Sara Staggs, a writer in Portland, OR, was diagnosed with epilepsy in 1981 when she was 18 months old. Treatment options for her then were limited to a few different medications. Today, there are more than two dozen drugs and many other therapeutic options. Staggs knows: She's tried almost everything, and while she's seen some improvement in the frequency of seizures, her epilepsy is still considered uncontrolled.
About one-third of the approximately 3.4 million Americans who have epilepsy have seizures that are not controlled by medication alone, according to data collected during the 2021 National Health Interview Survey. That statistic has remained constant over time, even when only one antiseizure medication was available, says Vikram Rao, MD, PhD, associate professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences.
But innovations in epilepsy treatment are accelerating, says Jacqueline A. French, MD, FAAN, professor of neurology at NYU Langone Health and a director of the Epilepsy Study Consortium. In years past, patients with uncontrollable seizures would see incremental improvements, if any, when they tried new therapies. Today, Dr. French says, the potential exists for treatments that end seizures as well as therapies that cure the underlying disease. “In maybe five years, we might have drugs in development that could take epilepsy away,” she says. “This is the evolution from ‘Let's try to eliminate your seizures' to ‘Let's try to eliminate epilepsy.'”
Given these possibilities, she and other epilepsy specialists are hopeful about the future. Here is what they consider promising.
Antiseizure Medications
Treating epilepsy always begins with antiseizure drugs, says Dr. Rao. Currently, patients have more than 30 options approved by the U.S. Food and Drug Administration (FDA), and some of them have control rates as high as 20 percent, he says. “To get one out of five people [with previously uncontrolled epilepsy] seizure free with medicine is really dramatic,” he says.
That was the case for a patient of Gregory Krauss, MD, professor of neurology at Johns Hopkins School of Medicine. The patient's weekly frontal lobe seizures caused him to jump up and down and use foul language. In 2015, Dr. Krauss enrolled the patient in a clinical trial for cenobamate (Xcopri). Within months the patient was seizure free and has remained so ever since. Cenobamate was approved by the FDA in 2019. Clinical trials show that about 20 percent of people who had drug-resistant epilepsy who added cenobamate to their regimen no longer had seizures.
Many of Dr. Krauss' patients have seen their seizures stop after standard antiseizure medications have failed. “I have many patients with drug-resistant epilepsy who try several new therapies in clinical trials and eventually [respond] to one of them,” he says.
Another drug in clinical trials, XEN1101, has proved effective for adults with focal epilepsy. In a phase 2b trial, results of which were published in JAMA Neurology in October 2023, those with drug-resistant epilepsy who took XEN1101 as add-on therapy reported a 33 to 53 percent reduction in monthly seizures, depending on the dose. Of participants who chose to extend the trial, 11 percent reported no seizures after a year or longer.
“A substantial group of people stopped having seizures altogether,” says Dr. French, who was the lead author on the study. “That's what we're striving for.” Even after the seizures stop, people must continue taking the drug as prescribed every day since the underlying disease is still present.
“Even if you've taken antiseizure drugs faithfully for a decade, if you miss two days, you're just as likely to have a seizure as when you started,” Dr. French says. “The fear of missing a single dose hangs over your head. We recognize this and want to change it.”
Other advances on the medication front include rescue therapies (fast-acting medications used for breakthrough seizures or seizure clusters) that can be administered via nasal spray.
Surgery
For many patients with uncontrolled epilepsy, surgery can be an effective treatment. A 2018 study in PLOS One found that for most people, surgery resulted in either no seizures or a significant and long-term reduction in seizures. The best candidates for this operation are those with relatively small, localized seizures that can be targeted precisely.
Two developments have made surgery more accessible. The first is laser ablation (laser interstitial thermal therapy), which destroys the suspected source of seizures through a small opening in the skull. The second is that insurance has started covering laser ablation, although some companies still consider it experimental.
The precursor to laser ablation is resective surgery, which requires a craniotomy or removal of a portion of the skull to get at the tissue or lesion causing the seizure. “If we tell families that we can make their children's seizures go away through open brain surgery, most say no,” says Adam P. Ostendorf, MD, an epileptologist and associate professor of pediatrics at Nationwide Children's Hospital in Columbus, OH. “But if we say the procedure can be done with holes about the size of the tip of your finger, about 50 percent of those families who would have said no now say yes,”
Laser ablation, which can cost more than $40,000, generally pays for itself in five to seven years in fewer medications and reduced office, emergency room, and hospital visits, he says. “And that's not including indirect costs like missing work or school.” No procedure is 100 percent successful, but Dr. Ostendorf now has patients who are cured and no longer take any medication. “We see them in our follow-up clinic and they look so happy,” he says. “After a year or so of monitoring them, we say, ‘Bye for now.' It's wonderful to see the consequences of unrelenting seizures lifted.”
While more adults with epilepsy are choosing laser ablation, many still balk at the idea. Dr. Rao understands. “This is your brain. This is the organ that is the most closely related to who we are, and the prospect of surgery on that organ is scary,” he says. “But we've been doing these surgeries for 50 years, and thousands happen each year. Roughly 80 percent of people are free of seizures after surgery, but there are no guarantees, and that means 20 percent of even the most carefully selected patients still have seizures.”
Dr. Rao believes those odds are worth it. “I tell these patients that surgery gives them a very good chance of seizure freedom, the best chance of any therapy I can offer,” he says. “I think it's safe, and if you are a good candidate, I think you should do it. I don't have anything else that offers this level of significant improvement.”
Neurostimulation
For some patients with focal epilepsy who are not candidates for surgery, doctors may recommend one of three implanted neurostimulation devices—vagus nerve stimulation (VNS), responsive neuro stimulation (RNS), or deep brain stimulation (DBS). They work differently, but they all deliver electrical energy to the brain to reduce seizures over time. The longer people have a neurostimulation device, the better their outcomes. In a review in Epilepsy & Behavior in 2023, the authors found that RNS and DBS were more effective than VNS at reducing seizures in patients with drug-resistant focal epilepsy.
“The truth is we don't fully understand how the devices work. We're still learning,” says Dr. Rao, noting that multiple studies have shown the devices to be effective. “DBS might have the effect of ‘calming' hyperexcitable circuits, but we don't think of it as acutely aborting seizures, as RNS does, for example. No approved devices are currently able to alert patients to an impending seizure.”
Stereoelectroencephalography
Finding the source of seizures is one of the goals before surgery, and stereoelectroencephalography (stereoEEG or sEEG) is increasingly being used to help with that, says John M. Stern, MD, director of the epilepsy clinical program at the David Geffen School of Medicine at UCLA. It's a minimally invasive and precise way to map the brain, locate the area of the seizure, and determine whether the seizure can be eliminated through surgery. If surgery is possible, stereoEEG can help surgeons determine how much tissue needs to be removed and how to avoid removing tissue important for brain function.
With the patient under general anesthesia, surgeons place a rigid frame on his or her head to keep it from moving. They then drill tiny holes in the skull and implant electrodes in the brain in areas where the seizures appear to originate. After surgery the patient has a CT scan and an X-ray of the skull so doctors can see the exact location of the electrodes.
From there, the patient proceeds to an epilepsy monitoring unit, where a team of doctors looks for seizure activity. The electrodes are connected to equipment that records brain activity, and a computer creates three-dimensional pictures of the start and spread of seizures. The data—location of the seizure, whether other brain functions are affected, and other factors—can inform treatment options, whether surgery, an implant, or antiseizure medications. StereoEEG provides diagnostic information during a hospital stay, and electrodes are removed before the patient returns home.
“With the collected information, doctors can personalize surgical treatment,” says Dr. Stern. That could mean removal of the brain tissue causing the seizures or placement of electrical stimulation devices that reduce seizures' severity and frequency. After some stereoEEG evaluations, doctors may decide against surgery.
With stereoEEG, doctors can “look deep inside the brain at parts we couldn't see before,” says Dr. Ostendorf. “Now we can use neurostimulation to treat patients that we couldn't help before. It gives us a totally new approach to therapy,” he says. “Before, we would have just shrugged our shoulders at these patients and said, ‘We're sorry. There's not a lot more we can do.'”
Gene Therapy
Increasingly, clinicians are screening people with epilepsy, especially children, for genetic mutations, says Anne Berg, PhD, adjunct professor of neurology in the division of epilepsy and clinical neurophysiology at the Feinberg School of Medicine in Chicago.
“Testing is helping us identify root causes of specific developmental brain disorders that ultimately lead to seizures as well as a host of other ramifications,” says Dr. Berg. “Identifying the genes and their associated molecular pathways opens up possibilities for precision therapies that could correct the disease process.” In theory, this may do more than lessen or eliminate seizures. It may also improve other key aspects of the disease.
“Here's an analogy,” she adds. “You can take a Band-Aid and cover a melanoma [skin cancer] so you can't see it, but that doesn't make it go away. A lot of seizure medications calm the seizures but don't treat the disease, and the disease has its own consequences.”
A study co-authored by Dr. Berg published in JAMA Neurology in 2022 found that genetic testing provided more information—about specific genes and other underlying diseases—that led doctors to adjust treatments (initiating, adding, changing, or stopping medication; referring to a specialist; or monitoring for other neurologic disorders), which in many cases improved outcomes.
In 2020, Blue Cross of California became the first health care plan in the country to cover whole genome sequencing—which captures changes in genes that can contribute to disease—to diagnose critically ill babies and provide precision care for children. If, after this testing, doctors are still unsure what is causing a patient's seizures, they have detailed sequencing to consult as science advances. For example, if they notice a variant in a certain gene but don't know what it means, they might have an answer or greater insight years later when researchers determine what that variant does. “You often don't have to repeat the test. You just have to reinterpret the results,” Dr. Berg says.
Stem Cell Therapies
Dr. Rao believes stem cell–based treatments have the potential to address the cause of epilepsy. “Anti-seizure medicines suppress symptoms. They don't address the root cause,” he says. “With stem cell therapies, if the root cause is an unbalanced electrical activity in circuits, maybe adding certain types of cells will normalize that balance and make the brain tissue less likely to generate seizures.”
Stem cells have no designated function and can renew and re-create functional tissue. In 2023, in a clinical trial funded by Neurona Therapeutics, doctors at the University of California, San Diego, injected stem cells that produce gamma-aminobutyric acid, which blocks overactive impulses between nerve cells and the brain, in seizure-prone parts of the brains of patients with drug-resistant epilepsy.
The hope is that the new cells will migrate and reduce excitability, thus limiting seizures. According to preliminary data, seizure frequency was reduced by 90 percent. “This approach has the potential to be curative, although much work remains to verify its efficacy and durability,” says Dr. Rao.
Harnessing Hope
“New technologies, amazing new treatments, and new discoveries are always in the pipeline, and they are being developed at a breathtaking pace,” Dr. Rao says. “Maybe not as fast as we or our patients would like, but things are evolving rapidly.”
Even artificial intelligence (AI) may be helpful one day, says Dr. Rao. By assimilating large amounts of accurate and evidence-based data, AI could help doctors make decisions about treatment, he says. “In principle, this might relieve doctors of the burden of determining the best course of action based on limited personal experience,” Dr. Rao says. “And AI could free physicians to do things machines can't do, like talk with patients, understand their goals, empathize with their concerns, and explain the rationale for diagnostic and treatment recommendations.”
It's the promise of a different future that keeps Sara Staggs trying new therapies. When she was younger, she avoided talking about her epilepsy. Now she's a patient advocate. Besides speaking to the press, she wrote Uncontrollable (Black Rose Writing, 2023), a novel about a woman who, like Staggs, could die if her seizures aren't addressed. While the main characters are fictional, the medicine and the procedures described are ones Staggs has experienced personally.
“To anyone with epilepsy, I want to say that I know that it's hard. I understand that if you have uncontrolled seizures, no matter if they're daily, weekly, or monthly, you're always thinking about them,” she says. “But you've got to have hope. At some point, there will be some medication or therapy that will work for you.”
Connecting to Community
Having epilepsy can feel lonely, says Phil Gattone, 37, who was diagnosed with the disorder at age 4. He remembers being bullied and shunned by schoolmates because he was different. What has kept him going—then and now—is the support of his family.
But he knows that others with epilepsy aren't so lucky. That's what prompted him to launch Neurish, a company that develops applications and software for people with epilepsy and their supporters. Its largest current project is FriendsWithEpilepsy.com, a social network for patients, caregivers, friends, and families that has more than 1,100 members. The network also has a news page with disease and treatment information.
“The website allows you to build your own support system, connecting you with people in your area and globally,” says Gattone, whose father was the longtime leader of the Epilepsy Foundation before retiring in 2020. “You can start a discussion or simply tell your story. You can ask questions or seek advice, and within minutes people start responding to you.”
Other organizations developing software to make living with and managing epilepsy easier include the Epilepsy Foundation, which has a searchable database of patient-friendly devices and apps. (The organization does not give recommendations.) My Medic Watch, for example, is a smartwatch app that can detect falls to alert caregivers. The Epsy app provides medication reminders and allows users to track seizures and triggers. Epihunter is a wearable device that recognizes absence seizures and alerts others when they happen. Epilepsy Journal is a free app available in multiple languages that can help people monitor their seizures. The Epilepsy Foundation also offers My Seizure Event Diary online.
Neurish is creating software for an epilepsy diary that will allow users to keep careful track of their seizures—timing, type, and duration—and record their feelings or make any other relevant notes.
“Recording your seizures might not necessarily help you predict future seizures, but it might allow you to spot a pattern,” Gattone says. “What's triggering the seizures? How do I feel before I have seizures? Are there certain things that happen that act as triggers?”
Gattone manages his own condition with a mix of medication and lifestyle changes, including getting adequate sleep and minimizing stress. “It's tricky because you always want to challenge yourself and be out there living and having fun, but at the same time, you have to recognize your limits,” he says. “Some people with epilepsy feel they're too different, like they're broken. That's completely wrong. Epilepsy is just one part of your life.”
