Sardinia is a high-risk area for multiple sclerosis (MS), with prevalence rates of 150 per 100,000 population. The study included 689 MS patients (female-male ratio 2.6) with disease onset between 1965 and 1999 in the province of Sassari. The mean annual incidence rate increased significantly from 1.1 per 100,000 population in 1965–1969 to 5.8 in 1995–1999, with no significant difference for gender and province sub-areas. The mean age at onset increased significantly during the same period from 25.7 to 30.6 years, while the proportion of patients with progressive initial course declined over time. The marked increase of MS incidence and the change of MS clinical phenotype over time cannot be explained by ascertainment bias only, thus pointing to a corresponding change in the distribution of exogenous risk factors in this highly genetically stable population.

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