Intrathecal administration of GABA agonists in the vegetative state

Abstract

Gamma aminobutyric acid (GABA) is an inhibitor neurotransmitter that plays many important roles in the central nervous system. Because the half-life time of GABA is very short in vivo, GABA itself is not used for clinical practice. An analogue of GABA, baclofen, is an agonist of GABA-B receptor, and has very strong antispastic effect by acting to the posterior horn of the spinal cord. However, baclofen poorly crosses through the blood brain barrier, and the antispastic effect is modest when administered orally. Therefore, direct continuous infusion of small doses of baclofen into the cerebrospinal fluid (intrathecal baclofen therapy, ITB) has become an established treatment for control of otherwise intractable severe spasticity. Spasticity is clinically defined as hypertonic state of the muscles with increased tendon reflexes, muscles spasm, spasm pain, abnormal posture, and limitation of involuntary movements. Spasticity is a common symptom after damage mainly to the pyramidal tract system in the brain or the spinal cord. Such damage is caused by traumatic brain injury, stroke, spinal cord injury, multiple sclerosis, and so on. Patients in persistent vegetative state (PVS) usually have diffuse and widespread damage to the brain, spasticity is generally seen in such patients. Control of spasticity may become important in the management of PVS patients in terms of nursing care, pain relief, and hygiene, and ITB may be indicated. Among PVS patients who had ITB to control spasticity, sporadic cases of dramatic recovery from PVS after ITB have been reported worldwide. The mechanism of such recovery of consciousness is poorly understood, and it may simply be a coincidence. On the other hand, electrical spinal cord stimulation (SCS) has been tried for many years in many patients in PVS, and some positive effects on recovery of consciousness have been reported. SCS is usually indicated for control of neuropathic pain, but it has also antispastic effect. The mechanism of SCS on pain is known to be mediated through the spinal GABA neuronal system. Thus, ITB and SCS have a common background, spinal GABA neuronal mechanism. The effect of GABA agonists on recovery of consciousness is not yet established, but review of such case studies becomes a clue to solve problems in PVS, and there may be hidden serendipity.