Lipid Peroxidation Metabolites as Biomarkers in Patients with Aneurysmal Subarachnoid Hemorrhage and Cerebral Vasospasm or Delayed Cerebral Ischemia: A Systematic Review

Introduction: Intracranial aneurysms (IAs) are often asymptomatic until they rupture, causing aneurysmal subarachnoid hemorrhage (aSAH). aSAH frequently leads to cerebral vasospasm (CVS), which can result in delayed cerebral ischemia (DCI), increasing the risk of severe neurological deficits and mortality. Identifying biomarkers for aSAH, CVS, and DCI, such as lipid peroxidation metabolites (LPMs), is essential for early prediction and timely intervention. We aimed to summarize current knowledge on LPMs as potential biomarkers.

Methods: A systematic review was conducted according to PRISMA guidelines. Two authors searched PubMed, Web of Science, and Scopus from the inception to June 2024 for studies on the association of fatty acid peroxidation metabolites with DCI following aSAH. The quality and risk of bias were assessed using the STROBE checklist. The extracted data included LPM concentrations, biological specimen type, sample collection timing, age, gender, aSAH clinical severity, Fisher’s grade, DCI definition, relation to DCI, and peak concentration timing.

Results: Of 519 records screened, 16 met inclusion criteria. Biological specimens for LPM measurements included blood - 5 studies, cerebrospinal fluid (CSF) - 11 studies, and urine - 2 studies. F2-Isoprostanes (F2-IsoPs), reported in seven studies, were linked with increased DCI risk, showing elevated levels between the first and third day post-aSAH. Higher concentrations of arachidonic acid (AA) metabolites - 6-keto-prostaglandin F1-α (6-keto-PGF1α), prostaglandin D2 (PGD2), and leukotriene C4 (LTC4) - were also associated with early DCI risk. Isofurans (IsoFs) predicted DCI risk between the fifth and eighth day post-aSAH, and elevated PCOOH on day two correlated with symptomatic vasospasm.

Conclusion : Our review suggests that higher concentrations of F2-IsoPs and AA derivatives may be associated with higher DCI risk in aSAH patients, especially within the first three days. These findings highlight the potential for LPMs as early biomarkers for DCI, enabling timely intervention to improve patient outcomes. Future studies should explore LPMs’ therapeutic applications.