Objective The early detection of MRI findings suggestive of immune reconstitution inflammatory syndrome (IRIS) in natalizumab-associated progressive multifocal leukoencephalopathy (PML) is of crucial clinical relevance in terms of treatment decision-making and clinical outcome. The aim of this study was to investigate the earliest imaging characteristics of PML-IRIS manifestation in natalizumab-treated patients with multiple sclerosis and describe an imaging pattern that might aid in the early and specific diagnosis.

Methods This was a retrospective study assessing brain MRI of 26 patients with natalizumab-associated PML presenting with lesions suggestive of PML-IRIS during follow-up. MRI findings were evaluated considering the imaging findings such as mass effect, swelling, contrast enhancement, new perivascular T2 lesions and signs suggestive of meningeal inflammation.

Results Contrast enhancement was the most common imaging sign suggestive of PML-IRIS, seen in 92.3% of the patients (with patchy and/or punctuate pattern in 70.8% and 45.8% respectively), followed by new T2 lesions with a perivascular distribution pattern (34.6%). In those patients with contrast enhancement, the enhancement was present in the lesion periphery in 95.8% of the patients. Contrast-enhancing lesions with a perivascular distribution pattern outside of the PML lesion were observed in 33.3% of the patients. The most common overall pattern was contrast enhancement in the border of the PML lesion with either a patchy or punctuate appearance in 88.5% of all patients.

Conclusions Contrast enhancement is the most common earliest sign of natalizumab-associated PML-IRIS with a frequent imaging pattern of contrast-enhancing lesions with either a patchy or punctuate appearance in the border of the PML lesion.