Effects of intrathecal baclofen therapy in subjects with disorders of consciousness: a reappraisal

Baclofen is a structural analogue of gamma-amino-butyric acid (GABA), which reduces spastic hypertonia of striated muscle due to a mechanism of GABAB-ergic inhibition of mono- and polysynaptic reflexes at the spinal level. There are reports of patients with severe disorders of consciousness that presented a substantial improvement following intrathecal baclofen (ITB) administration for severe spasticity. The neural mechanisms underlying the clinical recovery after ITB have not yet been clarified. Baclofen could modulate sleep-wake cycles that may be dysregulated and thus interfere with alertness and awareness. The diminished proprioceptive and nociceptive sensory inputs may relieve thalamo-cortical neural networks involved in maintaining the consciousness of the self and the world. ITB treatment might also promote the recovery of an impaired GABAergic cortical tone, restoring the balance between excitatory and inhibitory cortical activity. Furthermore, glutamatergic synapses are directly or indirectly modulated by GABAB-ergic receptors. Neurophysiological techniques (such as transcranial magnetic stimulation, electroencephalography, or the combination of both) can be helpful to explore the effects of intrathecal or oral baclofen on the modulation of neural cortical circuits in humans with disorders of consciousness.