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May 21, 2012

Epilepsy Surgery — A Medical Road Less Traveled
By Carolyn Gutierrez
For The Record
Vol. 24 No. 10 P. 24

Opting for surgery can give pharmaco-resistant patients a better chance at living a more normal life.

Approximately 30% to 40% of people with epilepsy have seizures that do not respond to traditional pharmaceutical treatment. Up to 50% of these drug-resistant epilepsy patients are potential candidates for brain surgery because their seizures originate from an area of the brain that can be easily accessed and removed without producing additional deficits.

“This is a tremendously underutilized procedure—probably the most underutilized of all accepted medical interventions,” says Jerome Engel, Jr, MD, PhD, head of the epilepsy program at UCLA. “It is estimated that less than 1% of patients in the United States, and indeed in the industrialized world, who are potential candidates for surgery are ever referred to an epilepsy center to find out whether they might be candidates, and it’s difficult for us to understand why.”

Engel and colleagues conducted a study of 38 patients at 16 US epilepsy centers comparing the outcomes of surgery for the most common form of surgically remediable epilepsy (mesial temporal lobe epilepsy [MTLE]) with those of MTLE patients treated only with medication. According to Engel, pharmaco-resistance for epilepsy is now defined as the failure of two adequate antiepileptic drug trials.

The researchers found that patients who underwent brain surgery soon after pharmaco-resistance while still continuing drug therapy after surgery fared better than those patients who continued with only drug therapy. Engel and colleagues believe these findings underscore the need for not only surgical intervention but also for surgical intervention earlier in a patient’s life.

“The longer you wait to do surgery,” says Engel, “the more likely the individual is to become permanently disabled because epilepsies, particularly the surgically remediable epilepsies, usually begin in childhood, adolescence, or early adulthood when critical acquisition of vocational skills and interpersonal skills are acquired. And if people go through that period with frequent intractable seizures, they don’t really develop the skills that are necessary to live independently.”

Not only are few patients with epilepsy ever referred to epilepsy centers, but when they are, according to Engel, they are referred an average of 22 years after the first onset of their epilepsy. “There’s lots of misinformation out there that is preventing these patients from being referred,” he says.

Traditional Epilepsy Surgery
Although MTLE is the most common form of surgically remediable epilepsy, there are many other kinds that can be treated surgically.

To determine whether surgery is viable, a patient is given a series of imaging tests beginning with inpatient video electroencephalography (EEG) monitoring. This scalp EEG records the patient’s brain activity for 24 hours to capture spontaneous seizures. Seizures are also recorded on video to correlate behavior with the EEG abnormalities, narrowing down where in the brain the seizures are coming from and pinpointing the exact type of epilepsy.

Neurologists also perform additional tests, including a high-resolution MRI, a PET scan, and a neuropsychological evaluation. These tests aid the specialists in determining whether the patient is a surgical candidate and if the epileptogenic tissue in the brain can be safely removed.

In some cases, if the specialists are unable to pinpoint the location of the seizure, invasive studies are conducted that involve implanting electrodes directly into the patient’s brain for additional video EEG monitoring. If it’s determined that the patient is a good candidate for surgery, he or she returns for a lobectomy or cortical resection, the two most common forms of epilepsy surgery.

“The surgery is just a straightforward procedure which carries very little risk,” Engel says. “The mortality rate from the surgery itself is essentially zero. The chances of developing an additional problem as a result of a complication of this surgery are about 6%. But in half of those cases, it’s transient and goes away within a year, so [the chances of] permanent problems from the surgery are about 3%. Convalescent time after the surgery is pretty short; it’s easier than for abdominal or thoracic surgery.”

Minor or temporary risks associated with lobectomies for epilepsy include brief sensory changes such as auras, partial loss of vision, motor ability, and speech.
Interestingly, because the brain does not feel any pain, the patient is sometimes awake during surgery. This can actually be helpful to the surgeons, as interacting with a patient who is awake can aid the surgical team in monitoring any possible risks or damage in brain function.

Following traditional epilepsy surgery, it can take anywhere from six weeks to three months for full recovery. Studies have shown that about 60% to 80% of patients who undergo the surgery are seizure free, with most patients continuing some sort of reduced epilepsy medication. It is thought that in most cases, the surgery improves the efficacy of antiepileptic medicines.

With MTLE, there is a scarlike lesion within the temporal lobe’s amygdala and hippocampus. These portions of the brain are normally responsible for mediating short-term memory, and scientists believe they are also responsible for turning short-term memory into long-term memory. With epilepsy, scarring in this portion of the brain leads to seizures, yet researchers have found that the MTLE scarring, or “seizure focus,” is in a fairly accessible spot—a particularly good location for epilepsy surgery. Studies have shown that if medication does not stop the seizures, MTLE was associated with better outcomes through epilepsy surgery, making it the preferred method of treatment for patients with this form of epilepsy.

Gamma-Knife Radiosurgery
Researchers are currently looking at gamma-knife radiosurgery as a viable noninvasive alternative for treating MTLE and other forms of pharmaco-resistant epilepsy. Developed in Sweden in the late 1950s, gamma-knife radiosurgery has long been used to treat deep-seated tumors in the head or neck or difficult-to-reach vascular malformations. As technology has refined the gamma knife’s precision through the years, it is now being studied as an effective treatment for MTLE alongside traditional cranial surgery.

After undergoing the same battery of tests that are performed before standard surgery, a patient proceeding with gamma-knife radiosurgery is fitted into a stereotactic frame to become stabilized during the procedure. The gamma knife is actually a domelike device that emits 201 finely focused but very weak beams of gamma radiation into the cranium. The beams simultaneously intersect at the precise location of the epilepsy lesion within the brain. A small but powerful radiation hot spot is applied to the lesion without disturbing the tissue outside of the focal point. Computer software guides the surgeon to the correct vantage points during the process, and the lesion is carefully damaged.

The patient is generally awake during radiosurgery and must lie still for anywhere between 30 minutes and several hours depending on the lesion’s size and shape. After the radiosurgery is complete, the patient may return home.

The main caveat in using gamma-knife radiosurgery to treat epilepsy is that destruction of the lesion occurs slowly over several months to one year or longer. The damages to the lesion are cumulative and take time, so patients who undergo this procedure may not see changes in their seizure patterns for several months. Seizures may still occur until the lesion has completely necrotized.

One risk associated with gamma-knife radiosurgery is headaches caused by swelling of brain tissue. In pilot studies, although there was a risk of swelling, it was believed that the swelling was not extensive enough to be considered dangerous. Overall, results from gamma-knife pilot studies were promising, and researchers believe the advantages of this noninvasive approach may outweigh any disadvantages.

Neurologist Mark S. Quigg, MD, of the University of Virginia School of Medicine, is one of the principal investigators in an international trial examining the effectiveness of gamma-knife radiosurgery compared with traditional surgery for treating MTLE. Known as the Radiosurgery or Open Surgery for Epilepsy (ROSE) trial, the study is following 217 volunteer patients with MTLE who have either had gamma-knife treatment or traditional cranial surgery. Researchers will measure the treatment’s effectiveness in halting seizures, cognitive function, quality of life, and cost.

“The gamma knife has been around for quite a long time,” Quigg says, “so there is a history of its use. But its application specifically for epilepsy in this particular scarring in the hippocampus and amygdala really hasn’t been done before. That’s what the purpose of this trial is: to see if the advantages of this minimally invasive tool can provide certain benefits to patients than that of standard surgery, which is of course well established.”

Quigg notes that in a pilot study of 30 patients who underwent gamma-knife radiosurgery, about two-thirds were seizure free after a three-year follow-up period. Gamma-knife surgery has also been shown to improve cognition.

Because it is essentially an outpatient procedure, gamma-knife radiosurgery is an appealing option in this cost-conscious environment, researchers say. In studies conducted on other applications of radiosurgery, it was found to cost one-half as much as traditional surgery.

However, the prolonged results when using the gamma knife to treat epilepsy may actually even out costs in the long run, Quigg notes. “Because of the delay in the effect of the gamma knife, we’re going to count all of the accumulated healthcare costs during the course of the trial because we want to see whether that delay in effect has a cost attached to it. That’s a very fair way, I think, to measure them out,” he says. “Traditional surgery is the gold standard. It’s very effective and very safe for most patients, but there are subtle disadvantages that we’re going to compare to the subtle disadvantages of the gamma knife.”

Improved Quality of Life
Perhaps the most profound findings in studies of both traditional epilepsy surgery and gamma-knife radiosurgery are the data supporting how they improve quality of life for epilepsy patients. Patients whose lives are disrupted by epilepsy have been found to have higher rates of comorbidities and lower rates of employment, marriage, and education levels than the general population.

When the seizure focus is removed through traditional surgery or ablated via the gamma knife, studies show long-term improvements in patients’ moods and their quality of life in general. In the long term, postoperative patients who are seizure free may be able to consider living independently, driving, and gaining employment.

Unfortunately, some epilepsy patients aren’t aware that surgery is an option, and those who are aware are often afraid of undergoing brain surgery. There’s also trepidation on the physician side, Quigg says.

 “I think that epilepsy surgery is underutilized mainly because of patient fear,” he notes, “but also because of referring physician reluctance. I think if we could offer a variety of procedures, the better patients could be served.”

Engel maintains that it is not the responsibility of the patient or the referring physician to decide who’s a candidate for epilepsy surgery. “If drugs don’t work, the patient should be referred to an epilepsy center where specialists can decide whether they’re a candidate or not,” Engel says. “And if they’re not a candidate, there may be other treatments or other approaches that might be helpful.”

According to the Epilepsy Foundation, epilepsy is the third most common neurological medical condition in the United States, behind only Alzheimer’s disease and stroke. Despite its prevalence, it remains widely misunderstood.

 “One of the things I think it’s important for patients and their families to know,” Quigg says, “is that sometimes just reduction in number of seizures isn’t the same as completely getting rid of them. That’s an important thing to consider because what we have shown is things like quality of life, employability, and certainly driving usually hinge upon being seizure free rather than having a reduction in seizures. That’s why I think epilepsy surgery is important to consider because if you just reduce the seizures, you’re not going to enjoy the large benefits that occur when seizures are completely gone. Settling for improved isn’t really improved.”

— Carolyn Gutierrez is a freelance writer based in New York City.