Serum Otolin-1 and Otoconin-90 are not elevated in vestibular migraine: a preliminary case-control study

TL;DR

This study found that serum Otolin-1 and Otoconin-90 levels are not elevated in vestibular migraine patients compared to healthy controls, suggesting these proteins may not be useful biomarkers for this condition.

Contribution

The study is the first to investigate Otolin-1 and Otoconin-90 as potential biomarkers for vestibular migraine, revealing their lack of diagnostic utility.

Findings

Serum Otolin-1 and Otoconin-90 levels were not significantly different between vestibular migraine patients and healthy controls.

Otolin-1 levels in VM patients decreased over time post-attack, showing a phase-dependent pattern.

The results suggest a central/functional pathophysiology for vestibular migraine rather than structural damage to otoconia.

Abstract

Vestibular migraine (VM) is a common cause of episodic vertigo but lacks objective diagnostic biomarkers. The symptomatic overlap of VM with benign paroxysmal positional vertigo (BPPV) and Meniere’s disease (MD) complicates differential diagnosis. Given that elevated serum Otolin-1 and Otoconin-90 (OC90) levels are established biomarkers in BPPV and MD, this study aimed to determine whether these otoconia-derived proteins are also altered in VM.

In this case-control study, 40 patients with definite VM and 143 age- and sex-matched healthy controls were included. Serum samples were collected during the interictal period. Otolin-1 and OC90 levels were quantified using enzyme-linked immunosorbent assays.

No significant differences were found in serum levels of Otolin-1 and OC90 between groups. The median (IQR) Otolin-1 level was 215.5 pg/mL (127.5–314.9) in the VM group vs. 200.6 pg/mL (127.7–284.2) in controls (Cliff’s δ = 0.08, p = 0.526). Similarly, the median (IQR) OC90 level was 39.8 ng/mL (29.4–60.8) compared to 32.7 ng/mL (27.9–77.9) in controls (Cliff’s δ = −0.07, p = 0.659). No correlations were observed between protein levels and clinical features. However, within the VM group, serum Otolin-1 levels were highest within 1-week post-attack and declined thereafter, showing a significant negative correlation with time (r = −0.372, p = 0.018). A similar phase-dependent pattern was observed for OC90 levels across the VM subgroups (p = 0.017), though without a significant correlation with continuous time.

These preliminary findings indicate that serum Otolin-1 and OC90 levels are not altered in patients with VM compared to healthy controls. Exploratory analysis revealed a phase-dependent decrease in Otolin-1 within the VM group post-attack. These results argue against significant structural damage to otoconia in VM and support a central/functional pathophysiology. While not positive diagnostic biomarkers, normal levels of these proteins may provide negative evidence to aid in differentiating VM from BPPV or MD, pending future validation.

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