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

Abstract

BackgroundBrain 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-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 presentationWe 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-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 conclusionHigh QSM and R2* values in U-fibers adjacent to WM lesions were early and seemingly time-independent radiological findings in the presented PML case. This, 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.

Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor

“…PML represents a life-threatening demyelinating disease of the brain as a result of infection with the JCV. 14 Since the AIDS epidemic, PML was reported exclusively in association with HIV, but more recently, there has been a shift toward other immunosuppressive conditions, including patients on immune-suppression therapy and patients with long-standing autoimmune inflammatory or hematologic malignancies. 15,16 In addition, several case reports on immunocompetent patients developing PML have also been published.…”

Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray–white matter junction correlates with iron-enriched macrophages

“…14,15 Using susceptibilityweighted imaging (SWI), linear juxtacortical hypointense (at the cortical-WM junction) changes are observed in association with PML lesions even prior to clinical manifestations in some individuals. [16][17][18][19][20][21] This is an attractive imaging biomarker of PML in the appropriate clinical context-patients on immunomodulatory/immunosuppressive therapies or an immunocompromised state. 22 PML paramagnetic changes have been interpreted as occurring in the cortex, deep cortical layers or adjacent U-fibers and its etiology has been enigmatic.…”

“…22 PML paramagnetic changes have been interpreted as occurring in the cortex, deep cortical layers or adjacent U-fibers and its etiology has been enigmatic. 18,21,23,24 Here, we evaluated the presence of juxtacortical susceptibility abnormalities in subjects with PML using 1.5 and 3 T MRI acquired as part of routine clinical practice, supplemented by dedicated research 7 T imaging. PCNSL was selected as a comparator given its similar clinical and neuroimaging presentations.…”

Possible progressive multifocal leukoencephalopathy and active multiple sclerosis under dimethyl fumarate: the central role of MRI in informing therapeutic decisions

“…Brain Magnetic Resonance Imaging (MRI) is a sensitive diagnostic tool for the PML detection [ 4 ], usually showing a heterogeneous pattern characterized by multifocal, often confluent, subcortical lesions with frequent involvement of the U-fibers [ 5 ]. Nevertheless the differential diagnosis between MS activity and PML can prove challenging, as highlighted by the proposal of early imaging biomarkers based on Susceptibility Weighted Imaging and Quantitative Susceptibility Mapping [ 6 ] and of applying high-resolution imaging to differentiate early PML- from MS-induced [ 7 ]. Here, we describe a case of clinical worsening in a MS patient under DMF therapy, in course of moderate lymphopenia, with negative viral title but with MRI signs highly suggestive of PML and concomitant MS disease activity.…”