Oct 20 2008

Treating Coma with Magnetic Stimulation

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There has recently been a number of news reports relating to coma, a fascinating topic and subject of active research, so there is no wonder that the public (and therefore the press) take an interest. Often, mainstream news stories focus on the notion of people “waking” from coma, or recovering from what was thought to be a permanent injury. This tends to hype the important, but subtle, progress that is being made.

The latest such story is of Josh Villa, a 26 year old gentleman who suffered a severe head injury in 2005 from a car accident. The injuries resulted in coma – the inability to be consciously awake – which evolved into a persistent vegetative state (PVS). By description, Josh was able to open his eyes but not respond to any external stimulation or interact with his environment. This meets the clinical definition of PVS.

Transcranial Magnetic Stimulation

His doctor, Theresa Pape, enrolled him is a study of transcranial magnetic stimulation (TMS). TMS uses strong magnetic fields to either induce or inhibit electrical activity in brain neurons. Therefore the technique can be used to turn off part of the brain, or stimulate it to be more active.

In this case TMS was used to stimulate the dorsolateral cortex in Villa – a part of the brain active in arousal. The hope was that by increasing activity in the dorsolateral cortex Villas entire brain would be more active, improving function. After 15 sessions of TMS over 6 weeks Villa was able to turn his head to someone speaking to him. After the treatments he contingued to slowly improve and eventually was able to say simple words like “help” and fragments like “erm”.Villa was then given another round of TMS treatments, but with no further improvement.  He has since been stable.

Villa’s current condition is best described as a minimally conscious state, which is one notch above PVS. In fact, patients in a minimally conscious state are not uncommonly misdiagnosed as PVS if subtle signs of activity are missed on exam. The question now is – how to interpret Villa’s improvment?

It is not implausible that TMS can produce the improvements observed in Villa. Essentially what is happening is that a damaged brain, which is close to the line of just barely being able to generate wakefulness, is being stimulated so that it functions a bit more. Specifically, TMS may result in hypersynchronization – neurons firing together, which may reinforce their activity.

Increased activation has been shown before with deep brain stimulation – implanting electrodes in the brain that provide an extra kick to the cortex and make it a bit more active. The brain normally requires such activation to be awake, so such artificial stimulation may be replacing lost activation is some cases, or simply increasing the levels of activation in others.

While useful, such techniques should not be considered “healing” – they are not healing the brain, just squeezing a bit more activity out of it. Can TMS cause actual healing? Villa’s improvement persisted even after the TMS sessions ended (although he did lose a bit of ground, some improvement remained). Therefore his increased function cannot be attributed entirely to active stimulation, although hypersynchronization would endure beyond stimulation.

But an alternate hypothesis  is the intriguing possibility that the stimulation increased repair of actual damage, perhaps by stimulating the activity of natural brain stem cells. Right now we have no way of knowing if this occurred.

It is also possible that Villa improved on his own, and would have improved the same amount even without the treatments. He was only a year out from his injury, well within the window where natural repair mechanisms could have produced the observed improvement in function. The TMS may have produced a temporary improvement over the background repair that was happening on its own.

The problem is that this is only one case, and with one case we cannot control for variables. What this study suggests is that there is a possible benefit from TMS and so further research is warranted.

TMS does have stronger evidence for benefit with neurological conditions such as Parkinson’s disease and tremor, but in these cases TMS is being used to inhibit brain activity, not increase it. The basic concept here is that there are systems in the brain where various structures provide feedback activation or inhibition to other structures so that a certain balance is maintained. If one structure is disease and not functioning, this can be partially compensated for by inhibiting another structure to help restore something closer to normal balance. Again – such an application does not “heal” damaged or diseased brain.

Magnetic Healing

I have been careful to discuss the mechanisms by which TMS may have clinical benefit, in patients with coma and other applications, partially because it is helpful to understand how an intervention might work. But also because magnetic therapy is a common type of unscientific or fraudulent treatment being sold to the public. Magnets are sold with a variety of medical claims, such as treating pain or arthritis.

TMS in no way relates to these dubious claims for magnet therapy. There are two primary differences. The first is that TMS uses a magnetic field much more powerful than the typical “refrigerator magnets” found in magnetic insoles or wraps. The plausibility of a biological effect from a magnetic field is directly tied to the strength of the magnet.

The second is that TMS is being used to affect the brain, which is an electromagnetic organ. While all cells have an electrical field potential across their membrane, the brain’s function depends upon cells evolved to use this electrical potential to actually conduct electrical signals. Therefore, the fact that magnetic stimulation can have a functional effect on the brain cannot be extrapolated to other tissues or organs.

Incidentally, the other tissue that uses electrical conduction as a key component of its function is muscle – heart, skeletal, and smooth muscle. The heart can also be treated with electrical stimulation – with a pacemaker or with cardioversion. Muscles can be stimulated electrically also. There is simply no analogy with the liver or pancreas, however. And (although I know many have pointed this out before) the iron in blood is not magnetic and does not respond to a magnetic field.

Details matter, and a therapeutic benefit from TMS of the brain for any specific indication should not be used to support TMS for other indications, or for magnetic therapy is general.

Conclusion

TMS is an interesting tool to explore brain function, and may have a therapeutic role as a means of providing stimulation to damaged brains to improve function. However, the data so far is preliminary. Further, there is no evidence to suggest that TMS actually heals brain damage.

I am intrigued and hopeful about recent research into treating coma victims, but results so far (from various forms of brain stimulation) have been modest. Generally speaking, patients improve one or two notches in brain function, and this may take them over a threshold where they can communicate better, but they remain profoundly neurologically damaged. It remains to be seen what the limits of brain stimulation as a therapeutic approach to coma are.

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