{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:04:12Z","timestamp":1791291852878,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":3813,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1994,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann\u2010Str\u00e4ussler\u2010Scheinker syndrome. Sporadic Creutzfeldt\u2010Jakob 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\u2010type amyloid plaques were found in 5% of patients with Creutzfeldt\u2010Jakob disease, 75% of those with kuru, and 100% of those with Gerstmann\u2010Str\u00e4ussler\u2010Scheinker syndrome; brain biopsy was diagnostic in 95% of cases later confirmed at autopsy, and proteinase\u2010resistant amyloid protein was identified in Western blots of brain extracts from 88% of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt\u2010Jakob disease (100%), kuru (95%), and sporadic Creutzfeldt\u2010Jakob 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<jats:sup>5<\/jats:sup> 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.<\/jats:p>","DOI":"10.1002\/ana.410350504","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T16:00:42Z","timestamp":1104595242000},"page":"513-529","source":"Crossref","is-referenced-by-count":614,"title":["Human spongiform encephalopathy: The national institutes of health series of 300 cases of experimentally transmitted disease"],"prefix":"10.1002","volume":"35","author":[{"given":"Paul","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"C. 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Carleton","family":"Gajdusek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02866081"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02870932"},{"key":"e_1_2_1_4_2","first-page":"906","article-title":"\u00dcber ein noch nicht beschriebenes Reflexph\u00e4nomen bei einer Erkrankung des zerebellaren Systems","volume":"78","author":"Gerstmann J","year":"1928","journal-title":"Wein Med Wochenschr"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.161.3839.388"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/209794a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/104.3.559"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/96.1.1"},{"key":"e_1_2_1_9_2","first-page":"91","volume-title":"Aging and dementia","author":"Traub R","year":"1977"},{"key":"e_1_2_1_10_2","first-page":"229","volume-title":"Slow transmissible diseases of the nervous system","author":"Bernoulli CC","year":"1979"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410050212"},{"key":"e_1_2_1_12_2","first-page":"132","article-title":"Zur Klinik, Neuropathologie und Pathogenese der Creutzfeldt\u2010Jakobschen Krankheit anhandvon 40 gesicherten F\u00e4llen","volume":"53","author":"G\u00e1lvez S","year":"1982","journal-title":"Nervenarzt"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1503"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.47.2.134"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200507"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00146403"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91518-F"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1675487"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90001-W"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90383-R"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198602273140904"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198607313150502"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(89)90095-2"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310308"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140104"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/94.4.715"},{"key":"e_1_2_1_27_2","doi-asserted-by":"crossref","unstructured":"DuffyP WolfJ CollinsG et al. 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