Thursday, December 08, 2011

A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago

1 Dec. / (8 pages)

Park, Hye Kyung/Huh, Chang Ho
Division of Infectious Disease Control


A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago

- First case in Korea but it has nothing to do with the variant CJD known as “human mad cow disease” -

- Currently, there is no risk of CJD transmission since new, safe dura mater alternatives are being used.

□ Korea Centers for Disease Control and Prevention (KCDC; Director Jun, Byung Yool) informed that the first case of iatrogenic Creutzfeldt-Jakob disease(iCJD) was confirmed in a patient who had received a human dura mater graft with the German-made brain tissue as results of biopsy and animal tests.

* iCJD: CJD contracted in the process of medical treatment caused by a transplanted tissue, etc

□This first victim of iCJD in Korea is a 54-year-old woman who had received a transplant of the membrane manufactured in Germany under the trade name Lyodura in 1987. She began displaying symptoms of CJD in June 2010, 23 years after she received the dura mater graft. Initially, the patient was suspected to have contracted sporadic CJD (sCJD) and she died in Nov. 2010 while the investigation was still being conducted.

○ It is presumed that the German-manufactured dura mater used had been taken from a cadaver of a patient infected with sCJD.

* Sporadic CJD(sCJD): It affects about one person in every one million people per year worldwide.

□ KCDC emphasized that iCJD has nothing to do with the variant CJD* and it was not contracted from the patient’s daily life but due to the transplantation of the German-made dura mater (Lyodura). It also added that then, the materials were not well controlled but now safe dura mater alternatives are being used.

* Variant CJD develops after one has eaten infected beef products from cows with BSE (Bovine Spongioform Encephalopathy ).

○ Also, it is said that since May 1987, the concerned manufacturer has been conducting a deactivation process against prions (an infectious agent composed of protein), known to cause CJD, to remove the possibility of CJD infection.

□ Around 400 cases of iCJD have been reported in 20 countries worldwide and approximately 200 cases of them broke out after the dura mater transplantations, over a half of which have taken place in Japan after the transplants of the concerned German-manufactured dura mater. The probability of developing iCJD after the brain tissue graft is 1/500 ~ 2,000.

□ According to the KCDC, a team of experts in cooperation with the Korean Neurological Association, and the Korean Neurosurgical Society, etc has been formed to trace people known to have received the surgery in the 1980s with their medical records and neurosurgical tests under their consents.


1. General Info of CJD

2. Domestic CJD control status

3. Q & As

General Info of CJD

󰊱 iatrogenic CJD

○iCJD is caused by surgical transplants of the dura mater or the cornea of a person infected with an abnormal form of a protein called a “prion protein”. It can also be passed on through injection of hormones extracted from a brain of an infected person.

Causes of iCJD

① It is passed on through contaminated injections of human growth hormones or gonadotropic hormone or through surgical transplants of the dura mater.

② It is caused by transplants of the cornea extracted from a patient confirmed or suspected of having a human prion disease.

③ It is caused by exposure to contaminated surgical equipment used on people with CJD.

󰊲 Types of CJD

There are four types of CJD

○ sporadic CJD, inherited CJD, and iatrogenic CJD according to the channel of infection and clinical features

- and variant CJD




Sporadic CJD


Degenerative brain disorder caused by the accumulation in the brain of an abnormal form of a protein called a “prion protein.”

(It affects 0.5~2 persons in every one million per year worldwide)

Inherited CJD

It is caused by a genetic mutation.

Iatrogenic CJD (iCJD)
It is caused by surgical transplants of the dura mater or the cornea of an infected person. It can also be passed on through injection of hormones extracted from a brain of an infected person.

※ Brain, spinal cord, and eyeball are most vulnerable to this disease

Variant CJD
It can develop after one has consumed prions contained SRMs of cattle with BSE (Bovine Spongioform Encephalopathy).

※ SRM: Specified risk materials that contain considerable amounts of abnormal protein called “prion protein,” which is the cause of mad cow disease, such as cow brain, intestines, and spinal cord, etc

CJD Control Status

󰊱 Operation of the monitoring system

○ It has been subject to the sentinel surveillance as CJD including vCJD was designated as a legal communicable disease in 2001.

- As it was designated as “Communicable Disease, Class III.”, it has become mandatory to report an outbreak of CJD.

○ Confirmation is made by an investigation of individual cases reported.

- Legal ground for the authority to issue an order for autopsy for the confirmation of the disease has been prepared (‘11~)

○ (In Korea) Less than 30 cases suspected of sCJD infection are reported each year.

[[No. of patients suspected of having contracted CJD (2001~Oct. 2011)]

(Unit: person)


(as of 26 Oct.)




* The numbers of CJD outbreak cases reported in 2009~2011 are tentative figures.

󰊲 Operation of the diagnosis system

○ Hallym University Sacred Heart Hospital has been running a CJD autopsy and diagnosis center from 2006

- 10 autopsies and 10 biopsies have been conducted so far.

Apr. 2006
Nov. 2011

Total (No. of cases)



* Result of Autopsy/Biopsy

-No case suspected of variant CJD has been found yet.

- 7 cases of sCJD

- 2 cases of Alzheimer’s disease

- One case of genetic CJD

- One case of iCJD (the case confirmed this time)

- 7 uncategorized cases (these are the cases showing clinical features suspected of being related to a prion disease that need to be compared with results of further clinical tests and investigations.)

- Two cases displaying no clinical features of CJD

Q & As

Related to Lyodura, a German-made dura mater ;

1. What is Lyodura?

☞ Lyodura is a medical product manufactured and introduced by B. Braun, a hospital supply company based in Germany in 1969. The raw material for Lyodura is the dura mater of a human cadaver and it is used in neurosurgery.

2. How is Lyodura related to iCJD?

☞ The first case of CJD caused by Lyodura was reported in US in 1987 and FDA recalled the product. The manufacturer added the prion deactivation process using NaOH.

☞ The second case was reported in New Zealand and CDC banned the use of the materials produced before May 1987. However, a worldwide recall of the product was not issued. Therefore, it is likely that many other countries have used the contaminated materials for some years.

☞ WHO recommends not using cadaveric dura mater grafts in 1997. (MMWR, CDC, 2008)

3.Is Lyodura being used in Korea, currently?

☞ Some Lyodura products are known to have been imported and used in the past but Korea now bans human dura mater imports.

☞ The concerned product was produced before Apr. 1987 and it didn’t go through the prion deactivation process.

* KFDA(founded in 1998) does not have a record of the importation of the concerned product and it is difficult to find and check related records or data with a company which imported the product since it was imported a long time ago.

4. How many patients have received transplants of Lyodura? And has there been any similar case since?

☞ Since more than 20 years have passed after the concerned Lyodura was used. Therefore, it is difficult to find and check related data. We are trying to find a proper way to identify the status of the use of the product* and there has been no similar case found yet.

* Records of imports of the product to be checked through the importers and medical records at large medical institutions to be examined, etc

☞ The number of patients who had received the transplants of Lyodura cannot be exactly identified. However, because the patient in this case was found to have received the transplant in 1987, it is likely that there are more cases of Lyodura transplants besides this one.

☞ Since this is the first case in Korea confirmed after CJD monitoring began in 2001. A further study of possible CJD outbreaks caused by Lyodura needs to be considered.

5. What are the products that are being used as an alternative dura mater? Is there any risk of iCJD infection by them?

☞ Currently, five dura mater alternative products are being imported through four companies. No CJD case has been reported concerning those products not just in Korea but also in other countries and given the manufacturing procedure, etc, there is no risk of CJD outbreak.

※ The safety test for medical treatment materials is implemented by KFDA in accordance with the “Medical Device Act,” “Regulations for Approval, etc of Medical Device (KFDA Notification)” and “Regulations for Reviewing Technical Document, etc of Medical Device (KFDA Notification).”

6. What are the causes of iCJD besides Lyodura?

☞ 1) It is passed on through contaminated injections of human growth hormones or gonadotropic hormone or through surgical transplants of the dura mater.

2) It is caused by transplants of the cornea extracted from a patient confirmed or suspected of having a human prion disease.

3) It is caused by exposure to contaminated surgical equipment used on people with CJD.

7. Isn’t it possible that CJD in this confirmed case was due to such causes described above other than the transplant of the dura mater?

☞ iCJD is mainly caused by the transplants of the dura mater and injections of human growth hormones.

8. The case was introduced first in a thesis. Hasn’t the government been aware of this case up to now?

☞ The published thesis was written before the animal tests were completed. The government was planning to announce the case with a result verified and confirmed through the animal tests and consultations with experts.

9. Isn’t it that the CJD monitoring system and epidemiological investigation have missed out on this case?

☞ The incubation period of the disease in this case between the patient’s exposure to the risk and the outbreak was 23 years, which was such a long time. Medical records concerning the risks and interviews with patients and guardians are being carried out through the epidemiological investigation. However, in this case, the surgery was done a long ago and the transplant of the dura mater was a part of a series of the operation that the patient received then. Therefore, the patient’s surgery record then had to be look at to find out necessary facts.

10. Is it possible that there is any CJD patients that were failed to be exactly categorized as in this case?

☞ The neural tissue test has to be conducted for confirmation of CJD. However, since there is culturally negative perception toward a brain biopsy or autopsy after one’s death in Korea, it is difficult to confirm the disease through the test. Therefore, CJD is being categorized based on major symptoms, results of a brain MRI, brain wave test, and cerebral spinal fluid examination, etc.

☞ Various risks and records of one’s travel to countries where the variant CJD broke out and one’s family history, etc are examined through interviews. However, since this disease has a long incubation period, if a patient cannot exactly remember related matters or details or it is difficult to have an interview with the person, sufficient data might not be able to be acquired.

11. Should iCJD be considered a medical malpractice?

☞ When the surgery was done, the risk of the concerned product was not known and it was widely used in neurosurgery.

Therefore, it seems difficult to say that the incident was caused by a doctor’s medical judgment or mischoice.

12. How do hospitals and the government deal with CJD patients now? How is the cadaver of a CJD patient treated?

☞ Since CJD is designated as the “Communicable Disease, Class III,” when a suspected patient is found, the hospital reports it to the KCDC which then carries out an epidemiological investigation.

☞ Hospital manages the patient according to the CJD control guidance. Since CJD is not infected through general contact, the patient doesn’t need to be isolated. If no damage or autopsy is done on the cadaver of the patient, waterproofing is done on the cadaver to keep the body fluid from flowing out.

13. How is a patient diagnosed with CJD being controlled? What action should be taken for a CJD patient who hasn’t been diagnosed yet?

☞ A patient doesn’t have to be isolated but shall observe general cautions for prevention of infection. Some scholars insist that after a biopsy for diagnosis is conducted and before a scar caused by the biopsy gets healed, there is a risk of infection due to exposure of body fluids such as cerebrospinal liquid or tissues that can cause the infection, thus requiring limited isolation of the patient.

☞ There is no way of controlling a CJD patient who hasn’t been diagnosed. Therefore, in order to ensure accurate CJD diagnosis at hospitals, training should be done on medical personnel.[보도참고자료]의인성CJD첫발견(최종).hwp.docx

2011/12/08 11:08 KST

S. Korea confirms second case of Creutzfeldt-Jakob disease

SEOUL, Dec. 8 (Yonhap) -- South Korea's health authorities on Thursday confirmed the country's second case of Creutzfeldt-Jakob disease (CJD), a degenerative neurological disorder.

A 48-year-old man was diagnosed with iatrogenic CJD (iCJD) on Wednesday, according to the Center for Disease Control. The person's identity was withheld for privacy reasons.

The report of the country's second-ever iCJD case comes after a 54-year-old woman was found last month to have died from the same disease that is often transmitted by the use of defective prion proteins found in surgical tissue graft products.

The woman had received brain surgery using Lyodura, a tissue graft product, some 23 years ago. The KCDC said the man in the latest case had also received Lyodura during brain surgery in 1988.

This form of CJD has an incubation period of more than 20 years but once symptoms occur, death usually takes place within a year.

CJD is the most common of so-called human prion diseases with one person in every 1 million diagnosed each year worldwide. It is an invariably fatal illness with death occurring after the onset of dementia, hallucinations, coordination dysfunction and seizures.

The animal form of the disease is called bovine spongiform encephalopathy (BSE) which is commonly called mad cow disease. BSE also leaves holes in the brain that resemble a sponge.



Prediction for Potential Risk Factors Through the Association Study Between Epidemiological Data and SNPs of Prion Protein Gene in the Korean Population and Suspected CJD Patients

Suyeon Kim,† Sol Moe Lee, Jae Wook Hyeon, Bo-Yeong Choi, Chi-Kyeong Kim, Jun Sun Park and Young Ran Ju

National Institute of Health, Korea CDC; Cheongwongun, Chungcheongbukdo, Korea;†Presenting author; Email:

Cases of the suspected CJD patients and reports of probable CJD have been increased due to a social uneasiness for import permission of beef from western countries reported BSE outbreak since 2008 in Korea CDC. It has been hard to definite diagnosis them due to Korean funeral culture though reports of probable sporadic CJD and genetic CJD have been increased in Korea. First of all, we need to clear the characteristics of PRNP gene in Korean population and to analyze the association between the endemic environmental factors and SNPs of the gene to predict the underlying cause.

We sequenced up to 5kb of the genomic region including the promoter region, exon I and exon II to analyze the correlation between SNPs of 185 suspected patients and diagnostic factors, and between SNPs of PRNP gene of 296 normal population and 60 epidemiologic factors like medical and familial history and diet. General statistical analyses were carried out by using SPSS statistic 18 (SPSS Inc., NY). Their significance levels were determined by the chi-square test (Fisher’s exact test).

We identified 19 SNPs in normal group and 15 SNPs gene in suspected patients’ group in their promoter and exon II regions. Our statistic analyses demonstrated that between rs1799990 (+385A>G; 129MV), rs28933385 (+598A>G; 200EK) and patient factors in suspected patients’ group showed significantly. In normal population group, between rs2756271 (-14605A>G), rs73612131 (-13537A>T), -14409 (C>T), rs1800014 (+655A>G; 219EK), +695(T>G; 232MR) and +591 (C>T; 197NN) SNPs and several demographic and dietary factors like an intake frequency of beef or ham were significantly associated.

In this study, we could predict the potential risk factors through the association study between SNPs of PRNP gene and several epidemiological factors. Especially, significance level of some dietary habits might show higher than other factors. However, we cannot entirely decide them risk factors of genetic markers in prion disease without identification of environmental or other causes of definite CJD patients though we found de novo SNP and significant result of PRNP. We expect to elucidate clearly their association through the combination of our results with other clinical information including additional clues.

PRION 2011

J Neurol Neurosurg Psychiatry 2002;72:792-793 doi:10.1136/jnnp.72.6.792

Short report

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

Wednesday, November 30, 2011

First iCJD Death Confirmed in Korea

Thursday, December 8, 2011

S. Korea confirms second case of iatrogenic Creutzfeldt-Jakob disease 48-year-old man

2011/12/08 11:08 KST

Tuesday, March 29, 2011


Monday, February 01, 2010

Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral ...


Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

Wednesday, August 24, 2011

There Is No Safe Dose of Prions

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011


Saturday, December 3, 2011

Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies

Volume 17, Number 12—December 2011

Saturday, November 19, 2011

Novel Prion Protein in BSE-affected Cattle, Switzerland

Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat

Volume 17, Number 12—December 2011

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease


Saturday, March 5, 2011


Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

Thursday, July 08, 2010

Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010

Tuesday, May 04, 2010

Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010

Monday, August 31, 2009

HUMAN BODY PARTS FOR SALE TO THE HIGHEST BIDDER Inside a Creepy Global Body Parts Business

Thursday, October 23, 2008

Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts – Japan, 1979-2008 : UPDATE

Sunday, December 16, 2007

Risk factors for sporadic Creutzfeldt-Jakob disease

some old history ;

Japan releases bad Lyodura lot numbers


Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Wed, 20 Sep 2000 14:53:39 -0800


text/plain (62 lines)

######### Bovine Spongiform Encephalopathy #########

This is hot, they actually published the bad lot numbers on the Lyodura in
the newspaper. NIH has fought off US residents for years. on the growth
hormone lot numbers, to protect their crazy man in North Carolina who
insisted on injecting crude pituitary extracts. Some recipients do want to
know whether they got an injection from a bad lot; some don't -- but I
never heard from anyone who wanted Big Brother making the decision for them.

There is a staggering amount of this Lyodura implanted in people: Japan
alone imported "12,545 boxes
of the dura mater, manufactured in 1982 by B. Braun Melsungen AG." It
doesn't say how many uses per box or how many boxes comprise a serial
number, or how many individuals were pooled per serial number.

It would be so cool if some serial number 2105 or so is still around --
then we could test it to see what species it came from (I say sheep, given
that is what their contract surgeon, who died of CJD a few years
thereafter, was removing as dura mater source).


CJD-linked product banned in U.S. was imported to ...

Kyodo World Service Wed, Sep 20, 2000

TOKYO, Sept. 21 (Kyodo) -- The government on Wednesday admitted to the
likelihood that Japan imported German medical products which reportedly
caused Creutzfeldt-Jakob Disease (CJD) even after the United States had
warned of the danger in 1987, contradicting its previous claims.

Kazuo Maruta, a senior official at the Health and Welfare Ministry, said
the German-made dried dura mater used for brain surgery produced in 1982
was likely to have been imported before 1997.

The U.S. Food and Drug Administration (FDA) in 1987 issued a domestic
advisory not to use such dura mater made in that year, after learning about
a report that it could cause CJD.

Symptoms of the disease include rapidly progressive dementia, loss of
cerebral functions, and paralysis of limbs, with parts of the brain
becoming sponge-like.

Maruta, chief of the ministry's Pharmaceutical and Medical Safety
Bureau, told members of the Health and Welfare Committee at the House of
Representatives that it is "likely" that the product, Lyodura with serial
numbers 2000 to 2999, was imported into Japan.

He cited a report by Tokyo importer Nihon B.S.S. which said 12,545 boxes
of the dura mater, manufactured in 1982 by B. Braun Melsungen AG, were
imported that year.

Health and Welfare Minister Yuji Tsushima also told the committee, "It
was impossible (for the government) to foresee the dangers of the product."

Previously, the ministry has denied the possibility of any imports,
insisting that Lyodura with the serial number 2105, which the U.S.
government said caused the first-discovered case of CJD, was not imported
into Japan.

The German firm recalled the 2105 Lyodura in early 1987 and the FDA
advised domestic medical facilities to abandon the product with serial
numbers from 2000 to 2999.

It was only 10 years later that the Japanese ministry prohibited use of
the product.

More than 40 people, including CJD victims and their relatives, have
filed two damages suits with the Tokyo District Court and the Otsu District
Court, Shiga Prefecture, accusing the Japanese companies involved and the
German firm of negligence, as well as the Japanese government.

############ ############

Re: Japan releases bad Lyodura lot numbers


Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Thu, 21 Sep 2000 06:36:13 -0800


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######### Bovine Spongiform Encephalopathy #########

It would be so cool if some serial number 2105 or so is still around --

then we could test it to see what species it came from (I say sheep, given

that is what their contract surgeon, who died of CJD a few years

thereafter, was removing as dura mater source).

You think that Lyodura grafts were made of other origin than human? Do you

have references to that? Thought they were of human origin solely and that

only animal products were used for ie. catgut / sutures?

I was surprised to find that xenotransplants have been going on for decades
on a truly massive scale in many countries. It is not just cowgut surgical
sutures, but anything and everything that doesn't set off too bad an immune
response. One of the more insiduous aspects of the BSE epidemic is the
large number of bovinebiologicals that came onto the international comodity
markets. We saw just one British company selling 40,000 bovine pericardium
patches at year for use in human heart valve replacements.

I posted many months back all the species used previously for dura mater
transplants in human, as seen in simple Medline searches. I also posted
some ideas on how to experimentally determine the species of origin for a
given piece of dura mater, be it still in the box or removed from a
iatrogenic CJD cadaver (there are a couple of intrinsic proteins that could
be seen with IgG).

I also posted a newspaper account of the German orthopedic surgeon employed
by this dura mater company to remove dura mater from sheep brain. The
cause of his CJD was never determined (though the diagnosis was not in
doubt); it could have been anything from handling sheep scrapie dura mater
to inherited. I don't know if he also handled human dura mater for the
company. Scrapie is only uncommonly reported in German sheep.

The idea here is not to make assumptions about the species origin of
Lyodura, but rather to test the species origin experimentally. The purpose
here is not to investigate the company.

Rather, Japan may have inadvertently done the scrapie-to-human
intra-cerebral injection experiment that medical ethics prevents us from
doing directly today. This would complement the successful in vitro
conversion experiments that you and your colleagues have published.

Given the scale of dura mater use in Japan, there may still be boxes left
of dura mater in the 2000-2999 serial number range. Or there may be
material recoverable from 2105 recipients. Given the low incidence of CJD
compared to scrapie, I would say that if any of the dura mater is sheep,
the whole episode can be probably be attributed to scrapie.


############ ############

Re: Japan releases bad Lyodura lot numbers


Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Thu, 21 Sep 2000 08:48:32 -0800


text/plain (169 lines)

######### Bovine Spongiform Encephalopathy #########


Mon, 19 Jul 1999 was when this came up. Here is the relevent Lancet article.

Transmission of Creutzfeldt-Jakob disease by handling of dura mater.

The Lancet Volume 341(8837) January 9, 1993 pp 123-124
Weber, Thomas; Tumani, Hayrettin; Holdorff, Bernd; Collinge, John; Palmer,
Mark; Kretzschmar, Hans A.; Felgenhauer, Klaus

Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by human pituitary growth
hormone, corneal transplants, and dura mater grafts (1). Possible accidental transmission has been
reported in only four people-a neurosurgeon (2), a pathologist (3), and two laboratory technicians
(4,5) . We have encountered an unusually rapid case of CJD probably acquired through handling of sheep and human dura mater.

In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of the left arm. A few days
later he had spatial disorientation, apraxia, and gait ataxia. In June he was admitted and a neurologist
suspected CJD on the basis of the clinical signs, typical electroencephalogram (EEG) pattern, and
history. An EEG in June revealed a typical pattern of periodic biphasic and triphasic sharp wave

We saw the patient in July, 1992. He was awake and oriented, with dyscalculia, dysgraphia, disturbed
vision, apraxia mainly of the left side, rigidity of wrists, spasticity of all muscles, myoclonus of the left
arm, increased tendon reflexes, ataxia of limbs and trunk, and incoordination of left arm. Within 3 weeks he had impaired consciousness and attention, mildly impaired memory, and threatening visual
hallucinations with restless turning. He had periodic states with movements of his head and eye-bulbs
resembling tonic adversive seizures. During sleep these motor disturbances stopped. 2 1/2 months later
the patient died.

This patient had worked with sheep and human dura mater from 1968 to 1972. He handled about 150
specimens of ovine origin and at least a dozen human preparations for research. Handling involved
opening skulls with a band saw, removing dura, and testing them either fresh (usually), preserved, or
lyophilised for mechanical qualities.

These specimens were sent to a company that has sold dura mater preparations by which CJD was
transmitted in six instances. No information was available from the company about a possible connection with this patient's disease and the earlier cases of transmitted CJD.

Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid obtained in July showed
neuron-specific enolase (NSE) at 82.0 ng/mL, compared with 16.7 ng/mL in serum of other cases (6).
Proton magnetic resonance spectroscopy of parieto-occipital and temporal grey matter, parietal white
matter, and thalamus revealed a 20-30% reduction of N-acetylaspartate, as described (7). DNA was
genotyped with allele-specific oligonucleotides (8) and was homozygous for methionine at the
polymorphic codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading frame
demonstrated normal sequence on both alleles, excluding known or novel pathogenic PrP mutations.

It is tempting to speculate that prions were transmitted to this patient from sheep or human dura mater
through small lacerations of his skin, but the patient and his wife did not remember any significant
injury during his four years of working with these samples. It cannot be excluded that this was a case
of sporadic CJD although this assumption is unlikely in view of the clinical course which was similar to iatrogenic CJD transmitted by peripheral inoculation, such as with human pituitary growth hormone or gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral inoculation with the
transmissible agent, for instance following dura mater grafts (2-5), present with a dementing picture,
as is usual in sporadic CJD, rather than with ataxia as in this case.


Iatrogenic scrapie from sheep dura mater?

Mon, 19 Jul 1999 Listserve and Lancet January 9, 1993 pp 123-124

An orthopaedic surgeon employed by the Lyodura company [Braun Melsungen] extracted dura mater from sheep and human cadavers and came down with fast CJD 22 years later. The ratio of sheep to human dura mater he collected was150 sheep to 12 humans. Apparently the surgeon and the sheep were German.

Scrapie has long been present in Germany but reported levels are very low, about a flock a year has to be destroyed. I am not aware of any high sensitivity tests or random screening every being used in Germany to assess the levels of preclinical animals.

This raises the question, what did the lyodura company do with so much dura mater from sheep? The
market for specialty surgical products was overwelmingly in humans in 1968. Are there companies
today that sell sheep dura mater for research? The Lancet article only says it was for research -- but
in what species? Perhaps dura mater gives an immune response across species after processing, ruling out its use in humans. But blood type or other genetic differences do not matter within humans, ie,
there is no tissue matching with dura mater.

How CJD could show up from a handful of human dura mater donations with sporadic CJD supposedly so rare -- this would be extraordinary bad luck that any of 150 sheep + 12 humans could have carried the disease. On the other hand, there would be no surprise at all if a case of subclinical scrapie showed up in 150 sheep. [While Germany only reports one case a year of scrapie and destroys the flock, the disease nonetheless persists, indicating under-reporting.]

This raises the question, have dura mater recipients or the surgeon subsequently been strain-typed?
This might give a very different outcome than other forms of iatrogenic CJD or simply co-classify with
pituitary growth hormone if route of infection (injected, oral, hereditary, etc.) is more important than
strain source.

Otherwise, iatrogenic scrapie (like cwdCJD) is somwhat unpredictable in its gel pattern (though strains
of scrapie in other primate species might be re-examined). The original scrapie strain is not be
identifiable directly because material was not likely retained. Strain-typing was not available at the
time of the article -- but Collinge was one of the authors.

There is little doubt that scrapie could be transfered to humans by intracerebral injection (based on lack
of species barrier in primates) and that processed pooled (human?) dura mater can carry sufficient
infectivity to cause CJD. Animal experiments have not commonly used sheep dura mater as experimental dose source.

If any humans received sheep dura mater, it is doubtful that this will be disclosed or that specific
recipients will be identified to their doctors. It is probably better to trace backwards from affected
recipients -- see if they strain-type out to be sheep.

Japan has been particularly hard hit by dura mater CJD (curious in itself) and researchers there might
be motivated to find out what happened. I am not aware of agricultural agencies that would impede
research over there.

############ ############

Re: CJD * Lyodura-B.Braun Melsungen AG, Germany

Jennifer Cooke jcooke@ACCESS.FAIRFAX.COM.AU

Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Wed, 29 Sep 1999 00:24:32 +1000


text/plain (55 lines)

Cear Terry,

I devoted most of one chapter in my book, Cannibals Cows & the CJD
Catastrophe (Random House Australia) to CJD deaths from dura mater
including Lyodura, that have been reported in the literature since the
initial FDA warning about Lyodura in 1987.

Several cases related to 1982 - either because the Lyodura was manufactured
in that year, or the operation of the victim took place in that year.
One confidential settlement I know of was to the family of a British man
who died of CJD in 1989 following a Lyodura graft in 1985.

There have now been four deaths in Australia from CJD after Lyodura grafts
- all of which related to operations carried out in 1982. The latest death
occurred in June this year - which means that the incubation period has now
blown out to more than 17 years for this type of peripheral infection.
Quite horrifying. I believe the family intends to sue ...


Jennifer Cooke


> From: Roland Heynkes


> Subject: Re: [BSE-L] CJD * Lyodura-B.Braun Melsungen AG, Germany

> Date: Tuesday, September 28, 1999 4:02 AM

> Dear Terry,

> > Terry S. Singeltary Sr., Bacliff, Texas USA -- Greetings, I was hoping

> > Roland or someone, could tell me if this Company (Lyodura-B.Braun

> > Melsungen AG, Germany) is still paying out settlements for the medical

> > deaths from CJD and their product?

> > How far back, has their product been found to be infected and or, was

> > found to be deadly in 1982?

> > Was the material in 1982 taken from cows or humans or both?

> >
> I am sorry but I don't know that and at the moment I am very busy in a

> colon cancer project. Therefore I cannot help you. But perhaps Herbert

> Schaefer in Spangenberg (Tel./Fax: 05663/1212) can help you. He works for

> the large German television transmitter ZDF and investigated the lyodura

> problem of this company some years ago.

> best regards
> Roland Heynkes
> Erkwiesenstr. 19
> D-52072 Aachen (Germany)
> Tel.: +49 (0)241/932070
> Fax: +49 (0)241/932071
> email:



011254 2002-03-29 10:07 60 CJD--LYODURA ''DEADLY HARVEST'' BSE-L

008699 2000-09-21 14:53 67 Re: Japan releases bad Lyodura lot numbers BSE-L

008695 2000-09-21 08:48 190 Re: Japan releases bad Lyodura lot numbers BSE-L

008692 2000-09-21 08:44 52 Re: Japan releases bad Lyodura lot numbers BSE-L

008694 2000-09-21 06:36 74 Re: Japan releases bad Lyodura lot numbers BSE-L

008691 2000-09-20 14:53 81 Japan releases bad Lyodura lot numbers BSE-L

006872 1999-09-29 14:05 96 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006871 1999-09-29 00:24 77 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006862 1999-09-27 19:02 48 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006860 1999-09-27 10:35 32 CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L


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