Background: Previous studies, dating back to the 1960s disclosed a progressive increase in multiple sclerosis (MS) incidence and prevalence in the Province of Padua. To further analyze whether this trend is the effect of the improved diagnostic procedures or is primarily related to a real increase risk of MS, we analyzed MS incidence and prevalence of the 5-year period 2011–2015. Methods: Patients with a diagnosis of MS or clinically isolated syndrome highly suggestive of MS were included in the study. All available sources of clinical and administrative information were evaluated. Mean annual incidence in the 5-year period 2011–2015 and the prevalence on December 31, 2015 were calculated. Results: The 2011–2015 mean incidence was 6.5/100,000/year, 7.9 for females, 4.1 for males. The overall prevalence was 182/100,000, 241 for females, 116 for males. Compared to the 2000–2009 period, mean age at onset, onset-diagnosis delay and F/M ratio did not significantly change. Since the 1960s, incidence and prevalence of MS linearly increased with no interposed plateau periods. Conclusions: MS incidence and prevalence further and significantly increased in the period 2011–2015. Our 1965–2015 data indicate a real increased risk of MS and stress a role of exogenous factors in MS susceptibility.

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