Sufficiency and necessity in migraine: how do we figure out if triggers are absolute or partial and, if partial, additive or potentiating?

Abstract

Migraine is, to a great extent, a genetically determined disorder and once it has manifested itself, it generally continues for years if not for decades. While the migraine is active, headaches can seemingly occur spontaneously but are often reportedly precipitated by events or factors, known as migraine triggers, the interplay of which is the topic of this paper. Among migraine triggers, the menstrual cycle is an important one that probably accounts for much of the excess of migraine in women compared with men. Much has also been written about stress as a trigger of migraine, with headache occurring after rather than during stress, when relaxation occurs. Stress is also 1 of the 4 most often acknowledged headache triggers in general, the others being fatigue, not eating on time, and lack of sleep. Singularly, the triggers are generally necessary but not sufficient, ie, not powerful enough to bring on headache by themselves and, hence, compounding of those triggers is usually required. There is evidence to suggest that the premenstrual phase has a magnifying effect on the stress-headache interaction. The same is true for low-sleep duration with the (predictive) model fitting best when stress and low-sleep duration are considered additive. Menstruation has been identified as possibly the only absolute trigger of headache that is both necessary and sufficient. The scientific study of migraine triggers requires knowledge not just of how often in an individual a trigger is followed by migraine headache but also of how often it is not. Having identified trigger-headache associations, it needs to be determined which triggers are causative in the individual, either singly or in combination with others. This requires running an experiment with the individual that involves behavioral intervention to change exposure to a given trigger and determine whether that improves migraine. The ubiquitous adoption of the smart phone as a personal-data entry device, along with the possibility of bringing the results of sophisticated statistical analysis into the hands of patients and physicians, may well provide us with an important set of tools that will finally allow the unravelling of the age-old migraine-trigger puzzle.