Real-time quaking-induced conversion(RT-QuIC)assay is a newly established PrPSc-detecting method.The development of RT-QuIC improves the diagnosis of sporadic Creutzfeldt–Jakob disease(sCJD),showing good sensitivity ...Real-time quaking-induced conversion(RT-QuIC)assay is a newly established PrPSc-detecting method.The development of RT-QuIC improves the diagnosis of sporadic Creutzfeldt–Jakob disease(sCJD),showing good sensitivity and specificity in many countries when the method was used in cerebrospinal fluid(CSF)samples.However,in China,the sensitivity and specificity of RT-QuIC has yet to be determined due to the lack of definitive diagnosis samples.展开更多
Objective: To evaluate the usefulness of diffusion weighted MRI (DWI) for the early diagnosis of Creutzfeldt Jakob disease (CJD). Methods: Thirty six consecutive patients (age 56 to 82 years) were enrolled, and 26 wer...Objective: To evaluate the usefulness of diffusion weighted MRI (DWI) for the early diagnosis of Creutzfeldt Jakob disease (CJD). Methods: Thirty six consecutive patients (age 56 to 82 years) were enrolled, and 26 were examined byDWI.Ninewere definite based on theWorld Health Organization criteria, and 27 were probable. The percentages ofDWI abnormalities, periodic sharp wave complexes (PSWCs) on the EEG, detection of CSF 14- 3- 3 protein, and increase of CSF neuron- specific enolase (>25 ng/mL) on the first examination were compared. For DWI, 32 patients (age 31 to 84 years) who showed progressive dementia or impaired consciousness served as disease controls. Results: The percentage of DWI abnormalities was 92.3% , of PSWCs 50.0% , of 14- 3- 3 protein detection 84.0% , and of NSE increase 73.3% . Two of the 32 control subjects were falsely positive on DWI. The sensitivity of DWI was 92.3% (95% CI 74.8 to 99.5% ) and specificity 93.8% (95% CI 79.2 to 99.2% ). In 17 patientswho did not showPSWCs on the first EEG, abnormalDWI findings were still clearly detec ted. Four patients who were negative for 14- 3- 3 protein also showed DWI abnormalities. DWI abnormalities were detected as early as at 3 weeks of symptom duration in four patients in whom PSWCs were not yet evident. Conclusions: DWI can detect characteristic lesions in the majority of patients with CJD regardless of the presence of PSWCs. DWI was the most sensitive test for the early clinical dia gnosis of CJD; consideration should be given to its inclusion in the clinical diagnostic criteria of CJD.展开更多
Objective: To assess if clinical features, prion protein codon 129, and molecular subtype correlate with MRI basal ganglia hyperintensity in sporadic Creutzfeldt Jakob disease (CJD)- . Methods: The authors studied 219...Objective: To assess if clinical features, prion protein codon 129, and molecular subtype correlate with MRI basal ganglia hyperintensity in sporadic Creutzfeldt Jakob disease (CJD)- . Methods: The authors studied 219 patients including 153 confirmed CJD cases for their neurologic symptoms and MRI findings. The MRI was assessed by a blinded investigator for the presence of high signal intensity on T2 weighted images in the basal ganglia. Results: Patients with basal ganglia high signal on T2 weighted images were more likely to present with rapid progressive dementia in an early stage and shorter disease duration (median 6.7 months and 8.6 months). Surpri singly, among the CJD cases, patients without signal increase of the basal gangliawere shown to have a higher frequency of extrapyramidal disturbances (82% vs 70% ). More striking differences were found for symptoms such as depression and sensory disturbances, which were more frequent among cases without signal increase. MRI was more likely to be diagnostic in patients with MV2 molecular subtype. Conclusions: Selected clinical and pathologic features correlate with the presence of basal ganglia high signal on T2 weighted MRI in patients with definite or probable CJD.展开更多
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)hav...Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.展开更多
朊蛋白病（creutzfeld jakob disease,CJD）是一类慢性进行性致死性神经系统变性疾病,是继癌症、艾滋病后又一严重威胁人类和动物健康的疾病.虽然该类疾病临床罕见,但应该引起足够的认识,一旦漏诊和误诊容易给患者家庭及社会造成一定的...朊蛋白病（creutzfeld jakob disease,CJD）是一类慢性进行性致死性神经系统变性疾病,是继癌症、艾滋病后又一严重威胁人类和动物健康的疾病.虽然该类疾病临床罕见,但应该引起足够的认识,一旦漏诊和误诊容易给患者家庭及社会造成一定的危害.本科2009年10月至2010年2月共收治2例CJD患者,现报道如下.展开更多
基金Supported by Chinese National Natural Science Foundation Grants[81630062,81572048]National Key Research and Development Project[2016YFC1202700,2017YFC1200500]the State Key Laboratory of Infectious Disease Prevention and Control,China CDC[2019SKLID501 and 2019SKLID603].
文摘Real-time quaking-induced conversion(RT-QuIC)assay is a newly established PrPSc-detecting method.The development of RT-QuIC improves the diagnosis of sporadic Creutzfeldt–Jakob disease(sCJD),showing good sensitivity and specificity in many countries when the method was used in cerebrospinal fluid(CSF)samples.However,in China,the sensitivity and specificity of RT-QuIC has yet to be determined due to the lack of definitive diagnosis samples.
文摘Objective: To evaluate the usefulness of diffusion weighted MRI (DWI) for the early diagnosis of Creutzfeldt Jakob disease (CJD). Methods: Thirty six consecutive patients (age 56 to 82 years) were enrolled, and 26 were examined byDWI.Ninewere definite based on theWorld Health Organization criteria, and 27 were probable. The percentages ofDWI abnormalities, periodic sharp wave complexes (PSWCs) on the EEG, detection of CSF 14- 3- 3 protein, and increase of CSF neuron- specific enolase (>25 ng/mL) on the first examination were compared. For DWI, 32 patients (age 31 to 84 years) who showed progressive dementia or impaired consciousness served as disease controls. Results: The percentage of DWI abnormalities was 92.3% , of PSWCs 50.0% , of 14- 3- 3 protein detection 84.0% , and of NSE increase 73.3% . Two of the 32 control subjects were falsely positive on DWI. The sensitivity of DWI was 92.3% (95% CI 74.8 to 99.5% ) and specificity 93.8% (95% CI 79.2 to 99.2% ). In 17 patientswho did not showPSWCs on the first EEG, abnormalDWI findings were still clearly detec ted. Four patients who were negative for 14- 3- 3 protein also showed DWI abnormalities. DWI abnormalities were detected as early as at 3 weeks of symptom duration in four patients in whom PSWCs were not yet evident. Conclusions: DWI can detect characteristic lesions in the majority of patients with CJD regardless of the presence of PSWCs. DWI was the most sensitive test for the early clinical dia gnosis of CJD; consideration should be given to its inclusion in the clinical diagnostic criteria of CJD.
文摘Objective: To assess if clinical features, prion protein codon 129, and molecular subtype correlate with MRI basal ganglia hyperintensity in sporadic Creutzfeldt Jakob disease (CJD)- . Methods: The authors studied 219 patients including 153 confirmed CJD cases for their neurologic symptoms and MRI findings. The MRI was assessed by a blinded investigator for the presence of high signal intensity on T2 weighted images in the basal ganglia. Results: Patients with basal ganglia high signal on T2 weighted images were more likely to present with rapid progressive dementia in an early stage and shorter disease duration (median 6.7 months and 8.6 months). Surpri singly, among the CJD cases, patients without signal increase of the basal gangliawere shown to have a higher frequency of extrapyramidal disturbances (82% vs 70% ). More striking differences were found for symptoms such as depression and sensory disturbances, which were more frequent among cases without signal increase. MRI was more likely to be diagnostic in patients with MV2 molecular subtype. Conclusions: Selected clinical and pathologic features correlate with the presence of basal ganglia high signal on T2 weighted MRI in patients with definite or probable CJD.
文摘Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnormalities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms underlying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Utilizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expression QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4110,NControls=13569),we implemented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Association Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD pathogenesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were associated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were associated with CJD at the transcriptional level.
文摘朊蛋白病（creutzfeld jakob disease,CJD）是一类慢性进行性致死性神经系统变性疾病,是继癌症、艾滋病后又一严重威胁人类和动物健康的疾病.虽然该类疾病临床罕见,但应该引起足够的认识,一旦漏诊和误诊容易给患者家庭及社会造成一定的危害.本科2009年10月至2010年2月共收治2例CJD患者,现报道如下.
