Abstract Background and aims Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high mortality and disability. Early prediction of hematoma expansion and long-term functional outcomes remains limited. Metabolomics, an analysis of small-molecule metabolites in biological samples, offers a promising path for identifying molecular signatures and biomarkers predictive of clinical trajectories in ICH patients. Methods We conducted a systematic review of the literature using MEDLINE/PubMed, focusing on ICH and human studies that utilize blood-based biomarkers. A total of 149 articles were identified. The PRISMA flow diagram was utilized. Nine pivotal studies were chosen to represent a range of biomarker types and their associations with stroke type, hematoma expansion, and 90-day outcomes. The biomarkers examined include apolipoproteins (ApoC-I, ApoC-III), glial fibrillary acidic protein (GFAP), copeptin, and TNF-α gene variants. Methodologies included Surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS), immunoassays, and PCR-based genetic profiling. Results Plasma ApoC-I and ApoC-III levels differentiated hemorrhagic from ischemic stroke with high specificity (p 0.001). GFAP levels were significantly elevated in ICH patients within six hours of symptom onset (p 0.001). Elevated copeptin levels correlated with hematoma volume (r = 0.32) and were predictive of 30-day mortality and unfavorable 90-day outcomes (p = 0.003 and p = 0.04) TNF-α gene polymorphisms demonstrated gender-specific associations with spontaneous deep ICH risk. Conclusions We have identified metabolomic markers associated with hemorrhagic stroke. Future research should focus on validating the clinical significance of these markers, exploring their potential to guide therapeutic interventions aimed at preventing hematoma expansion, and improving outcomes. Conflict of interest Jorge Ortiz Garcia: nothing to disclose, Leila Gachechiladze: nothing to disclose, Dharambir Sanghera: nothing to disclose, Evgeny Sidorov: nothing to disclose.
Garcia et al. (Fri,) studied this question.