MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology; NHS Highland Mental Health Services, Argyll and Bute Hospital; NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery
Behavioural and psychiatric symptoms (BPS) are major features of the prion diseases with a great impact on patients and carers, but up to now have been subjected to very little systematic clinical research. We have prospectively studied 368 patients, providing an unprecedented opportunity to study these symptoms across the range of prion disease types. The prevalence of BPS was high in all disease types, ranging from 70% in inherited prion disease due to PRNP point mutation (IPD-point) to 96% in variant CJD (vCJD). Prevalence at the onset of disease was more variable, ranging from 24% (IPD-point) to 92% (vCJD). We describe the clinical characteristics and natural history of the commonly occurring symptoms. Observational clinical data on 189 courses of symptomatic drug treatment shows that use of antidepressants, antipsychotics, benzodiazepines and acetyl cholinesterase inhibitors was reported to be beneficial in a substantial proportion of patients (between 15% and 60%) and that no severe adverse events were reported.
We show that specific disease types and PRNP codon 129 genotypes independently predict the presence of psychotic symptoms and the presence of BPS at disease onset, suggesting that prion strain is largely responsible for the heterogeneity seen in these clinical features. However, we also show that, in sporadic CJD, younger age at onset independently predicts the presence of BPS at onset. We discuss the implications of these findings both for clinical practice and for our understanding of the biological mechanisms underlying the complex symptoms of prion disease.
IT seems we have come full circle from the 'ORIGINAL 10' i.e. the 1st 10 adolescents in the UKBSEnvCJD only theory. and now we find us at the 1st 10 in USA, or is it the first 10, or the tip of the iceburg, many that went undocumented ??
Seven main threats for the future linked to prions
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential. In particular the L-type Atypical BSE agent might be similarly or even more virulent to humans than the Classical BSE agent. While mankind has been in contact with the major TSE of small ruminants for centuries, there is no epidemiological evidence to suggest that classical scrapie is zoonotic; however, experimental transmission data on humanised mice and non-human primates have been very scarce so far.
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story