Panencephalopathic Creutzfeldt-Jakob disease in the Netherlands and the UK: clinical and pathological characteristics of nine patients

Aims: The panencephalopathic type of Creutzfeldt-Jakob disease (PECJD) has extensive abnormalities in cerebral white matter as well as the cortex. PECJD has rarely been described in Caucasians and debate continues on its classification and pathogenesis. We describe our experience of PECJD over a 14-year period of surveillance for CJD in the Netherlands and the UK. Methods: Between 1993 and 2006, nine cases of PECJD were identified. Clinical, histological and biochemical characteristics of all patients were analysed and compared; all cases were classified clinically as sporadic CJD. Results: The median age at onset was 57.8 years and median disease duration was 22 months. The average brain weight was 887 g. Most patients showed a two-stage clinical course with initial rapid deterioration to a state of akinetic mutism, which then persisted over a longer time scale. Neuropathological findings were characterized by severe global atrophy with status spongiosus. Cerebral white matter involvement tended to be associated with either disease duration or severity of cerebral cortical lesions. Five patients could be classified into the MM1 subtype of sporadic CJD, one patient into the MM2 subgroup and another into the MV2 subgroup. Two patients were heterozygous at codon 129 in the prion protein gene and contained both type 1 and type 2 PrPres isoforms in the brain. Conclusions: We believe that white matter pathology in PECJD represents an end-stage pattern that reflects secondary degeneration due to widespread cortical neuronal loss that occurs in the early part of the disease, rather than representing a primary lesion.