Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis

Background: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. Methods: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. Results: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78–10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01–8.03) and for late-onset cases, it was 5.48 (95% CI 4.10–7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. Conclusions: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy.