A Biomarker Coming of AGE: Skin Autofluorescence Predicts Functional Outcome after Aneurysmal Subarachnoid Hemorrhage

Early risk stratification following aneurysmal subarachnoid hemorrhage (aSAH) is clinically challenging. Beyond the initial hemorrhage severity, chronic metabolic vulnerability may contribute to secondary brain injury. Skin autofluorescence (SAF) is a rapid, noninvasive bedside biomarker that quantifies advanced glycation end product (AGE) accumulation. The prognostic relevance after aSAH has not been characterized previously.

In a prospective single-center cohort study, SAF was measured during the index hospital stay in consecutive adult patients with confirmed aSAH. The primary endpoint was poor functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 4-6. Secondary endpoints included delayed cerebral ischemia (DCI; defined as delayed neurological deterioration ≥ 1 h and/or new cerebral infarction not attributable to other causes) and radiographic vasospasm. Associations were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses.

A total of 50 patients completed 90-day follow-up; 22 (44%) experienced poor functional outcome. SAF demonstrated a strong association with poor functional outcome (logistic regression coefficient 2.28, p = 0.001), yielding an approximate odds ratio of 9.8 per unit increase. Discriminative performance was excellent (AUC 0.81). An optimal SAF cutoff value of ≥ 2.6 yielded a sensitivity of 0.82, specificity of 0.71, positive predictive value of 0.69, and negative predictive value of 0.83. SAF showed a moderate association with DCI (p = 0.045; AUC 0.68) but not with radiographic vasospasm (p = 0.35). These results remained robust in multi-predictor models after controlling for baseline disease severity.

Bedside SAF predicts poor 90-day functional outcome following aSAH and is associated with DCI, but not with radiographic vasospasm. These findings support a pathophysiological role for chronic metabolic vulnerability in determining secondary brain injury severity and functional recovery after aSAH. The prospective cohort is currently being expanded, and external validation in larger prospective multicenter cohorts is warranted.