A mother places hope in novel hardware to control daughter’s epilepsy

On the morning of Thursday, Feb. 23, Candace Arick was packing her son’s lunch when she heard the familiar beeping. The siren-like alert emanated from an iPad she keeps with her nearly 12 hours a day; it notifies her when her daughter, Norah, is having a seizure. Norah, 7, lives with a pervasive form of epilepsy that causes around a half-dozen seizures per day, primarily during sleep. But nearly one month prior, surgeons had implanted a new medical device, called a vagus nerve stimulator, within Norah’s body to hopefully bring her seizures under control.

Out of habit, Candace started the timer on her phone. She raced from the kitchen to Norah’s room. There, she saw her daughter locked in a major seizure, stretched rigid in her bed, as if unseen forces were pulling her apart from head to toes. Norah’s arms reached stiffly over her head and her face was blank and tense. She was breathing fast, nearly hyperventilating.

Candace wondered: would the new device work and stop Norah’s seizure before she crossed into a state of exhaustion? If so, it would mean Candace and Norah would have a new, reliable partner in the fight against Norah’s epilepsy. If not, Candace would need to dose her daughter with so-called “rescue meds” to quell the seizure, leaving Norah upset and fatigued for the rest of the day.

Candace worked quickly to turn on Norah’s vagus nerve stimulation (VNS) device. She picked up a magnet attached to a strap that fit on her wrist like a watch, designed to switch on the VNS device. Candace pressed the magnet against Norah’s chest four times, once every minute. Meanwhile, she checked her timer. If Norah’s seizure lasted for five minutes, Candace would have to administer the rescue medication. The seconds ticked by while Candace waited anxiously as the seizure wracked Norah’s brain.

Candace and Norah had just joined the thousands of other families in the US who have used electricity to stop seizures. The VNS device aims to help patients gain some measure of control over drug-resistant epilepsy, which is very difficult to treat, yet fairly common, affecting as many as 30% of epilepsy patients. Failure to control these seizures results in a cornucopia of negative symptoms, including permanent brain injury or even death in the worse cases. Families of children with drug-resistant epilepsy often feel overwhelmed by the medications and lifestyle adaptations necessary to curb the impact of the seizures. Now, more and more families are electing to use VNS devices to help bring their child’s epilepsy under control.

While the VNS device has been available since the late 1990s, it’s only in recent years that physicians and families have gained enough experience with it to be confident that it provides a good alternative to drug treatments. A science paper that reviewed over 100 clinical studies of vagus nerve stimulation in patients under the age of 18, published in the journal Neurology in 2021, showed that VNS devices are safe and effective in reducing seizures by over 50% in roughly 50% of patients. And, in the last few years, patients and families have had the option to self-administer electricity to “break” a seizure with the swipe of a magnet.

Back in Norah’s bedroom on that Thursday morning, Candace hoped to see these benefits in her own daughter. Four minutes and 45 seconds after Candace started her watch, with fifteen seconds to spare, Norah’s body began to relax. Her arms lowered to rest by side and her face softened. Then, she opened her eyes and smiled up at Candace.

Candace was overjoyed. For the first time in many years, she felt hopeful about Norah’s future.

A shockingly long history

Though VNS devices have been available in the US for over two decades, many patients who could benefit from the therapy never hear about it. But in the field of neurology, VNS has a long history.

Nearly a century before Candace was born, a neurologist in New York attempted to curb seizures using electricity delivered to the neck. James Corning ventured to stop seizures by pressing the two tongs of a large wishbone-like implement into either side of his patients’ necks, presumably to suppress the blood flow to the brain. In 1884, he reported adding a jolt of electricity delivered through the apparatus. But the method was abandoned by Corning and his colleagues because of inconsistent results.

A century later, the idea was revived and refined in clinical trials of vagus nerve stimulation. In the early 1990s, an electrical engineer named W. Brent Tarver helped conduct some of the first human trials. While the experiments worked perfectly — the patients were safe and walked away with no obvious signs of harm — it took time to erase pre-existing fears. During one early human experiment, Tarver remembers a nurse storming out of the operating room after discovering the purpose of the surgery. “I know what happens when you stimulate the vagus, you stop the heart!” Tarver remembered the nurse exclaiming, adding, “I’m not going to be involved with this.”

Now, researchers like Tarver can point to over 125,000 patients worldwide, 35,000 of whom are children, who have had a VNS device implanted to treat epilepsy. The Food and Drug Administration approved vagus nerve stimulation in 1997 for patients over 12 years old with epilepsy not treatable by anti-seizure medications. VNS grew in popularity in the 2000s as more surgeons were trained to implant the devices. Throughout that time, surgeons implanted the device in younger patients for “off-label” use outside the specifications approved by the FDA. In 2017, VNS hit a turning point in pediatric epilepsy care when the FDA officially approved VNS for children as young as 4 years old. Tarver knows of patients as young as one year old with a VNS device.

Scrolling to a solution

Yet Candace Arick had never heard about vagus nerve stimulation until her daughter had struggled with epilepsy for six years. And then, it happened almost by accident, as Candace was scrolling TikTok one day. There, she saw a mother of a child with epilepsy talking about a treatment called vagus nerve stimulation. Candace wondered if it would work for Norah, who was diagnosed with epilepsy as a toddler.

Norah had traveled a difficult medical journey since birth. She spent nearly all of her first eight months of life in the hospital. She endured two intestinal ruptures and septic shock, which is a dangerous drop in blood pressure caused by a widespread infection. Much of Norah’s small intestines were removed following the intestinal ruptures, leaving her with short-bowel syndrome that made it difficult for her to tolerate food; Norah eats food smoothies now, and the rest of her nutrients are injected via a G-tube port into her stomach. A brain injury, caused by the lack of oxygen to her brain during septic shock, means she currently has the cognitive capacity of a one-year-old. She also lives with cerebral palsy, which makes it hard for her to walk and speak. The brain injury is also thought to have caused her epilepsy.

Candace remembers Norah’s first seizure at home when she was 14 months old. Norah was sitting in her high chair when, suddenly, her cheery face blanked and her head dropped to her chin. Her arms straightened out away from her body. For nearly a minute, Candace watched her distressed daughter helplessly. The seizure finally passed, leaving Norah disoriented and tired.

From then on, Norah’s life was punctured by seizures, sometimes up to 20 times per day. A variety of triggers could set off her seizures, including loud noises, like construction equipment or yelling, heat or stomach issues. But sometimes a seizure would appear out of the blue when Candace was brushing Norah’s hair. More recently, her seizures crop up during relaxation or sleep; Candace has been startled to find her daughter beginning to seize while they are snuggling on the couch.

Doctors prescribed an endless parade of medication to try to control Norah’s seizures. Candace estimates Norah has tried six or seven anti-seizure drugs. Each caused side effects, including grogginess or nausea. At the time that Candace learned of VNS on TikTok, Norah was stable on three medications. But Candace knew that soon, even higher doses would not keep her daughter’s seizures at bay.

Chasing stability

Norah is not the only one struggling with medications. Edward Novotny, a neurologist and director of the epilepsy program at Seattle Children’s Hospital, says that it becomes more difficult to treat seizures in pediatric epilepsy patients as they grow. The nature of seizures shifts in response to a maturing metabolism and brain. At the same time, children develop tolerance to anti-seizure medications, meaning the drugs stop working well for children the longer they take them. This prompts a catch-the-tail chase for the right drug, at the right time.

“Epilepsy in children is very dynamic,” said Novotny. “It’s a sort of battle between the two things.”

But this also makes Norah and other children like her a perfect candidate for neuromodulation devices, which speak in the language of the nervous system, using electricity to disrupt the synchronous pulses in the brain that characterizes a seizure. Anti-seizure drugs, in contrast, spread throughout Norah’s body on the journey to her brain, where they modify the chemistry of individual brain cells. “Neuromodulation is really growing as an alternative in pediatrics,” Novotny said.

One day after Candace saw the TikTok video on VNS, a neurologist slightly outside Norah’s typical circle of doctors suggested VNS to treat Norah’s seizures. Within a few weeks, Candace had scheduled the procedure for Norah. If all went according to plan, surgeons would implant the device on Monday, Jan. 30.

“Therefore, why wait?”

Vagus nerve stimulation, Norah’s new epilepsy treatment, is not a cure — cures are hard to come by in even the most straightforward epilepsy cases. But for Norah and other patients with epilepsy who have run out of options, VNS can make the seizures easier to live with by shortening them and reducing their intensity.

Seizures are caused when the brain malfunctions: abnormal brain activity temporarily interrupts the electrical functions of the brain. VNS attempts to interrupt the disruption with small zaps of electrical current injected into the vagus nerve. Nerves are long cells that stretch from the brain to a muscle or organ. The vagus nerve — specifically, the left vagus nerve — extends from the brain to the gut along the left side of a person’s neck. Information, in the form of electrical signals, darts between the brain and heart, stomach, or other organs.

Illustration by Nathan Michaelson. Epilepsy is typically treated with oral anti-seizure medications, which take minutes to hours to travel to the brain through the bloodstream. Vagus nerve stimulation is a new epilepsy treatment that controls seizures by pulsing electricity into the vagus nerve on the left side of the neck. The vagus nerve quickly transmits the electricity up to the brain and interrupts the seizure.

VNS devices add more electrical information to the flow of traffic traveling along the vagus nerve. The vagus nerve relays the electricity to the brain. Traditional VNS devices inject electricity into the vagus nerve at regular intervals, often every five minutes for 30 seconds. The newest VNS model, which came on the market in 2017, adds an extra dose of electricity when it detects increases in heart rate, a sign of an upcoming seizure, making the device more useful for patients with epilepsy.

Experts believe the brain adapts to neuromodulation devices over time — but they’re not sure exactly how. The longer the device is implanted, the current thinking goes, the more the brain positively responds to the electrical stimulation, boosting the benefits to patients. Patients may also be able to wean themselves off medications, avoiding the side effects of drugs, said Novotny.

“Therefore, why wait?” Novotny asked. “Not everyone gets a great benefit, but the individuals that do benefit from these devices get a cumulative benefit over time.”

A path to coexistence

The night before the surgery, Norah kicked her feet in the bath water, poking her toes above the bubbles piled high around her. Candace laid her hand on the left side of Norah’s chest, a few inches below her collarbone. “This is where you’ll get an ouchie tomorrow,” Candace said.

The next day, a Monday, Norah arrived early in the morning at Akron Children’s Hospital. She giggled as a case worker placed the gas mask over her nose and mouth to anesthetize her so she wouldn’t feel the surgery, then she was wheeled into a surgery suite with her stuffed white unicorn tucked safely in her arms.

There, pediatric neurosurgeon Tsulee Chen made two two-inch incisions, one on the left side of Norah’s neck and another below her left collarbone. Chen implanted the VNS device, which consists of two main components: three small slinky-like coils wrapped around Norah’s vagus nerve, and a battery in Norah’s chest that connects to the coils and generates the electricity. Chen said the vagus nerve looks like a linguini noodle and each coil is roughly the length of two grains of cooked rice.

Norah went home the next day. Ten days later, Norah returned to the hospital so that a doctor could activate her device. The doctor set the VNS device to deliver a pulse of electricity to Norah’s vagus nerve for 30 seconds every 5 minutes. Norah and Candace soon headed home to see how much, if at all, their lives would change.

For the first week, Norah did not have any noticeable seizures. Norah was sleeping better, in Candace’s opinion. One night, an hour after Norah went to bed, Candace tiptoed into Norah’s room to deliver her normal anti-seizure medications via her G-tube and heard her daughter quietly snoring. Norah’s sleep is often fitful, so this peaceful sleep so early in the night struck Candace as new — and adorable.

The seizures started up in the second week. They were unusually short, ten seconds or less, barely enough time for Candace to swipe the magnet during the seizure. Candace thought she saw the seizure stop right after the magnet swipe, but it was hard to tell.

Meanwhile, Norah was more consistently happy and content than she’d ever been, according to Candace. “It’s just really crazy to see such a huge change in her personality already,” Candace said at the end of the second week. “It has to be the VNS because nothing else has changed. I don’t think she’s ever been happy like she has been in the past three days.”

Then, the Big Seizure disrupted the positive two-week trend. Candace dutifully swiped the magnet every minute, as instructed, while holding the rescue medications in her hand. It was painful to watch her daughter adopt the familiar seizure posture for nearly five minutes, but the unopened rescue medications buoyed Candace’s mood. The VNS had stopped the seizure in its tracks, just in time.

Candace and Norah went to a neurologist appointment later that day — they’ll go every two weeks to increase the electricity dose for three months. The neurologist pulled the data from the VNS device. On the tablet, the neurologist could see the device turned on by itself multiple times in the early morning hours when it detected small seizures during sleep. Candace’s magnet swipes from the morning also showed up.

Now, Candace must wait and see how it works. She said she is more comfortable swiping the magnet when she notices pre-seizure activity. If Norah responds well to the VNS after six months, maybe her medications can be reduced, or some even taken away entirely. As Norah nears her eighth birthday, Candace hopes her daughter’s personality will blossom; Norah’s vocabulary may even increase, or perhaps she will learn to walk independently.

“If we can coexist with her seizures — I don’t know if she will ever be seizure free,” Candace said. “But if they can tame them down to where they don’t affect her as much, that’s just huge.”

© 2023 Elissa Welle / UC Santa Cruz Science Communication Program