An autopsied case of MM1 + MM2‐cortical with thalamic‐type sporadic Creutzfeldt‐Jakob disease presenting with hyperintensities on diffusion‐weighted MRI before clinical onset

Abstract

A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrP ) and type 2 PrP . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrP would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrP . We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.

An autopsy case of Creutzfeldt‐Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction

“…Based on the present case, we corroborate the hypothesis that characteristic MRI findings in the cerebral neocortex can provide a foundation for suspecting V180I gCJD. We speculate that hyperintensity on diffusion‐weighted imaging of the CJD brain can be attributed to spongiform changes rather than gliosis, neuropil rarefaction, or PrP deposition . Thus, it is proposed that MRI findings in V180I gCJD are strongly associated with the presence of VaSNoC‐type vacuoles.…”

MM1‐type sporadic Creutzfeldt‐Jakob disease with 1‐month total disease duration and early pathologic indicators

“…Conversely, DWI hyperintensity was observed in the insular cortex, and mild spongiform changes without apparent gliosis were present. Based on our previous observations, we speculated that DWI hyperintensity indicates spongiform changes more so than gliosis or neuropil rarefaction . Manners et al also reached the same conclusion based on their clinicopathological observations .…”

“…Several case reports have described the presence of DWI hyperintensities before the clinical onset of CJD, and the existence of the preclinical stage of CJD is proposed based on this observation . We believe that this stage (regions with PrP deposition, spongiform changes and DWI hyperintensity, but no apparent clinical symptoms of CJD) may be considered prodromal.…”

“…Strangely, DWI hyperintensity was not apparent in the cerebellar cortex, although extensive spongiform changes were noted in the molecular layer of the cerebellum. It seems paradoxical, but a previous report contained similar findings, and there is no established theory to explain the paradox. At present, we speculate that the reason is related to the complicated arrangement of fibers in the cerebellar molecular layer, which contains numerous dendritic arbors of Purkinje cells and huge array of parallel fiber tracts from granule cells…”

Autopsied case of sporadic Creutzfeldt–Jakob disease classified as MM1+2C‐type

“…Although this classification system is useful in the identification of major sCJD subgroups, there are some individual cases that are difficult to classify on this basis, such as those that present with combined subtypes . To better understand these combined cases, comprehensive analyses of clinical and neuropathological findings, as well as analyses of the PrP gene and PrP Sc type, should be used . Although MM1+2C‐type sCJD cases have been infrequently identified, the definition is fundamentally based on Western blot analysis rather than neuropathological analysis …”