Clinicopathological phenotype of codon 129 valine homozygote sporadic Creutzfeldt-Jakob disease

The naturally occurring polymorphism at codon 129 of the human prion protein gene (PRNP) influences susceptibility to sporadic Creutzfeldt-Jakob Disease (CJD); the majority of the patients are methionine homozygotes at this locus, while valine homozygotes represent only 10% of cases. The aim was to study the clinical and neuropathological phenotype of sporadic CJD in valine homozygotes, to estimate the reliability of current clinical diagnostic criteria, and to identify any consistent and distinct features. Twelve cases of sporadic CJD with a codon 129 valine homozygote genotype were identified at the National CJD Surveillance Unit in Edinburgh. In addition to a retrospective clinical analysis, tissue blocks were stained by conventional techniques and by immunocytochemistry for prion protein. Frozen brain tissue was available from five cases for Western blot analysis of PrPRES, which in all cases showed a type 2 mobility. The cases included four males and eight females, average age 63.6 years, with a mean duration of illness of 6 months. Eleven patients presented with ataxia, and none had the characteristic EEG changes found in sporadic CJD. The neuropathological phenotype comprised spongiform change and prion protein immunopositivity most marked in the subcortical grey matter and cerebellum, prion protein positive plaque-like deposits in all regions, laminar deposition of prion protein in the cerebral cortex, and hippocampal involvement (which is seldom reported in sporadic CJD). In conclusion, these cases exhibited a fairly uniform phenotype, which is relatively distinct from sporadic CJD in methionine homozygotes, and thus diagnosis may be difficult using existing clinical criteria.     

Sporadic Creutzfeldt-Jakob disease mimicking variant Creutzfeldt-Jakob disease

BACKGROUND: The determination of the form of prion disease and early diagnosis are important for prognostic, public health, and epidemiologic reasons. OBJECTIVE: To describe a patient with sporadic Creutzfeldt-Jakob disease (sCJD) who had a clinical history and initial electroencephalogram and magnetic resonance imaging findings consistent with variant CJD (vCJD). RESULTS: Results of a repeated electroencephalogram were suggestive of sCJD, and a subsequent brain biopsy confirmed this diagnosis. CONCLUSIONS: This case cautions against relying solely on T2- and diffusion-weighted pulvinar hyperintensity and clinical features to differentiate between vCJD and sCJD, and further supports established diagnostic criteria for vCJD.     

Sporadic Creutzfeldt-Jakob disease: phenotypic variability

Prion disease are characterized by cerebral deposition of an abnormal protease-resistant isoform of a membrane-bound glycoprotein called prion protein. Sporadic Creutzfeldt-Jakob disease (CJDs) is the most frequent, accounting for approximately 85% of all human prion disease. The identification of a new variant of Creutzfeldt-Jakob disease has reinforced the need for a detailed analysis of phenotypic variability of CJDs. CJDs is typically characterized by rapidly progressive dementia, myoclonus, periodic sharp-wave electroencephalographic activity, and wide-spread spongiform degeneration. However, variations in clinical presentation, disease duration, as well as type and distribution of lesion have been consistently observed. The physicochemical properties of PrPsc in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability. Continued attention to clinically atypical cases is required to monitor the real incidence of CJDs. To reach this goal neuropathological examination, including the search for PrPsc, and molecular genetic analysis of human prion protein gene (PRNP) should be increasingly applied to atypical neurodegenerative diseases.     

Sporadic Creutzfeldt-Jakob disease: a description of two cases

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and devastating illness. It is the most frequently encountered form of the spongiform encephalopathies with 50 new cases a year in the UK. It presents with a myriad of symptoms reflecting central nervous system dysfunction and is characterized by a rapidly progressive dementia leading to death. The disease process can pose multiple challenges: diagnostic conundrums, complexities in management, and palliative care issues. Good coordinated care between services and information is paramount in adequate management and delivery of care for patients suffering from sCJD.Psychiatry services frequently become involved in the assessment and management of sCJD.     

Sporadic Creutzfeldt-Jakob disease in two coworkers

We report the coincidence of pathologically confirmed sporadic CJD in two unrelated schoolteachers who shared a school wing for 9 months. The first developed ataxia, tremulousness, and dementia 5 months after his last contact with his colleague. Diagnosis of CJD was made 2 months later by brain biopsy. Eight months later, the second teacher developed similar symptoms and died after 9 months. Whether this unique coincidence reflects mere chance or some form of direct viral transmission is unknown. Continued epidemiologic surveillance for any future "coincidence" is warranted.     

散发型克雅氏病一例报告及文献复习

克雅氏病(Creutzfeldt-Jakob disease,CJD)又称皮质一纹状体一脊髓变性、亚急性海绵状脑病,是指由朊病毒蛋白(PrP)感染所致的一种中枢神经系统变性疾病,具有传染性和致死性.现将我科收治的一例散发型CJD(sCJD)病例临床演变过程汇报如下.     

Sporadic Creutzfeldt-Jakob disease and surgery: a case-control study using community controls

BACKGROUND: The cause of sporadic Creutzfeldt-Jakob disease (CJD) is unknown. Previous studies found a link with a history of surgery but had methodologic problems. OBJECTIVE: To help elucidate medical and associated risk factors for sporadic CJD as part of the 1993 to 1995 European Union collaborative studies of CJD. METHODS: Medical and associated risk factors from 326 patients with sporadic CJD, taken from population-based studies performed between 1993 and 1995 in France, Germany, the Netherlands, and the UK, were compared with 326 community controls recruited by telephone in 2000. RESULTS: A history of surgery was significantly associated with the risk of sporadic CJD (odds ratio [OR]: 1.8; 95% CI: 1.2 to 2.6), which was not dependent on the number of surgical procedures, and was stronger in females (OR: 2.5; 95% CI: 1.5 to 4.0). Gynecologic (OR: 1.5; 95% CI: 1.0 to 2.3) and "other" operations (any operation other than neurologic, eye, ear, gallbladder, gastrointestinal, and gynecologic operations, tonsillectomy, and appendectomy) (OR: 1.5; 95% CI: 1.1 to 2.1) were associated with risk of CJD. Tonsillectomy (OR: 0.3; 95% CI: 0.2 to 0.5) and appendectomy (OR: 0.6; 95% CI: 0.4 to 0.8) were observed less frequently in cases. An increased risk was also found with a history of ear piercing in females (OR: 1.6; 95% CI: 1.1 to 2.5) and psychiatric visit(s) (OR: 2.6; 95% CI: 1.5 to 4.3). CONCLUSIONS: These results support the hypothesis that cases of sporadic CJD may result from hitherto unrecognized surgical contamination events. However, because of the limits of the study design, the rarity of the disease, and the potential for bias, the results should be interpreted with caution.     

Sporadic Creutzfeldt-Jakob disease presenting with nonconvulsive status epilepticus

Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by a spongiform encephalopathy in humans. Although the characteristic triad of myoclonus, dementia, and periodic EEG activity is easy to recognize, unusual manifestations of the disease may be challenging and create a diagnostic dilemma. We report a case of CJD that occurred in a 26-year-old patient who presented with a receptive (Wernicke's) aphasia secondary to nonconvulsive status epilepticus.     

A novel phenotype of sporadic Creutzfeldt-Jakob disease

An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype.     

Sporadic Creutzfeldt-Jakob disease with MM1-type prion protein and plaques

The authors report a 75-year-old woman with atypical sporadic Creutzfeldt-Jakob disease (CJD) characterized by MM1-type prion protein (PrP) (methionine homozygosity at codon 129 in the PrP gene and type-1 protease-resistant PrP) and PrP plaques. This patient is the first case of sporadic CJD with plaque-forming MM1-type PrP, suggesting either a shared prion strain with the plaque-forming subset of dural graft-associated CJD or shared host genetic factors that are unrelated to the PrP genotype.     

Creutzfeldt-Jakob disease: a disease overview

Creutzfeldt-Jakob disease (CJD) is the most common form of the human transmissible spongiform encephalopathies, also known as prion diseases. This is a rare neurological disorder which ultimately results in death. Technologists must familiarize themselves with the clinical symptoms and EEG patterns of this disease since appropriate precautions must be taken. This is especially important when running electroneurodiagnostic (END) studies on patients with rapidly progressive dementia or a suspected or known case of CJD. An overview of the various forms of CJD, clinical symptoms, characteristic EEG results, transmission modes, diagnostic tests, and prevention methods are addressed.     

Review: Creutzfeldt-Jakob disease: prion protein type, disease phenotype and agent strain

The human transmissible spongiform encephalopathies or human prion diseases are one of the most intensively investigated groups of rare human neurodegenerative conditions. They are generally held to be unique in terms of their complex epidemiology and phenotypic variability, but they may also serve as a paradigm with which other more common protein misfolding disorders might be compared and contrasted. The clinico-pathological phenotype of human prion diseases appears to depend on a complex interaction between the prion protein genotype of the affected individual and the physico-chemical properties of the neurotoxic and transmissible agent, thought to comprise of misfolded prion protein. A major focus of research in recent years has been to define the phenotypic heterogeneity of the recognized human prion diseases, correlate this with molecular-genetic features and then determine whether this molecular-genetic classification of human prion disease defines the biological properties of the agent as determined by animal transmission studies. This review seeks to survey the field as it currently stands, summarize what has been learned, and explore what remains to be investigated in order to obtain a more complete scientific understanding of prion diseases and to protect public health.