Evidence map›Paper›PMID 39624459›Full record

ArticleEClinicalMedicine2024

Apomorphine for prolonged disorders of consciousness: a multimodal open-label study.

Leandro R D Sanz, Nicolas Lejeune, Emilie Szymkowicz, Estelle A C Bonin, Rajanikant Panda, Arianna Sala, Aurore Thibaut, Rodrigo Huerta-Gutierrez, Nadia Dardenne, David Dikenstein and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. The Gray Zone of Consciousness: Cognitive Motor Dissociation.Current neurology and neuroscience reports · 2025
    Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Leandro R D SanzComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Nicolas LejeuneComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Emilie SzymkowiczComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Estelle A C BoninComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Rajanikant PandaComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Arianna SalaComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Aurore ThibautComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Rodrigo Huerta-GutierrezInstitute of Public Health and Center for Stroke Research, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Nadia DardenneUniversity and Hospital Biostatistics Center (B-STAT), Faculty of Medicine, University of Liège, Liège, Belgium.
David DikensteinCHN William Lennox, Groupe Hospitalier Saint-Luc, UCLouvain, Ottignies-Louvain-la-Neuve, Belgium.
Sébastien Van GoethemCHN William Lennox, Groupe Hospitalier Saint-Luc, UCLouvain, Ottignies-Louvain-la-Neuve, Belgium.
Didier LedouxCentre du Cerveau, University Hospital of Liège, Liège, Belgium.
Roland HustinxDepartment of Nuclear Medicine, University Hospital of Liège, Liège, Belgium.
Johan StenderDepartment of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
Neal M FarberNeuroHealing Pharmaceuticals Inc., Waban, MA, USA.
Ross D ZafonteDepartment of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
Nicholas D SchiffFeil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA.
Steven LaureysComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Olivia GosseriesComa Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: 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 open-label controlled study using multimodal outcome measures investigates the action of apomorphine in severely brain-injured patients. Methods: Thirteen PDoC patients received 30-day subcutaneous apomorphine treatment (n = 6) or standard care (control group, n = 7) in a neurological rehabilitation centre between February 2018 and January 2021. 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. Registration: EudraCT 2018-003144-23; Clinicaltrials.govNCT03623828. Findings: 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. Interpretation: 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. Funding: University and University Hospital of Liege, Belgian National Funds for Scientific Research, Fund Generet of the King Baudouin Foundation, AstraZeneca Foundation, Leon Fredericq Foundation and NeuroHealing Pharmaceuticals Inc.

Indexed as

ApomorphineComaDisorders of consciousnessHigh-density electroencephalographyMinimally conscious stateNeuroimagingPositron emission tomographySevere brain injuryTreatmentUnresponsive wakefulness syndromeVegetative state

Identifiers

PMID39624459
PMCPMC11609466

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.