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CLINICAL INFECTIOUS DISEASES

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 Clinical Infectious Diseases

 Volume 43, Issue 3

 Pp. 340-346.

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Clinical Infectious Diseasescid.oxfordjournals.org

1. Clin Infect Dis. (2006) 43 (3): 340-346. doi: 10.1086/505215

Creutzfeldt-Jakob Disease: A Rare

Cause of Dementia in Elderly Persons
1. Richard Knight⇓
+ Author Affiliations

1. National Creutzfeldt-Jakob Disease Surveillance Unit, Edinburgh, United

Kingdom
1. Reprints or correspondence: Richard Knight, NCJDSU, Bryan Matthews Building,
Western General Hospital, Crewe Rd., Edinburgh EH4 2XU, United Kingdom
(R.Knight@ed.ac.uk).

Next Section

Abstract
Creutzfeldt-Jakob disease (CJD) exists in inherited, acquired (variant and
iatrogenic), and spontaneous (sporadic) forms. Although iatrogenic and variant
forms of CJD usually affect relatively young persons, all forms may affect elderly
persons, especially sporadic CJD. Sporadic CJD is a rare cause of dementia
among middle-aged and elderly persons, and typical cases are clinically fairly
distinct from more common forms of neurodegenerative dementias. However,
clinical diagnosis can be a challenge for those who are not experienced with the
disease. Fortunately, certain investigations can be very helpful. Although many
cases of CJD (especially sporadic CJD) are not thought to be acquired illnesses,
there is still a potential for onward transmission, and certain precautions are
necessary to protect public health.

Creutzfeldt-Jakob disease (CJD) is an illness that has had major medical, media,
and political impact, despite its rarity, essentially because of its potential
transmissibility with 1 form of CJD being a zoonosis. Much attention has been
focussed on variant CJD, but the most common form is sporadic CJD, a rare but
important cause of dementia among middle-aged and elderly persons. Sporadic
CJD is currently thought to be a spontaneously occurring neurodegenerative
illness that is not primarily acquired by infection, but onward transmission from
affected individuals may occur.

Previous SectionNext Section

Background
What is CJD? Jakob first described this illness in 1921; a description in an earlier
article by Creutzfeldt was retrospectively and mistakenly included for what we
now call CJD [1]. Scientific developments have led to changes in the nosology of
CJD over the years, with other diseases of humans and animals being found to
be related (table 1). Two of the most important findings were the
demonstration of the transmissibility and the central role of the prion protein
(PrP), hence the term “prion diseases” [2, 3].

CJD is now divided into 4 forms on the basis of cause and clinico-pathological
profile (table 1). Unfortunately, the media (and, indeed, others) sometimes fail
to carefully distinguish them.

The neuropathological features of prion disease are essentially

neurodegenerative: neuronal loss, astrocytic proliferation, spongiform change,
and deposition of an abnormal disease-related form of PrP in tissues [4, 5]. All
prion disease are brain illnesses typically involving dementia; they are
universally progressive, fatal, and presently incurable.

What is PrP? PrP is a normal cellular protein, of uncertain function, that, in

humans, is encoded by the PrP gene (PRNP), which is located on chromosome
20. In prion diseases, there are post-translational conformational changes,
from the normal predominantly α-helical structure (PrPC) to a more β-sheeted
form (PrPSc). The precise mechanism of this change is unclear, and its cause is
believed to vary with different prion diseases. Once the process begins, PrPSc
continues to cause PrPC to convert in an auto-catalytic amplification. PrPSc and
PrPC have different physico-chemical properties. In particular, PrPSc is relatively
insoluble, is relatively resistant to protease degradation, tends to accumulate in
tissues, and forms amyloid deposits. PrPSc is related to disease pathogenesis
and infectivity, but the precise relationships are unclear [3, 6]. Following
protease treatment of PrPSc, a significant core protein remains (designated
PrPRes) that is found in 2 different sizes (type I and type II). In addition, there are
different glycosylation patterns of the disease-related protein (A and B). Thus,
the underlying PrP found in disease can be classified (e.g., as IIB) [7–9]. These
resultant protein types vary between different forms of prion disease; thus, they
help to distinguish them.

What is the role of PRNP? PRNP, the relevant gene, is important in the disease
process. In genetic forms, the role is believed to be directly causal, but PRNP
has effects in all forms of CJD. In particular, there is a common polymorphism
at codon 129 of the open reading frame, whereby either methionine (M) or
valine (V) may be encoded. This genotype affects susceptibility to prion
diseases, may influence the incubation period in acquired cases, and can even
affect the clinico-pathological phenotype of the resulting disease (figure 1) [8,
10].

Figure 1
Percent distribution of PRNP-codon 129 genotypes in the United Kingdom,
based on 5 normal population studies of spontaneous Creutzfeldt-Jakob
disease (sCJD) cases from 1990 to 2005 and variant Creutzfeldt-Jakob disease
(vCJD) cases up to January 2006.

What is the nature of the transmissibility? CJD has characteristics that are not
unique. Other neurodegenerative illnesses (such as Alzheimer disease) involve
the deposition of an abnormally folded protein; however, CJD is transmissible.
The precise nature of the infective agent is uncertain. PrPSc is generally
associated with infectivity and the “prion theory” holds that PrPSc is either itself
the agent or a major component of it and that no specific DNA and/or RNA is
involved [2, 4].

Previous SectionNext Section

How Common is CJD, aHow Does it Present?

Genetic CJD. Genetic CJD is associated with a number of mutations of the PRNP
gene that are currently believed to be directly pathogenic. The inheritance is
autosomal dominant with generally complete or high penetrance (varying
somewhat from mutation to mutation). The clinico-pathological disease
phenotype is rather variable, depending at least in part on the particular
underlying mutation [11]. Genetic CJD is very rare, causing around 5 deaths per
year in the United Kingdom. There are 2 important facts for the nonspecialist.
First, genetic CJD can clinically mimic other forms of CJD, and a family history
of the illness may be absent. Second, despite its inherited nature, disease onset
can be late in life and is, therefore, a very rare cause of dementia in elderly
persons [11].

Sporadic CJD. Sporadic CJD has a worldwide distribution, with an annual

mortality rate of approximately 1–2 deaths per million cases. Principally, it
affects middle-aged and elderly persons (in the United Kingdom, the median
age at death is 67 years [range, 20–95 years]) [12, 13]. There is a sharply
increasing incidence associated with increasing age, but with a decrease in
incidence among persons >70 years old, it is uncertain whether this represents
a true decrease in incidence or a reflection of underascertainment of cases
among very elderly persons (figure 2). The cause is unknown; the current theory
favors either a spontaneous change in PrP structure or a somatic PRNP mutation
that leads to an abnormal form of protein. However, it remains possible that
sporadic CJD is an acquired illness, and 2 case-control studies have reported
prior surgery as a risk factor [14, 15]. Spontaneous occurrence would be
expected to produce a continuing increase in the number of cases with
increasing age, and it is certainly possible that cases among elderly persons are
overlooked, being misdiagnosed as other conditions without autopsy being
performed. In 1997, De Silva et al. [16] argued that cases in elderly persons in
the United Kingdom were not being overlooked, noting that cases of sporadic
CJD in elderly persons were not different from cases in younger persons and
that the typical clinical picture was relatively striking and unusual. A more
recent publication cited evidence to the contrary, reporting that the greatest
relative increase in the number of cases of sporadic CJD in the United Kingdom
from 1970 to 1999 had been among persons ⩾70 years old [17]. This trend has
continued, with an increase in the number of CJD-related deaths per year in the
⩾70-years-old age group in England and Wales from ∼1 to ∼25 in recent years
(figure 2) [13]. Many cases of sporadic CJD follow a relatively uniform course;
patients present with a rapidly progressive dementia that is accompanied by
other features, including cerebellar ataxia, visual loss, and myoclonus. There is,
however, a significant degree of clinical (and corresponding pathological)
heterogeneity that is especially found in the features at onset. For example,
some individuals present with an isolated cerebellar ataxia or an isolated
progressive visual loss (leading to cortical blindness) prior to the development
of progressive cognitive impairment [12, 18]. The typical clinical progression of
sporadic CJD is strikingly rapid; the median duration in the United Kingdom is 4
months, with approximately two-thirds of patients dying within 6 months.
Some cases even progress from the first symptom to death in 4 weeks, and the
patient's condition may worsen on an almost daily basis. The ability to walk and
speak are often lost early. In a typical case, the progression culminates in a
terminal akinetic mute state with myoclonus. In some cases, the illness
progresses more slowly, with durations of ⩾1 year in slightly less than 15% of
patients and of ⩾2 years in only 5% of patients [12, 18]. Even when accounting
for possible underascertainment of cases, sporadic CJD is a rare cause of
dementia among elderly persons, compared with typical causes, such as
Alzheimer disease, but the usual clinical picture is striking and rather distinct
from the usual presentations of more common neurodegenerative illnesses.
There are highly atypical cases of sporadic CJD that include slowly progressie
dementia syndromes that can be difficult to differentiate from more common
illnesses, such as Alzheimer disease, but these are exceptionally rare. The basis
for this heterogeneity is not entirely understood, and a detailed discussion is
outwith the remit of this review. However, this heterogeneity does, in part,
reflect different codon 129 genotypes, and there is some correlation with the
disease-related PrP type. A molecular- and clinico-pathological classification of
sporadic CJD has been proposed, with cases being designated as MM1, MV2,
and so on [8]. Although certain clinico-pathological features tend to be
associated with certain PRNP-129–PrP-type combinations, such classification is
not altogether clear cut. In addition, there are recent reports of >1 PrP type
being found in a single brain [7, 9, 19].
Figure 2
Mortality rates (per 1 million persons) associated with sporadic Creutzfeldt-
Jakob disease in the United Kingdom across different age groups showing
increases over 3 time periods, particularly among elderly persons.

Iatrogenic CJD. Iatrogenic CJD is simply CJD (most likely sporadic CJD) that is
transmitted from one person to another by medical or surgical treatment (table
2) [20]. It is important to note that all forms of prion disease are potentially
transmissible, even, remarkably, autosomal dominantly inherited genetic
diseases. In addition, there are increasing concerns that variant CJD will lead to
significant secondary transmission, with 2 reported cases of probable blood
transmission [21, 22].

Figure 3
Age at death (or age in January 2006, if alive) for 159 persons with variant
Creutzfeldt-Jakob disease in the United Kingdom, by age decades.

Table 1
Prion diseases.

Table 2
Iatrogenic Creutzfeldt-Jakob disease (CJD): recognized causes and worldwide
occurrence.

Patients with cases related to human growth hormone typically present as with
progressive cerebellar ataxia with only late cognitive impairment, and are
usually relatively young, reflecting the use of human growth hormone treatment
during childhood [12, 18] The clinical features of other forms of iatrogenic CJD
are generally similar to those of sporadic CJD.
Variant CJD. Variant CJD was first identified in 1996, and the earliest that onset
of symptoms has been identified is 1994 [23]. It is considered to be a result of
bovine spongiform encephalopathy in cattle entering human food, with the risk
period in the United Kingdom being generally accepted as being approximately
1980–1996 [24].

Most cases to date have occurred in the United Kingdom (the country with the
highest incidence of bovine spongiform encephalopathy), but cases have been
identified in other countries, especially France (table 3).

Table 3
Cases of variant Creutzfeldt-Jakob disease worldwide, as of January 2006.

The current UK data suggest an epidemic that is decreasing, with deaths in the
United Kingdom having peaked in the year 2000 (with only 9 deaths in 2004
and 5 in 2005 that have been identified to date) [25]. However, caution must be
expressed regarding the interpretation of these figures, not least because all
patients who have been tested to date (139 of 159 patients in the United
Kingdom) have had PRNP-129 MM (figure 1), and there are good theoretical
reasons for believing that other 129 genotypes will be affected and that they
will have a longer incubation period. There is evidence that, in variant CJD,
lymphoreticular tissues (such as tonsil and appendix tissues) are affected prior
to brain involvement [26, 27]. A survey of routine surgical appendix specimens
showed that 3 of >12,000 were positive for variant CJD—related PrPRes. By
simple extrapolation, this could mean that there are ∼237 people per 1 million
of the UK population with bovine spongiform encephalopathy infection [27].
Following dietary exposure to bovine spongiform encephalopathy, an
incubation period of at least a few years would be expected, and it is possible
that subclinical infection might occur (with reticulo-endothelial colonization but
with no clinical disease).

The age distribution of variant CJD is striking; patients are notably young
(figure 3). The median age at onset is 26 years, contrasting with the age profile
of sporadic CJD [12, 18]. However, older individuals have been affected, 1 of
whom is 74 years old (figure 3). Interestingly, the age profile has not changed
over the period of the UK epidemic; it is not clear whether this reflects age-
related dietary exposure, an age-dependent incubation period, or age-
dependent susceptibility. However, variant CJD is, at least presently, a very rare
cause of dementia in elderly persons. The relatively uniform clinical and
pathological features have not varied by age and are different from those of
sporadic CJD. The typical presenting symptoms are psychiatric or behavioral in
nature, often involving depression, social withdrawal, and anxiety; initial
diagnoses have often been for a psychiatric illness [28]. Other features may be
present, notably, persistent, painful sensory symptoms. After a mean of 6
months, ataxia develops, often with choreiform, dystonic, or myoclonic
involuntary movements. Progressive cognitive impairment ensues, and other
signs may occur, including rigidity and hyperreflexia. The later stages are
similar to those of sporadic CJD, with terminal akinetic mutism occurring in
many cases. The mean survival time is 14 months, but some patients have
survived >3 years after onset of the first symptom (figure 3) [12, 18, 29].

Previous SectionNext Section

How do I Diagnose CJD?

General points. There is no simple, noninvasive test for CJD in living patients;
definitive diagnosis requires neuropathological examination of brain tissue (by
brain biopsy or during autopsy). Biopsy is an invasive procedure, and it is
arguably reasonable only in cases for which there is a possibility of an
otherwise undiagnosed and potentially treatable illness. Fortunately, in the
majority of cases, a highly probable diagnosis can be made using typical clinical
features and other investigations, but the involvement of a clinical neurologist
is usually required. Various common and characteristic clinical features have
been incorporated into diagnostic criteria accepted by the World Health
Organization [29, 30].

The exclusion of other possible diagnoses depends on the clinical context.

Investigations have 2 broad roles: to confirm and/or exclude other possibilities
and to detect abnormalities supportive of a diagnosis of CJD. Advice regarding
diagnosis can be obtained from a variety of expert organizations (see
Appendix).

Genetic and iatrogenic CJD. Genetic CJD is confirmed by detection of a relevant

PRNP mutation (on a blood test) in an appropriate context (i.e., in the clinical
picture of prion disease and/or neuropathological confirmation). The diagnosis
of iatrogenic CJD depends on the identification of a relevant preceding
procedure.

Sporadic CJD. The diagnosis of sporadic CJD may be supported by 3

investigations: electroencephalogram, CSF analysis, and cerebral MRI [18, 31].

In a majority of cases (but not all), the electroencephalogram shows

generalized, synchronous, periodic discharges at some stage. Although not
totally unique to sporadic CJD, these findings in an electroencephalogram are
very suggestive in the appropriate clinical context. If sporadic CJD is not found
initially, the electroencephalogram can be repeated, perhaps on a weekly basis
[18, 31].

Estimation of the CSF 14-3-3 level is very helpful (the National Creutzfeldt-
Jakob Disease Surveillance Unit [NCJDSU] provides a national CSF 14-3-3
service; see Appendix). A lumbar puncture will usually be performed for
suspected cases as an important part of excluding other possible illnesses.
Since 14-3-3 is a normal neuronal protein that is found in elevated levels in
most cases of sporadic CJD, it must be stressed that a CSF 14-3-3 test result
may be positive in a variety of neurological conditions; the test's specificity for
sporadic CJD is highly context dependent. Also, a negative test result cannot
absolutely exclude sporadic CJD [31].

Cerebral imaging, preferably MRI, is indicated in all suspected cases to exclude

other possible illnesses. However, in sporadic CJD, certain characteristic MRI
changes may be observed, particularly high signal changes in the anterior basal
ganglia [32, 33].

Variant CJD. In variant CJD, an electroencephalogram does not typically show

the periodic pattern of sporadic CJD. The CSF 14-3-3 test is not as sensitive or
as specific as it is in sporadic CJD [34]. The cerebral MRI is extremely helpful; in
>90% of cases, a characteristic high signal change is observed in the posterior
thalamus (the “pulvinar sign”); this is not absolutely specific, but other possible
causes should be relatively easily distinguished on clinical grounds. It is usually
seen on T2-weighted images, but fluid-attenuation inversion recovery (FLAIR)
sequences are significantly more sensitive [33, 35]. MRI scans have revealed the
sign at only 3 months of illness; if findings of an initial scan are negative, then
a repeat scan is worth consideration. The involvement of reticulo-endothelial
tissue in variant CJD means that tonsil biopsy may detect variant CJD—related
PrPSc; the procedure is relatively invasive, and negative findings cannot
absolutely exclude the diagnosis. However, it can be diagnostically useful,
particularly in clinically uncertain or MRI-negative cases [18].

Previous SectionNext Section

What are the Infection Risks of CJD?

Secondary transmission of all cases of CJD can occur in certain circumstances,
as demonstrated by the occurrence of iatrogenic CJD. In sporadic CJD, CNS
tissues have the highest potential for infectivity; the risk of variant CJD may be
greater because of the involvement of lymphoreticular tissues. A number of
policies have been instituted to reduce the risk of onward transmission (e.g.,
policies regarding blood transfusion and surgery). However, routine contact and
nursing care does not carry any risk. If invasive procedures are to be
performed, then suitable precautions should be taken. In the United Kingdom,
the Department of Health has guidance available on its Web site, and the UK
Health Protection Agency has a CJD Incidents Panel to provide advice on issues
regarding possible transmission (see Appendix). Other countries will have their
own arrangements. Some families and clinicians may wish to consider
endoscopically inserted percutaneous endoscopic gastronomy (PEG) feeding
tubes. In the United Kingdom, the NCJDSU is able to loan specific endoscopes
for this purpose (see Appendix).

Previous SectionNext Section

What Should I do if I Have a Suspected Case?

Although CJD is not a formally notifiable disease in the United Kingdom,
clinicians (and pathologists) have been asked to notify the National Creutzfeldt-
Jakob Disease Surveillance Unit and the National Prion Clinic of any suspected
cases (see Appendix below), both for research and public health protection
purposes. Within the United Kingdom, both units are able to provide advice
regarding diagnosis and management, and both may wish to see the patient
and the family. Currently, there is no proven effective treatment for CJD, but the
NPC is responsible for the UK Medical Research Council—funded Prion-1
treatment trial (see Appendix below), and trials of potential treatments are
being considered in other countries. Within the United Kingdom, NCJDSU is
responsible for a Department of Health—funded National Care Package that can
provide advice (and funding) for care givers. There is also a recommendation to
inform the local consultant for Communicable Disease Control of any suspected
case of CJD, and there are similar arrangements in other countries. There are
experienced, helpful support organizations (see Appendix below).

Previous SectionNext Section

Conclusions
CJD is a very rare illness that may be acquired by infection and secondarily
transmitted. The most common form (sporadic CJD) affects only approximately
1–2 people per million per year, most of whom are middle aged or elderly, with
possible underascertainment of cases among people with older age. The illness
profile is usually a striking one, but most clinicians will not have had much (if
any) previous experience with cases, and there is no simple, noninvasive
diagnostic test for living patients. However, the clinical features and certain
investigations should allow a reasonably confident clinical diagnosis in most
instances, and there are national surveillance and research units in the United
Kingdom and many other countries that can provide advice and help.

Previous SectionNext Section

Acknowledgments
I am grateful to Jan McKenzie (National Creutzfeldt-Jakob Disease Surveillance
Unit) for her help in the preparation of this manuscript.

Potential conflicts of interest. R.K. has spoken at meetings organized by

Baxter's.

Previous SectionNext Section

Appendix
There are a number of organizations (whose Web sites may link to other
sources of information) that can provide advice and support:

The National Creutzfeldt-Jakob Disease Surveillance Unit, Edinburgh, United

Kingdom (http://www.cjd.ed.ac.uk)

The CJD Incidents Panel at the Health Protection Agency, London, United
Kingdom (http://www.hpa.org.uk)

The National Prion Clinic, Queen Square, London, United Kingdom

(http://www.uclh.nhs.uk)

The UK MRC PRION-1 Trial (http://www.prion.ucl.ac.uk)

The CJD Support Network (http://www.cjdsupport.net)

The Human Bovine Spongiform Encephalopathy Foundation

(http://www.hbsef.org)

The CJD Foundation, Akron, Ohio (http://www.cjdfoundation.org)

The UK Department of Health
(http://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/CJD)

 Received January 17, 2006.

 Revision received March 13, 2006.

 © 2006 by the Infectious Diseases Society of America

Previous Section

References
1. ↵
1. Katscher F

. It's Jakob's disease, not Creutzfeldt's. Nature 1998;393:11-0.

MedlineWeb of ScienceGoogle Scholar

2. ↵
1. Prusiner SB
2. Prusiner SB

. Prion biology and Diseases. In: An introduction to prion biology and

diseases; Prusiner SB, editor. New York: Cold Spring Harbour
Laboratory Press; 2004. p. 1-87.

Google Scholar

3. ↵
1. Prusiner SB
2. Prusiner SB
 . Prion biology and diseases. In: Development of the prion concept;
Prusiner SB, editor. New York: Cold Spring Harbour Laboratory Press;
2004. p. 89-141.

Google Scholar

4. ↵
1. Clark CM,
2. Trojanowski JQ
3. Ironside JW

; Clark CM, Trojanowski JQ. Neurodegenerative diseases. USA:

McGraw-Hill; 2000. General features of prion diseases; p. 329-40.

Google Scholar

5. ↵
1. Prusiner SB
2. DeArmond SJ,
3. Ironside JW,
4. Bouzamondo-Bernstein E,
5. Peretz D,
6. Fraser JR

; Prusiner SB. Prion biology and diseases. New York: Cold Spring
Harbour Laboratory Press; 2004. Neuropathology of prion diseases;
p. 777-856.

Google Scholar

6. ↵
1. Prusiner SB
2. Prusiner SB,
 3. Scott MR,
4. DeArmond SJ,
5. Carlson G

. Transmission and replication of prions. In: Prusiner SB, editor. Prion

biology and diseases. New York: Cold Spring Harbour Laboratory
Press; 2004. p. 187-242.

Google Scholar

7. ↵
1. Head MW,
2. Bunn TJR,
3. Bishop MT,
4. et al

. Prion protein heterogeneity in sporadic but not variant Creutzfeldt-

Jakob disease: UK cases 1991–2002. Ann Neurol 2004;55:851-9.

CrossRefMedlineWeb of ScienceGoogle Scholar

8. ↵
1. Parchi P,
2. Giese A,
3. Capellari S,
4. et al

. Classification of sporadic Creutzfeldt-Jakob disease based on

molecular and phenotypic analysis of 300 subjects. Ann Neurol
1999;46:224-33.

CrossRefMedlineWeb of ScienceGoogle Scholar

9. ↵
1. Polymenidou M,
2. Stoeck K,
3. Glatzel M,
4. Vey M,
5. Bellon A,
6. Aguzzi A

. Coexistence of multiple PrPSc types in individuals with Creutzfeldt-

Jakob disease. Lancet 2005;4:795-0.

Google Scholar

10. ↵
1. Windl O,
2. Dempster M,
3. et al

. Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom:

a systematic analysis of predisposing mutations and allelic variation
in the PRNP gene. Hum Genet 1996;98:259-64.

CrossRefMedlineWeb of ScienceGoogle Scholar

11. ↵
1. Kovacs GG,
2. Trabattoni G,
3. Hainfellner JA,
4. Ironside JW,
5. Knight RSG,
6. Budka H
 . Mutations of the prion protein gene: phenotypic spectrum. J Neurol
2002;249:1567-82.

CrossRefMedlineWeb of ScienceGoogle Scholar

12. ↵
1. Prusiner SB
2. Will RG,
3. Alpers MP,
4. Dormont D,
5. Schonberger LB

. Infectious and sporadic prion diseases. In: Prusiner SB, editor. Prion
biology and diseases. New York: Cold Spring Harbor Laboratory
Press; 2004. p. 629-71.

Google Scholar

13. ↵

The 13th National Creutzfeldt-Jakob Disease Surveillance Unit

annual report. 2004.

14. ↵
1. Ward HJT,
2. Everington D,
3. Croes EA,
4. et al

. Sporadic Creutzfeldt-Jakob disease and surgery: A case-control

study using community controls. Neurology 2002;59:543-8.

Abstract/FREE Full Text

15. ↵
1. Collins S,
2. Law MG,
3. Fletcher A,
4. Boyd A,
5. Kaldor J,
6. Masters CL

. Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a

case-control study. Lancet 1999;353:693-7.

CrossRefMedlineWeb of ScienceGoogle Scholar

16. ↵
1. De Silva R,
2. Findlay C,
3. Awad I,
4. Harries-Jones R,
5. Knight R,
6. Will R

. Creutzfeldt-Jakob disease in the elderly. Postgrad Med J

1997;73:557-9.

Abstract/FREE Full Text

17. ↵
1. Henry C,
2. Lowman A,
3. Will RG
 . Creutzfeldt-Jakob disease in elderly people. Age Ageing
2002;31:7-10.

FREE Full Text

18. ↵
1. Rabenau HF,
2. Cinatl J,
3. Doerr HW
4. Knight R,
5. Brazier M,
6. Collins SJ

. Human prion diseases: cause, clinical and diagnostic aspects. In:

Rabenau HF, Cinatl J, Doerr HW, editors. Prions: a challenge for
science, medicine and the public health system. Basel, Switzerland:
Karger; 2004. p. 72-97.

Google Scholar

19. ↵
1. Yull HM,
2. Ritchie DL,
3. Langeveld JPM,
4. et al

. Detection of type 1 prion protein in variant Creutzfelt-Jakob

disease. Am J Pathol 2006;168:151-7.

CrossRefMedlineWeb of ScienceGoogle Scholar

20. ↵
1. Brown P,
 2. Preece M,
3. Brandel J-P,
4. et al

. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology

2000;55:1075-81.

Abstract/FREE Full Text

21. ↵
1. Llewelyn CA,
2. Hewitt PA,
3. Knight RSG,
4. et al

. Possible transmission of variant Creutzfeldt-Jakob disease by blood

transfusion. Lancet 2004;363:417-21.

CrossRefMedlineWeb of ScienceGoogle Scholar

22. ↵
1. Peden AH,
2. Head MW,
3. Ritchie DL,
4. Bell JE,
5. Ironside JW

. Preclinical vCJD after blood transfusion in a PRNP codon 129

heterozygous patient. Lancet 2004;364:527-9.

CrossRefMedlineWeb of ScienceGoogle Scholar

23. ↵
 1. Will RG,
2. Ironside JW,
3. Zeidler M,
4. et al

. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet

1996;347:921-5.

CrossRefMedlineWeb of ScienceGoogle Scholar

24. ↵
1. Knight R

. The relationship between new variant Creutzfeldt-Jakob disease

and bovine spongiform encephalopathy. Vox Sang 1999;76:203-8.

CrossRefMedlineWeb of ScienceGoogle Scholar

25. ↵

The National Creutzfeldt-Jakob Disease Surveillance Unit annual

report. 2005.

26. ↵
1. Hilton DA,
2. Fathers E,
3. Edwards P,
4. Ironside JW,
5. Zajicek J

. Prion immunoreactivity in appendix before clinical onset of variant

Creutzfeldt-Jakob disease. Lancet 1998;352:703-4.

CrossRefMedlineWeb of ScienceGoogle Scholar

27. ↵
1. Hilton DA,
2. Ghani AC,
3. Conyers L,
4. et al

. Prevalence of lymphoreticular prion protein accumulation in UK

tissue samples. J Pathol 2004;203:733-9.

CrossRefMedlineWeb of ScienceGoogle Scholar

28. ↵
1. Spencer MD,
2. Knight RSG,
3. Will RG

. First hundred cases of variant Creutzfeldt-Jakob disease:

retrospective case note review of early psychiatric and neurological
features. BMJ 2002;324:1479-82.

Abstract/FREE Full Text

29. ↵
1. World Health Organization (WHO)

. WHO Manual for Strengthening Diagnosis and Surveillance of

Creutzfeldt-Jakob disease. Geneva: WHO; 1998.

30. ↵
1. World Health Organization (WHO)

. The revision of the surveillance case definition for variant

Creutzfeldt-Jakob disease (vCJD). Geneva: WHO; 2002.
31. ↵
1. Zerr I,
2. Pocchiari M,
3. Collins S,
4. et al

. Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of

Creutzfeldt-Jakob disease. Neurology 2000;55:811-5.

Abstract/FREE Full Text

32. ↵
1. Finkenstaedt M,
2. Szudra A,
3. Zerr I,
4. et al

. MR imaging of Creutzfeldt-Jakob disease. Radiology

1996;199:793-8.

MedlineWeb of ScienceGoogle Scholar

33. ↵
1. Collie DA,
2. Sellar RJ,
3. Zeidler M,
4. Colchester AFC,
5. Knight R,
6. Will RG

. MRI of Creutzfeldt-Jakob disease: imaging features and

recommended MRI protocol. Clinical Radiology 2001;56:726-39.
 CrossRefMedlineWeb of ScienceGoogle Scholar

34. ↵
1. Green AJE,
2. Thompson EJ,
3. Stewart GE,
4. et al

. Use of 14-3-3 and other brain-specific proteins in CSF in the

diagnosis of variant Creutzfeldt-Jakob disease. J Neurol Neurosurg
Psychiatry 2001;70:744-8.

Abstract/FREE Full Text

35. ↵
1. Collie DA,
2. Summers DM,
3. Sellar RJ,
4. et al

. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar

sign: MR imaging findings in 86 neuropathologically confirmed
cases. Am J Neuroradiol 2003;24:1560-9.

Abstract/FREE Full Text

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2. Abstract
3. Background
4. How Common is CJD, aHow Does it Present?
5. How do I Diagnose CJD?
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