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While polioviruses are being eradicated globally by vaccination, EV71 still has the potential to cause a large outbreak such as that in Taiwan in 1998, in which there were many fatalities. In this study, we determined the neurovirulence of EV71 by neuropathological analysis of cynomolgus monkeys after experimental infection with five EV71 strains, which were isolated from individual patients with fatal encephalitis; meningitis; and hand, foot, and mouth disease. After intraspinal inoculation, the monkeys developed neurological manifestations within 1\u20136 days post\u2010inoculation, irrespective of the inoculated strains. These manifestations included not only pyramidal tract signs such as flaccid paralysis, but also extrapyramidal tract signs such as tremor and ataxia. Histological and viral examinations confirmed virus replication in the spinal cord, brainstem, cerebellar cortex, and dentate nuclei, and cerebrum. The strains isolated during the 1970s and 1990s showed no particular differences with respect to neurotropism. Thus, it is clear that EV71 has a wider neurotropism than that of polioviruses. J. Med. Virol. 67:207\u2013216, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.2209","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T23:24:15Z","timestamp":1030317855000},"page":"207-216","source":"Crossref","is-referenced-by-count":97,"title":["Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71"],"prefix":"10.1002","volume":"67","author":[{"given":"Noriyo","family":"Nagata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Ami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Tano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Harashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Suzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Miyamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsutaro","family":"Sata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,4,3]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(99)00019-2"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365549950163734"},{"key":"e_1_2_1_4_1","first-page":"783","article-title":"Studies on the pathogenesis of fixed rabies virus in rats","volume":"33","author":"Baer GM","year":"1965","journal-title":"Bull WHO"},{"key":"e_1_2_1_5_1","first-page":"119","article-title":"The pathogenesis of street rabies virus in rats","volume":"38","author":"Baer GM","year":"1968","journal-title":"Bull WHO"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(74)91684-5"},{"key":"e_1_2_1_7_1","unstructured":"BodianD.1949.Poliomyelitis: pathologic anatomy. 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