Tumor associated epilepsy: Dr. Katie Peters

Reported by Nancy Volkers

In this episode of Sharp Waves, we welcome renowned neurologist and neuro-oncologist Dr. Katie Peters from the Preston Robert Tisch Brain Tumor Center to discuss the important connection between brain tumors and epilepsy. Dr. Peters shares her expertise on how brain tumors can contribute to seizure disorders, the challenges patients face, and the latest approaches to diagnosis, treatment, and care. Whether you're a healthcare professional, patient, caregiver, or simply interested in neuroscience, this insightful conversation offers valuable perspectives on navigating these complex neurological conditions. Tune in for an engaging discussion with one of the field's leading experts.

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Podcast Transcript

Nancy Volkers: Welcome to this episode of Sharp Waves. This week we are talking about brain tumors and epilepsy, and we have Dr. Katie Peters here with us. I'm going to let her introduce herself with a little more detail. Dr. Peters?

Dr. Katie Peters: Hey, thank you so much, Nancy. My name again is Dr. Katie Peters. I'm a neurologist and neuro-oncologist at the Preston Robert Tisch Brain Tumor Center at Duke University. And I'm delighted to be here today.

Nancy Volkers: We're delighted to have you.

So, talking about brain tumors and epilepsy, can you set the stage a little bit? What percentage of epilepsy, ballpark, is caused by brain tumors, and how many people with brain tumors will have epileptic seizures?

Dr. Katie Peters: That's a great question because I feel like once we sort of put those two together, both populations get a little bit nervous and worried. So it's nice to dispel any myths.

For all patients with epilepsy, only about 4% will have a known brain tumor diagnosis associated with it. So it is pretty rare that if you have an epilepsy disorder, you're going to have an associated brain tumor.

But for our patients who are diagnosed with brain tumors, about one-third of them will initially present with a seizure and will have what we call brain tumor-related epilepsy because of those events. Then during the disease course or trajectory, somewhere between 30% and 90% of those patients will end up having some kind of seizure. It really is dependent on a myriad of factors, including tumor location. We're also learning more and more about how the type of tumor can sometimes dictate whether you have a seizure or not.

Nancy Volkers: Well, that leads perfectly to my next question. I don't know how many types of primary brain tumors there are, so just for the audience, we're talking about primary brain tumors—tumors that originate in the brain, not metastatic tumors. We will touch on that later, but not tumors that started somewhere else and spread to the brain.

What types of primary brain tumors convey a higher risk of tumor-related epilepsy compared to other types?

Dr. Katie Peters: Interestingly enough, the types of brain tumors that are associated more with underlying seizures and epilepsy tend to be what we call low-grade tumors. These are tumors that are a little bit more indolent.

In the neuro-oncology world, we grade tumors by how aggressive they look under the microscope. We then have another layer of tumor classification where we look at the genetic underpinning or molecular markers. But it tends to be those lower-grade tumors—the ones that look less aggressive under the microscope.

Part of the reason is that they tend to be located in places associated with seizures. For example, there are certain types of tumors that like to occur in the temporal lobe, so they're more likely to be associated with epilepsy and seizures. Whereas tumors in the back of the brain, particularly the posterior fossa, may cause neurologic symptoms but are not usually associated with epileptic syndromes.

So again, it's really those low-grade tumors. There are also other factors we'll discuss later that predispose patients to developing seizures.

Nancy Volkers: Great. Thank you.

There's a term—I'm not sure how to pronounce it—it looks like LEATS, L-E-A-T-S. Could you describe this term? It's used a lot in the literature on brain tumors and epilepsy. Could you talk about the different types of brain tumors that fall under that umbrella?

Dr. Katie Peters: Yeah, so this is an interesting category. I'll be honest, it's not terminology I use a lot because I'm more in the tumor world, but I can see how it's useful.

LEATS stands for long-term epilepsy-associated tumors. These fit into a subsection of particular tumors that are WHO Grade 1 tumors. The classic examples are tumors that like to occur in the temporal lobes.

One is a ganglioglioma. Another is a dysembryoplastic neuroepithelial tumor, or DNET. These are both WHO Grade 1 tumors associated with refractory epilepsy. They tend to occur near the cortex and, in some circumstances, may be connected to focal cortical dysplasia, which is also associated with epilepsy.

There are also newer entities, such as diffuse astrocytoma with MYB alterations and a very rare tumor called PLNTY, which stands for polymorphous low-grade neuroepithelial tumor of the young.

The good news about these tumors is that if they can be identified and are surgically accessible, a skilled neurosurgeon can often remove them, which may significantly improve or even control the patient's epilepsy.

Nancy Volkers: That leads perfectly into my next question. What is the prognosis for somebody with a brain tumor that is causing epilepsy? Maybe we could talk first about the tumors that can be surgically treated.

Dr. Katie Peters: For the tumors we just described, those LEATS tumors tend to be well-defined and more circumscribed, which means surgeons can often achieve a very good resection. Those patients can do quite well both from a survival perspective and an epilepsy perspective.

When we move into the Grade 2 category, we're talking about diffuse low-grade tumors. These tumors are more infiltrative. The brain is a little bit like Jell-O floating in cerebrospinal fluid, and these tumor cells spread into normal brain tissue. Because of that, complete surgical resection is essentially impossible.

Patients with diffuse low-grade tumors, such as IDH-mutant diffuse gliomas, can enjoy long survival, but the tumor will eventually recur and require additional therapies.

High-grade gliomas are unfortunately very aggressive malignant tumors. They can grow quickly and, while they can be associated with seizures, they are not as seizure-prone as lower-grade tumors. These tumors almost always recur and carry significant morbidity.

Nancy Volkers: Thank you. So alternatives to surgery—do people with tumor-associated epilepsy take anti-seizure medications? Are they provided options for VNS or DBS? Are certain medications preferred?

Dr. Katie Peters: That's a great question and it's very important.

Most patients who have both a brain tumor and a seizure will end up taking anti-seizure medication. If a patient has a brain tumor but has never had a seizure, we do not recommend prophylactic anti-seizure medication. That's part of the American Academy of Neurology guidelines.

However, if they've had a seizure, we do recommend treatment.

It's important to balance medication side effects because our patients may also be receiving chemotherapy, radiation, corticosteroids, or anticoagulants. We generally try to use the lowest effective dose and prefer monotherapy whenever possible.

A common medication we use is levetiracetam. We tend to avoid enzyme-inducing anti-seizure medications because they can interfere with chemotherapy, corticosteroids, and other treatments.

If patients require multiple anti-seizure medications, that's often when we involve epilepsy specialists. VNS and DBS can be used, but those circumstances are relatively uncommon.

Nancy Volkers: Can you talk a little bit about mechanisms? What causes the seizures?

Dr. Katie Peters: Absolutely. This is an area that's very close to my heart because it's fascinating.

The first mechanism is the obvious one: a tumor is an abnormal mass in the cortex, and it creates an irritable focus.

Another mechanism involves disruption of the blood-brain barrier. As tumors grow and alter the surrounding environment, they can increase the likelihood of seizures.

But the most interesting mechanisms involve communication between tumor tissue and brain tissue. Research has shown that glutamate transport becomes dysregulated around tumors. Glutamate is an excitatory neurotransmitter, and excess glutamate can create a pro-seizure environment.

Some tumor mutations may also directly promote seizures. One example is the BRAF V600E mutation, which occurs in tumors such as PLNTY, gangliogliomas, and pleomorphic xanthoastrocytomas.

Perhaps the most exciting discovery involves IDH1 and IDH2 mutations. These mutations produce a molecule called 2-hydroxyglutarate, which resembles glutamate and can promote seizures.

We now have a class of drugs called IDH inhibitors. One of them, vorasidenib, has been FDA approved. It blocks the mutant enzyme and reduces 2-hydroxyglutarate levels.

A recent study published in Lancet Neurology showed that patients taking vorasidenib experienced reduced seizure frequency. That could be because the drug shrinks tumors, lowers 2-hydroxyglutarate levels, or both.

Nancy Volkers: Very cool. So the tumor is actually producing a molecule that's a lot like glutamate.

Dr. Katie Peters: Exactly.

Nancy Volkers: Thank you so much for joining me today.

Dr. Katie Peters: Thank you. It was a great session.