Cluster Analysis of Migraine-associated Symptoms (CAMS) in Youth: A Retrospective Cross-sectional Multicenter Study

Objective: To conduct a retrospective cross-sectional multicenter study to validate the relationships between migraine-associated symptoms.

Background: Symptoms associated with headache-photophobia and phonophobia, nausea, and/or vomiting-are required criteria for migraine diagnosis based on the International Classification of Headache Disorders-Third Edition (ICHD-3). However, individuals with migraine report high rates of other symptoms (e.g., lightheadedness, difficulty thinking). We recently completed a single-center study assessing the relationships between an expanded set of migraine-associated symptoms.

Methods: A pre-registered cross-sectional multicenter retrospective analysis was conducted on standardized questionnaire data of youth ages 6-17 years from two headache registries at pediatric tertiary care centers. Cluster Analysis of Migraine-associated Symptoms (CAMS) was implemented to assess associations between 11 migraine-associated symptoms. We explored differences between the two centers, and how CAMS was associated with demographics, including sex and age, and headache burden.

Results: There were 10,721 participants who were 66.5% female and had a median (interquartile range) age of 13 (10-15) years. The first three CAMS dimensions accounted for 46.5% of the variance and were consistent across sites. The first dimension indicated those reporting any migraine-associated symptoms were likely to report multiple. The second dimension separated symptoms into those included in ICHD-3 migraine diagnostic criteria and non-ICHD symptoms (e.g., lightheadedness, difficulty thinking). The third dimension separated sensory hypersensitivity and vestibular symptoms. An abundance of migraine-associated symptoms correlated with greater headache severity (Spearman's ρ = 0.18, 95% confidence interval [CI] 0.17-0.20; small effect size) and disability (ρ = 0.26, 95% CI 0.25-0.28; small effect size). We also observed differences in associated symptoms across age and sex.

Discussion: Associations between an expanded set of migraine-associated symptoms are informative for headache burden and reveal intriguing changes across child development and sex. We were able to replicate findings across two centers, indicating that these symptom clusters are inherent to migraine.