Favorable Systemic Immune-Inflammation Status Enhances the Neuroprotective Effects of Butylphthalide in Ischemic...

Among revascularized acute ischemic stroke patients, residual poor outcomes may partially arise from dysregulated poststroke inflammatory and immune responses.

In this secondary analysis of the BAST trial, the systemic immune-inflammation index (SII) was calculated for 837 patients with acute ischemic stroke who underwent revascularization at baseline and on Day 14 after treatment, and patients were categorized into four distinct SII change patterns. Network pharmacology analysis was conducted to explore potential mechanisms linking butylphthalide, inflammation-related pathways, and ischemic stroke outcomes.

Compared with the persistent unfavorable group, both the unfavorable-to-favorable and persistent favorable groups had higher odds of a favorable modified Rankin Scale (mRS) score (odds ratio (OR) = 2.79, 95% confidence interval (CI): 1.64, 4.73, p_FDR < 0.001; OR = 2.60, 95% CI: 1.66, 4.06, p_FDR < 0.001) and an mRS score of 0-2 on Day 90. These groups also had lower risks of recurrent stroke, vascular events, and death within 90 days. Patients with persistent favorable SII who received butylphthalide showed the most favorable observed outcome profile, including the highest proportion of favorable mRS score on Day 90 (OR = 3.60, 95% CI: 1.97, 6.58, p_FDR < 0.001) and a higher proportion of mRS score 0-2 on Day 90 (OR = 4.38, 95% CI: 2.23, 8.62, p_FDR < 0.001) and the lowest risk of recurrent vascular events. Network pharmacology findings suggested that these exploratory associations may involve multi-pathway regulation of neuroinflammation, cellular stress responses, and vascular pathology.

Favorable or improving SII status during the acute phase of ischemic stroke was associated with better 90-day functional outcomes and lower vascular risk. Patients with persistently favorable SII who were assigned to butylphthalide showed the most favorable observed outcome profile.