Prion Disease Diagnosis

464185873Back in the day when I was dissecting cadavers, a note of warning swirled around the cadaver lab, advising students to read the tags accompanying their specimens to see if dementia was listed in causes of death.  If so, the advice was to double-glove, in order to avoid potential contagion with prions.  Yikes!  What are these unseen, subviral beasties about, that can survive an often prolonged bath in formalin and phenol and produce dementia in those unlucky enough to become infected?  On PodMed this week, Rick and I discuss one of them: Creutzfeldt Jakob disease, the subject of two very elegant studies in this week's New England Journal of Medicine, that may well result in a means to easily diagnose the condition in people.  First a bit of background, then let's look at the studies.

Prions are misfolded forms of a normal protein found inside cells known as the prion protein. Once inside a cell, in contrast to viruses that subvert cellular machinery in order to generate more copies of themselves, the prions simply replicate again and again, ultimately producing many copies of themselves that accumulate mostly in the central nervous system, although very minute amounts are seen elsewhere in the body. The cardinal clinical symptom is dementia.  It is the presence of these aforementioned very minute amounts of prion in other tissues that are exploited in these two studies: one in urine and the other in brushings of the olfactory epithelium at the top of the nasal cavity. If brought to clinical fruition these studies represent a great advantage over other diagnostic techniques such as brain biopsy (!) or post-mortem examination.

Urine was used to test for the presence of prions in a study of two groups of patients: 68 with one form of Creutzfeldt Jakob known as sporadic, and 14 with a variant form transmitted to humans from cows.  Regarding this group of people, the condition in cows is bovine spongiform encephalopathy.  Current known cases of the variant form number 228 but estimates are that as many as 30,000 people in the UK may be infected.

Samples obtained from these folks were centrifuged and the pellet utilized in something known as 'the protein misfolding cyclic amplification (PMCA) assay.'  This assay produces many copies of the prion so that it can be detected, and detect it they did, with almost 93% sensitivity and 100% specificity.

How about the olfactory epithelial brushings study?  This much more humane than biopsy of olfactory epithelium technique produced the following impressive results: [samples] "were positive in 30 of 31 patients with Creutzfeldt–Jakob disease (15 of 15 with definite sporadic Creutzfeldt–Jakob disease, 13 of 14 with probable sporadic Creutzfeldt–Jakob disease, and 2 of 2 with inherited Creutzfeldt–Jakob disease) but were negative in 43 of 43 patients without Creutzfeldt–Jakob disease, indicating a sensitivity of 97%... and specificity of 100%... for the detection of Creutzfeldt–Jakob disease."  Both studies used controls with dementia resulting from other causes as controls.

Good news, then, for detection, and very impressive technology.  Rick and I agree, however, that the likelihood that either of these methods will be widely applied to many is low. And of course then we have the problem of effective intervention, but that's another story. Other topics this week include 'immunonutrition' in JAMA  , an update on Ebola in NEJM and in CDC communications, and a lack of efficacy with brief drug interventions in JAMA .  Until next week, y'all live well.




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