Update article
The French surveillance network of Creutzfeldt–Jakob disease.
Epidemiological data in France and worldwide
Le réseau de surveillance français de la maladie de Creutzfeldt–Jakob.
Données épidémiologiques en France et dans le monde
J.-P. Brandela,
http://origin-cdn.els-cdn.com/sd/entities/REcor.gif"
>,
b, c, d,
http://origin-cdn.els-cdn.com/sd/entities/REemail.gif"
alt="E-mail the corresponding author">, L. Peckeub, c, d, S. Haïka,
http://origin-cdn.els-cdn.com/sd/entities/REcor.gif">,
b, c, d
a Cellule nationale de référence des maladies de Creutzfeldt-Jakob, groupe
hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l’Hôpital, 75651 Paris
cedex 13, France b Inserm, UMR-S-975, équipe maladie d’Alzheimer-Maladies à
prions, Paris, France c CNRS, UMR 7225, Paris, France d Centre de recherche de
l’institut du cerveau et de la moelle épinière (CRICM), UMRS 975, équipe
Alzheimer's and Prion Diseases, université Pierre-et-Marie Curie-Paris 06,
Paris, France Available online 12 April 2013
http://dx.doi.org/10.1016/j.tracli.2013.02.029,
How to Cite or Link Using DOI
Abstract
France, involved for a long time in the epidemiological surveillance of
transmissible spongiform encephalopathy (TSE), created a national network of
surveillance in 1991, because of the description of the first cases of
Creutzfeldt–Jakob disease (CJD) linked to a treatment by growth hormone of human
origin and the observation of cases of cats infected with the agent of the
bovine spongiform encephalopathy in the United Kingdom (UK). The French
surveillance network is integrated into the European network of surveillance
since its creation in 1993. As in other countries, sporadic CJD is the most
frequent form of TSE in France with an annual mortality rate of 1.44 per
million. Genetic forms are most often associated with a mutation at codon 200.
Among the cases of iatrogenic CJD, 13 cases of CJD after duramater grafts were
observed and 119 related to treatment with growth hormone. France is the country
worst affected in Europe and the world by this latter form, before the USA and
UK. Since 1996, 27 cases of variant of CJD (vCJD) has been observed, making
France the second country in the world most affected after the UK. No cases of
transfusion-associated vCJD have been observed.
Résumé La France, impliquée depuis longtemps dans la surveillance
épidémiologique des encéphalopathies spongiformes transmissibles (EST), a créé
un réseau national de surveillance, dès 1991, en raison de la description des
premiers cas de maladie de Creutzfeldt–Jakob (MCJ) liée à un traitement par
hormone de croissance d’origine humaine et de l’observation de chats contaminés
par l’agent de l’encéphalopathie spongiforme bovine (ESB) au Royaume-Uni (RU).
Le réseau de surveillance français est intégré au réseau de surveillance
européen depuis sa création en 1993. Comme dans les autres pays, la MCJ
sporadique est la forme d’EST la plus fréquente en France avec un taux annuel de
mortalité de 1,44 par million. Les formes génétiques sont le plus souvent liées
à la mutation du codon 200. Parmi les cas de MCJ iatrogènes, 13 cas de MCJ après
greffes de dure-mère ont été observés et 119 cas liés à un traitement par
hormone de croissance. La France est le pays le plus atteint d’Europe et du
monde par cette dernière forme, devançant les États-unis et le RU. Un total de
27 cas de variante de la MCJ (vMCJ) a été observé depuis 1996, faisant de la
France le second pays du monde le plus touché après le RU. Aucun cas
post-transfusionnel de vMCJ n’a été observé.
Keywords Transmissible spongiform encephalopathy; Epidemiology;
Surveillance network; Creutzfeldt–Jakob disease; Sporadic; Genetic; Iatrogenic;
vCJD Mots clés Encéphalopathie spongiforme transmissible; Épidémiologie; Réseau
de surveillance; Maladie de Creutzfeldt–Jakob; Sporadique; Génétique; Iatrogène;
vMCJ
There are no figures or tables for this document.
http://origin-cdn.els-cdn.com/sd/entities/REcor.gif"
>
Corresponding authors. Cellule nationale de référence des maladies de
Creutzfeldt–Jakob, groupe hospitalier Pitié-Salpêtrière, AP–HP, 47-83, boulevard
de l’Hôpital, 75651 Paris cedex 13, France. Copyright © 2013 Published by
Elsevier Masson SAS
Note to users: Corrected proofs are Articles in Press that contain the
authors' corrections. Final citation details, e.g., volume/issue number,
publication year and page numbers, still need to be added and the text might
change before final publication.
Although corrected proofs do not have all bibliographic details available
yet, they can already be cited using the year of online publication and the DOI
, as follows: author(s), article title, journal (year), DOI. Please consult the
journal's reference style for the exact appearance of these elements,
abbreviation of journal names and use of punctuation.
When the final article is assigned to an issue of the journal, the Article
in Press version will be removed and the final version will appear in the
associated published issue of the journal. The date the article was first made
available online will be carried over.
Maladie de Creutzfeldt-Jakob
Publié le 21/04/2011 - Dernière
mise à jour le 02/04/2013
Nombre de cas décédés
certains ou probables de MCJ en France par année de signalement pour les
suspicions, par année de décès pour les cas de MCJ décédés
Mise à jour du 31 mars
2013
Année
|
Suspicions signalées
|
MCJ
sporadique
|
MCJ iatrogène hormone de
croissance
|
Autre MCJ
iatrogène
|
MCJ génétique
|
vMCJ certain ou probable
décédé
|
vMCJ probable non
décédé
|
Total
MCJ
|
1992 |
71
|
38
|
7
|
2
|
4
|
0
|
0
|
51
|
1993 |
63
|
35
|
12
|
1
|
7
|
0
|
0
|
55
|
1994 |
90
|
45
|
5
|
3
|
7
|
0
|
0
|
60
|
1995 |
112
|
59
|
8
|
1
|
6
|
0
|
0
|
74
|
1996 |
200
|
68
|
10
|
0
|
10
|
1
|
0
|
89
|
1997 |
296
|
80
|
6
|
1
|
5
|
0
|
0
|
92
|
1998 |
457
|
81
|
8
|
1
|
13
|
0
|
0
|
103
|
1999 |
589
|
92
|
8
|
0
|
5
|
0
|
0
|
105
|
2000 |
823
|
88
|
9
|
0
|
8
|
1
|
0
|
106
|
2001 |
1102
|
109
|
5
|
0
|
15
|
1
|
0
|
130
|
2002 |
1046
|
107
|
2
|
2
|
13
|
3
|
0
|
127
|
2003 |
1089
|
108
|
8
|
1
|
10
|
0
|
0
|
127
|
2004 |
887
|
97
|
8
|
0
|
9
|
2
|
0
|
116
|
2005 |
928
|
83
|
4
|
1
|
10
|
6
|
0
|
104
|
2006 |
1314 |
124 |
5 |
0 |
8 |
6 |
0 |
143 |
2007 |
1372 |
138 |
1 |
0 |
15 |
3 |
0 |
157 |
2008 |
1476 |
105 |
5 |
0 |
12 |
0 |
0 |
122 |
2009 |
1485 |
114 |
4 |
0 |
14 |
2 |
0 |
134 |
2010 |
1614 |
150 |
0 |
0 |
10 |
0 |
0 |
160 |
2011 |
1609 |
94 |
0 |
0 |
5 |
0 |
0 |
99 |
2012 |
1693 |
78 |
0 |
0 |
5 |
0 |
2 |
85 |
2013 |
471 |
10 |
0 |
0 |
0 |
0 |
0 |
10 |
* 4 décès de MCJ
iatrogènes par hormone de croissance extractive sont survenus en
1991.
Au total, 27 cas de vMCJ
certains ou probables ont été identifiés en France. A ce jour, tous sauf les
deux derniers cas signalés en 2012 sont décédés.
Ces 27 cas de vMCJ
présentent les caractéristiques suivantes : il s'agit de 12 hommes et 15 femmes,
pour une médiane des âges lors de leur décès ou de leur diagnostic de 36 ans
(entre 19 et 58 ans). Parmi eux, 8 personnes résidaient en Ile-de-France et 19
dans d’autres régions.
Pour les 25 cas décédés de
vMCJ, les décès sont intervenus en 1996 (1 cas), 2000 (1 cas), 2001 (1 cas),
2002 (3 cas), 2004 (2 cas), 2005 (6 cas) en 2006 (6 cas), 2007 (3 cas) et 2009
(2 cas).
Tous les cas identifiés à
ce jour étaient homozygotes Met-Met pour le codon 129 du gène de la protéine
prion (PRNP) ; ils ne présentaient aucun facteur de risque identifié pour les
autres formes reconnues de MCJ. Un cas avait séjourné très régulièrement au
Royaume-Uni pendant une dizaine d'années à partir de
1987.
Télécharger
Monday, April 15, 2013
Dr. Stephen B. Thacker Director Centers for Disease Control and
Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS)
dies from Creutzfeldt Jakob Disease CJD
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Saturday, March 23, 2013
CJD Incidents Panel to be disbanded
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Tuesday, March 05, 2013
A closer look at prion strains Characterization and important implications
Prion
7:2, 99–108; March/April 2013; © 2013 Landes Bioscience
Wednesday, March 20, 2013
GAO-13-244, Mar 18, 2013 Dietary Supplements FDA May Have Opportunities to
Expand Its Use of Reported Health Problems to Oversee Product
From: Terry S. Singeltary Sr.
Sent: Tuesday, March 19, 2013 2:46 PM
To: gomezj@gao.gov
Wednesday, February 20, 2013
World Organization for Animal Health Recommends United States' BSE Risk
Status Be Upgraded
Statement from Agriculture Secretary Tom Vilsack:
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Thursday, February 21, 2013
National Prion Disease Pathology Surveillance Center Cases Examined January
16, 2013
16 YEAR OLD SPORADIC FFI ?
Monday, January 14, 2013
Gambetti et al USA Prion Unit change another highly suspect USA mad cow
victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes
along with this BSe
Monday, December 31, 2012
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State,
2006–2011-2012
Tuesday, December 25, 2012
CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25,
2012
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
Wednesday, June 13, 2012
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion
poker goes up again $
Thursday, April 4, 2013
Variably protease-sensitive prionopathy in the UK: a retrospective review
1991–2008
Brain (2013) 136 (4): 1102-1115. doi: 10.1093/brain/aws366
Sunday, March 31, 2013
Creutzfeldt Jakob Disease CJD worlds youngest documented victim, 11 years
old, shall we pray
YEAR 2000
-------- Original Message --------
Subject: Biotechnology for growth hormone deficiency CJD, FRANCE
Date: Wed, 23 Feb 2005 15:11:02 –0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
##################### Bovine Spongiform Encephalopathy
#####################
Biotechnology for growth hormone deficiency Growth hormone Philippe Cramer,
MD France Biotech Julien Martinet, D pham France Biotech Text reviewed by Pr
Raja Brauner (Hôpital Saint-Joseph, Paris) and Pr Pierre Thomopoulos (Hôpital
Cochin, Paris)
N O V E M B R E 2 0 0 4
snip...
TREATMENT OF GH DEFICIENCY BEFORE BIOTECHNOLOGY The first replacement
therapies were used in the United States in the 1950s and in Europe at the
beginning of the 1970s. At that time GH was obtained by extraction from the
pituitary glands of human cadavers. Unlike insulin (where insulins of porcine
and bovine origin were used until the early 1980s), it is not possible to use a
hormone of animal origin in humans because hormones are species specific.
The only indication for this treatment was pituitary dwarfism. The growing
need for growth hormone was such that it led to the use of pituitary glands from
various sources. In France, for instance, Bulgarian pituitaries were imported
from 1982. Between 1983 and1988, around half of all pituitaries were imported.
The dramatic side effect of pituitary-derived GH was the appearance of
Creutzfeldt- Jakob disease (CJD). The first reported death from CJD in a patient
undergoing growth hormone therapy was in 1984, but it was not until two other
deaths from CJD in 1985 that the American FDA envisaged the possibility of a
correlation between CJD and pituitary-derived GH (see Appendix). Approximately
one hundred cases of CJD have been reported in France. The first response to
this infection was the treatment of pituitary extract with urea 8M to deactivate
the prions.
snip...
BIOIMPACT CREUTZFELDT-JAKOB DISEASE (CJD) Creutzfeldt-Jakob disease (CJD)
is a rare and fatal neuro-degenerative disease, described for the first time in
1920, classified amongst the transmissible spongiform encephalopathies which can
affect several species of animal. It leads to dementia, myoclonic jerks and
ataxia. The disease normally affects adults between 50 and 75, but all
generations are concerned when transmission is iatrogenic. Its distribution is
sporadic, with an incidence of one case per million inhabitants. The majority of
cases are sporadic (80%), 15% are of genetic origin, predominantly by
transmission, and 5% are iatrogenic in origin (of which more than 90% of cases
are associated with pituitary-derived growth hormone). There is currently no
cure for this disease. According to the national network monitoring CJD in
France, from January 1992 to October 2003, 8.3% of deaths from CJD originated
from growth hormone therapy (86 cases out of 1037). Out of a total of 1361
patients studied who were treated with batches of pituitary-derived growth
hormone suspected to be tainted, the average incubation time observed in the 55
patients who contracted CJD was 9 to 10 years, with a probability that 95% of
cases were declared after ages 14 to 16 years. In addition, it was observed that
80% of patients infected were homozygous for codon 129 of gene PRNP (met-met or
val-val), and this gene is therefore considered to indicate predisposition to
CJD. These homozygous patients present an incubation time which is shorter than
that for heterozygous individuals with the same gene. A new variant of this
disease (nvCJD) appeared in Britain in 1996 under the name mad cow disease.
After having studied other possibilities, scientists have adopted the theory of
contamination of food by the agent causing bovine spongiform encephalopathy,
BSE.
snip...
TSS
SHORT REPORT
Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth
hormone
E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn
...............................................................
J Neurol Neurosurg Psychiatry 2002;72:792-793
A 47 year old man is described who developed pathology proven
Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human
derived growth hormone (hGH) as part of a diagnostic procedure. The patient
presented with a cerebellar syndrome, which is compatible with iatrogenic CJD.
This is the longest incubation period described so far for iatrogenic CJD.
Furthermore, this is the first report of CJD after diagnostic use of hGH. Since
the patient was one of the first in the world to receive hGH, other cases of
iatrogenic CJD can be expected in the coming years.
Prion diseases are potentially transmissible. Human to human transmission
was first reported in 1974, when a 55 year old woman was described who developed
symptoms of Creutzfeldt-Jakob disease (CJD) 18 months after a corneal
transplant.1 Since then, transmission has been reported after stereotactic
electroencephalographic (EEG) depth recording, human growth hormone (hGH) and
gonadotrophin treatment, and dura mater transplantation.2-5 More than 267
patients with iatrogenic CJD are known today and their number is growing.6 The
most important iatrogenic cause of CJD is still contaminated cadaveric hGH.
Exposure to contaminated hGH occurred before 1985, when recombinant growth
hormone became available. In a recent study, incubation periods in 139 patients
with hGH associated CJD were found to range from 5-30 years, with a median of 12
years.6 One of the factors influencing incubation time is genotype on
polymorphic codon 129 of the prion protein gene.7 The incubation time is
significantly shorter in people who are homozygous for either methionine or
valine on this polymorphism.7
We describe the second patient with hGH related CJD in the Netherlands. The
patient developed the disease 38 years after hGH injections. To our knowledge,
this is the longest incubation period described for any form of iatrogenic CJD.
Further-more, our patient was not treated with hGH but only received a low dose
as part of a diagnostic procedure.
CASE REPORT
This patient presented at the age of 47 years with paraesthesia in both
arms for six months, difficulty with walking for four weeks, and involuntary
movements of mainly the upper extremities of two weeks' duration. He did not
notice any change in cognitive function, although his twin sister had noticed
minor memory disturbances. There was no family history of neurological disease.
During childhood the patient had experienced a growth delay compared with his
twin sister and with the average in the Netherlands. When he was 9 years old, a
nitrogen retention test with 6 IU hGH over five days was performed to exclude
growth hormone deficiency. Since the result was not decisive, a quantitative
amino acid test was performed, which measures 30 amino acids during fasting and
one, two, and three hours after growth hormone injection. No abnormal amino acid
concentrations were found making the diagnosis of primordial dwarfism most
likely. Therefore, no treatment with hGH was given.
On neurological examination we found a slight dysarthria without aphasia.
Cranial nerve function was normal. Walking was unstable and wide based. During
movements of the upper extremities myoclonic jerks were present. Sensation,
muscle tone, and strength were normal. Co-ordination was impaired in all four
limbs with a disturbed balance. Tendon reflexes were brisk at the arms and
increased at the legs with a clonus in the ankle reflex. Plantar responses were
both normal. On the mini mental state examination, the patient scored 30/30.
Routine laboratory investigation, thyroid function, vitamin concentrations (B-1,
B-6, B-12, and E), and copper metabolism were normal. Admission EEG examination
showed generalised arrhythmic slow activity with diffuse spikes and spike waves.
EEG examination two months later showed a further slowing of the rhythm with
bilateral diphasic sharp waves but was not typical for CJD. Cerebral magnetic
resonance imaging was normal. Cerebrospinal fluid examination showed 1 cell/3
µl, normal glucose and protein concentrations, and a strongly positive 14-3-3
protein test. The patient was homozygous for methionine on the PRNP codon 129
polymorphism. On clinical grounds, CJD was diagnosed. Within one month the
patient's condition deteriorated rapidly and because of severe disturbances in
coordination and progressive myoclonus he became bedridden. An eye movement
disorder developed with slow saccadic and dysmetric eye movements. Temperature
became unstable with peaks of 39°C without an infectious focus, for which a
disorder of autoregulation was presumed. Until a very advanced stage, cognitive
function was intact. The patient died five months after admission. The diagnosis
of CJD was confirmed at necropsy. The brain weighed 990 g and showed clear
cortical and cerebellar atrophy. Spongiosis, neuronal loss, and gliosis were
found predominantly in the putamen, caudate nucleus, and basotemporal and
cerebellar cortex; the cerebellum was the most severely affected of these.
Vacuoles ranged from 2-12 µm. No amyloid or Kuru plaques were found.
Immunohistochemical staining (3F4 antibody 1:1000, Senetek, USA) was clearly
positive for prion protein accumulation in a "synaptic" distribution. Most
deposition was found in the stratum moleculare of the cerebellum.
DISCUSSION
We describe a 47 year old patient who developed pathology proven CJD 38
years after hGH injections. The patient was never treated with hGH but received
a small dose as part of a diagnostic procedure. The onset of CJD was signalled
by prodromal symptoms of paraesthesia followed by a rapidly progressive ataxia.
The disease presentation and course with predominantly cerebellar and eye
movement disorders are compatible with iatrogenic CJD caused by hGH treatment.6
8
Growth hormone treatment was first described in 1958 but hGH was not
produced on a larger scale from human pituitary glands until the beginning of
the 1960s. In the Netherlands growth hormone extraction started in 1963 and was
soon centrally coordinated. Until 1979 growth hormone was extracted
non-commercially from pituitaries by a pharmaceutical company. In 1971
commercial products also became available. Our patient was one of the first to
receive hGH in the Netherlands but the origin of this product was not recorded.
A causal relation can therefore not be established with full certainty, but
coincidentally receiving growth hormone and developing this very rare disease is
unlikely. Since the clinical course in this relatively young patient is in
accordance with an iatrogenic cause, we think the probability is high that the
hGH injections explain the development of CJD in this patient.
The first Dutch patient with hGH related CJD died in 1990. 9 During several
periods from 1963 to 1969 she received intramuscular injections of hGH. During
an unknown period the hGH was derived from South America. At age 39, 27 years
after starting the treatment, she developed an ataxic gait, slurred speech,
sensory disorders, and myoclonus, but her cognitive function remained normal.
Postmortem examination of the brain confirmed the diagnosis of CJD.9 Following
the identification of this patient, a retrospective study was started to trace
all 564 registered hGH recipients who were treated before May 1985. Until
January 1995, none of these was suspected of having CJD.10 Since 1993
prospective surveillance for all forms of human prion disease has been carried
out in the Netherlands and, apart from the patient described above, a further
two patients with iatrogenic CJD have been identified, who developed the disease
after dura mater transplantation.11
An incubation period as long as 38 years had never been reported for
iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55
patients with hGH related CJD in a cohort of 1361 French hGH recipients. The
median incubation period was between 9 and 10 years. Under the most pessimistic
model, the upper limit of the 95% confidence interval varied between 17 and 20
years. Although the infecting dose cannot be quantified, it can be speculated
that the long incubation period in our patient is partly explained by the
administration of a limited amount of hGH. This hypothesis is supported by
experimental models, in which higher infecting doses usually produce shorter
incubation periods.6 Since our patient was one of the first in the world to
receive hGH, this case indicates that still more patients with iatrogenic CJD
can be expected in the coming years. Another implication of our study is that
CJD can develop even after a low dose of hGH. This case once more testifies that
worldwide close monitoring of any form of iatrogenic CJD is mandatory.
ACKNOWLEDGEMENTS
We are grateful to M Jansen PhD MD for his search for the origin of the
growth hormone and P P Taminiau MD. CJD surveillance in the Netherlands is
carried out as part of the EU Concerted Action on the Epidemiology of CJD and
the the EU Concerted Action on Neuropathology of CJD, both funded through the
BIOMED II programme, and is supported by the Dutch Ministry of Health. This
surveillance would not have been possible without the cooperation of all Dutch
neurologists and geriatricians. ........................................
Authors' affiliations
E A Croes, G Roks*, C M van Duijn, Genetic Epidemiology Unit, Department of
Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO
Box 1738, 3000 DR Rotterdam, Netherlands
P C G Nijssen, Department of Neurology, St Elisabeth Hospital, PO Box
90151, 5000 LC Tilburg, Netherlands
G H Jansen, Department of Pathology, University Medical Centre Utrecht,
Heidelberglaan 100, 3584 CX Utrecht, Netherlands
*Also the Department of Neurology, St Elisabeth Hospital
Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit,
Department of Epidemiology and Biostatistics, Erasmus University Medical Centre
Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands;
vanduijn@epib.fgg.eur.nl
Received 27 December 2001 In revised form 1 March 2002 Accepted 12 March
2002
Competing interests: none declared
REFERENCES
1 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission
of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-3.
2 Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental
person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet
1977;i:478-9.
3 Koch TK, Berg BO, De Armond SJ, et al. Creutzfeldt-Jakob disease in a
young adult with idiopathic hypopituitarism: possible relation to the
administration of cadaveric human growth hormone. N Engl J Med
1985;313:731-3.
4 Cochius JI, Burns RJ, Blumbergs PC, et al. Creutzfeldt-Jakob disease in a
recipient of human pituitary-derived gonadotrophin. Aust NZ J Med
1990;20:592-3.
5 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease
probably acquired from a cadaveric dura mater graft: case report. J Neurosurg
1988;69:766-9.
6 Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob
disease at the millennium. Neurology 2000;55:1075-81.
7 Huillard d'Aignaux J, Costagliola D, Maccario J, et al. Incubation period
of Creutzfeldt-Jakob disease in human growth hormone recipients in France.
Neurology 1999;53:1197-201.
8 Billette de Villemeur T, Deslys JP, Pradel A, et al. Creutzfeldt-Jakob
disease from contaminated growth hormone extracts in France. Neurology
1996;47:690-5.
9 Roos RA, Wintzen AR, Will RG, et al. Een patiënt met de ziekte van
Creutzfeldt-Jakob na behandeling met humaan groeihormoon. Ned Tijdschr Geneeskd
1996;140:1190-3.
10 Wientjens DP, Rikken B, Wit JM, et al. A nationwide cohort study on
Creutzfeldt-Jakob disease among human growth hormone recipients.
Neuroepidemiology 2000;19:201-5.
11 Croes EA, Jansen GH, Lemstra AF, et al. The first two patients with dura
mater associated Creutzfeldt-Jakob disease in the Netherlands. J Neurol
2001;248:877-81.
P.4.4
Possible iatrogenic Creutzfeldt-Jakob Disease in an adult male 50 years
after treatment with human chorionic gonadotrophin
Brian Appleby1, Paul Brown2 1Johns Hopkins University School of Medicine,
USA; 2CEA/DSV/iMETI/SEPIA, France
Background: Known causes of iatrogenic Creutzfeldt-Jakob disease (iCJD)
include cadaverous corneal transplants, dural mater grafts, human growth hormone
(hGH), neurosurgical depth electrodes, and neurosurgical instrument
contamination. Four cases of iCJD from human gonadotrophin have been described
to date, all of whom have been women.
Objectives: To present a case of possible iCJD from human chorionic
gonadotrophin (hCG) and review data from four other cases Methods: Case report
and descriptive analysis
Results: A 62-year-old Caucasian man developed ataxia that resulted in
frequent falls and an initial diagnosis of benign positional vertigo. Further
workup including brain magnetic resonance imaging (MRI), electroencephalogram
(EEG), and a lumbar puncture were unrevealing. A cerebrospinal 14-3-3 protein
analysis was indeterminate. At the end of the third month of his illness, he
developed short-term amnesia, disorientation, and confabulation. A repeat EEG
showed generalized slowing without evidence of periodic sharp wave complexes and
a repeat 14-3-3 analysis was positive. A second brain MRI showed hyperintensity
in the basal ganglia on diffusion- weighted images. He died following a
four-month illness. Severe vacuolization was noted on microscopic examination
and Western blot analyses detected type II prion proteins. Genomic analyses
detected a silent polymorphism at codon 117 and valine homozygousity at codon
129 of the prion protein gene. Further review of his medical records revealed a
history of cryptorchidism and treatment with hCG as a child in the
1940’s-1950’s.
Discussion: This case report describes a possible case of iCJD from hCG
injections and is unique in that the patient was male and the incubation period
approached 50 years. His clinical presentation, EEG findings, and codon 129
homozygousity are similar to previously described cases.
Tuesday, November 23, 2010
Prosecutors call for prison terms for CJD growth hormone doctors
TSS
<< Home