CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF
DEMENTIA
To the Editor: Creutzfeldt-Jakob disease (CJD) is a progressive
neurodegenerative condition with negative prognosis caused by an isoform of the
prion protein.1,2 Partly because of its low prevalence, physicians often neglect
it in the differential diagnosis of cognitive decline and as possible cause of
dementia in older persons. CJD is usually characterized by rapidly progressive
impairment of cognitive function associated with myoclonus, pyramidal, and
extrapyramidal dysfunction; cerebellar and visual disturbances; akinetic mutism,
or any combination of these. This report presents a paradigmatic case of CJD
recently diagnosed at the Department of Geriatrics, University Hospital Agostino
Gemelli (Rome, Italy).
CASE REPORT A 72-year-old man was admitted to the Geriatric Acute Care Unit
in September 2009 because of rapid cognitive decline (characterized by
confusion, memory impairment, and visual hallucinations) that had started
suddenly the previous month. He had been previously admitted to two other
hospitals for these symptoms. He had been hastily discharged from both with a
primary diagnosis of “Alzheimer’s disease” and referred to specific outpatient
clinics. Upon admission, he was unable to walk without assistance and showed
behavioral disorders (irritability, mood swings, psychomotor agitation). He had
congestive heart failure, chronic atrial fibrillation, chronic obstructive
pulmonary disease, and obesity. He had also had a heart pacemaker VVI implanted
2 years before for sick sinus syndrome. Routine blood tests and urinalysis were
substantially within normal ranges. He underwent two serial
electroencephalograms (EEGs), which detected periodic sharp wave complexes.
Because magnetic resonance imaging could not be done because of his pacemaker, a
head computed tomography (CT) scan was performed, revealing abnormal density
signaling in the white matter (in particular at the subcortical region and
semioval center) with slight dilatation of ventricles. Myoclonus, rigidity,
postural instability with cerebellar ataxia, pyramidal and extrapyramidal signs,
and speech disorders progressively appeared during the first days of his
hospital stay. He subsequently developed a hypokinetic, mute state and cortical
blindness. Lumbar puncture could not be performed because of the rapid
deterioration of his clinical condition and also considering the presence of the
spikes in the EEGs. He died from pneumonia 4 months after the onset of cognitive
decline. Upon autopsy, macroscopic examination revealed moderate cortical
atrophy of the brain. Histological examination showed spongiform degeneration,
neuronal loss and astroglial proliferation (Figure 1A). Immunohistochemical
examination showed the presence of abnormal deposits of prion protein (Figure
1B). Alzheimer’s disease–type pathology with early signs of beta-amyloid
deposits was also observed.
DISCUSSION By sharing common features with other dementia types3–7 and
being rare8 (with an incidence rate estimated as one to two cases per million
people per year), CJD can easily be missed or misdiagnosed. The diagnosis of CJD
is based on clinical and instrumental (EEG, cerebrospinal fluid, magnetic
resonance imaging) parameters,9 but special attention is required to make a
correct diagnosis. A definite diagnosis requires neuropathological demonstration
of the presence of the prion protein. In the current case, the presence of CJD
was determined by comprehensively assessing the patient and building up the
diagnosis based on the presence of rapid cognitive decline and neurological
features. These elements were all present (to differing extents) at the previous
in-hospital evaluations the patient received for the same condition, but his
condition was too quickly labeled as “Alzheimer’s disease.” Moreover, the EEG
was a useful diagnostic tool to validate the clinical hypothesis. It could be
argued that reaching the correct diagnosis did not change the history of the
patient, but the determination of the likely etiology of dementia is important
in establishing the prognosis and management of the patient.10 Although no known
treatment is currently available for CJD, an earlier diagnosis might have
allowed a more-suitable allocation of the patient to a second-level healthcare
facility better designed to respond to his needs.
Therefore, diagnostic suspicion of CJD should always be considered
(regardless of age) in any patient presenting with rapidly progressive dementia,
especially if associated with other neurological signs (pyramidal,
extra-pyramidal, or cerebellar). The present case emphasizes the need to
carefully and comprehensively approach the differential diagnosis of dementia to
avoid incorrect diagnoses that may merely increase the burden of the disease on
a patient and his or her relatives. A prompt and correct diagnosis may then
allow the optimal allocation of the patient to the proper clinical setting.
Finally, potentiating of facilities and resources able to take care of older
adults rapidly and efficiently after their in-hospital stay is crucial in an
aging society.
Francesco Cerullo, MD Giovanni Gambassi, MD, PhD Department of
Gerontology, Geriatrics and Physiatry Catholic University of the Sacred Heart
Rome, Italy Franca Del Nonno, MD Andrea Baiocchini, MD Department of Pathology,
National Institute for Infectious Diseases, Istituto Di Ricovero e Cura a
Carattere Scientifico “Lazzaro Spallanzani” Rome, Italy Piero Parchi, MD, PhD
Department of Neurological Science University of Bologna Bologna, Italy Matteo
Cesari, MD, PhD Institut du Vieillissement, Universite´ de Toulouse Toulouse,
France
ACKNOWLEDGMENTS
Conflict of Interest: The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the authors
have no financial or any other kind of personal conflicts with this paper.
Author Contributions: Francesco Cerullo, Giovanni Gambassi: Diagnosis and
preparation of manuscript. Franca Del Nonno, Andrea Baiocchini, Piero Parchi:
Diagnosis. Matteo Cesari: Preparation of manuscript. All of the authors read the
final version of the manuscript. Sponsor’s Role: None.
REFERENCES
1. Glatzel M, Stoeck K, Seeger H et al. Human prion diseases: Molecular
and clinical aspects. Arch Neurol 2005;62:545–552. 2. Zou WQ, Gambetti P. Prion:
The chameleon protein. Cell Mol Life Sci 2007;64:3266–3270. 3. Crecelius C.
Diagnosis and treatment of non-Alzheimer’s dementias. J Am Med Dir Assoc
2003;4:H25–H29. 4. Geschwind M, Haman A, Miller B. Rapidly progressive dementia.
Neurol Clinic 2007;25:783–789. 5. Iida T, Doh-ura K, Kawashima T et al. An
atypical case of sporadic Creutzfeldt-Jakob disease with Parkinson’s disease.
Neuropathology 2001; 21:294–297. 6. Josephs KA, Tsuboi Y, Dickson DW.
Creutzfeldt-Jakob disease presenting as progressive supranuclear palsy. Eur J
Neurol 2004;11:343–346. 7. Marin LF, Felı´cio AC, Bichuetti DB et al. Clinical
findings in Creutzfeldt- Jakob disease mimicking dementia with Lewy bodies. Arq
Neuropsiquiatr 2008;66:741–743. 8. Pruisiner SB. Shattuck
lecture-neurodegenerative diseases and prions. N Engl J Med 2001;344:1516–1526.
9. Zerr I, Kallenberg K, Summers DM et al. Updated clinical diagnostic criteria
for sporadic Creutzfeldt-Jakob disease. Brain 2009;132:2659– 2668. 10. Espinoza
RT. Improving the recognition and management of dementia in long-term care:
Obstacles and opportunities. J Am Med Dir Assoc 2006;7:128–130.
Letters
JAMA. 2001;285(6):733-734. doi: 10.1001/jama.285.6.733
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr Bacliff, Tex
Since this article does not have an abstract, we have provided the first
150 words of the full text.
KEYWORDS: creutzfeldt-jakob disease, diagnosis.
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
References 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.
Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.
2000;284:2322-2323.
Published March 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease
in the United States
Terry S. Singeltary, retired (medically)
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Published March 26, 2003
THE PATHOLOGICAL PROTEIN
BY Philip Yam
Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
Are prion diseases more prevalent than we thought?
Researchers and government officials badly underestimated the threat that
mad cow disease posed when it first appeared in Britain. They didn't think
bovine spongiform encephalopathy was a zoonosis-an animal disease that can
sicken people. The 1996 news that BSE could infect humans with a new form of
Creutzfeldt-Jakob disease stunned the world. It also got some biomedical
researchers wondering whether sporadic CJD may really be a manifestation of a
zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD
is?
Revisiting Sporadic CJD
It's not hard to get Terry Singeltary going. "I have my conspiracy
theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's
most relentless consumer advocate when it comes to issues in prion diseases. He
has helped families learn about the sickness and coordinated efforts with
support groups such as CJD Voice and the CJD Foundation. He has also connected
with others who are critical of the American way of handling the threat of prion
diseases. Such critics include Consumers Union's Michael Hansen, journalist John
Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web
site. These three lend their expertise to newspaper and magazine stories about
prion diseases, and they usually argue that prions represent more of a threat
than people realize, and that the government has responded poorly to the dangers
because it is more concerned about protecting the beef industry than people's
health.
Singeltary has similar inclinations. ...
snip...
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North
America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember,
the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been
documented in North America, along with the typical scrapie's, and atypical
Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these
TSE in different species have been rendered and fed to food producing animals
for humans and animals in North America (TSE in cats and dogs ?), and that the
trading of these TSEs via animals and products via the USA and Canada has been
immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances
and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD
only theory in 2009. With all the science to date refuting it, to continue to
validate this old myth, will only spread this TSE agent through a multitude of
potential routes and sources i.e. consumption, medical i.e., surgical, blood,
dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and
the urgent need to make all human TSE in the USA a reportable disease, in every
state, of every age group, and to make this mandatory immediately without
further delay. The ramifications of not doing so will only allow this agent to
spread further in the medical, dental, surgical arena's. Restricting the
reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO
age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge,
Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al
and many more, that the world of TSE Transmissible Spongiform Encephalopathy is
far from an exact science, but there is enough proven science to date that this
myth should be put to rest once and for all, and that we move forward with a new
classification for human and animal TSE that would properly identify the
infected species, the source species, and then the route.
CJD Singeltary submission to PLOS ;
No competing interests declared.
see full text ;
seems the sites showing the cases in other EU countries from sporadic CJD
have been taken down. however, from my files ;
IF we look at sporadic incidence of CJD in UK from 1993 to 2003, the
incidence rose from 37 in 1993 to 77 in 2003. THIS seems to show an increase to
me? I do not understand the statement ;
However, in the period following the first published description of vCJD in
1996, there was no increasing trend in the reported annual number of U.K.
sporadic CJD deaths (52).
IF we go further and look at some of the other documented BSE countries,
you will the increase of sporadic CJD there as well ;
Canada from 2 to 25
France from 35 to 108
Germany 21+ to 96
Italy 27 to 76
snip...
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive
cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which
the diagnosis of vCJD has been excluded.
Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215
cases in 2009, the highest recorded year to date. sporadic CJD is on a steady
rise, and has been since 1996.
I also urge you to again notice these disturbing factors in lines 5 and 6
;
5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive
cases;
6 Includes 23 (22 from 2010) cases with type determination pending in which
the diagnosis of vCJD has been excluded.
========end=====tss=====2011
From: Terry S. Singeltary Sr.
Sent: Wednesday, May 16, 2012 3:29 PM
To: BSE-L@LISTS.AEGEE.ORG
Subject: [BSE-L] Alzheimer’s disease and Transmissible Spongiform
Encephalopathy prion disease, Iatrogenic, what if ?
Proposal ID: 29403
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both disease, and it’s variants, in many cases are merely
names of the people that first discovered them. Both diseases are incurable and
debilitating brain disease, that are in the end, 100% fatal, with the
incubation/clinical period of the Alzheimer’s disease being longer than the TSE
prion disease. Symptoms are very similar, and pathology is very similar. I
propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation
disease, and that Alzheimer’s is Transmissible, and is a threat to the public
via the many Iatrogenic routes and sources. It was said long ago that the only
thing that disputes this, is Alzheimer’s disease transmissibility, or the lack
of. today, there is enough documented science (some confidential), that shows
that indeed Alzheimer’s is transmissible. The risk factor for friendly fire, and
or the pass-it-forward mode i.e. Iatrogenic transmission is a real threat, and
one that needs to be addressed immediately.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease. TSE prion disease survives ashing to 600 degrees celsius, that’s around
1112 degrees farenheit. you cannot cook the TSE prion disease out of meat. you
can take the ash and mix it with saline and inject that ash into a mouse, and
the mouse will go down with TSE. Prion Infected Meat-and-Bone Meal Is Still
Infectious after Biodiesel Production as well. the TSE prion agent also survives
Simulated Wastewater Treatment Processes. IN fact, you should also know that the
TSE Prion agent will survive in the environment for years, if not decades. you
can bury it and it will not go away. TSE prion agent is capable of infected your
water table i.e. Detection of protease-resistant cervid prion protein in water
from a CWD-endemic area. it’s not your ordinary pathogen you can just cook it
out and be done with. that’s what’s so worrisome about Iatrogenic mode of
transmission, a simple autoclave will not kill this TSE prion agent.
Conclusions
There should be a Global Congressional Science round table event (one of
scientist and doctors et al only, NO CORPORATE, POLITICIANS ALLOWED) set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics let science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already. what’s the use of science progressing human life to
the century mark, if your brain does not work?
combined cannot exceed 350 Words
shortened to proper word count ;
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease
have both been around a long time, and was discovered in or around the same time
frame, early 1900’s. Both diseases are incurable and debilitating brain disease,
that are in the end, 100% fatal, with the incubation/clinical period of the
Alzheimer’s disease being longer (most of the time) than the TSE prion disease.
Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals,
transmission studies, and observations of loved ones and friends that have died
from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant
Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long
incubation disease, and that Alzheimer’s is Transmissible, and is a threat to
the public via the many Iatrogenic routes and sources. It was said long ago that
the only thing that disputes this, is Alzheimer’s disease transmissibility, or
the lack of. The likelihood of many victims of Alzheimer’s disease from the many
different Iatrogenic routes and modes of transmission as with the TSE prion
disease.
Conclusions
There should be a Global Congressional Science round table event set up
immediately to address these concerns from the many potential routes and sources
of the TSE prion disease, including Alzheimer’s disease, and a emergency global
doctrine put into effect to help combat the spread of Alzheimer’s disease via
the medical, surgical, dental, tissue, and blood arena’s. All human and animal
TSE prion disease, including Alzheimer’s should be made reportable in every
state, and Internationally, WITH NO age restrictions. Until a proven method of
decontamination and autoclaving is proven, and put forth in use universally, in
all hospitals and medical, surgical arena’s, or the TSE prion agent will
continue to spread. IF we wait until science and corporate politicians wait
until politics lets science _prove_ this once and for all, and set forth
regulations there from, we will all be exposed to the TSE Prion agents, if that
has not happened already.
end...tss
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
source references
Ann N Y Acad Sci. 1982;396:131-43.
Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob
disease).
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.
Abstract
Ample justification exists on clinical, pathologic, and biologic grounds
for considering a similar pathogenesis for AD and the spongiform virus
encephalopathies. However, the crux of the comparison rests squarely on results
of attempts to transmit AD to experimental animals, and these results have not
as yet validated a common etiology. Investigations of the biologic similarities
between AD and the spongiform virus encephalopathies proceed in several
laboratories, and our own observation of inoculated animals will be continued in
the hope that incubation periods for AD may be even longer than those of CJD.
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
Tuesday, October 4, 2011
Molecular Psychiatry
advance online publication 4 October 2011; doi: 10.1038/mp.2011.120
De novo induction of amyloid-ß deposition in vivo
Our results suggest that some of the typical brain abnormalities associated
with AD can be induced by a prion-like mechanism of disease transmission through
propagation of protein misfolding. These findings may have broad implications
for understanding the molecular mechanisms responsible for the initiation of AD,
and may contribute to the development of new strategies for disease prevention
and intervention. Keywords: amyloid; prion; protein misfolding; disease
transmission
see more here ;
Wednesday, September 21, 2011
PrioNet Canada researchers in Vancouver confirm prion-like properties in
Amyotrophic Lateral Sclerosis (ALS)
snip...end
Thank You for accepting my submission
# 29403, Alzheimer’s disease and Transmissible Spongiform Encephalopathy
prion disease, Iatrogenic, what if ? and the opportunity to present it, at the
Alzheimer’s Association International Conference 2012 (AAIC), as a poster
presentation. However, with great sadness, I must regretfully decline the
invitation due to a medical reasons, and traveling to Canada, of which is not
possible. ...
Thank You,
With Kindest Regards,
I am sincerely,
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net
From:
Sent: Saturday, April 07, 2012 8:20 PM
To: Terry S. Singeltary Sr.
Subject: RE: re-submission
Dear Terry,
Yes, your proposal was accepted as a poster presentation. Please decline
the invitation if appropriate.
Best Regards,
______________________________________
Alzheimer’s Association – National Office
225 North Michigan Avenue – Floor 17
Chicago, Illinois 60601
=============snip...end...source reference...# 29403==========
Wednesday, May 16, 2012
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Proposal ID: 29403
see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of
CJD TSE prion disease as Alzheimers ;
Monday, July 23, 2012
The National Prion Disease Pathology Surveillance Center July 2012
TSS