PROLONGED COMAS AND STRESS: POSSIBLE DRUG THERAPY?

PROLONGED COMAS AND STRESS:

POSSIBLE DRUG THERAPY?

By Renato COCCHI, MD, neurologist and medical psychologist

Key words: Coma, stress, GABA, glutamate, EEG, drug therapy, carbamazepine, speculation.

I consider comas as an extreme brain reaction to stress. Of course it would be hard to consider any type of coma so. When we are faced to comas "sine materia", like anoxic comas, this assertion seems easier to be accepted.

Some prolonged comas can have unexpected awakenings after years, although the physicians ' contrary opinion. This is a challenging medical and ethical problem with heavy economical implications.

On the other hand an Italian rehabilitative centre soon recently claimed to be able to successfully treat such comas with stimulatory therapies, mainly with music.

We need to develop a coherent frame of reference to understand those awakenings, eventually not so rare.

As an example, in July 1999 we have read the news that another 20-year young man awoke from a coma that has lasted two years. This coma followed a motorbike accident. In these two years, during his stay in the hospital of Terracina (Italy) he had many surgical operations and sensory stimulation therapies. Although the doctors told the family of the futility of these treatments the parents never accepted it and 10 days before they had taken their son home. His awakening was first manifested with a gesture and soon after by asking for food.

I do not think this to be a miraculous event but rather a medical problem. So I should like to put forward some ideas that I have developed over the years.

Perhaps we lack a coherent frame of reference for understanding phenomena like these, which appear to us so unexpected.

We have the misleading idea that a negative outcome (the coma) can only derive from a whole negative process (lack of brain "energy").

The opposite is also possible at least in part. The coma could be the exit of an excess of "energy," like type B GABAergic inhibition and glutamergic overstimulation, both because of an extreme stress. Of course the starting point is a negative process, the decrease of type A GABAergic inhibition (Horger and Roth, 1995).

As for comas, their EEG with very slow waves (delta waves) could confirm that GABA is involved, when we make an analogy with what happens by using GABAergic drugs like valproate, gabapentin or vigabatrin in normal or epileptic people.

As far as increased glutamergic overstimulation, this usually results following sustained stress reactions (Horger and Roth, 1995).

Any stimulation - sensorily and/or emotionally targeted or even surgical stimulation (a side-effect of any surgical aim) - can decrease the excess of glutamate by consumption.

The perceptive neuronal pathways use mainly glutamate as their neurotransmitter (see Budai and Larson, 1998 for many references).

By this way the "spontaneous" awakening from the coma could come out by a reverse cascade of events, although not fully clarified mainly for the action of glutamate on type A GABAergic receptors (Horger and Roth, 1995).

Consumption is a not yet underlined mechanism of the human body biology but the need to do something at weekends by several "neurotic" Ss (often the so-called "job-addicts") can lead us to understand it. Their behaviour (they cannot rest otherwise they became irritated or suffer from psychosomatic symptoms like headaches), is a diffused behaviour of consumption. I wrote the same for rocking in autistic or other PDD children or in depressed children too, where it owns an evident calming action as the "artificial" rocking of the cradle testifies for it (Cocchi, 1997).

On the other hand, as for epilepsy we can act on EEG-waves by using correct drugs. The little known rule of the thumb should be: When EEG detects slow waves we can try to balance them by prescribing accelerating drugs like benzodiazepines or carbamazepines. When EEG detects rapid waves we can try to decrease them by using slowing drugs like valproate and so on. I have previously reported the use of accelerating drugs in treating people with pseudodementia showing delta-theta waves and I monitored their positive effects by QEEG (Cocchi, 1996).

As a concluding anecdote, when I was working in the Pesaro psychiatric hospital, about in first seventies, one day I was called suddenly because a young man had hang himself. Immediately helped, he was into a serious coma. By intuition I decided to inject 10mg diazepam i.v.. To everybody surprise he directly awoke from the coma.

Now I know that in this way I reopened type A GABAergic receptors with diazepam, so reducing synaptic GABA overacting on type B GABAergic receptors. By backwards, glutamic acid decarboxylase (GAD) could have restarted its action and so it reduced glutamate by increasing its transformation into GABA.

By directly acting on these three points - with diazepam for promoting type A GABAergic inhibition, with carbamazepine as a brain Ca++ antagonist (Crowder and Bradford, 1987) for decreasing type B GABAergic inhibition and with pyridoxine for improving GAD activity with pyridoxal-phosphate, cofactor of all decarboxylases - could we act on comas? Of course, to give diazepam to a comatose person should appear a heretical suggestion but I tried to explain the rationale and QEEG can daily monitor the progress (if any) of such a trial.

Prolonged comas are a medical challenge, and these "spontaneous" awakenings shall force the doctors to delay any final decision with increased hospital costs, for not to say of related ethical problems.

You can ask me why I do not put into action this suggestion by myself? I do not work in an intensive care unit, and in Italy doctors do not like new procedures, if they do not have any foreign corroboration.