Treatment-Resistant Epilepsy: Neurologists Say “Don’t Give Up”
Treatment-resistant epilepsy affects roughly one third of people with epilepsy and can be vexing for clinicians and patients alike. Once two therapies have failed, additional drugs are thought to offer little help; the condition often worsens, or at best stabilizes, leaving patients with a changing roster of medications and little hope for continued improvement.
However, research from the Human Epilepsy Project 2 (HEP2) – a long-term, multicenter, observational study of patients with treatment-resistant focal epilepsy – has called that conventional wisdom into question. The center’s recent findings, published in JAMA Neurology, show that treatment-resistant focal epilepsy can improve over time, independent of changes in medications or devices.
David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center at Oregon Health & Science University in Portland, was not surprised by these results. “Several previous studies have shown that the reality is much more dynamic, and people may move in and out of extended periods of seizure freedom,” he said, pointing to a 2016 study in Epilepsia and his own commentary on this study in Epilepsy Currents. “These periods of seizure freedom or improved seizure control without seizure freedom can be very important to our patients.”
Nor were the results surprising to the co-senior author of the study, Jacqueline French, MD, professor in the NYU Epilepsy Center and founder/director of NYU’s Epilepsy Study Consortium. “As an epileptologist, it would be pretty depressing for me to believe that all my attempts to improve outcomes in people with treatment-resistant epilepsy were fruitless,” she told MedCentral. “My personal experience is that lots of people do get better.”
Active Management for Refractory Epilepsy
In the study, Dr. French and colleagues analyzed data for up to 3 years from 126 patients at 10 epilepsy centers across the United States. They found that 68.3% of participants had a significant reduction in seizure frequency – 13% were seizure-free for 3 months, 7.8% were seizure-free for 6 months, and 3% were seizure-free for at least 1 year. One participant was seizure-free for 15 months. There was no significant difference in seizure reduction based on device or medication changes.
More than half of those who experienced seizure reductions had an antiseizure medication added during the study. “This suggests,” the authors wrote, “that continued active management with medication adjustments may play a role in improving seizure outcomes.”
The team also found no significant seizure trajectory between non-device cohorts and cohorts using neuromodulation devices (eg, deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation), suggesting that participants both with and without devices experienced similar improvements over time. However, the authors noted that this does not imply that these devices are ineffective. Instead, “they may contribute to an overall treatment approach where active management plays a key role in seizure reduction,” they wrote in the paper.
Longer Study Needed to Change Practice
Nicole Bentley, MD, associate professor in the department of neurosurgery at the University of Alabama at Birmingham, said that the results are consistent with what she sees clinically. “Adding a new seizure medication will result in improved seizure frequency, or even seizure freedom, in the short term,” she said. However, she also said that over the longer term (longer than the time period studied) seizures tend to return to baseline. “Overall, the cohort was studied in a relatively short time window, and it would be great to see longer-term outcomes.”
Dr. Bentley also took issue with the conclusions that implanted devices and additional medications have similar results. “I would say to interpret this with caution, as it is well established that improvement in seizure frequency and severity with device implantation builds over time, even over several years, and the time period studied here does not capture that effect,” she said. “Additionally, the number of patients implanted with devices is overall low, underpowering the statistical analysis.”
Despite Treatment-Resistant Label, Good News Remains
Drs. Bentley, Spencer, and French all agree that the take-home message for clinicians is not to give up just because the patient continues to have seizures. “Some neurologists may be discouraged by this label of ‘treatment-resistant epilepsy’ and feel that it is not worthwhile to make active treatment changes because of the perception that they are unlikely to help,” Dr. Spencer said. “This study contradicts that notion and should encourage us to continue to make active changes in treatment.”
Dr. Bentley also stressed the role of surgical intervention and neuromodulation, stating that “although we are in early stages, and I think we have a lot to learn with these devices, I do think they contribute to improvement and seizure frequency over the longer term.”
Dr. Spencer agreed, pointing out that the medical devices have been shown to reduce the risk of sudden death in epilepsy and that patients with treatment-resistant epilepsy enrolled in drug studies are less likely to experience sudden unexpected death in epilepsy (SUDEP) in the active arm of treatment compared with placebo treatment.
“I think there are two pieces of good news,” Dr. French added. “Number one is that there is an enormous amount of development in epilepsy drugs. Every couple of years we get a new therapy. And number two, which I think is even more important, is that we are getting better therapies. So the bar has been raised.” Specifically, the therapies in development “have to achieve a higher standard than the ones that were in development a decade ago. Otherwise, they’re just not going to make it in a competitive marketplace. The only downside is getting them paid for. That is the fly in the ointment.”
Source: https://www.medcentral.com/neurology/treatment-resistant-epilepsy-neurologists-say-dont-give-up