[en] Background and aims:
Treatment with apomorphine, a dopamine agonist, has exhibited promising effects on the recovery of patients with disorders of consciousness (DOC) due to traumatic brain injury. This prospective open-label clinical trial aims to confirm its efficacy and investigate its action on brain activity.
Methods:
Patients with chronic DOC were administered subcutaneous apomorphine for 30 days. They were monitored 30 days before initiation, during treatment and 30 days after withdrawal. Outcome measures included Coma Recovery Scale – Revised (CRS-R), actigraphy, positron emission tomography (PET) and electroencephalography-based (EEG) metrics such as network centrality and a multivariate machine-learning classifier.
Results:
A 47-year-old woman in an unresponsive wakefulness state (UWS) due to a ruptured aneurysm underwent apomorphine treatment. CRS-R indicated a minimally conscious state (MCS) diagnosis in 1/9 assessment before treatment, increasing to 6/8 during treatment, and 4/5 after withdrawal (Fig.1).
Actigraphy showed higher mean activity and normalised power after treatment.
Compared to healthy controls, PET whole-brain metabolism revealed a 59% metabolic decrease before treatment and 51% after, with significant increases in right cortical areas. (Fig.2)
EEG multivariate classifier corresponded to UWS before treatment and MCS after, with significant increase in most individual markers.
Functional connectivity measured by network centrality increased predominantly in alpha frequency after treatment. (Fig.3)
Conclusion:
After treatment, this patient showed multimodal improvements with more frequent conscious behaviours and increased brain activity measures. These results suggest that the action of apomorphine on the recovery of DOC patients may be associated with measurable neuroimaging changes. Results of two subsequently treated patients will be reported.
Clinical trial identifiers: EudraCT 2018-003144-23; Clinicaltrials.gov NCT03623828
Research center :
Coma Science Group - GIGA Consciousness
Disciplines :
Neurology
Author, co-author :
Sanz, Leandro ; Université de Liège - ULiège > Consciousness-Coma Science Group
Lejeune, Nicolas ; Université de Liège - ULiège > Form. doct. sc. méd. (paysage)
