PMC5138460_01
Overview. Survey of treatment decisions and laboratory and MRI findings of the patient under discussion. In detail, 1.5 T T1 weighted Gadolinium enhanced (T1W GAD) and 1.5 T fluid attenuated inversion recovery (FLAIR) images are presented.
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MRI at 1.5 T revealed PML-suspicious bifrontal confluent lesions with (sub)cortical involvement. Moreover, multiple milky-way-like Gadolinium enhancing and T2 weighted (T2w) hyperintense punctate lesions were detected by MRI in these areas (Figure 1). T MRI performed immediately after PLEX did not show any signs of PML progression (Figure 1), and PCR did again not reveal JCV DNA in CSF. Thus, fingolimod was reinitiated on 22th of April 2015 to prevent possible rebound effects after discontinuation of NTZ, and monthly MRIs were performed. One month later (22th of May 2015) a control MRI at 1.5 T showed slightly enlarging FLAIR hyperintense lesions (Figure 1). The patient remained clinically stable, and MRI (26th of January 2016) showed decreasing PML lesions without any signs of Gadolinium enhancement (Figure 1, EDSS 3.0).
Signs of IRIS at the time of PML diagnosis. 1.5 T T1w Gadolinium enhanced MR images are presented. Extensive Gadolinium enhancement suggestive of IRIS (black arrows) was observed at the edge of confluent PML lesions.
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In addition, perilesional contrast enhancement around confluent PML-suspicious lesions suggestive of IRIS was detectable (Figure 2).
No signs of abnormal diffusion. Diffusion weighted MRI at 1.5 T ((a) and (c)) did reveal neither signs of central hyperdiffusibility (circles) nor signs of restricted diffusion (circles) at the edge of PML lesions (black arrows, (b) and (d)). Both of which were reported to be characteristic for PML lesions.
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Diffusion weighted MRI did not show intralesional hyperdiffusivity nor signs of restricted diffusion at the edge of the lesions (Figure 3); both of which are considered to be typical of PML. The patient remained clinically stable, and MRI (26th of January 2016) showed decreasing PML lesions without any signs of Gadolinium enhancement (Figure 1, EDSS 3.0).
7 T T2* weighted imaging in PML. A 7 T T2* weighted (T2*w) image with a spatial resolution of (0.2 x 0.2) mm is shown. Please note the difference in lesion morphology between periventricular oval MS lesions that are centered on a small venous vessel (arrows) and confluent PML lesions (circle) that also involve U-fibers and subcortical areas.
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Ultrahigh field MRI at 7 Tesla was performed five days after discontinuation of fingolimod confirming initial 1.5 T MRI findings by detailing confluent PML-suspicious lesions with (sub)cortical involvement (Figure 4) and by delineating numerous punctate Gadolinium enhancing lesions (Figure 5, circles) on top of MS-suspicious ring-enhancing lesions (Figure 5, white arrows).
Patterns of Gadolinium enhancement on 7 T VIBE images. A maximum intensity projection map of a 7 T T1 weighted Gadolinium enhanced volumetric interpolated brain examination ((a), VIBE) and an exemplary VIBE image (b) are displayed. PML-suspicious punctate Gadolinium enhancing lesions are clearly visible (circles). Ring-enhancing lesions (e.g., arrows) suggestive of MS lesions are delineated.
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Ultrahigh field MRI at 7 Tesla was performed five days after discontinuation of fingolimod confirming initial 1.5 T MRI findings by detailing confluent PML-suspicious lesions with (sub)cortical involvement (Figure 4) and by delineating numerous punctate Gadolinium enhancing lesions (Figure 5, circles) on top of MS-suspicious ring-enhancing lesions (Figure 5, white arrows).
Neuropathological findings. Histology revealed areas of focal demyelination as indicated by a loss of myelin basic protein (a) and proteolipid protein (b). Despite the presence of prominent CD8 dominated inflammatory infiltrates (c), SV40-positive cells (JCV-infected cells, (d)) could not be detected.
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The biopsy showed demyelinating lesions with a prominent CD8 dominated inflammatory infiltrate with numerous plasma cells (Figure 6).