Evaluation of Inner Ear–Specific Serum Biomarkers for Differentiating Vertigo From Stroke in the Emergency Department

Acute dizziness is a common emergency department (ED) presentation, and distinguishing benign peripheral vertigo from central causes such as ischemic stroke remains clinically challenging. Delayed or missed diagnosis of posterior circulation stroke contributes to significant morbidity. This study aimed to evaluate whether circulating inner ear-specific biomarkers could differentiate peripheral vestibular pathology from central neurologic causes of dizziness using human blood and serum samples.

Blood samples were collected from ED patients presenting with dizziness who underwent standard diagnostic evaluation for either peripheral vertigo or suspected stroke. Enzyme-linked immunosorbent assays (ELISAs) were performed to quantify serum levels of two candidate biomarkers, otolin-1 and prestin, selected based on prior associations with inner ear pathology. Standard curves demonstrated acceptable linearity and assay performance. Biomarker concentrations were compared between patients diagnosed with vertigo and those with ischemic stroke. All ELISA assays were performed by an investigator blinded to clinical diagnosis and final patient classification.

ELISA standard curves demonstrated good linearity for both analytes (otolin-1 R² = 0.962; prestin R² = 0.979), confirming acceptable assay performance. Both biomarkers were reliably detectable in human serum and quantified across the validated dynamic ranges (otolin-1: 0-2400; prestin: 0-1600). Across samples, measured concentrations demonstrated substantial inter-sample variability with overlapping distributions, thus, no evidence of diagnostic separation or clinical significance between clinical entities was observed.

In this cohort, circulating levels of otolin-1 and prestin did not differentiate peripheral vertigo from ischemic stroke in ED patients despite adequate assay performance. These findings suggest that isolated inner ear-specific serum protein biomarkers may be insufficient for clinical discrimination between these entities. Future directions include expanded cohort analysis, integration of multimarker panels, and metabolomic and biomarker discovery approaches to improve diagnostic accuracy in acute dizziness.