June 2017 | Volume 8 | Article 294 1 CASE REPORT published: 19 June 2017 doi: 10.3389/fneur.2017.00294 Frontiers in Neurology | www.frontiersin.org Edited by: Mike P. Wattjes, VU University Medical Center, Netherlands Reviewed by: Jérôme Hodel, American Printing House for the Blind, United States Friedemann Paul, Charité Universitätsmedizin Berlin, Germany *Correspondence: Sirio Cocozza siriococozza@hotmail.it † These authors have contributed equally to this work. Specialty section: This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology Received: 24 March 2017 Accepted: 07 June 2017 Published: 19 June 2017 Citation: Pontillo G, Cocozza S, Lanzillo R, Borrelli P, De Rosa A, Brescia Morra V, Tedeschi E and Palma G (2017) Brain Susceptibility Changes in a Patient with Natalizumab-Related Progressive Multifocal Leukoencephalopathy: A Longitudinal Quantitative Susceptibility Mapping and Relaxometry Study. Front. Neurol. 8:294. doi: 10.3389/fneur.2017.00294 Brain Susceptibility Changes in a Patient with Natalizumab-Related Progressive Multifocal Leukoencephalopathy: A Longitudinal Quantitative Susceptibility Mapping and Relaxometry Study Giuseppe Pontillo 1† , Sirio Cocozza 1 * † , Roberta Lanzillo 2 , Pasquale Borrelli 3 , Anna De Rosa 2 , Vincenzo Brescia Morra 2 , Enrico Tedeschi 1 and Giuseppe Palma 4 1 Department of Advanced Biomedical Sciences, University “Federico II”, Naples, Italy, 2 Department of Neurosciences, Reproductive and Odontostomatological Sciences, University “Federico II”, Naples, Italy, 3 IRCCS SDN, Naples, Italy, 4 Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy Background: Brain MRI plays an essential role in both diagnosis and follow-up of the JC virus infection of the brain. Recently, MR studies with susceptibility-weighted imaging (SWI) sequences have shown hypointensities in U-ibers adjacent to white matter (WM) lesions of progressive multifocal leukoencephalopathy (PML). This inding has been con- irmed with the use of quantitative susceptibility mapping (QSM), allowing to hypothesize a paramagnetic effect in these regions. Here, we report the irst 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, subacute cognitive decline and received a laboratory-conirmed diagnosis of PML, leading to immediate drug discontinuation. Three months later, she suffered a new clinical exacerbation, with a brain scan revealing signiicant inlammatory activity compatible with the radiological diagnosis of an Immune Reconstitution Inlammatory Syndrome (IRIS). She was then treated with corticosteroids until the clinico-radiological spectrum became stable, with the inal outcome of a severe functional impairment. Quantitative maps obtained in the early symptomatic stage clearly showed increased QSM and R2* values in the juxtacorti- cal WM adjacent to PML lesions, which persisted during the subsequent disease course. Discussion and conclusion: High QSM and R2* values in U-ibers adjacent to WM lesions were early and seemingly time-independent radiological indings in the presented PML case. This, coupled to the known absence of signiicant 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. Keywords: multiple sclerosis, progressive multifocal leukoencephalopathy, neuroinlammation, neuroimmunology, MRI, susceptibility-weighted imaging