Objective:To test whether level of perceived stress and reductions in levels of perceived stress (i.e., "let-down") are associated with the onset of migraine attacks in persons with migraine.Methods: Patients with migraine from a tertiary headache center were invited to participate in a 3-month electronic diary study. Participants entered data daily regarding migraine attack experience, subjective stress ratings, and other data. Stress was assessed using 2 measures: the Perceived Stress Scale and the Self-Reported Stress Scale. Logit-normal, random-effects models were used to estimate the odds ratio for migraine occurrence as a function of level of stress over several time frames.Results: Of 22 enrolled participants, 17 (median age 43.8 years) completed .30 days of diaries, yielding 2,011 diary entries including 110 eligible migraine attacks (median 5 attacks per person). Level of stress was not generally associated with migraine occurrence. However, decline in stress from one evening diary to the next was associated with increased migraine onset over the subsequent 6, 12, and 18 hours, with odds ratios ranging from 1.5 to 1.9 (all p values , 0.05) for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points. Findings were similar using the Self-Reported Stress Scale.Conclusions: Reduction in stress from one day to the next is associated with migraine onset the next day. Decline in stress may be a marker for an impending migraine attack and may create opportunities for preemptive pharmacologic or behavioral interventions. Neurology ® 2014;82:1395-1401 GLOSSARY GAD-7 5 Generalized Anxiety Disorder-7 item; OR 5 odds ratio; PHQ-9 5 Patient Health Questionnaire-9 item; PSS 5 Perceived Stress Scale; SRSS 5 Self-Reported Stress Scale.Migraine is a common headache disorder with substantial personal and societal burden.1,2 This burden may be amplified by the unpredictable nature of attacks, 3 although attacks are sometimes predictable based on trigger factors and premonitory features. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Premonitory features include changes in mood or behavior that precede the onset of an attack. Trigger factors, measurable precipitants associated with an increased probability of an attack, can include stressful events, hormonal changes, weather changes, and certain foods, although some studies demonstrate reduced odds for migraine attacks in relation to certain variables. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] In patient surveys, perceived stress was associated with migraine onset in up to 80% of respondents. [13][14][15][16] Diary studies have shown that "daily hassles" significantly increase in the 2-to 3-day period before a migraine day. 15,16 In an electronic diary study, emotional factors including irritability and intolerance (40.0% vs 33.7%) were more common on migraine days than control days.4 Some studies have examined the effects of reductio...