Spatial and temporal trends of multiple sclerosis mortality in Spain, 1992–2022

OBJECTIVES: To analyze mortality from multiple sclerosis (MS) in Spain from 1992 to 2022 by geographic region, age, and sex, while considering possible period and cohort effects. METHODS: This is a retrospective population-based ecological study. Mortality data was obtained from the Spanish National Statistics Institute. Deaths with MS listed as the underlying cause were identified using the International Classification of Diseases (ICD): ICD-9 code 340 for 1992-1998 and ICD-10 code G35 for 1999-2022. They were analyzed using spatial Age-Period-Cohort models fitted with INLA Integrated Nested Laplace Approximation (INLA), and Joinpoint regression was applied to assess national trends in age-standardized mortality. RESULTS: During the period studied (1992-2022), a total of 6524 people died from MS in Spain (2701 males and 3823 females), with mortality exhibiting an annual increase of 1% in both sexes without statistically significant differences; the female-to-male ratio rose from 0.898 in 1992 to 1.472 in 2022, indicating a relative increase in mortality among females compared to males (though not statistically significant); a clear north-south gradient in MS mortality was identified, and the cohort at highest risk comprised individuals born between 1950 and 1960. CONCLUSION: MS mortality increased in both sexes over the 1992-2022 period, and a north-south gradient was observed in Spain. Although overall sex differences in the increase in age-standardized mortality were not statistically significant, the female-to-male ratio showed an upward tendency over time, a finding that should be interpreted as a population-level association rather than evidence of causality.