Clinical features of acute flaccid myelitis temporally associated with an enterovirus D68 outbreak: Results of a nationwide survey of acute flaccid paralysis in Japan, August-December 2015

Pin Fee Chong, Ryutaro Kira, Harushi Mori, Akihisa Okumura, Hiroyuki Torisu, Sawa Yasumoto, Hiroyuki Shimizu, Tsuguto Fujimoto, Nozomu Hanaoka, Susumu Kusunoki, Toshiyuki Takahashi, Kazunori Oishi, Keiko Tanaka-Taya, Etsushi Toyofuku, Tetsuhiro Fukuyama, Tatsuharu Sato, Yuya Takahashi, Akane Kanazawa, Masato Hiyane, Takao FukushimaTaira Toki, Ryoko Hayashi, Sonoko Kubota, Wakako Ishii, Manami Akasaka, Haruna Miyazawa, Mitsuo Motobayashi, Mari Asaoka, Takashi Shiihara, Yoshitaka Miyoshi, Tomohiko Tsuru, Kenta Ikeda, Masaru Matsukura, Ryoko Nakamura, Kengo Moriyama, Yuji Sugawara, Yuichi Takami, Takako Fujita, Tamami Yano, Mariko Kasai, Takashi Uchida, Masashi Fujita, Mitsugu Uematsu, Atsuko Hata, Hideto Ogata, Tomoyuki Miyamoto, Kataharu Sumi, Yu Ishida, Eri Takeshita, Tomoya Kawazoe, Takayoshi Kawabata, Chiharu Miyatake, Akiko Yakuwa, Yu Kakimoto, Hiroshi Terashima, Masaya Kubota, Yuichi Abe, Michiaki Nagura, Hideo Yamanouchi, Satomi Mori, Yukihiko Konishi, Mariko Ikegami, Yuko Tomonaga, Yumiko Takashima, Kazushi Ichikawa, Nobuko Moriyama, Chizu Oba, Mitsuru Kashiwagi, Sosuke Yoshikawa, Kenichi Tanaka, Genrei Ohta, Ayako Hattori, Daisuke Ieda, Sahoko Ono, Tomoshige Tanimura, Kyoko Ban, Nobuyoshi Sugiyama, Nozomi Kouzan, Yuki Yamada, Mika Inoue, Kenichi Sakajiri, Ken Ohyama, Miho Yamamuro, Hidetoshi Ishigaki, Azusa Seino, Shuichi Igarashi, Takahito Nakamoto, Kanae Sugimoto, Mitsuhiro Ochi, Eri Hamanaka, Kazuki Ohi, Hidefumi Kawasaki, Masahiko Nishitani, Hiroshi Uno, Masaru Inoue, Mai Okuyama, Ayako Yamamoto, Ryota Sato, Norihiko Azuma, Sakiko Mabuchi, Yoko Shida, Yu Hashimoto, Motoi Yoshimura, Yuki Matsuhisa, Kotaro Nakano, Yukio Yamashita, Eriko Kikuchi, Asuka Yamamoto, Naru Igarashi, Noboru Yoshida, Shingo Nishiki, Daisuke Yasutomi, Nobuyoshi Kusano, Ryohei Wakahara, Masayuki Furuyama, Hitoshi Mikami, Hiroaki Taniguchi, Yasuhiro Yoshii, Atsushi Narabayashi, Tomofumi Nakamura, Yasuo Kaburagi, Akiko Nagasao, Motoi Kuwahara, Kenichi Kaida

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

Abstract

Background. Acute flaccid myelitis (AFM) is an acute flaccid paralysis syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. Methods. An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens. Results. Fifty-nine AFM cases (58 definite, 1 probable) were identified, including 55 children and 4 adults (median age, 4.4 years). Te AFM epidemic curve showed strong temporal correlation with EV-D68 detection from pathogen surveillance, but not with other pathogens. EV-D68 was detected in 9 patients: 5 in nasopharyngeal, 2 in stool, 1 in cerebrospinal fluid (adult case), and 1 in tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from 1-to 4-limb involvement, but all definite cases had longitudinal spinal gray matter lesions on magnetic resonance imaging (median, 20 spinal segments). Cerebrospinal fluid pleocytosis was observed in 50 of 59 cases (85%), and 8 of 29 (28%) were positive for antiganglioside antibodies, as frequently observed in Guillain-Barré syndrome. Fifty-two patients showed variable residual weakness at follow-up. Good prognostic factors included a pretreatment manual muscle strength test unit score >3, normal F-wave persistence, and EV-D68-negative status. Conclusions. EV-D68 may be one of the causative agents for AFM, while host susceptibility factors such as immune response could contribute to AFM development.

Original languageEnglish
Pages (from-to)653-664
Number of pages12
JournalClinical Infectious Diseases
Volume66
Issue number5
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Acute flaccid myelitis
  • Antiganglioside antibodies
  • Enterovirus D68
  • Nationwide survey
  • Prognostic analysis

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