The Paradoxical Prognostic Value of Endogenous Melatonin in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Mild-to-Moderate versus Malignant Infarctions
DOI:
https://doi.org/10.37275/bsm.v10i6.1607Keywords:
Acute ischaemic stroke, Biomarker, Melatonin, Meta-analysis, PrognosisAbstract
Background: Acute ischaemic stroke (AIS) is a leading global cause of morbidity and mortality. While endogenous melatonin is widely proposed as a neuroprotectant, recent clinical evidence suggests a paradoxical, severity-dependent prognostic relationship. This meta-analysis synthesises evidence regarding this paradox and its prognostic implications.
Methods: A systematic search of major databases through March 2026 identified observational studies correlating endogenous melatonin levels with AIS clinical outcomes. Data were stratified by stroke severity phenotype, and standardised mean differences were calculated using random-effects meta-regression models.
Results: Ten observational studies comprising 847 AIS patients were included. A striking paradox emerged: in patients with mild-to-moderate stroke, lower melatonin concentrations were associated with poor clinical outcomes. Conversely, in malignant middle cerebral artery infarctions, higher melatonin concentrations were paradoxically linked to worse clinical outcomes, including increased mortality. Extreme overall heterogeneity (I²=97.85%) was substantially resolved (I²=0%) upon proper severity stratification.
Conclusion: The prognostic implications of endogenous melatonin fundamentally differ according to stroke severity phenotype. This severity-dependent paradox likely reflects context-dependent alterations in melatonin signalling pathway efficacy. Mechanistic investigations and well-designed prospective trials are urgently warranted to elucidate the underlying pathophysiology.
Authors
- Merry Angeline1*
- Desak Ketut Indrasari Utami2
- Kumara Tini2
- 1Specialised Residency Training Program, Department of Neurology, Faculty of Medicine, Universitas Udayana/Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Indonesia
- 2Department of Neurology, Faculty of Medicine, Universitas Udayana/Prof. Dr. I.G.N.G. Ngoerah General Hospital, Denpasar, Indonesia
Corresponding author Merry Angeline — merryangeline2012@gmail.com
Article history
- Submitted
- Accepted
- Published
Downloads
Published
Issue
Section
License
As our aim is to disseminate original research article, hence the publishing right is a necessary one. The publishing right is needed in order to reach the agreement between the author and publisher. As the journal is fully open access, the authors will sign an exclusive license agreement.
The authors have the right to:
- Share their article in the same ways permitted to third parties under the relevant user license.
- Retain copyright, patent, trademark and other intellectual property rights including research data.
- Proper attribution and credit for the published work.
For the open access article, the publisher is granted to the following right.
- The non-exclusive right to publish the article and grant right to others.
- For the published article, the publisher applied for the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
