Fast awakening from minimally conscious state with apomorphine

Abstract

Background: Traumatic brain injury (TBI) can induce long-term severe disorders of consciousness. Evidence suggests an underlying dopaminergic deficit. Dopamine agonists may therefore play an important role in recovery of consciousness. Objective: To explore the response to continuous subcutaneous administration of apomorphine in a patient who had remained in minimally conscious state for 104 days and to evaluate the anatomical substrate of the effect. Design: A prospective, open-label, daily treatment, dose-escalation single case clinical study, with retrospective diffusion tensor image (DTI) evaluation. Results: On the fist day of treatment, the patient was able to move his limbs on command and answer yes/no questions which had not been the case prior to apomorphine administration. Subsequently there was a full recovery of consciousness and substantial functional recovery that was sustained even after apomorphine discontinuation. At the highest dose, mild dyskinesias were observed. These resolved with a lowering of the dose. DTI demonstrated a decrease of thalamocortical and corticothalamic projections in this MCS patient compared to normal volunteers. Conclusion: Although this is an open-label single-patient case report, the data are consistent with the theory that a dopaminergic deficit underlies MCS and that it may be overcome with apomorphine administration.

Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury

“…This lack of integration could be due to selective damage of the thalamus, present in more than 80% of these patients [4]. Thalamocortical projections from the intralaminar nucleus are reduced following a severe TBI [8], affecting the nigro-striatal dopaminergic system. Indeed, in post-traumatic VS or MCS patients, abnormalities of dopaminergic neurotransmission such as reductions of the dopamine transporter and expression of D 2 receptors have been reported [9].…”

Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain

“…Dopaminergic drugs may directly increase the dopaminergic tone within the c-TH, enhancing its output (37,38). It is also likely that dopaminergic drugs at the striatum may counterbalance the observed deficits in the direct and indirect pathway (via D 1 and D 2 , respectively) (39), and the net gain would be the reduction of the inhibitory input to the c-TH.…”

Pharmacological and electrical stimulation in chronic disorders of consciousness: New insights and future directions

“…Because the diagnostic criteria for MCS are new, there are fewer functional neuroimaging studies of MCS compared with VS patients; nevertheless, thalamocortical and corticothalamic projections are also important in the physiopathology of MCS. Half of all MCS patients experience selective damage to the thalamus [24]. Therefore, a common mechanism of the interventions in this study might involve the thalamus and its reciprocal projections to the cortex by targeting the thalamus directly (such as with DBS or dopaminergic drugs) to modulate secondary cortical areas, indirectly via the spinal cord (i.e.…”