case_images: PMC11739107_01
case_images: Brain MRI 8 months after symptom onset. (A) Diffusion-weighted imaging (DWI) reveals hyperintensity bilaterally in most cortices with additional restricted diffusion in the insula, caudate, putamen, and thalami. (B) Apparent diffusion coefficient (ADC) image shows hypointensity in hyperintense DWI sites, indicating restricted diffusion.
case_images: fncel-18-1518542-g0001.jpg
case_images: PMC11739107_01_fncel-18-1518542-g0001.jpg
case_images: F1
case_images: Repeat MRI several months later demonstrated additional restricted diffusion in the insula, caudate, putamen, and thalami (Figures 1A, B).
case_images: Histopathology and western blot profile of the index case. (A) Low-power H&E-stained section demonstrates pallor of subcortical white matter, consistent with secondary axonal degeneration (H and E x 20). (B) Cerebral cortical sections were remarkable for status spongiosis, rather than classical spongiform degeneration, secondary to advanced neuronal degeneration (H&E x 200). (C) Subcortical white matter was remarkable for severe axonal loss with reactive astrocytosis and scattered lipid-laden macrophages (H&E x 200). (D, E) 3 F4 immunohistochemical staining showed classical granular staining throughout the full-thickness of the cerebral cortex and cerebellar molecular layer. (F) Proteinase K (PK)-undigested PrPSc appears as a well-defined band of ~25 kDa (*), a less defined one of ~21 kDa (#), and a smear on the ~29-30 kDa region (bracket; lanes 1, 2). After digestion with PK, PrPSc is visualized as a doublet of ~ 25 and 21 kDa (lanes 3, 4, 8-10). Type 1 (T1, lane 6) and type 2 (T2, lane 7) controls were obtained from sCJDMM1 and -MM2, respectively. Numbers atop PrPSc bands indicate the relative molecular mass. FC, Frontal cortex; OC, occipital cortex; CE, cerebellum. Loading volume of lanes 8 and 9 is 4-fold that of lanes 3 and 4, respectively.
case_images: fncel-18-1518542-g0002.jpg
case_images: PMC11739107_01_fncel-18-1518542-g0002.jpg
case_images: F2
case_images: Neuropathologic examination revealed a pale, thin neocortex with marked neuronal loss and gliosis ("status spongiosis;" Figures 2A-C). Classical spongiform degeneration was not discernible (Figure 2). Immunoreactive PrP deposits were detected by immunohistochemistry throughout the neocortex and cerebellum (Figures 2D, E). No intracellular PrP deposits in Purkinje cells were observed (Figure 2E). Western blot analyses showed PK-resistant PrP bands at a slightly higher molecular weight than type 1 PrP associated with classic sCJD MM1, suggesting an atypical glycoform (AG) of PrP protein (sCJDMVAG; Figure 2F; Tanev and Yilma,; Zanusso et al.,; Galeno et al.,).