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

Journal of Translational Medicine

Research

Alexia L McKnight¹  Lawrence A Minkoff²  Doru T Alexandrescu³  Thomas E Ichim⁴  Diane L Sutton⁵  Joel M Stutman⁶  Raymond W Sweeney⁷  Gary Smith⁸  Perry L Habecker⁹  Constantin A Dasanu^1,10  Bruce V Thomsen^1,11 

[1] Assistant Professor of Radiology, University of Pennsylvania School of Veterinary Medicine, New Bolton Center, 19348, Kennett Square, PA, USA;Executive Vice President, Fonar Corporation, Marcus Drive, Melville, NY, USA;Georgetown Dermatology, 20010, Washington, DC, USA;Medistem Inc., 92101, San Diego, CA, USA;National Scrapie Program Coordinator, United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services, 20737, Riverdale, MD, USA;Professor and Chairman (Retired), Medical Computer Science Program, College of Health Related Professions, Downstate Medical Center, State University of New York, Brooklyn, NY, USA;Professor of Medicine & Chief, Section of Medicine, Department of Clinical Studies, New Bolton Center, 382 West Street Road, 19348, Kennett Square, PA, USA;Professor of Population Biology and Epidemiology & Chief, Section of Epidemiology and Public Health, Department of Clinical Studies, New Bolton Center, 382 West Street Road, 19348, Kennett Square, PA, USA;Professor, The Pennsylvania Animal Diagnostic Laboratory System at New Bolton Center and the Laboratory of Pathology and Toxicology, School of Veterinary Medicine, University of Pennsylvania, 382 W. Street Road, 19348, Kennett Square, Pennsylvania, USA;Saint Francis Hospital and Medical Center, 06105, Hartford, CT, USA;United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Laboratories, 50010, Ames, IA, USA;

关键词: Bovine Spongiform Encephalopathy;    Scrapie;    Body Condition Score;    Retropharyngeal Lymph Node;    Lymph Tissue;   

DOI  :  10.1186/1479-5876-8-125

 received in 2010-04-01, accepted in 2010-11-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMagnetic 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?"MethodsScrapie, 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.ResultsOur 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 PrPSc positive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC).ConclusionsOur 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 PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2) that the amount of PrPSc 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.

【 授权许可】

CC BY   
© McKnight et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.