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Increased occurrence of migraine aura and spreading depolarizations at altitude

by Melissa M. Cortez, Katelyn M. Reinhart, Cecilia Martindale, Leon S. Moskatel, J. Gary Urry, Zubair A. Ahmed, Anna Newman, Kendra Pham, Jared Bartell, Todd Schwedt, Sheena Aurora, Kathleen B. Digre, Susan K. Baggaley, and K.C. Brennan

Posted: August 13, 2025
Server: medRxiv
DOI: 10.1101/2025.08.09.25333153

Background and Objectives

Test the hypothesis that migraine aura is more prevalent at altitude.

Methods

This report includes iterative examination of the association of aura and altitude using multiple studies derived from varying sources, including cross-sectional chart reviews, a cross-sectional multicenter registry study, a cross-sectional cross-institutional electronic medical record database study, and altitude chamber experiments in mice.

Results

We identify an association between increasing elevation and the presence of migraine aura. All four lines of clinical evidence converge on an altitude phenotype, with higher elevations being associated with higher odds of clinically defined aura. In data from mice housed in altitude chambers, we show that susceptibility to spreading depolarization (SD) is increased with simulated elevation, providing a candidate mechanism for the altitude phenotype.

Discussion

The increased susceptibility to aura and SD with elevation may provide a unique opportunity to develop targeted strategies for both research and clinical mitigation, relevant to the nearly 1 billion people living at higher elevations worldwide.

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