Clinicopathologic characteristics of five autopsied cases of dura mater-associated Creutzfeldt-Jakob disease

Abstract

We present five cases of dura mater-associated Creutzfeldt-Jakob disease (dura-CJD) that were analyzed clinicopathologically and review previous reports. The average age at dura mater transplantation was 54.4 +/- 7.3 years, and the average age at CJD onset was 66.0 +/- 8.2 years, with an average latency period of 11.6 +/- 1.1 years. The average age at death was 67.6 +/- 8.7 years, with an average CJD disease duration of 16.8 +/- 10.4 months. Symptoms of CJD onset in four patients who received dura mater transplantation below the cerebellar tent reflected cerebellar or brainstem dysfunction, whereas symptoms of one patient who received transplantation above the cerebellar tent reflected cerebral cortical involvement. All patients showed rapidly progressive cognitive impairment, and both periodic sharp-wave complexes on electroencephalogram and myoclonus were observed in the early disease stage. Neuropathologic evaluation showed one case of subacute spongiform encephalopathy and four cases of panencephalopathic-type CJD. Widespread cerebral neocortical, subcortical gray matter and cerebellar cortical involvement were observed to varying degrees, and severity tended to be associated with CJD disease duration. There were no instances of kuru plaques or florid plaques. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition. No differences between our dura-CJD cases and typical cases of sporadic CJD were found with respect to clinicopathologic findings, except history of dura mater transplantation. Although a specific association between the dura mater graft site and neuropathologic observations was not evaluated in the present study, the initial symptoms appear to be closely related to the graft site, indicating a direct transmission of CJD from the graft site to the adjacent brain.