Drug-resistant Seizures Often Take Years To Develop

"This study opens the door for early identification of patients who will later develop drug-resistant partial epilepsy, which may in turn allow us to identify ways of preventing some forms of epilepsy from ever becoming drug-resistant," says lead author Anne T. Berg, Ph.D., of Northern Illinois University in DeKalb, who is part of a large multicenter team directed by Susan Spencer, M.D., at Yale University in New Haven, Connecticut. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and appears in the January 28, 2003, issue of Neurology.*

In the new study, researchers looked at patients who had surgery for drug-resistant partial epilepsy to identify factors that predict when seizures will become intractable, or no longer controllable with medications. They also studied the incidence of previous seizure-free periods in this group. Partial epilepsy results from abnormal neuronal activity that originates in a single part of the brain, usually in one of the temporal lobes.

Epilepsy is a disorder in which clusters of nerve cells, or neurons, in the brain display patterns of abnormal activity. This activity can cause a variety of symptoms, including convulsions. Physicians have described dozens of different kinds of epilepsy. "Epilepsy is not a single disorder – like cancer, it's a multitude of disorders with varying symptoms, prognoses, and implications for specific treatment," says Dr. Berg. Partial epilepsy accounts for about 40-50 percent of childhood epilepsy and 90 percent of adult-onset epilepsy, she adds. Other types of epilepsy result from abnormal neuronal activity in many parts of the brain.

In this study, researchers looked at 333 patients who had undergone surgery for partial seizures and who were part of a larger ongoing study to examine the outcomes of epilepsy surgery. Most of these patients had temporal lobe epilepsy, or TLE. The researchers examined medical records and conducted structured interviews with these patients to determine the duration, frequency, and types of seizures the patients experienced. They found that patients' average age when they had their first seizure was 14.6 years, while the average age at which they underwent surgery was 36.7 years. The 282 patients for whom historical data were available had been diagnosed with epilepsy an average of 9 years before their epilepsy became intractable. Intractable epilepsy in this study was defined as a failure of two medications to control seizures.

The researchers also asked about periods when the patients had been seizure-free. About one quarter of the patients said they had been seizure-free for a year or more. Twenty-four patients (8.5 percent) were seizure-free for 5 years or more. A seizure-free period of 1 year or longer was most common in people who were younger than 5 when they were diagnosed. The results show that a history of seizure-free periods is common in people who later develop intractable seizures.

The study identified several factors that were related to the amount of time before seizures became intractable. These factors included age of onset, type of surgery the patients received, history of febrile (fever-related) seizures, and atrophy of the hippocampus, the region of the brain that is affected in TLE. Of these factors, age of onset had the strongest relationship with the amount of time until intractability, Dr. Berg says. In patients whose seizures began before age 5, it took an average of 15 years for their seizures to become intractable. In patients whose epilepsy began during their 30s and 40s, however, seizures tended to become intractable immediately or within only a few years.

"Consistent with other reports, many individuals in our study did indeed have epilepsy that became intractable within a short time after its initial onset. What is startling, however, is the large number of patients who experienced prolonged periods of seizure control before their seizures became intractable," Dr. Berg says. Based on the 15-year average time it took for early-onset seizures to become intractable, Dr. Berg says that studies of epilepsy prognosis need to proceed for at least that amount of time in order to identify patients who might develop intractable seizures late in the course of the disorder.

The results of this study pertain only to partial epilepsy, primarily TLE, and cannot and should not be generalized to other forms of epilepsy, Dr. Berg notes.

"These data give us some clues, but they only begin to scratch the surface. We need careful, prospective long-term studies in order to accurately understand the long-term prognosis of partial epilepsy," says Dr. Berg. She and her colleagues are now conducting additional studies to determine which patients develop intractable seizures.

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The NINDS is a component of the National Institutes of Health, within the U.S. Department of Health and Human Services, and is the nation's primary supporter of biomedical research on the brain and nervous system.

*Berg AT, Langfitt J, Shinnar S, Vickrey BG, Sperling MR, Walczak T, Bazil C, Pacia SV, Spencer SS, for the Multicenter Study of Epilepsy Surgery. "How long does it take for partial epilepsy to become intractable?" Neurology, January 28, 2003, vol. 60, pp. 186-190.