BOSTON - Clinical trial results are so striking that neurologists should advocate for early surgical evaluation of patients with mesial temporal lobe epilepsy (MTLE), according to physicians at Boston's Beth Israel Deaconess Medical Center and Harbor-UCLA Medical Center in Torrance, California.
In an editorial in the March 7 edition of the
Journal of the American Medical Association, co-authors Donald L. Schomer, MD, a neurologist at BIDMC and Roger J. Lewis, MD, PhD, an emergency medicine physician and expert in clinical trial design at Harbor-UCLA Medical Center, say the results from a trial reported in that issue warrant the recommendation despite the fact the study was terminated early due to low enrollment.
"Seventy-three percent of the patients who had surgery were seizure-free after two years. In the same time period zero patients who were surgery eligible - but for whom surgery was delayed - were seizure-free," says Schomer, a Professor of Neurology at Harvard Medical School. "That's a very significant finding and should be taken into account when treating patients early in this disorder."
More than 2.5 million people in the United States have received treatment for epilepsy in the past five years. About 60 percent of those patients have partial epilepsy where the focus, or place in the brain where the seizure begins, can be identified on radiographic imaging. One of the more common forms of partial epilepsy is mesial temporal lobe epilepsy (MLTE).
In spite of improvements in antiepileptic drugs (AEDs), more than thirty percent of people with epilepsy continue to experience debilitating seizures.
"We know there are risks associated with having seizures and there are often serious adverse effects of medications, so surgery may be a good option for many patients," says Schomer. "There's also a lot of documentation about diagnosing MLTE and locating the seizure focus as well as about positive outcomes after surgery, but up until now, there has been only one other prospective study that recommended surgical intervention."
The study Schomer and Lewis examined looked at patients who had experienced fewer than two years of disabling seizures from MTLE. The study group received a standardized anteromesial temporal resection (AMR), a surgery in which the area of seizure focus is removed from the brain. The control group, while eligible for surgery, delayed surgery and remained on anti-seizure medications.
The intent was to enroll 200 patients, but only 38 total patients had been enrolled in the study before it was terminated by the Data and Safety Monitoring Board. The low enrollment was likely due to the fact that the centers chosen for the study infrequently see and evaluate patients who are within two years of being diagnosed with mesial temporal lobe epilepsy, a requirement to participate in the study. Additionally, patients who have undergone such evaluations and are appropriate for surgery often do not wish to delay this form of treatment
"Studies can be stopped for various reasons. A review board may determine that there is too much associated risk, or the evidence of treatment difference may be overwhelming," says Lewis. "This study was stopped because there weren't enough participants, but not before some impressive outcomes were unequivocally identified."
Not only did three quarters of the patients who received surgery remain seizure-free, but they also reported improved quality of life, which often correlates with seizure freedom. While the patients who received surgery did suffer some memory loss and were no more likely to return to work than the nonsurgical intervention group, Schomer and Lewis believe the benefits of seizure freedom outweigh the deterrents. They also note that the disappointing effect of the surgery on employment may relate more to the lack of availability of appropriate rehabilitative services for both groups of patients.
"We feel pretty strongly that stopping this trial early did not bias the findings and that this study along with we already know about seizures and seizure surgery makes a strong case for recommending surgery for this type of epilepsy when it's indicated," says Schomer. Lewis adds, "Although the trial was stopped much earlier than planned-albeit for good reasons-it answered the key question regarding how best to prevent further, disabling seizures in this patient population."
Though not addressed in the study, Schomer and Lewis also stress the "critical importance of early diagnosis." They say "recognizing the signs and symptoms of epilepsy early in the primary care setting and getting patients referred to level III and level IV epilepsy centers is essential for patients to receive the attention they need, including medical management, neurosurgical evaluations, counseling, and work training."
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently
ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit