Cortical Hyperintensity on Diffusion-weighted Images as the Presymptomatic Marker of Sporadic Creutzfeldt-Jakob Disease

Abstract

We herein report a sporadic Creutzfeldt-Jakob disease (sCJD) patient followed from the presymptomatic phase to death. A 67-year-old woman had abnormal hyperintense cortical lesions on diffusion-weighted magnetic resonance imaging (MRI) one year before the onset. The levels of 14-3-3 protein and total tau protein, and findings from a real-time quaking-induced conversion test were normal at first but became abnormal after disease onset. Although there are four reports of presymptomatic sCJD identified by MRI, this is the first case report in which all three biomarkers had been assessed before and after the disease onset. MRI might be the most sensitive modality for detecting presymptomatic sCJD patients.

Selective vulnerability to atrophy in sporadic Creutzfeldt‐Jakob disease

“…ª 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association frontal regions, [39][40][41][42][43] similar to regions where we detected atrophy with VBM. Furthermore, our findings are consistent with studies in human genetic prion disease showing atrophy in cortical association regions.…”

“…We found five case reports of neurologically normal persons who had brain MRIs for reasons unrelated to sCJD (e.g., carotid bulb tumor, studies assessing utility of annual MRI for standard of clinical care, etc) and who became symptomatic with sCJD between 3 and 14 months later. Overall, these cases showed DWI abnormalities (reduced diffusion) in the presymptomatic phase of disease in association cortices including the bilateral temporo‐parietal‐occipital junction, lateral parietal, precunei, and mesial frontal regions, 39–43 similar to regions where we detected atrophy with VBM. Furthermore, our findings are consistent with studies in human genetic prion disease showing atrophy in cortical association regions 10,11 .…”

Case Report: Extremely Early Detection of Preclinical Magnetic Resonance Imaging Abnormality in Creutzfeldt–Jakob Disease With the V180I Mutation

“…In our case of V180I CJD, a cortical DWI hyperintense change was successfully detected in the extremely early stage of the disease before the emergence of CJD symptoms (Figure 1B). To the best of our knowledge, abnormal DWI lesions have been detected in seven previously reported CJD cases before the onset of symptoms (Table 1) (5)(6)(7)(8)(9)(10)(11). Six of these were sporadic CJD (5,(7)(8)(9)(10)(11), and one was a case of genetic CJD with V180I mutation (6), as in our case.…”

“…To the best of our knowledge, abnormal DWI lesions have been detected in seven previously reported CJD cases before the onset of symptoms (Table 1) (5)(6)(7)(8)(9)(10)(11). Six of these were sporadic CJD (5,(7)(8)(9)(10)(11), and one was a case of genetic CJD with V180I mutation (6), as in our case. The duration between initial MRI detection and symptom onset was 2-16 months, consistent with that in our case where the initial MRI abnormality was detected 6 months before the onset of CJD symptoms (action tremor) and 9 months before the diagnosis.…”

Bilateral lesions of the basal ganglia and thalami (central grey matter)—pictorial review

“…The MRI criteria for sCJD are DWI signal abnormality from either at least two cortical regions or both the caudate nucleus and putamen [ 87 , 88 ]. Cortical DWI hyperintensity also appears to be a presymptomatic marker, as the abnormalities on MRI have been found to antedate the onset of sCJD [ 89 ]. Bilateral symmetric posterior thalamic hyperintensity on FLAIR and DWI is known as the pulvinar sign (which along with involvement of dorsomedial thalami gives the “hockey stick” appearance) and is considered pathognomonic for vCJD, however only if the signal in the thalami is brighter than in the caudate and putamina [ 87 ].…”