HOW IS CJD DIAGNOSED?
A
definitive diagnosis can only be made by examination of brain
tissue (biopsy or autopsy). This is the only current method of
confirming the diagnosis of both sporadic CJD and variant CJD.
Diagnostic
tests that are not confirmatory but are used in conjunction with
clinical symptoms to help make a diagnosis of what is termed “possible”
or “probable” CJD include:
Magnetic
resonance imaging (MRI) - is the most useful diagnostic test
for CJD. The recommended imaging is T2 and proton density axial
images with 3 mm slice thickness, FLAIR axial and sagittal images
at 3 mm slice thickness, T1 images, and diffusion-weighted images
(DWI).
MRIs can have findings of likely CJD and are useful in ruling
out other neurological diseases. vCJD and sCJD have different
finds on MRI.
Electroencephalogram
(EEG) – Distinctive abnormalities may be seen in patients
with CJD but are not definitive. As the disease progresses, EEG
findings also change. In the early stages of sCJD, the EEG may
be normal or may show non-specific slowing. With progression,
biphasic or triphasic periodic complexes that evolve into periodic
sharp wave complexes appear. In vCJD cases, EEG findings are usually
absent or they may be defined as nonspecific, slow wave abnormalities.
Cerebral Spinal Fluid (CSF):
Protein
14-3-3 - CSF contains a protein called 14-3-3 and elevated
levels may be seen in patients with CJD. The 14-3-3 immunoassay
is not a screening test but may be helpful in clinically diagnosing
patients exhibiting rapidly progressive dementia and is used
when a diagnosis of CJD is suspected.
Test results for
examination of the 14-3-3 protein in the CSF are reported as
elevated, not elevated, or ambiguous. An elevated level of 14-3-3
protein in the CSF may be positive in a number of neurological
diseases, including CJD, and hence it is not considered a confirmatory
test for CJD. Other conditions such as a recent stroke, neoplasm,
or encephalitis can cause elevated levels of the 14-3-3 protein.
Blood in the CSF sample can also cause the 14-3-3 protein to
be elevated. A negative CSF cannot exclude the diagnosis of
CJD while a positive test could reflect another disease.
A few specialty
laboratories test for the presence of the 14-3-3 protein. The
National Prion Disease Pathology Surveillance Center (NPDPSC)
at Case Western Reserve University is the preferred laboratory
to send CSF for 14-3-3 testing.
Tau
protein - is another CSF protein that may be elevated
in CJD. The NPDPSC has begun testing all CSF sent for 14-3-3
protein for tau protein as well. Tau protein appears to be a
more sensitive test than 14-3-3. A positive test for tau protein,
however, is also NOT a definitive diagnostic test for CJD, and
must be interpreted in the context of clinical disease and pathological
examination of brain tissue. Elevations in tau protein, for
example, may also be found in the much more common dementing
illness, Alzheimer’s disease.
Other - A variety of other CSF diagnostic tests
have been reported in small series, including the S100 protein,
and neuron specific enolase. These are of unproven diagnostic
utility at present, but may become more used as they are studied
further.
POSTMORTEM
TESTING - confirmatory diagnosis of CJD requires pathologic
examination of brain tissue.
Brain biopsy may
detect CJD but should not be used to rule it out. False negatives
can occur because samples collected may not include the brain
tissue where the abnormal prions are present.
Autopsy, which involves
the entire brain, is definitive and is the most reliable means
of confirming a diagnosis of CJD and ruling in or out a diagnosis
of vCJD or some other possibly new form of transmissible spongiform
encephalopathy (TSE).
In the United States,
the NPDPSC provides free autopsy and laboratory services. This
national reference center (established by the CDC in collaboration
with the American Association of Neuropathologists) provides
state-of-the-art prion disease diagnostic testing.
The CA Department
of Public Health encourages providers to obtain autopsies in
all clinically diagnosed or suspected CJD cases regardless of
age, in order to confirm the precise type of CJD. Our continued
efforts to conduct surveillance for CJD and variant CJD will
be greatly enhanced by increasing the proportion of CJD cases
that are confirmed through autopsy and tissue examination
Arrangements
for autopsy and laboratory testing can be made through the National
Prion Disease Pathology Surveillance Center. For details regarding
the collection and shipment of clinical specimens, as well as
additional resources available at the National Prion Center,
can be obtained from its website (http://www.cjdsurveillance.com)
or call (216) 368-0587.
DIAGNOSTIC TESTING - Provided by The
National Prion Disease Pathology Surveillance Center (NPDPSC)
1) CSF examination
for elevated levels of the 14-3-3 protein
2) DNA analysis on blood or brain tissue for the presence of
a genetic mutation. This test can only determine if a case has
a familial prion disease. For other prion disease the genetic
analysis may help to identify the specific type of prion disease.
3) Western Blot to determine the presence of the abnormal protease
resistant prion protein (PrPsc). If the abnormal protein is
present, the case is positive.
4) Histology and Immunohistochemistry – tissue is examined
under a microscope to look for distinct histological abnormalities.
Immunohistochemical staining is done to characterize the findings
and to help determine the type of prion disease
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