Fig. 1

Clinical course and histopathology of DNL as well as MS lesions. The clinical course is illustrated in (a) with the expanded disability status scale (EDSS, score ranging from 0 to 10 with higher numbers indicating more severe disability), relapses (red arrows) and MS-specific treatment indicated over time. Clinical stability was achieved with natalizumab (Ntz) and alemtuzumab (Alz), but numerous relapses occurred with interferon beta-1b (IFNb1b) and fingolimod (FTY) treatment. Eight months after alemtuzumab infusions were given, DNL developed (b-h), characterized by multifocal disseminated necrotic lesions within the white matter (arrows in b and c, LFB/PAS), but not grey matter (arrowheads in b). In addition to DNL, typical MS lesions were present (arrowheads in C indicate remyelinated MS lesion). DNL lesions were characterized by acute and complete tissue destruction with a loss of myelin (d, LFB/PAS), oligodendrocytes and astrocytes (e, anti-GFAP), pronounced axonal damage (f, anti-APP, insert shows many APP-positive, brown stained damaged axons in higher magnification) and numerous macrophages (g, KiM1P) in the absence of lymphocytic infiltration (h, anti-CD3). In contrast, MS lesions showed demyelination (i, LFB/PAS) with axonal preservation (not shown), lymphocytic inflammation (j, anti-CD3) and a sparse infiltrate with macrophages (k, KiM1P). Scale bars represent 200 μm in b (valid for b and c) and d (valid for d-i and k) as well as 100 μm in j