Pathophysiology and treatment approaches for perihematomal edema following spontaneous intracerebral hemorrhages

To summarize the involvement of perihematomal edema (PHE) in the progression of spontaneous intracerebral hemorrhage (sICH) correlated with the clinical outcome under systematic, structured review. This review was conducted and reported with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. Literature searching was conducted using Cochrane Library, Embase, PubMed, Scopus, Web of Science, and CNKI search engines with predefined keywords. Minimally invasive surgical hematoma evacuation and mannitol application demonstrate broad clinical utility with promising prospects. The outcomes of clinical trials involving MW01-6-189WH and diroximel fumarate remain inconclusive. Fingolimod and minocycline, currently in the experimental phase, require large-scale RCTs to further validate their efficacy. Numerous interventions showing therapeutic potential for PHE in preclinical studies face challenges in clinical translation, including individual variability, blood–brain barrier protection, and difficulties in conducting clinical trials. Different treatment strategies are proposed based on distinct stages of pathological progression, and emerging therapeutic approaches are summarized. Existing interventions are categorized into three tiers according to their level of evidence, with future development directions and key challenges from basic research to clinical application outlined for each category.