Abstract
IntroductionThe coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.Case presentationA 74-year-old Caucasian woman showed a sporadic Creutzfeldt–Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.Neuropathological findings showed: spongiform change in the patient’s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous.ConclusionMolecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt–Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.
Highlights
The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.Case presentation: A 74-year-old Caucasian woman showed a sporadic Creutzfeldt–Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes
Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt–Jakob disease
A novel form of sporadic prion disease, termed variably protease-sensitive prionopathy (PSPr or VPSPr), has recently been reported [1]. This form comprises, to date, a low number of cases worldwide [1,2,3,4,5,6], and in the USA it was estimated to account for 3% of sporadic Creutzfeldt–Jakob disease [1]
Summary
The first 129VV protease-sensitive prionopathy series reported [1] and further characterized (PSPr or VPSPr) [2,4,6] presented with neurobehavioral and psychiatric signs such as behavior and mood changes, speech deficit and cognitive impairment, followed by progressive motor decline and dementia. Co-occurrence of different PKsensitivity PrP types in the same PSPr patient has, to the best of our knowledge, not yet been reported [1,2,4,6], even though coexistence of different classical PK-resistant PrP forms is a common finding in other prion diseases [7,8,9,10,11,12,13,14,15]. This observation constitutes a novel finding which broadens the spectrum of molecular and clinicopathological features of spongiform encephalopathies.
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