Medicine: Ending Epilepsy With a Map
As her chest tightened and her surroundings segued into slow motion, Yelena knew what was coming. Unable to help herself, her head jerked sharply left. Awareness leached away, her body convulsed and she thrashed wildly for minutes on end while the seizure ran its course.
On a good day, there were only four seizures, recalls Yelena’s mother. Some days there were five or six. At age 13, when Yelena began seizing frequently despite medication and diet, she left school and her mother quit work to look after her. The two, who moved to Israel from Russia nine years before, stayed home together, waiting to cope with the next attack and the exhausted confusion that followed.
Yelena, now 15, has epilepsy—one of 50,000 epileptics in Israel among 50 million worldwide (most of them in the developing world) and among the 60 percent for whom there is no known cause. They are in exalted company. The prophet Ezekiel, Socrates, Joan of Arc and Muhammad are historical figures believed to have suffered from epilepsy. Once called the “sacred disease” and variously believed to come from the gods, to result from a curse or to signal demonic possession, we now know epilepsy is a malfunction of the brain’s electrical system.
“Instead of transmitting and receiving messages in short, controlled bursts of electrical energy, brain cells begin firing wildly and continuously,” explains Dr. Moni Benifla, an epilepsy and pediatric neurosurgeon who heads Pediatric Neurosurgery at the Hadassah–Hebrew University Medical Center at Ein Kerem. “This creates a tsunami of energy surging through part or all of the brain that brings on a seizure. The most generalized is the tonic-clonic [once called grand mal] seizure, in which the muscles contract sharply and consciousness is lost.”
Yelena and her mother first consulted Dr. Benifla 18 months ago. Today, the teenager is seizure-free and back at school, following super-high-tech diagnosis and surgery not only unavailable to historical epileptics, but nonexistent anywhere until even a few years ago.
“For the 3 in every 10 epileptics like Yelena, whose disease is intractable, there was no relief before that,” says Dr. Odeya Bennett Back, epileptologist and pediatric neurologist at Hadassah. “None of the 20 existing anticonvulsant drugs prevented their seizures, nor did a high-fat/ low-carbohydrate ketogenic diet work for them.”
When properly selected, 70 percent of those who undergo this high-tech surgery are cured. One intractable epileptic whom Dr. Benifla and his team have successfully treated was 55. “She had suffered epilepsy since she was a small child,” he says. “For half a century, her entire life revolved around her seizures. Now that she’s seizure-free, she’s had to build a life virtually from scratch.”
The principle of the treatment that has cured this woman, Yelena and other similar epileptics is simple.
“It is removing the brain tissue that triggers the seizures,” says Dr. Benifla. “The two great stumbling blocks are, first, identifying that tissue and, second, removing it without causing collateral damage—leaving the patient paralyzed, say, or unable to speak.”
Despite the huge scientific advances of the past half century, the brain is still largely an unexplored continent. While scientists worldwide are engaged in mapping it—its regions, functional lobes, specialized centers, thick neuron “bundles” (neuron circuits, single neurons, neuron junctions and neuron parts)—navigating it is still much like trying to find your way through a sprawling city without a map.
“To identify the culprit brain tissue, we record the patient’s seizures over several days, simultaneously by video camera and by EEG, which picks up brainwaves through electrodes attached to the scalp,” says Dr. Benifla. “We then compare the videotape, the EEG trace and an MRI of the patient’s brain. If all point to the same abnormality, we’ve pinpointed the epileptogenic zone, the place where the seizures are generated, and the patient is a good candidate for surgery.”
With Yelena, the videotape provided an early clue. “Her seizures always began with her head swinging sharply left,” says Dr. Benifla. “Because movement on the right side is controlled by the brain’s left hemisphere, we knew the epileptogenic zone had to be on the left. But with the MRI indicating one area as the seat of the seizures and the EEG showing another, there was no exact locus. The next step was invasive EEG monitoring.”
For Yelena and other patients with unclear test results, surgery is in two steps. “Step 1 is diagnostic,” explains Dr. Benifla. “Because the EEG electrodes attached to the scalp haven’t provided a clear enough picture, we remove part of the skull and attach electrodes directly onto the brain. We then partially replace the skull over the electrodes, their leads dangling through the as-yet-unrepaired crack in the skull to be connected to the EEG.”
Hadassah is one of only 80 centers worldwide to map directly from the brain in this way. Yelena awoke from her first surgery with her head wrapped in a turban, the wires from 92 electrodes trailing from inside her skull, down the back of her neck and into the EEG.
“She and her mother both knew what to expect,” says Dr. Benifla. “Yelena had been psychologically evaluated, and a medical social worker was on hand throughout the demanding days of treatment.”
For the next 96 hours, Yelena’s seizures were recorded by video-EEG. The electrodes resting on her brain showed that although her seizures involved her whole brain, they always began at a point in its lower part. “We had pinned down the locus,” says Dr. Benifla. “Now we had to know its function.”
Enter functional magnetic resonance imaging (fMRI), a neuroimaging technique developed 20 years ago. It measures changes in blood flow and relates them to neural activity in the brain and spinal cord, thus revealing brain function—and enabling Hadassah neurologists not only to help epileptic patients but to contribute to the global effort to map brain function down to each neuron.
To discover the jobs performed by the square inch of brain tissue that generated Yelena’s seizures, the team recorded reactions in her brain as she performed certain tasks, while the electrodes were in place on her brain. She counted backward, wiggled her thumb and thought about different verbs—running, jumping—while the medical team watched what happened to the electrical activity recorded directly from the brain.
To their joy, they saw no activity in the locus linked to speech, comprehension, sensation or movement.
Yelena was told there would probably be no adverse affects from surgery, but there was no guarantee against a functional deficit. Her response: “I don’t even care if I end up paralyzed! Just stop these terrible seizures and give me a life!”
Eighteen months after surgery, Yelena came for a periodic checkup. “She is in school, she baby-sits her brother’s children, she has lots of friends and even a boyfriend whom her mother doesn’t care for,” says Dr. Benifla, smiling. “What could be more normal for a 17-year-old!”
Some patients are less fortunate than Yelena—for instance, if fMRI mapping shows that the epileptic locus controls a vital function, and that its removal will result in a functional deficit. “The decision then is whether to do nothing and let the seizures continue unchecked,” says Dr. Bennett Back, “to resect part of the area in the hope of reducing the seizures or to remove it all, knowing the patient will pay a price. Clearly, each patient is different, and for some the price is worth paying.”
She describes a 3-year-old whose severe seizures regularly brought him to pediatric intensive care. “The child was seizing so frequently he was on continuous I.V. medication, for which he was intubated,” she says. “The only way to get him out of the PICU was to stop the seizures, and the only way to do that was to resect the brain tissue where they were generated—even though the epileptic focus was within the child’s motor area. When he came out of surgery, half this little boy’s body was paralyzed. But with time and intensive rehabilitation, his paralysis has been converted to no more than weakness. Today, he walks and functions fully.”
The youngest patient on whom the team operated was 10 months old. “There is no minimum age,” says Dr. Benifla. “In fact, the earlier the better to minimize the effects of medications and seizures on a child’s behavior and brain development, and to maximize the brain’s plasticity in promoting full recovery.”
Only 150 years ago, epileptics in France were institutionalized alongside the criminally insane. To this day, in parts of Africa, they are thought to be possessed by evil spirits. As scientists gain greater understanding of the condition, they are erasing its stigma, finding ways to ease the lives of its victims and, in mapping the millions of miles of the brain’s neuronal wires, perhaps opening paths to curing not only epilepsy but other crippling disorders.