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From: TSS ()
Subject: Young-onset CJD: age and disease phenotype in variant and sporadic forms
Date: March 23, 2007 at 8:38 am PST

Young-onset CJD: age and disease phenotype in

variant and sporadic forms

Manuel Coratoa,b,c

Cristina Ceredaa

Emanuela Covaa

Carlo Ferraresec,d

Mauro Ceronia,b,e

a Laboratory of Experimental Neurobiology, IRCCS “C.

Mondino Institute of Neurology” Foundation, Pavia, Italy

b Department of Neurology, Policlinico di Monza, Monza,


c Department of Neuroscience and Biomedical Technologies,

University of Milan-Bicocca, Milan, Italy

d Department of Neurology, University of Milan-Bicocca, S.

Gerardo Hospital, Monza, Italy

e Department of Neurological Sciences, University of

Pavia, Italy

Reprint requests to: Prof. Mauro Ceroni

Department of Neurological Sciences, University of Pavia

Via Mondino, 2 - 27100 Pavia - Italy


Accepted for publication: December 28, 2006


Since 1996, there have been over 140 reports of a

Creutzfeldt-Jakob disease variant (vCJD), with a striking

prevalence of these cases in the UK. The main peculiarity

of vCJD is its onset in young people, but other

features also distinguish it from sporadic CJD. Despite

epidemiological data suggesting a link with bovine

spongiform encephalopathy, the origin of vCJD is not

completely understood. We hypothesized that the onset

of vCJD at a young age might contribute to the disease

phenotype. We searched the Medline/PubMed

database for all case reports of CJD in the under-30s

and selected 20 sporadic CJD patients with a median

age at onset of 25.5 years. Our series displays a long

disease duration and other vCJD-like features, suggesting

that CJD in young people is different from classic

CJD and that the vCJD phenotype may be partly related

to young age.

KEY WORDS: CJD, sporadic CJD, survival, variant CJD, young.



We analyzed a small sample of CJD patients, whose

disease was characterized by young age at onset. The

cases included in our series came from different countries

and were reported at different times. The series

was found to present several atypical features showing

that CJD in young people is different from the classic

form of CJD occurring in middle age. Yet it must be emphasized

that all the reports analyzed were found to

concern sCJD and that none of the cases described fulfilled

all the clinical and pathological criteria for a diagnosis

of vCJD.

The most interesting finding in our CJD patient series

was the prolonged survival time compared to the mean

survival duration observed in the classic form of CJD.

Until a few years ago, there were no available studies

examining the duration of CJD in different age groups.

In a recent paper by Boesenberg et al. (24), the authors

Young-onset CJD

Functional Neurology 2006; 21(4): 211-215 213

Table III - Clinical, laboratory and pathological features of sCJD in young patients.

Reference Sex Age Survival Presenting Periodic Amyloid Codon PrP

(years) (months) symptom(s) EEG plaques 129 type

(25) M 25 18 Ataxia n.r. No n.r. n.r.

(26) F 29 51 Ataxia Yes Yes n.r. n.r.

(27) M 16 28 Dementia Yes No n.r. n.r.

(28) F 26 34 Ataxia No No n.r. n.r.

(29) F 19 4 Psychiatric Yes No n.r. n.r.

(30) F 14 24 Dementia No No n.r. n.r.

(31) M 27 24 Ataxia No Yes n.r. n.r.

(18) F 19 10 Dementia No No n.r. n.r.

(18) M 23 3 Dementia No No n.r. n.r.

(18) F 27 3 Dementia No No n.r. n.r.

(32) F 21 4 Ataxia No No n.r. n.r.

(33) F 28 4 Dementia + ataxia Yes No MM n.r.

(33) M 29 10 Dementia No No VV 1

(33) M 27 15 Dementia No No MV 1

(34) M 27 21 Dementia No No VV 1

(35) F 30 73 Altered vision + ataxia Yes Yes MM 2

(36) M 24 19 n.r. No n.r. VV 1

(36) M 27 18 n.r. No n.r. VV 1

(36) F 19 17 n.r. No n.r. VV 1

(37) F 19 24 Psychiatric + sensory No No VV 1

11F/9M 25.5 18 5/19 3/17

(median) (median)

n.r: not reported.

analyzed the clinical syndrome in a series of 52 sCJD

patients aged 50 years or younger at disease onset, and

found that they had a prolonged mean disease duration

compared with patients older than 50 years. Our analysis

also suggests that younger CJD patients survive

longer than older ones and this observation is supported

by several other findings both in sporadic reports (17,

23,38) and in studies of long-duration CJD cases (39). A

recent article has also shown that young age at disease

onset is one of the major factors influencing survival in

CJD (40). In addition, the only late-onset vCJD case reported

had a disease duration of just 7 months (41),

whereas the mean survival in vCJD is around 14

months. Factors possibly contributing to an age-related

disease duration may include the more protracted palliative

treatments in young people and the increased frailty

of elderly people.

In our series, molecular analysis was available in nine

cases; six of these were found to belong to the VV1 CJD

subtype. However, the study of Boesenberg et al. confirms

that the difference between young and older patients

does not depend on the codon 129 genotype.

They also found a similar proportion of type 1 and type

2 glycotypes in young compared to older sCJD patients


In addition to prolonged survival time, our series presented

other features atypical of classic CJD, but resembling

vCJD. For example, in 41% of cases the disease presented

with a cerebellar syndrome and in 73% of patients the

EEG recording did not show the periodic discharges typical

of classic CJD. We have no useful data regarding the

presence of the 14.3.3 protein in the cerebrospinal fluid in

our series, since detection of 14.3.3 was performed in only

four patients. Nevertheless, Boesenberg et al. report a

similar proportion of positive 14.3.3 testing in young and

older sCJD patients (24).

Contrary to our expectations, we did not find an increased

number of cases presenting amyloid plaques.

Many researchers have hypothesized a correlation between

the presence of amyloid plaques and the disease

duration in CJD, since neuropathological lesions like

amyloid plaques may take several years to develop, as

suggested by the presence of PrP plaques in Gerstmann-

Straussler-Scheinker disease (42). In a Japanese

study, neuropathological examination in 45 patients affected

by sCJD revealed that PrP plaques were preferentially

found in cases with a long disease duration (43).

Since amyloid plaques were reported in only 3 out of 17

patients, we think that further studies are needed to verify

this hypothesis.

Our observations demonstrate that some peculiarities of

vCJD may be present in sCJD cases and may be very

common in young CJD patients, thus emphasizing the

need for more caution when diagnosing vCJD on the basis

of single atypical features. The hypothesis that the

long duration of vCJD depends on the patient’s young

age at onset is supported by the finding that many

young patients affected by sCJD also have prolonged

survival. Our findings do not modify the view that vCJD

cases are related to the BSE epidemic, because, as we

stated earlier, the possibility that vCJD had been present,

but undiagnosed, before the onset of BSE has been

completely ruled out. Nevertheless, if our hypothesis of

a relationship between age and survival is confirmed,

the possibility that BSE may be transmitted to elderly

people with a clinical pattern that differs in part from that

of vCJD should be reconsidered. In our opinion, this is a

very important issue, since the prevalence of vCJD in

young people remains the most obscure point in current

understanding of the vCJD epidemic.

snip...see full text ;

18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.


64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.

Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the


3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse

Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.

***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than
classical BSE in humans.***

6:30 Close of Day One

1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...

There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance

He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.

Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

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?

Full Text

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.






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