Apomorphine is a dopaminergic candidate therapy to improve recovery in patients with prolonged disorders of consciousness (PDoC). Behavioural improvements were previously described in non-controlled case series, but its efficacy and neural mechanisms remain largely unknown. This recently published open-label controlled study was led by researchers of the Coma Science Group, at the University of Liège, Belgium. It uses multimodal outcome measures to investigate the action of apomorphine in severely brain-injured patients.
Thirteen PDoC patients received 30-day subcutaneous apomorphine treatment (n = 6) or standard care (control group, n = 7) in a neurological rehabilitation centre. The apomorphine group was monitored 30 days before treatment initiation, during treatment and one year after treatment. Primary outcome measure was defined as changes in behavioural diagnosis using the Coma Recovery Scale—Revised (CRS-R). CRS-R index, recovery of new conscious behaviours, DoC-feeling scores, high-density electroencephalography, and fluorodeoxyglucose positron emission tomography were employed as secondary outcome measures. The control group was monitored with repeated CRS-R only.
Groups (apomorphine vs. control: odds ratio 8.9, 95% CI 3.3–17.8) and study phase (treatment vs. baseline, apomorphine group only: odds ratio 3.9, 95% CI 1.5–10.1) significantly influenced positive changes in behavioural diagnosis. At one-year post-injury, 4/6 patients in the apomorphine group and 1/7 patients in the control group had improved their diagnosis. Similarly, CRS-R index was significantly influenced by study phase (treatment vs. baseline). All items on the DoC-feeling score were rated higher after treatment than before by both family and medical staff. Patients in the apomorphine group recovered more conscious behaviours than control patients. Alpha-band whole-brain connectivity and participation coefficient, as well as alpha-band parieto-temporal connectivity and frontal participation coefficient were higher after treatment than at baseline. Whole-brain metabolism increased by a relative mean of 13.8% after treatment compared to baseline, with a significant effect of timing (pre-vs. post-treatment scans) on regional SUV.
Long-lasting consciousness improvements were observed in patients treated with apomorphine, compared to controls and compared to baseline. Changes in brain connectivity and metabolism were observed after treatment, providing insights into possible neurophysiological mechanisms and target areas. This open-label study confirmed the feasibility and safety of apomorphine treatment, which may represent a key therapeutic option for PDoC.
Key Points:
- Subcutaneous apormorphine is a promising candidate therapy to improve recovery in prolonged disorders of consciousness
- This open-label controlled study demonstrated the feasibility and safety of its use in this population
- Patients treated with apomorphine demonstrated a significant positive change in behavioral diagnosis compared to the control group
- Brain activity assessed by FDG-PET and high-density EEG were increased between the pre-treatment and the post-treatment measurements
- Further clinical trials using a placebo-controlled randomized design are necessary to confirm the efficacy of this therapy in clinical use and better target the profile of responders.
References:
Sanz et al. Apomorphine for prolonged disorders of consciousness: a multimodal open-label study. eClinicalMedicine, Volume 78, 102925, December 2024.
DOI: https://doi.org/10.1016/j.eclinm.2024.102925 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00504-2/fulltext
Co-author:
Nicolas Lejeune, Coma Science Group, GIGA Consciousness, University of Liège, Liège, Belgium
Publish on behalf of the Scientific Panel on Coma and chronic disorders of consciousness