Discussion
Crecutzfeldt-Jakob disease is a prion transmitted disease, which
comprises sporadic CJD, iatrogenic CJD, familial CJD, and variant CJD.
sCJD accounts for 85-90% of the total cases1. In the
early stage of the disease, the clinical presentations are atypical and
diverse, including vertigo, personality change, headache, cortical
blindness, hallucination, seizure, and stroke-like paralysis, which
could mimic other conditions. In this case, the initial onset symptom is
dizziness, which could masquerade as a posterior circulation stroke. The
other posterior circulation symptoms, including vertigo, nystagmus, and
cerebellar dysfunctions accompanying dizziness, were also investigated
in the other studies. We undertook a review of the current literature,
searching for reports in which dizziness was described as the first
onset symptom on CJD patients(Table 1). Interestingly, with the
progression of the disease, the typical manifestations gradually present
within four weeks. The follow-up period between first onset symptoms as
dizziness and classical manifestations of CJD were also summarized in
Table 1. The clinician should pay attention to these early-onset
symptoms, which are the key clues for considering the early stage of
CJD, and further MRI scans and CSF investigation were required.
Due to the variant symptoms of CJD, Neuroimaging investigation is useful
in making an early diagnosis of CJD when lacking the characteristic
clinical manifestations. The imaging abnormalities could involve
cingulate, striatum, thalamus, and neocortical cortex (precentral gyrus
was always spared). One study showed that signal hyperintensity on the
MRI DWI sequence had 96% sensitivity and 93% specificity for
differentiating CJD from other rapid dementia diseases. The
hyperintensity was more evident on DWI than FLAIR (Fluid-attenuated
inversion recovery), and the restricted diffusion was noted on
ADC3, 4. One study showed that a serial MRI scan
within the disease course is necessary for reaching the diagnosis of CJD5. Cortical DWI hyperintensity with normal ADC mapping
has been reported in autoimmune encephalitis(AE), which is a key
neuroimaging clue to distinct AE from sCJD6. A PET-CT
scan is useful for improving diagnostic accuracy by showing a
hypometabolic pattern in CJD patients7. In this case,
the classical ribboning lesion involved the patient’s bilateral
hemispheres, including frontal, temporal, occipital, and parietal lobes
on the DWI sequence, which was consistent with the previous
study3. Pulvinar and hockey stick signs could be
observed in 90% of the vCJD case and have 100% specificity for the
diagnosis of vCJD8. sCJD can be further classified
into six subtypes MM1, MM2, MV1, MV2, VV1, and VV2, according to the
different molecular strains. One study showed that the VV1 subtype is
more vulnerable for the cortical involvement while sparing the basal
ganglia and thalami9. The relationship between MRI
imaging and subtypes is still unclear and needs to be further
investigated. Interestingly, the disease had little effect on this
patient’s motor function during its course, probably due to the
precentral gyrus sparing.
EEG was a noninvasive assessment tool for the diagnosis of CJD. The
typical EEG manifestations are the periodic triphasic sharp waves.
Periodic sharp-wave complexes(PSWC) can develop in half of the late
stage of CJD patients10. However,this EEG pattern was
not specific to CJD and was also observed in other neurological
diseases, including Lewy body dementia, metabolic encephalopathies, and
non-convulsive status epilepticus. EEG abnormalities were showed lower
sensitivity and specificity in detecting the early stage of
CJD8.
The CSF analysis also played a key role in the diagnosis of probable
CJD. Several studies indicated that cerebral fluid real-time
quaking-induced conversion
(RT-QuIC) of prion protein has a
high specificity for CJD 1, 11, which provides more
evidence for the diagnosis of CJD. However, the current
RT-QuIC technology is not useful
in detecting the misfolded prions in vCJD patients. One study reported
that RT-QuIC, combined with using protein multiplication cyclic
amplification (PMCA), could discriminate vCJD from other
subtypes11. Although the gold standard for the final
diagnosis of CJD is a pathological biopsy, the procedure was not
recommended for the sake of the transmissible nature of the disease and
its invasiveness.