Figure 2. MRI and histopathologic findings from the patient's initial episode.

(A–D) Prebiopsy MRI; (E) postbiopsy MRI. (A) T2-weighted image (T2WI) revealed concentric lesions in the left parietal white matter. (B–D) Magnified images of the parietal lobe depicted in (A) (rectangle). MRI findings and the presence of peripheral diffusion-weighted image (DWI) hyperintense lesions with gadolinium enhancements at lesion edges were similar to the results obtained during the patient's relapse (B, DWI; C, postgadolinium T1-weighted image; D, T2WI). (E) Postbiopsy MRI clearly indicated the resected area (red arrows) (T2WI). (F–P) histopathological findings for the biopsied brain (left parietal). (F–H, I–K, and L–N) Same areas, respectively. (F) Concentric demyelinating lesions were clearly recognizable by Klüver-Barrera myelin staining (scale bar = 500 μm). (G) Glial fibrillary acidic protein (GFAP)–positive hypertrophic astrocytes were observed beyond the edge of the demyelinating layers (GFAP [brown], scale bar = 500 μm). (H) Hypoxia-inducible factor-1α (HIF-1α) was upregulated around the outer edges of demyelinating lesions (HIF-1α [brown], scale bar = 500 μm). (I–K) High-magnification images of a selected area depicted in (F) (rectangle). Dotted lines mark the border between demyelinated and myelinated layers. (I) Myelin staining clearly revealed the boundary of demyelinated and myelinated regions (Klüver-Barrera myelin staining, scale bar = 200 μm). (J) Hypertrophic astrocytes were seen even in the nondemyelinating area. However, astrocytes were different morphologically in demyelinated and myelinated regions (balloon-shaped in the demyelinated area and star-shaped in the myelinated area; GFAP [brown], scale bar = 200 μm). (K) HIF-1α upregulation was particularly prominent in hypertrophic astrocytes (HIF-1α [brown], scale bar = 200 μm or 20 μm in inset of a single astrocyte). (L) Numerous activated macrophages had infiltrated the demyelinating lesions (myelin basic protein [blue]/CD68 [brown], scale bar = 150 μm). (M) CC motif chemokine 2 (CCL2) expression was evident in the cytoplasm of hypertrophic astrocytes (inset, scale bar = 20 μm), which were located mainly in peripheral demyelinating layers (CCL2 [brown], scale bar = 150). (N) Infiltrating cells (microglia and macrophages) in demyelinating layers expressed CC chemokine receptor type 2 (CCR2), especially in peripheral demyelinating layers (CCR2 [brown], scale bar = 150 μm). (O, P) Interleukin-1β (IL-1β) was not expressed in myelinated layers (O). However, in the demyelinating lesions, Il-1β expression was detected in macrophages and, to a lesser extent, in hypertrophic astrocytes (P) (IL-1β [brown], scale bar = 20 μm).