Beyond the Headache:  Autonomic Reflex Dysfunction and Sensory Hypersensitivity Contribute to Orthostatic Intolerance in Migraine

Objective : We sought to determine: 1.) the relationship between headache frequency and autonomic reflexes, and 2.) mechanisms underlying orthostatic intolerance (OI) in patients with migraine. Methods : Adults with migraine (N = 30) underwent autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal/adrenergic baroreflex sensitivity (BRS-V/A). Postural Orthostatic Tachycardia Syndrome (POTS) and orthostatic hypotension/hypertension were diagnosed during tilt table testing. A cold pressor test (CPT) evaluated sympathetic vasomotor function. Participants completed the Migraine Disability Assessment (MIDAS), the 2011 Fibromyalgia (FM) Survey Criteria, chronic overlapping pain condition (COPC) screener, and Compass-31. Results : Monthly headache days correlated with CASS (p = 0.001), BRS-V (p < 0.001), and the systolic blood pressure response to CPT (p = 0.003) in the expected direction with increasing ANS reflex dysfunction correlating to increasing number of headache days. During tilt testing, OI was prevalent (25/30; 83%) and reported by all patients with chronic migraine. An abnormal cardiovascular response to tilt was present in the majority (63%) of which POTS was the most common etiology (56.2%). Patients reporting OI during tilt table testing despite a normal cardiovascular response (33%) had higher FM scores (15.8 ± 3.6 vs. 7.5 ± 4.6; p < 0.01) and a greater prevalence of non-headache COPCs (88.8% versus 20.0%, p = 0.02), compared to participants who were asymptomatic during tilt. Conclusions : There are two etiologies of OI in patients with migraine: 1.) an abnormal cardiovascular response to tilt (concordant OI) and, 2.) sensory hypersensitivity (discordant OI).