Intrathecal baclofen in patients with persistent vegetative state: 2 hypotheses

Sporadic cases of recovery from persistent vegetative state
(PVS) after administration of intrathecal baclofen (ITB) have
been reported without giving any possible explanation for its
paradoxical effect. We summarize our recent findings on 5
patients with PVS treated with ITB and make some speculations
on the mechanisms responsible for the observed clinical
improvement. The patients developed spasticity and were
judged eligible for ITB therapy. Two weeks after pump implantation,
patients began to show a clinical improvement that,
at the end of the 6 months’ follow-up, was stable in all but 1
patient, ranging from a mere increased alertness to a full
recovery of consciousness, as revealed by changes of the Coma
Recovery Scale–Revised (CRS-R) score. Our findings suggest
that ITB might favor a variable degree of clinical improvement.
A proposal for a pharmacodynamic explanation of this effect
has not been formally put forward. We hypothesize 2 possible
mechanisms: first, a modulation confined to spinal cord segmental
activities and to neuronal centripetal outputs reaching
the cortex; and second, a modulation of sleep-wake cycles that,
although present, may be dysregulated and interfere with alertness
and awareness. Although our research is confined to a few
subjects, it provides follow-up information by means of the
CRS-R that is a validated standardized neurobehavioral instrument
expressly designed for use in patients with PVS. Our
observations indicate that further systematic investigation of
the mechanisms and the putative clinical applications of ITB
should be undertaken.