Pages

Thursday, April 18, 2013

The French surveillance network of Creutzfeldt–Jakob disease. Epidemiological data in France and worldwide UPDATE

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, Corresponding author contact informationhttp://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, Corresponding author contact informationhttp://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.




Corresponding author contact informationhttp://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



Données épidémiologiques

 
 

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


Cc: siggerudk@gao.gov ; youngc1@gao.gov ; oighotline@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