scholarly journals Transmission Properties of Atypical Creutzfeldt-Jakob Disease: a Clue to Disease Etiology?

2015 ◽  
Vol 89 (7) ◽  
pp. 3939-3946 ◽  
Author(s):  
Atsushi Kobayashi ◽  
Piero Parchi ◽  
Masahito Yamada ◽  
Paul Brown ◽  
Daniela Saverioni ◽  
...  
Keyword(s):  
Present Report ◽  
Phenotypic Expression ◽  
Prion Strain ◽  
Transmission Properties ◽  
Plaque Type ◽  
History Of ◽  
Jakob Disease ◽  
Phenotypic Features ◽  
Codon 129 ◽  
Sporadic Cjd

ABSTRACTThe genotype at polymorphic codon 129 of thePRNPgene has a profound influence on both phenotypic expression and prion strain susceptibility in humans. For example, while the most common sporadic Creutzfeldt-Jakob disease (CJD) subtype, sporadic CJD-MM1 (M1 strain), induces a single phenotype after experimental transmission regardless of the codon 129 genotype of the recipient animal, the phenotype elicited by sporadic CJD-VV2 (V2 strain), the second most common subtype, varies according to the host codon 129 genotype. In particular, the propagation of the V2 strain in codon 129 methionine homozygotes has been linked only to acquired forms of CJD such as plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but has never been observed in sporadic CJD cases. In the present report, we describe atypical CJD cases carrying codon 129 methionine homozygosity, in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously thought to represent sporadic CJD, might actually represent acquired CJD caused by infection with the V2 strain. Thus, careful analyses of phenotypic features and transmission properties in atypical cases may be useful to distinguish acquired from sporadic cases of CJD.IMPORTANCESusceptibility to and phenotypic expression of Creutzfeldt-Jakob disease (CJD) depend on both the prion strain and genotype at polymorphic codon 129 of thePRNPgene. For example, propagation of the second most common sporadic CJD strain (V2 strain) into codon 129 methionine homozygotes has been linked to plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but has never been observed in sporadic CJD. In the present report, we describe atypical CJD cases in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously considered to represent sporadic CJD, might actually represent acquired CJD caused by infection with the V2 strain.

scholarly journals An Evaluation of Rapidly Progressive Dementia Culminating in a Diagnosis of Creutzfeldt–Jakob Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Parmvir Parmar ◽  
Curtis L. Cooper ◽  
Daniel Kobewka
Keyword(s):  
Differential Diagnosis ◽  
Cognitive Deficits ◽  
Autoimmune Encephalitis ◽  
Illustrative Case ◽  
Visual Hallucinations ◽  
Progressive Dementia ◽  
History Of ◽  
Jakob Disease ◽  
Clinical Description ◽  
Sporadic Cjd

Rapidly progressive dementia is a curious and elusive clinical description of a pattern of cognitive deficits that progresses faster than typical dementia syndromes. The differential diagnosis and clinical workup for rapidly progressive dementia are quite extensive and involve searching for infectious, inflammatory, autoimmune, neoplastic, metabolic, and neurodegenerative causes. We present the case of a previously highly functional 76-year-old individual who presented with a 6-month history of rapidly progressive dementia. His most prominent symptoms were cognitive impairment, aphasia, visual hallucinations, and ataxia. Following an extensive battery of tests in hospital, the differential diagnosis remained probable CJD versus autoimmune encephalitis. He clinically deteriorated and progressed to akinetic mutism and myoclonus. He passed away 8 weeks after his initial presentation to hospital, and an autopsy confirmed a diagnosis of sporadic CJD. We use this illustrative case as a framework to discuss the clinical and diagnostic considerations in the workup for rapidly progressive dementia. We also discuss CJD and autoimmune encephalitis, the two main diagnostic possibilities in our patient, in more detail.

Intracranial Procedures and Expected Frequency of Creutzfeldt-Jakob Disease

2015 ◽  
Vol 46 (1) ◽  
pp. 1-8
Author(s):  
Joseph Y. Abrams ◽  
Ryan A. Maddox ◽  
Lawrence B. Schonberger ◽  
Ermias D. Belay
Keyword(s):  
The United States ◽  
Annual Number ◽  
Considerable Proportion ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
History Of ◽  
Jakob Disease ◽  
Sporadic Cjd

Background/Aims: To assess the frequency and characteristics of intracranial procedures (ICPs) performed and the number of US residents living with a history of ICP. These data are used to calculate the expected annual number of sporadic Creutzfeldt-Jakob disease (CJD) cases among US residents with a history of ICP. Methods: The Nationwide Inpatient Sample provided data on the frequency and types of ICPs, and data from the National Center for Health Statistics was used to produce age-adjusted mortality rates. A model was constructed, which estimated long-term survival and sporadic CJD rates among ICP patients based on procedure type and age. Results: There were an estimated 2,070,488 ICPs in the United States from 1998 to 2007, an average of over 200,000 per year. There were an estimated 2,023,726 US residents in 2013 with a history of ICP in the previous 30 years. In 2013, there was expected to be 4.1 sporadic CJD cases (95% CI 1-8) among people with a history of ICP in the past 30 years. Conclusions: The considerable proportion of US residents living with a history of ICP is important information for retrospective assessments of CJD or any other suspected long-term outcome of ICPs.

Polymorphism at codon 129 ofPRNP affects the phenotypic expression of Creutzfeldt-Jakob disease linked to E200K mutation

2000 ◽  
Vol 48 (2) ◽  
pp. 269-270 ◽  
Author(s):  
Gianfranco Puoti ◽  
Giacomina Rossi ◽  
Giorgio Giaccone ◽  
Tazeen Awan ◽  
Patricia M.-J. Lievens ◽  
...  
Keyword(s):  
Phenotypic Expression ◽  
E200k Mutation ◽  
Jakob Disease ◽  
Codon 129

SPORADIC CREUTZFELDT-JAKOB DISEASE PRESENTING WITH A ‘JERKY ALIEN LIMB’

2015 ◽  
Vol 86 (11) ◽  
pp. e4.186-e4
Author(s):  
Maruthi Ravi Vinjam ◽  
Steven Butterworth ◽  
Richard Davey
Keyword(s):  
Cognitive Function ◽  
Acute Onset ◽  
Motor Tasks ◽  
Initial Examination ◽  
Alien Limb ◽  
Simple Motor ◽  
History Of ◽  
Jakob Disease ◽  
Time Of Presentation ◽  
Sporadic Cjd

A 64 yr old right-handed mechanic presented with four weeks history of clumsy right hand with ongoing problems at work. He described stiffness and problems with co-ordination. At the time of presentation he was noted to be walking with his right arm behind him and not being aware of this. His initial examination showed Mini Mental Score of 26/30, with ongoing involuntary movements of his right arm (Video).Video shows spontaneous elevation of right arm with occasional myoclonic jerks. Video also demonstrates patient's difficulty in following simple motor tasks and his comments that his arm “has a mind of its own”.His MRI head (Figure 1) showed typical cortical ribboning pattern described in sporadic CJD and CSF Protein for 14-3-3, s100b and RT-QUIC findings were consistent with the diagnosis of CJD.Over next 4 weeks his cognitive function rapidly deteriorated with progressive worsening of his myoclonus. He died 4 weeks after his hospital discharge.There are three broad varieties of alien limb phenomenon (ALP) types described in the literature, frontal, callosal and sensory. Jerky (myoclonic) ALP is well described in patients with CJD, so CJD should be in the differentials in any patient presenting with sub-acute onset of ALP.

scholarly journals Phenotypic diversity of genetic Creutzfeldt–Jakob disease: a histo-molecular-based classification

2021 ◽  
Author(s):  
Simone Baiardi ◽  
Marcello Rossi ◽  
Angela Mammana ◽  
Brian S. Appleby ◽  
Marcelo A. Barria ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Prion Protein ◽  
Phenotypic Diversity ◽  
Phenotypic Variability ◽  
Phenotypic Traits ◽  
Specific Effects ◽  
Jakob Disease ◽  
Phenotypic Features ◽  
Codon 129

AbstractThe current classification of sporadic Creutzfeldt–Jakob disease (sCJD) includes six major clinicopathological subtypes defined by the physicochemical properties of the protease-resistant core of the pathologic prion protein (PrPSc), defining two major PrPSc types (i.e., 1 and 2), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein gene (PRNP). How these sCJD subtypes relate to the well-documented phenotypic heterogeneity of genetic CJD (gCJD) is not fully understood. We analyzed molecular and phenotypic features in 208 individuals affected by gCJD, carrying 17 different mutations, and compared them with those of a large series of sCJD cases. We identified six major groups of gCJD based on the combination PrPSc type and codon 129 genotype on PRNP mutated allele, each showing distinctive histopathological characteristics, irrespectively of the PRNP associated mutation. Five gCJD groups, named M1, M2C, M2T, V1, and V2, largely reproduced those previously described in sCJD subtypes. The sixth group shared phenotypic traits with the V2 group and was only detected in patients carrying the E200K-129M haplotype in association with a PrPSc type of intermediate size (“i”) between type 1 and type 2. Additional mutation-specific effects involved the pattern of PrP deposition (e.g., a “thickened” synaptic pattern in E200K carriers, cerebellar “stripe-like linear granular deposits” in those with insertion mutations, and intraneuronal globular dots in E200K-V2 or -M”i”). A few isolated cases linked to rare PRNP haplotypes (e.g., T183A-129M), showed atypical phenotypic features, which prevented their classification into the six major groups. The phenotypic variability of gCJD is mostly consistent with that previously found in sCJD. As in sCJD, the codon 129 genotype and physicochemical properties of PrPSc significantly correlated with the phenotypic variability of gCJD. The most common mutations linked to CJD appear to have a variable and overall less significant effect on the disease phenotype, but they significantly influence disease susceptibility often in a strain-specific manner. The criteria currently used for sCJD subtypes can be expanded and adapted to gCJD to provide an updated classification of the disease with a molecular basis.

scholarly journals Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Roberta Galeno ◽  
Michele Angelo Di Bari ◽  
Romolo Nonno ◽  
Franco Cardone ◽  
Marco Sbriccoli ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Prion Strain ◽  
Bank Voles ◽  
Jakob Disease ◽  
Codon 129

ABSTRACT In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrPTSE) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrPTSE MVAG), showing that PrPTSE MVAG is composed of multiple conformers with biochemical properties distinct from those of PrPTSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MVAG to bank voles and gene-targeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrPTSE deposition patterns, and PrPTSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MVAG. IMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two different major conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combinations of pathological prion protein types with codon 129 genotypes results in the identification of 3 or 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding of the pathogenesis of the disease and of possible mechanisms of prion transmission.

Verrucous Psoriasis Successfully Treated with Ixekizumab: A Case Report with Review Literature

2020 ◽  
Vol 103 (9) ◽  
pp. 948-951
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Case Report ◽  
Rare Variant ◽  
Psoriasis Vulgaris ◽  
Review Literature ◽  
Antituberculous Therapy ◽  
Plaque Type ◽  
History Of

Verrucous psoriasis is a rare variant of plaque-type psoriasis with only about 35 cases reported. The authors reported a man with a history of psoriasis vulgaris for seven years, presented with progressive verrucous hyperkeratotic plaques on both legs for three years. His earlier investigations favored the diagnosis of tuberculosis verrucosa cutis. After completing the antituberculous therapy, the lesions persisted. The later investigations favored a rare subtype of psoriasis named verrucous psoriasis. Keywords: Verrucous psoriasis, Tuberculosis verrucosa cutis, Mycobacterium tuberculosis, Ixekixumab

scholarly journals Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

2021 ◽  
Vol 22 (4) ◽  
pp. 2099
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Radoslav Matej
Keyword(s):  
Prion Protein ◽  
Fluorescent Microscopy ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Key Characteristics ◽  
Jakob Disease ◽  
Immunohistochemical Methods ◽  
Confocal Fluorescent Microscopy ◽  
Codon 129

Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.

scholarly journals Atypical Creutzfeldt-Jakob Disease Evolution after Electroconvulsive Therapy for Catatonic Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Iria Grande ◽  
Juan Fortea ◽  
Ellen Gelpi ◽  
Itziar Flamarique ◽  
Marc Udina ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Disease Duration ◽  
Psychiatric Symptoms ◽  
Psychiatric Admission ◽  
Disease Evolution ◽  
Clinical Recovery ◽  
Jakob Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Electroencephalogram Eeg ◽  
Codon 129

We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT) was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI), diffusion changes, and electroencephalogram (EEG) findings the case was reoriented to Creutzfeldt-Jakob disease (CJD). The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrPSc. On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.

Effects of long-term protection from grazing on phenotypic expression in geographically separated mountain rough fescue populations

2014 ◽  
Vol 94 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D. J. Thompson ◽  
W. D. Willms
Keyword(s):  
Plant Communities ◽  
Phenotypic Expression ◽  
Highly Sensitive ◽  
History Of ◽  
Genetic Makeup ◽  
Rough Fescue ◽  
Geographic Sources ◽  
Lake Site ◽  
Summer Grazing

Thompson, D. J. and Willms, W. D. 2014. Effects of long-term protection from grazing on phenotypic expression in geographically separated mountain rough fescue populations. Can. J. Plant Sci. 94: 33–39. Whether or not long-term grazing or protection from grazing alters the genetic makeup of grass populations has been debated. Mountain rough fescue [(Festuca campestris (Rydb.)], which is highly sensitive to summer grazing, and becomes dominant in plant communities with long-term protection, was chosen to address this question. Plants from three geographic sites (Stavely in AB, Milroy in the Kootenay trench, BC and Goose Lake on the BC interior plateau) with divergent grazing histories were vegetatively propagated from tillers. Daughter plants were planted into two field nurseries (at Kamloops, BC, and Stavely, AB) and morphological measurements were taken in two field seasons post-establishment. Plants from all three populations were taller, flowered earlier, and were more productive at the Kamloops nursery site. Of the three geographic sources, plants from the Goose Lake site were most distinct with narrower leaves, later flowering, and greater yield. Plants with a long history of grazing had slightly shorter fertile tillers and leaves than plants with a history of long-term protection.

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