."
The paper appeared about the same time we received the prescription from Robbie's neurologist. Today, six months later, our insurance company has yet to authorize the prescription.
We haven't pushed it because Robbie began to improve dramatically as he was weaned from one drug, then another. At least one of the drugs seemed to make things worse.
Today he is taking a single anticonvulsant, Depakote, valproic acid. He has shown no symptoms at all for many months. Not a twitch. Doing very well in school. Got an "A" in Phy Ed. Plays the clarinet like nobody's business. Knock on wood.
Scientists believe that valproic acid works by building up gamma-aminobutyric acid (GABA) in the brain. GABA is an amino acid that acts as a neurotransmitter, a substance that transmits nerve impulses across a synapse or junction between nerve cells. High concentrations of GABA seem to inhibit the ability of nerve membranes to transmit signals and thus for the entire system to get overexcited.
But how it works is less important. That it does work means, for now at least, we won't have to watch Robbie grimace with pain as an IV is put into the back of his hand.
It means, for the moment, we won't have to worry when he comes down for breakfast whether he has left his dream behind.
Wake me up dreaming
coming down from the high road
out of the darkness
now i know how the blind man feels
all i ask is to come down easy
Some 40 million people in the world have epilepsy. Some two million new cases occur each year. It is the most common serious brain disorder in every country.
Most people with epilepsy have no access to treatment of any kind. Most go through their lives shunned by those around them, just as they were in Hippocrates' time.
Last year the World Health Organization, the International League Against Epilepsy, and the International Bureau for Epilepsy launched a global initiative to improve health care services, treatment, and social acceptability of people with epilepsy. Public and professional education of the "hidden, neglected, and treatable" disorder figures prominently in the initiative.
For the eight million people with epilepsy who have access to medical treatment, nearly all of them in Europe, Japan, Australia and North America, things look much brighter. Seizures can be controlled in about three-quarters of newly diagnosed children and adults.
In intractable cases, advances in neuroimaging are making it possible to uncover and treat subtle brain lesions responsible for seizures. A new medical device that stimulates the vagus nerve, a nerve descending from the medulla oblongata, was approved by the FDA last year. Stimulation of the vagus nerve produces an antiepileptic effect by inhibiting the ability of neurons to fire uncontrollably.
Revolutionary treatments for inherited epilepsies, perhaps a third of all cases, are not that far off. They will be based on fundamental science arising out of the Human Genome Project.
An "explosion of new drugs" will give physicians a larger armamentarium in the near future, a larger arena in which to explore the "tolerability" factor.
Matching the right drug with the right patient. How simple it sounds. How painfully difficult it can be to do.
--William Hoffman firstname.lastname@example.org
Disclaimer: The opinions expressed herein are the writer's own.
Medical illustration by Robbie at age six. Is it an ear? A kidney?