Human spongiform encephalopathy: The national institutes of health series of 300 cases of experimentally transmitted disease

Authors

  • Dr. Paul Brown MD,

    Corresponding author
    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
    • Building 36, Room 5B21, National Institutes of Health, Bethesda, MD 20892
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  • C. J. Gibbs Jr. PhD,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • Pamela Rodgers-Johnson MD,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • David M. Asher MD,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • Michael P. Sulima,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • Alfred Bacote,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • Lev G. Goldfarb MD,

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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  • D. Carleton Gajdusek MD

    1. Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroks, National Institutes of Health, Bethesda, MD
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Abstract

We present a synthesis of clinical, neuropathological, and biological details of the National Institutes of Health series of 300 experimentally transmitted cases of spongiform encephalopathy from among more than 1,000 cases of various neurological disorders inoculated into nonhuman primates during the past 30 years. The series comprises 278 subjects with Creutzfeldt-Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann-Sträussler-Scheinker syndrome. Sporadic Creutzfeldt-Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the freqauent early appearance of cerebellar and visual/oculomotor signs, and a broad spectrum of clinical features during the subsequent course of illness, which was usually fatal in less than 6 months. Characteristic spongiform neuropathology was present in all but 2 subjects. Microscopically visible kuru-type amyloid plaques were found in 5% of patients with Creutzfeldt-Jakob disease, 75% of those with kuru, and 100% of those with Gerstmann-Sträussler-Scheinker syndrome; brain biopsy was diagnostic in 95% of cases later confirmed at autopsy, and proteinase-resistant amyloid protein was identified in Western blots of brain extracts from 88% of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt-Jakob disease (100%), kuru (95%), and sporadic Creutzfeldt-Jakob disease (90%), and considerably lower for most familial forms of disease (68%). Incubation periods as well as the durations and character 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 105 median lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and except for cerebrospinal fluid, was never detected in bodily secretions or excretions.

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