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Background: Progressive multifocal leukoencephalopathy (PML) is a severe adverse event of natalizumab (NTZ). The administration of NTZ with extended interval dosing (EID) has been proposed as a strategy to potentially reduce the incidence of PML while maintaining its therapeutic efficacy., Methods: In the current paper, we describe 4 cases of NTZ-PML in EID included in the Italian PML cohort., Results: The patients developed PML after at least 38 NTZ infusions. Their John Cunningham virus (JCv) index was > 1.5, and patients had not previously used immunosuppressant. Two patients were asymptomatic at PML onset, while two had mild motor impairment of the right hand and anomia, respectively. All of them had undetectable viral load but one (37 JCv copies/ml). In all patients, MRI revealed unilobar lesions with deferred contrast enhancement suggestive of immune reconstitution. The clinical course ended with a favorable clinical outcome (ΔEDSS up to 1)., Conclusions: Although PML in EID seems to occur less frequently than in conventional dosing regimen, strict monitoring of high-risk patients contributed to the indolent course observed in the four described cases, characterized by a prolonged pre-symptomatic phase, paucisymptomatic onset, low JCv load, less severe functional impairment during immune reconstitution, and a mild disability burden.

182 new cases of primary intracranial neoplasia were diagnosed in the province of Bolzano in the five years 1980-84, yielding a crude incidence of 8.4 cases per 100.000 inhabitants per year. Histological verification was available in 86% of cases. The age-specific incidence rate is 7.9 in males and 9 in females and the most affected age group 60 to 64 years. The tumor incidence for Bolzano city is 13.6 per 100.000 population per year compared with 6.8 per 100.000 for the rest of the province.