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MM1-type sporadic Creutzfeldt-Jakob disease with 1-month total disease duration and early pathologic indicators
Yasushi Iwasaki1, Hiroko Kato2, Tetsuo Ando2
1Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
Abstract:
A 62-year-old man presented with abnormal behavior and cognitive impairment. Diffusion-weighted images (DWI) obtained on MRI showed extensive hyperintense regions in the cerebral cortex and striatum. Myoclonus was recognized, and the patient died 1 month after the onset; his condition did not reach the akinetic mutism state. The brain weighed 1300 g and showed no apparent atrophy. Extensive spongiform changes were observed in the cerebral neocortex, striatum, thalamus and cerebellar cortex, but gliosis was mild or absent. Neuropil rarefaction and neuron loss were not apparent. Mild proliferation of anti- GFAP-positive astrocytes was observed in the cerebral cortex, but unaffected regions were noted. Regions without spongiform changes and GFAP-positive astrocytes included the hippocampal formation and subiculum. PrP immunostaining showed extensive diffuse synaptic-type PrP deposition in the gray matter, including the hippocampal region, but it was also mild. PrP gene analysis revealed no mutation with methionine homozygosity at polymorphic codon 129. Western blot analysis of proteinase K-resistant PrP indicated type 1 PrPSc . The clinicopathological findings of the present case confirm several hypotheses: (i) the earliest pathologic evidence observed by HE staining in CJD are spongiform changes; (ii) DWI hyperintense regions indicate these spongiform changes; and (iii) regions without spongiform changes, gliosis and proliferation of GFAP-positive astrocytes, but with PrP deposition, exist in the early disease stage.
Insights
This study details a Creutzfeldt-Jakob disease (CJD) case, showing early spongiform changes on MRI and PrP deposition in unaffected brain regions. These findings offer insights into early CJD pathology.
Area of Science:
- Neuropathology
- Neuroimaging
- Prion Diseases
Background:
- Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder characterized by rapidly progressive dementia.
- Early diagnosis of CJD remains challenging, necessitating a deeper understanding of its initial pathological hallmarks.
Observation:
- A 62-year-old man presented with cognitive impairment and abnormal behavior, later developing myoclonus.
- MRI diffusion-weighted images (DWI) revealed extensive hyperintense signals in the cerebral cortex and striatum.
- Post-mortem examination showed widespread spongiform changes in gray matter, with mild or absent gliosis and minimal neuron loss.
Findings:
- Spongiform changes, identified by HE staining, represent the earliest pathological evidence in CJD.
- DWI hyperintensities on MRI correlate with these early spongiform changes.
- The study identified brain regions with PrP deposition but lacking spongiform changes or gliosis, suggesting these areas are involved in early disease stages.
Implications:
- This case supports the hypothesis that spongiform changes are the earliest pathological sign of CJD.
- DWI MRI findings can indicate the presence and extent of early spongiform changes.
- Understanding PrP deposition in unaffected areas is crucial for early CJD detection and therapeutic strategies.