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Wednesday, November 19, 2008

Deep Brain Stimulation Cures Urge To Break Glass

Deep Brain Stimulation (DBS) is in. There's been much buzz about its use in severe depression, and it has a long if less glamorous record of success in Parkinson's disease. Now that it's achieved momentum as a treatment in psychiatry, DBS is being tried in a range of conditions including chronic pain, obsessive-compulsive disorder and Tourette's Syndrome. Is the hype justified? Yes - but the scientific and ethical issues are more complex, and more interesting, than you might think.

Biological Psychiatry have just published this report of DBS in a man who suffered from severe, untreatable Tourette's syndrome, as well as OCD. The work was performed by a German group, Neuner et. al. (who also have a review paper just out), and they followed the patient up for three years after implanting high-frequency stimulation electrodes in an area of the brain called the nucleus accumbens. It's fascinating reading, if only for the insight into the lives of the patients who receive this treatment.
The patient suffered from the effects of auto-aggressive behavior such as self-mutilation of the lips, forehead, and fingers, coupled with the urge to break glass. He was no longer able to travel by car because he had broken the windshield of his vehicle from the inside on several occasions.
It makes even more fascinating viewing, because the researchers helpfully provide video clips of the patient before and after the procedure. Neuropsychiatric research meets YouTube - truly, we've entered the 21st century. Anyway, the DBS seemed to work wonders:
... An impressive development was the cessation of the self-mutilation episodes and the urge to destroy glass. No medication was being used ... Also worthy of note is the fact that the patient stopped smoking during the 6 months after surgery. In the follow-up period, he has successfully refrained from smoking. He reports that he has no desire to smoke and that it takes him no effort to refrain from doing so.
Impressive indeed. DBS is, beyond a doubt, an exciting technology from both a theoretical and a clinical perspective. Yet it's worth considering some things that tend to get overlooked.

Firstly, although DBS has a reputation as a high-tech, science-driven, precisely-targeted treatment, it's surprisingly hit-and-miss. This report involved stimulation of the nucleus accumbens, an area best known to neuroscientists as being involved in responses to recreational drugs. (It's tempting to infer that this must have something to do with why the patient quit smoking.) I'm sure there are good reasons to think that DBS in the nucleus accumbens would help with Tourette's - but there are equally good reasons to target several other locations. As the authors write:
For DBS in Tourette's patients, the globus pallidus internus (posteroventrolateral part, anteromedial part), the thalamus (centromedian nucleus, substantia periventricularis, and nucleus ventro-oralis internus) and the nucleus accumbens/anterior limb of the internal capsule have all been used as target points.
For those whose neuroanatomy is a little rusty, that's a fairly eclectic assortment of different brain regions. Likewise, in depression, the best-known DBS target is the subgenual cingulate cortex, but successful cases have been reported with stimulation in two entirely different areas, and at least two more have been proposed as potential targets (Paper.) Indeed, even once a location for DBS has been chosen, it's often necessary to try stimulating at several points in order to find the best target. The point is that there is no "Depression center" or "Tourette's center" in the brain which science has mapped out and which surgery can now fix.

Second, by conventional standards, this was an awful study: it only had one patient, no controls, and no blinding. Of course, applying usual scientific standards to this kind of research is all but impossible, for ethical reasons. These are people, not lab rats. And it does seem unlikely that the dramatic and sustained response in this case could be purely the placebo effect, especially given that the patient had tried several medications previously.

So what the authors did was certainly reasonable under the circumstances - but still, this article, published in a leading journal, is basically an anecdote. If it had been about a Reiki master waving his hands at the patient, instead of a neurosurgeon sticking electrodes into him, it wouldn't even make it into the Journal of Alternative and Complementary Medicine. This is par for the course in this field; there have been controlled trials of DBS, but they are few and very small. Is this a problem? It would be silly to pretend that it wasn't - there is no substitute for good science. There's not much we can do about it, though.

Finally, Deep Brain Stimulation is a misleading term - the brain doesn't really get stimulated at all. The electrical pulses used in most DBS are at such a high frequency (145 Hz in this case) that they "overload" nearby neurons and essentially switch them off. (At least that's the leading theory.) In effect, turning on a DBS electrode is like cutting a hole in the brain. Of course, the difference is that you can switch off the electrode and put it back to normal. But this aside, DBS is little more sophisticated than the notorious "psychosurgery" pioneered by Walter Freeman performed back in the 1930s and that have since become so unpopular. I see nothing wrong with that - if it works, it works, and psychosurgery worked for many people, which is why it's still used in Britain today. It's interesting, though, that whereas psychosurgery is seen as the height of psychiatry barbarity, DBS is lauded as medical science at its most sophisticated.

For all that, DBS is the most interesting thing in neuroscience at the moment. Almost all research on the human brain is correlational - we look for areas of the brain which activate on fMRI scans when people are doing something. DBS offers one of the very few ways of investigating what happens when you manipulate different parts of the human brain. For a scientist, it's a dream come true. But of course, the only real reason to do DBS is for the patients. DBS promises to help people who are suffering terribly. If it does, that's reason enough to be interested in it.

See also: Someone with Parkinson's disease writes of his experiences with DBS on his blog.

ResearchBlogging.org
I NEUNER, K PODOLL, D LENARTZ, V STURM, F SCHNEIDER (2008). Deep Brain Stimulation in the Nucleus Accumbens for Intractable Tourette's Syndrome: Follow-Up Report of 36 Months Biological Psychiatry DOI: 10.1016/j.biopsych.2008.09.030

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