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

TLDR

The authors synthesize clinical, neuropathological, and biological data from 300 experimentally transmitted spongiform encephalopathy cases in nonhuman primates over 30 years. The series includes 278 Creutzfeldt‑Jakob disease cases (234 sporadic, 36 familial, 8 iatrogenic), 18 kuru, and 4 Gerstmann‑Sträussler‑Scheinker syndrome cases, providing a comprehensive dataset for transmission and pathology analysis. Sporadic CJD presented with a mean onset age of 60, early cerebellar and visual signs, and a fatal course within six months; spongiform pathology was nearly universal, amyloid plaques varied by disease type, brain biopsy was diagnostic in 95 % of cases, transmission rates were 100 % for iatrogenic CJD, 95 % for kuru, 90 % for sporadic CJD, and 68 % for familial forms, incubation periods varied widely, and infectivity was concentrated in brain tissue (~10⁵ LD₅₀ / gm) with negligible presence in other tissues.

Abstract

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 10 5 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.