Extended Phenotyping of Migraine in Children: A Cross-Sectional Study in a Specialist Children's Headache Clinic

Background The extended pediatric migraine phenotype may exhibit differences to adults, leading to diagnostic challenges. Objective To perform a cross-sectional systematic study characterizing the extended phenotype of pediatric migraine. Methods New patients with migraine presenting to the Children's Headache Clinic were included (n=105). Data was collected via a detailed symptom questionnaire at the first clinical encounter, including patient demographics, headache history and phenotype and medication use, and was analyzed using descriptive statistics, Cohen's kappa (k), Spearman correlation (ρ) and Poisson and binomial logistic regression models within SPSS. Results Patients were 65% female and aged 5-17 years (median 14, IQR 11-15), with a mean disease duration of 4.7 years (SD 2.8). Baseline monthly headache frequency was 1-30 days (median 30, IQR 12-30). Attack duration varied between 2-168 hours (median 12, IQR 5-72). The majority (81%) had bilateral headache. Premonitory symptoms (PS) were reported by 93% (range 0-7; mood change and tiredness most commonly), cranial autonomic symptoms (CAS) by 58% (range 0-6; pallor and lacrimation most commonly) and premonitory CAS by 23%. Vertigo (53%) and allodynia (16%) were present. The laterality of headache and CAS showed agreement (k=0.5, P<0.001). For every year of disease duration, 1.07 times more PS were reported (95% CI 1.03-1.12, P<0.001). The number of CAS (OR 2.13, 95% CI 1.2-3.8, P=0.01) significantly predicted allodynia. Conclusion There is a more enriched PS phenotype with disease chronicity in children. CAS and allodynia may be markers of central sensitization via shared neurobiological mechanisms, not requiring peripheral nociceptor activation. The extended pediatric migraine phenotype may exhibit differences to adults, leading to diagnostic challenges. To perform a cross-sectional systematic study characterizing the extended phenotype of pediatric migraine. New patients with migraine presenting to the Children's Headache Clinic were included (n=105). Data was collected via a detailed symptom questionnaire at the first clinical encounter, including patient demographics, headache history and phenotype and medication use, and was analyzed using descriptive statistics, Cohen's kappa (k), Spearman correlation (ρ) and Poisson and binomial logistic regression models within SPSS. Patients were 65% female and aged 5-17 years (median 14, IQR 11-15), with a mean disease duration of 4.7 years (SD 2.8). Baseline monthly headache frequency was 1-30 days (median 30, IQR 12-30). Attack duration varied between 2-168 hours (median 12, IQR 5-72). The majority (81%) had bilateral headache. Premonitory symptoms (PS) were reported by 93% (range 0-7; mood change and tiredness most commonly), cranial autonomic symptoms (CAS) by 58% (range 0-6; pallor and lacrimation most commonly) and premonitory CAS by 23%. Vertigo (53%) and allodynia (16%) were present. The laterality of headache and CAS showed agreement (k=0.5, P<0.001). For every year of disease duration, 1.07 times more PS were reported (95% CI 1.03-1.12, P<0.001). The number of CAS (OR 2.13, 95% CI 1.2-3.8, P=0.01) significantly predicted allodynia. There is a more enriched PS phenotype with disease chronicity in children. CAS and allodynia may be markers of central sensitization via shared neurobiological mechanisms, not requiring peripheral nociceptor activation.