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Introduction Sleep disruption and sleep architectural changes in relation to migraine are not well characterized. Disruption in sleep may serve as a risk for migraine or result from migraine. We leveraged a large clinical cohort to examine the hypothesis that those with migraine have greater degrees of sleep architectural alterations and sleep disordered breathing (SDB). Methods This was a polysomnogram-based retrospective case (migraine) control (non-migraine) study of patients aged >18 matched 1:3 on age, sex, race, body mass index (BMI), and year of polysomnogram. Two domains were considered: 1)Sleep architecture (arousal index:AI, (primary predictor), total sleep time (TST), percentage of sleep stage time) and 2)SDB (apnea hypopnea index (AHI:primary predictor), mean oxygen saturation) were considered. Comparisons were performed by two-sample t-test or Wilcoxon rank sum test for continuous variables, and chi-square test or Fisher’s exact test for categorical variables. Results 4,783 migraine cases (47.5 ±13.3 years, 76.4% Caucasian, body mass index:BMI 33.7 ±8.6kg/m2) were matched to 14,287 controls. In migraine patients vs those without, TST was lower (359.0[307.0, 421.0] minutes vs 363.0[306.0, 432.5] minutes,p=0.01), percentage of N2 was higher (67.8%[59.6, 75.6] vs 67.0%[58.4, 74.8],p<0.001), percentage of REM was lower (16.7% [10.0, 22.0] vs 17.0% [11.1, 22.2],p=0.012), AHI was lower (7.4 [2.6, 17.0] vs 9.5 [3.7, 22.1],p<0.001), AI was lower (19.6 [12.8, 30.9] vs 22.6 [14.7, 34.9],p<0.001), and mean oxygen saturation was higher (93.7%±2.4 vs 93.3±2.6,p<0.001). Conclusion In this largest study of its kind, we identify novel associations of migraine in relation to curtailed sleep and sleep architectural alterations, i.e. increase in N2 and reduced REM sleep and lower AI compared to contemporaneously matched controls. Directionality of these relationships requires further elucidation given the cross-sectional nature of this study. Interestingly, we observed lower degree of sleep apnea and hypoxia burden in patients with migraine. As Calcitonin Gene-Related Peptide (CGRP), a neuropeptide increased during and between migraine attacks in migraine patients, and serotonin are implicated in arousals due to apnea-related increases in CO2, there is biologic plausibility for migraines patients to exhibit potential protection from SDB. Further investigation is needed to confirm these findings. Support (If Any)

Introduction The importance of sex as a biological variable on the relationship of migraine and sleep disturbance has not been well-characterized. Given evidence of 1)bidirectional relationships of poor sleep and migraine severity and 2)greater activation of brain regions involved in emotional processing in women compared to men with migraine, we hypothesized that sleep architectural disruption may contribute to sex-specific differences in quality of life measures, particularly those attributed to emotional processing. Methods This was a retrospective cohort study of migraine patients aged >18 years seen in the Cleveland Clinic headache program with polysomnogram data. Migraine burden was measured by the 20-item migraine-specific quality of life(MSQOL) encompassing three domains: emotional function(EF), role function-preventative, and role function-restrictive. Linear regression models were used to assess the association of each MSQOL domain with sleep architectural measures and the statistical interaction with sex was examined. Coefficients and 95% confidence intervals were estimated and compared with adjustment of age, race, body mass index(BMI) and comorbidities. Results Of 245 patients with migraine,37(15.1%) were male. Males had higher AHI (10.0 [5.3, 18.5] vs. 5.7[1.8, 11.4], p=0.006). The difference in MSQOL-EF scores was not statistically significant (males:73.3[53.3,86.7] vs. females:60.0 [33.3,80.0], p= 0.066). There was no statistical difference in percent N2 or REM between sexes, though males had greater %N1, and lower %N3 (10.9[5.9,19.2] vs. 6.6[4.1,11.9],p=0.039). The association of MSQOL-EF with percent of N2 and REM sleep differed by sex. For each 5% increase in N2, there was a 5% reduction of MSQOL-EF 2.08 (-2.08, 95%CI [-6.86,2.70],p=0.39) in females compared to a 6.84 reduction in males (-6.84, 95%CI [-15.9,2.22],p=0.14), p-value for interaction=0.044. For each 5% increase in REM, MSQOL-EF increased 1.26 (1.26, 95%CI [-3.68,6.21],p=0.61) in females, and increased by 6.27 in males (6.27, 95%CI [-3.11,15.6], p=0.19),p-value for interaction=0.044. Conclusion Although males had greater sleep disruption compared to females, there was no significant difference in MSQOL-EF scores. However, sex-specific differences of extent of sleep stage composition and MSQOL-EF were observed suggesting influence of sleep architectural alterations on greater responsivity of migraine emotional processing in men versus women. Future investigation should better characterize longitudinal relationships and underlying neurobiological mechanisms underlying these findings. Support (if any) Association of Migraine Disorders