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Brain Susceptibility Changes in a Patient with Natalizumab-Related Progressive Multifocal Leukoencephalopathy: A
Giuseppe Pontillo1, Sirio Cocozza1, Roberta Lanzillo2
1Department of Advanced Biomedical Sciences, University "Federico II", 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-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, 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 Conclusion:
High 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.
Insights
Quantitative MRI, specifically quantitative susceptibility mapping (QSM) and R2* maps, can aid in diagnosing and monitoring progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. These imaging techniques reveal early, persistent changes in white matter lesions associated with natalizumab-treated PML.
Area of Science:
- Neuroimaging
- Radiology
- Neurology
Background:
- Brain Magnetic Resonance Imaging (MRI) is crucial for diagnosing and monitoring JC virus-associated progressive multifocal leukoencephalopathy (PML).
- Susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) reveal hypointensities in U-fibers adjacent to white matter (WM) lesions in PML, suggesting a paramagnetic effect.
- This study presents the first longitudinal assessment of QSM and R2* maps in natalizumab-associated PML.
Observation:
- A 42-year-old woman with multiple sclerosis (MS) developed PML after natalizumab treatment, followed by an Immune Reconstitution Inflammatory Syndrome (IRIS) exacerbation.
- Quantitative MRI maps showed elevated QSM and R2* values in juxtacortical WM adjacent to PML lesions during the early symptomatic stage.
- These quantitative MRI findings persisted throughout the disease course.
Findings:
- High QSM and R2* values in U-fibers adjacent to WM lesions were early radiological findings in the PML case.
- These paramagnetic changes were time-independent and persisted during the disease course.
- Active MS lesions typically lack significant paramagnetic effects.
Implications:
- Quantitative MRI, using QSM and R2* mapping, may serve as an additional diagnostic and follow-up tool for natalizumab-related PML in MS patients.
- These techniques can help differentiate PML from other inflammatory conditions in MS.
- Longitudinal quantitative MRI assessments can provide valuable insights into PML pathophysiology and treatment response.
