Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt–Jakob disease
Prion infectivity in the spleen of a PRNP heterozygous individual with
subclinical variant Creutzfeldt–Jakob disease
Matthew T. Bishop1,*, Abigail B. Diack2,*, Diane L. Ritchie1, James W.
Ironside1, Robert G. Will1,* and Jean C. Manson2,* + Author Affiliations
1 National Creutzfeldt–Jakob Disease Research and Surveillance Unit,
University of Edinburgh, Bryan Matthews Building, Western General Hospital,
Crewe Road, Edinburgh, EH4 2XU, UK 2 Neurobiology Division, The Roslin Institute
and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter
Bush, Midlothian, EH25 9RG, UK Correspondence to: Professor Jean Manson, Head of
Neurobiology Division, The Roslin Institute and Royal (Dick) School of
Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG,
UK E-mail: jean.manson@roslin.ed.ac.uk Received August 13, 2012. Revision
received January 10, 2013. Accepted January 14, 2013.
Summary
Blood transfusion has been identified as a source of human-to-human
transmission of variant Creutzfeldt–Jakob disease. Three cases of variant
Creutzfeldt–Jakob disease have been identified following red cell transfusions
from donors who subsequently developed variant Creutzfeldt–Jakob disease and an
asymptomatic red cell transfusion recipient, who did not die of variant
Creutzfeldt–Jakob disease, has been identified with prion protein deposition in
the spleen and a lymph node, but not the brain. This individual was heterozygous
(MV) at codon 129 of the prion protein gene (PRNP), whereas all previous
definite and probable cases of variant Creutzfeldt–Jakob disease have been
methionine homozygotes (MM). A critical question for public health is whether
the prion protein deposition reported in peripheral tissues from this MV
individual correlates with infectivity. Additionally it is important to
establish whether the PRNP codon 129 genotype has influenced the transmission
characteristics of the infectious agent. Brain and spleen from the MV blood
recipient were inoculated into murine strains that have consistently
demonstrated transmission of the variant Creutzfeldt–Jakob disease agent. Mice
were assessed for clinical and pathological signs of disease and transmission
data were compared with other transmission studies in variant Creutzfeldt–Jakob
disease, including those on the spleen and brain of the donor to the index case.
Transmission of variant Creutzfeldt–Jakob disease was observed from the MV blood
recipient spleen, but not from the brain, whereas there was transmission from
both spleen and brain tissues from the red blood cell donor. Longer incubation
times were observed for the blood donor spleen inoculum compared with the blood
donor brain inoculum, suggesting lower titres of infectivity in the spleen. The
distribution of vacuolar pathology and abnormal prion protein in infected mice
were similar following inoculation with both donor and recipient spleen
homogenates, providing initial evidence of similar transmission properties after
propagation in PRNP codon 129 MV and MM individuals. These studies demonstrate
that spleen tissue from a PRNP MV genotype individual can propagate the variant
Creutzfeldt–Jakob disease agent and that the infectious agent can be present in
the spleen without CNS involvement.
snip...
Discussion
This study provides definitive evidence that spleen tissue from an
asymptomatic individual contains variant Creutzfeldt–Jakob disease infectivity
and that the variant Creutzfeldt–Jakob disease agent retains infectivity
following passage through an MV genotype host. The findings are of importance as
there has been uncertainty as to whether prion protein immunostaining in
peripheral tissues from non-clinical variant Creutzfeldt–Jakob disease
necessarily correlated with infectivity (Hilton et al., 2004; Wadsworth et al.,
2011). The demonstration of infectivity in such tissues underlines the potential
for asymptomatic carriers of variant Creutzfeldt– Jakob disease infection to
pose a risk of secondary transmission of infection through blood transfusion or
contamination of surgical instruments. The incubation times recorded in this
study would suggest moderate but significant levels of infectivity are present
in the spleen of the MV genotype recipient, raising the possibility that other
peripheral tissues and the blood of this individual are also infected, as
indicated by immunohistochemistry in the initial report of this case (Peden et
al., 2004). Furthermore the confirmation that there is prion infectivity in an
individual with a PRNP codon 129 MV genotype indicates that this genetic
subgroup, which accounts for 50% of the UK population, can act as carriers of
variant Creutzfeldt–Jakob disease infection.
Our results also provide initial evidence that the variant
Creutzfeldt–Jakob disease transmission properties in the MV blood recipient
spleen tissue are similar to those of the MM blood donor. This is a critical
issue for public health as there is a potential for these infectious agents to
change characteristics, including virulence, after serial transmission or
following passage in a different genetic background. The relative stability of
the agent also makes it more likely that the clinical phenotype of variant
Creutzfeldt–Jakob disease infection in an MV background may be similar to that
of the well-recognized clinical phenotype in an MM background. While a first
passage of an agent between species is not normally sufficient to confirm strain
identity, the similarities identified at first passage in this study are
striking. We are now undertaking a more extensive strain comparison by our
standard serial-passage method using inocula derived from this primary
transmission experiment (Ritchie et al., 2009). This will help establish whether
the strain characteristics have indeed remained stable following passage through
an MV host.
This study has established that variant Creutzfeldt–Jakob disease
infectivity can be replicated within a PRNP codon 129 MV genotype host and
within a non-CNS tissue, in the absence of variant Creutzfeldt–Jakob disease
pathology in the brain. This demonstrates the potential for asymptomatic
carriage of variant Creutzfeldt–Jakob disease infection in the UK population,
underlining the risk of a silent subclinical epidemic that could result from
transfer of infection through blood transfusion or surgery (Garske and Ghani,
2010). It is imperative therefore that continued active surveillance and
infection control measures for variant Creutzfeldt– Jakob disease are continued
into the future.
Key words variant Creutzfeldt–Jakob disease infection subclinical blood
transfusion prion
Abbreviations
HuMM transgenic mouse line expressing human prion protein with MM genotype
at codon 129 PrPSc disease associated (‘scrapie’) form of the prion
protein
© The Author (2013). Published by Oxford University Press on behalf of the
Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/),
which permits unrestricted non-commercial use, distribution, and reproduction in
any medium, provided the original work is properly cited.
MARCH 2010
CJD SUPPORT NETWORK
In a fourth case an elderly lady died of un-related causes and was found to
show evidence of accumulation of prions in her spleen and one lymph node.
A fifth, plasma related transmission has recently been identified in a
patient with haemophilia who also died of other causes and was found to have
evidence of abnormal prion protein accumulation in his spleen.
Saturday, January 20, 2007
Fourth case of transfusion-associated vCJD
infection in the United Kingdom
Saturday, January 20, 2007
Fourth case of transfusion-associated vCJD
infection in the United Kingdom
Subject: Fourth case of transfusion-associated vCJD infection in the United
Kingdom
Date: January 18, 2007 at 8:32 am PST
Fourth case of transfusion-associated vCJD infection in the United
Kingdom
Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance
editorial office
A suspected case of variant Creutzfeldt-Jakob disease (vCJD) has recently
been diagnosed in a patient in the United Kingdom (UK), who received a blood
transfusion from a donor who later developed vCJD [1]. This is the fourth case
of probable transfusion transmission of vCJD infection in the UK. Three of the
four recipients developed symptoms of vCJD. The first symptomatic case of vCJD
associated with blood transfusion was identified in December 2003. This
individual developed vCJD six and a half years after transfusion of red cells
donated by an individual who developed symptoms of vCJD three and a half years
after donation.
A second case of vCJD 'infection' was identified a few months later in a
person who had received red cells from a donor who developed symptoms of vCJD 18
months after donation. This patient (the second case) died from causes unrelated
to vCJD five years after transfusion. Post-mortem investigations found abnormal
prion protein in the spleen and a cervical lymph node., However, prion protein
was not found in the brain, and no pathological features of vCJD were
found.
A third case developed symptoms of vCJD six years after receiving a
transfusion of red blood cells, and died two years and eight months later. The
donor of the blood involved developed vCJD about 20 months after donating
it.
These three cases have been published as case reports and in the findings
of the ongoing collaborative study between the National Blood Services, the
National CJD Surveillance Unit, and the Office for National Statistics. This
study aims to collect evidence about transmission of CJD or vCJD via the blood
supply [2,3,4,5].
The new, fourth case is in a patient who developed symptoms of vCJD eight
and a half years after receiving a transfusion of red blood cells from a donor
who developed vCJD about 17 months after this blood was donated [1]. The donor
to this case also donated the vCJD-implicated blood transfused to the third
case. As for all other reported clinical vCJD cases that have been tested for
genotype, this patient is a methionine homozygote at codon 129 of the prion
protein gene. The patient is currently alive.
All four cases had received transfusions of non-leucodepleted red blood
cells between 1996 and 1999. Since October 1999, leucocytes have been removed
from all blood used for transfusion in the UK. The effect of leucodepletion on
the reduction of the risk of transmission of vCJD from an infective donation is
uncertain.
This fourth case of vCJD infection associated with blood transfusion
further increases the level of concern about the risk of vCJD transmission
between humans by blood transfusion, although much remains unknown. This
reinforces the importance of the existing precautions that have been introduced
to reduce the risk of transmission of vCJD infection by blood and blood products
[6]. No cases of vCJD have been associated with fractionated plasma products.
The small group of living recipients of vCJD-implicated blood transfusion in the
UK have been informed of their potential exposure to vCJD by blood transfusion,
asked to take certain precautions to reduce the risk of onward person-to-person
transmission of vCJD during health care, and offered specialist neurological
evaluation and advice.
This article has been adapted from reference 1
References: Health Protection Agency.
Fourth case of variant CJD associated
with blood transfusion (press release).
Press release, 18 January 2007.
Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, et al.
Possible transmission of variant CJD disease by blood transfusion. Lancet 2004;
363:417-21. Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical
vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet
2004 ; 364: 527-9. Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, et al
Clinical presentation and pre-mortem diagnosis of blood transfusion-associated
variant CJD. Lancet 2006;368:2061-67. Hewitt PE, Llewelyn CA, Mackenzie J, Will
RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK
Transfusion Medicine Epidemiology review study. Vox Sang. 2006;91(3):221-230.
Department of Health [London]. Further precautions to protect blood supply.
Press release 2004/0104, 16 March 2004.
HPA Press Statement
18 January 2007
4th case of variant CJD infection associated with blood transfusion
A new case of variant-Creutzfeldt-Jakob disease (vCJD ) associated with a
blood transfusion has recently been diagnosed.
This latest patient has been diagnosed with vCJD about nine years after
receiving a blood transfusion from a donor who later went on to develop vCJD. A
transfusion from the same blood donor was also associated with one of the
previously identified cases. The patient is still alive and is under specialist
care.
This fourth case of vCJD infection associated with blood transfusion
increases the concern about the risk of vCJD transmission between humans via
blood transfusion. All four cases relate to the transfusion of blood components:
no cases have been reported relating to treatment with plasma products.
The patient is one of a small number (less than 30) of living individuals
who are known to have received a blood transfusion in the UK from a donor who
later developed vCJD. All these individuals have previously been informed of
their potential exposure to vCJD and asked to take certain precautions to reduce
the chance of passing on vCJD to other people via healthcare procedures, such as
surgery.
The Health Protection Agency has been in contact with doctors caring for
the other patients who have been exposed to blood transfusions from donors who
later developed vCJD. This is to ensure that they are informed of this new
development and provide access to the latest information and specialist advice
about their risk due to blood transfusion.
Professor Peter Borriello, Director of the HPA's Centre for Infections
said, "This new case of vCJD infection increases our concern about the risk to
the small group of people who had blood transfusions from donors who unknowingly
at the time of donation must have had vCJD infection. However, this new case
does not change our understanding of the risk for other people in any specific
way. It does however reinforce the importance of the precautions that have
already been taken to reduce the risk of transmission of vCJD infection by
blood."
Dr Angela Robinson, Medical Director of NHS Blood and Transplant said,
"Blood transfusions are often given to save or prolong the life of patients who
are very ill and the benefit of receiving a transfusion when needed must always
be balanced against any possible risk. Nonetheless, our primary concern is the
safety of our patients through maintaining the quality of blood used for medical
treatment. Since 1997, the NBS has introduced a range of precautionary measures
against the risk of vCJD."
vCJD is a rare disease, and less than 2% of the vCJD cases reported to date
in the UK have been associated with blood transfusion.
Notes to Editors:
To date, there have been 66 people identified in the UK who have received
vCJD implicated blood transfusions. The transfusions received by these 66
individuals were donated by eighteen different donors who were diagnosed with
vCJD after their blood donation. Of these 66 people, 40 have died of illnesses
other than vCJD, including one patient who was found to have evidence of vCJD in
parts of their body after their death. Including the new (4th) case, 3 of these
people who have received vCJD implicated blood transfusions have developed
symptoms of vCJD. There are 23 people who have received vCJD implicated blood
transfusions who are alive and have not been diagnosed with vCJD.
The identification of cases of variant-CJD associated with blood
transfusion has depended on the Transfusion Medicine Epidemiology Review, a
collaborative study between the National Blood Services, the National CJD
Surveillance Unit and the Office of National Statistics. For further information
about this study see Hewitt et al Creutzfeldt-Jakob disease and blood
transfusion: results of the UK Transfusion Epidemiology Review study. Vox
Sanguinis 2006 91:221-230.
'Blood Transfusion' means transfusion with labile blood components (e.g.
red cells, platelets, fresh frozen plasma). This latest case (and the previous
three referred to) relate to transfusion of blood components and not treatment
with plasma products (i.e. products that are manufactured from plasma). To date,
no case of vCJD has been associated with treatment with plasma-products (e.g.
clotting factors used to treat individuals with bleeding disorders such as
haemophilia).
This fourth case has been classified by the National CJD Surveillance Unit
( www.cjd.ed.ac.uk ) as a 'probable' case of vCJD. Of the 158 vCJD cases that
have died (data to 5 Jan 2007), all 112 that have undergone post-mortem (46 have
not) have been 'confirmed' by neuropathological examination (examination of
brain tissue).
The first clinical case of vCJD associated with transfusion was identified
in December 2003. A case of vCJD 'infection' associated with transfusion was
identified a few months later. The patient had no symptoms but evidence of
infection (abnormal prion proteins) was identified in a post mortem
investigation. The individual died from causes unrelated to vCJD.
Following the first case of vCJD associated with a blood transfusion in
2003, the Department of Health asked all recipients of blood transfusions not to
donate blood as a precautionary measure to protect the blood supply from
vCJD.
Patients who are informed that they are considered to be 'at risk' of vCJD
for public health purposes are asked to take the following precautions to reduce
the chance of passing on vCJD to other people: Not to donate blood, tissues or
organs and To inform their healthcare providers of their 'at-risk' status so
that special procedures may be arranged for certain instruments used in their
healthcare (NB. Their GPs are also asked to do this.)
A range of measures have been put in place by the Department of Health to
minimise the possible risk of vCJD being passed through blood:
Since 1997 all cases of vCJD that are reported to the National CJD
Surveillance Unit and diagnosed as having 'probable' vCJD, result in a searc h
of the UK Blood Services blood donor records. If the patient has donated blood,
any unused parts of that blood are immediately removed from stock. The fate of
all used components of blood from the donor is traced, and surviving recipients
informed of their risk. In July 1998, the Department of Health announced that
plasma for the manufacture of blood products, such as clotting factors, would be
obtained from non-UK sources. Since October 1999, white blood cells (which may
carry the greatest risk of transmitting vCJD) have been removed from all blood
used for transfusion. In August 2002 the Department of Health announced that
fresh frozen plasma for treating babies and young children born after 1 January
1996 would be obtained from the USA, extended to all children under 16 years of
age (Summer 2005). In December 2002, the Department of Health completed its
purchase of the largest remaining independent US plasma collector, Life
Resources Incorporated. This secures long-term supplies of non-UK blood plasma
for the benefit of NHS patients. Since April 2004, blood donations have not been
accepted from people who have themselves received a blood transfusion in the UK
since 1980. This has been extended to include apheresis donors and donors who
are unsure if they had previously had a blood transfusion (August 2004). Since
late 2005, blood donations have not been accepted from donors whose blood was
transfused to patients who later developed vCJD. The UK Blood Services continue
to promote the appropriate use of blood and tissues and alternatives throughout
the NHS.
The likelihood of a person who may be infected with vCJD going onto develop
symptoms of the disease is uncertain, and may depend on individual
susceptibility. It is possible that infected individuals may never develop
symptoms.
For further information contact the HPA press office on 0208 327
7098/7097/6055
Specialist care for vCJD is available from The NHS National Prion Clinic,
based at The Hospital for Neurology and Neurosurgery, Queen Square, London http://www.nationalprionclinic.org/
The National CJD Surveillance Unit is based at the Western General Hospital
Edinburgh: www.cjd.ed.ac.uk
For further information about vCJD go to:
http://www.hpa.org.uk/infections/topics_az/cjd/menu.htm
http://www.dh.gov.uk/PolicyAndGuidan...pics/CJD/fs/en
Thursday, February 14, 2013
Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain
and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by
VM Transmission Studies
please see ;
>>> Fourth, PrPSc was consistently detected in the spleen, similar
to mice infected with BSE-C.
Thursday, February 14, 2013
Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain
and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by
VM Transmission Studies
see latest nvCJD USA blood recalls;
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
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Thursday, January 17, 2013
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection
control of CJD, vCJD and other human prion diseases in healthcare and community
settings (updated January 2013)
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob
Disease CJD Greenville Memorial Hospital
Thursday, August 02, 2012
CJD case in Saint John prompts letter to patients Canada CJD case in Saint
John prompts letter to patients
Friday, February 10, 2012
Creutzfeldt-Jakob disease (CJD) biannual update (2012/1) potential
iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous
Tonsil Archive
Monday, November 26, 2012
Aerosol Transmission of Chronic Wasting Disease in White-tailed Deer
Thursday, December 29, 2011
Aerosols An underestimated vehicle for transmission of prion diseases?
PRION www.landesbioscience.com
please see more on Aerosols and TSE prion disease here ;
Saturday, February 12, 2011
Another Pathologists dies from CJD, another potential occupational death ?
another happenstance of bad luck, a spontaneous event from nothing, or
friendly fire ???
Tuesday, December 14, 2010
Infection control of CJD, vCJD and other human prion diseases in healthcare
and community settings part 4, Annex A1, Annex J,
UPDATE DECEMBER 2010
Tuesday, September 14, 2010
Transmissible Spongiform Encephalopathies Advisory Committee; Notice of
Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)
Thursday, September 02, 2010
NEUROSURGERY AND CREUTZFELDT-JAKOB DISEASE Health Law, Ethics, and Human
Rights The Disclosure Dilemma
Thursday, August 12, 2010
USA Blood products, collected from a donor who was at risk for vCJD, were
distributed July-August 2010
Sunday, August 01, 2010
Blood product, collected from a donors possibly at increased risk for vCJD
only, was distributed USA JULY 2010
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
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
Wednesday, June 02, 2010
CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated:
May 2010
Tuesday, May 11, 2010
Current risk of iatrogenic Creutzfeld–Jakob disease in the UK: efficacy of
available cleaning chemistries and reusability of neurosurgical instruments
Tuesday, May 04, 2010
Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010
Tuesday, March 16, 2010
Transmissible Spongiform Encephalopathy Agents: Safe Working and the
Prevention of Infection: Part 4 REVISED FEB. 2010
Monday, August 17, 2009
Transmissible Spongiform Encephalopathy Agents: Safe Working and the
Prevention of Infection: Annex J,K, AND D Published: 2009
Monday, July 20, 2009
Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD)
risk in neurosurgery and eye surgery units
Friday, July 17, 2009
Revision to pre-surgical assessment of risk for vCJD in neurosurgery and
eye surgery units Volume 3 No 28; 17 July 2009
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June
12, 2009 (Singeltary submission)
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan,
1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number
2-February 2009 Research
Wednesday, August 20, 2008
Tonometer disinfection practice in the United Kingdom: A national survey
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007
(occupational exposure to prion diseases)
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in
Endodontic Practice in Absence of Adequate Prion Inactivation
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
CJD: update for dental staff.
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to
Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion
risk factors there from
Article in Press
2011 TO 2012 UPDATE
Saturday, December 3, 2011
Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform
Encephalopathies
Volume 17, Number 12—December 2011
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
Monday, February 7, 2011
FDA’s Currently-Recommended Policies to Reduce the Possible Risk of
Transmission of CJD and vCJD by Blood and Blood Products 2011 ???
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease (SEE
VIDEO)
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? (see video at
bottom)
Wednesday, April 25, 2012
USA MAD COW DISEASE AND CJD THERE FROM SINGELTARY ET AL 1999 – 2012
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health
Crisis
full text with source references ;
Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
SKROLL down a bit for Mom's autopsy of hvCJD. ...
TSS
posted by Terry S. Singeltary Sr. | 7:43 AM
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