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CCE Seizure Disorders: Massachusetts General Hospital


In therapeutics, the MGH Epilepsy Service participates in clinical trials for drugs and devices, including a current clinical trial using an implanted device that detects the beginning of abnormal electrical activity.

Massachusetts General Hospital Epilepsy Service
Boston, Massachusetts

Experiencing a seizure for the first time can be frightening for the patient. But treating patients right from the onset of epilepsy also can be a great teaching tool for fellows and provide important data for researchers.

Those are some of the reasons that Massachusetts General Hospital (MGH) Epilepsy Service started its "First Seizure Clinic" a decade ago. While many clinics are too busy to deal with a potential one-time event, MGH views seeing patients early as a benefit.

"We think it's important that our fellows see patients at that end of the spectrum, as well as the more refractory or long-standing cases that we typically see in referral," says Andrew Cole, MD, director of the MGH Epilepsy Service and an associate professor of neurology at Harvard Medical School. Seeing patients at the earliest stage of disease also helps researchers build a cohort of patients who can be followed longitudinally in order to study the natural history of seizure disorders and who are available for clinical trials, he says.

Above all, Cole says it's valuable for many patients to receive a definitive opinion early on. For practical reasons, many patients see their primary care physicians or a local neurologist for evaluation before going to a progressive and specialized epilepsy center, such as the one at MGH. But if they can be seen immediately upon new-onset of seizures, it can lead to better treatment.

Cole arrived at MGH to start the Epilepsy Service in 1992. In that time, he says he has seen three "revolutions" in the treatment of epilepsy: therapeutics, diagnostics, and genetics. MGH is at the forefront in all three areas in both research and treatment.

New devices and technology

In therapeutics, the MGH Epilepsy Service participates in clinical trials for drugs and devices, including a current clinical trial using an implanted device that detects the beginning of abnormal electrical activity and delivers electrical stimulation to normalize it before a seizure begins.

"Devices are intrinsically interesting," Cole says. "Their ultimate value has yet to be determined, but it's clearly a different approach, and it's one that lends itself to a lot of creative thought and has substantial potential."

Besides drug therapies and devices, Cole says new medication delivery systems are the future of epilepsy treatment.

"There's a lot of interest in novel treatment strategies," he says. "That indicates that currently available treatments are not satisfactory for a significant fraction of patients, and those people are desperate for other approaches. That's what we're all trying to develop."

The second "revolution," Cole says, is in imaging technology. Magnetic resonance imaging machines have become more powerful, moving from a 1.5 T magnet to as high as a 7 T magnet, increasing the resolution and becoming more sensitive to detecting subtle pathologies.

"There are many patients who had MRIs 10 years ago, and when we look at them carefully now in new studies, we see things that we weren't seeing," Cole explains. "Those can sometimes translate very directly into appropriate surgical therapy and cure."Such advances help identify patients who are surgical candidates and make it possible to remove smaller portions of the brain, as well as to operate on more complex patients. The MGH Epilepsy Service does about 50 focal resections annually. Focal resection is one key reason that neurologist Judd Jensen, MD, from Penobscot Bay Neurology in Rockport, Maine, sends his most difficult patients to MGH. He also sends patients who aren't responding to treatment, are difficult to diagnose, and those who want a second opinion.

He says that as a community neurologist, it is reassuring to refer patients to a center that treats a variety of cases and one that has physicians who communicate with him something he says doesn't always happen when he refers patients to large medical centers.

"Dr. Cole is a leading national expert in epilepsy, and so he has the advantage of seeing unusual cases," says Jensen. "He's always been great about getting patients in who need to be seen. Also, he always calls me when he sees one of my patients."In fact, Cole says, every case is presented to and discussed among all the service's physicians, so patients have the added advantage of numerous physicians' opinions on the best treatment.

Genetic research

"We have a vigorous program studying the physiology of epilepsy," Cole says. "That is, looking at the actual signals from intracranial electrodes that are implanted in the course of surgical investigation to try to understand the circuitry that contributes to the epilepsy abnormality."

MGH researchers are also looking into the genetics of epilepsy. Although Cole estimates that upward of 100 epilepsy genes have already been identified, he calls that "the tip of the iceberg." The Epilepsy Service has just launched a research program to gather DNA from patients in order to further understanding of the genetics of the disease.

"Genes for epilepsy are complex," Cole says. "First of all, it's a complicated disease which has multiple genetic contributions to it. Second of all, there may be some genes that are directly causative of epilepsy. In other words, it's that defect that makes the seizures happen. That might be the case with certain ion channel abnormalities. But there are other genes that might confer risk of epilepsy, so that people who have a specific genetic make-up might be at higher risk of developing seizures should something else happen to them."

In addition, Cole adds, that researchers are also investigating a third category of genes that cause epilepsy: those that lead to the abnormal brain development that causes seizures.

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