A 59-year-old Japanese man presented with depressed mood, insomnia, abnormal behavior and dementia. Visual and gait disturbance with ataxia also developed. Diffusion-weighted MRI showed widespread regions of hyperintensity in the bilateral cerebral cortex. The patient died at 62 after a progressive clinical course of 32 months. Myoclonus, periodic sharp-wave complexes on EEG, and akinetic mutism state were not observed. Neuropathologic examination showed widespread cerebral neocortical involvement with both large confluent vacuole-type, alongside fine vacuole-type spongiform changes. Mild spongiform degeneration was observed in the striatum and lateral thalamus. Severe neuron loss with hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus was present. Cerebral white matter showed diffuse myelin pallor indicating panencephalopathic-type pathology. In the cerebellar cortex, severe Purkinje neuron loss was observed, but no spongiform degeneration in the molecular layer or neuron loss in the granular cell layer. PrP immunostaining showed widespread perivacuolar-type PrP, irregular plaque-like PrP, and synaptic-type PrP depositions in the cerebral neocortex. Mild PrP deposition was observed in the striatum, lateral thalamus and brainstem, whereas PrP deposition was not apparent in the medial thalamus and inferior olivary nucleus. PrP gene analysis showed no mutations, and methionine homozygosity was observed at codon 129. Western blot analysis of protease-resistant PrP showed type 2 PrP pattern. MRI and cerebral neocortical pathology suggested MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD), whereas the clinical course and pathology of the medial thalamus and inferior olivary nucleus suggested MM2-thalamic-type sCJD. We believe this was a combination of MM2-cortical-type and MM2-thalamic-type sCJD, which explains the broad spectrum of MM2-type sCJD findings and symptoms.
- Creutzfeldt-Jakob disease
- Large confluent vacuole
- Perivacuolar-type prion protein deposition
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology