Emory大精神神経学教授Dr. Helen Maybergは、「精神医学における非常に悪い歴史がある」と言う。フライングと焚きつけは止めてほしい。
ボン大学精神科Dr. Thomas Schlaepferは、肥満・拒食症・内気・中毒など考えられる最もクレージーな適応だ。誰でも早くゲームのゴールにたどり着きたい。混乱すれば全てが台無しとなる。
With deep brain stimulation, experts want to tread carefully
By Andreas von Bubnoff
June 1, 2009
With the flurry of tests being done on deep brain stimulation for a variety of conditions, some warn that the field is moving too fast.
They say it must not repeat the mistakes made during the era of lobotomy surgeries between 1939 and 1951, when thousands of patients were treated with little or no proof that lobotomies worked and with little or no follow up.
"There is a very bad history in psychiatry," says Dr. Helen Mayberg, professor of psychiatry and neurology at Emory University in Atlanta. "I don't want people to jump the gun and blow it for everybody."
Adds Dr. Thomas Schlaepfer, vice chairman of the department of psychiatry of the University of Bonn, Germany, "I [have] reviewed studies for obesity, anorexia, shyness, addiction, the most crazy indications you can think about. Everyone wants to get in the game early. . . . If things go haywire it might kill the whole field."
For one thing, deep brain stimulation is brain surgery. There can be complications -- such as bleeding, stroke, coma, death and infection.
Other risks may depend on where the electrodes are placed in the brain. After deep brain stimulation for Parkinson's disease, for example, patients may have problems with swallowing, obsessive compulsive disorder, gambling and dementia, and there may be an increased suicide rate.
It is unclear, Mayberg says, whether these effects are related to the stimulation or merely reflect the progression of the disorder.
Mayberg says that, over five years, no side effects have been observed in patients treated for depression with deep brain stimulation in a part of the brain called area 25. Perhaps, she speculates, the area where deep brain stimulation is done in Parkinson's disease patients has more signal traffic between nerve cells than does area 25.
But Schlaepfer suggests that side effects aren't yet observed in patients treated for depression because the number of treated patients is still too small.
Schlaepfer says the two large clinical trials being conducted on deep brain stimulation for depression may be premature.
In a trial, he says, one needs to keep the area of stimulation constant in every patient. But only about 50 depressed patients so far have been treated with deep brain stimulation, and "it's just not enough to make an informed decision on what the right target [in the brain] is," he says. "This research is mainly driven by industry and not by public funding, [and] it's going a little bit too fast for my taste."
Dr. Joseph Fins, chief of the division of medical ethics and a professor at Weill Cornell Medical College in New York, thinks the Food and Drug Administration may have acted too soon in granting a "humanitarian device exemption" to deep brain stimulation for severe obsessive-compulsive disorder. This will allow patients to receive the therapy outside of clinical trials, he says -- and there won't be a systematic collection of data, making effectiveness that much harder to establish.
In addition, small experiments on just a few patients don't always get published, says Dr. Andres Lozano, professor of neurosurgery at the University of Toronto and president of the World Society for Stereotactic and Functional Neurosurgery. "Sometimes there are only two patients," Lozano says. "Then, unless [the findings] are published, you don't necessarily hear about them."
Some have suggested guidelines for patient selection. And in a February editorial in the journal Biological Psychiatry, Dr. Wayne Goodman of the National Institute of Mental Health and NIMH director Dr. Thomas Insel called for a registry of all deep brain stimulation studies to make sure that all cases get follow-up to learn what does and doesn't work.
Deep brain stimulation research also raises ethical questions, such as how to make sure patients who may have diminished capacity to consent understand the risks and benefits of participating in the trials. In 2007, researchers met to discuss such issues. Recommendations will be published in an upcoming paper.
Some issues with deep brain stimulation have to do with what happens when the procedure succeeds. One of his depression patients, Schlaepfer says, lost his girlfriend because she couldn't deal with his newly found independence.
"She didn't like [that] he was not a poor guy anymore and started to be more normal," Schlaepfer says, "which was something [we] never anticipated."
Deep brain stimulation a puzzling process
June 1, 2009
Surprisingly little is known about how deep brain stimulation works, in spite of the fact that tens of thousands of Parkinson's and other movement disorder patients have been treated with the therapy.
"Right now it's not only not known which cells are the target, but also if they turn [their activity] up or down" in response to the stimulation, says Dr. Karl Deisseroth of Stanford University. "It's that level of confusion."
In the case of Parkinson's disease, stimulation of the brain's subthalamic nucleus has the same effect as damage to the subthalamic nucleus. In other words, even though the treatment stimulates the subthalamic nucleus, it may have the same effect as inhibiting it.
In other cases -- for example in treating minimally conscious patients -- deep brain stimulation seems to have the opposite effect to damaging the targeted brain area.
Deep brain stimulation being tested with brain injury, Alzheimer's, obesity and more
But tests for DBS' use with traumatic brain injury, Alzheimer's, obesity, anorexia and addiction are being conducted on small numbers of patients and not in formal clinical trials.
By Andreas von Bubnoff
June 1, 2009
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."
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