Brainstorm
Epileptic seizures that are untreatable with medications may be controlled with fine-tuned surgical techniques and a recent innovation, the vagus nerve stimulator.
by Christopher Tedeschi
Like an electrical system gone haywire in the midst of a lightning storm, epilepsy can wrack the brain's neural circuitry.
Scores of medications have been used in an attempt to control epileptic seizures and the electrical disturbances in the brain that cause them. In many cases, regular medication can be so effective that patients rarely have to deal with epilepsy's intrusion into their daily lives.
But for others, medication may be of little help, even after seemingly endless tinkering with dosages and combinations. For some, the side effects of strong anti-seizure medications may outweigh the benefits. In these cases-dubbed medically intractable epilepsy-brain surgery can provide some long sought-after solutions.
The Epilepsy Program at USC University Hospital offers a range of surgical choices for patients who may feel that they have exhausted the options for controlling their seizures.
"Medically intractable patients are those in whom seizures are not eliminated with at least two medications and who have had intractable epilepsy for at least two years," explains Christopher DeGiorgio, M.D., associate professor of neurology and neurological surgery and director of the USC Epilepsy Program.
Roughly 30 to 40 percent of epilepsy patients do not respond to medication, and about 20 percent are good surgical candidates.
The main goal of surgery, DeGiorgio says, is to rein in seizures that have become out-of-control. "Surgery can be a definitive solution," he explains. "We know that eliminating seizures improves quality of life, and we know that surgery often eliminates seizures."
Physicians are not sure of the exact origin of most epilepsy cases-why a particular area of the brain begins to "misfire." Research indicates that trauma, like a head injury, can play a role, and that seizures due to high fever in infants could have some connection with the development of the disease later in life.
As a seizure begins, electric signals from one particular group of nerve cells somewhere in the brain become so strong that they overwhelm the signals sent out by neighboring cells. The errant signal can spread to a particular region of the brain, or travel throughout the entire brain in a matter of seconds. A seizure shows itself as a blank stare, an out-of-control movement of a particular part of the body or a loss of motor control altogether, or as a violent convulsion.
In many adult patients with epilepsy, the seizure's source-or focus-can be localized to a small area of brain tissue, most often in the area of the brain called the temporal lobe. Temporal lobe seizures account for more than 75 percent of total epilepsy cases. Surgery to remove the part of the temporal lobe responsible for seizure onset is called a temporal lobectomy.
"The ideal patient for surgery," explains DeGiorgio, "has temporal lobe epilepsy that can be localized, along with some atrophy, or shrinkage, of the brain area called the hippocampus." Patients with temporal lobe epilepsy often experience confusion, staring spells or distinct auras, but only rarely have generalized, "grand mal" seizures.
Nonetheless, DeGiorgio contends, surgery for intractable epilepsy remains an overlooked solution to the problem. "Surgery is underutilized because not enough patients are referred for epilepsy surgery. Patients with temporal lobe epilepsy are frequently treated only medically, although more patients are now deciding to undergo the procedure."
Although surgery for intractable epilepsy has the potential to eliminate seizures once and for all, patients must consider some important factors before deciding to give it a try. The most common problems that occur after part of the temporal lobe is removed, DeGiorgio says, include memory loss-in particular, trouble remembering names-and mild to moderate speech problems.
Localizing an epileptic focus is the first stage in planning surgery. At USC University Hospital, DeGiorgio and the associate director of the Epilepsy Program, Christi Heck, M.D., an assistant professor of neurology, use multiple tools to pinpoint the exact section of brain that is causing the trouble.
First, patients undergo an EEG-a test that measures the electrical activity of the brain through a series of electrodes placed on the scalp. Technicians Carl Henderson, REEGT, and Thomas Smith, REEGT, guide patients through the monitoring procedure and guarantee that the team has enough information to decide exactly where epileptic seizures originate. Advanced imaging scans like PET (positron-emission tomography) and MRI (magnetic resonance imaging) help to locate the focus.
In some cases, when a seizure cannot be pinpointed using these methods, electrodes placed directly on the surface of the brain must be used to find the seizure's source. The procedure is invasive and painstakingly detailed, but the results often pay off.
Neuropsychologist Carol McCleary, Ph.D., assistant professor of neurology, helps to localize seizures by using cognitive methods to help find the region from which seizures originate. Through a series of tests called neuropsychological assessment, McCleary can not only help surgeons zero in on an epileptic focus, but she can help to track changes in a patient's brain function both before and after surgery.
Explains McCleary: "It's important to localize the seizure damage to one part of the brain, and psychological tests can find functional damage from seizures, even though no structural damage may show up on an MRI."
The psychological testing can be divided into two main areas: cognitive function and emotional status. Emotional status is important, she says, since it can affect memory, progress after surgery, and the performance on tests used to assess other brain functions.
"The best predictor of post-surgical emotional status is pre-surgical emotional status," explains McCleary. Fighting depression and maintaining a strong, positive attitude can make a real difference in the success of epilepsy surgery.
"Psychological tests help add to the evidence that localizes a seizure. For example, we know that the left side of the temporal lobe plays a role in verbal memory, while the right side is responsible for visual memory. Patients can show characteristic patterns on memory tests depending on where a seizure is originating."
McCleary has been conducting research to help find better ways to determine where the focus of a seizure is located. By incorporating tests that examine language skills, visual-spatial skills, and "executive functions" like organization and planning, she hopes to find patterns that allow her to report back to physicians and surgeons exactly how epilepsy is changing the way someone's brain works. Knowing a patient's strengths and weaknesses enables McCleary to help patients compensate for weak areas after an area of brain is removed. For example, a patient with a decreased ability for verbal memory, can compensate using visual memory techniques.
Once an epileptic seizure starts, the overloaded electrical signals that it generates can quickly spread from one side of the brain to the other-and even to a particular location on the opposite side of the brain that corresponds to the location of the focus. This "mirroring" effect can mean confusion for surgeons who need to make sure that they're going after the real source of a seizure, rather than a copycat region on the opposite side of the brain.
"It's very important that neuropsychologists come up with more specialized tests that can differentiate between left and right temporal lobe damage," McCleary explains.
Once the source of epileptic seizures has been precisely determined, neurosurgeons can remove the area in the brain that is starting the electrical chain reaction that can eventually spread throughout the central nervous system. Using a combination of advanced imaging techniques and high-tech microscopic navigation, Michael Apuzzo, M.D., the Edwin M. Todd/Trent H. Wells Jr. Professor of Neurological Surgery, and his neurosurgical team can reach the area of brain that is the focus of the seizures, and then remove as little tissue as possible.
After surgery, patients with seizures originating outside of the temporal lobe have about a 30 to 50 percent chance of becoming entirely seizure-free. Patients with temporal lobe epilepsy have even better odds: up to 80 percent are post-operatively seizure-free.
In the past year, an alternative treatment has become available for thousands of patients with medically intractable epilepsy. Called the vagus nerve stimulator, the small device is a permanent implant that provides electrical stimulation to the vagus nerve in the neck. The electrical stimulation has been shown to reduce seizure frequency dramatically in patients who have not responded well to medication.
In mid-July the U.S. Food and Drug Administration granted full approval for the device, based partly on results from USC studies. DeGiorgio served as a principal investigator for a large multi-center study of the stimulator.
The vagus nerve stimulator, DeGiorgio explains, like temporal lobectomy, can be most helpful for patients whose epilepsy did not respond to drug treatment. The device is valuable to those patients who are not candidates for epilepsy surgery, or who do not want to risk a major surgical procedure.
Roughly the size of a pocket watch, the stimulator is implanted in the patient's upper chest by a neurosurgeon. An electrical lead running up the left side of the patient's neck connects to the vagus nerve. Every few minutes, the device delivers an electrical pulse to the nerve. When a patient feels a seizure coming on, the device is activated manually by placing a small magnet against the chest.
The results for some patients have been dramatic. "For the first time in so many years, I have started to not be concerned about when my next seizure will occur," says Carl Spencer, who received the vagus nerve stimulator in the multi-center study. Before the implant, Spencer reported having several seizures every few days. He recently went more than four weeks without having a single seizure.
Patients can combine the vagus nerve stimulator with the medications that were not effective when taken alone.
"Now that I am out of the controlled study, we have started to aggressively treat my symptoms with new medication," says Spencer. "I now see an even greater decrease in seizure frequency."
As a key partner in a multi-center study of the vagus nerve stimulator, USC results showed 30 percent of the patients in the study had a 75 percent reduction in seizures and 11 percent had more than a 75 percent reduction. One patient treated at USC has been entirely seizure free since the implantation of the device.
Recent USC evidence also shows that epileptic seizures over a long period of time can cause subtle biochemical changes in the brain, potentially leading to neurological problems years in the future. If the vagus nerve stimulator can help to stop those seizures before they start, DeGiorgio says, then the residual damage may be lessened as well.
Meanwhile, DeGiorgio, Heck, Apuzzo, McCleary and the epilepsy team continue to approach epilepsy from different angles. From well-established procedures like temporal lobectomy to innovative approaches like vagus nerve stimulation, multidisciplinary approaches to epilepsy treatment have come a long way in the past few decades. A combination of surgery and medical treatment, individually tailored for each patient, can help to take some of the mystery, fear and frustration that can come with a lifetime of epilepsy.
