Aug 02 2007

Waking the Comatose

A research team lead by Dr. Nicholas Schiff recently reported very encouraging results from their treatment of a 38 year old man who had been in a minimally conscious state (MCS) for six years. The patient was the victim of assault with severe brain injury. Two years ago he was given a new experimental treatment involving the implantation of electrodes for brain stimulation. In the past two years the patient has made a significant recovering, gaining the ability to eat, to perform simple tasks, and to engage in limited speech.

Stories of people “waking from coma” are always dramatic and emotional, and also need to be placed into a rather complex and evolving medical context. With coma, doctors walk the line cautiously between hope and realism. On the one side they risk the peril of giving false hope to grieving loved ones who need to accept the situation and cope with it. On the other they risk “therapeutic nihilism,” giving up too soon and relegating a patient prematurely to custodial care. Whenever such cases of remarkable recoveries come up there is much wringing of hands and even accusations of how this line was not treaded optimally.

In reality, doctors have a large body of statistical evidence behind them and can make very accurate predictions of who is likely to recover and who is not. But even with a high degree of accuracy, there are still going to be surprises.

As background it is essential to understand a bit about consciousness and coma, for not all comas are created equally. In order to be conscious a person requires at least one hemisphere of the brain be mostly functioning and they require a functioning brainstem. The cortical hemispheres contain the gray matter – that part of the brain that thinks. So it makes sense that a certain minimal amount of gray matter is necessary to generate consciousness. As gray matter is damaged or inhibited from functioning one’s level of consciousness decreases until it descends beyond that fuzzy boundary into unconsciousness. When such unconsciousness is persistent we call that coma.

But interestingly the cortex by itself cannot generate consciousness. It requires constant prodding by a diffuse region in the brainstem (that primitive part at the base of the brain that connects the brain and the spinal cord) called the brainstem activating sytem. This region sends a constant barrage of electrical signals through the thalamus (the relay center of the brain) and then onto the cortex. Without this constant stimulation the cortex will lapse into sleep and coma.

It is possible, therefore, that someone’s cortex, with all of their memories and personality, can be intact but they are permanently asleep because their brainstem is damaged. This is a very different kind of coma than that which results from diffuse cortical damage – although the end result may be very similar and of no consequence to the individual.

Therefore when considering coma, generally or in an individual, the exact type and severity of coma needs to be carefully defined before any meaningful statements or predictions can be made.

In this case the victim suffered from diffuse brain injury. I do not know the extent of brainstem damage, and there might have been some, but by reports there was definitely diffuse cortical damage. The extent of damage was characterized as a minimally conscious state. In this state the person displays signs of some consciousness. They may react to their environment and may even attempt to verbalize. Patients in a MCS have a poor prognosis for good recovery, but some do improve significantly.

MCS needs to be distinguished from a persistent vegetative state (PV), in which there are, by definition, no signs of consciousness. PV states carry a grim prognosis with a small chance of any meaningful recovery that diminishes further over time. Very rarely a patient in a PV state may improve into a MCS.

This new treatment involves implanting electrodes in the thalamus connected to a devise that is used for deep brain stimulation (used to treat Parkinson’s disease or severe depression). The purpose is to increase the stimulation of the cortex, which makes sense once we know that the cortex needs this stimulation normally in order to be awake. In this case being reported the patient immediately showed subtle signs of improvement and over the last two years had continued to improve.

This is certainly an important breakthrough, but it is still one baby step. It is important to recognize that this is a single case and it remains to be seen how widely applicable this treatment will be. Also, the patient remains severely neurologically impaired. The ability to eat without a feeding tube, to interact more meaningfully with others, to say a few words is without doubt a real benefit. But we should not leap to visions of people in a MCS suddenly progressing to lead a normal life. This is not like the movies where someone wakes from a coma and is suddenly cognitively normal.

The challenge for the future is to build on this new tool. What we have now is a treatment that for some patients in a certain kind of coma (MCS) may produce an improvement in wakefulness and therefore neurological function, but still leaves the patients significantly impaired. But this is showing us the way to a new therapeutic approach in coma patients. Perhaps the development of more sophisticated implantable computer chips will treat such comas more effectively. Computer chips may even take over for damaged parts of the brain. Parallel research is also under way into using stem cells to replace damaged brain cells. I therefore think we are seeing the beginning of turning coma into a treatable condition.

We are also getting better at assessing the neurological function of people in a coma. Previously we could only infer neurological function from the neurological exam. While highly predictive in most cases, it is limited in the assessment of MCS patients because we cannot test cortical function. Because patients in a MCS cannot interact significantly with the examiner it is not possible to assess their higher cortical functions. Until recently we have had to be content to use electroencephalograms to look at electrical activity and MRI’s to look at anatomical integrity.

Recently, however, there have been studies using function MRI scanning (fMRI) to look at cortical activation in MCS patients while giving them a verbal task. Early results show more cortical activity than was expected, giving hope that some MCS patients may have more going on in their brains than was apparent. The studies also show that their brains have much less activity than normal controls – no surprise since they are in a MCS from brain damage.

Therefore, in combination with developing actual treatments for some patients in MCS we are developing the tools to better predict who is likely to respond to treatment.

Like most medical progress, these developments are incremental, but they do represent significant milestones. As a practicing neurologist I cannot overemphasize how much I look forward to having such tools to help assess and treat these unfortunate patients. And of course this is nothing compared to what it can mean for the patients themselves and their families.

We continue to walk the line between hope and realism, but the line just got a bit wider and better illuminated.

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