'Pacemaker for the brain' being studied

Brenda Talavera was pretty matter-of-fact when her doctor suggested that they implant a stimulator the size of a small cell phone inside her brain.

"If it was going to make me better, do it," the Seattle woman said while standing in her living room filled with hockey memorabilia. "If it didn't work, they could remove it."

Talavera, 39, had suffered from debilitating seizures since she was 13. They were so violent that she never remembered having them. Her only proof to herself was the same bite mark on the same part of her tongue after each one. She estimates that she suffered more than 10 a month. Medication alone didn't help.

As she reached adulthood, her only solace was knowing the grocery store where she worked was near a fire station. The firefighters who were called every time she had a seizure knew her well.

In 2006, she became the second patient enrolled in the pivotal trial (or final phase) at Swedish Medical Center that would implant a Responsive Neurostimulator System underneath her scalp. The trial, which is being conducted at 28 U.S. sites, will determine whether the Food and Drug Administration approves the treatment.

It works like a pacemaker for the brain, and is designed to detect abnormal electrical activity and deliver small amounts of electrical stimulation to prevent seizures, said Dr. Ryder Gwinn, director of epilepsy and functional neurosurgery at the Swedish Neuroscience Institute. Swedish enrolled 11 patients in Seattle and at Oregon Health Sciences University, where it is jointly conducting the trial.

The RNS is connected to one or two wires containing electrodes that are placed within the brain or rest on the brain surface where doctors determine the seizures start. It's different for each patient, and physicians use MRI scans to figure out where to place the electrodes. Gwinn said there is a period of adjustment as the device regulates to each patient's seizure activities.

The device stores about four seizures' worth of information, which is downloaded to a laptop computer using a hand-held wand Talavera hovers over her head every night. Then she hits a button and all of her seizure information for the day is sent directly to Gwinn.

"She can have a seizure and I can see it on my computer an hour later," he said.

The gold standard for treating epileptic seizures that can't be controlled by medication alone is to find the source of the seizure and remove that part of the brain, Gwinn said. But physicians want to be able to treat seizures without removing tissue and believe the implant is less dangerous.

From previous studies, "there were very few side effects and any effects (such as flashes of light or extra stimulations) can be adjusted to each patient. With permanent tissue removal, once it's done, it's done," Gwinn said.

Gwinn doesn't have specific numbers yet to prove how well the implants are working, but anecdotally, he sees that many of his patients' seizures have diminished.

Dr. John Miller, director of the University of Washington Regional Epilepsy Center at Harborview, calls the approach "very interesting research," but said the university declined to participate in the trial several years ago, partly because there was little experimental work done on animals before going directly to human trials. He also said there hasn't yet been enough evidence of significantly decreasing seizures to justify the risk of the surgical implant.

"It's not yet clear that the device makes people seizure-free and taking patients from 10 seizures to five doesn't really change their life that much," Miller said. "We're not at that point, but that may change -- the device is still under development and improving, but I'm reluctant to consider it for my patients at this time."

Gwinn expects the FDA to approve the epilepsy implant. A similar brain implant to help control tremors in Parkinson's disease patients was approved in 2002. While he doesn't know how much the device will eventually cost patients if approved, he said it would likely be cost-effective compared with how much patients pay now for weekly or monthly hospital visits and expensive medications.

"This is really just a first-generation device to treat epilepsy," Gwinn said. "It will take another five years to be perfected, but just the effectiveness I've see so far warrants its introduction."

Talavera keeps a diary of how many seizures she has and how severe they are. At 73 weeks into the trial, she said she is down to fewer than six a month, and they are much smaller and less severe.

When asked about how she feels about the good results so far with the implant, she's still matter-of-fact about the process, simply saying, "That's something good, less seizures."

EPILEPSY

What is a seizure? A seizure happens when a brief, strong surge of electrical activity affects part or all of the brain. It can last from a few seconds to a few minutes and have many symptoms, including convulsions and loss of consciousness.

How common are they? One in 10 adults will have a seizure. More than 3 million people in the U.S. have some form of epilepsy. About 200,000 new cases of seizure disorders and epilepsy are diagnosed each year.

What causes them? Seizures are symptoms of abnormal brain function, but the causes are usually unknown. Head trauma or genetic factors can be causes.

Source: Epilepsy Foundation

Cause of severe pediatric epilepsy disorder discovered

Researchers at the University of California, San Diego School of Medicine have discovered that convulsive seizures in a form of severe epilepsy are generated, not on the brain's surface as expected, but from within the memory-forming hippocampus.

The scientists hope that their findings - based on a mouse model of severe epilepsy - may someday pave the way for improved treatments of childhood epilepsy, which affects more than two percent of children worldwide. Their study will be published online by the Proceedings of the National Academy of Science ( PNAS ) the week of March 16.

"A parent of an epileptic child will tell you that they think their child is going to die during their attacks," said senior author Joseph Gleeson, MD, director of the Neurogenetics Laboratory at the UC San Diego School of Medicine, professor in the department of neurosciences and Howard Hughes Medical Institute Investigator. "Parents of children with epilepsy, especially the most severe types of epilepsy, are desperate for a deeper understanding of the causes of the problems and for the development of new treatments."

One of the major causes of epilepsy in children is an alteration in the development of the cerebral cortex. The cerebral cortex is the main folded part of the brain, containing a large percentage of brain cells, and is integral to purposeful actions and thoughts. However, this complex structure is subject to all kinds of defects in development, many of them due to defective genes and many associated with epilepsy.

Cortical dysplasia, meaning disordered development of the cerebral cortex, is identified in 25 to 40 percent of children with the most severe and difficult-to-treat forms of epilepsy. These children often come to the attention of specialists due to stagnation in the acquisition of language and balance skills and accompanying epilepsy. The symptoms displayed by these children can range from very subtle - such as small muscle jerks or eyelid fluttering - to dramatic whole body, tonic-clonic spasms (a series of contractions and relaxations of the muscle) that can affect basic bodily function.

The Gleeson team, led by researchers Geraldine Kerjan, PhD and Hiroyuki Koizumi, PhD, has been studying a disorder called "lissencephaly." (In Greek, leios means smooth, and kephale means brain or head.) Children with lissencephaly have a smooth brain surface that lacks the normal hills and valleys that are characteristic of the human brain. The researchers were recently successful in developing a mouse model that showed some of the features of this disorder, usually the first step toward understanding the cause of a genetic disorder. But the severe epilepsy that is associated with lissencephaly was never displayed in any of the previous animals, so the team kept removing gene after gene until they hit upon a strain that showed epilepsy.

"We study the gene "doublecortin," which is defective in some forms of epilepsy and mental retardation in humans," said Kerjan, lead author of the study. "However, only after we removed a combination of two of the genes in the doublecortin family did we uncover epilepsy."

According to Gleeson, the findings were dramatic, as almost none of the mice in this strain survived to adulthood. Thinking that the deaths might be due to epilepsy, the scientists recorded electroencephalograms, which measure electrical activity produced by the firing of neurons in the brain, and found severe epilepsy in all of the mice tested. Even more surprising was the site of the epileptic focus - or site from which the seizures were generated - which was located beneath the surface of the brain, in the hippocampus.

"Researchers had thought that the cause of the seizures in this disease must be the brain surface, since this is the part that looks the most abnormal on brain MRI scans," said Gleeson. "However, we found that the epilepsy focus was actually deeper in the brain, within the hippocampus, the main memory-forming site."

The research team intends to continue studying in studying the mice, to explore potential mechanisms and utilize this model to test new treatments.