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Deep brain stimulation being tested with brain injury, Alzheimer's, obesity and more

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Other conditions

Deep brain stimulation for depression and epilepsy is already being tested in large clinical trials, but it has only been tested in a few patients for other conditions such as traumatic brain injury, Alzheimer's disease, obesity, anorexia and addiction.

Reports, when published, are of only a few people and are not part of formal clinical trials with placebos or blinded participants and scientists. Thus, though the data are intriguing, they must be viewed very guardedly, researchers say.

Brain injury: Dr. Nicholas D. Schiff at Weill Cornell Medical College in New York was part of a team that used deep brain stimulation to help a man who was in a minimally conscious state after a traumatic brain injury.

The man had been hit on the side of the head, which caused bleeding and swelling of the brain. He was initially in a coma, then in a vegetative state for about 12 weeks and then in a minimally conscious state for six years.

His eyes were closed much of the time, he could not swallow, and he had to be fed by a tube in his stomach, Schiff says. On rare occasions, he could move his thumb to trigger a communication device. He did utter words on rare occasions but could not give verbal responses in formal testing.

The man received deep brain stimulation in the central thalamus, an area in the middle of the skull that controls arousal, sleep and wakefulness. After treatment, he could chew and swallow, communicate in short sentences and use his hands or limbs to demonstrate the functional use of objects.

This is the first case, Schiff says, where deep brain stimulation has clearly been shown to improve people with traumatic brain injury. To prove that deep brain stimulation was the reason for the man's improvement, the six-month study had one-month-long phases where the device was turned on or off and his condition was observed to get better or worse.

He also was at the "higher end" of a minimally conscious state, in that he could follow commands. Schiff says that in other cases, such as Terri Schiavo, the 41-year-old brain-damaged woman who became the centerpiece of a national right-to-die battle, deep brain stimulation didn't work because the brain damage was just too great.

Schiff says the team has Food and Drug Administration approval to treat 12 patients.

Obesity: Dr. Andres Lozano, professor of neurosurgery at the University of Toronto and president of the World Society for Stereotactic and Functional Neurosurgery, used deep brain stimulation to treat obesity in a 420-pound man.

The patient lost about 25 pounds but later regained the weight. One possible reason? He turned off the device at night to snack.

That's why patients in the first deep brain stimulation-obesity experiments in the U.S. don't have the option to turn off their devices, says Dr. Donald M. Whiting of the Allegheny General Hospital in Pittsburgh, who is conducting the U.S. obesity trials with colleague Dr. Michael Oh.

So far, only two patients have been treated, chosen because they failed numerous diets as well as gastric bypass surgery.

Carol Poe from Morgantown, W.Va., joined the trial in February and says that nine weeks after the device was turned on she had lost 11.5 pounds.

But it's too soon to say if the therapy worked, Whiting says, because the initial effects could be due to a placebo effect from the surgery -- the patient knew you did something and thus expects a change that may not last.

Whiting has FDA approval to treat just three patients for now. He says he stimulates -- and thereby theoretically down-regulates -- the lateral hypothalamus, a brain area that acts as the feeding center of the brain. Animals with damage in this area simply stop eating.

The theory, Whiting says, is that the area has a certain density of receptors for hunger hormones that determine a person's metabolism level and energy set point, and the stimulation changes that.

Indeed, Whiting says, he does get the appropriate responses from the patients during the surgery. When he hits the right spot with the electrode, they report feeling nauseated, and even belch.

Alzheimer's: Lozano of the University of Toronto is also using deep brain stimulation to try to improve memory in patients with mild or early Alzheimer's disease.

Lozano discovered the area he stimulates by accident. While stimulating the hypothalamus to treat obesity in his 420-pound patient, the man -- who was under only local anesthesia -- remembered things from his life that happened 20 years earlier.

"He got a flashback," Lozano says. "He was in a park with his girlfriend. He could tell us what kind of day it was, what kind of clothes he was wearing, what they were saying, et cetera. As we turned off the stimulation, this memory would go away [and when] we turned it back on, it would reappear immediately." The case was published last year in the Annals of Neurology.

Lozano also found that whenever the electrode was on, the man remembered pairs of related words in a test better than when it was off. And brain imaging showed that the stimulation turned on the memory circuit in his brain.

Lozano has now started a pilot study to treat patients who have mild or early Alzheimer's disease. "We have operated on six patients so far," Lozano says. "So far, it appears safe and promising."

Addiction and anorexia: Dr. Bomin Sun, associate professor of neurosurgery at the Shanghai Jiatong University Rui Jin Hospital in China, has been testing deep brain stimulation for treating people with heroin addiction and anorexia. He targets the nucleus accumbens, inhibiting that brain region. Brain imaging shows that this area becomes overly active in people with these conditions, Sun says.

Sun has so far used deep brain stimulation to treat three anorexic girls who refused to eat and had body mass indexes of less than 14 when they were treated. He says they are now all back to normal weight.

He also treated two heroin addicts. One, he says, is cured, and the other only needs to take methadone once a day instead of heroin injections, he says. Neither of the findings are published in journal articles, although the heroin addiction cases are to be published in an upcoming book, "Neuromodulation."

health@latimes.com

Copyright © 2014, Los Angeles Times
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