Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation

Abstract

The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.

Multiparameter MR Imaging in the6-OPRIVariant of Inherited Prion Disease

“…11 In a recent study of patients with the 6-OPRI mutation, significant cortical thinning was seen in the precuneus, inferior parietal cortex, supramarginal gyrus, and lingula. 9 Our study confirms these findings, with gray matter volume loss in such patients predominantly involving the perisylvian cortex, precuneus, and lingual gyrus and without significant involvement of the mesial temporal lobe structures. These cortical changes relate well to clinical symptoms documented in patients with the 6-OPRI mutation.…”

“…Some types of IPD (E200K, V201I) have clinical and radiologic features similar to sporadic Creutzfeldt-Jakob disease, 42 but apart from patients carrying the P102L mutation, 9 the imaging features of other mutations are not well described in the literature. A comparison of 6-OPRI MR imaging findings with those from other IPD mutations would be particularly informative.…”

“…Brain atrophy has rarely been quantified in IPD, apart from a case report of a presymptomatic P102L gene carrier demonstrating early parietal atrophy 10 and a recent demonstration of parietal and occipital cortical thinning in patients with the 6-OPRI mutation. 9 Quantitative MR imaging techniques such as MTR and MD mapping have revealed significant regional and whole-brain differences between patients with symptomatic prion disease and control participants. [11][12][13][14] However, these studies used region-ofinterest or histogram analyses, possibly missing or diluting regionally specific changes.…”

“…In the United Kingdom, large kindreds presenting with 6 additional repeats in the octapeptide region (6-OPRI mutation), have been followed up for more than 2 decades with detailed reports of clinical symptoms 8 and neuropsychological features 9 but without systematic analysis of imaging findings. These pa-tients characteristically present with frontoparietal dysfunction progressing for 7-15 years (mean, 11 years) that culminates in an akinetic mute state.…”

Imaging of the6-OPRIMutation Prion Disease: An Entity Distinct from Typical Creutzfeldt-Jakob Disease?

“…5 This present study extended the findings of this previous work in using voxel-based analysis of advanced MR imaging in several patients with 6-OPRI mutations. The authors discovered volume reductions, decreases in magnetization transfer ratio, and diffusivity increases within subcortical gray matter structures as well as some cortical structures including the perisylvian cortex and precuneus.…”