HUMAN SPONGIFORM ENCEPHALOPATHY - THE NATIONAL-INSTITUTES-OF-HEALTH SERIES OF 300 CASES OF EXPERIMENTALLY TRANSMITTED DISEASE

We present a synthesis of clinical, neuropathological, and biological details of the National Institutes of Health series of 300 experimenta lly transmitted cases of spongiform encephalopathy from among more tha n 1,000 cases of various neurological disorders inoculated into nonhum an primates during the past 30 years. The series comprises 278 subject s with Creutzfeldt-Jakob disease, of whom 234 had sporadic, 36 familia l, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients wit h Gerstmann-Straussler-Scheinker syndrome. Sporadic Creutzfeldt-Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the frequent early appearanc e of cerebellar and visual/oculomotor signs, and a broad spectrum of c linical features during the subsequent course of illness, which was us ually fatal in less than 6 months. Characteristic spongiform neuropath ology was present in all but 2 subjects. Microscopically visible kuru- type amyloid plaques were found in 5% of patients with Creutzfeldt-Jak ob disease, 75% of those with kuru, and 100% of those with Gerstmann-S traussler-Scheinker syndrome; brain biopsy was diagnostic in 95% of ca ses later confirmed at autopsy, and proteinase-resistant amyloid prote in was identified in Western blots of brain extracts from 88% of teste d subjects. Experimental transmission rates were highest for iatrogeni c Creutzfeldt-Jakob disease (100%), kuru (95%), and sporadic Creutzfel dt-Jakob disease (90%), and considerably lower for most familial forms of disease (68%). Incubation periods as well as the durations and cha racter of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease. Infectivity reached average levels of nearly 10(5) med ian lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and, except f or cerebrospinal fluid, was never detected in bodily secretions or exc retions.