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Zhao et al. Developments in auxiliary examination of CJD

14-3-3 protein with the sensitivity of only 53%. [21] And relevance to myoclonus. Different from sCJD, vCJD
[35]
in another analysis of 420 CJD patients confirmed shows non-specific slow-wave abnormalities or normal
by biopsy, the specificity was only 28%. [22] The levels waves in EEG, but no typical PSWCs. [5,30] In iatrogenic
of 14-3-3 protein in vCJD and fCJD subtypes are CJD patients, the region of PSWCs is corresponding
different. [17] Distinct from sCJD, vCJD has about only to the site of operation. In genetic CJD patients, the
50% positive rate of 14-3-3 protein. Furthermore, positive rate of PSWCs is only about 10%. The source
GSS and FFI are nearly negative for 14-3-3 protein and the pathophysiological mechanism of PSWCs
testing. [5] remain unclear, although cortical and subcortical
mechanisms have been proposed. The PSWCs of
With the progress of the research, some other CJD are diffused discharges and may have multiple
biomarkers of CSF are found. Total tau (t-tau) and cortical sources or alternating ways of activation in
phosphorylated tau (p-tau) proteins in CSF are cortex, involving a subcortical pacemaker. Frontal
considered as useful biomarkers of CJD. Tau is a brain intermittent delta activity and triphasic wave-like
microtubule-associated protein which can assemble activity are supposed to be forerunners of PSWCs and
into filamentous structures by itself that forming appear when cortical and subcortical gray matter are
neurofibrillary tangles under pathological conditions. involved. Basal ganglia, thalamus and frontal cortex
This kind of tau neurofibrillary tangles, referred to as have also been suggested to be involved in generating
tauopathies, is a common feature in neurodegenerative PSWCs in CJD, but, experimental studies based on
disease such as Alzheimer’s disease. Recent studies animal model are needed to validate this hypothesis.
[36]
show increased T-tau levels and increased T-tau to PSWCs are also found in toxic encephalopathy,
P-tau ratios in CJD patients, with the diagnostic encephalitis and metabolic encephalopathy, especially
[23]
accuracy about 79.6%. Levels of tau in CSF have hepatic encephalopathy. Sometimes unilateral
[24]
[33]
also been suggested as a marker for molecular PSWCs can be observed in acute unilateral cerebral
subtype (codon 129 genotype) of sCJD. Other injury like cerebral infarction, encephalopyosis, and
[25]
CSF biomarkers, such as neuron specific enolase, brain tumor. There are few breakthroughs in PSWCs
brain-specific creatine kinase, S100β protein and for CJD diagnosis in recent years, compared to the
desmoplakin, have also been investigated as potential in-depth studies on medical imaging of CJD. Further
biomarkers, but have yet to be used clinically. Perhaps investigations of the pathophysiological mechanism of
the combination of more than one CSF marker could PSWCs and the relevance to clinical manifestation are
contribute to the differential diagnosis of CJD. [26-29] warranted.

EEG Diffusion weighted imaging
EEG is a reliable non-invasive diagnostic method for Diffusion weighted imaging (DWI) is a form of
CJD, especially sCJD, and was extensively used in functional MR imaging which can detect the Brownian
clinic even prior to 14-3-3 protein testing. The typical motion of water molecules in the pathological state by
[30]
feature of sCJD patient in EEG is periodic sharp wave the means of Echo Planar Imaging technology. It is
complexes (PSWCs). The duration of PSWCs is usually sensitive to the cytotoxic edema and is applied in the
100-600 ms and the intervening background among diagnosis of cerebral infarction most frequently. DWI
PSWCs is generalized slow waves with low amplitude. is also the most widely used, intensive studied and
PSWCs appear relatively later than the onset of clinical highly valued MRI sequence for accurate radiological
symptoms. In the early stages of disease, EEG usually diagnosis and differential diagnosis of CJD at present.
shows diffuse slow waves. PSWCs become apparent The typical performance of DWI on CJD patients is the
by 8 to 12 weeks after the disease onset in most cases abnormal ribboning hyperintensities in cerebral cortex
and occur even later in a few cases, but disappear and/or the abnormal hyperintensities in basal ganglia
in the end-stages of disease. Thus, the time to take region. DWI signal changes reflect the presence of
EEG examination is extremely important. [31,32] In the micro-vacuolation of brain tissue causing spongiform
regular EEG examination, the sensitivity of PSWCs degeneration, which is confirmed by autopsy. And
[37]
is 64-66%, [32,33] and the specificity is about 80%. it correlates well with the clinical manifestation and
[34]
Twenty-four-hour ambulatory EEGs could increase PrPsc accumulation. The sensitivity of DWI for
[38]
the sensitivity to about 79.6%. EEG recording can diagnosis is about 85-96%, and the specificity is about
[19]
increase the accuracy of the diagnosis from “possible” 93%, which is superior to that of conventional MRI
to “probable” sCJD if generalized PSWCs are (T1, T2 and FLAIR). [19,39-41] In a study on the diagnostic
demonstrated. Continuous video EEG monitoring may utility of CSF biomarkers and DWI, MRI-DWI was
be useful in identifying the connection between clinical the best predictor, with a diagnostic accuracy of
symptoms and EEG signal. In fact, PSWCs had some 97%. T-tau had a diagnostic accuracy of 79.6%,
138 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ July 21, 2017