PREreview del Increased occurrence of migraine aura and susceptibility to spreading depolarizations at altitude

In addition to experimental and observational evidence for noteworthy vulnerability to cortical spreading depolarizations (SDs) in high-altitude settings, this study investigates the association between altitude and the occurrence of migraine auras. The authors provides evidence for the findings that, self-reported migraine aura prevalence rises with residential elevation using registry data from the American Registry for Migraine Research (ARMR). Hypoxic conditions and simulated altitude lower the threshold for SD initiation, according to supporting laboratory work in animal models and in vitro tissue. One of this work's main strengths is the way it combines experimental neuroscience with human epidemiology.

Major issues

• Due to possible selection bias, registry participants might not be a part of typical of the high-altitude population as a whole. External validity would be enhanced by additional information on geographic distribution and recruitment.

• There is no clear and obvious way to account for variations in lifestyle between altitude groups, comorbidities, medication use, or socioeconomic status. These might affect the frequency of migraine aura. Standalone evidence purely do to altitude is required.

• The cross-sectional human data does not support the idea that aura prevalence rises with altitude. There is still a chance of reverse causation or confounding environmental factors (such as changes in barometric pressure, UV exposure or lifestyle).

• Generalizability of animal models: Although evidence of rodent SD susceptibility is strong, extrapolation to human migraine aura is intrinsically restricted and needs to be handled more carefully.

• Rather than depending solely on p-values, results from human data would benefit from explicit effect sizes (odds ratios with 95% CIs).

Minor issues

• Describe in detail the geographic distribution of participants by altitude, the inclusion/exclusion criteria, and the ARMR recruitment procedure.

• Incorporate adjusted analyses that account for potential confounders like lifestyle factors, comorbid conditions, age, sex, BMI, and migraine subtype.

• Provide effect sizes and confidence intervals for the correlation between aura prevalence and altitude.

• Include a section on the animal work's limitations that acknowledges the variations in neurovascular physiology among species.

• Make the definitions and classifications of altitude levels in the human and animal components more clear.

• When interpreting human data, temper causal claims and place an emphasis on association.

Competing interests

The author declares that they have no competing interests.