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From: TSS (
Subject: Barriers to Creutzfeldt-Jakob Disease Autopsies, California
Date: August 24, 2004 at 2:48 pm PST

-------- Original Message --------
Subject: Barriers to Creutzfeldt-Jakob Disease Autopsies, California
Date: Tue, 24 Aug 2004 13:45:07 -0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy


Barriers to Creutzfeldt-Jakob Disease Autopsies, California

Janice K. Louie,*†Comments
Shilpa S.
Gavali,* Ermias D. Belay,‡ Rosalie Trevejo,† Lucinda H. Hammond,*
Lawrence B. Schonberger,‡ and Duc J. Vugia*†
*California Emerging Infections Program, Richmond, California, USA;
†California Department of Health Services, Berkeley, California, USA;
and ‡Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Suggested citation for this article


Creutzfeldt-Jakob disease (CJD) surveillance relies on autopsy and
neuropathologic evaluation. The 1990–2000 CJD autopsy rate in
California was 21%. Most neurologists were comfortable diagnosing
CJD (83%), but few pathologists felt comfortable diagnosing CJD
(35%) or performing autopsy (29%). Addressing obstacles to autopsy
is necessary to improve CJD surveillance.

Transmissible spongiform encephalopathies (TSEs) are rare, progressively
fatal, neurodegenerative illnesses. Human TSEs include classic
Creutzfeldt-Jakob disease (CJD) and the recently described variant CJD
associated with eating bovine spongiform encephalopathy–infected cattle
products in Europe (1
). The recent
identification of bovine spongiform encephalopathy in the United States
underscores the importance of maintaining enhanced surveillance to
monitor for the possible occurrence of variant CJD in this country (2,3

In California, CJD is not reportable. Since 1999, the California CJD
Surveillance Project of the California Emerging Infections Program, a
collaboration of the California Department of Health Services and the
U.S. Centers for Disease Control and Prevention, has conducted enhanced
surveillance for classic and variant CJD. Methods include review of
state mortality data and follow-up investigation of CJD-related deaths
that occur in persons <55 years of age, since >98% of cases of variant
CJD in the United Kingdom have occurred in this age group. As part of
this enhanced surveillance, medical records for 33 deceased California
residents <55 years old from 1996 through 2003 have been investigated
with criteria for CJD developed by the World Health Organization and
Centers for Disease Control and Prevention; none met the criteria for
variant CJD.

Currently, pathologic review of brain tissue obtained by biopsy or
autopsy is the only means of confirming a diagnosis of CJD. Autopsy
remains the preferred method for obtaining tissue, as brain biopsy can
result in serious complications (e.g., brain hemorrhage or abscess
formation) and may not yield adequate amounts of tissue for analysis.
The main role of brain biopsy is to exclude other, potentially treatable
conditions (4 ).

In this article, we describe results from analysis of California
mortality data from 1990 through 2000. We also summarize responses
generated from a statewide survey of neurologists and pathologists
regarding the challenges to diagnosing CJD and variant CJD, including
obtaining autopsy in suspected cases.

The Study

Data from the 1990–2000 Death Public Use File (underlying cause of death
only) and 1990–1999 Multiple Cause-of-Death Data (underlying or
contributing causes of death) were obtained from the Center for Health
Statistics, California Department of Health Services (5
). Deaths among
California residents with an International Classification of Diseases,
9th Revision, code 046.1 or 10th Revision, code A81.0 listed anywhere on
the death record were included in our analysis. Both data files included
report of autopsy as a variable, with the exception of the Multiple
Cause-of-Death Data for 1997 to 1999, when autopsy performance was not
recorded. Statistical analysis was performed by using SAS software (SAS
Institute, Cary, NC).

From July to December 2002, questionnaires regarding experience with
diagnosing CJD were sent to 1,241 California neurologists identified as
members of the American Academy of Neurology and 574 pathologists
identified as members of the California Society of Pathologists and the
American Association of Neuropathologists. Approval was obtained from
the Committee for the Protection of Human Subjects of the State of

Review of mortality data identified 263 CJD-related deaths in California
from 1990 through 2000. Of these, 244 were identified from the 1990–1999
Multiple Cause-of-Death Data, and an additional 19 deaths were
identified from the 1990–2000 Death Public Use File. A total of 42 (16%)
cases identified by the Multiple Cause-of-Death Data were not detected
in the Death Public Use File. Overall, 26 (10%) of the 263 CJD-related
deaths were in persons <55 years of age. Only two deaths occurred in
persons <30 years of age. The overall autopsy rate, which for 1997 to
2000 only includes autopsies performed on persons for whom CJD was
recorded as the underlying cause of death, was 53 (21%) of 251 persons:
11 (44%) of 25 persons <55 years of age, and 42 (19%) of 226 persons >55
years of age. For two deaths, autopsy performance was not recorded.

Of 1,241 questionnaires mailed to neurologists, 428 (34%) were
completed, including 310 (25%) from respondents involved in patient
care. Responses regarding the neurologists' experience with diagnosing
CJD and performing autopsy are summarized in Tables 1
and 2
. Most
neurologists (83%, 255/307) felt comfortable clinically recognizing
classic CJD. More than one third (36%, 74/207) had not considered
arranging for autopsy in their CJD patients, although most reported
access to histopathologic services (75%, 223/297). The most commonly
cited barrier to obtaining autopsy was family reluctance to give consent
(79%, 192/242).

Of 574 questionnaires mailed to pathologists, 284 (49%) were completed.
Tables 1 and
2 summarize
the responses. Thirty-five percent (96/273) and 15% (40/274) of
pathologists were comfortable recognizing the neuropathologic features
of classic CJD and variant CJD, respectively. Infection control concerns
(77%, 143/185), lack of experience (62%, 69/111), and institutional
limitations (53%, 111/210) were cited as major obstacles to autopsy
performance, and less than half of respondents reported that confirming
the diagnosis of CJD (47%, 92/197) or ruling out variant CJD (45%,
87/193) was an important reason to pursue autopsy.


Our analysis suggests that autopsy rates for CJD in California are low.
The results of our surveys, which attempted to discern the reasons for
this low rate, imply that both neurologists and pathologists have
similar perceptions of the value of obtaining histopathologic evaluation
for CJD but for different reasons. Most neurologists appeared to be
comfortable clinically diagnosing CJD, with more than one third
reporting they had never considered pursuing autopsy for CJD cases. In
contrast, pathologists appeared to be less comfortable making a
histopathologic diagnosis, indicating that autopsy performance was
limited by infection control concerns, lack of experience with CJD
cases, and institutional restrictions.

Our results have some limitations. Approximately 10% of CJD cases may
have atypical signs and symptoms that can obscure the diagnosis. To the
extent that these cases are misdiagnosed and not autopsied, they could
contribute to overestimation of the autopsy rate. On the other hand,
death certificate analysis can be an insensitive indicator of the true
rate of autopsy, and autopsy performance information was unavailable for
1997 to 2000 from the Multiple Cause-of-Death Data. Both factors could
lead to possible underestimation of the true autopsy rate. Given that
some CJD cases will have had confirmatory brain biopsy or strongly
suggestive clinical features and diagnostic studies, the autopsy rates
cited may apply mostly to patients for whom a satisfactory antemortem
diagnosis could not be made. Interpreting survey results is limited by
the low response rate; neurologists and pathologists who are experienced
in diagnosing CJD may be more likely to respond, which would introduce bias.

The public health benefits of performing autopsy on patients with
suspected CJD should not be underestimated. Autopsy and histopathologic
analysis remain important ways to confirm a diagnosis of CJD and help
define the usual occurrence of subtypes of classic CJD, thereby
facilitating the recognition of emerging TSEs (1,6,7
). Autopsy rates
for nonforensic deaths have declined dramatically during the past 40
years, with national hospital rates currently <5%, possibly resulting in
missed diagnoses of the actual cause of death in 8% to 25% of cases
(8–11 ). The
reasons for the decline are multifaceted and include escalating cost of
autopsy borne by hospitals and county medical examiners, lack of direct
reimbursement, fear of litigation, and increasing reliance on modern
technology to determine a diagnosis antemortem (10

Our survey results suggest that infection control concerns play a role
in low autopsy rates for CJD, whether because of fears about the risk of
acquiring CJD from handling contaminated tissue or because of liability
considerations at the institutional level. More realistically, brain
autopsy can be performed safely as long as CJD-specific infection
control guidelines are strictly followed (12–13
). Nonetheless,
concerns about potentially acquiring CJD through autopsy procedures
should be acknowledged and recognized as an opportunity to address
proper infection control techniques.

Enhancing surveillance for variant CJD and other emerging prion diseases
will require educating neurologists and pathologists, addressing the
perceived obstacles to obtaining autopsy, and encouraging the use of
available resources that provide expertise and technical assistance in
evaluating CJD. For example, brain tissue can be submitted to the
National Prion Disease Pathology Surveillance Center (NPDPSC) in
Cleveland, Ohio, for free state-of-the-art diagnostic testing (14
). The
availability of a national center of expertise may facilitate obtaining
tissue evaluation; since the inception of NPDPSC, the number of
referrals to the facility has more than doubled, from 104 in 1997 to 265
in 2002, and the number of TSE cases confirmed from those referrals
increased from 60 in 1997 to 151 in 2002 (14
). Regional
academic institutions, such as the University of California, San
Francisco, Memory and Aging Center, can also provide expertise and
assistance with diagnostic testing. Such resources are vital to
maintaining vigilance for cases of CJD and potentially emerging human
TSEs, such as variant CJD or possibly a human form of chronic wasting
disease in the United States.


We gratefully acknowledge Laura Dalla Betta, Stephen DeArmond,
Michael Geschwind, Ryan Maddox, Jennifer Martindale, Bruce Miller,
Gretchen Rothrock, James Sejvar, and Mark Starr for their invaluable
advice and support.

Dr. Louie served as project clinician for the California
Creutzfeldt-Jakob Disease Surveillance Project, a joint
collaborative project of the California Department of Health
Services and the Centers for Disease Control and Prevention. Her
research interests include the study of emerging infectious diseases.


1. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the
occurrence of emerging forms of Creutzfeldt-Jakob disease in the
United States
Neurology. 2003;60:176–81.
2. Tan L, Williams MA, Khan MK, Champion HC, Nielsen NH. Risk of
transmission of bovine spongiform encephalopathy to humans in the
United States.

JAMA. 1999;281:2330–9.
3. Centers for Disease Control and Prevention. Preliminary
investigation suggests BSE-infected cow in Washington state was
likely imported from Canada [monograph on the Internet]. 2003 Dec
29 [cited 2004 Jul 10]. Available from:
4. Will RB, Alpers MP, Dormont D, Schonberger LB, Tateishi J.
Infectious and sporadic prion diseases. In: Prusiner SB, editor.
Prion biology and disease. Cold Spring Harbor (NY): Cold Spring
Harbor Laboratory Press; 1999. p. 465–507.
5. Center for Health Statistics. California's death public use tape
documentation. Sacramento (CA): California Department of Health
Services; 1997.
6. U.K. Creutzfeldt-Jakob Disease Surveillance Unit. Investigations
undertaken in possible CJD cases [monograph on the Internet]. 2002
Oct 15 [cited 2004 Jul 10]. Available from:

7. Fatal degenerative neurologic illnesses in men who participated in
wild game feasts—Wisconsin, 2002.

MMWR Morb Mortal Wkly Rep. 2003;52:125–7.
8. Burton EC. The autopsy: a professional responsibility in assuring
quality of care.

Am J Med Qual. 2002;17:56–60.
9. The autopsy as an outcome and performance measure [monograph on
the Internet]. File inventory, evidence report/technology
assessment no. 58. AHRQ publication no. 03-E002. Rockville (MD):
Agency for Healthcare Research and Quality; 2002 Oct [cited 2004
Jul 10]. Available from:
10. Brooks JP, Dempsey J. How can hospital autopsy rates be increased?

Arch Pathol Lab Med. 1991;115:1107–11
11. Hasson J, Schneiderman H. Autopsy training programs: to right a

Arch Pathol Lab Med. 1995;119:289–91.
12. WHO infection control guidelines for transmissible spongiform
encephalopathies: report of a WHO consultation [monograph on the
Internet]. Geneva: World Health Organization; 1999 Mar 26 [cited
2004 Jul 10]. Available from:

13. Questions and answers regarding Creutzfeldt-Jakob disease
infection-control practices [monograph on the Internet]. Atlanta:
Centers for Disease Control and Prevention; 2003 May 21 [cited
2004 Jul 10]. Available from:
14. National Prion Disease Pathology Surveillance Center [homepage on
the Internet]. [cited 2004 Jul 10]. Available from:

Table 1. Knowledge and experience of California neurologists,
pathologists, and neuropathologists in diagnosing Creutzfeldt-Jakob
disease (CJD)


Neurologists n/N (%)

Pathologists n/N (%)

Neuropathologists n/N (%)


Have evaluated a case of CJD

212/310 (68)

56/259 (22)

18/33 (55)

Median no. (range) of CJD cases evaluated

3 (0–30)

2 (0–30)

10 (0–50)

Type of practice

Private practice/private hospital

144/308 (47)

122/278 (44)

8/33 (25)

Outpatient HMOa/managed care

55/308 (18)

Community hospital/clinic

1/308 (<1)

68/278 (24)

4/33 (12)

University affiliated

82/308 (27)

37/278 (13)

10/33 (30)

Veterans hospital

13/308 (4)

3/278 (1)

1/33 (3)

County medical examiner or coroner

7/278 (3)

2/33 (6)


15/308 (5)

41/278 (15)

5/33 (15)

Can recognize the clinical or pathologic features of classic CJD

255/307 (83)

96/273 (35)

25/28 (89)

Can recognize the clinical or pathologic features of variant CJD

120/305 (39)

40/274 (15)

18/28 (64)

Have not considered arranging for an autopsy for CJD patients under
their care

74/207 (36)

Pathology group available at facility to perform autopsy on suspect CJD

223/297 (75)

74/259 (29)

17/28 (61)

Pathology group available at facility to confirm diagnosis of suspect
CJD with histopathologic analysis

223/297 (75)

91/254 (36)

18/27 (67)

aHMO, health maintenance organization.

Table 2. Perceptions of California neurologists, pathologists, and
neuropathologists regarding performance of autopsy in Creutzfeldt-Jakob
disease (CJD)


Neurologists n/N (%)

Pathologists n/N (%)

Neuropathologists n/N (%)


Important reasons to obtain autopsy for CJD patients

Autopsy is needed to confirm CJD diagnosis

92/197 (47)

11/21 (52)

Autopsy is needed to rule out variant CJD or other TSEa forms

168/231 (73)

87/193 (45)

12/20 (60)

Barriers to performing autopsy and histopathologic analysis for CJD

Clinicians do not feel autopsy is required for diagnosis

94/221 (43)

72/198 (36)

7/21 (33)

Facilities not able/willing to perform autopsies on CJD patients

75/234 (32)

111/210 (53)

8/22 (36)

Families are reluctant to give consent for autopsy

192/242 (79)

57/202 (28)

6/22 (27)

Cost of autopsy is a concern to patient's family

113/234 (48)

34/202 (17)

8/20 (40)

Cost of autopsy is a concern to hospital/institution

78/234 (34)

40/199 (20)

8/21 (38)

Infection control is a concern regarding autopsy

102/235 (44)

143/185 (77)

9/11 (82)

Facilities are inadequate to perform autopsy

24/185 (13)

5/11 (45)

Infection control is a concern regarding histopathologic evaluation

62/111 (56)

4/8 (50)

No available pathologists experienced in recognizing histopathologic
features of CJD

69/111 (62)

1/8 (13)

aTSE, transmissible spongiform encephalopathy.

Suggested citation for this article:
Louie JK, Gavali SS, Belay ED, Trevejo R, Hammond LH, Schonberger LB, et
al. Barriers to Creutzfeldt-Jakob disease autopsies, California. Emerg
Infect Dis [serial on the Internet]. 2004 Sep [date cited]. Available


with the risks from ICJD alone should warrant such actions.

new atypical TSEs showing up in man and animal, all the more
reason to make human TSEs reportable Nationally and Internationally.

TO top that, the USDA et al have lied to us for 24 years about
BSE/TSE in the USA bovine.

TO flounder any further, will continue the spread of this agent...

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

disease in the United States

Email Terry S. Singeltary:

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

Terry S. Singeltary Sr.

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

In Reply to: Re: Monitoring the occurrence of emerging forms of
Creutzfeldt-Jakob disease in the United States [FULL TEXT]
posted by TSS
on March 27, 2003 at 7:15 am:

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States

IN the reply from Dr. Maddox to Terry S. Singeltary Sr., he states;


If BSE causes a sporadic CJD-like illness in humans, an increase in
sporadic CJD cases would be expected to first occur in the United
Kingdom, where the vast majority of vCJD cases have been reported. In
the United Kingdom during 1997 through 2002, however, the overall
average annual mortality rate for sporadic CJD was not elevated; it was
about 1 case per million population per year. In addition, during this
most recent 6-year period following the first published description of
vCJD in 1996, there was no increasing trend in the reported annual
number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the
UK has shown no increase in the proportion of sporadic CJD cases that
are homozygous for methionine (Will RG, National CJD Surveillance Unit,
United Kingdom, 2003; personal communication)...


THERE seems to be some difference of opinion;

Mouse model sheds new light on human prion disease


Professor John Collinge said “We are not saying that all or even most
cases of sporadic CJD are as a result of BSE exposure, but some more
recent cases may be – the incidence of sporadic CJD has shown an upward
trend in the UK over the last decade. While most of this apparent
increase may be because doctors are now more aware of CJD and better at
diagnosing it, serious consideration should be given to a proportion of
this rise being BSE-related. Switzerland, which has had a substantial
BSE epidemic, has noted a sharp recent increase in sporadic CJD.

news_archive/public-news-archive_nov_dec_02/public- bse_and_sporadic_cjd.htm

ALSO, Dr. Maddox states;

make routine mortality surveillance a useful surrogate for ongoing CJD

THIS has proven not very useful in the U.K.;



One reason for this was the _inaccuracy_ in coding of cases correctly
certified as CJD Coding is carried out by staff who are not medically
qualified and it is not surprising that coding errors occur in the
processing of large numbers of certificates. In 1982, 12,000
certificates per week were processed at the office of population
censuses and surveys bu 15 coders and 6 checkers (Alderson et al.,
1983). The occurrence of both inter- and intra-observer coding errors
has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH
certification and coding discovered in this study _support_ the
introduction of a more accurate system of death certificates and a more
detailed and specific coding system...


AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE
to other species will invariably present pathology typical of a
scrapie-like disease.


DR. Maddox states here;

In collaboration with appropriate local and state health departments and
the National Prion Disease Pathology Surveillance Center, CDC is
facilitating or conducting such surveillance and case- investigations,
including related laboratory studies to characterize CJD and CWD prions.

HOWEVER in a recent article in the UPI out of Washington;

CJD screening may miss thousands of cases

By Steve Mitchell UPI Medical Correspondent Published 7/21/2003 3:00 PM


In addition, the NPDPSC sees less than half of all the CJD cases each
year, so the CDC's investigational system not only is missing many of
the misdiagnosed CJD cases, it also is not conducting autopsies on most
of the detected cases.


ALSO in Philip Yams book 'The Pathological Protein';

''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance
system has errors but stated that most of the errors will be confined to
the older population''....

THERE has been a _documented_ case of nv/v CJD in a 74 year old, so the
errors Schonberger speaks of (above) would be of significant importance,
if one believes in the nv/v CJD 'only' theory.

NOW we have _documented_ cases of very young CJD victims in the USA
continuing to appear in several different states.

HOW does Dr. Maddox explain this, and does he still believe that a
National CJD surveillance program with a CJD questionnaire to every
victims family is still not warranted?

WITH CWD and Scrapie running rampant in the USA, with BSE now
_documented_ in North America, with the feeding of ruminant-to-ruminant
animal protein still happening in the USA in 2003 even though there has
been a partial voluntary ban on ruminant feeding since 8/4/97, with only
48,000 BSE/TSE tests done on USA cattle in some 14 years of
surveillance, when in any given year there are 100 million cattle in the
USA, with all this, i think refusing to make CJD/TSEs reportable
Nationally in the USA is not ONLY a grave mistake, but in my opinion,
should be looked at with great suspicion...

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, TEXAS USA 77518

Terry S. Singeltary Sr. wrote:


Barriers to Creutzfeldt-Jakob Disease Autopsies, California

Janice K. Louie,*†Comments ........snip...END

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