Rachael Malez, 13, is one of among a third of epilepsy patients worldwide who doesn’t respond well to seizure medication, and among the many who can’t undergo surgery and don’t see success with a ketogenic diet, two other options commonly used to treat the condition. But in June, the Food and Drug Administration (FDA) approved a new device for epilepsy in patients 12 and older, giving hope to families of patients like Rachael.
The implant, called the AspireSR generator, detects changes in heart rate that can signal a seizure. The device then generates an electrical current that travels through the longest cranial nerve in the body— the vagus nerve— and into the brain to mitigate a seizure when it strikes, improve recovery time from the event, and, ideally, abort it all together. A seizure occurs when there is a sudden surge of electrical activity in the brain that causes physical convulsions, disruptions to the senses and sometimes loss of consciousness.
“We don’t know exactly how far she’ll come, but we’re hoping that there will definitely be an improvement,” Rachael’s mother, Ruth Malez, 54, told FoxNews.com. “We want [Rachael] to understand and to know what’s going on around her more, and participate in life in general.”
Doctors at Children’s Hospitals and Clinics of Minnesota implanted Rachael with the AspireSR device on Thursday, July 30. After allowing for the nerve to heal, two weeks later they turned on the device. Rachael, of St. Michael, Minnesota— about 25 miles northwest of Minneapolis— is among the first adolescent patients in the United States to be implanted with this version of the generator.
It’s too early to tell whether the AspireSR device will help Rachael, said Rachael’s physician Dimitrios Arkilo, a doctor in pediatric neurology and epilepsy at the Minnesota Epilepsy Group. Her condition is the result of two rare, life-threatening disorders, Aicardi syndrome and Lennox-Gastaut syndrome. But doctors are working on determining the precise parameters of the device for Rachael, and they hope to see early results in the next few months.
Studies have shown that about 82 percent of epilepsy patients experience increased heart rate during the onset of a seizure. Vagus nerve stimulation (VNS) typically results in a 50 percent reduction of seizures, Arkilo said.
Stopping seizures before they strike
The vagus nerve affects various anatomical functions— extending from two branches on the left and right sides of the chest to the brain, heart, lungs and intestines, among other parts of the human body. Because the vagus nerve plays a role in sending messages from the body to the brain, researchers hypothesized that interfering with it could help treat epilepsy. Dr. Basim M. Uthman, vice chair and professor of clinical neurology, and professor of clinical neuroscience at Weill Cornell Medical College, helped pioneer VNS in the late 1980s.
“When [the AspireSR] generates that electrical impulse, this pulse travels along the nerve up to a relay station— it’s called the nucleus solitaries— from there, it will project to different areas of the brain, including the hippocampus. So our hope was that this was interrupting that ongoing seizure activity and hopefully stopping the seizure,” Uthman, also a neurology consultant at the Hamad Medical Corporation and the Academic Health System in Qatar, told FoxNews.com.
The AspireSR device features a hockey-puck-shaped, pacemaker-like generator that is implanted in the chest under the collarbone. To implant the device, doctors wind electrodes around the left vagus nerve through a 6-centimeter incision in the neck, take the wires attached to those electrodes and tunnel them through a cylindrical device placed under the skin, and then connect them to the generator.
Potential complications of implanting VNS generators like the AspireSR device include chest wound infections or bleeding, but the procedure isn’t as risky as brain surgery, said Andreas Alexopoulos, staff physician and director of clinical and research fellowship programs in epilepsy EEG and clinical neurophysiology at the Cleveland Clinic, who specializes in surgical management of epilepsy.
Epilepsy patients who have only focal seizures, or seizures centralized in one part of the brain, can see a reduction in seizures from brain surgery. But Rachael’s epilepsy is diffused, so surgery isn’t a good treatment option.
Implanting the AspireSR generator is an outpatient surgery that usually takes one hour to perform, and requires two to three hours for recovery. Meysam Kebriaei, a pediatric neurosurgeon at Children’s Hospitals and Clinics of Minnesota, who implanted the AspireSR in Rachael, said her surgery was typical in those respects and “went very smoothly.”
Customizing vagus nerve stimulation
There are five different versions of this type of VNS device that have been tested on patients since the late ’80s. While current version of the AspireSR generator measures 52 millimeters by 52 millimeters and weighs 25 grams, its predecessor was about 40 percent smaller and 35 percent lighter, Alexopoulos said. The reason the latest model heavier and larger is its new feature: a pacemaker-like function.
Uthman said previous versions of the VNS generator were programmed to turn on for about 30 seconds then be off for five minutes in an open loop. If caregivers noticed an epilepsy patient was about to undergo a seizure, they could flash a magnet over the implanted device, manually activating the electrical current if it was in the “off” phase.
“The open loop idea is supposed to reduce the number of seizures overall, as if you’re taking a medicine every day … and what you expect is the medicine will reduce the number of seizures over time,” Alexopoulos told FoxNews.com. But with a closed-loop, “the device can deliver the stimulation at the time of the seizure, and hopefully abort the seizure, or usually make it shorter or less severe. The essential difference is that this stimulation can be delivered at the time of the seizure because it can sense changes in the heart.”
Rachel’s doctor Arkilo and his colleagues are continually observing how stimulations from the AspireSR are impacting Rachael’s seizures, and they are continually adjusting its parameters to try to reduce the frequency of her convulsions. They use a wand and a tablet to wirelessly draw information from the device. A doctor can place the wand over the patient’s chest to draw data and can use a synced tablet to program the device by stimulation frequency, length and strength, as well as by pulse width.
The AspireSR logs heart rate changes and records the correlation of the device’s electrical current generation with these changes, which indicates how accurately the device prevents seizures. In Rachael’s most recent visit to Arkilo’s office, the AspireSR was successfully sensing and delivering a stimulus to 90 percent of her seizures.
Holding onto hope for improvement
While the device hasn’t yet reduced the frequency of Rachael’s seizures, it has already allowed her parents to reduce her daily medication, a success doctors didn’t expect to see so soon. That consequence alone has provided a welcome respite for her family, as Rachael has tried every epilepsy medication available in the U.S.— about 20— since early childhood. When Rachael was between the ages of 6 months and 2 years old, she had more than 50 seizures a day, and in 2011 she went from having one to two seizures a day to between five and 15 daily. At that point, she began going to the hospital frequently due to seizure injuries, like falling forward during a convulsion.
To prevent head injuries in the event of a fall, Rachael always wears a helmet, and because her diagnoses have rendered her ambulatory, she is wheelchair bound. Her father, Stephen Malez, usually carries her up and down the family’s two-story home to her bedroom upstairs two to three times a day.
Rachael now takes five anticonvulsant medications for her seizures: Vimpat, Sabril and Felbatol, Clonazepam, plus another medication she’s taking as part of a clinical trial, which her parents and doctors could not disclose due to a confidentiality agreement.
She suffers from several types of seizures: focal and generalized seizures, consisting of tonic, tonic clonic, focal with and without a change in the level of consciousness, as well as myoclonic. The medication she must take for cluster seizures have daylong sedative effects. For long seizures, Rachael takes a form of liquid Valium called Diazepam, and, as is common among epilepsy patients, she is at a high risk of infection and pneumonia, Arkilo noted. Today, Rachael’s parents must rush her to the hospital once a month on average.
“The only thing worse than having to be in a hospital for a child with epilepsy is having to come back,” Arkilo said. “That’s the number-one goal for Rachael: not having to be readmitted for a seizure.”
About 5 percent of patients implanted with a VNS generator experience pain around the neck and mouth, vocal paralysis, vomiting and mood changes, “but usually the changes are improvement,” said Alexopoulos, the Cleveland Clinic physician.
Uthman, the neurologist at Cornell, has observed that patients implanted with previous devices request re-implantation after eight to 10 years, the battery life of the device. He echoed Alexopoulos, saying the AspireSR doesn’t come with nearly as many side effects as medications do, like rashes, liver problems, or weight increases.
“That’s the beauty of it,” Uthman said.
Rachael’s family said her epilepsy has impacted them financially and emotionally, but it hasn’t affected the spirit of the young girl, who likes Christmas lights, objects that jingle when you shake them, and her 2-and-a-half-year-old Labrador retriever, Sally.
“[Rachael] is very loving, very happy,” Stephen Malez, 54, told FoxNews.com. “She’s probably going through a lot of frustrations in her mind with all the seizures, and I think that’s the reason she likes to snuggle up next to somebody and be loved.”
“It has been a rough road from the very beginning,” Malez said, “but she was the number-one priority, and so we’ve done everything we could.”