Visual, vestibular, and ocular motor changes during nitroglycerin-triggered vestibular migraine

Intravenous nitroglycerin (NTG) is a well-established model for provoking migraine attacks, but it has not previously been used to characterize vestibular migraine (VM). Different types of nystagmus have been reported during spontaneous VM attacks. We aimed to measure changes in nystagmus during NTG-induced migraine in participants with VM.

We studied 20 participants with definite VM (Barany-International Classification of Headache Disorders, 3rd edition criteria) undergoing NTG provocation in a prospective, within-subject repeated-measures pharmacological provocation study under three conditions at the National Institute for Health and Care Research King's Clinical Research Facility, London, between November 2024 to December 2025. Median (interquartile range [IQR]) age was 32 (29 to 38) years, and 16/20 were female. 3D video-oculography was used to quantify total slow-phase velocity (SPV) (°/s) of nystagmus without fixation in the center, left, right, up, and down positions. Recordings were repeated before NTG, after NTG, and after subcutaneous sumatriptan. Subjective vestibular symptoms and headache intensity were quantified with an ordinal numeric scale. Longitudinal changes in SPV were analyzed.

All the participants developed headache, with median peak severity 6/10 (IQR 4 to 7). Vestibular symptoms were triggered in 14/20 participants following NTG, with a median maximum intensity of 2.5 (IQR 0 to 4). Median (IQR) summed SPV (°/s) was 2 (1 to 3.25) at baseline, 1.5 (0 to 4.75) following NTG, and 1 (0 to 2.75) after sumatriptan. In Tweedie generalized linear mixed-effects models, no significant group-level effect of condition on total SPV was detected. Estimated marginal means were 1.87 (95% confidence interval [CI] 1.02 to 3.41) at baseline, 2.10 (95% CI 1.16 to 3.80) following NTG, and 1.73 (95% CI 0.93 to 3.19) after sumatriptan. Compared with baseline, neither NTG (β = 0.118, standard error [SE] = 0.267, P = 0.658) nor sumatriptan (β = -0.078, SE = 0.278, P = 0.780) showed significant effects. NTG provocation was associated with complex perceptions such as visual symptoms (10/20) and Alice in Wonderland syndrome type or dissociative symptoms (6/20), including derealization/depersonalization, metamorphopsia, macropsia and pelopsia, dysmorphopsia, and distorted passage of time.

Quantitative slow phase velocity measures of nystagmus did not show a uniform group-level change during NTG provocation in VM, despite frequent subjective vestibular symptoms. VM episodes may reflect altered central sensory processing and vestibular hypersensitivity rather than changes in vestibulo-oculomotor output.