Creutzfeldt-Jakob disease of long duration: clinicopathological characteristics, transmissibility, and differential diagnosis.

Five to 10% of patients with Creutzfeldt-Jakob disease have a clinical course that extends for 2 years or more. In the present series 33 (9%) of 357 histopathologically verified cases, including 15 (7%) of 225 transmitted cases, fell into this long-duration category, the longest transmitted case having had a 13-year duration. As a group these cases were characterized by a higher familial representation (30%), a younger age at onset (average, 48 years), and lower frequencies of myoclonus (79%) and periodic electroencephalographic activity (45%) than occur in series of unselected cases. The clinical course most often showed a long, very slowly progressive first stage, with symptoms limited to intellectual deterioration or behavioral abnormalities, followed by a shorter, rapidly progressive terminal stage with both mental and physical deterioration. Although transmission of disease by primate inoculation was less successful in this group of long-duration cases (64%) than in cases of shorter duration (88%), incubation periods and durations of illness in the inoculated animals bore no relation to the duration of illness in the patients. Clinical differentiation from other chronic dementing processes, particularly Alzheimer's disease, can prove impossible; however, the correct pathological diagnosis was readily evident by light microscopic examination, and spongiosis was at least as prominent as gliosis in all but 4 (15%) of the 27 patients studied postmortem, the same frequency found in case series not selected for length of illness.