Differential Diagnosis of Jakob-Creutzfeldt Disease
Original Contribution| ONLINE FIRST
Differential Diagnosis of Jakob-Creutzfeldt Disease
Ross W. Paterson, MRCP; Charles C. Torres-Chae, MPA; Amy L. Kuo, MS, RN,
GNP; Tim Ando, BA; Elizabeth A. Nguyen, BS; Katherine Wong, BS; Stephen J.
DeArmond, MD, PhD; Aissa Haman, MD; Paul Garcia, MD; David Y. Johnson; Bruce L.
Miller, MD; Michael D. Geschwind, MD, PhD Arch Neurol. 2012;():1-5.
doi:10.1001/archneurol.2013.79. Text Size: AA A Published online September 24,
2012 ABSTRACT
ABSTRACT | METHODS | RESULTS | COMMENT | AUTHOR INFORMATION |
REFERENCES
Objectives To identify the misdiagnoses of patients with sporadic
Jakob-Creutzfeldt disease (sCJD) during the course of their disease and
determine which medical specialties saw patients with sCJD prior to the correct
diagnosis being made and at what point in the disease course a correct diagnosis
was made.
Design Retrospective medical record review.
Setting A specialty referral center of a tertiary academic medical
center.
Participants One hundred sixty-three serial patients over a 5.5-year period
who ultimately had pathologically proven sCJD. The study used the subset of 97
patients for whom we had adequate medical records.
Main Outcome Measures Other diagnoses considered in the differential
diagnosis and types of medical specialties assessing patients with sCJD.
Results Ninety-seven subjects' records were used in the final analysis. The
most common disease categories of misdiagnosis were neurodegenerative,
autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most
common individual misdiagnoses were viral encephalitis, paraneoplastic disorder,
depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central
nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy.
The physicians who most commonly made these misdiagnoses were primary care
physicians and neurologists; in the 18% of patients who were diagnosed correctly
at their first assessment, the diagnosis was almost always by a neurologist. The
mean time from onset to diagnosis was 7.9 months, an average of two-thirds of
the way through their disease course.
Conclusions Diagnosis of sCJD is quite delayed. When evaluating patients
with rapidly progressive dementia with suspected neurodegenerative, autoimmune,
infectious, or toxic/metabolic etiology, sCJD should also be included in the
differential diagnosis, and appropriate diagnostic tests, such as diffusion
brain magnetic resonance imaging, should be considered. Primary care physicians
and neurologists need improved training in sCJD diagnosis.
Wednesday, June 27, 2012
First US BSE Case Since 2006 Underscores Need for Vigilance
Neurology Today 21 June 2012
PO-028: Oral transmission of L-type bovine spongiform encephalopathy
(L-BSE) in primate model Microcebus murinus
Nadine Mestre-Frances,1 Simon Nicot,2 Sylvie Rouland,1 Anne-Gaëlle
Biacabe,2 Isabelle Quadrio,3 Armand Perret-Liaudet,3 Thierry Baron,2 Jean-Michel
Verdier1 1IN SER M UM2; Montpellier, France; 2Anses; Lyon, France; 3Hopitaux
Civils de Lyon; Lyon, France
An atypical form of bovine spongiform encephalopathy has been identified in
cattle in Europe, North America and Japan and was designed as L-type BSE (L-BSE)
due to the lower apparent molecular mass of the unglycosylated, protease-
resistant prion protein (PrPres) detected by western blot compared with
classical BSE. Experimental evidences from studies in transgenic mice expressing
human PrP and in primate models suggest a higher risk of transmission to humans
of the L-BSE form than for classical BSE agent. However, a major unresolved
issue concerns the potential transmissibility of the L-BSE agent by oral route.
To address this question, we infected mouse lemurs (Microcebus murinus), a
non-human primate model, with L-BSE by intracerebral or oral route.
Four adult lemurs were intracerebrally (IC) inoculated with 5mg of L-BSE
infected brain homogenate of an atypical French BSE case (02-2528). Four young
and four adult animals were fed with 5 mg or 50 mg of infected brain. After
sacrifice, the brain tissues were biochemically and immunocytochemically
investigated for PrPres.
The 4 animals IC inoculated died at 19 and 22 months postinoculation (mpi).
They developed blindness, tremor, abnormal posture, incoordinated movements,
balance loss. Symptoms get worse according to the disease progression, until
severe ataxia. Severe spongiosis was evidenced into the thalamus, the striatum,
the mesencephalon, and the brainstem, whereas into the cortex the vacuolisation
was weaker. Strong deposits of PrPres were detected into the thalamus, the
striatum, and the hippocampus whereas in the cerebral cortex, PrPres was
prominently accumulated in plaques.
The orally inoculated animals showed similar clinical symptoms occurring
between 27 and 34 mpi. Disease was characterized by progressive prostration,
loss of appetite and poor appearance of the fur. Only one adult animal showed
disequilibrium. PrPres was strongly accumulated only in the striatum and
thalamus and weakly into the cortex. No plaques were evidenced. Two animals that
were orally challenged at the age of two years are still alive and healthy 34
months after inoculation. The western blot analysis showed uniform molecular
profiles, irrespective of the route or dose of infection, and included notably a
PrPres form with low apparent molecular mass (~19 kDa) similar to the PrPres in
the original cattle brain. However, the PrPres profile in lemurs was
characterized by a higher proportion of di- and mono-glycosylated species (up to
95% of the total signal) than in the bovine L-BSE inoculum (~80%). In addition,
small amounts of PrPres were detected by western blotting in the spleen of three
animals (one intra-cerebrally inoculated and two fed with 5 mg of cattle
brain).
Here, we demonstrate that the L-BSE agent can be transmitted by oral route
from cattle to young and adult mouse lemurs. In comparison to IC inoculated
animals, orally challenged lemurs were characterized by longer survival periods
as expected with this route of infection.
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical
BSE prions as the only TSE agents demonstrated to be zoonotic so far but the
possibility that a small proportion of human cases so far classified as
"sporadic" CJD are of zoonotic origin could not be excluded. Moreover,
transmission experiments to non-human primates suggest that some TSE agents in
addition to Classical BSE prions in cattle (namely L-type Atypical BSE,
Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
see follow-up here about North America BSE Mad Cow TSE prion risk factors,
and the ever emerging strains of Transmissible Spongiform Encephalopathy in many
species here in the USA, including humans ;
Wednesday, August 01, 2012
Behavioural and Psychiatric Features of the Human Prion Diseases:
Experience in 368 Prospectively Studied Patients
Monday, August 06, 2012
Atypical neuropathological sCJD-MM phenotype with abundant white matter
Kuru-type plaques sparing the cerebellar cortex
Monday, August 20, 2012
CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF
DEMENTIA
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Monday, August 6, 2012
TAFS BSE in USA August 6, 2012
BSE in USA
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
SNIP...
What irks many scientists is the USDA’s April 25 statement that the rare
disease is “not generally associated with an animal consuming infected
feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown,
one of the world’s experts on this type of disease who retired recently from the
National Institutes of Health. "(The agency) has no foundation on which to base
that statement.”
“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the
origins of atypical cases of BSE,” she said
The argument about feed is critical because if feed is the cause, not a
spontaneous mutation, the California cow could be part of a larger outbreak.
SNIP...
==============================================
Saturday, August 4, 2012
Final Feed Investigation Summary - California BSE Case - July 2012
=============================================
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE
INVESTIGATION JULY 2012
Summary Report BSE 2012
Executive Summary
Saturday, August 4, 2012
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
Sunday, August 26, 2012
Detection of PrPSc in peripheral tissues of clinically affected cattle
after oral challenge with BSE
2011 Monday, September 26, 2011
L-BSE BASE prion and atypical sporadic CJD
see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of
CJD TSE prion disease as Alzheimers ;
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
*********************
Monday, August 20, 2012
CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF
DEMENTIA
*********************
TSS
posted by Terry S. Singeltary Sr. at
7:37 PM
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