Ivan Osorio, University of Kansas Medical Center.

A New Way to Treat Epilepsy

Epilepsy has been recognized as a unique disorder for thousands of years, with references to its symptoms occurring throughout the ages, from Babylonian tablets to the Bible. Julius Caesar was perhaps its best-known victim. Derived from the Greek word "epilambabein," meaning to seize or attack, epilepsy is a neurological condition that makes people susceptible to changes in sensation, awareness or behavior due to brief electrical disturbances of the brain.

These disturbances, known as seizures, vary from a few moments of sensory disruption, to periods of unconsciousness or staring spells, to convulsions. Regardless of how the seizure manifests itself, the result is same—€”disruption to the sufferer's life.

Through the Department of Energy's Global Initiatives for Proliferation Prevention (GIPP) program, partners across the government, medical and private industries are working together to write a new page in the history of epilepsy. Partners include Ivan Osorio of the University of Kansas Medical Center and Flint Hills Scientific, LLC, based in Lawrence; Mark Frei, Flint Hills's CEO; the National Nuclear Security Administration's Kansas City Plant; BioFil, a small, private science company in Sarov, Russia; and Argonne National Laboratory. The ultimate aim is to create a personal automatic radiotelemetric device to detect and either block or prevent epileptic seizures.

"I've worked in epilepsy for many years," Osario said. "I handle the cases that don't respond to or aren't fully controlled by medication, which is about 20 to 40 percent of all cases. These patients have at least one seizure a month—€”enough to severely disrupt their lives." Epilepsy interferes with both the patient's work life and personal life, and often leads to isolation and depression. Currently, 2.7 million people in the United States suffer from epilepsy.

"It became very clear to me that medications, although very useful, don't work for a good number of patients. So I decided to look at other ways of dealing with this," Osorio said. Since a large number of patients suffer from seizures that are concentrated in one spot in the brain. Osorio along with Mark Frei decided to look at local, direct brain intervention.

The men first contacted the Kansas City Plant for help with implementing into a portable device an algorithm they had developed for real-time detection, warning and quantification of seizures. KCP engineers Jerry Elarton, since retired, and Kevin Koepsel worked with Osorio and Frei to develop the first electronic, portable device to detect and warn of impending seizures. This first prototype was developed at the Kansas City Plant in the late 1990s. (See original telemetry device photo.) The contact laid the foundation for what would later become a GIPP partnership.

Having developed a critical first detection/warning prototype, the team started looking at implantable devices to warn about an impending seizure and trigger an automatic therapy. The automatic therapy that the device triggers could be electrical, cooling of a brain region, or even local delivery of a drug. But it's the cooling version that Osorio, Frei and the rest of the GIPP epilepsy prevention team are working on today.

The system works by measuring the patient's brain temperature via a probe implanted in the patient's brain. When the probe detects a change in brain patterns, the changes are sent wirelessly to a telemetry device, which activates a cooling system prior to the seizure occurring. Coolant is delivered to the implanted probe inserted in the brain via a connecting tube.

This portable system as described above contains three main parts: (1) an implantable sensor (measures local temperature of the brain area to detect an epileptic seizure); (2) a brain tissue cooling device (that initiates cessation of the seizure); and (3) a telemetry system (that enables information exchange between the sensor and cooling device, and includes digital signal processing).

The implantable temperature sensor has already been developed by BioFil with Argonne engineers under the leadership of Sami Gopalsami and Paul Raptis. The passive sensor can measure changes in brain temperate of 1/1000 of a degree. A prototype cooling probe has been developed by BioFil and Argonne; however, the size needs to be reduced before it can be implanted into a human brain. If too large, the probe could damage the brain area where it is inserted.

Argonne, assisted by the Kansas City Plant, is developing the conduits for the coolant between the brain and the telemetry system, and Flint Hills Scientific is working on the prototyping. Like the probe, it requires an extremely small diameter—€”ideally, about the size of a hair. Right now, it is about 1 millimeter thick and 40 millimeters long.

KCP's main mission is the miniaturization of the telemetry system and the integration of all epilepsy prevention system components. Using its expertise in miniaturization, the Kansas City Plant has greatly improved upon its original prototype of the wireless telemetry system, reducing it to the size of a pager. But the plant wants to make it even smaller. The goal, according to engineer Dean Oliver, is to get it down to the size of a half dollar within the next few months. "Antennas, radio board and battery systems will all get smaller, so they can run off of button cells, similar to calculators," Dean said. The smaller the device, the less obtrusive it is for the patient. While currently an external device, if small enough, it could be implanted in the patient. The telemetry system is computer controlled, and KCP has developed custom code for it.
Integration of coolant system, the probe and the telemetry system is ongoing.
Osorio expects the GIPP team will have a complete prototype to test within the next five years. "We're making excellent progress. In fact, we are leaders in nonconventional treatment of epilepsy, thanks in large part to the support of the GIPP program," he said.

GIPP research projects are selected for their commercial potential and are designed to lead to peaceful, long-term employment and income for former Soviet Union weapons workers. The program benefits from the Russians' expertise, and research and development can be conducted at a frac