Abstract
BACKGROUND: Hematoma expansion (HE) typically portends a poor prognosis in spontaneous intracerebral hemorrhage (ICH). Several radiographic and laboratory values have been proposed as predictive markers of HE. AIM: To perform a systematic review and meta-analysis on the association of neutrophil-to-lymphocyte ratio (NLR) and HE in ICH. A secondary outcome examined was the association of NLR and perihematomal (PHE) growth. METHODS: Three databases were searched (PubMed, EMBASE, and Cochrane) for studies evaluating the effect of NLR on HE and PHE growth. The inverse variance method was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies' estimates of the logarithm odds ratio (OR). Given heterogeneity of the studies, a random effect was applied. Risk of bias was analyzed using the Newcastle-Ottawa Scale. The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The protocol was registered in PROSPERO (No. CRD42024549924). RESULTS: Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis. Among those, HE was investigated in eight studies, whereas PHE growth was evaluated in three. Blood sample was obtained on admission in ten studies, and at 24 hours in one study. There was no consensus on cut-off value among the studies. NLR was found to be significantly associated with higher odds of HE (OR = 1.09, 95%CI: 1.04-1.15, I (2) = 86%, P < 0.01), and PHE growth (OR = 1.28, 95%CI: 1.19-1.38, I (2) = 0%, P < 0.01). Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders. CONCLUSION: The available literature suggests that a possible association may exist between NLR on admission and HE, and PHE growth. Future studies controlled for systemic confounders should be designed to consolidate this finding. If confirmed, NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.