New treatment options for people with drug-resistant epilepsy

Doctor

An estimated 65 million people worldwide have some form of epilepsy; one in 26 Americans will develop epilepsy in their lifetime. Many of these people are able to control their seizures with medications, but between 30 to 40 percent have what’s called drug-resistant or medically refractory epilepsy, in which they don’t respond to standard anti-seizure medications.

James Tao, MD, PhD, is a neurologist at the University of Chicago Medicine who specializes in the diagnosis and management of epilepsy. We spoke to him about the different surgical and neurostimulation treatment options for patients with drug-resistant epilepsy.

Are you able to use any of the standard medications for someone with drug-resistant epilepsy?

This is obviously a very significant challenge in managing a patient with drug-resistant epilepsy. We try to use combinations of different medications, typically with different mechanisms of action, hopefully to achieve the best effectiveness in terms of seizure control.

We also try to minimize the side effects because when you use multiple medications, side effects are always a big concern. Often times we are trying to strike a balance between good seizure control versus minimizing side effects. This is easier said than done with medications. A lot of times it's trial and error. Some patients may prefer to have the seizures controlled as much as they can, while other patients feel like the side effects are really debilitating. They would accept an extra seizure a month to have fewer side effects or have a better quality of life between seizures.

With the medication, patients will have a seizure baseline, from a few seizures a year to seizures every month or every week. Some patients may have seizures every day. Unfortunately, this is a reality for most patients with drug-resistant epilepsy.

What are the side effects from epilepsy medications?

Most patients feel very sleepy, drowsy or lack energy. Others have cognitive impairment. Their memory gets impaired because of the medications, or their ability to speak can also be impaired. There are also a lot of metabolic side effects. Many of these medications can disturb liver function. They can cause bone density issues. A lot of times these drugs can interfere with treatments for other medical conditions such as diabetes or high cholesterol. These side effects are very common and they can be worse in drug-resistant patients where we may be trying combinations of medications.

Have the mainstream drugs been improving over the years?

It's kind of stagnant to some degree. One of the challenges is that in the 1980s, we only had a handful of traditional seizure medications. Now we have 25 medications, but the percentage of people with drug-resistant epilepsy is still the same. What's really changed now is that some of the new generation of medications actually have a better side effect profile with comparable effectiveness. So now we treat with medications with fewer side effects, which is significant for our patients, too, because the side effects can be just as debilitating as seizures.

For a patient who is drug-resistant, what are some of the other options besides medications?

Traditionally, there are a few options available for people with medically refractory epilepsy. The most common one is epilepsy surgery, which has been performed since the 1940s. It is a very mature procedure, very reliable, but most of the surgical treatment is still open brain surgery. For a patient with focal epilepsy, where the seizures are being caused by one part of the brain, you try to remove the seizure focus. Somewhere between 60 and 70 percent of patients with drug-resistant epilepsy who have this surgery become seizure-free, which is the standard of care if the medications were not to work. So, any patient who has drug-resistant epilepsy should be evaluated for surgery.

Open brain surgery is effective but also carries higher risk for complications, pain and psychological impacts. Recently, minimally invasive epilepsy brain surgery has advanced quite significantly, particularly a procedure called laser ablation for patients with epilepsy. In that surgery, we insert a small laser fiber and burn away the seizure focus but don’t have to open up the skull.

Our center is one of the leading centers for epilepsy laser ablation in the country. We have been performing these techniques for the last five or six years and have been developing quite a bit of knowledge and expertise. Nowadays, 80 to 90 percent of the epilepsy surgery in our center is minimally invasive through laser ablation. We think this is a paradigm shift in technique. Patients with epilepsy should be considered for the minimally invasive technique if possible. If it doesn't work, then the open brain surgery is still available to them.

Are there other options besides surgery?

Unfortunately, only a small percentage of patients are eligible for surgical treatment because the seizure focus has to be in a location that can be safely removed without an impact on their functions like language, strength, vision, etc. But in some of these patients, the seizure focus cannot be clearly localized or the seizure focus overlaps with important brain functions. Then we cannot perform surgery for them. What do we do?

Now we have neuromodulation or neurostimulation devices. The FDA has approved three different devices: vagal nerve stimulation (VNS), responsive neurostimulation (RNS) and deep brain stimulation (DBS).

How do they work?

They are very similar technologically. VNS is implanted like a pacemaker under the skin near the collarbone. The wires actually do not go into the brain. They are wrapped around the vagus nerve in the neck area. This one can be used for anyone who has epilepsy because it does not require a clear seizure location, and it is quite easy to implant.

RNS, however, requires knowledge of where the seizure focus is, then the device is implanted on the skull. They take a piece of bone out and fit the generator on the skull. Then there are two wires implanted inside the brain around the seizure focus. When the seizure comes, the device can detect it and send a strong electrical shock to abort the seizure. This device is very similar to a cardiac defibrillator. It's probably the most effective of all three devices in our experience, although it’s a little bit more invasive.

DBS is very similar, implanted inside the brain in the thalamus, a different part of the brain. It does not require a knowledge of the seizure focus but uses the wires to stimulate different areas to control seizures.

How effective are these devices?

In general, VNS reduces seizures by about 50 percent. They are not cures, but they improve the symptoms. For RNS, the expectation is around 60 to 70 percent seizure reduction over five years. DBS supposedly has comparable benefit to RNS, although we have less experience with it.

What other new developments are on the horizon?

Another major development is the use of marijuana or cannabis for treating epilepsy. It has been approved by the FDA for two pediatric epilepsy syndromes, one called Dravet syndrome, and another called Lennox Gastaut syndrome. Both of these types of epilepsy carry a high risk of intellectual impairment. The FDA approved CBD oil under a brand name called Epidiolex, and it has been proven to be effective for controlling seizures in these patients. We have a few patients in our clinic who show a benefit too, so this is a promising drug.

What is the outlook for patients with drug-resistant epilepsy?

I think we have made significant advances in the last few years. The major development is obviously the marijuana or CBD oil because it’s a completely different category of seizure medication that might be promising in combination with other medications.

We are also very excited about the minimally invasive surgery. This is a paradigm shift in surgical treatment. This technique is not available in any other country, and most of the epilepsy centers in the United States still don't use this technique. I think this will become the first-line surgical option for people with drug resistant epilepsy. And there is a lot of potential in the neurostimulation area. We are still in the process of building experience in terms of how these devices can be best used for different patients, but people really believe in the benefits.

James Tao, MD, PhD

James Tao, MD, PhD

James Tao, MD, PhD, specializes in the diagnosis and management of seizure disorders and epilepsy syndromes. Dr. Tao is interested in the use of surgery and vagal nerve stimulation for treating patients with medically resistant epilepsy.

Learn more about Dr. Tao