We report a patient of familial Creutzfeldt-Jakob disease (fCJD) with a causative point mutation of V180I in the prion protein gene (fCJD with V180I). A high-signal region on brain MRI was located at the cerebral cortex in the early stage (Figure 1A-D; Figure 2A-D), which progressively spread to the occipical lobe over the parieto-occipical sulcus and finally to the bilateral frontal white matter over four years follow-up (Figure 1E-H; Figure 2E-H), but without PSD of EEG. This V180I mutation is the most common cause of fCJD in Japan, with only two cases reported from Europe [8, 9]. Compared with sporadic CJD (sCJD), fCJD with V180I showed (1) older onset age, (2) slower disease progression, (3) unique clinical symptoms such as frequent cognitive dysfunction without visual or cerebellar symptoms, (4) a lower positive rate of NSE and 14-3-3 protein in CSF, and (5) a lack of PSD in EEG throughout the course of the disease . Our patient was compatible with the clinical and laboratory characteristics of this fCJD with V180I.
DWI is a useful technique for the early diagnosis of CJD [2–5], and diffuse cortical high-intensity signals in DWI and FLAIR image are characteristic feature of fCJD with V180I. However, serial changes on DWI and FLAIR image during the long-term period of fCJD with V180I have not been fully reported. Kono et al. reported that the abnormal lesions of a fCJD patient with V180I began from the left cerebral cortex to the contralateral cerebral cortex and the basal ganglia, with sparing the occipital, parieto-occipital lobes, and the cerebellum until the terminal stage at 25 months after the onset . However, the present case involved involved the occipital cerebral cortex and the frontal white matter over 4 years follow-up.
Serial EEG of fCJD with V180I usually shows a diffuse slow basic pattern without PSD, although most patients of sCJD demonstrate PSD in EEG, which is an accepted diagnostic marker for sCJD . The present case showed a similar course of EEG to typical fCJD with V180I. The general slower high-voltage basic rhythm of EEG (Figure 3B) at four years after the onset may reflect a severe deterioration in brain function such as akinetic mutism, not but apallic syndrome.
Spongiform degeneration is a typical pathologic change of CJD characterized by vacuoles in the neuropil, gliosis, and nerve cell loss in the gray matter [11, 12]. In fCJD cases with V180I, increased DWI signals and a hypoperfusion region on single photon emission computed tomography (SPECT) could reflect such spongiform changes . In addition, Iwasaki et al. reported a widespread fibrous gliosis with hypertrophic astrocytosis and proliferation of macrophages in the cerebral white matter in the brain of fCJD with V180I . Thus, in the present case of fCJD with V180I, the prominent white matter lesions of the frontal lobe might reflect secondary axonal degeneration due to widespread cerebral neocortical involvement (Figure 2G,H).
In conclusion, during the long follow-up period of fCJD with the present V180I case, MRI finding spread from the frontal, temporal, and parietal cortical lobe to occipital cortical lobe, with the possibly secondary change of the frontal white matter. In addition, EEG findings corresponded the symptom progression even after akinetic mutism at 18 months. Thus, the present case suggests that serial DWI, FLAIR, and EEG follow-up is useful for early diagnosis of CJD and for monitoring disease progress.