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.