Autonomic Dysfunction among Migraineurs with and without Complaints of Orthostatic Intolerance: Evidence for Small Fiber Nerve Damage

Abstract

Background and Objective: Migraineurs often complain of orthostatic intolerance (OI), and its recognition is vital to appropriate treatment. This study attempts to identify and characterize autonomic dysfunction, comparing a sample of migraineurs with OI with a sample of migraineurs without OI. Methods: In a prospective cohort study, we examined one migraine sample complaining of OI for > 6 months (Group 1) and another group without OI (Group 2), using a 70-degree, 45-minute head-up passive tilt-table (HUT45) test, electrocardiographic R-R interval measurements during deep breathing, blood pressure and heart rate monitoring during Valsalva and release, QSART, and skin biopsy for nerve fiber density. We compared results with standard, 10-minute head-up passive tilt-table (HUT10) results to determine which test promoted greater sensitivity, specificity and diagnostic accuracy. Descriptive statistics were computed for each group, defined by the presence or absence of OI. We conducted several receiver operating characteristic analyses to determine whether certain clinical characteristics were predictive of symptoms of OI. Results: Thirty-nine Group 1 and 22 Group 2 subjects were studied and were similar demographically. Thirty eight of 39 (97.4%) Group 1, versus 15/22 (68.2%) Group 2 subjects, manifested abnormal HUT45 results, a significant difference (p=0.002). The HUT45 showed higher sensitivity (0.59; 95% CI: 0.42-0.74) than the standard 10-minute tilt-table test (HUT10) for all expressions of OI (0.31; 95% CI: 0.17-0.48). No differences in autonomic laboratory or skin biopsy findings distinguished the groups. We detected biopsy-proven small fiber neuropathy in 22/39 (56.4%) Group 1 and 10/22 (45.5%) Group 2 subjects. Discussion and Conclusions: In migraineurs, OI is an expression of autonomic dysfunction. We found evidence for a peripheral autonomic deficit on skin biopsy in 45% or more of both groups of migraineurs. Extending the head-up tilt table test to 45-minutes increases diagnostic sensitivity, spares patients misdiagnosis and unnecessary testing, and satisfies the principle of ecological validity.