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Is Sporadic Creutzfeldt-Jakob Disease Systemic?

These findings suggest that sCJD poses more risk -- but also provides more diagnostic opportunity -- than previously realized.

The common perception about sporadic Creutzfeldt-Jakob disease (sCJD) is that the disease begins and ends in the brain. However, researchers now report the presence of prions or scrapie prion protein (PrP^Sc) in extraneural organs of patients with sCJD.

The authors examined the autopsied organs from 36 patients with proven sCJD by using phosphotungstic acid precipitation to enrich PrP^Sc preparations by up to three orders of magnitude. PrP^Sc was found in 10 of 28 spleen specimens and in 8 of 32 skeletal-muscle specimens. Three patients had PrP^Sc in both spleen and muscle. The authors estimate that the levels of PrP^Sc found in extraneural organs were about 10,000-fold lower than levels found in the brain. The presence of extraneural PrP^Sc correlated with two uncommon phenotypes of sCJD that are characterized by long disease duration. The authors speculate that the long duration of illness in these phenotypes increases the likelihood of spillover of cerebral PrP^Sc to extraneural areas.

Comment: This study forces us to rethink sCJD and raises new concerns about its transmission. The presence of PrP^Sc in peripheral tissues raises the possibility of an increased risk for iatrogenic transmission, but it also increases the feasibility of developing a blood diagnostic test. These results also call into question previous findings that ruled out the presence of PrP^Sc in skeletal muscle of bovine spongiform encephalopathy (BSE)-affected cattle and suggest that such specimens should be reexamined with modern, more sensitive techniques. A clear understanding of prion-protein distribution in humans and in animals is critically needed to provide efficient disease protection. The recent discovery of BSE in North America gives these issues added urgency.

— Wen-Quan Zou, MD, PhD, and Pierluigi Gambetti, MD

Dr. Zou is Instructor, Division of Neuropathology, Case Western Reserve University and National Prion Disease Pathology Surveillance Center, Cleveland. Dr. Gambetti is Professor and Director, Division of Neuropathology, Case Western Reserve University and National Prion Disease Pathology Surveillance Center, Cleveland.

Published in Journal Watch Neurology February 26, 2004

Citation(s):

Glatzel M et al. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003 Nov 6; 349:1812-20.

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