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BACKGROUND: Sporadic Creutzfeldt-Jakob Disease (SCJD) is a severe neurodegenerative disorder characterized by rapid progression and extensive neuronal loss. Disulfidptosis is an innovative type of programmed cell demise characterized by an accumulation of disulfide bonds within the cellular cytoplasm, subsequently triggering functional disruption and cell demise. METHODS: Through literature review and analysis, we identified 18 candidate disulfidptosis-related genes (DRGs) involved in cellular processes. The dataset used for analysis, GSE124571, was obtained from the Gene Expression Omnibus database. Gene-gene and protein-protein interactions were analyzed using the GeneMANIA and STRING databases, respectively. We also performed enrichment analysis, differential expressed genes analysis, weighted gene correlation network analysis analysis, immune infiltration, consensus clustering, and matrix correlation. RESULTS: The analysis showed that 12 out of 18 DRGs were significantly changed between SCJD and control groups. The DRGs had strong interactions such as physical interactions, co-expression and genetic interactions, and were enriched in biological processes and pathways related to actin cytoskeletal regulation. The study most notably identified 3 hub genes (WASF2, TLN1 and G6PD) important for SCJD and emphasized the functional significance of the identified hub genes. The role of the immune system in the pathogenesis of SCJD. The study found that the composition of immune cells in SCJD brain tissue is altered. Consensus clustering provided insights into immune infiltration and hub gene expression in SCJD subgroup. CONCLUSIONS: Our study reveals the possible involvement of disulfidptosis in SCJD and highlights the significance of identified hub genes as potential biomarkers and therapeutic targets for SCJD.

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Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.

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Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and fatal neurodegenerative disorder belonging to a group of diseases known as prion disease. Characterized by the formation of abnormal prion proteins in the brain, these conditions lead to tissue damage and vacuolation, giving the brain a sponge-like appearance. sCJD represents the most prevalent form of CJD, accounting for roughly 85% of all CJD cases. We report a case with unusual clinical manifestations. The patient experienced progressive neurological symptoms and MRI progression.

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Background: As a rare neurodegenerative disease, sporadic Creutzfeldt-Jakob disease (sCJD) is poorly understood in the elderly populace. This study aims to enunciate the multidimensional features of sCJD in this group. Methods: A case of probable sCJD was reported in a 90-year-old Chinese man with initial dizziness. Then, available English literature of the elderly sCJD cases (aged 80 years and over) was reviewed and analyzed. Patients (15 cases) were subdivided and compared geographically. Results: In the elderly sCJD cohort, the onset age was 84.9 ± 4.5 years and the median disease duration was 6.8 months, with respiratory infection/failure as the commonest death cause. Various clinical symptoms were identified, with cognitive disorder (86.7%) as the commonest typical symptom and speech impairment (66.7%) as the most atypical one. Restricted hyperintensities were reported in 60.0% cases on DWI, periodic sharp wave complexes in 73.3% cases on electroencephalogram, and cerebral hypoperfusion/hypometabolism in 26.7% cases on molecular imaging. The sensitive cerebrospinal fluid biomarkers were total tau (83.3%), 14-3-3 protein (75.0%), and PrP RT-QuIC (75.0%). Neuropathological profiles in the cerebral cortex revealed vacuolar spongiosis, neuronal loss, gliosis, and aging-related markers, with synaptic deposit as the commonest PrP pattern (60.0%). The polymorphic PRNP analysis at codon 129 was M/M (90.9%), with MM1 and MM2C as the primary molecular phenotypes. Latency to first clinic visit, hyperintense signals on DWI, and disease duration were significantly different between the patient subgroups. Conclusion: The characteristics of sCJD are multidimensional in the elderly, deepening our understanding of the disease and facilitating an earlier recognition and better care for this group.

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Prion disease is an infectious and fatal neurodegenerative disease. Western blotting (WB)-based identification of proteinase K (PK)-resistant prion protein (PrPres) is considered a definitive diagnosis of prion diseases. In this study, we aimed to detect PrPres using formalin-fixed paraffin-embedded (FFPE) specimens from cases of sporadic Creutzfeldt-Jakob disease (sCJD), Gerstmann-Sträussler-Scheinker disease (GSS), glycosylphosphatidylinositol-anchorless prion disease (GPIALP), and V180I CJD. FFPE samples were prepared after formic acid treatment to inactivate infectivity. After deparaffinization, PK digestion was performed, and the protein was extracted. In sCJD, a pronounced PrPres signal was observed, with antibodies specific for type 1 and type 2 PrPres exhibited a strong or weak signals depending on the case. Histological examination of serial sections revealed that the histological changes were compatible with the biochemical characteristics. In GSS and GPIALP, prion protein core-specific antibodies presented as PrPres bands at 8-9 kDa and smear bands, respectively. However, an antibody specific for the C-terminus presented as smears in GSS, with no PrPres detected in GPIALP. It was difficult to detect PrPres in V180I CJD. Collectively, our findings demonstrate the possibility of detecting PrPres in FFPE and classifying the prion disease types. This approach facilitates histopathological and biochemical evaluation in the same sample and is safe owing to the inactivation of infectivity. Therefore, it may be valuable for the diagnosis and research of prion diseases.

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Sporadic Creutzfeldt-Jakob disease (sCJD) is an uncommon prion disease, also a fatal degenerative brain disorder. We aimed to illustrate 2 clinical cases, a 60-year-old female and a 57-year-old male, who came to the hospital due to rapidly progressive cognitive decline. A 1.5T brain MRI in both patients detected cortical and basal ganglia signal abnormalities with diffuse, asymmetrical features. The patient underwent electroencephalography and cerebrospinal fluid tests, which showed abnormal waves and a positive 14-3-3 protein test in the CSF samples of both patients. According to the 2018 US Centers for Disease Control and Prevention (CDC) diagnostic criteria, we finally diagnosed these patients with sCJD.

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Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.

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Sporadic Creutzfeldt-Jakob disease is characterized by rapid cognitive and neuropsychiatric impairment. The Heidenhain variant of Creutzfeldt-Jakob disease is known for isolated visual disturbance that precedes other features. Periodic sharp wave complexes on EEG are typical of sporadic Creutzfeldt-Jakob disease, but at the onset, the electroclinical pattern may be unclear and suggest the hypothesis of a non-convulsive status epilepticus. Furthermore, non-convulsive status epilepticus and sporadic Creutzfeldt-Jakob disease could coexist simultaneously. We report the case of a patient admitted to our hospital for progressive psychiatric and cognitive disorders. In the initial phase, based on clinical, EEG, and neuroradiological features, a diagnosis of possible non-convulsive status epilepticus was made. Subsequently, the rapid neurological degeneration led to the diagnosis of Creutzfeldt-Jakob disease confirmed by cerebrospinal fluid real-time quaking-induced conversion. Non-convulsive status epilepticus could mimic Creutzfeldt-Jakob disease or be present in overlap. Antiseizure drugs may be started when the etiology is unclear, but overtreatment should be avoided when invasive treatment protocols fail, and the neurological progression suggests an encephalopathy.

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BACKGROUND: Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging (MRI) abnormalities in the cerebral cortex, basal ganglia, thalamus, and cerebellum could indicate severe acute diseases caused by a variety of factors. Although their MRI patterns may resemble those of CJD, clinical history, additional MRI findings, and laboratory testing are all necessary to provide a reliable difference. Here, we report a misdiagnosed case of probable VV1 subtype of sporadic CJD (sCJD) in which follow-up MRI supported the diagnosis. CASE PRESENTATION: A 41-year-old male patient attended the Neuropsychiatry Department with rapidly progressive dementia, akinetic mutism, and difficulty walking and speaking. His problem began with forgetfulness, disorganized behavior, and disorganized speech 7 months earlier which progressed rapidly and was accompanied by aphasia, apraxia, agnosia, and akinetic mutism in the last 2 months. On neurologic examination, hypertonia, hyperreflexia, frontal ataxia, bradykinesia, gait apraxia, and aphasia were noted. Based on clinical features and rapid symptoms progression the likely diagnosis of CJD was suspected. MRI and electroencephalography (EEG) were advised. MRI revealed features of diffuse cortical injury of both cerebral hemispheres also involving bilateral corpus striatum with evidence of cerebral volume loss. EEG showed lateralized periodic theta slow waves on the right side. According to the CDC's diagnostic criteria for CJD, the diagnosis of probable sCJD was established. Supportive care and symptomatic treatment are provided for the patient. After a 1-month follow up the patient's condition deteriorated significantly. The time-lapse from the first reported symptom to death was about 13 months. CONCLUSION: The need of addressing CJD in patients presenting with rapidly progressive dementia is highlighted in this case report. In the early stages of the disease, interpretation of MRI results might cause diagnostic difficulties; therefore, follow-up MRI is critical in obtaining the correct diagnosis.

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Background: Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder, with few months as a usual duration from onset to death. Case presentation: In this case report, a patient of Sporadic CJD (sCJD) who presented one month after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The diagnosis of this case was established after confirming findings from clinical, neurophysiology, radiological, and laboratory features of this disease. Conclusion: Putting in mind all the updated data on the pathogenesis of CJD and the immune responses to SARS-CoV-2, we can suggest that COVID-19 can lead to accelerated pathogenesis and exaggerated manifestations of this fatal neurodegenerative disease.

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Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of prion diseases. The causes of sCJD are still unknown and exogenous factors may play a role. Worldwide, the number of patients with sCJD has progressively increased over time. This increase can be partly explained by increasing life expectancy and better case ascertainment, but a true increase in the number of sCJD cases cannot be excluded. We estimated mortality rates from sCJD in France (1992-2016) and studied variation in mortality rates by age, period, and time.We included all cases aged 45-89 years old who died with a probable/definite sCJD diagnosis based on the French national surveillance network. We used age-period-cohort (APC) Poisson regression models to study variation in mortality rates by sex, age, period, and time.A total of 2475 sCJD cases aged 45-89 years were included. Mortality rates increased with age, reached a peak between 75 and 79 years, and decreased thereafter. Mortality rates were higher in women than men at younger ages and lower at older ages. The full APC model with a sex×age interaction provided the best fit to the data, thus in favour of sex, age, period, and cohort effects on mortality rates. In particular, mortality rates increased progressively with successive birth cohorts.Based on 25 years of active surveillance in France, we show evidence for sex, age, period, and cohort effects on sCJD mortality. The identification of cohort effects suggests that environmental exposures may play a role in sCJD etiology.

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INTRODUCTION: Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) is characterised by a wide range of neuropsychiatric symptoms and elevated thyroid antibodies. SREAT can mimic sporadic Creutzfeldt-Jakob disease (sCJD) and distinguishing between both entities is important because SREAT responds to corticosteroids. MATERIAL AND METHODS: Data of patients reported to the National Reference Centre for the Surveillance of CJD in Göttingen, Germany between August 1994 and October 2008 was retrospectively reviewed. In the case and control groups, 49 patients had SREAT and 48 had sCJD with elevated thyroid antibodies. RESULTS: Antibodies against thyroid peroxidase were the most common antibodies in both SREAT (86%) and sCJD (88%), followed by antibodies against thyroglobulin (SREAT, 63.3%; sCJD, 39.6%; p = 0.020) and TSH-receptor-antibodies (SREAT, 14.3%; sCJD, 2.1%; p = 0.059). Epileptic seizures were observed more frequently in the SREAT group (SREAT, 44.9%; sCJD, 12.5%; p < 0.001). Dementia (SREAT, 61.2%; sCJD, 100%; p < 0.001), ataxia (SREAT, 44.9%; sCJD, 89.6%; p < 0.001), visual impairment (SREAT, 22.4%; sCJD, 50%; p = 0.005), extrapyramidal disorder (SREAT, 32.7%; sCJD, 60.4%; p = 0.006), myoclonus (SREAT, 38.8%; sCJD, 81.3%; p < 0.001) and akinetic mutism (SREAT, 6.1%; sCJD, 37.5%; p < 0.001) were observed more frequently in sCJD. Cerebrospinal fluid (CSF) pleocytosis was observed more frequently in SREAT patients (SREAT, 33.3%; sCJD, 6.4%; p = 0.001), as was a pathological increase in protein concentration (SREAT, 68.8%; sCJD, 36.2%; p = 0.001). CONCLUSIONS: In a case of encephalopathy, the diagnosis of SREAT should also be considered in suspected cases of CJD so as to be able to start corticosteroid treatment quickly.

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Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.

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In this study, we report on a case of probable sporadic Creutzfeldt-Jakob disease (sCJD) diagnosed after a difficult course of status epilepticus (SE) in a patient with poststroke epilepsy. The patient was admitted with progressive cognitive decline and convulsive SE; therefore, it was initially thought that the patient had developed SE due to nonadherence to antiseizure medication (ASM) use, but despite treatment with ASMs after admission, no improvement was noted in consciousness disturbance or lateralized periodic discharges (LPDs) on electroencephalogram (EEG) examination. After a refractory course, the progression of LPDs to generalized periodic discharges (GPDs) on EEG and abnormal magnetic resonance imaging (MRI) findings met the diagnostic criteria of sCJD. Even if the patient had epilepsy, such as poststroke epilepsy, as in this case, it is essential to consider other underlying causes, including CJD in cases of superrefractory SE.

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Creutzfeldt-Jakob disease (CJD) is characterized by a broad phenotypic spectrum regarding symptoms, progression, and molecular features. Current sporadic CJD (sCJD) classification recognizes six main clinical-pathological phenotypes. This work investigates the molecular basis of the phenotypic heterogeneity of prion diseases through a multi-omics analysis of the two most common sCJD subtypes: MM1 and VV2. We performed DNA target sequencing on 118 genes on a cohort of 48 CJD patients and full exome RNA sequencing on post-mortem frontal cortex tissue on a subset of this cohort. DNA target sequencing identified multiple potential genetic contributors to the disease onset and phenotype, both in terms of coding, damaging-predicted variants, and enriched groups of SNPs in the whole cohort and the two subtypes. The results highlight a different functional impairment, with VV2 associated with higher impairment of the pathways related to dopamine secretion, regulation of calcium release and GABA signaling, showing some similarities with Parkinson's disease both on a genomic and a transcriptomic level. MM1 showed a gene expression profile with several traits shared with different neurodegenerative, without an apparent distinctive characteristic or similarities with a specific disease. In addition, integrating genomic and transcriptomic data led to the discovery of several sites of ADAR-mediated RNA editing events, confirming and expanding previous findings in animal models. On the transcriptomic level, this work represents the first application of RNA sequencing on CJD human brain samples. Here, a good clusterization of the transcriptomic profiles of the two subtypes was achieved, together with the finding of several differently impaired pathways between the two subtypes. The results add to the understanding of the molecular features associated with sporadic CJD and its most common subtypes, revealing strain-specific genetic signatures and functional similarities between VV2 and Parkinson's disease and providing preliminary evidence of RNA editing modifications in human sCJD.

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Although sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disease and often difficult to diagnose at the earliest onset, meticulous clinical examination, electroencephalography, and neuroimaging findings will help in diagnosis.

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Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition and a human prion disease. Rapid progressive dementia, myoclonus, visual disturbances, cerebellar signs, and pyramidal/extrapyramidal symptoms are observed in such patients. However, these are non-specific symptoms and can manifest in a variety of other conditions. The occurrence of sporadic CJD in a patient with multiple sclerosis (MS) is rare. This is the case of a 54-year-old man on natazulimab for MS who developed rapid neurocognitive changes along with visual changes, imbalance issues, and mood changes. Diagnosis of sporadic CJD (sCJD) was confirmed through clinical features, physical examination and electroencephalogram findings, cerebral spinal fluid analysis, and later magnetic resonance imaging findings. sCJD with MS being a rare phenomenon, its recognition requires a high index of suspicion, careful chronological evaluation of the patient's symptoms, and relevant investigations that can aid in reaching the diagnosis.

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Creutzfeldt-Jakob disease (CJD) is a low-prevalence, fatal neurodegenerative disease. Parkinsonism as first symptom of CJD is rare. We present a case manifesting difficulty falling asleep as unspecific prodromal symptom and parkinsonism as initial symptom. The patient received positron emission tomography/computed tomography (PET/CT) of dopamine transporter (DAT) using 18 F-FP-CIT. The DAT-scan demonstrated presynaptic dopaminergic deficit in bilateral posterior putamen, which supports the hypothesis of nigrostriatal pathway dysfunction in CJD.

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Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrPC) into the transmissible 'scrapie-type' prion form (PrPSc). Neuropathologic evaluation of brains with sCJD reveals abnormal PrPSc deposits primarily in grey matter structures, often associated with micro-vacuolar spongiform changes in neuropil, neuronal loss, and gliosis. Abnormal PrPSc deposits have also been reported in the retina of patients with sCJD, but few studies have characterized the morphology of these retinal PrPSc deposits or evaluated for any retinal neurodegenerative changes. We performed histopathologic and morphometric analyses of retinal and brain prion deposits in 14 patients with sCJD. Interestingly, we discovered that the morphology of retinal PrPSc deposits generally differs from that of brain PrPSc deposits in terms of size and shape. We found that retinal PrPSc deposits consistently localize to the outer plexiform layer of the retina. Additionally, we observed that the retinal PrPSc deposits are not associated with the spongiform change, neuronal loss, and gliosis often seen in the brain. The stereotypic morphology and location of PrPSc deposits in sCJD retinas may help guide the use of ocular imaging devices in the detection of these deposits for a clinical diagnosis.

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