Graft-related disease progression in dura mater graft-associated CreutzfeldtJakob disease: A cross-sectional study

Objectives: Details of abnormal prion protein (PrP^Sc) propagation in the human central nervous system (CNS) are unclear. To assess the spread of PrP^Sc through the human CNS, we evaluated dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) cases focusing on sites of grafting and dCJD pathological subtypes. Design: A cross-sectional study. Setting: nationwide surveillance data of human prion diseases in Japan over the past 12 years were applied for the study. Participants: Clinical data were obtained from 84 dCJD patients. Outcome measures: The clinical courses in cases of dCJD were analysed according to the grafting sites (supratentorial and infratentorial groups) and the pathological subtypes (non-plaque and plaque types). Results: Of the 84 cases of dCJD in this study, 36 (43%) were included in the supratentorial group and 39 (46%) were included in the infratentorial group. As initial manifestations, vertigo (p=0.007) and diplopia (p=0.041) were significantly more frequent in the infratentorial group than in the supratentorial group. During their clinical course, cerebellar signs appeared more frequently in the infratentorial group than in the supratentorial group (p=0.024). In the non-plaque type cases (n=53), the infratentorial group developed vertigo more frequently than the supratentorial group (p=0.017); moreover, cerebellar signs appeared more frequently in the infratentorial group (p=0.014). However, there was no significant difference between groups in the plaque type (n=18). Conclusions: The high frequency of clinical manifestations related to brain stem and cerebellar dysfunction in the non-plaque type dCJD with infratentorial grafting suggests that PrP^Sc commonly shows direct propagation into the CNS from contaminated dura mater grafts.