From: Terry S. Singeltary Sr. (216-119-143-141.ipset23.wt.net)
Subject: Creutzfeldt-Jakob disease: Possible medical risk factors (October 1985)
Date: December 27, 2004 at 2:57 pm PST
CJD Human TSE is not caused by Trauma
Trauma does not _cause_ CJD.
Trauma may activate the agent that is already there.
Imagine a brain that is riddled with holes, but functional,
then a sudden physical blunt trauma or even mental trauma
starts the break down process.
but trauma is not a cause/source of the TSE agent.
the TSE agent was already there and working...
> No significant associations were found for a number of medical
> illnesses. However, it has been noted previously that respiratory
> illness sometimes precedes dementia.[18, 23] Thus, a role for stress
> or antecedent illness as a trigger for activation of latent CJD should
> not be ruled out.
Creutzfeldt-Jakob disease: Possible medical risk factors (October 1985)
Sun, 18 Feb 2001 13:11:17 -0800
"Terry S. Singeltary Sr."
Bovine Spongiform Encephalopathy
######### Bovine Spongiform Encephalopathy #########
Possible medical risk factors
Article abstract--To explore possible risk factors
in the past medical history of patients with Creutzfeldt-dakob disease
(CJD), we conducted a case-control study among 26 cases and 40 matched
controls. Statistically significant odds ratios were obtained for
intraocular pressure testing;, injury
to or surgery on the head, face, or neck; and trauma to other parts of
the body. The odds ratios were nearly significant for head trauma and
procedures requiring sutures. These data suggest that the CJD agent may
be acquired by inoculation through injury or during surgery, and perhaps
on certain absorbable sutures of animal origin. The tonometer used for
glaucoma testing may also be a vehicle of transmission.
Zpreh Davanipour, DVM, PhD;
Milton Alter, MD, PhD;
Eugene Sobel, PhD;
David Asher, MD;
and D. Carleton Gajdusek, MD
Creutzfeldt-Jakob disease (CJD) is an infectious, spongiform
encephalopathy caused by an
unconventional "slow" virus. Little is known about its modes of
transmission and natural infection. However, three instances of
iatrogenic transmission have been documented, one involving corneal
transplantation and two following the use of stereotactic
intracerebral electrodes. Masters et al called attention to
surgical operations among patients, and Kondo and Kuroiwa reported an
excess of physical injuries among cases compared
with controls. These reports suggest that
inoculation during physical injuries or during surgical procedures could
be a mode of transmission of the CJD agent. To explore this possibility,
we carried out an epidemiologic study among patients
and matched controls in which we inquired about past medical history.
Methods. The study was restricted to patients with CJD who resided in
Pennsylvania and other
surrounding mid-Atlantic states in the United States. Twenty-three cases
were ascertained from records of the Laboratory of Central Nervous
System Studies, National Institutes of Health. Three additional
unrelated cases were identified through relatives of these patients. All
subjects satisfied the
diagnostic criteria of Masters et al. In 20 patients (77%), the
diagnosis was confirmed by pathologic as well as clinical findings, and
the disease was successfully transmitted to animals from 8 of these 20
patients. The-6-other patients were classified as probable cases based
on clinical and laboratory findings. Due to dementia or death of
patients, surrogate respondents for CJD cases were identified among
close relatives who had known the patients well. Usually the family
member who provided information about a patient was the spouse. In
addition, whenever possible, sibs or parents of the patients were also
questioned about events in the patient's early life, such as childhood
Eighteen family and 22 hospital controls were also interviewed. The
family control was a blood relative other than the patient's surrogate
who matched the patient in sex and age ( + or - 10 years). Each hospital
control was randomly selected from a sex- and age (+ or - 5
years)-matched pool of 10 individuals admitted at about the same time to
the same hospital where the case diagnosis was made. If this person was
unavailable, another one was chosen at random from the nine remaining
in the pool, etc. Additional details of methods, demographics, general
background information, and possible dietary risk factors have been
described elsewhere. There
were no detectable differences in age, sex, race, religion, US-born
versus foreign-born, country of birth, ethnicity, educational levels,
and smoking history between cases and controls.
In the interviews, conducted by telephone, a pretested questionnaire
was used to obtain information about a wide range of topics in the past
medical history. Inquiry was made about physical trauma, general
surgery, oral surgery, dental work, eye examinations including tests for
intraocular pressure, blood transfusions, immunizations, childhood
illnesses, cancer, chronic or infectious diseases, allergies, and
neurologic or mental disorders. Data were collected for the following
time periods: birth through 14 years, from age 15 through 3 years before
onset, and within 2 years prior to onset. Time intervals for controls
October 1985 NEUROLOY:35 1483
using an assigned date which was the same as the
date of onset of symptoms in corresponding matched cases.
A preliminary view of the data was obtained using
the Statistical Package for the Social Sciences.
Odds ratios and confidence intervals were calculated using a computer
program provided by Thomas.
Table 1. Odds ratios for various exposures comparing cases versus all
Within 2 years Age 15 through 3 Birth
before onset years before onset age 15
Intraocular 9.2aa 3.1 --
Head-face-neck 1.6 3.5a 0.8
Head trauma - 4.0a -
Other trauma 1.6 4.0aa 0.4
Suture 3.3 2.9* --
admission 0.05* 0.5 0.2
transfusion -- 0.6 --
Endodontic -- 0.3 --
Cancer 0.4 0.3 --
Myocardial 0.8 2.4 --
Hypertension 0.6 0.9 --
Liver/kidney 0.8 1.6 --
Influenza 1.4 2.1 2.1
Diabetes 1.0 1.0 --
Gastroenteritis 1.7 2.6 --
Peptic ulcer 1.6 2.6 --
Warts -- 0.2 --
Herpes simplex 1.4 0.9 2.0
Herpes zoster 0.8 0.8 --
Surgical 1.6 1.1 --
alog the back
German measles 1.2
* = p < 0.10.
a = p < 0.05,
aa= p < 0.01.
--= Odds ratios not calculable due to zero frequencies.
Table 2. Comparison of cases and controls for exposures suggesting
[[[sorry, i cannot duplicate this table,
some day i will take a class, after they
admit we have a TSE in the cattle population
and after they admit it's all tied together
and that sporadic CJD did not fall from
Fisher's exact tests were performed using biomedical statistical
software from the University of California at Los Angeles. The reported
were based on two-sided tests.
Results. In table 1, odds ratios for various items
in the past medical history comparing cases and all controls are noted
for each of the three time intervals. The results revealed several
positive and a few negative associations. Odds ratios were also
calculated comparing patients with each of the two sets of controls:
family controls and hospital controls. Table 2 shows the responses of
patients, each set of controls, and both sets of controls combined, as
well as odds ratios for items in the past medical history that yielded
positive associations. Tests of intraocular pressure for glaucoma within
2 years of onset were reported more frequently by patients than family
controls (OR = 11.8, p < 0.01) and all controls (OR - 9,2, p < 0.01).
When patients were compared with hospital controls, the odds ratio was
also large (OR = 7.1) and approached statistical significance (p < 0.1).
Injuries or surgical operations on the head, face,
or neck were reported more frequently by patients than either hospital
controls (OR = 6.0, p < 0.05)
or all controls combined (OR = 3.5,p < 0.05) for the interval age 15
through 3 years before onset. Head trauma/concussion for the same time
interval also gave a large and nearly significant odds ratio when
comparisons were made between patients and hospital controls as well as
all controls (ORs = 6.7 and 4.0, respectively; p < 0.1). Trauma to other
parts of the body besides the head (eg, limb, chest, abdomen,
hip) was reported more often by patients compared with family controls
(OR = 13.8, p < 0.005) and all controls (OR = 4.0, p < 0.01).
Procedures requiring sutures were reported more frequently (p < 0.1)
among cases than hospital controls (OR = 3.7) or all controls (OR = 2.9)
for the period age 15 through 3 years before onset.
Odds ratios below 1 were found for the frequency of hospital admissions,
blood transfusions, and
endodontic procedures. When cases were compared with hospital controls
as well as with all controls, hospital admissions were significantly
less often reported among patients 2 years before onset. The results
comparing receipt of blood or having had a dental root canal procedure
also demonstrated odds ratios significantly less than 1 when cases were
compared with hospital controls.
No statistically significant odds ratios were noted for cancer,
myocardial infarction, hypertension, liver or kidney disease, upper
infection, influenza, diabetes, gastroenteritis, peptic ulcer, warts,
childhood disease, herpes simplex, herpes zoster, allergies, or
neurologic diseases. Odds ratios for invasive diagnostic or surgical
procedures to the back (eg, epidural or spinal anesthesia, disk
were not significantly different in cases and controls. In addition to
the comparisons between cases and controls, comparisons were also made
between blood relatives of cases and blood relatives of controls, a
history of neurologic or mental disease (eg, CJD, Parkinson's disease,
MS, schizophrenia, severe depression, and brain tumor) among the two
sets of blood relatives gave odds ratios with values greater than 2, but
not statistically significant.
Discussion. Comparison of the frequency of responses to a given item in
the past history of patients and controls can highlight differences that
have significance in terms of cause, pathogenesis, or
mode of transmission. When an agent is a slow virus with a long
incubation period, as in the case of
CJD, past history must be investigated for the
entire life span before onset of symptoms. This increases the difficulty
of obtaining reliable and valid information. Moreover, when dementia is
major manifestation of the illness, a secondary source of information,
such as a surrogate respondent, must be relied upon for past medical
history. We have previously discussed other considerations, such as
interviewer bias, small sample size, multiple comparisons, and
the interviews by telephone. Based upon prior findings and clues, the
current study focused on three medical history comparisons:
trauma/surgery, glaucoma testing, and upper respiratory infection.
Of the three comparisons, the former two were found significant.
Focusing in on only three comparisons, the problem of multiple
comparisons leading to
random significant results is not relevant.
The results suggest that testing intraocular
pressure may be a risk factor in the development of CJD. Intraocular
pressure is measured by a
tonometer. Contact or indentation tonometry, in
which the instrument is placed on the anesthetized eye, is used more
frequently than noncontact or applanation tonometry. In view of the fact
that the cornea may transmit CJD,[1.7] and given the resistance of the
etiologic agent to common disinfectants,[8.9] the intraocular pressure
tests are a plausible means of transmission because tonometers are not
adequately disinfected between applications.
Injuries or surgical operations on the head, face, and neck area may
provide a portal of entry for infection by the slow virus. Clinical
signs would be delayed until the virus reached the brain.
Mechanical trauma may activate an existing but dormant CJD infection,
leading to clinical manifestations, although this has not been observed
in experimental spongiform encephalopathies. The virus-like agent might
be disseminated through nerves, blood, or the lymphatic system. An
is provided by the scrapie agent, another slow virus that causes
pathologic changes in sheep and goats like those of CJD. Scrapie can
spread through nerve fibers after intracerebral inoculation, and
retinopathy has been induced by the scrapie agent. Neural
dissemination of scrapie after intraocular inoculation of hamsters has
also been reported. Viremia has been demonstrated in blood samples
of CJD patients, yet not in animals infected with scrapie. Lymph
nodes are one of
the primary sites from which the agent can be isolated.
Procedures requiring sutures occurred more often in patients. This
finding is noteworthy because some absorbable suture materials such as
surgical gut (catgut) are prepared from the intestinal submucosa of
sheep. A characteristic and distinct fibril (scrapie-associated fibril)
has been seen in humans and animals with spongiform
One method of suture sterilization involves gamma-irradiation by
cobalt-60 with a dose of 2.5 megarads (suture manufacturing companies,
personal communication, 1984). If the suture materials were
scrapie-infected, that dose would not kill the agent since 37% of the
infectivity remains even after a dose of 4.5 megarads.[16, 17] Thus,
sutures derived from materials prepared from sheep intestine could play
an etiologic role in CJD and might account for the greater frequency of
surgery and suturing in the histories of patients than in controls.
Blood relatives of cases were reported to have had a neurologic or
mental disorder more frequently than controls, although the difference
was not statistically significant. A similar finding was reported by
Bobowick et al. However, there was
no evidence in their study nor in ours that the neuropsychiatric
disorders in relatives progressed
to clinical CJD. Nonetheless, it may be relevant because familial
aggregates of CJD have recently
been reported in which the course was unusually
long, and typical hallmarks of the disease, such as myoclonic jerks and
characteristic electroencephalographic abnormalities, were absent? It is
conceivable that cases of neurologic or psychiatric disturbances in the
families of the patients represent atypical manifestations of CJD. This
possibility deserves more careful scrutiny.
Some responses, such as frequency of hospital admissions and blood
significantly lower among patients than hospital controls. However, this
may imply that the illnesses of hospital controls required multiple
admissions. Alternatively, the surrogate respondents may have
underreported these events for cases. Dental procedures in patients and
controls were of interest in view of the fact that experimental oral
transmission of spongiform encephalopathy has been successful, and
is believed to account for the transmission of kuru while cannibalism
was still practiced in the burial rituals of New Guinea highlanders.
Carp investigated the effect of gingival scarification
October 1985 NEUROLOGY 35 1485
on transmission of scrapie. All scarified mice, but only 71% of the
nonscarafied mice, developed scrapie. In addition, among those that
developed scrapie, those with scarification had a significantly shorter
incubation period. Although a negative association between CJD and
endodontic surgery was demonstrated in the present study, we would still
recommend careful inquiry into the dental history of patients with CJD
diagnosis so that detailed dental history will be documented for future
No significant associations were found for a number of medical
illnesses. However, it has been noted previously that respiratory
illness sometimes precedes dementia.[18, 23] Thus, a role for stress
or antecedent illness as a trigger for activation of latent CJD should
not be ruled out.
The main findings of the present case-control study were that testing
for intraocular pressure, trauma
to and surgery on the head and neck, and use of sutures were more often
reported by patients than controls. Given the biologic properties of the
agent and previously demonstrated iatrogenic and experimental modes of
transmission of spongiform encephalopathies, a plausible connection with
our observations can be made. If these results are indicative of a
causal relationship, then tonometric testing for glaucoma, trauma,
sutures, and injury or operation in the head-face-neck area may be modes
of transmission for CJD. Future studies of the possible source of the
infection in humans and the mode of natural transmission should consider
these possible risk factors. Detailed medical histories, in which these
events are specifically queried, should be obtained for all patients in
whom CJD is diagnosed.
The authors are grateful to the study participants and the families of
patients for their generous cooperation. We also thank the many
hospitals that made identification of the patients and their families
>From the Neuroepidemiology. Section. Department of Neurology. Temple
University School of Medicine
(Drs. Davanipour. Alter and Sobel). Philadelphia,
PA: and the labratory of Central Nervous System Studies. NINCDS.
National Institutes of Health (Drs Asher and Gajdusek), Bethesda. MD.
Presented in part at the thirty-seventh annual meeting of the American
Academy of Neurology.
Dallas. TX. April 1985.
Accepted for publication January 24, 1985.
Address correspondence and reprint requests to Dr. Davanipour.
Department of Neurology. Temple University, School of Medicine.
Philadelphia. PA 19140.
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1486 NEUROLOGY 35 -- October 1985
Terry S. Singeltary Sr., Bacliff, Texas USA