Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.

Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And today, we are highlighting the latest exciting developments in epilepsy surgery. Joining me is Dr. Adeel Ilyas. He's a neurosurgeon and an Assistant Professor of Neurosurgery at UAB Medicine. Dr. Ilyas, thank you so much for joining us today. I'd like you to start by setting the table for us on the prevalence of epilepsy and how treatment has evolved over the last 10 to 20 years. What have we learned a little bit more than we knew a decade ago?

Adeel Ilyas, MD: First of all, thank you so much for having me. Epilepsy is a prevalent condition, maybe more so than people might realize. It affects about 1-2% of the world's population, and it particularly affects low-income patients, patients without access to resources and also affects those in the deep south.

The first step in epilepsy treatment is accurate diagnosis of epilepsy. And that involves an EEG. It involves a physical exam, understanding what the patient experiences when he or she has a seizure. At that point, once the epilepsy has been diagnosed, medication is the first line of treatment, and there are all sorts of medications. Various therapies have come about recently, and we're not going to get into all that. But the patient should ideally be referred to an epileptologist, someone who specializes in the medical management of epilepsy.

And the key point here is that after treatment, appropriate treatment, that's an appropriate dosage and duration of two anti-seizure medications, if the patient continues to have seizures, at that point, the diagnosis is drug-refractory or medically-refractory epilepsy. Numerous studies have shown that when a patient is drug refractory, the chance of adding more seizure medication, so third, fourth, or fifth seizure medication, the probability of achieving seizure freedom is significantly less. In other words, adding more medication does not greatly improve the chance for seizure freedom. So, the recommendation is that once a patient has failed two appropriately dosed seizure medications, that he or she be referred to a comprehensive or level IV epilepsy center for the surgical evaluation of epilepsy.

Melanie Cole, MS: Well, thank you for that. So Dr. Ilyas, UAB is a level IV epilepsy center and the only one in Birmingham and Central Alabama. Can you tell us a little bit about the center and the multidisciplinary team that you've assembled? And tell us a little bit about what's exciting there.

Adeel Ilyas, MD: So, there are multiple facets of epilepsy and epilepsy surgery. There is the epileptologist, patient's neurologist who specializes in epilepsy treatment. There is the social worker and the team responsible for coordinating care for the patient. There's a neuropsychologist. Epilepsy is a disease, not only of seizures, but also of cognition. Patients who experience multiple seizures over time can suffer memory problems difficulty with processing, difficulty with understanding visuospatial constructions, language difficulties. So, all of these cognitive problems are a component of epilepsy as well.

And so, in our level IV Center, comprehensive Epilepsy Center, we have a dedicated neuropsychologist who also evaluates these patients. Then, there is the Epilepsy Monitoring Unit. This is a dedicated space in the hospital where patients are admitted. There is equipment geared toward understanding their seizure dynamics. There is staff that is trained in the management of epilepsy patients to help treat seizures and to help patients as they're being evaluated in the hospital. So, that's a critical component as well. And then, there's the epilepsy surgeon. As an epilepsy surgeon, I implant electrodes. These are either depth electrodes or subdural grids that either penetrate the brain or lie on the surface of the brain to record activities directly from the brain to help localize seizures. I do other procedures such as brain resections and removal of the epileptogenic tissue in the brain. And there are other procedures as well that we can talk about. But all of these people and facilities are integral to creating a comprehensive, holistic management team for epilepsy patients.

Melanie Cole, MS: We're going to expand a little on the surgical options available, but how have they evolved over time to encompass a wider variety of epilepsy types and applying epilepsy to more patients? Can you speak a little bit about how that's changed and why it's encompassing a wider variety?

Adeel Ilyas, MD: So, in terms of, as a neurosurgeon, procedures that I do, epilepsy surgery is one of the most effective neurosurgical procedures that is backed by level one evidence. The number needed to treat is two for an anterior temporal lobectomy for the treatment of temporal lobe epilepsy. So, there's, like we mentioned here, there's different types of epilepsies. And one of them, the most common, drug refractory epilepsy is temporal lobe epilepsy.

So, a surgery to remove the parts of the brain and the temporal lobe that are producing seizures is incredibly effective. So, that's one type of surgery that is a resection or removal of the seizure focus. And we do this type of surgery when the patient has what's called focal onset epilepsy. The epilepsy arises from a specific part in the brain, a focus of the brain. And that, if removed, renders the patient seizure-free, which is truly life-changing for these patients. Imagine not knowing when another seizure will happen. The physical injury associated with seizures, the risk for sudden death. These patients have a standardized mortality ratio of about 3, 3.3. So, removal of the seizure focus is of incredible benefit.

Now, some patients who have a seizure focus that instead of removal of, we can do what's called stereotactic laser ablation or a laser interstitial therapy, LIT. And in this procedure, instead of doing an open craniotomy and resection, we stereotactically-- that means using a specialized coordinate system-- place laser into the brain, into that seizure focus, and deliver a controlled burn of that seizure focus to eliminate it from the brain. So, that has really become mainstay, I would say, of epilepsy therapy now. And probably, it began in the past decade or so, but it's an evolving and effective therapy. So, open resection and laser ablation or LIT are two options for definitive treatment of focal onset epilepsies.

Now, in some cases, we are unable to, or the epilepsy itself does not have a focal onset. So if that's the case, then we have other therapeutic options that have only sort of come about recently and we're still understanding how to best utilize these. So, these are neuromodulatory options. And in neuromodulatory options, there are two, maybe three main subcategories.

So, the first is vagal nerve stimulation. Vagal nerve stimulation has been around for, I would say, 20 years, maybe more than that. And in this procedure, we place a coil around the vagus nerve, the left vagus nerve to deliver electrical stimulation that helps reduce the severity and frequency of seizures. So, that's vagal nerve stimulation. Number two is deep brain stimulation. Deep brain stimulation has been used in movement disorders, patients with Parkinson's disease and tremors, dystonia. It's been used for many years. And recently, we've begun to use it for the treatment of epilepsy as well.

 So, we placed an electrode into a deep structure of the brain called the thalamus, and we deliver electrical stimulation continuously to the thalamus to again reduce the seizure frequency and severity. And finally, there is responsive neurostimulation. In responsive neurostimulation, we implant electrodes at the place where seizures we think may be beginning or also sometimes into a deep structure such as the thalamus for detection and stimulation when seizures occur. So, these are three emerging neuromodulatory options. Some are approved for usage, and others are more experimental and exploratory. So, it's important to talk with the epilepsy surgeon about available options and what can be used in a specific case of epilepsy.

Melanie Cole, MS: Dr. Ilyas, as we get ready to wrap up, and I'd like you to speak about what you see happening in the world of epilepsy surgery, what you would like to see happen? And do you feel that despite the growing appreciation for the deleterious effects of drug-resistant epilepsy, as you've been discussing here today, do you feel there are too few surgical referrals? And if so, to what do you attribute that as you see what's going on in your field?

Adeel Ilyas, MD: I am glad you brought that up. If I could convey one message in this talk, it would be epilepsy is a chronic and debilitating disease. We know that after two seizure medications, the likelihood of seizure freedom with the addition of more medications incredibly low.

And so, it is extremely important for patients to be referred to an epilepsy level IV epilepsy center for a surgical evaluation. I think the number of patients who have drug-refractory epilepsy versus the number that are refer referred, there's a big discrepancy. And patients are being unreferred. And in my mind, that is a potential disservice to these patients.

There are multiple reasons and a lot of studies have been done as to why patients are not referred. And sometimes it's because patients fear having brain surgery, which is completely understandable. I would say that in our era, brain surgery for epilepsy surgery is safe. We have a lot of new technologies to help localize seizures. And if we can't localize them to help mitigate seizure burden, and I think, if anything, at least a conversation with an epilepsy surgeon or with the epileptologist, who is an expert in surgical management, would be fruitful to help address and alleviate some of these concerns.

And for the providers, it's really important to develop a connection to refer these patients to our center and to others that do advanced epilepsy care and comprehensive epilepsy care, including surgical treatment.

Melanie Cole, MS: Thank you so much, Dr. Ilyas, for joining us today and sharing what's going on in the exciting world of epilepsy surgery. Thank you so much. And for more information, you can visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole.