Abstract Background and aims Symptom onset time determines eligibility for reperfusion therapies in acute ischemic stroke, but many patients present with unknown onset. We developed a plasma lipidomic biomarker score (WHEN) to estimate time-from-onset in carotid-territory large vessel occlusion (LVO). Methods Consecutive suspected stroke admissions (May 2021–May 2023) were screened. Carotid-territory LVO patients underwent untargeted and targeted plasma lipidomics (LC–MS). In known-onset cases, biomarkers associated with early onset were identified across strata (≤3 h, 3–6 h, 6 h). The WHEN score assigned 1 point per biomarker below a predefined cutoff and was applied to unknown-onset patients. Results Among 1,031 admissions, 167 (16.2%) had carotid-territory LVO: 60/167 (35.9%) unknown onset and 107/167 (64.1%) known onset. Known-onset distribution was ≤3 h: 83/167 (49.7%), 3–6 h: 16/167 (9.6%), and 6 h: 8/167 (4.8%). Baseline characteristics (pre-stroke mRS, vascular risk factors, age, sex) were similar across groups. In the known-onset subgroup, five lipid biomarkers showed individual discrimination (ROC AUC 0.70) and formed the WHEN score (range 0–5), which discriminated early onset with AUC 0.841 (95% CI 0.739–0.943). A WHEN score ≥3 was observed in 81.8% of unknown-onset patients and 68.4% of known-onset patients, suggesting that many unknown-onset LVO cases resemble an early (3 h) lipidomic profile. Conclusions A plasma lipidomic-derived WHEN score may help estimate onset time in unknown-onset carotid-territory LVO, potentially expanding access to time-sensitive reperfusion therapies. External validation and prospective impact studies are warranted. Conflict of interest Nothing to disclose
Pereira-Preigo et al. (Fri,) studied this question.