PMC

Quantification of inflammation and virally infected cells within demyelinating lesions in MS–PML–IRIS, ongoing MS–PML, and non-MS PML. Numbers of T cells (CD3), CD8+ T cells (CD8), B cells (CD20), plasma cells (CD138), and virally infected cells (PAb2003) were analyzed within demyelinating lesions in MS–PML–IRIS, ongoing MS–PML, and control groups. The median and range are indicated

MRI characteristics of a patient with histologically confirmed active natalizumab-associated PML. Axial FLAIR (a) and corresponding contrast-enhanced T1-weighted images (b) are shown (case 5). Linear enhancement at the lesion edge as well as diffuse and speckled enhancement within lesions are found (open arrows in b). The enhancement pattern does not allow differentiation between active PML and IRIS. The biopsied area is indicated (closed arrow in a)

High numbers of plasma cells are evident in natalizumab-associated PML with IRIS. Strikingly high numbers of plasma cells are found in MS–PML–IRIS lesions (a). Lower numbers are present in inflammatory PML cases (b). In MS–PML–IRIS, plasma cells are also evident in nondemyelinated white and grey matter (c, d) (a–d CD138). Original magnifications: a–d ×100. Scale bars 200 μm. a + d Patient 2, b inflammatory PML control, c patient 1

Histology of IRIS is characterized by extensive T-cell inflammation in natalizumab-associated PML. An inflammatory demyelinating lesion with pronounced inflammation is shown (a H&E, b LFB/PAS). T cells are dominated by CD8+ T cells (c CD3, d CD8). Inflammation is also evident in adjacent nondemyelinated white and grey matter (e + f CD3). Original magnifications: a + b ×40; c–f ×100. Scale bars 200 μm. Patient 2

MRI characteristics of patients with natalizumab-associated PML and histologically confirmed IRIS. Axial FLAIR images (a, c, e) of MS patients, cases 1, 2, and 3, with corresponding contrast-enhanced T1-weighted images (b, d, f) are shown. Different patterns of enhancement in IRIS can be seen, ranging from faint peripheral enhancement to intense enhancement of the lesions (open arrows in b, d, and f). The area of biopsy is indicated (closed arrows in a, c, and e)