For many people with epilepsy, seizures persist despite the best available medications.
The constant, unpredictable risk of seizures sharply limits the kinds of activities a person can participate in. Ongoing seizures also can lead to an early death. Sudden Unexpected Death from EPilepsy, or SUDEP, is not fully understood, but may result from seizure damage to areas of the brain that regulate breathing or blood pressure.
Now, in a small pilot study, researchers at UCLA have demonstrated that a vibrating device applied to the hand or foot can reduce the frequency of seizures by more than 40% in patients with severe epilepsy.
"Wearable devices are revolutionizing neuroscience, cardiology and diabetes care," says Christopher DeGiorgio, MD, vice chair of the department of neurology at the David Geffen School of Medicine at UCLA. "This non-invasive device stimulates deep brain structures in the cerebellum and may reduce seizures in those with severe epilepsy."
Though more research is needed, peripheral cerebellar stimulation, invented by Ron Harper, PhD, distinguished research professor of neurobiology at the medical school, has the potential for advancing the care of people with severe epilepsy.
The study was a first test of how well patients can tolerate the treatment and whether it would reduce seizure activity.Dr. DeGiorgio recruited five patients between the ages of 22 and 36, all at high risk of SUDEP due to uncontrolled seizures, to participate in the trial. Every participant had previously tried at least three medications, and none had successfully controlled the seizures.
The results were published in the journal Frontiers in Neurology.
For many patients with epilepsy, medications either don’t work or the side effects make them intolerable at high enough doses to see a benefit. For those patients, there’s a lack of options, says Dr. Harper, lead author on the study.
“The interventions we have are pretty scarce,” he says.
Surgery to remove the troublesome part of the brain can help some patients, as can electrical stimulation targeting brain regions or specific nerves affecting seizure onset, but those options are expensive and invasive.
“There is a part of the brain located just under the back of the skull, called the cerebellum,” he says. “If you stimulate particular sites within that structure, often that stimulation shuts down seizures.”
Stimulating the cerebellum directly involves surgery to implant an electrode, which is invasive and carries a risk of infection.
Link between cerebellum and hand and foot nerves
In search of a non-invasive treatment, Dr. Harper hit on the connection between the cerebellum and the nerves in the hands and feet.
“Every neonatologist knows that if a neonatal patient stops breathing, you rub the sole of the foot and they’ll start breathing again,” he says. “Well, what is that? That’s activating the proprioceptors of the foot.”
Proprioceptors are a type of nerve cell that help us feel where we are in space. Being able to keep your balance with your eyes closed, or to touch your fingertip to your nose without looking, are examples of proprioception. The nerve fibers project to the cerebellum and are activated with running or walking.
These proprioceptor nerves also help stimulate breathing. Though it may seem surprising that nerves in the feet can trigger breathing, it makes evolutionary sense, Dr. Harper explains.
“If you come across a lion, you have to run, but you don’t have time to build up the CO2 that’s normally needed to enhance breathing for your survival,” he says. “If we relied on CO2 to increase breathing in such an encounter, the whole species would have died out.”
Fortunately, during the course of evolution, limb motion was reflexively coupled with breathing, so running concurrently increased air exchange.
Given that proprioceptive nerve impulses activated by running can travel from the feet (and hands – a holdover from when running involved all fours) to the cerebellum, and electrically stimulating the cerebellum can reduce seizure frequency, the researchers decided to test whether stimulating the proprioceptors in the feet and hands could slow the frequency of seizures.
“We thought, if the cerebellum is playing this role in coupling breathing with running, and it suppresses epilepsy, why not activate it in the same way?” Dr. Harper says. “Lo and behold, it works.”
Decline in seizures
The device uses a dime-sized vibrating disc taped to the ball of the foot or the palm of the hand. Study participants wore the device overnight and researchers tallied their seizures over the course of the study period. Three of the patients participated for 12 weeks; two continued using the device for 24 weeks. The two who stuck with it longest experienced the largest drop in seizure frequency.
None of the participants reported unpleasant side effects from using the device, but those who quit after 12 weeks cited the nuisance factor of dealing with it each night. A simpler, more convenient gadget could improve compliance, Dr. Harper says.
In addition to reducing the number of seizures, the device seemed to improve the patients’ mental function.
“We talked to their caretakers and they universally said, ‘he’s much brighter, he’s paying attention more, he’s more alert,’” Dr. Harper says. “They really improved, cognitively and behaviorally. We didn’t have hard measures on that aspect, except for an improved behavioral score; these are largely anecdotal reports, but that’s a good outcome.”
This cognitive boost could result from the reduction in seizures, or it may be due to improvements in sleep quality from better breathing overnight, Dr. Harper says.
This study, although tiny, suggests that non-invasive vibratory nerve stimulation in the hands or feet can reduce seizure frequency safely and without medications. Further studies are in the works to explore the effect of proprioceptor stimulation combined with stimulation targeting other brain areas, and to develop a more user-friendly device.
Caroline Seydel is the author of this article.
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