Temporal Lobe Epilepsy Seizures Appear to Begin Hours Prior to Clinical Symptoms

Scientists studying epilepsy at the University of Pennsylvania Medical Center are finding a pattern of human brain activity that indicates the conditions triggering seizures can take hours to develop.

The work points toward a method to short-circuit epileptic seizures and convulsions before they strike, through the use of implantable brain devices and medications, according to Brian Litt, MD, author of the study. It appears tomorrow (Thursday) in the April issue of the journal Neuron.

"This study is part of a large collaborative effort to control symptoms of a condition that dominates the lives of otherwise healthy individuals by its dramatic unpredictability," Litt said. "The potential to use our findings to help people with poorly controlled seizures world-wide is enormous."

About 50 million people throughout the world suffer from epilepsy. Almost 25 percent have seizures that are not controlled by any available therapy.

Although epilepsy is the most common neurologic disease after stroke, its cause cannot be identified in a large percentage of cases. Recently, scientists looking for changes in the brain that predict seizures have had some success using mathematically-based chaos theory. But those studies have generally been limited in scope -- they concentrate on a period of minutes prior to seizures -- and are further limited by the difficulty of applying an abstract theory to what actually happens inside the brain.

Litt and his colleagues, on the other hand, relied on the traditional method of measuring brain activity through EEG (electroencephalograpy) readings for five epilepsy patients who were being evaluated for surgery and had therefore stopped taking anti-seizure medication. The EEG readings tracked the patients for periods ranging from four to 14 days.

Using electrodes implanted in both sides of the brain, the scientists examined "a continuous stream of data for reproducible patterns associated with seizures, and found a chain of events that predicted that seizures were going to occur," Litt said.

The researchers discovered cycles of abnormal brain activity -- epileptic discharges -- lasting 15 to 30 minutes. The discharges became more frequent over a period of hours as they led to brief, asymptomatic seizures at specific points in the brain. Those smaller seizures triggered a steady increase in activity that spread across the brain and culminated in clinical seizures.

Litt likened this cascade of events to a match striking over and over, lighting and re-lighting a fuse in the affected part of the brain. The fuse goes out and re-ignites more and more frequently, until finally it ignites the energy that leads to clinical seizures. In some of the study patients, the process lasted up to seven hours.

"This information provides a real opportunity to stop abnormal activity in epileptic brain regions before seizures develop," Litt said. Although substantial work remains before the study findings can be put to clinical use, he believes scientists may eventually be able to implant devices in the brain that will abort seizures by reacting to, and diffusing, the cycle of increasing abnormal brain activity.

Litt collaborated in the study with Rosanna Esteller; Javier Echauz, PhD; Maryann D'Alessandro; Rachel Shor; and George Vachtsevanos, PhD, all of the Georgia Institute of Technology, along with Thomas Henry, MD; Page Pennell, MD; Roy Bakay, MD, and Charles Epstein, MD, of Emory University. Marc Dichter, MD, PhD, of Penn also collaborated in the study.

Along with Vachtsevanos, Echauz and Esteller, Litt is co-founder of IntelliMedix, a company devoted to this research.

The study was funded by IntelliMedix (in which Drs. Litt, Vachtsevanos, Echauz and Esteller have a financial interest), the Epilepsy Foundation, the Whittaker Foundation, the American Epilepsy Society, the National Institutes of Health and the University of Pennsylvania Research Foundation.

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