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Neurology Now:
doi: 10.1097/01.NNN.0000433473.41023.79
Departments: The Waiting Room

This Way In: New Research Into Epilepsy

Eastman, Peggy

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New research is bringing hope to people who have seizures, according to speakers at a conference in Bethesda, MD, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), part of the federal National Institutes of Health.

“Progress in the last six years provides cause for optimism,” said James O. McNamara, M.D., professor of neurosciences at Duke University School of Medicine, at the NINDS conference, called Curing the Epilepsies 2013: Pathways Forward. “I look at this glass today as half full and not half empty,” he adds.

About 2.3 million Americans have epilepsy, a brain disorder characterized by a person's continuing tendency to have seizures. A seizure, which is caused by the abnormal or excessive activity of brain cells, can cause temporary loss of awareness or consciousness and disturbances of movement, sensation, mental function, or mood. Just as there are different forms of epilepsy, scientists say there are probably different causes of seizures. New clues to some of these causes are emerging.

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CHILDHOOD EPILEPSY LINKED TO HPV

In one tantalizing new finding reported at the NINDS conference, researchers have linked a widespread virus to a common form of childhood epilepsy. Researchers led by Peter Crino, M.D., Ph.D., professor of neurology at Temple University and Shriners Hospitals Pediatric Research Center in Philadelphia, PA, found human papillomavirus type 16 (HPV16) in the brains of children with focal cortical dysplasia, which is found in about half of people with epilepsy that doesn't respond to drug therapy.

HPV16 is also known to cause cervical cancer in women. Infection with HPV16 is thought to have been passed to the children's brains from their mothers during the babies' development in the womb. Dr. Crino found evidence of HPV16 in 50 brain tissue samples of patients with focal cortical dysplasia. Dr. Crino examined 36 brain tissue samples from patients who did not have focal cortical dysplasia, and none of the 36 samples tested positive for HPV16.

His finding does not prove that HPV16 causes this form of childhood epilepsy, Dr. Crino is quick to say. More research is needed. But, he notes, if further studies confirm his research, it may be possible to prevent focal cortical dysplasia. That's because two vaccines, Gardasil and Cervarix, protect against HPV16. “HPV infection is an epidemic, and it has prompted the medical community to recommend large-scale vaccination,” he says.

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RENEWED INTEREST IN KETOGENIC DIET

Other research presented at the NINDS conference offered a glimpse into how the high-fat, low carbohydrate ketogenic diet works to prevent seizures. “What is perhaps most intriguing about recent studies of the ketogenic diet is the evidence for its broad protective properties on nerve cells in the brain,” says Jong Min Rho, M.D., professor of pediatrics and clinical neurosciences at the University of Calgary, Alberta, Canada. This protective effect seems to decrease seizures in some people, he notes. Although the mechanisms are not well defined, he notes that scientists believe the protection results from reduced inflammation along with added reserves of energy for nerve cells.

The ketogenic diet is most effective in children, Dr. Rho tells Neurology Now, but staying on the diet is not easy. Because the ketogenic diet is extremely high in fat, and carbohydrates are nearly eliminated, it is very different from the typical American diet. In fact, the ketogenic diet mimics the biochemical changes that occur when people have limited access to food. Because maintaining this diet is a challenge, he cautions that a team of medical specialists, including a dietician, is necessary to help families implement it. “My experience is that whether the diet works or not is largely dependent on the dietician,” Dr. Rho says.

Asked if there are any harmful side effects from the diet because it is high in fat, such as an increased risk of heart disease, Dr. Rho says there do not seem to be. According to a 24-week study of obese patients on the ketogenic diet, the level of total cholesterol (a risk factor for heart disease, if it is high) actually decreased. HDL cholesterol—the good kind—increased significantly, while triglycerides (a risk factor for heart disease, if they are elevated) fell. Although scientists and doctors have worked to improve the effectiveness and tolerability of the ketogenic diet, the ultimate goal—which has not yet been achieved—is creating a “ketogenic diet in a pill,” Dr. Rho says.

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SURGERY FOR TREATMENT-RESISTANT SEIZURES

Antiepileptic drugs (AEDs) are effective in controlling seizures in more than two-thirds of people, and AEDs for specific seizure types have recently been approved. But medications fail to control seizures in about 30 percent of people with epilepsy. For these treatment-resistant seizures, surgery should be considered, according to some research presented at the NINDS conference.

Today, surgery is becoming less invasive, and improved imaging techniques are helping us map the brain to find the location of the seizures, notes Edward Chang, M.D., associate professor of neurological surgery and chief of epilepsy surgery at the University of California, San Francisco. Nevertheless, surgery is underused, according to Dr. Chang. Why? “Because many people think brain surgery is too dangerous. Actually, it is very safe overall,” he says, adding that surgery should be considered as an option for people who have tried multiple AEDs without success.

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SUDEP

Researchers at the NINDS conference also shed light on sudden unexpected death in epilepsy (SUDEP). According to NINDS figures, about one person dies from SUDEP per 1,000 people with epilepsy. Men younger than age 60 who have had epilepsy with no known cause for 15 years or more, who have frequent tonic-clonic seizures (formerly called grand mal), and who take multiple AEDs are at highest risk of SUDEP.

Scientists now believe that SUDEP in some people may be due to changes in breathing or heartbeat (see cover story, page 16), which raises the possibility of therapy with drugs that enhance breathing and implantation of cardiac devices to regulate the heart. “It is well known that seizures alter breathing and the activity of the heart,” says George B. Richerson, M.D., Ph.D., chair of the Department of Neurology at the University of Iowa.

Because of new findings on SUDEP, Dr. Richerson recommends that all patients who have their brain activity studied for epilepsy should also undergo respiratory monitoring. During respiratory monitoring, a person wears a special device to determine whether there is any shortness of breath or difficulty in breathing.

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FOR MORE INFORMATION

For more Neurology Now coverage of epilepsy, go to http://bit.ly/xMSLvd.

© 2013 American Academy of Neurology

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