Isla Ritchie was diagnosed with epilepsy in 2014 when she was 11. Her neurologist prescribed various medications to control her tonic-clonic and absence seizures, but she continued to have breakthrough events. During an absence seizure, she would stare blankly into space for a few minutes before returning to her normal alertness without knowing what she had missed. Ritchie's tonic-clonic seizures were more disruptive: Her limbs would shake, her muscles would stiffen, and she'd lose consciousness. If she was standing, she would fall. Sometimes a seizure would last more than five minutes, and she'd need rescue medication to stop it.
Ritchie and her parents investigated whether she could have brain surgery, but she wasn't a candidate due to seizure activity on both sides of her brain. In 2015, however, the family, who live in Houston, learned about vagus nerve stimulation (VNS), a procedure in which a device is implanted in the chest to stimulate the vagus nerve—which runs from the brainstem through the neck to the chest and stomach—with electrical impulses. They decided to try it along with Ritchie's antiseizure medication regimen.
After surgeons implanted the device in October 2015 and fine-tuned the stimulation over six months, Ritchie's seizures gradually tapered off. Four years have passed since her last one. “I can't even compare my quality of life to how it was in middle school,” says Ritchie, now 19 and a first-year student at Baylor University in Waco, TX. “Back then, my head felt so fuzzy I couldn't process things. Now I feel like a 10 out of 10. I've come a long way, and I no longer worry every day about having a seizure.”
Life-Changing Treatment
The vagus nerves—one on each side of the neck—are part of the parasympathetic nervous system, often called the “rest and digest” system because it helps the body relax after periods of stress or danger and regulates bodily functions such as digestion and heart rate. The vagus nerves provide a bridge between the brain and peripheral organs, and they play an important role in memory, emotion, and pain, among other bodily functions.
The idea to stimulate the vagus nerve in people with neurologic disorders came from a researcher who experimented on animals with hereditary seizures in the 1980s and found that VNS stopped their seizures, says George Morris, MD, MPH, FAAN, medical director for epilepsy at Ascension Medical Group in Milwaukee.
The U.S. Food and Drug Administration (FDA) approved VNS for the treatment of drug-resistant seizures in humans in 1997. Since then, the FDA has approved the procedure to treat drug-resistant depression, cluster headache and migraine, and for stroke recovery. It's also being investigated as a treatment for multiple sclerosis, rheumatoid arthritis, diabetes, post-traumatic stress disorder, Parkinson's disease, cognitive disorders, and traumatic brain injury.
Stopping Seizures
VNS for epilepsy involves a pacemaker-like device surgically implanted under the skin in the left chest area; a wire is attached to the generator, placed under the skin, and wound around the vagus nerve in the neck. The device is programmed to deliver electrical stimulation at regular intervals along the left vagus nerve to the brainstem, which then sends signals to certain areas of the brain; the person with the device doesn't feel the stimulation.
Despite its varied applications for neurologic disorders, it isn't clear how VNS improves these conditions. The results of an animal study, published in the Proceedings of the National Academy of Sciences in May 2022, showed that activating the vagus nerve reduced inflammation, which contributes to many different diseases, both neurologic ones and others. VNS also may positively affect rewiring of the brain and alter the balance between activity in the sympathetic nervous system (which is responsible for the body's fight-or-flight response) and the parasympathetic nervous system.
VNS is used in addition to medication for people with epilepsy. “The goal is to reduce the number of seizures,” says Lily Wong-Kisiel, MD, FAAN, a pediatric epileptologist and associate professor of neurology at Mayo Clinic in Rochester, MN. It also may allow people to decrease the dose of their antiseizure medication.
Although it doesn't cure epilepsy, VNS appears to become more effective at reducing seizures over time, unlike pharmacological therapies, says Dr. Morris. A study published in Neurosurgery in 2016 involving 5,554 people with intractable epilepsy on the VNS therapy patient outcome registry found that within the first four months of having the VNS device implanted, 49 percent of people saw a reduction in their seizure frequency, while 63 percent experienced a drop in seizures two to four years after having it implanted.
To manage seizures, VNS can be set on three modes: normal, auto-stimulation, and magnet. In normal mode, the device delivers electrical stimulation at regular intervals, so the person doesn't need to do anything. Auto-stimulation mode, available on newer devices, delivers an extra dose of stimulation based on an increase in heart rate. “Heart rate goes up in many people with epilepsy during and sometimes before a seizure,” Dr. Wong-Kisiel says. The additional stimulation may stop a seizure or shorten it once it's underway.
Swiping a magnet across the implanted generator to activate the stimulation is another way to disrupt a seizure. This is especially helpful for people who have an aura—a warning or a sense that a seizure is imminent—that precedes a seizure. “The magnetic activation stops or shortens a seizure two-thirds of the time,” says Angus Wilfong, MD, professor and chief of pediatric neurology at the Barrow Neurological Institute at Phoenix Children's Hospital and professor of child health and neurology at the University of Arizona College of Medicine–Phoenix.
VNS can cause temporary changes in the voice—making it sound hoarse or raspy—when the stimulator fires. But these are fleeting side effects and usually lessen over time, says Dr. Wilfong, adding that unlike antiseizure medications, VNS does not cause weight loss or gain.
In 2013, the American Academy of Neurology (AAN) updated its guideline for using VNS to treat epilepsy, stating that it may be considered adjunctive treatment for children with partial or generalized epilepsy. The guideline also notes that in adults having the procedure, an improvement in mood may be an additional benefit.
Overall, VNS may be considered progressively effective in patients over multiple years of use. In July 2022, the AAN reaffirmed the guideline.
Easing Headache Attacks
Anna Williams, 47, has had migraine since she was a kid and developed cluster headache (an abrupt headache with an excruciating burst of pain that occurs in groups or clusters before temporarily going away) in 2013, which became chronic in 2017. She tried different medications for her migraine and cluster attacks but ended up with mood side effects she couldn't tolerate. Eventually, she found some relief with a newer type of drug, which helped reduce the duration of the headaches, but she wanted more relief.
In May 2021, Williams found out about a handheld, noninvasive VNS device called gammaCore, which delivers self-administered electrical stimulation through the skin to either the right or left branch of the vagus nerve in the neck. She began using it twice a day to prevent cluster headaches, and within three months her chronic attacks disappeared.
“Initially, I was so focused on the cluster headaches that I didn't consider gammaCore for migraine,” says Williams, a mother of two teenagers in New Albany, IN. “Once the clusters were in remission, I was able to get my migraine under control by using gammaCore preventively.” Williams had cluster attacks mostly on the left side of her head and migraine attacks mostly on the right, so she began using the device on both sides of her neck three times a day.
A noninvasive portable device like gammaCore can prevent or weaken a migraine or cluster headache when it is held against the side of the neck so electrical stimulation can be delivered through the skin. “It can be applied to either side [of the neck], and the person can control the intensity of the stimulation,” says Deborah I. Friedman, MD, MPH, FAAN, a neurologist and neuro-ophthalmologist in Dallas.
A study in a 2018 issue of the Journal of Headache and Pain found that these devices were significantly more effective than a sham device (acting as a placebo) in reducing the pain of migraine attacks. And in a review of studies published in a 2018 issue of the Journal of Pain Research, investigators found that VNS led to a significant reduction in pain and a decrease in the duration of cluster attacks compared with sham stimulation.
“The stimulation seems to decrease pain signaling and dampen the sympathetic activity in the nervous system, which plays a role in migraine and cluster headaches and supports parasympathetic activity,” says Robert Cowan, MD, FAAN, professor of neurology and neurological sciences at Stanford University School of Medicine in California. “It also helps protect the brain from something called cortical spreading depression, which is like a slow-moving wave of altered brain activity that causes changes in nerve firing and blood vessel function and plays a role in migraine with aura.” When it's used preventively for chronic migraine or cluster headaches, people see a significant decrease in the number of headache days per month, Dr. Cowan says.
Doctors typically prescribe the device for people whose migraine and cluster headache attacks don't respond to medication or who can't tolerate the medications, Dr. Cowan says. In other cases, neurologists prescribe them in conjunction with medication.
Noninvasive VNS has no side effects and can be used during pregnancy and in children, Dr. Friedman says. But it's expensive and often not covered by insurance. GammaCore, for example, can cost $200 a month for those paying out of pocket. The manufacturer, however, has a patient assistance program to help eligible patients pay for the device.
“It's important for people to know these types of devices are out there,” Dr. Cowan says. “The challenge is paying for them. We would use them more if they weren't so expensive or if they were covered by insurance.”
Boosting Stroke Rehab
In one of its newer applications, VNS may enhance stroke recovery. “It has huge effects, but we aren't sure why,” says A.M. Barrett, MD, FAAN, chair of neurology at the UMass Chan Medical School and UMass Memorial Health Care System and chief of neurology at the VA Central Western Massachusetts Healthcare System.
A study in a 2021 issue of The Lancet investigated the effects of VNS therapy on people who had lost arm function as a result of an ischemic stroke. Those who did VNS therapy along with rehabilitation three times a week for six weeks saw twice the level of improvement in their arm function compared with those who received a sham stimulation along with their rehabilitation. “When you stimulate this nerve in the neck, it sends impulses through the brain that make it more amenable to rewiring and plasticity [reorganization],” says study co-author Steven C. Cramer, MD, FAAN, professor of neurology at UCLA and medical director of research at the California Rehabilitation Institute in Los Angeles. “Combining vagus nerve stimulation with occupational or physical therapy may result in more brain remodeling and improvements in behavior,” Dr. Cramer says.
The therapy can begin six months after a stroke, once acute inflammation has healed, and there's no upper limit to how long after the stroke it can begin, says Michelle P. Lin, MD, MPH, a stroke neurologist at Mayo Clinic in Jacksonville, FL.
In another new development, research suggests that a noninvasive VNS device placed on the skin of the ear may modulate activity in the vagus nerve after stroke. A study in a 2022 issue of Neural Regeneration Research found that when people who had had an ischemic or hemorrhagic stroke used this device along with conventional rehabilitation, they experienced significant improvement in their motor and sensory functions and emotional responses compared with the control group that had been given a sham transcutaneous VNS device with conventional rehabilitation.
Dr. Barrett is excited about the possibilities of VNS for stroke rehabilitation, especially since the U.S. Centers for Disease Control and Prevention reported that fewer than four out of 10 stroke survivors pursue or receive outpatient therapy. Experts say VNS also may help ease depression and improve cognitive skills and leg movements after a stroke. “I've seen people recover from drug-resistant depression with the use of VNS,” says Dr. Barrett. “And I've seen it help with depression-related cognitive symptoms.”
It certainly has helped Anna Williams and Isla Ritchie. Williams says VNS put her cluster headache attacks into remission, and she has had only one migraine since July 2022. “It gave me my life back in so many ways,” Williams says. “By using the newer medication with the gammaCore, I can now be more involved in my children's lives. I can go for daily walks with them, and I can travel again.”
These days, Ritchie, who lives on Baylor's campus, belongs to the Honor Society as well as numerous clubs and a sorority. She's also a dancer, choreographer, and entrepreneur: She and her mother launched a business called Go Bag, which contains necessities for unexpected trips to the ER. “VNS changed my life in a really positive way,” Ritchie says. “I can live my own dream and not be dependent on my parents.”
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