Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion protein at codon 180

Abstract

We report a 66-year-old woman with histologically diagnosed Creutzfeldt-Jacob disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated expansion of the high cortical signal on T2-weighted images, which differs from previous MRI reports of CJD. This patient followed an atypical clinical course: 16 months had passed before she developed akinetic mutism, and periodic sharp waves had not been detected on EEG after 2 years in spite of her akinetic mutism. Brain biopsy showed primary spongiform changes in the grey matter, and a point mutation of the prion protein gene at codon 180 was discovered using polymerase chain reaction direct sequencing and Tth 111 I cutting. This is the first case with the point mutation of the codon 180 variant with an atypical clinical course and characteristic MRI findings.

MR Imaging of Familial Creutzfeldt-Jakob Disease: A Blinded and Controlled Study

“…Our results, along with the previous reports of fCJD, also suggest that the imaging findings in fCJD are in general similar to those seen in sCJD. 5,15,17,[19][20][21][22]33,34 These results are consistent with fCJD having clinical and neuropathologic features seen in the most common molecular subtype of sCJD, which is the MM1 subtype. 14 The basal ganglia signal intensity changes are important markers for CJD.…”

“…[15][16][17][18][19] A collaborative surveillance project of genetic prion cases indicated that approximately 50% of a small number (not specified) of patients with fCJD due to the E200K mutation had abnormal MR images, but specific imaging results were not described. 33 There are also larger imaging studies focused on sCJD that combined a few fCJD patients with sCJD patients into a single subject group but report the MR findings of the combined sample.…”

“…[3][4][5][6][7][8][9][10][11][12][13] fCJD has imaging findings and neuropathology that are, in general, similar to the most common forms of sCJD; however, most imaging studies on fCJD consist primarily of case reports or studies focused on sCJD that combine a few fCJD patients into a single CJD patient sample. 8,[14][15][16][17][18][19][20][21][22] fCJD studies are limited not only by small sample sizes but also by nonstandardized imaging protocols and clinical and pathophysiologic heterogeneity. The complex interactions with disease duration and cognitive and neurologic severity have also made it difficult to interpret studies, especially because the sample sizes are small.…”

Autopsy-Proven Creutzfeldt-Jakob Disease with a Codon 180 Mutation Showing Dissociation between Diffusion-Weighted Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography Findings

“…No kuru or amyloid plaques were detected in the central nervous system. These findings were consistent with pathological changes reported in cases with CJD with a codon 180 mutation [3,4,6] . Immunoblot analysis of prion protein could not be performed due to technical problems.…”

“…In most cases occurrence is sporadic, but a small proportion of cases are familial. Among various associated mutations of the prion protein (PrP) gene identified by genetic analyses, a point mutation at codon 180 has been confirmed in only 7 patients, who characteristically showed a relatively long survival, old-age onset, absence of periodic synchronous discharges on electroencephalography (EEG) and lack of affected family members [3][4][5][6][7][8] . We report another CJD case with the same mutation of PrP, where neuroradiologic findings showed an unexpected and possibly informative dissociation.…”