Brain Susceptibility Changes in a Patient with Natalizumab-Related Progressive Multifocal Leukoencephalopathy: A Longitudinal Quantitative Susceptibility Mapping and Relaxometry Study

Abstract Background Brain MRI plays an essential role in both diagnosis and follow-up of the JCV infection of the brain. Recently, MR studies with Susceptibility-Weighted Imaging (SWI) sequences have shown hypointensities in U-fibers adjacent to white matter (WM) lesions of Progressive Multifocal Leukoencephalopathy (PML). This finding has been confirmed with the use of quantitative susceptibility mapping (QSM), allowing to hypothesize a paramagnetic effect in these regions. Here we report the first longitudinal assessment of QSM and R2* maps in natalizumab-associated PML, to evaluate serial changes in susceptibility contrast images and their role in PML diagnosis and follow-up. Case presentation We report the case of a 42-year old woman with Multiple Sclerosis (MS) who eventually developed, after the 28th natalizumab infusion, sub-acute cognitive decline and received a laboratory-confirmed diagnosis of PML, leading to immediate drug discontinuation. Three months later she suffered a new clinical exacerbation, with a brain scan revealing significant inflammatory activity compatible with the radiological diagnosis of an Immune Reconstitution Inflammatory Syndrome (IRIS). She was then treated with corticosteroids until the clinico-radiological spectrum became stable, with the final outcome of a severe functional impairment. Quantitative maps obtained in the early symptomatic stage clearly showed increased QSM and R2* values in the juxtacortical WM adjacent to PML lesions, which persisted during the subsequent disease course. Discussion and Conclusions High QSM and R2* values in U-fibers adjacent to WM lesions was an early and seemingly time-independent radiological finding in the presented PML case. That, coupled to the known absence of significant paramagnetic effect of new active MS lesions, could support the use of quantitative MRI as an additional tool in the diagnosis and follow-up of natalizumab-related PML in MS.