Epilepsy Treatments Aim to Press Reset Button on a Misfiring Brain

Nearly 3 million Americans have some form of epilepsy, a neurological disorder in which the brain produces sudden bursts of electrical energy that lead to seizures. There are more than 40 different kinds of epilepsy described in the medical literature, and can involve a wide range of symptoms from loss of consciousness, to spasms and jerking, to loss of muscle tone, to “absence” seizures in which the person loses awareness for usually only a few seconds at a time.

No matter what the specific type of epilepsy, these seizures can be debilitating and limit people’s lives in every way imaginable. People with uncontrolled epilepsy can’t drive to work. A mother with uncontrolled epilepsy fears dropping and injuring her baby in the throes of a seizure. Children are embarrassed at school. Lawyers or accountants climbing the corporate ladder may worry about having a seizure during an important presentation.

One-third of people with epilepsy find that the anticonvulsant medications that have long been a mainstay of treatment for the disorder control their seizures well — but another third have their seizures only partially controlled by these drugs. (The medications also come with a host of side effects, like mental fogginess.) And the final third have “pharmacologically intractable epilepsy” — meaning that drugs don’t control their seizures at all.

In the past, for such patients, the only solution has been a tricky and dangerous surgery to remove the damaged areas of the brain (temporal or frontal lobectomy). Unfortunately, those damaged areas usually lie in regions that involve learning and memory, such as the hippocampus. No matter how precisely the surgeon cuts, the odds of damaging normal brain function are high.

So what’s the alternative? Until recently, not much. But over the past decade, medical science and electrical engineering have come together in exciting ways to try to “reboot” misfiring brains. Two techniques, vagus nerve stimulation (VNS) and deep brain stimulation (DBS), both involve the implantation of neural devices. Much like pacemakers for the heart, these devices (electrodes and a small battery) send small, targeted jolts of electricity to specific spots within the brain or nervous system in order to disrupt the abnormal electrical patterns that set off seizures.

VNS was approved by the U.S. Food and Drug Administration for the treatment of partial-onset epilepsy in 1997. Unlike DBS, the VNS stimulator isn’t implanted in the brain itself. Instead, it’s placed within the chest (as pacemakers are) and connected to the left vagus nerve, which is found in the neck, by a lead wire system. The VNS system sends its signals automatically, but if a person notices the “aura” they sometimes feel before a seizure, they can pass a magnet over the generator in their chest for a few seconds, which can sometimes head off or shorten the impending seizure.

According to the Epilepsy Foundation, about 32,000 people have had vagus nerve stimulators implanted so far, most with partial seizures. Estimates of improvement rates vary, but most sources agree that between one-fourth and one-third of patients experience significant improvement in their seizures.

That’s actually a very good result, when you consider the fact that people getting VNS implants are those whose epilepsy did not respond at all to medications — those who have the most intractable seizures. (Nonetheless, people who receive VNS implants still continue to take their seizure medications.)

Deep brain stimulation involves actual brain surgery: implanting the neural device deep within the brain, usually under local anesthesia so that surgeons can talk to the patient while placing the neurostimulator to make sure they are not disrupting normal brain function.

DBS has been used in more than 40,000 patients with Parkinson’s disease so far, with promising results (also see “Young-Onset Parkinson’s Adds New Dimension to Crippling Disease” in the April 2009 issue of The Washington Diplomat). The political journalist Michael Kinsley recently spoke before Congress about the impact DBS has had on his life, saying, “Now I walk around with wires in my head and two pacemaker-type batteries in my chest. But thanks to these devices and these pills, I am walking around.”

But DBS is still considered experimental in people with epilepsy because unlike VNS, it involves actually cutting into the brain, so implantation is obviously riskier. The device’s manufacturer, Medtronic, is now conducting a large-scale clinical trial of DBS in epilepsy, and a spokesperson told the Los Angeles Times in June that it would submit data to the FDA within the year.

Data from the trial, presented at a scientific meeting in 2008, showed that deep brain stimulation reduced seizures by 38 percent, which appears to be slightly better than the improvements seen with VNS. On the other hand, the control group whose device was kept turned off also improved, by 14.5 percent, possibly due to a placebo effect.

This approach to treatment may be the wave of the future for people with intractable epilepsy. In fact, there are now more than 30 active or completed clinical trials of some form involving brain stimulation for patients with epilepsy listed in www.clinicaltrials.gov. These include several involving another type of neural stimulation, transcranial magnetic stimulation (TMS), which was approved for patients with major depressive disorder in October 2008.

To find out more, search for the terms “epilepsy AND stimulation” on www.clinicaltrials.gov, or contact the Epilepsy Foundation at (800) 332-1000 or www.epilepsyfoundation.org.

About the Author

Gina Shaw is the medical writer for The Washington Diplomat.