When Rosalba Zamora was 20 years old, she witnessed her first epileptic seizure. A middle-aged man walked into the department store in Mexico where she worked and collapsed. As Zamora watched him violently and uncontrollably convulse on the ground, she thought, “If that ever happened to me, I would want to die.”
Two years later Zamora had a seizure herself. She and a friend had just moved from a rural town to bustling Mexico City, and neither had been able to find a job. Zamora climbed into the top bunk one night stressed and overtired—both conditions that would prove triggers for epileptic seizures for the rest of her life. She remembers nothing of that first seizure, only the aftermath.
“I woke up on the floor next to the bunk bed,” said Zamora. Her friend, who had been sleeping below, was crying hysterically, shaken and scared. “We had no idea what had happened.”
Though more than 50 million people worldwide have epilepsy, including 3 million in the United States alone, it remains one of the world’s most misunderstood neurological conditions. While some people, like Zamora, have sporadic seizures and can live relatively normal lives, others may be burdened by several a day. Seizures come in as many as 40 different varieties, ranging from a momentary absence of awareness to severe and prolonged convulsions.
“I know that I shake, but I don’t know what they feel like because I’m asleep,” said Zamora. “And my husband is the only one who sees them because they happen at night.” He doesn’t explain much and Zamora doesn’t ask. Zamora also has short periods of dizziness or disorientation during the day, which may also be small seizures, according to her physician. But the convulsive seizures come only when she sleeps and last just a minute or two.
What scientists know about epilepsy is that seizures are caused by a sudden surge of electrical activity in the brain. If normal brain activity is like a stadium full of people all talking to each other normally, a seizure is the rowdy section that heaves and hoots in unison for a few frenzied moments when its team scores, then returns to normal “conversation.” Which section of the brain has the electrical outburst varies from person to person.
While scientists have determined the what of a seizure, they can’t seem to figure out why. A century of studies has revealed that epilepsy can stem from trauma to the brain: head injury, infection, brain tumor, complications at birth, alcoholism. But for more than 50 percent of people diagnosed, including Zamora, science just cannot explain why the neuronal power surges begin. The cause of the epilepsy is inexplicable, idiopathic.
Over the centuries, different cultures have come up with numerous ways to explain epilepsy. In ancient Babylonia, a seizure meant a person had been captured and released by the devil. In China, some scholars described it as an excess of “yin,” the negative force that must be in balance with “yang” for bodily harmony. In Africa, explanations range from sorcery to the revenge of ancestral spirits. In Laos, the Hmong believe that epilepsy indicates a person’s potentially great powers of healing. But for Zamora and others like her, epilepsy hardly feels like healing. It feels alienating because it is so misunderstood.
“Treating epilepsy is more than just dealing with a condition,” explained Dr. Christianne Heck, epileptologist and assistant professor of clinical neurology at USC’s Keck School of Medicine. “It’s about fighting for people’s rights. People with epilepsy look normal because they are.”
Tim de Villiers, a civil engineer who has had epilepsy since age 10, thinks education about the disease should start in schools to prevent misconceptions. "Ignorant people in general tend to fear someone who has epilepsy," said De Villiers, who runs a social support organization called Epicare for people with epilepsy and their families. "But the condition is not as dramatic as all that."
Because of the stigma surrounding epilepsy and the embarrassment of public seizures, many patients are too afraid to tell others, so they stay home in the safe environment of their families. The effect can be extremely isolating, according to De Villiers. "People put themselves in boxes but have the potential to lead very normal lives," he said. "Because of the barriers that they put up around themselves, they focus inward. This becomes very stressful and can actually increase the seizures."
Most physicians require their patients to keep a detailed calendar of the seizures, in an effort to find patterns and triggers. Zamora, who thanks to the anticonvulsant drug Dilantin only has a few seizures a year, said that stress and irregular sleep patterns incite the attacks.
For others, triggers can be anything from anxiety and menstruation to constipation and alcohol. De Villiers said it’s about figuring out what your triggers and then determining your thresholds. He knows he can only drink so much red wine before he’s taking a risk. “It's not about giving up what you enjoy," he stressed.
About 70 percent of people with epilepsy are able to control their seizures with a combination of medications, the first line of defense. Many, however, suffer from side effects like severe dizziness, drowsiness, twitching and nausea. Unlike antibiotics, which cure infection, anticonvulsant medications treat the symptoms of epilepsy by altering the way the brain’s neurons transmit electricity, thus reducing the prevalence of seizures. The 30 percent of patients who don’t respond to medication—almost a million people in the United States alone—are left searching for often hard-to come-by alternatives.
In the 1950s, neuroscientists discovered that in some cases the problem can be solved by removing the culprit: the part of the brain that is the source of the seizures is surgically excised, much as a physician might remove a gangrenous toe. But to remove the problematic region, physicians must be able to pinpoint it, as well as ensure that removal of that part of the brain will not seriously impede the brain’s function, such as language, vision, or memory. In many cases, patients cannot afford the medical monitoring required, or surgery doesn’t lend itself to their particular variety of seizure.
Neurostimulation is without question the most promising area of epilepsy research. In the 1990s, scientists found that the brain’s electrical outbursts (and therefore seizures) can be significantly reduced by gently stimulating the vagus nerve in the neck, which travels to the brain. Since its approval by the FDA in the late 1990s, a device called the Vagus Nerve Stimulator (VNS) has been offering hope to patients for whom medication is insufficient. The VNS is a device implanted near the collarbone that delivers mild electrical stimulation to the vagus nerve at regular intervals (for example, for 30 seconds every three minutes). A handheld magnet can also be held over the implanted device to manually activate it if the patient feels a seizure coming on.
But the VNS stimulates at programmed intervals, not in response to individual seizures. Often, by the time a patient recognizes the aura (a feeling or indication that warns a seizure is coming) it is too late for the patient or family members to manually switch on the stimulator. So, scientists have created an implantable device designed to detect seizures before they begin—and prevent them.
Whereas the Vagus Nerve Stimulator stimulates the nerve leading to the brain, the groundbreaking Responsive Neurostimulator (RNS) stimulates the brain directly. Developed by Neuropace Inc., the device is implanted inside the skull, and from it run two wires to the part of the brain where the seizures originate. When the device detects the “signature” of an oncoming seizure, it delivers just enough electrical stimulation to suppress it. It may prove the answer for patients who don’t respond to medications and are not candidates for surgery.
The USC Medical Center-Keck School of Medicine, along with 27 other medical research institutions around the country, joined Phase II of the clinical trial to test the Responsive Neurostimulator in early 2007. Around 280 people with epilepsy from across the country will receive the device and try it out for two to three years before the FDA can approve it for commercialization.
Four patients have been enrolled in the trial at USC thus far and two have already had stimulators implanted. Dr. Heck, principal investigator, said that USC will ultimately implant 10-12 devices. “It’s very exciting,” she said. “We may finally have something for patients who really have no other options.” Once the FDA approves the Spanish-language paperwork, Heck said she and her colleagues will be able to recruit patients from their clinic that treats Los Angeles’ poorest people with epilepsy.
Every Friday morning at the Los Angeles County Hospital-USC Medical Center, the waiting room on the fourth floor of the Outpatient Treatment Center fills to the brim with people looking for options. The patient roster for each week is booked months in advance, but still the patients, seen on a “first-come, first-served” basis, must wait hours to meet with the five or six resident physicians who work at the epilepsy clinic as part of their neurology rotation. “We see the worst of the worst cases here,” said Dr. Laura Kalayjian, who oversees the resident physicians. “At least 30 percent of these patients cannot control their epilepsy.” Because the condition itself is not understood, treatment is always hit or miss.
In one examination room, a man with a Vagus Nerve Stimulator described the side effects of his latest cocktail of epilepsy drugs. Sadly, the man’s stimulator had offered no reprieve from the seizures and had long been turned off. Physicians have been tinkering with his combination of medications ever since. In another room, an older woman broke down sobbing as she explained the difficulty of dealing with both epilepsy and depression. She had forgotten one dose of her medication and had an embarassing seizure several days later. Down the hall, a somber resident physician reluctantly went into an examination room to tell a woman that he must report her seizures to the Department of Motor Vehicles; she might lose her license. In yet another room, a young man with a buzz cut showed off a six-inch scar from brain surgery ten days before. He had not had a seizure since surgery, and hoped that if he continued his medication, it would stay that way.
“Wanna see a Lamictol baby?” shouted a gleeful Dr. Kalayjian, poking her head from a doorway. Pregnancy for women with epilepsy is an uncertain undertaking. Lamictol and other anticonvulsants can cause malformative birth defects, including cleft palate and deformed limbs. Mothers-to-be must work very closely with physicians such as Dr. Kalayjian, who specialize in epilepsy issues unique to women, to minimize risk by carefully controlling their medications.
Eager to hear an epilepsy success story, several physicians gathered to see Dr. Kalayjian’s patient. Inside the room, two proud young Mexican parents sat beside their pink, six-pound, one-week old son Alberto. Alberto’s mother, epileptic since childhood, had been understandably terrified prior to giving birth. “He’s perfect,” sighed Dr. Kalayjian.
If the Responsive Neurostimulator is a success, it could provide an alternative to medication for expecting mothers. And with advancements in technology and treatment come advancements in understanding about epilepsy. Scientists are gradually determining what frequencies and levels of stimulation are most effective for particular seizures. A few years down the road, physicians may be able to easily tailor neurostimulation devices to patients with the push of a few buttons.
It’s been almost 40 years since Rosalba Zamora fell off the bunk bed in Mexico City. And while she’s had seizures throughout her life, almost six months have passed since the last. She doesn’t need a neurostimulator, as her epilepsy can be managed well enough with medication, though she’s fascinated by the idea. “If it could improve the quality of my life, I’d probably do it,” she said. With a mischievous smile, she added, “As long as magnets wouldn’t start flying at my head.”
