Seizure Treatment: Major Advances in Epilepsy Surgery Cure More People

More than ever before, people with epilepsy are living normal lives. The key is to get treatment, typically a medication, for seizures—the unpredictable disruptions in the brain’s electrical system that are the hallmark symptom of epilepsy. But treatment is more difficult for people with refractory epilepsy—a subtype of the condition in which medication doesn’t work well or at all. For years, their only option was to undergo an invasive operation, and many were told they weren’t eligible for surgery and would have to live with the seizures.

But brain surgery techniques have been advancing, which has meant a revolution for those with refractory epilepsy.

“Care has changed so much, even in the last several years, that many people who were once told they weren’t candidates for epilepsy surgery are now eligible,” says Lawrence Hirsch, MD, a Yale Medicine neurologist, epilepsy specialist (or epileptologist), chief of the Yale School of Medicine Division of Epilepsy and EEG (a test that measures electrical activity in the brain), and co-director of the Yale Comprehensive Epilepsy Center.

The advances are myriad. Some changes are new; others are existing treatments that have undergone various refinements. They include brain-mapping techniques that help surgeons preserve areas responsible for critical functions, such as memory and language, and minimally invasive approaches that allow the brain to be accessed through tiny holes in the skull using a robot for precision. Usually, the latter is done to remove the abnormal tissue in the brain responsible for the condition, but if that’s not an option, a device may be implanted to help control seizures.

Treatment, in general, is more comfortable, less invasive, and safer.

Dr. Hirsch and other Yale Medicine epilepsy specialists answered questions about the latest approaches and advances in refractory epilepsy treatment and how they are giving more patients a better quality of life—and, in some cases, providing a cure.

Epilepsy is the broad term for a brain disorder that causes seizures. The diagnosis is given to people after they’ve had two or more seizures that last a few seconds or minutes and that are not a symptom of another acute or reversible medical condition. In some cases, epilepsy is a symptom of pre-existing conditions such as stroke, brain tumors, or moderate to severe traumatic head injury, though often there is no apparent cause.

About 3 million adults and 470,000 children have “active epilepsy,” according to the Centers for Disease Control and Prevention (CDC). The agency bases its latest statistics on national data sources, including the 2015 National Health Interview Survey (NIHS), a continuing survey that collects data on a broad range of topics. The CDC defined active epilepsy in adults in the NHIS as having a history of doctor-diagnosed epilepsy or a seizure disorder and currently taking medication to control it or having had one or more seizures in the past year (or both).

There are two main types of seizures: focal (or partial) seizures, which affect one area of the brain, and generalized seizures, which affect both sides of the brain.

Seizures affect people differently, and one person can have different types of seizures. They can be as simple as a brief period of limb twitching while fully alert or suddenly feeling dazed—so quick as to be barely noticed. Or they can be more severe, including losing consciousness, falling to the ground, and having whole-body stiffening and/or muscle jerks or spasms. The most severe type of seizure is known as a “bilateral tonic-clonic” seizure, commonly referred to as a “convulsion” or “grand mal” seizure.

Medication is still the first line of treatment for epilepsy. There are more than two dozen drugs that can lower the level of electrical activity in the brain, helping to prevent or reduce the number of seizures. “This usually affords patients the choice of a medication with no side effects,” says Dr. Hirsch. “Years ago, many accepted side effects as a trade-off for seizure control, but that is no longer necessary for the majority of patients.”

While drugs won’t cure epilepsy, they allow an estimated 70% of people with the condition to manage it to the point where it barely interferes with their daily life, explains Dr. Hirsch. Some people may be able to stop taking their epilepsy medication if they have had no seizures for several years, but others will need medication all their lives.

“Unfortunately, the 30% of people who don’t benefit from drugs often struggle with their epilepsy,” says neurosurgeon Eyiyemisi Damisah, MD, an epileptologist and chief of Epilepsy Surgery for Yale Medicine. “We often see patients who have tried multiple medicines, but they were either ineffective or had intolerable side effects. So, they’ve continued to have seizures.”

Epilepsy surgery might be considered if two or more anti-seizure medications (without significant side effects) are tried and don’t stop the seizures, giving the condition the classification of refractory epilepsy. The goal of surgery is to identify and target the area (or areas) in the brain causing the seizures and remove or otherwise disable it, without harming nearby areas that regulate important functions, such as speech or memory.

Sometimes, surgery is a straightforward process—for instance, when an abnormal lesion in the brain is easily identified and located in an area where it is safe to remove. But there are cases where a visible lesion can’t be identified, and a procedure to implant a device that can manage seizures may be the better option (more on that below).

Any epilepsy surgery includes careful planning. For the patient, this can mean multiple tests to better understand the cause of their epilepsy. “It's a very extensive and extremely well-thought-out process,” says neurologist and epileptologist Adithya Sivaraju, MD, MHA. For some patients, the span of time to complete these tests can be as long as a few months, including a hospital admission.

For surgical evaluations, it is important to record seizures in the Epilepsy Monitoring Unit, a special unit in the hospital where the patient undergoes continuous video and EEG monitoring (more on that below). Medication is often lowered while in this unit to help capture a seizure.

The surgical planning process also includes (but is not limited to) MRI and/or PET scans, as well as tests that create different pictures of the brain to show abnormalities that could be responsible for seizures.

The most common test for epilepsy is an electroencephalogram (EEG), which involves pasting electrodes to the patient’s scalp to evaluate the electrical activity in the brain. If a patient is having a seizure, an EEG recording often shows the activity as rapid spiking that can help clarify the type of epilepsy a person has and from which region of the brain the seizures arise. For instance, generalized spikes can represent generalized seizures (coming from all parts of the brain).

If other tests are inconclusive, an intracranial (inside the skull) EEG can provide more information. This involves an invasive procedure performed under general anesthesia; however, the procedure is usually less invasive than it was 10 years ago, when it involved temporarily removing a section of the skull.

In many cases, the intracranial EEG requires only very small electrodes to be inserted into the brain through tiny holes in the scalp; this is also referred to as “stereo-EEG.” Computers, robots, and extensive imaging of the brain and blood vessels allow this to be done very safely and comfortably, explains Dr. Sivaraju.

Once the procedure is complete, the patient moves to the Epilepsy Monitoring Unit with equipment to record their brain activity 24/7 for a few days or up to two weeks. “This can help us determine, within almost a centimeter of precision, the part of the brain we need to target,” Dr. Sivaraju says.

The intracranial EEG is also a tool used for brain mapping, a process to determine the locations that regulate key functions to make sure they don’t overlap with an area that will undergo surgery. “If we are going to resect [or remove] a certain part of the brain, we must ensure that we're not causing any functional deficit to the patient,” says Dr. Sivaraju. “We map in great detail where the language representation is—meaning the part of the brain that processes language and makes it possible to read, write, and comprehend,” he says. “We also map motor and sensory function—the location in the brain responsible for the movement and sensation of your thumbs, hands, legs, elbows, and arms.”

When the brain tissue causing the seizures is identified, there are two types of surgery to eliminate it:

Resection (or cutting out the tissue causing the seizures): This is the traditional surgical treatment. While resection is the most invasive strategy, it’s also the best chance for complete freedom from seizures, and even those patients whose seizures aren’t eliminated will have a better chance for an improved quality of life. “Resection works best when the surgeon can pinpoint a single clear location in the brain that is not linked to a function,” says Dr. Sivaraju.

Several surgical procedures for epilepsy treatment were first developed at Yale, including one of the most commonly used resection techniques for removing parts of the temporal lobe, which is the most common area for seizure disorders. Yale Comprehensive Epilepsy Center co-director and neurosurgeon Dennis Spencer, MD, and his late wife, neurologist Susan Spencer, MD, pioneered the use of electrodes to determine exactly which part of the temporal lobe the seizures were originating from, followed by surgery to remove only that area.

"We are now able to look at those patients over 30 years and find that the outcomes are very good," says Dr. Spencer. "Patients who are good candidates for temporal lobe resection have a 75% chance of fully controlling their seizures."

Laser ablation to destroy the abnormal tissue: Laser ablation, also known as thermal ablation, is less invasive than resection (although it still uses general anesthesia and a probe placed into the brain in the area to be ablated). It can be effective for patients whose seizures emanate from a small region of the brain in a specific location that is easy to access and target.

This approach uses real-time intraoperative high-resolution MRI guidance to insert a small probe through a tiny hole in the skull to deliver a set amount of energy to the area that will be treated. The energy is changed to heat that burns away the tissue causing the seizures. (Yale has a dedicated MRI scanner in a specialized operating suite for these types of procedures.)

Laser ablation does not offer the same cure rates as resection, but it has a lower risk of side effects, requires a shorter hospital stay, and offers a quicker recovery. Dr. Sivaraju says the “seizure freedom” rate from laser ablation is about 60% compared with 70% or 75% for similar cases treated with resection. In some cases, laser ablation is performed first, and resection is planned if the seizures continue.

A third option, called neurostimulation (or neuromodulation), involves implanting devices in the body to control the seizures. Scientists have known for decades that seizures can be silenced using stimulation to the cerebral cortex, the portion of the brain responsible for such functions as consciousness, thought, memory, language, and personality.

Neurostimulation is considered when surgery or laser ablation is too difficult or risky, often because a clear focal point of seizure origin does not exist or can’t be identified. It is also considered when the region of seizure onset overlaps with important functions and, therefore, cannot be removed or ablated with a laser. “Before, when the medications didn't work and we thought a patient wasn't a good candidate for surgery, there were no other options,” says neurologist and epileptologist Imran Quraishi, MD, PhD. “Now, pretty much anyone with refractory seizures can benefit from some type of neuromodulation.”

An implanted device works like a dimmer switch that lessens the intensity and frequency of seizures and sometimes stops them before they start, Dr. Quraishi explains. “For most patients, the seizures still happen, but generally they'll be milder and less frequent than before.”

The rate of complete freedom from seizures is lower than with resection or laser ablation, and most patients also continue to take medication to treat the seizures. “If you put devices in a hundred patients, over time, at least 70 of them would have a 50% reduction in their seizure frequency,” Dr. Quraishi says. “Neurostimulation can make a significant difference.”

Some forms of neurostimulation are still being tested, and scientists are studying exactly how they reduce seizures. But three are approved by the U.S. Food and Drug Administration (FDA):

Responsive nerve stimulation (RNS): Approved in 2013 for adults 18 and older, RNS continuously monitors for seizures at their source and directly targets that source when it recognizes that a seizure may be starting. The device is implanted just under the skull, and two small attached wires go to the place in the brain where seizures have been identified as starting. When it senses potential seizure activity, RNS immediately delivers small bursts of stimulation that can help brain activity return to normal and minimize an oncoming seizure or stop it before it happens. The device also records brain and seizure activity, providing extensive data that is available online for physicians to monitor their patients’ epilepsy and help guide their treatment.

Deep Brain stimulation (DBS): This approach was FDA-approved for epilepsy in 2018 for people ages 18 and older. Similar to a pacemaker for the heart, DBS involves a device (like a battery pack) implanted in the chest. The device is attached to a wire that is snaked up under the skin to the brain to transmit ongoing stimulation, with the goal of blocking abnormal signals. The surgeon also makes two tiny holes in the scalp through which electrodes are inserted to reach deep into the middle of the brain, specifically in the thalamus, a central networking system that connects areas of the brain. “The thalamus is a central hub; if you stimulate that area, you can affect the whole brain,” Dr. Quraishi says.

In June 2020, the FDA also approved the Percept PC for deep brain stimulation. Yale was the first epilepsy center in the U.S. to implant the device for epilepsy. The device also records a patient’s brain signals from the thalamus, which is used to help adjust the device by determining how often to send the pulses.

Vagus nerve stimulation (VNS): Approved for epilepsy in 1997 for adults (and more recently for children 4 years of age and older), this device is implanted in the chest. An attached wire sends mild pulses of electrical stimulation to the vagus nerve in the neck, which transmits the pulses to the brain. Patients can wear a magnet on their wrist or a belt, and if they believe they are having a seizure—either experiencing an “aura” or a general sense that a seizure is about to happen—they (or someone else) can pass the magnet over the device in the chest to send an extra pulse of stimulation, which may help stop the seizure. The device is programmed to send pulses at regular intervals, with the goal of reducing electrical activity in the brain to lessen or prevent seizures. One common side effect of VNS is voice hoarseness while it is stimulating.

At one time, all patients were kept awake for epilepsy procedures, and it can still be helpful if surgery is performed near a part of the brain that controls such functions as movement or speech. In cases like these, a surgeon may ensure the safety of those areas by asking questions during surgery and monitoring the patient’s ability to respond.

But thanks to the extensive brain-mapping process, awake surgeries are usually not necessary, and many patients report that knowing they will be under general anesthesia means less pre-surgical anxiety, Dr. Sivaraju adds.

“While planning an epilepsy surgery can be a long process, the surgery itself has become easier, if only because minimally invasive approaches allow surgeons to avoid removing a section of the skull to access the brain in many cases,” says Dr. Damisah, who performs all types of epilepsy surgeries, from device implantations to laser ablations to resections. “Almost half of my epilepsy surgeries are performed robotically through 2-millimeter holes,” she says. “This makes hospital stays shorter and the precision a lot more accurate, and people do better.”

Patients have an extensive support network with a large team of brain specialists, including surgeons, anesthesiologists, neurologists, technologists, neuropsychologists, psychiatrists, and social workers, among others.

Still, the anticipation of surgery in the brain can spark anxiety. “There is an understandable fear people have when considering undergoing a brain procedure,” Dr. Hirsch says. “But epilepsy surgery is very safe and well tolerated. And there can be an immense benefit.”

Each treatment has unique risks that must be weighed against the benefit of potentially curing or at least reducing seizures, which also pose risks if they are not treated (more on that below). But the risk for epilepsy resection, the most invasive surgical procedure, is very low, usually around 1% for significant lasting complications that could include any damage to such functions as mood, memory, speech, or vision, explains Dr. Hirsch. The risk for side effects is even lower with laser ablation and neurostimulation.

There are cases where a patient may choose a resection that has a high chance of providing freedom from seizures, knowing that it will cause a small functional deficit—for example, a small loss of peripheral vision. “There are some cases where a small deficit might be acceptable for some patients if it means they can achieve seizure freedom. In those cases, we discuss all of it in detail with the patient,” Dr. Sivaraju says.

However, the goal is to avoid any impact on function, Dr. Sivaraju explains. Pre-surgical testing, tools such as functional brain mapping, and minimally invasive approaches have made it more possible to achieve this, he adds.

“The smartest strategy for managing risk is to have the surgery at a comprehensive epilepsy center with extensive epilepsy surgery experience, and by a surgeon who has performed the particular surgery many times,” Dr. Hirsch says.

“Patients should consider surgery as soon as it’s clear they can’t easily control their seizures with medication,” Dr. Hirsch says. “And this generally takes only two medication trials.”

One issue is that epilepsy can worsen over time if it goes untreated, he adds. Seizures can start to spread in the brain. If this happens, the risk of injury and death increases. “We start to see falls, head injuries, cognitive decline, especially with regards to memory, and other injuries, such as burns and dislocated shoulders,” he says.

Perhaps the biggest risk of unmanaged epilepsy is what’s called “sudden, unexpected death in epilepsy (SUDEP),” which is not well understood and affects 1 in 1,000 people with epilepsy each year. “The number is even higher in surgical candidates,” says Dr. Hirsch. “However, these odds are markedly reduced with successful epilepsy surgery.” In addition, people who have had seizures for years are more likely to develop cognitive issues, and many develop mood disorders, especially depression and anxiety, Dr. Hirsch adds.

But when they seek care, people find they have many options. If one treatment doesn’t work, there is a good chance that another one will cure—or at least reduce—their seizures, Dr. Sivaraju explains.

“We wouldn’t have been able to say this a decade ago,” he says, “but we now know that for every patient, there is something we can offer that may be better than medication, and it can significantly improve their seizures and quality of life.”