Investigators measured plasma otolin-1 in 245 adults presenting to emergency departments with isolated acute-onset continuous dizziness (iAOCD) to test whether the inner ear–specific glycoprotein could differentiate peripheral from central causes. The cohort included 179 patients adjudicated with peripheral vestibular disorders and 66 with central diagnoses by an expert panel blinded to biomarker results. Median concentrations did not separate groups: 517.6 pg/mL for peripheral cases versus 487.9 pg/mL for central cases (p = 0.349). The distribution plots showed substantial overlap across groups, and receiver operating characteristic analysis returned an overall AUC of 0.539 (95% CI 0.455–0.623), indicating no useful discriminatory performance in this clinical sample.
The study drew from the PROVIDE prospective multicenter cohort and used a stratified sampling approach to ensure representation of central causes. Patients were included if they presented within 24 hours of symptom onset and lacked new focal neurological deficits; exclusion criteria and enrollment procedures followed the PROVIDE protocol. Blood was collected at ED presentation in K3-EDTA tubes, centrifuged, aliquoted and stored at −80°C until analysis. Otolin-1 concentrations were measured with a commercially available ELISA kit (MyBiosource catalog number MBS167289) following the manufacturer’s instructions. Laboratory staff were blinded to clinical data and final diagnoses. Final diagnoses were established by an expert panel using clinical findings, diffusion-weighted MRI and 3-month outpatient follow-up; the panel did not have access to otolin-1 results.
Because early imaging can miss posterior circulation infarctions, the authors examined whether sampling time influenced the biomarker signal. They stratified patients into a hyperacute subgroup (<4.5 hours from symptom onset) and an acute subgroup (4.5–24 hours). In the hyperacute window, median otolin-1 concentrations were 522.1 pg/mL for peripheral iAOCD and 535.3 pg/mL for central iAOCD (p = 0.711). In the 4.5–24 hour window median values were 508.1 pg/mL versus 484.4 pg/mL (p = 0.155). ROC analyses within these windows yielded AUCs that included 0.50 in their confidence intervals (hyperacute AUC 0.474; acute AUC 0.574), showing no reliable time-dependent discrimination.
The investigators also compared otolin-1 across the central diagnosis group and individual peripheral diagnoses such as vestibular neuritis, benign paroxysmal positional vertigo (BPPV) and Ménière’s disease. Median concentrations did not differ significantly between central iAOCD and any specific peripheral subgroup. Although several peripheral cases displayed higher otolin-1 concentrations than the observed central range, the overall pattern was one of overlap rather than separation. Prior literature cited in the source shows elevated otolin-1 in BPPV and other peripheral vestibular syndromes compared with asymptomatic controls, but those disease-versus-control contrasts do not translate into useful central-versus-peripheral discrimination in an acute ED population.
The authors noted several constraints inherent to their design. The selected sample of 245 subjects came from a larger PROVIDE cohort; while the stratified approach ensured central-case representation, diagnostic groups were not randomized and baseline clinical differences between groups (including vascular risk factor prevalence) were expected. Missing data were not imputed and general laboratory tests followed local institutional protocols. The ELISA platform and pre-analytic handling were standardized per protocol, but the source did not report any alternative assay validations or repeat-measure stability testing beyond the manufacturer instructions. Importantly, the study found broad overlap of otolin-1 concentrations between central and peripheral causes and weak ROC performance, which together indicate that otolin-1 alone cannot be recommended as a stand-alone diagnostic biomarker to rule in or rule out central causes of iAOCD in the emergency setting.
Several clinical questions remain open based on the reported data. The study did not provide evidence that combining otolin-1 with bedside diagnostics such as the HINTS examination, clinical scoring tools, or other circulating markers improves discrimination—these combined-performance analyses were not reported. The mechanism underlying elevated otolin-1 in some peripheral cases but not universally, and whether chronic versus acute otolithic turnover drives plasma levels, was discussed as a biological possibility in the source but not resolved by these data. Future research will need to test whether serial sampling, multimarker panels, or integration with clinical algorithms alters diagnostic utility; the present trial did not address those approaches.
In sum, within this prospective, multicenter ED cohort using blinded adjudication and a commercial ELISA platform, plasma otolin-1 concentrations did not distinguish central from peripheral causes of iAOCD and therefore lack sufficient discriminatory value as a single diagnostic test in the acute setting.