case_images: PMC11390624_01
case_images: Brain biopsy of the left frontal lobe in Case 1. HE (A), KB (B), MBP (C), and MOG (D) staining showing myelin destruction with inflammatory cell infiltration. A motor neuron marker (SMI31) staining demonstrating axonal damage in demyelinated lesions (E). Inflammatory cells expressing CD68 (F). Astrocyte loss can be observed to be relatively preserved by AQP4 (G) and GFAP (H) staining. Scale bar, 250 microm. Higher-magnification brain biopsy of the left frontal lobe in Case 1 is shown (I-L). HE (I) and CD68 (J) staining showing the CD68-positive small round cell infiltrates around small blood vessels. Absence of Elastica van Gieson (EVG) staining reveals that vessels with CD68-positive cell infiltration are veins (K). Berlin blue staining (BB), which demonstrates iron deposits, shows that hemorrhagic lesions are not detected around the vessels; therefore, the involvement of vasculitis is negative (L). (A-H) Scale bar, 250 microm; (I-L) scale bar, 100 microm. HE, hematoxylin and eosin; KB, Kluver-Barrera staining; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; AQP4, aquaporin4; GFAP, glial fibrillary acidic protein; EVG, Elastica van Gieson; BB, Berlin blue staining.
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case_images: PMC11390624_01_fimmu-15-1426236-g001.jpg
case_images: f1
case_images: Histopathological studies from previous hospitals showed reduced myelin sheath staining and myelin phagocytosis by Kluver-Barrera (KB) staining and highly reduced staining by myelin basic protein (MBP) and MOG immunostaining ( Figures 1A-D ). Severe axonal loss can be observed in the demyelinating lesion ( Figure 1E ). H ). Hemorrhagic lesions are not observed in areas with inflammatory cell infiltration ( Figures 1I-L ); thus, vasculitis was not involved. Moreover, demyelinating lesions were highly observed at these round cell infiltrating areas and these findings were known as "perivenous demyelination and inflammation," which was characteristic in ADEM ( Figures 1A-F ,  I-K ).
case_images: Brain MRI lesions in Case 1 during pre-treatment (A, B) and post-treatment (C). Axial FLAIR (A) and CE T1 (B) sequences of brain MRI during pre-treatment. A large bilateral frontal FLAIR hyperintense lesion can be observed (A). Extensive white matter lesions with linearly radiating gadolinium enhancement are observed around the ventricles. (B) Axial FLAIR of the brain MRI post-treatment (C). Immunological treatment improved the FLAIR high-intensity lesions, but significant cerebral atrophy could be observed. The timeline scheme of MRI, brain biopsy, and immunological therapy of Case 1 (D). FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; CE, contrast enhancement; CSF, cerebrospinal fluid; IVIG, intravenous immunoglobulin therapy.
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case_images: f2
case_images: Before performing brain biopsy and initiating steroid therapy, the areas of white matter lesions showed linear-radiating gadolinium enhancement and high signal intensity on T2-weighted MRI ( Figures 2A, B ). Steroid therapy decreased the area of these lesions ( Figure 2C ), and the patient's level of consciousness improved; however, severe cerebral atrophy persisted. Rehabilitation was performed and the patient became ambulatory ( Figure 2D ).
case_images: PMC11390624_02
case_images: Brain biopsy of the left occipital lobe in Case 2. HE (A), KB (B), MBP (C), and MOG (D) stain showing the myelin destruction with inflammatory cell infiltration. SMI31 stain reveals that the axonal damage in the demyelinated sight is relatively mild compared to that in Case 1 (E). Inflammatory cell expressing CD68 (F). Immunohistochemistry against AQP4 (G) and GFAP (H) demonstrates that the astrocyte damage is not clear. Scale bar, 250 microm. Brain MRI lesion in Case 2 during pre-treatment and post-treatment is shown (I-K). Axial FLAIR (I) and CE T1 (J) sequence of brain MRI during pre-treatment. A large FLAIR-hyperintense lesion is located in bilateral deep white matter (I). Widespread white matter lesions with a linear-radiating gadolinium enhancement can be observed (J). Axial FLAIR of brain MRI during post-treatment. Immunological treatment had no effect on FLAIR high-intensity lesion progression, but the cerebral volume is relatively preserved (K). The timeline scheme of MRI, brain biopsy, immunological therapy, and adverse events of Case 2 (L). HE, hematoxylin and eosin; KB, Kluver-Barrera staining; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; AQP4, aquaporin4; GFAP, glial fibrillary acidic protein; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; CE, contrast enhancement; CSF, cerebrospinal fluid; IVIG, intravenous immunoglobulin therapy.
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case_images: PMC11390624_02_fimmu-15-1426236-g003.jpg
case_images: f3
case_images: A brain biopsy performed at the previous hospital indicated myelin destruction and an ADEM-like lesion, similar to that in Case 1 ( Figures 3A-H ). In contrast to Case 1, SMI31 immunostaining did not show severe axonal loss within the demyelinated lesions, and only swollen axons can be observed ( Figure 3E ). Figures 3I, J ). FLAIR high-intensity lesion on MRI after immunological treatment ( Figure 3K ) was not altered ( Figures 3I, K, L ), but the cerebral volume was relatively preserved compared to that in Case 1 ( Figures 4A, B ).
case_images: The progression of brain atrophy in Case 1 was significantly more advanced compared to that in Case 2 as can be observed in the MRI T1 images. (A) The brain volumes in MRI T1 sequences of Case 1 and Case 2 were compared pre-treatment and post-treatment. (B) The brain volumes measured using ImageJ for both were analyzed with a one-way analysis of variance (ANOVA). MRI, magnetic resonance imaging.
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case_images: f4
case_images: Figures 3I, J ). FLAIR high-intensity lesion on MRI after immunological treatment ( Figure 3K ) was not altered ( Figures 3I, K, L ), but the cerebral volume was relatively preserved compared to that in Case 1 ( Figures 4A, B ).