Friday, June 17, 2011

Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease

Original Article

Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease

Numthip Chitravas MD1, Richard S. Jung MD1, Diane M. Kofskey BS, MBA2, Janis E. Blevins BS2, Pierluigi Gambetti MD2, R. John Leigh MD1, Mark L. Cohen MD3,*

Article first published online: 14 JUN 2011

DOI: 10.1002/ana.22454

Copyright © 2011 American Neurological

Abstract

Objective:

Heightened awareness of Creutzfeldt-Jakob disease (CJD) among physicians and the lay public has led to its frequent consideration in the differential diagnosis of patients with rapidly progressive dementia (RPD). Our goal was to determine which treatable disorders are most commonly mistaken for CJD.

Methods:

We performed a retrospective clinical and neuropathological review of prion-negative brain autopsy cases referred to the US National Prion Disease Pathology Surveillance Center at Case Western Reserve University from January 2006 through December 2009.

Results:

Of 1,106 brain autopsies, 352 (32%) were negative for prion disease, 304 of which had adequate tissue for histopathological analysis. Alzheimer disease (n = 154) and vascular dementia (n = 36) were the 2 most frequent diagnoses. Seventy-one patients had potentially treatable diseases. Clinical findings included dementia (42 cases), pyramidal (n = 20), cerebellar (n = 14), or extrapyramidal (n = 12) signs, myoclonus (n = 12), visual disturbance (n = 9), and akinetic mutism (n = 5); a typical electroencephalogram occurred only once. Neuropathological diagnoses included immune-mediated disorders (n = 26), neoplasia (n = 25, most often lymphoma), infections (n = 14), and metabolic disorders (n = 6).

Interpretation:

In patients with RPD, treatable disorders should be considered and excluded before diagnosing CJD. Misdiagnosed patients often did not fulfill World Health Organization criteria. RPD with positive 14-3-3 cerebrospinal fluid protein should not be regarded as sufficient for the diagnosis of CJD. Adherence to revised criteria for CJD, which include distinctive magnetic resonance imaging features of prion disease, is likely to improve diagnostic accuracy. ANN NEUROL 2011;

http://onlinelibrary.wiley.com/doi/10.1002/ana.22454/abstract;jsessionid=AC0684920CD22EDB421AE9FCAF845301.d03t03




REALLY ???

Just how good are those MRI diagnosis Gambetti et al wants to use ???

let's take a look shall we ;


Gambetti claims ;


"Adherence to revised criteria for CJD, which include distinctive magnetic resonance imaging features of prion disease, is likely to improve diagnostic accuracy. ANN NEUROL 2011"


PLEASE SEE ;


outside MRI reads (from the radiology reports) only had a 35% (27/76) sensitivity. Outside radiologists missed 65% of sCJD diagnoses. For two scans/subjects, neither inside nor outside reads diagnosed CJD. Among outside misreads, 47% (n=23/49) noted the abnormalities typical of sCJD but did not mention prion disease. 53% (n=26/49) of outside misreads did not note the MRI abnormalities of CJD.

Asia-Oceania Symposium on Prion Diseases AOSPD July 24-25 2010

Keynote Lecture

Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease

Michael D. Geschwind

Memory and Aging Center, University of California-San Francisco, USA mgeschwind@memory.ucsf.edu

CJD Quinacrine Study

Quinacrine eliminates prions in vitro, but its effect on the survival of sCJD patients is unknown. In February 2005, we began randomized, double-blinded, and placebo-controlled (50:50) quinacrine treatment study for sCJD. Enrollment to the treatment study ended in January 2009; study data collection ended 5/1/2009. The primary outcome was survival from randomization. Secondary outcomes included change in neurological exam, neurocognitive testing, ADL and behavioral scales, and tertiary outcomes included change in brain MRI, EEG, and MEG.

Results: 69 subjects were consented and 54 randomized to the study drug. 15 subjects were not randomized, due to various ineligibility critera and declining to participate in research. Three randomized subjects later were found to have PRNP mutations (data not included). Survival from randomization and from first symptom onset was not significantly different between the two study arms. Mean, median and range of survival times from randomization were 5.51, 4.42 and 0-18 months versus 6.98, 4.17 and 0-22 months for the placebo and quinacrine arms, respectively. Kaplan-Meier survival curve based on intention to treat analysis (ITT) showed no significant survival difference (LogRank P=0.12) between the two arms. Nor was there a difference in survival through Month 2, during the completely randomized phase of the trial (LogRank P=0.43).

Discussion: The ITT analysis based on our study design did not show a survival benefit of quinacrine in sCJD, although it is possible that quinacrine might still have an effect in some patients with prion disease.

Improved diagnosis of prion disease

Improved diagnosis - CSF. Our most recent cross-sectional CSF biomarker data suggests that the 14-3-3 protein has about 55% sensitivity and 74% specificity, elevated neuron-specific enolase (NSE; >35 ng/ml) has 65% sensitivity and 91 % specificity, and total tau protein (>1200 pg/ml) has 72% sensitivity 89% for sCJD diagnosis. We now recommend also testing for total tau, and possibly, NSE levels in the CSF of patients with suspected sCJD, but as with all CSF tests that are not identifying prions, the results must be interepreted with caution. None of these CSF tests is as sensitive or specific as MRI.

Improved Diagnosis - MRI. Brain MRI has high sensitivity and specificity for sporadic Jakob-Creutzfeldt disease (sCJD), based on the pattern of grey matter FLAIR, DWI and ADC abnormalities (restricted diffusion or T2 hyperintensity in cortex (cortical ribboning), basal ganglia and/or thalamus). As a large national CJD referral center, we noted that many brain MRls in sCJD subjects are misread by radiologists. Upon review of the outside scans sent to our center and the corresponding MRI reads by outside neurologists, we determine the frequency of missing a CJD diagnosis on brain MRls read, and what non-CJD diagnoses are considered, by radiologists.

Results: There were 66 sCJD subjects with 76 scans - some had multiple scans at different time points. 39% (26) are autopsy proven, 7.5% (5) autopsy pending, 26% (17) declined autopsy, 7.5% (n=5) are still alive and 20% (n=13) pathology status is unknown. Inside MRI reads done at UCSF had a sensitivity for CJD of 97% (74/76), outside MRI reads (from the radiology reports) only had a 35% (27/76) sensitivity. Outside radiologists missed 65% of sCJD diagnoses. For two scans/subjects, neither inside nor outside reads diagnosed CJD. Among outside misreads, 47% (n=23/49) noted the abnormalities typical of sCJD but did not mention prion disease. 53% (n=26/49) of outside misreads did not note the MRI abnormalities of CJD. Other diagnoses considered by radiologists will be presented.

Conclusion/Relevance: MRI is highly sensitive for sCJD diagnosis, but most MRls are misread. Radiologists need to be aware of the typical MRI features of CJD.




http://www.ec-pro.co.jp/aospd2010/img/AOSPD2010_Agenda_100706.pdf




http://www.ec-pro.co.jp/aospd2010/welcomingaddress.htm



http://www.ec-pro.co.jp/aospd2010/index.htm



SEE MORE HERE ;


Tuesday, June 14, 2011

Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html



Saturday, January 22, 2011

Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html




Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein 17 May 2011

Wednesday, May 18, 2011

Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein 17 May 2011 Journal of Molecular Neuroscience DOI: 10.1007/s12031-011-9543-1

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html



http://prionopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html




Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html





Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html




***+++***


Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html




Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report

http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html




IBNC

"All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein."

Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

SEAC 102/2

http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html





Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html




Tuesday, April 26, 2011

sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)

http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html





Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)


snip...


Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.


snip...


see full text ;


http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html





Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...


http://www.neuroprion.org/en/np-neuroprion.html


http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



http://prionpathy.blogspot.com/


Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf




Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html





Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html





Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html




DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!!

Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)


END...TSS



Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/cdc-assesses-potential-human-exposure.html



Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html





TSS

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