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Zhao et al. Developments in auxiliary examination of CJD

nervous system (CNS) degeneration that manifests (14 months, mean), prominence of psychiatric and
as rapidly progressive dementia, cerebellar ataxia, sensory symptoms, and negative of PSWCs. [5]
visual disturbance, and pyramidal/extrapyramidal
tract signs, etc. Relatively rare symptoms of CJD The clinical manifestations of CJD lack specificity,
include epilepsy, bulbar palsy, amyotrophy and stroke- thus it is difficult to distinguish from other dementia
like episodes. Onset of disease in most patients is diseases such as Alzheimer disease, autoimmune
at 64-66 years and death typically occurs 1-2 years encephalitis, neurologic paraneoplastic syndrome
thereafter. The causative agent in CJD is prion scrapie and hepatolenticular degeneration, just depending
protein (PrPsc), which results from the misfolding of on clinical symptoms. And the detection of PrP or
prion protein and is able to self-replicate. the genetic diagnosis has not been extensively
used clinically. Therefore, auxiliary examinations are
Four subtypes of CJD have been reported, including important for accurate diagnosis of CJD. 14-3-3 protein
sporadic (sCJD), familial or genetic (fCJD or gCJD), testing and electroencephalogram (EEG) are the
iatrogenic (iCJD) and variant (vCJD). sCJD is the traditional technologies that are widely used. Diffusion
most common type and accounts for 85-95% of all weighted imaging has been intensively studied,
cases. It occurs worldwide without geographic or which has a high sensitivity and plays a significant
[1]
seasonal clustering, [1,2] and may arise because of role in diagnosis. Recently, scientists propose some
random mutation or post-translational modification of emerging auxiliary examination methods, such as the
the PrP gene (PRNP). Based on the genotype and new biomarkers in cerebrospinal fluid (CSF), diffusion
biochemical properties, sCJD is classified into six tensor imaging, magnetic resonance spectroscopy and
different molecular strains: MM1, MM2, MV1, MV2, 18F-fluorodeoxyglucose positron emission tomography/
VV1, and VV2. [3,4] MM1/MV1 is the most common and computed tomography (18F-FDG PET/CT). We make
typical type with 60-70% of sCJD and has very high a review on the progress of auxiliary examinations on
positive rate in magnetic resonance imaging (MRI), CJD as follows.
periodic sharp wave complexes (PSWCs) and 14-3-
3 protein testing. VVI is negative in PSWCs and has AUXILIARY EXAMINATION
a longer duration of illness-about 21 months. [3-6] fCJD
accounts for about 10% of prion disease cases. It CSF biomarkers
[7]
shows autosomal dominant inheritance of mutations 14-3-3 protein is the most widely used CSF biomarker
in PRNP with high penetrance，and over 50 different for CJD diagnosis. It has the highest expression
mutations in PRNP have been found. The common in neuron synapses and plays a role in signal
[8]
form of fCJD results from mutation at codon 200, and transduction, neurotransmission, cell differentiation
the phenotype in patients is similar to that of sCJD. and apoptosis. [15,16] 14-3-3 protein can be detected in
[9]
Some other forms of fCJD with the phenotype different CSF of CJD patients and in the neurofibrillary tangles
from sCJD have been classified as distinct types such upon pathologic examination. [17] The mechanism by
as Gerstmann Sträussler-Scheinker disease (GSS) which 14-3-3 protein induces CJD onset is unknown,
and fatal familial insomnia (FFI). GSS even could and the diagnostic value of 14-3-3 protein is
[5]
have a much longer disease duration lasting 5 years. controversial. Some previous studies have reported
The first iCJD case (a person who was infected by the high sensitivity (85-97%) and specificity (68-97%)
corneal transplant from a CJD patient) was reported of the immunoblot test for 14-3-3 protein in CJD
in 1974. CJD can be transmitted by intracerebral diagnosis. [17,18] When 14-3-3 protein testing is taken
[10]
electrodes, corneal transplantation, dura mater grafts, among unselected patients with rapidly progressive
injections of growth hormone extracted from human dementia (disease duration less than 12 months),
pituitary glands and contaminated neurosurgical the false positive rate is about 12%. But in some
instruments. Blood transfusion or blood products of other studies about pathology confirmed cases, the
CJD patients are also infectious. vCJD was first negative rate is very high. [19] And the contamination
[11]
described in 1996, and was associated with ingestion of CSF by 14-3-3 protein containing blood cells
of beef with bovine spongiform encephalopathy (BSE). may lead to false-positive results. In addition, the
After the spread of BSE in the UK and the transmission expression of 14-3-3 protein is also found in many
to humans in 1980s-1990s, the secondary spread of conditions of neuronal injury such as infectious
the disease appeared in the 2000s from asymptomatic diseases of the CNS, metabolic encephalopathy and
infected individuals to others by routes such as blood in the acute stage of cerebral infarction, reducing
transfusion or organ grafting. [12-14] vCJD has different the specificity of 14-3-3 protein testing. [20] One study
manifestations from sCJD such as younger age at showed that only 17 of 32 confirmed sCJD patients
onset (28-29 years, mean), longer disease course (biopsy- or autopsy-confirmed) had positive results of
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ July 21, 2017 137