Progressive multifocal leukoencephalopathy: MRI findings in HIV-infected patients are closer to rituximab- than natalizumab-associated PML

Alleg, Manel; Solis, Morgane; Baloglu, Seyyid; Cotton, François; Kerschen, Philippe; Bourre, Bertrand; Ahle, Guido; Pruvo, Jean-Pierre; Leclerc, Xavier; Vermersch, Patrick; Papeix, Caroline; Maillart, Élisabeth; Houillier, Caroline; Chabrot, Cécile Moluçon; Claise, Béatrice; Malak, Sandra; Martin-Blondel, Guillaume; Bonneville, Fabrice; Caulier, Alexis; Marolleau, Jean-Pierre; Bonnefoy, Jérôme Tamburini; Agape, Philippe; Kennel, Céline; Roussel, Xavier; Chauchet, Adrien; De Seze, Jérôme; Fafi-Kremer, Samira; Kremer, Stéphane

OBJECTIVES: To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. MATERIALS AND METHODS: In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. RESULTS: The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. CONCLUSION: Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. KEY POINTS: • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.