Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein.
OBJECTIVE
Human transmission of bovine spongiform encephalopathy causes the fatal neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD) and, based on recent human prevalence studies, significant subclinical prion infection of the UK population. To date, all clinical cases have been fatal, totaling 228 mostly young adults residing in the United Kingdom.


METHODS
Here we describe the investigation and case history of a patient recently diagnosed as having vCJD in the United Kingdom. Although his presentation, imaging findings, cerebrospinal fluid investigation results, and clinical progression were typical of other cases, tonsillar biopsy and subsequent examination of multiple tissues at autopsy showed minimal deposition of disease-associated prion protein in peripheral lymphoreticular tissue. The result of a blood test for vCJD, the Direct Detection Assay for vCJD, was negative.


CONCLUSIONS
These findings suggest that some patients with vCJD have very low peripheral prion colonization and therefore may not have detectable prion deposition in diagnostic tonsillar biopsy or markers of prion infection in blood. These results have implications for accurate interpretation of diagnostic tests and prevalence studies based on lymphoreticular tissue or blood.
National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London, England2Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, En.
Simon
S
Mead
Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, England.
Jonathan D F
JD
Wadsworth
National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London, England.
Marie-Claire
MC
Porter
Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, England.
Jacqueline M
JM
Linehan
The Walton Centre NHS Foundation Trust, Fazakerley, Liverpool, England.
Wojciech
W
Pietkiewicz
Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, England.
Graham S
GS
Jackson
Division of Neuropathology, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, England.
Sebastian
S
Brandner
National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London, England2Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, Queen Square, London, En.
John
J
Collinge
D000328:Adult; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D017809:Fatal Outcome; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology; D008297:Male; D014066:Palatine Tonsil / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D006113:United Kingdom
D011328:Prions