Conference Coverage

New Approaches Have Not Increased the Rate of Epilepsy Surgery


 

BETHESDA, MARYLAND—Surgery cures half of patients with refractory temporal lobe epilepsy, yet it is still highly underused, in part because of misperceptions about the risks and benefits, according to Edward F. Chang, MD.

Numerous studies have shown that 60% to 70% of patients are free of seizures one year after surgery and that at least half have seizure freedom over the long term, said Dr. Chang, Associate Professor in Residence of Neurological Surgery and Physiology at the University of California, San Francisco. The surgery also entails “well-documented quality of life improvements,” he said at Curing the Epilepsies 2013: Pathways Forward, a meeting sponsored by NINDS.

Data Support the Safety and Efficacy of Epilepsy Surgery

Based on the current evidence, the American Academy of Neurology, the American Epilepsy Society, and the American Association of Neurological Surgeons jointly published a guideline statement in 2003 that recommended the referral of patients with refractory epilepsy for surgery. But physicians are still not heeding that guidance, said Dr. Chang. His survey of clinicians showed that the rate of surgery had not increased in a five-year period after the joint recommendation.

Dr. Chang characterized the finding as “very depressing, in terms of how we are using evidence,” especially because the burden of epilepsy has increased. In some cases, patients have lived with epilepsy for as long as 30 years before being referred for surgery, he said.

Surgery is safe and effective, and the side effects are predictable, Dr. Chang noted. The number needed to treat for one patient with refractory temporal lobe epilepsy to become seizure free is two—a number that parallels the use of antibiotics for pneumonia. “We are below the standard of care,” said Dr. Chang. Clinicians and patients shy away from surgery because “brain surgery is too dangerous,” he said. Physicians do not understand the data, he added. Drug and device makers also are “spending millions of dollars telling patients there are other options,” he said, but if “we address this basic utilization problem, we’d see an immediate and substantial reduction ... in the burden of epilepsy worldwide.”

Making Surgery Less Intimidating

Several advances in surgical technique that have occurred in the past few years might make wary neurologists and patients more comfortable with the procedure. For instance, transcortical approaches use a small incision to go through the white matter to the hippocampus. With the subtemporal approach, “you don’t have to go through any lateral cortex at all,” noted Dr. Chang.

“Even for relatively large lesions that are quite deep in the brain, we can do these minimally invasive approaches by going underneath the lateral temporal cortex and selectively removing the hippocampus,” he added.

Nonsurgical, minimally invasive techniques under development have the potential to yield outcomes similar to those of surgery. NINDS is funding a pivotal trial of stereotactic radiosurgery. In this procedure, a device selectively delivers radiation to the hippocampus and mesial lobe and spares the lateral temporal areas. Overall, it is fairly safe, but some patients have severe swelling for as long as a year after the procedure, and most have no effect for at least a year.

Another approach being studied uses MRI to guide laser thermoablation. “A lot of us are quite excited about this,” said Dr. Chang. The MRI allows the clinician to place the laser accurately and study how much the tissue is heated, which can help researchers determine whether tissue has been damaged and whether the damage might be irreversible.

MRI-guided focused ultrasound uses the same principles as radiosurgery to target structures deep in the brain, said Dr. Chang. The procedure is in phase III trials for essential tremor.

On the other hand, “a lot of irrational exuberance” surrounds these technologies, he noted. It is not clear how to validate them, especially because clinicians have yet to determine how to validate other surgical approaches. A big obstacle for the surgery trials is the difficulty in recruiting patients. Many individuals do not want to participate, because they do not want to be randomized.

Research Could Improve Surgical Outcomes

Researchers also are trying to understand epileptogenesis better, to learn how to reduce procedural side effects, and to learn to predict effects on cognitive function. To achieve these goals, “we need to understand more about how human cognition works,” said Dr. Chang. Brain-mapping studies are showing that most aspects of cognition are not centered in one specific, focused area.

“Just like we’re thinking now that seizures are part of a distributed network, we also need to understand comorbidities and morbidity from surgical approaches in the same kind of framework,” he said. Until surgery is better used and studied, it is unlikely that neurology can truly understand the safety and effectiveness of the minimally invasive approaches, concluded Dr. Chang.

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