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Charging Ahead

As even its most enthusiastic practitioners concede, deep-brain stimulation in its current state is still relatively crude. But the future of brain pacemakers-greater sophistication and miniaturization, broader application-is unfolding at a rapid pace. “This is just the tip of the iceberg,” says Hans O. Lders, chairman of neurology at the Cleveland Clinic. Patients with epilepsy, he points out, are usually treated with antiseizure medication and, failing that, with a radical form of elective surgery to remove the part of the brain that becomes hyperactive during repeated attacks. More than two million Americans suffer from epilepsy, and roughly half of them have seizures that originate in the same region of the brain again and again. “At least 20 or 30 percent of these patients cannot be controlled with drugs,” Lders says. “What to do with them? This is where deep-brain stimulation comes in.”

During the past year, the Cleveland group has implanted brain pacemakers in five epilepsy patients: two of the five have shown significant improvement, according to Lders. And the prognosis may soon get even better with new pacemaker technologies. The next generation of stimulation devices will be the so-called closed-loop pacemakers, electrodes designed to both monitor brain electrical activity and deliver stimulation when necessary-rather than provide continuous electrical pulses. Already, a large, external version of this pacemaker has been tested in eight patients at the University of Kansas Medical Center with “excellent results,” according to Ivan Osorio, who heads the research effort. And several groups are working with Minneapolis, MN-based Medtronic, currently the only company marketing these pacemakers, to develop a miniaturized version that could be incorporated into a chip. The strategy is to take advantage of the fact that epileptic seizures are often preceded by an electrical overture, or “aura,” that warns of the coming neural storm minutes before the actual symptoms appear. “You sense what is going on in the brain, and you stimulate only when an epileptic seizure is coming on,” Lders explains.

The power packs used in brain pacemakers are also evolving. Currently, the packs are about the size of a pager and are implanted just below the collarbone-surgery that includes a painful procedure to hook up the pacemaker’s power supply to the electrode. The bioengineering group at Cleveland Clinic is working with Medtronic to miniaturize the power packs to about the size of a quarter, which could potentially allow surgeons to implant the devices behind a patient’s ear.

The catalogue of diseases targeted for electronic stimulation is evolving as rapidly as the technology. Obsessive-compulsive disorder, for example, is just now becoming a candidate for the treatment. In 1999, Bart J. Nuttin, a doctor at Catholic University in Leuven, Belgium, reported in The Lancet on the use of brain pacemakers to treat four patients with the disorder who were resistant to any other therapy; three of the four patients benefited from the new therapy. A 39-year-old woman who had suffered severe symptoms for more than two decades, for instance, experienced “an almost instantaneous feeling of being relieved of anxiety and obsessive thinking” when the electrode stimulator was turned on.

It won’t be long before severe depression, too, may be experimentally treated with deep-brain electrical stimulation. Studies have shown that stimulation of the subthalamic nucleus has a significant impact on mood, says Cleveland Clinic’s Montgomery, “and that might translate into therapy for depression.”

Among the most daring potential applications of the technology is the use of electrical stimulation to improve the condition of patients with severe brain injuries. An estimated 5.3 million Americans are currently living with disabilities as a result of brain injuries, and a significant number of them are in minimally conscious states. Nicholas D. Schiff and Fred Plum of Weill Medical College in New York are developing diagnostic tools to identify brain-injured patients who retain some capacity for coordinated neural activity; such patients, they argue, might benefit from deep-brain stimulation. “We’re not talking about people in comas, and we’re not talking about people in semi-vegetative states,” Schiff says. But brain-imaging technologies indicate that some patients have states of awareness that fluctuate. “It’s just a matter of, Can you identify patients that have some cognitive states that are better than others and use deep-brain stimulation to push them into this better state?’ In the next year or so, we might be able to pilot this therapy.”

The University of Grenoble’s Benabid has even shown-in rats, for the time being-that eating behaviors can be affected by brain pacemakers. High-frequency stimulation of the hypothalamus, another deep-brain structure, seems to spur appetite, and thus could be used as a last-resort treatment for severe anorexia nervosa; low-frequency stimulation seems to decrease appetite, and could be used to treat what he calls “malignant obesity.” But Benabid, for one, is in no hurry to rush into behavior modification using brain pacemakers. “We have to be very cautious about this,” he says. “You mention obesity, and people say, Wow, that’s a big market here!’ I don’t like to hear big market.’ We think we could provide some patients with a solution for something when nothing else is available. The danger is that the easier the procedures become-less invasive, less morbidity-the more tempting they are.”

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