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Physicians Update

 
Fall 2013

Targeted Surgery Can Benefit Children with Medically Refractory Epilepsy

The danger of uncontrolled seizures in infants and children over any period of time — including the likelihood of poor long-term developmental outcomes and the risk of premature mortality — makes it essential that pediatric patients whose seizures cannot be controlled by medication are promptly referred to a center that specializes in pediatric epilepsy. Gary Mathern, MD, director of UCLA’s Pediatric Epilepsy Surgery Program, notes that not all patients referred to his program are recommended for surgery — but for those who are, at least three-fourths can be made completely or nearly seizure-free.

Dr. Mathern operates on a young patient.Dr. Mathern operates on a young patient. Epilepsy surgery in children involves different types of operations, from focal resections for different etiologies to cerebral hemispherectomy — removal of half of the brain.

How is epilepsy defined, and what proportion of epilepsy cases can be controlled by medication?
Epilepsy is commonly defined as having two or more unprovoked seizures separated by at least 24 hours. The rate of newly diagnosed seizures for those under age 15 is about 500 cases per 1-million children per year. Of these, about 70 percent are controlled or nearly controlled by anti-epilepsy drugs. Of the remaining 30 percent of children with epilepsy, about half have more than a seizure per month. About 15 percent of children with epilepsy are medically refractory, which is defined as failure of two-to-three anti-epilepsy drugs and with frequent-enough seizures that they affect the child’s life. Of those with medically refractory epilepsy, about one-third are candidates for epilepsy surgery.

Has drug therapy for epilepsy improved?
There have been anti-epilepsy drugs around since the 1940s, and there has been an explosion of drugs that have been approved since the 1990s. The new drugs have reduced the side effects, but the bottom line is that the incidence of medically refractory epilepsy has not changed.

Which patients are most likely to respond to medication?
Broadly, the etiology of epilepsy can be divided into three groups. About 30 percent of cases are presumed to be genetic — and among this group, there is about a 90-percent response rate with drug treatment. The second group — about 20 percent of the patients — have a structural brain problem, something we can identify on imaging studies. This group fares the worst on drugs; only about a 50-percent response rate. These are also generally the patients who might be candidates for surgery. And then for the remaining 50 percent of cases, we are unable to diagnose the cause.

The important thing from the perspective of referring physicians is that among children with structurally caused epilepsy, after they have failed to respond to two or three drugs, the chance of continued medical therapy controlling the epilepsy is less than 5 percent. So there is no reason to continue trying more drugs before referring to a specialty center.

Dr. Mathern Beyond the daily impact, what is the long-term danger of continued uncontrolled seizures?
Having medically refractory epilepsy has two major impacts on a child’s life. Frequent seizures, especially during the formative years of early brain development — before age 5 and especially before age 2 — are strongly linked to significant developmental delay that is generally not reversible. These children don’t gain their intellectual capacities at the same rate as other children, and our data suggest that if you don’t obtain seizure control within about 18 months of onset in a child, that child ending up with an IQ above 80 is difficult if not impossible. Frequent seizures are also associated with premature death, generally from accidents and sudden unexpected death related to epilepsy.

This poor natural history of the disease — cognitive problems along with increased mortality — justifies a surgical intervention in medically refractory patients if a targeted area can be identified, particularly because of our success rates. So it is critically important that a child whose seizures are not adequately controlled by two-tothree trials of anti-epilepsy drugs be referred to a specialty center for evaluation and treatment — both to confirm the cause and to address whether there are alternate treatments. UCLA’s Pediatric Epilepsy Surgery Program is one such specialty center, with more than 25 years of experience in the field.

What does epilepsy surgery in children involve, and what are the outcomes at UCLA?
Epilepsy surgery in children involves different types of operations, from focal resections for different etiologies to cerebral hemispherectomy — removal of half of the brain. Many of these are very rare, which is another reason for having a child and family come to a major referral center where there is experience in rare conditions. UCLA has operated on more than 750 children, with published outcome measures and quality metrics that are among the best in the world. Our short-and long-term seizure-free outcomes are 75-to-80 percent, and are sustained over many years postsurgery.These outcomes have improved over time, due to the tireless efforts of our team. This is a team effort — including the pediatric epileptologist and surgeon, who work together to assess the risks and benefits of surgery in a particular case; and the expertise of the anesthesiologists, pathologists, pediatric intensive care unit and the imaging group that has worked with us to develop new technologies to identify subtle legions that would have been missed five or six years ago.

Dr. Mathern Do those technologies help to identify more surgical candidates?
Yes. We are better at identifying structural abnormalities in the brain than we were even 10 years ago. We are able to move children from the group whose epilepsy has an unknown origin to the group with a known structural cause by using more advanced imaging, as well as through refinements in our EEG technique. It’s important to stress that referral to our center doesn’t mean that every child gets surgery. We start with a comprehensive evaluation by our team of experts. Tests may include inpatient video EEG monitoring to capture and characterize the seizures; and imaging, such as FDG-PET and MRI. If the child is truly medically refractory and we have a target, then we will offer surgery.





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