Temporal trends and regional disparities in multiple sclerosis burden in Italy, 1990-2023.

BACKGROUND: Multiple sclerosis (MS) is a major cause of chronic neurological disability, and its burden has shifted from premature mortality toward long-term disability. Italy, with its marked north-south gradients and the exceptional epidemiology of Sardinia, offers a unique setting to examine whether this transition has occurred uniformly across regions and sexes. METHODS: Using Global Burden of Disease 2023 subnational estimates, we analysed MS burden in Italy from 1990 to 2023 across five macro-areas. Age-standardized disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and the YLL/YLD ratio were evaluated by sex. Temporal trends were quantified using log-linear regression to estimate annual percentage change (EAPC). Non‑linearities were assessed using Joinpoint regression. We assessed sex-specific differences, changes in proportional composition of DALYs, and heterogeneity of trends across macro-areas. RESULTS: DALY rates increased in all macro-areas, with the steepest rises in Sardinia and South+Sicily, and the smallest increase in the Center. YLDs rose faster than YLLs everywhere, producing a consistent decline in the YLL/YLD ratio and confirming a shift toward disability-dominated burden. EAPCs were positive for DALYs and YLDs in all regions and sexes, highest in Sardinia. Joinpoint regression revealed multiple inflection points. Sex differences were present but smaller than geographic differences. Global interaction tests showed significant heterogeneity across macro-areas for all outcomes. CONCLUSIONS: MS burden in Italy has increased substantially, consistent with a rising population‑level disability burden, which may reflect higher prevalence, longer survival, and evolving epidemiological dynamics. Differences across macro‑areas require continued region‑specific epidemiological monitoring.