Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

BACKGROUND: Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" METHODS: Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. RESULTS: Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrP(Sc )positive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrP(Sc )negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC). CONCLUSIONS: Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrP(Sc )positive only in lymph tissues but PrP(Sc )negative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrP(Sc )within the brain or 2) that the amount of PrP(Sc )in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.