Elkan R. Gamzu

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

Background: The prognosis of long-term severe disorders of consciousness due to traumatic brain injury is discouraging. There is little definitive evidence of the underlying mechanisms, but a deficiency of the dopaminergic system may be involved. Methods: In a prospective open-labelled clinical study, the feasibility, relative efficacy and safety of continuous subcutaneous (s.c.) administration of apomorphine in Vegetative State (VS) or Minimally Conscious State (MCS) patients due to severe traumatic brain injury (TBI) was tested. Apomorphine was administered to eight patients. Outcome measures were the Coma Near-Coma Scale (CNCS) and Disability Rating Scale (DRS). Results: Drug management was implemented without any problems. There was improvement in the primary outcomes for all patients. Awakening was seen as rapidly as within the first 24 hours of drug administration and as late as 4 weeks. Seven of the patients had completely recovered consciousness. All improvements were sustained for at least 1 year, even after apomorphine was discontinued. Drug-related adverse events were all anticipated and resolved after the dose was reduced. Conclusion: Based on this open-label pilot study, continuous s.c. apomorphine infusion appears to be feasible, safe and potentially effective in improving consciousness in patients in VS and MCS due to severe TBI.

Fast awakening from minimally conscious state with apomorphine

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.

Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia

The current study evaluated under double-blind placebo-controlled conditions, the safety and efficacy of 400 mg pramiracetam sulphate TID in treating memory and other cognitive problems of males who have sustained brain injuries. The results of the study indicate that subject performance in measures of memory, especially delayed recall, evidenced clinically significant improvements after the administration of pramiracetam sulphate as compared to placebo. This improvement was maintained during an 18-month open-trial period on the medication as well as during a 1-month follow-up period after the pramiracetam was discontinued.