Sporadic CJD

Asante, E. A. et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J. 21 6358-6366,2002. 

About 85% of all cases of prion disease are sporadic CJD. These are thought to arise by spontaneous conversion of PrPc to PrPSc. Inherited (familial) forms of CJD, GSS, and FFI are also known. 

Type 1 Prps<" is found in the majority of sporadic CJD (sCJD) cases, some familial CJD (fCJD) cases, and at small... 

BSE is not transmissible to humans. However, there appears to be a strong connection between BSE and a variation of Creutzfeldt-Jakob disease, known as variant Creutzfeldt-Jakob disease (vCJD), another disease grouped with other TSEs. Evidence to date indicates that there has never been a case of vCJD transmission from person to person, but rather it is thought to spread from the consumption of cattle products contaminated with BSE. BSE and vCJD share many characteristics, to the point of being nearly indistinguishable from each other. Clinical studies have shown that mice inoculated with BSE showed the same pattern of incubation time, clinical signs, and brain lesions as mice inoculated with tissues from patients with vCJD. This provides evidence that BSE and vCJD are of the same strain . Furthermore, these two diseases were not similar to other TSEs such as sporadic CJD and known scrapies strains. 

Recently a serious public health problem has arisen by showing that a prion disease in cattle can cross species barriers and infect humans. This occurred when cattle were fed meal made from sheep infected with scrapie. The cattle developed BSE (commonly called mad cow disease ). Subsequently, when people consumed prion-contaminated beef, a small number, primarily in Great Britain, developed a variant of CJD (vCJD) approximately five years afterward. The variant form of CJD is a unique form of prion disease occurring in a much younger population than would be expected from inherited or sporadic CJD. Both BSE and vCJD share many similar pathologic characteristics suggesting an etiologic link between human vCJD and cattle BSE. 

Further evidence supporting Hectd2 as a candidate gene was provided in an association study of HECTD2 SNPs in human prion diseases [68]. From the UK, patients with variant CJD and sporadic CJD were genotyped and compared to a control population. From PNG, kuru patients were genotyped and compared to... 

Quantitation of prions in CSF samples from scrapie positive hamsters by RT-QuIC gave SD50 values of 105 6 and 104 7 per mL, respectively. Detection of prions in brain samples from TSE positive sheep and deer was also described. One important version of RT-QuIC has been shown to have 81% sensitivity and 100% specificity in discriminating sporadic-CJD and non-CJD patients based on CSF samples [52],... 

What triggers the appearance of the third form of CJD, sporadic CJD , which with one or two cases per million people, per year, worldwide constitutes the major proportion of all TSE in humans, remains unclear. In these cases no connection with mutations in the PRNP gene can be found. Somatic mutations in the PRNP gene have been suggested, although such speculation could not be confirmed experimentally as yet. 

Electroencephalogram (EEC) In human medicine electroencephalographic findings are brought in as a further diagnostic aid. The so-called periodic sharp wave complexes appear with 60-70% of patients with sporadic CJD. 

Table 2 shows the sensitivity and specificity of selected surrogate marker test procedures in comparison with other diagnostic techniques in sporadic CJD. Sensitivity and specificity refer to a given selection of patients whose neurological and psychiatric condition fits in the differential diagnosis context. 

Table 2 Sensitivity and specificity of diagnostic techniques in sporadic CJD...

An immvmoassay investigation detected 14-3-3 proteins in CS fluids from every one of the 20 patients investigated, who were definitely suffering from sporadic CJD, whereas the results of CS fluid analysis of 20 patients with dementia due to other diseases were negative for 14-3-3. The authors, therefore, rate the immvmoassay as highly sensitive and specific for the diagnosis of CJD. 

In general, the 14-3-3 immunoassay can be considered as a sensitive and specific parameter in the diagnosis of sporadic CJD. The 14-3-3 test is not suited for diagnosis of vCJD, since the sensitivity with these patients lies at just over 50%. 

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