Exploration of Association of Menarche with Age at Onset of Pediatric Nmo
Objectives: To assess the effect of age at puberty onset on the age of onset of NMO in children and adolescents.
Methods: This is a multicenter cohort study of 84 pediatric NMO patients collected at 9 clinical centers across the U.S between 2011-2015. Clinical data are recorded in a standardized database forms managed by the University of Utah. 381 Pediatric controls were collected at the same centers as part of a case:control MS study. Age at menarche and Tanner staging is recorded at clinical visits. Patients were classified as NMO IgG positive or negative.
Results: Of the 84 pediatric NMO patients, 65 were girls and 19 were boys. The sex ratio of patients with onset <10 years was 3.7 girls:1 boy and for onset 10 years and older it was 3.25 girls:1 boy. 48% of NMO-IgG+ girls, and 52% of NMO-IgG negative girls had first symptoms of NMO prior to menarche. Mean age at menarche was younger in post-menarcheal-onset NMO girls (11.3 years versus 12.0 years, p=0.04 from Van Elteren’s test adjusting for race/ethnicity), compared to controls collected at the same centers. Age at menarche and age at onset were not correlated in all girls (Spearman’s r=0.21, p=0.21), but were positively correlated among post-menarcheal-onset girls (Spearman’s rho=0.42, p=0.03). In girls, 29 had Tanner stage data within 12 months of onset, with 8 stage 1, 3 stage 2, 5 stage 3, 9 stage 4, and 4 stage 5. In the boys, 6 had Tanner staging measured within 12 months of first symptom onset. Of these, 1 was Tanner stage (pubic hair) 2, 3 were stage 3, and 1 each were stages 4 and 5.
Conclusions: Approximately half of pediatric girls with NMO had onset prior to menarche, regardless of NMO IgG status. There is a female predominance both pre- and post-pubertal-onset patients. Further studies are required to explore the role of sexual dimorphism and sex hormones in NMO.