Premorbid vulnerability beyond stroke severity: Prognostic value of the modified frailty index-5 in young adults...

Young-onset ischemic stroke (≤50 years) is associated with substantial long-term disability despite high rates of successful reperfusion following endovascular thrombectomy (EVT). Established predictors do not fully explain outcome variability. The prognostic role of premorbid vulnerability and intra-procedural hemodynamics in this population remains unclear.

We conducted a single-center retrospective cohort study of consecutive patients aged ≤ 50 years undergoing EVT for anterior circulation large-vessel occlusion (2015-2024). Premorbid vulnerability was assessed using the modified Frailty Index-5 (mFI-5). The primary outcome was poor functional outcome at 90 days (modified Rankin Scale [mRS] 3-6). Multivariable logistic regression was used to evaluate associations, adjusting for admission NIHSS, ASPECTS, successful reperfusion, and time to reperfusion. Model performance and reclassification were assessed using AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Among 220 patients, 24.5% had poor outcomes. Higher mFI-5 was independently associated with poor outcome (adjusted odds ratio ∼2.1 per point, p < 0.001), with a threshold effect at mFI-5 ≥ 2 (absolute risk increase 31.4%). Model discrimination improved with mFI-5 (AUC ∼0.77; ΔAUC up to 0.097). Risk reclassification was significant (NRI 0.736; IDI 0.109), driven primarily by improved identification of patients with favorable outcomes. No interaction was observed between mFI-5 and NIHSS. Among hemodynamic variables, cumulative MAP ≤ 70 mmHg was not independently associated with outcome, whereas ≥ 40% MAP reduction showed a borderline association.

Premorbid vulnerability independently predicts functional outcome after EVT for anterior circulation large vessel occlusion in young adults and improves prognostic precision beyond established predictors. Its primary value lies in refining risk among lower- and intermediate-risk patients. Hemodynamic associations were less robust. These findings are exploratory and require external validation.