Production mechanisms and roles of antibodies to glutamate receptor in ac ute encephalitis.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: 独立行政法人国立病院機構(静岡てんかん・神経医療センター) (2011); National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders (2009-2010)
• Principal Investigator: TAKAHASHI Yukitoshi 独立行政法人国立病院機構(静岡てんかん・神経医療センター), 臨床研究部, 部員(統括診療部長) (70262764)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Shigeko (60393120)
• Project Period (FY): 2009 – 2011
• Keywords: 急性脳炎 / 辺縁系脳炎 / 卵巣奇形腫 / GluRψ2(NR2B) / GluRζ1(NR1) / アポトーシス / サイトカイン

Research Abstract

In CSF from patients with non-herpetic acute limbic encephalitis(NHALE), antibodies to GluRψ2(NR2B) and GluRζ1(NR1) we re related with clinical evolution. Antibodies to NMDAR seemed to internalize extra-synaptic NMDAR, because those antibod i es prevent ed apoptosis of rat cultured neurons. Those antibodies seemed not to inte rnalize synaptic NMDAR, because those did not affect phosphorylation of CREB(cAMP-Responsive-Element-Binding protein). These may contribute to the relatively better outcome of NHALE.

Research Products

• [Journal Article] Toxic epidermal necrolysis in a 4-year-old boy successfully treated with plasma exchange in combination with methylprednisolone and i. v. immunoglobulin. (2012)
  • Author(s): Aihara Y, Oyama Y, Ichikawa K, Takeshita S, Takahashi Y, Kambara T, Aihara M
  • Journal Title: J Dermatol
  • DOI: doi:10.1111/j.1346-8138.2012.01534.x.
  • Peer Reviewed
• [Journal Article] Influence of concomitant antiepileptic drugs on plasmalamotrigine concentration in adult Japanese epilepsy patients (2012)
  • Author(s): Yoshiaki Yamamoto, Yushi Inoue, Kazumi Matsuda, Yukitoshi Takahashi, Yoshiyuki Kagawa
  • Journal Title: Biol. Pharm. Bull Volume: 35-4 Pages: 487-493
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22466551
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• [Journal Article] Efficacy of stiripentol in a mouse model of severe myoclonic epilepsy in infancy (2012)
  • Author(s): Dezhi Cao, Hideyuki Ohtani, Ikuo Ogiwara, Sanae Ohtani, Yukitoshi Takahashi, Kazuhiro Yamakawa, Yushi Inoue
  • Journal Title: Epilepsia
  • DOI: doi:10.1111/j.1528-1167.2012.03497.x
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• [Journal Article] Evaluation of serum cytokines levels in toxic epidermal necrolysis and Stevens-Johnson syndrome in compared with other delayed-type adverse drug reactions (2011)
  • Author(s): Yuki N omura, Michiko A ihara, Setsuko M atsubara, Yuko I kezawa, Takeshi K ambara, Yukoh A ihara, Yukitoshi T akahashi
  • Journal Title: J Dermatol Volume: 38-11 Pages: 1076-9
  • DOI: doi:10.1111/j.1346-8138.2010.01170.x.Epub2011Mar2.
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• [Journal Article] Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome (2011)
  • Author(s): Masako Sakauchi, Hirokazu Oguni, Ikuko Kato, Makiko Osawa, Shinichi Hirose, Sunao Kaneko, Yukitoshi Takahashi, Rumiko Takayama, Tateki Fujiwara, ZenroI kezawa
  • Journal Title: Epilepsia Volume: 52-6 Pages: 1144-1149
  • DOI: doi:10.1111/j.1528-1167.2011.03053.x.
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• [Journal Article] Temporal changes in brain MRI findings in Rasmussen syndrome (2011)
  • Author(s): E Yamaza ki, Y Takahashi, N Akasaka, T Fujiwara, Y Inoue
  • Journal Title: Epileptic Disorders Volume: 13 Pages: 229-239
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21926050
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• [Journal Article] Atsushi Muraguchi, Hisashi Mori, Detection of autoantibody against extracellular epitopes of N-methyl-D-aspartate receptor by cell-based assay (2011)
  • Author(s): Shiho Takano, Yukitoshi Takahashi, Hiroyuki Kishi, Yoshiharu Taguchi, Shutaro Takashima, Kortaro Tanaka
  • Journal Title: Neurosci Res Volume: 71-3 Pages: 294-302
  • URL: http://dx.doi.org/10.1016/j.neures.2011.07.1834
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• [Journal Article] CDKL5 alterations lead to early epileptic encephalopathy in both genders (2011)
  • Author(s): Jao-Shwann Liang, Keiko Shimojima, Rumiko Takayama, Jun Natsume, MinobuShichiji, Kyoko Hirasawa, Kaoru Imai, Tohru Okanishi, Seiji Mizuno, Akihisa Okumura, Midori Sugawara, Tomoshiro Ito, Hiroko Ikeda, Yukitoshi Takahashi, Hirokazu Oguni, Katsumi Imai, Makiko Osawa, Toshiyuki Yamamoto
  • Journal Title: Epilepsia Volume: 52-10 Pages: 1835-1842
  • DOI: doi:10.1111/j.1528-1167.2011.03174.x.
  • Peer Reviewed
• [Journal Article] Lamotrigine is favorable for startle-induced seizuresShort title ; LTG for startle-induced seizures (2011)
  • Author(s): Hiroko Ikeda, Katsumi Imai, Hitoshi Ikeda, Hideo Shigematsu, Takeo Shishido, Rumiko Takayama, Tateki Fujiwara, Yukitoshi Takahashi, Yushi Inoue
  • Journal Title: Epileptic disorder Volume: 13-3 Pages: 277-283
  • DOI: doi:10.1684/epd.2011.0458
  • Peer Reviewed
• [Journal Article] Focal encephalopathy with recurrent episodes of epileptic statusand cluster mimicking hemiconvulsion. hemiplegia. epilepsys yndrome (2011)
  • Author(s): Rie Miyata, Naoyuki Tanuma, Masaharu Hayashi, Yukitoshi Taka hashi
  • Journal Title: Brain & Development
  • URL: http://dx.doi.org/10.1016/j.braindev.2011.06.011
  • Peer Reviewed
• [Journal Article] Cutaneous adverse drug reaction in patients with epilepsy after acute encephalitis (2011)
  • Author(s): Yukiko Mogami, Yukitoshi Takahashi, Rumiko Takayama, Hideyuki Ohtani, Hiroko Ikeda, Katsumi Imai, Hideo Shigematu, Yushi Inoue
  • Journal Title: Brain & Development
  • DOI: doi:10.1007/s00415-011-6291-7
  • Peer Reviewed
• [Journal Article] Subacute cerebellar ataxia and atrophy developed in a young woman with systemic lupus erythematosus whose cerebrospinal fluid was positive for antineuronal cell antibody (2011)
  • Author(s): Iwasaki Y, Okamoto A, Shoda H, Takahashi Y, Fujio K, Kawahata K, Yamamoto K
  • Journal Title: Lupus
  • DOI: doi:10.1177/0961203311418270
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• [Journal Article] Late delirious behavior with 2009 H1N1 Influenza ; mild autoimmune-mediated encephalitis? (2011)
  • Author(s): Jun-ichi Takanashi, Yukitoshi Takahashi, Atsushi Imamura, Kazuhiko Kodama, Akimitsu Watan abe, Koji Tominaga, Kazuhiro Muramatsu, A. James Barkovich
  • Journal Title: Pediatrics
  • URL: http://dx.doi.org/10.1016/j.braindev.2011.11.004
  • Peer Reviewed
• [Journal Article] Twenty-one-year course of adult-onset Rasmussen's encephalitis and bilateral uveitis : case report (2010)
  • Author(s): Kashihara K, Ohno M, Takahashi Y
  • Journal Title: J Neurol Sci Volume: 294(1-2) Pages: 127-30
  • URL: http://dx.doi.org/10.1016/j.jns.2010.03.016
  • Peer Reviewed
• [Journal Article] Nationwide survey(incidence, clinical course, prognosis) of Rasmussen s encephalitis (2010)
  • Author(s): Ayako Muto, Hirokazu Oguni, Yukitoshi Takahashi, Yukiyoshi Shirasaka, Yukio Sawaishi, Tamami Yano, Toru Hoshida, Hitoshi Osaka, Satoru Nakasu, Noriyuki Akasaka, Kenji Sugai, Akie Miyamoto, Satoru Takahashi, Motomasa Suzuki, Iori Ohmori, Shin Nabatame, Makiko Osawa
  • Journal Title: Brain Dev Volume: 32-6 Pages: 445-53
  • DOI: doi:10.1016/j.braindev.2009.10.004
  • Peer Reviewed
• [Journal Article] Detection of DNA of six human herpesviruses in the cerebrospinal fluid of immunocompetent non-herpetic acute limbic encephalitis patients (2010)
  • Author(s): Yoshikawa T, Asano Y, Takahashi Y
  • Journal Title: Microbiol Immunol Volume: 54-8 Pages: 471-474
  • DOI: doi:10.1111/j.1348-0421.2010.00234.x
  • Peer Reviewed
• [Journal Article] Correspondence : a further case of opsoclonus-myoclonus syndrome associated with Mycoplasma pneumoniae infection (2010)
  • Author(s): Takashi Shiihara, Yukitoshi Takahashi
  • Journal Title: European Journal of Pediatrics Volume: 169-5 Pages: 639
  • DOI: doi:10.1007/s00431-009-1105-y
  • Peer Reviewed
• [Journal Article] A substantial number of Rasmussen syndrome patients have increased IgG, CD4+T cells, TNFα, and Granzyme B in CSF (2009)
  • Author(s): Takahashi Yukitoshi, Jyun Mine, Yuko Kubota, Etsuko Yamazaki, Tateki Fujiwara
  • Journal Title: Epilepsia Volume: 50 Pages: 1419-1431
  • DOI: doi:10.1111/j.1528-1167.2008.01977.x
  • Peer Reviewed
• [Journal Article] Stiripentol open study in Japanese patients with Dravet syndrome (2009)
  • Author(s): Yushi Inoue, Yoko Ohtsuka, Hirokazu Oguni, Jun Tohyama, Hiroshi Baba, Katsuyuki Fukushima, Hideyuki Ohtani, Yukitoshi Takahashi, Shunya Ikeda
  • Journal Title: Epilepsia Volume: 50-11 Pages: 2362-2368
  • DOI: doi:10.1111/j.1528-1167.2009.02179.x
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• [Journal Article] Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in non-herpetic acute limbic encephalitis (2009)
  • Author(s): Ichiyama T, Takahashi Y, Matsushige T, Kajimoto M, Fukunaga S, Furukawa S
  • Journal Title: J Neurol Volume: 256 Pages: 1846-1850
  • DOI: doi:10.1007/s00415-009-5207-2
  • Peer Reviewed
• [Journal Article] Autoantibodies to glutamate receptor GluRepsilon2 in a patient with limbic encephalitis associated with relapsing polychondritis (2009)
  • Author(s): Kashihara K, Kawada S, Takahashi Y
  • Journal Title: J Neurol Sci Volume: 287 Pages: 275-277
  • URL: http://dx.doi.org/10.1016/j.jns.2009.08.004
  • Peer Reviewed
• [Journal Article] Detection of anti-glutamate receptorε2 and anti-N-methyl-D-aspartate receptor antibodies in a patient with sporadic Creutzfeldt
  • Author(s): Koji Fujita, Tatsuhiko Yuasa, Yukitoshi Takahashi, Keiko Tanak a, Shuji Hashiguchi, Katsuhito Adachi, Yuishin Izumi, Ryuji Kaji
  • Journal Title: Jakob disease, J Neurol
  • DOI: doi:10.1007/s00415-011-6291-7
  • Peer Reviewed
• [Presentation] シンポジウム2小児免疫性中枢神経疾患の臨床-最近の進歩-非ヘルペス性辺縁系脳炎の免疫病態 (2011)
  • Author(s): 高橋幸利、山崎悦子、最上友紀子、西村成子
  • Organizer: 第53回日本小児神経学会
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  • Year and Date: 20110526-28
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  • Organizer: 第44回日本てんかん学会
  • Place of Presentation: 岡山
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• [Presentation] Limbic encephalitis associated with ovarian teratoma (2009)
  • Author(s): Takahashi Y., Yamazaki, E., Nishimura, S., Tsunogae, H
  • Organizer: 19th World Congress of Neurology
  • Place of Presentation: Bangkok
  • Year and Date: 20091024-30
• [Book] 小児てんかん診療マニュアル改訂第2版
  • Author(s): 高橋幸利
  • Publisher: 診断と治療社
• [Remarks] 「急性辺縁系脳炎等の自己免疫介在性脳炎・脳症」の診断スキーム-20101017
  • URL: http://www.shizuokamind.org/wp-content/uploads/2012/03/06-1-2-15.pdf
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  • Industrial Property Rights Holder: 国立病院機構
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• [Patent(Industrial Property Rights)] 頭部保護具 (2011)
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• [Patent(Industrial Property Rights)] 抗体測定方法及び小脳炎の診断マーカー (2009)
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  • Filing Date: 2009-08-26