[en] Aims: Treatment with apomorphine, a dopamine agonist, has exhibited behavioral effects on the recovery of patients with disorders of consciousness (DOC)[1,2], but its action on brain activity remains unknown. We report the preliminary results of a prospective open-label study using multimodal assessment methods, which aims to confirm the efficacy and investigate the mechanism of apomorphine treatment among post-coma patients.
Methods: Three patients with chronic DOC (1 female, 2 males; 47, 34 and 23 years old; 1 hemorrhage, 2 traumatic; 3.5, 4.5 and 3 months since onset) were administered subcutaneous apomorphine for 30 days. They were followed 30 days before initiation, during treatment and 30 days after withdrawal. Outcome measures included Coma Recovery Scale – Revised (CRS-R)[3], positron emission tomography (PET)[4,5] and electroencephalography-based (EEG) measures such as functional connectivity[6] and multivariate machine-learning classification[7,8].
Results: At baseline, patients 1 and 2 were diagnosed with the CRS-R as minimally conscious state (MCS) minus[9,10] (language-independent signs of consciousness), and patient 3 as MCS plus (language-related signs of consciousness). After the initiation of apomorphine, patient 1 improved to MCS plus, patient 2 remained in MCS minus but showed a new sign of consciousness and more consistent behaviors, and patient 3 emerged from the MCS.
PET revealed an improvement of global brain metabolism after compared to before apomorphine treatment for all three patients (difference of +43%, +26%, and +4% for patient 1, 2 and 3 respectively). Functional connectivity measured by EEG network centrality also increased after treatment for all patients in the alpha frequency bands. EEG multivariate classifier improved after treatment for two patients (difference of +25%, +20%, -1% for patient 1, 2, and 3 respectively) with significant increase in most individual EEG markers.
Conclusion: After treatment, patients showed multimodal improvements with more frequent conscious behaviors and increased brain activity measures compared to baseline observations. These results suggest that the action of apomorphine on the recovery of DOC patients may be associated with measurable neuroimaging changes. Additional results from the subsequent placebo-controlled randomized controlled trial[11] will be necessary to confirm the efficacy and further define the neural effects of apomorphine treatment in severely brain-injured patients.
Research Center/Unit :
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)
Acknowledgments:
We thank the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (F.R.S-FNRS), NeuroHealing Pharmaceuticals Inc., the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907, the Luminous project (EU-H2020-fetopenga686764), the Center-TBI project (FP7-HEALTH- 602150) and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778234; LS and NL are research fellows and SL is research director at F.R.S-FNRS; we thank Eurogenerics and Britannia Pharmaceuticals Ltd. for providing clinical trial materials.
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