When an alarm isn't enough, try a dopamine agonist instead?

April 17th, 2010 in Uncategorized 0 comments

After a serious accident, victims can sustain grave injuries, such as severe traumatic brain injury (TBI), resulting in focal lesions and/or diffuse axonal injury. This can result in a coma that can develop into a Vegetative State (VS) or Minimally Conscious State (MCS), wherein the victim regains arousal, but with low awareness. Studies of these states suggest a deficiency in dopamine, a neurotransmitter involved with general stimulation, wakefulness, and circadian rhythms. Thus, to treat VS/MCS patients, dopamine agonists, such as l-dopa , bromocriptine, and amantadine, have been used. These agonists are plagued with issues, namely that they are either too weak (bromocriptine and amantadine) or may result in complications due to administration method (l-dopa). Thus, a group of researchers have recently tested apomorphine, which is potent and is a broadly acting dopamine agonist, to attempt treating VS/MCS. In fact, apomorphine is so potent, that it is the drug of last resort in Parkinson’s Disease (PD). The researchers continuously administered apomorphine subcutaneously (via pump) to a 25-year-old male patient for 12 hours a day (followed by 12 hours of rest period) over 179 days. They saw results as early as the first day, when the patient was able to move his limbs on command and answer yes/no questions (which did not happen preceding treatment). Following this, their patient even made a full recovery of consciousness and regained substantial functional ability. This regain of consciousness and function continued pas discontinuation of treatment. Though there were side effects in the form of dyskinesias at high doses, the treatment resulted in remarkable recovery at lower doses. Using Diffusion Tensor Imaging (DTI), an MRI technique, the researchers found a decrease of thalamocortical and corticothalamic projections (compared to the control). It may be that VS/MCS is a result of thalamocortical and corticothalamic dopaminergic deficiencies, which can be a treated quite easily with apomorphine. If it is a universal cause of VS/MCS in trauma victims, we may soon expect apomorphine widely used to revive comatose patients.

Source:
Fridman EA, Krimchansky BZ, Bonetto M, Galperin T, Gamzu ER, Leiguarda RC, et al. Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury. Brain injury : [BI]. 2010;24(4):636-41

-Neil Datta