Atypical sporadic CJD‐MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease

Abstract

We describe an atypical neuropathological phenotype of sporadic Creutzfeldt-Jakob disease in a 76-year-old man. The clinical symptoms were characterized by progressive dementia, gait ataxia, rigidity and urinary incontinence. The disease duration was 6 weeks. MRI did not show prominent atrophy or hyperintensities in cortical areas, striatum or thalamus. Biomarker examination of the cerebrospinal fluid deviated from that seen in pure Alzheimer's disease. Triphasic waves in the EEG were detected only later in the disease course, while 14-3-3 assay was positive. PRNP genotyping revealed methionine homozygosity (MM) at codon 129. Neuropathology showed classical CJD changes corresponding to the MM type 1 cases. However, a striking feature was the presence of abundant kuru-type plaques in the white matter. This rare morphology was associated with neuropathological signs of intranuclear inclusion body disease and advanced stage of argyrophilic grain disease. These alterations did not show correlation with each other, thus seemed to develop independently. This case further highlights the complexity of neuropathological alterations in the ageing brain.

Atypical Creutzfeldt-Jakob disease with PrP-amyloid plaques in white matter: molecular characterization and transmission to bank voles show the M1 strain signature

“…However, disease duration and the associated advanced pathology, although notoriously favoring the extent of plaque formation, cannot be the only causal factors since it is well established that most CJDMM1 patients with prolonged disease duration do not develop plaque-type depositions in the white matter. Moreover, the observations by Gelpi et al and Berghoff et al [ 1 , 9 ] in cases characterized by a short disease course, combined with our findings in case #5 and in a similar p-CJDMM1 case we recently obtained, also characterized by mild white matter changes (P. Parchi personal communication), clearly indicate that white matter amyloid plaques may develop early in the disease course and independently from a severe white matter damage. Interestingly, in our p-CJDMM1 cases, the onset and progression of clinical symptoms, including akinetic mutism, seem to be significantly delayed compared to np-CJDMM1 patients with similar disease duration.…”

Tau pathology in Creutzfeldt‐Jakob disease revisited

“…One of these had subcortical NFTs and argyrophilic tufted astrocytes in the cortex and striatum compatible with concomitant PSP type pathology (Table and Figure ). One case showed additional features of intranuclear inclusion body disease and two Lewy bodies (Braak stage 4) . The distribution of spongiform change and the morphology of PrP deposition were not distinct when compared to CJD cases without widespread tau pathology.…”

“…Of note however, CJD is a very rare disease and the chance of concomitant affection by other rare disorders such as PSP is very low. Nevertheless, similar rare constellations are known for PSP and MSA , for CJD and INIBD and for CJD with MSA . Furthermore, hippocampal sclerosis with TDP‐43 pathology has not yet been described in CJD, which usually lacks TDP‐43 immunoreactive inclusions .…”

Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine

“…Interestingly, these inclusions are labelled by antibodies against neurodegeneration-related proteins, such as optineurin or FUS [ 238 , 239 ]. Although INIBD is rare, it has been reported in community based studies [ 18 ] and can also be associated with other rare NDDs like CJD [ 240 ].…”