Epilepsy Can Defeat Drugs

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By Melissa Tennen

People with epilepsy may go for years with no seizures, thanks to medication. And then, with no explanation, the drugs simply stop working.

That much researchers know. But a new study sheds light on this phenomenon.

The younger the patient, the longer it may take for the person to develop drug-resistant seizures, or intractable seizures, says the study from the National Institute of Neurological Disorders and Stroke and Yale University School of Medicine. The form of epilepsy is called partial epilepsy, which means the recurring seizures begin in a part of the brain.

At least 20 percent of people with partial epilepsy do not achieve relief from medication, forcing them to consider other treatments including a rare surgery that removes brain tissue.

This research describes for the first time a time frame for response to medications before the drug resistance sets in.

“With this landmark study, we may be able to predict who will develop intractable seizures,” says Robert J. DeLorenzo. M.D., Ph.D., P.M.D., George Bliley professor of neurology and professor of pharmacology, toxicology, biochemistry and molecular biophysics at the Virginia Commonwealth School of Medicine. He was not part of the study. “This is a completely new field of epilepsy research. And we are only just beginning to scratch the surface.”

Researchers looked at 333 patients who had undergone surgery for partial seizures. These individuals are part of an ongoing larger study that examines the results of such surgery.

Researchers already know that resistance to drugs mostly strikes people who have partial epilepsy, or recurring seizures that happen in part of the brain.

Scientists found that those with intractable seizures had an average of nine years before their condition became drug-resistant. Seizures were said to be resistant if at least two anticonvulsant medications did not work. Also, about one-quarter of the patients said they had had seizure-free periods of a year or more, and 8.5 percent had seizure-free periods of five years or more.

“We don’t know why exactly,” says Susan Spencer, M.D., director of a large multicenter team doing the research and professor of neurology at Yale University School of Medicine. “But now that we know this happens, we can look for ways we can intervene and prevent this from happening.”

Reasons unknown

These findings set off a cascade of questions among researchers.

“Who are the people whose seizures won’t get under control? How does that happen? Does it happen quickly or slowly? Can you examine a patient’s history and tell when the epilepsy can become drug resistant?” Spencer says.

In patients who developed seizures before age 5, it took an average of 15 years for seizures to become intractable, according to the study. However, for people who started in their 30s or 40s, the seizures shortly became intractable or within a few years thereafter. The average age of a first seizure was 14.6 years while the average for surgery was 36.7 years.

“Understanding the mechanism of resistance in this type of seizure is paramount since drug failure may lead to the decision to proceed with surgical therapy,” says Jeffrey L. Noebels, M.D., Ph.D., professor of neurology, neuroscience and molecular genetics in the department of neurology at the Baylor College of Medicine in Houston.

“It is important to remember that the absence of clinical seizures does not mean that brain activity has returned to normal, so the underlying biochemistry of the epileptic lesion may continue to change over time, which we know to be true from molecular studies,” Noebels says. “We need medicines that can not only stop seizures, but prevent the changes that lead to drug resistance.”

Researchers know that developing epilepsy is based on what genes say. But not everyone who has the genetic component develops the condition.

Some causes of acquired epilepsy are brain damage, brain tumors, strokes, lead or other poisoning and lack of oxygen reaching the brain during childbirth. However, in 70 percent of cases, no known cause is ever found. About 30 percent of the 125,000 new cases every year begin in childhood, particularly in early childhood and around the time of adolescence. Another period of relatively high incidence is in people over the age of 65, the Epilepsy Foundation says.

Types of seizures

Epilepsy is a condition of recurring seizures. In normal brain functioning, millions of tiny electrical charges pass constantly between the nerve cells of the brain and other parts of the body. When a seizure occurs, a signal triggers that something has gone wrong with the electrical system of the brain. The most easily recognized seizure is the convulsion seizure, characterized by shaking movements of the body accompanied by a period decreased mental awareness. Other, less obvious forms of seizures may affect a person’s awareness, muscle control or sensory perception.

About 60 percent of people with epilepsy have partial seizures. One type is called simple partial seizure when the person remains conscious but may experience unusual feelings or sensations. Another type known as a complex partial seizure, the person may have a change or loss of consciousness. The change in consciousness may be an altered or dreamlike experience.

Epilepsy is first treated with medication. People who have more than one type of seizure may have to take more than one kind of drug, although doctors try to control seizures with one drug if possible. Nearly two dozen drugs exist to treat the condition.

“If you talk to most primary care physicians, they’ll say that treating patients with epilepsy is not a problem. Patients can keep it under control with medications and may never have another seizure,” DeLorenzo says.

The study is part of larger research looking at what happens to patients who have had surgery for partial seizures. Spencer and her team wonder: Do they become more or less depressed? Can they reason as well or better than they did before? Does quality of life improve? How can we predict who will respond with getting a cure of seizures without no negative effects?

“In our society, having a seizure once a week or even once a month could be a big problem. You can’t drive a car, hold down a job. It’s a very serious problem,” DeLorenzo says.

Additional Information About Seizure

First Aid Measures for a Seizure

First aid measures for a seizure depend on the type and severity of the seizure. Protecting the person from injury is a primary concern, especially during a grand mal seizure, when consciousness may be altered. Remove the person from danger or nearby hazards like moving objects, water and electricity. Try to protect the person’s head from injury by providing a cushion against the ground. If possible, turn the person onto their side so that the secretions from their mouth are able to better drain.

Do not ever attempt to pry open and insert something into the mouth of a person who is having a seizure. These efforts are more likely to cause harm than do any good. Likewise, do not attempt to restrain the person. Stay with a person following the seizure, until their mental alertness returns. There is usually a period of confusion after a grand mal seizure and the person may not be aware of their surroundings. If the seizures continue, one after the other, it is best to call 911.

Treatment Plan

Treatment for epilepsy can include medication, surgery, diet restriction or a new therapy called vagus nerve stimulation.

Medication

The choice of medication is based on your seizure type, the pattern on your EEG, how well the medicine controls your seizures, and how you tolerate the medication. Some types of epilepsy respond better to certain medications than others. Seizure patterns can change and medication may need to be altered. Choosing the appropriate medication depends on many factors. An antiepileptic drug (AED) may work well for one person, and not for another. You and your doctor can work together to find the best medication for you.

Surgery

It may be necessary to have a surgery for treating seizures while anticonvulsants fail. In some case it can control seizure activity by removing the pieces of brain tissue if the seizures are confined to a small segment of the brain.

Diet therapy

Diet therapy, specifically a ketogenic diet, may be used to treat seizures, especially those occurring in children. A ketogenic diet changes the way the body derives energy and has a seizure-preventing effect in children. The introduction of a ketogenic diet must be closely supervised by a physician and often requires that a child be hospitalized initially. Although this diet was first introduced 80 years ago, before the advent of most anticonvulsants, it has gained renewed popularity in recent years, particularly in children whose seizures do not respond to medication.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) is a newer type of treatment for hard-to-control seizures. VNS involves surgically placing a small battery inside the chest that is attached to wires that are programmed to deliver small bursts of electrical energy into the brain.

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