Pupillary Nystagmus as an Objective Neuro-Otological Biomarker in Vestibular Migraine: A Quantitative Pupillometric...

Background: Vestibular migraine (VM) is a common cause of episodic vertigo, yet its diagnosis remains primarily clinical and is often complicated by the absence of reliable objective biomarkers. Pupillary nystagmus, reflecting spontaneous oscillations of pupil diameter, has been proposed as a potential clinical sign of VM, but its quantitative characterization remains limited. Objective: The objective of this study is to evaluate the diagnostic value of pupillary nystagmus in VM and to provide a quantitative assessment using infrared pupillometry. Methods: In this case-control study, 137 patients with vestibular migraine and 102 healthy controls underwent comprehensive neuro-otological evaluation, including vestibular testing and pupillometric assessment. Pupillary activity was recorded using a dedicated infrared pupillometer, and oscillatory dynamics were quantified using the Pupillary Unrest Activity Level (PUAL), which was derived through spectral analysis (Larson-Neice algorithm). Statistical comparisons were performed using non-parametric methods. Results: PUAL values differed significantly between VM patients and controls (Mann-Whitney test p < 0.001), demonstrating a clear separation between groups. A cut-off value of 0.325 was identified as the upper limit of normality, suggesting that elevated PUAL values may indicate vestibular migraine. Conclusions: Pupillary nystagmus represents a clinically accessible sign that can be objectively quantified through infrared pupillometry. The PUAL index provides a measurable parameter reflecting altered vestibulo-autonomic dynamics in VM and may serve as a promising neuro-otological biomarker. The integration of pupillometric analysis with clinical evaluation may improve diagnostic accuracy and support the development of objective diagnostic tools in vestibular migraine.