Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies

Abstract

A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Sträussler-Scheinker syndrome (n = 24) and fatal familial insomnia (n = 41). Overall survival for each disease type was assessed by the Kaplan-Meier method and the multivariate analyses by the Cox proportional hazards model. In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.

Genotype-phenotype analysis in inherited prion disease with eight octapeptide repeat insertional mutation

“…Another striking finding was a significant inverse correlation between early age of onset and long disease duration, a pattern that has been described in a large British 6-OPRI kindred 18 and in sporadic prion diseases. 19 This inverse correlation in IPD with 6-and 8-OPRI can be contrasted with what is seen in HD and kuru where a direct correlation between early age of onset and shorter survival has been described. 20,21 Similar to IPD with 6-OPRI, age of onset was not correlated with age of death.…”

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

“…In fact, in our study, there was a trend for MV and PrP-type 2A patients to be younger and with a longer disease course (data not shown). Therefore, patients with an early disease onset and a less rapidly progressive disease course would present with less age-dependent neuronal vulnerability and less acute neuronal damage [25], leading to a less pronounced release of brain-derived proteins into the CSF. This is in agreement with the fact that, in our hands, S-100b, a protein that reflects astrocytic gliosis was the only marker independent of patients molecular characteristics, while 14-3-3, t-tau and p-tau, that reflect neuronal damage, were all influenced by codon 129 genotype and PrP-type.…”

Dendritic Cells Infiltrating Human Non-Small Cell Lung Cancer Are Blocked at Immature Stage

“…CJD is associated with progression from normal function to death in under a year in approximately 90% of patients. 5 Those reporting the history of patient with CJD witness a cognitive and neurological disorder leading to obvious progressive changes in everyday functions over periods of weeks or a month's duration, rather than noticing change over 6 months to a year, which would be more typical of a common dementia.…”