Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution.

Early diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter. All Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant. (1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort. Considering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3-4  months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.

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Déclaration de conflit d'intérêts

Competing interests: SC and AS have nothing to disclose. LP declares received consulting fees from Biogen and Novartis; speaker honoraria from Biogen, Genzyme, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme. LP also acts as member of steering committee Agenzia Italiana del Farmaco on natalizumab. RC received consulting fees from TEVA, Biogen, Merck Serono, Genzyme, Roche, GeNeuro, Novartis and Medday. MPC received speaker honoraria from Biogen. SG received speaker honoraria from Biogen and Novartis. RC received consulting fees from Novartis, Biogen and lecture fees and/or travel grants from Novartis, Biogen, Celgene, Genzyme and Sanofi-Aventis. These relationships are not related to the content in the manuscript. No other disclosures were reported.