In Epilepsy Care, Non-pharmacologic Research Takes Center Stage

What were the biggest stories in epilepsy care this year?

Laura Jehi, MD: There were quite a few stories this year. One of the big ones was the approval of responsive neural stimulation (RNS), also known as NeuroPace. I think that was one of the biggest things that patients and physicians equally have been waiting for.

We have a patient population that continues to have intractable epilepsy despite the currently available medications and surgery options. So, we’re always looking for new ways to treat them, and NeuroPace is an attractive new technology that is less invasive than doing a surgical resection, and at the same time has the theoretical advantage of stimulating the focus that the seizures are coming from. Theoretically at least, it is a treatment option that we hope will give us a more targeted treatment compared to the vagus nerve stimulation (VNS) that is now being used. It offers hope for patients who are not deemed to be candidates for traditional resective epilepsy surgery.

We have quite a few patients that we have implanted already here at the Clinic, but it’s too early to tell. What we know from it is from the results of the clinical trial: around half the patients had around a 50 percent reduction in their seizures. That’s really the only solid knowledge we have about it.

Evelyn S. Tecoma, MD, PhD: One thing that a lot of people are talking about is the use of medical marijuana. That seems to be captivating everyone from patients to physicians to family members. Several nationally broadcast stories have created a lot of buzz and lot of questions and a lot of hope.

I do think that there are people with very specific forms of epilepsy who are benefiting, but those hopeful anecdotes need to be verified in a multicenter, randomized, double blinded research protocol. Some studies are currently underway in the pediatric population. Another thing holding back research right now is the fact that marijuana is a Schedule I substance, the most highly restricted, making it hard for researchers to develop protocols that fit into a university or private practice setting because of the restrictions.

With so many types and causes of epilepsy, it is likely that there are sub-populations that will benefit from medical marijuana, especially with the use of CBD oil, which has very low psychoactive properties. I don’t think it’s going to be a panacea for the vast majority of patients but I think it’s going to be a pretty good start for a lot of sub-populations. Patients should continue to work closely with their neurologists as they try these substances, as concomitant drugs may need to be adjusted.

Regarding therapeutic development, there are new ways of approaching epilepsy surgery with minimally invasive techniques like MRI guided laser ablation. In carefully selected patients, where the seizure focus is known, the lesion can be approached through a small opening in the skull, instead of a traditional craniotomy. With heat generated by the laser, the surgeon can destroy a small amount of tissue at a time under MRI guidance. For the right patient, I think this provides a minimally invasive alternative to traditional epilepsy surgery. Patients may go home the same or next day in most cases.

What were some of the important overlooked stories?

Dr. Jehi: There were studies that have been published related to the genetics of the epilepsies. There are many large consortia like Epi4K or EPGP studies that have been really working hard to try to identify some genetic causes for different types of epilepsy syndromes. They have been identifying several changes in the genetic composition, if you want, of patients with different types of epilepsy.

I think maybe one of the reasons why some of those papers were overlooked is because it’s still very challenging to translate their findings to the clinical realm. We do the genetic analysis and we find changes but it is hard for us to know what’s the pathological and what’s the normal variation, and how do those things truly relate to the epilepsy. Nonetheless I think it’s a big step in us trying to understand the disease, and it’s a necessary step if we’re going to target our treatments in the future and understand the pathology of epilepsy better. I think any work that goes along those lines is work that deserves to be acknowledged and encouraged because it will help us down the road.

Another one that made some splash but should have received more attention is some epidemiological work that was done to look at the constitution of intractable epilepsy patients electing surgery and the distribution among the different types of epilepsies that are now getting surgery. There is some data to show that, in addition to mesial temporal sclerosis, we have many other significant types of pathologies that may be becoming more and more relevant when it comes to surgery. This is a finding that I think deserves to be highlighted and acknowledged because it drives a lot of clinical work as far as thinking where we should focus our treatments, but also our research. So far it’s mostly been focused on understanding temporal lobe epilepsy very well, but not so much so on extratemporal epilepsy.

What do you think 2015 has in store for epilepsy care? Are there any studies you’re looking forward to? Are there any new trends in patient management that might emerge?

Dr. Jehi: It will probably hold a lot of NeuroPaces being implanted and us really learning how effective the device is.

We only have the results from the clinical trial, but we don’t know very well how to target it, and how to adjust it, and how does it compare to the other methods of stimulation— mainly VNS—so we will be learning a lot more about these things within the next year.

What I hope, is that we will able to use knowledge that we are getting from observational studies and from randomized studies, so that we can provide better patient-centered care and have more information that would guide us with providing individualized care. I hope in 2015 we will be able to at least plan the work—the types of studies that are necessary—so we can implement that type of personalized medicine. Whether it be better ways to identify their comorbidities like depression, anxiety, and get the screening done earlier, get the treatment done earlier. Or whether it be with ways to provide them with the medications that they need rather than the ones they may have side effects from. Learn more about better ways to do personalized medicine in epilepsy.

Dr. Tecoma: Probably more of these minimally-invasive surgeries and (NeuroPace). I think we need to see how that plays into the armamentarium of the typical epilepsy center. Up until now we’ve had vagus nerve stimulation, which provides indirect brain stimulation via the vagus nerve, and has been widely used in refractory epilepsy for over 15 years.

RNS is a technology that both detects and treats seizures if you know the seizure focus. It is implanted into the skull with electrodes placed on or into the brain at the sites of seizure onset. The device provides an electrical stimulation to the brain (which cannot be felt by the patient) in response to EEG signals that indicate a seizure in progress. It’s not that easy for a patient to accept the idea of attaching a battery operated electrical delivery device to their skull. We need to see how it plays out in a typical epilepsy center population, now that clinical trials have been completed; so far the only patients whose outcomes have been reported are those in clinical trials, and they are reported in improve over time with longer use of the device. There is also a learning curve for programmers and physicians in choosing the patients and matching stimulation parameters to the epilepsy syndrome.

Lara Jehi, MD, Director of Clinical Research at the Epilepsy Center in the Cleveland Clinic

Evelyn S. Tecoma MD, PhD, Professor of Neurosciences at the University of California, San Diego and Associate Director of the UCSD Epilepsy Center