Elucidation of the pathogenesis and development of novel therapies in immune-mediated autonomic neuropathies

• Project/Area Number: 25461276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Koike Haruki 名古屋大学, 医学(系)研究科(研究院), 准教授 (80378174)
• Co-Investigator(Kenkyū-buntansha): IIJIMA Masahiro 名古屋大学, 医学系研究科, 寄附講座講師 (40437041) ; SOBUE Gen 名古屋大学, 大学院医学系研究科, 特任教授 (20148315)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 自律神経ニューロパチー / 自己免疫性自律神経節障害 / 急性自律神経性感覚性ニューロパチー / 免疫性自律神経ニューロパチー / 急性自律性神経感覚性ニューロパチー / ギランバレー症候群 / 急性自律性感覚性ニューロパチー / 急性自律性感覚性運動性ニューロパチー / ニューロパチー

Outline of Final Research Achievements

From the point of view of the autonomic neuropathy, at least three subgroups have been proposed on the basis of the concomitance or absence of sensory or motor dysfunctions: 1. pure autonomic neuropathy, 2. autonomic neuropathy with sensory impairment, and 3. autonomic neuropathy with sensory and motor impairment. Some of the patients with pure autonomic neuropathy had slow progression mimicking neurodegenerative diseases. Pathological findings indicated neuronopathy of the autonomic ganglia in patients with pure autonomic neuropathy, while both autonomic and sensory ganglia were affected in patients with sensory impairment. Intravenous immunoglobulin, plasma exchange, or steroids alone or in combination were suggested to be effective even in cases with long-standing autonomic neuropathy.

Research Products

• [Journal Article] Clinicopathologic features of folate-deficiency neuropathy. (2015)
  • Author(s): Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, Katsuno M, Doi H, Tanaka F, Sobue G.
  • Journal Title: Neurology Volume: 84 Issue: 10 Pages: 1026-1033
  • DOI: 10.1212/wnl.0000000000001343
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): A multicenter, double-blind trial (2015)
  • Author(s): Koike H, Akiyama K, Saito T, Sobue G
  • Journal Title: J Neurol Volume: 262 Issue: 3 Pages: 752-9
  • DOI: 10.1007/s00415-014-7618-y
  • Peer Reviewed
• [Journal Article] 急性自律性感覚性ニューロパチー (2015)
  • Author(s): 小池春樹
  • Journal Title: 日本臨床 Volume: 73 増刊7 Pages: 452-457
• [Journal Article] アミロイドニューロパチー (2015)
  • Author(s): 小池春樹、 祖父江元
  • Journal Title: Peripheral Nerve Volume: 26 Pages: 15-24
• [Journal Article] 急性感覚性ニューロパチーと急性自律神経ニューロパチー (2015)
  • Author(s): 小池春樹
  • Journal Title: BRAIN and NERVE: 神経研究の進歩 Volume: 67 Pages: 1377-1387
• [Journal Article] 血管炎の新しい分類と基本的な考え方 – 中枢神経血管炎の位置づけ (2015)
  • Author(s): 小池春樹、 祖父江元
  • Journal Title: BRAIN and NERVE: 神経研究の進歩 Volume: 67 Pages: 243-248
• [Journal Article] 傍腫瘍性ニューロパチー (2015)
  • Author(s): 大山健、 小池春樹、 祖父江元
  • Journal Title: 日本臨床 Volume: 73 増刊7 Pages: 782-787
• [Journal Article] 抗MAG抗体陽性ニューロパチー (2015)
  • Author(s): 川頭祐一、 小池春樹、 祖父江元
  • Journal Title: 日本臨床 Volume: 73 増刊7 Pages: 440-445
• [Journal Article] インフルエンザ感染を契機にFisher症候群の急激な症候悪化を呈したCIDPの1例 (2015)
  • Author(s): 両角佐織、 安井敬三、 長谷川康博、 小池春樹、 祖父江元
  • Journal Title: Peripheral Nerve Volume: 26 Pages: 93-97
• [Journal Article] IgM M蛋白血症を伴うニューロパチー (2015)
  • Author(s): 川頭祐一、 小池春樹
  • Journal Title: 医学のあゆみ Volume: 255 Pages: 539-542
• [Journal Article] ステロイド治療が有効であったサイトメガロウィルス感染後の急性運動・感覚・自律神経ニューロパチーの1例 (2015)
  • Author(s): 打田祐人、 小池春樹、小栗卓也、加藤秀樹、湯浅浩之、三竹重久
  • Journal Title: 臨床神経学 Volume: 55 Pages: 339-344
  • NAID: 130005073106
• [Journal Article] 脱髄性ニューロパチーランビエ絞輪部における分子病態 (2015)
  • Author(s): 川頭祐一、 小池春樹、 祖父江元
  • Journal Title: Annual Review神経 Volume: 2015 Pages: 219-225
• [Journal Article] Clinicopathological features of sarcoidosis manifesting as generalized chronic myopathy (2015)
  • Author(s): Maeshima S, Koike H, Noda S, Noda T, Nakanishi H, Iijima M, Ito M, Kimura S, Sobue G
  • Journal Title: J Neurol Volume: 262 Issue: 4 Pages: 1035-45
  • DOI: 10.1007/s00415-015-7680-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Axonal loss influences the response to rituximab treatment in neuropathy associated with IgM monoclonal gammopathy with anti-myelin-associated glycoprotein antibody (2015)
  • Author(s): Kawagashira Y, Koike H, Ohyama K, Hashimoto R, Iijima M, Adachi H, Katsuno M, Chapman M, Lunn M, Sobue G
  • Journal Title: J Neurol Sci Volume: 348 Issue: 1-2 Pages: 67-73
  • DOI: 10.1016/j.jns.2014.11.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of intravenous immunoglobulin for treatment of Lambert-Eaton myasthenic syndrome without anti-presynaptic P/Q-type voltage-gated calcium channel antibodies: A case report (2015)
  • Author(s): Okada A, Koike H, Nakamura T, Motomura M, Sobue G
  • Journal Title: Neuromuscul Disord Volume: 25 Issue: 1 Pages: 70-2
  • DOI: 10.1016/j.nmd.2014.08.006
  • Peer Reviewed / Open Access
• [Journal Article] What is the prototype of familial amyloid polyneuropathy? (2014)
  • Author(s): Koike H, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 85 Issue: 7 Pages: 713-713
  • DOI: 10.1136/jnnp-2013-306241
  • Acknowledgement Compliant
• [Journal Article] Muscle atrophy in chronic inflammatory demyelinating polyneuropathy: a computed tomography assessment (2014)
  • Author(s): Ohyama K, Koike H, Katsuno M, Takahashi M, Hashimoto R, Kawagashira Y, Iijima M, Adachi H, Watanabe H, Sobue G
  • Journal Title: Eur J Neurol Volume: 21 Issue: 7 Pages: 1002-10
  • DOI: 10.1111/ene.12426
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Slowly progressive folate-deficiency myelopathy: Report of a case (2014)
  • Author(s): Okada A, Koike H, Nakamura T, Watanabe H, Sobue G
  • Journal Title: J Neurol Sci Volume: 336 Issue: 1-2 Pages: 273-5
  • DOI: 10.1016/j.jns.2013.10.032
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mononeuritis multiplex with tumefactive cellular infiltration in a patient with reactive lymphoid hyperplasia with increased immunoglobulin G4-positive cells (2014)
  • Author(s): Yokoi S, Kawagashira Y, Ohyama K, Iijima M, Koike H, Watanabe H, Tatematsu A, Nakamura S, Sobue G
  • Journal Title: Hum Pathol Volume: 45 Issue: 2 Pages: 427-30
  • DOI: 10.1016/j.humpath.2013.07.047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cutaneous arteritis associated with peripheral neuropathy: two case reports (2014)
  • Author(s): Riku Y, Ikenaka K, Koike H, Niimi Y, Senda J, Hashimoto R, Kawagashira Y, Tomita M, Iijima M, Sobue G
  • Journal Title: J Dermatol Volume: 41 Issue: 3 Pages: 266-7
  • DOI: 10.1111/1346-8138.12416
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunoglobulin G for the Treatment of Chronic Pain: Report of an Expert Workshop (2014)
  • Author(s): Tamburin S, Borg K, Caro XJ, Jann S, Clark AJ, Magrinelli F, Sobue G, Werhagen L, Zanette G, Koike H, Spath PJ, Vincent A, Goebel A
  • Journal Title: Pain Med Volume: 15 Issue: 7 Pages: 1072-82
  • DOI: 10.1111/pme.12319
  • Peer Reviewed
• [Journal Article] Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsy. (2014)
  • Author(s): Sone J, Kitagawa N, Sugawara E, Iguchi M, Nakamura R, Koike H, Iwasaki Y, Yoshida M, Takahashi T, Chiba S, Katsuno M, Tanaka F, Sobue G
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 85(3) Issue: 3 Pages: 354-356
  • DOI: 10.1136/jnnp-2013-306084
  • Peer Reviewed
• [Journal Article] Schwann cell involvement in the peripheral neuropathy of spinocerebellar ataxia type 3. (2014)
  • Author(s): Suga N, Katsuno M, Koike H, Banno H, Suzuki K, Hashizume A, Mano T, Iijima M, Kawagashira Y, Hirayama M, Nakamura T, Watanabe H, Tanaka F, Sobue G
  • Journal Title: Neuropathol Appl Neurobiol. Volume: 40 Issue: 5 Pages: 628-639
  • DOI: 10.1111/nan.12055
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis (2014)
  • Author(s): Riku Y, Atsuta N, Yoshida M, Tatsumi S, Iwasaki Y, Mimuro M, Watanabe H, Ito M, Senda J, Nakamura R, Koike H, Sobue G
  • Journal Title: BMJ Open Volume: 4 Issue: 5 Pages: e005213-e005213
  • DOI: 10.1136/bmjopen-2014-005213
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autonomic manifestations in acute sensory ataxic neuropathy: a case report. (2013)
  • Author(s): Ohyama K, Koike H, Masuda M, Sone J, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, Nakamura T, Watanabe H, Sobue G.
  • Journal Title: Auton Neurosci Volume: 179 Issue: 1-2 Pages: 155-158
  • DOI: 10.1016/j.autneu.2013.03.009
  • Peer Reviewed
• [Journal Article] Autoimmune autonomic ganglionopathy と acute autonomic and sensory neuropathy (2013)
  • Author(s): 小池春樹，祖父江元
  • Journal Title: 臨床神経学 Volume: 53 Pages: 1326-1329
  • NAID: 130004505433
• [Journal Article] Differential recovery in cardiac and vasomotor sympathetic functional markers in a patient with acute autonomic sensory and motor neuropathy. (2013)
  • Author(s): Ohyama K, Yasui K, Hasegawa Y, Morozumi S, Koike H, Sobue G.
  • Journal Title: Intern Med Volume: 52 Pages: 497-502
  • NAID: 130003365895
  • Peer Reviewed
• [Journal Article] Wide range of clinicopathological features in immune-mediated autonomic neuropathies. (2013)
  • Author(s): Koike H, Sobue G.
  • Journal Title: Clin Exp Neuroimmunol Volume: 4 Pages: 46-59
  • Peer Reviewed
• [Journal Article] The spectrum of immune-mediated autonomic neuropathies: insights from the clinicopathological features. (2013)
  • Author(s): Koike H, Watanabe H, Sobue G.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84 Issue: 1 Pages: 98-106
  • DOI: 10.1136/jnnp-2012-302833
  • Peer Reviewed
• [Presentation] アミロイドニューロパチー (2015)
  • Author(s): 小池春樹
  • Organizer: 第68回日本日本自律神経学会総会
  • Place of Presentation: 愛知県名古屋市 ウインクあいち
  • Year and Date: 2015-11-29
  • Invited
• [Presentation] 治療につながる末梢神経病理診断 (2015)
  • Author(s): 小池春樹
  • Organizer: 第33回日本神経治療学会総会
  • Place of Presentation: 愛知県名古屋市 名古屋国際会議場
  • Year and Date: 2015-11-26
  • Invited
• [Presentation] Peripheral neuropathies: from bedside to pathology (2015)
  • Author(s): Koike H
  • Organizer: 52nd Argentine Congress of Neurology
  • Place of Presentation: Mar del Plata, Argentine
  • Year and Date: 2015-09-22
  • Int'l Joint Research / Invited
• [Presentation] Acquired neuropathies manifesting small-fiber predominant loss (2015)
  • Author(s): Koike H
  • Organizer: 2nd Argentine Congress of Neurology
  • Place of Presentation: Mar del Plata, Argentine
  • Year and Date: 2015-09-22
  • Int'l Joint Research / Invited
• [Presentation] Early- vs. late-onset forms of familial amyloid polyneuropathy (2015)
  • Author(s): Koike H
  • Organizer: 2nd Argentine Congress of Neurology
  • Place of Presentation: Mar del Plata, Argentine
  • Year and Date: 2015-09-22
  • Int'l Joint Research / Invited
• [Presentation] 遺伝性圧脆弱性ニューロパチー（HNPP）の臨床病理像と外科治療の試み (2015)
  • Author(s): 小池春樹
  • Organizer: 第26回日本末梢神経学会学術集会
  • Place of Presentation: 長野県松本市 ホテルブエナビスタ
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] 専門医に必要な末梢神経・筋病理学の素養と利用可能な教育資源，研修機会 (2015)
  • Author(s): 小池春樹
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟県新潟市 朱鷺メッセ
  • Year and Date: 2015-05-20
  • Invited
• [Presentation] MORPHOLOGY OF NONMYELINATING SCHWANN CELLS IN CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (2014)
  • Author(s): Haruki Koike, Mie Takahashi, Ken Ohyama, Yuichi Kawagashira, Masahiro Iijima, and Gen Sobue
  • Organizer: Inflammatory Neuropathy Consortium
  • Place of Presentation: Hyatt Regency Hotel, Dusseldorf, Germany
  • Year and Date: 2014-07-13 – 2014-07-16
• [Presentation] Muscle Atrophy in Chronic Inflammatory Demyelinating Polyneuropathy: A Computed Tomography Assessment (2014)
  • Author(s): Ken Ohyama, Haruki Koike, Masahisa Katsuno, Mie Takahashi, Rina Hashimoto, Yuichi Kawagashira, Masahiro Iijima, Hiroaki Adachi, and Gen Sobue
  • Organizer: Inflammatory Neuropathy Consortium
  • Place of Presentation: Hyatt Regency Hotel, Dusseldorf, Germany
  • Year and Date: 2014-07-13 – 2014-07-16
• [Book] 今日の治療指針 2016 (2016)
  • Author(s): 小池春樹、赤水尚史、有賀徹、一瀬雅夫、太田伸生、小澤敬也、金子一成、上條吉人、神田隆、木村正、楠田聡、上阪等、坂部貢、坂本泰二、巽浩一郎、戸倉新樹、永田真、夏目長門、丹生健一、深川雅史ら
  • Total Pages: 2192
  • Publisher: 医学書院
• [Book] 自律神経機能検査 (2015)
  • Author(s): 小池春樹、 祖父江元、田村直俊、岩瀬敏、朝比奈正人、榊原隆次、内田さえ、大林光念、小野弓絵、黒澤美枝子、仙波恵美子、谷山紘太郎、原直人、間野忠明、宮本智之、山元敏正、高橋昭、水本結、上山敬司、安東由喜雄ら
  • Total Pages: 508
  • Publisher: 文光堂
• [Book] 免疫症候群（第2版）I (2015)
  • Author(s): 小池春樹、 祖父江元、田中正美、市山高志、黒澤和大、藤井敬之、藤田之彦、上田昌美、桑原基、神林隆道、小川剛、竹下幸雄、千葉厚郎、桑原聡、中根俊成、鈴木重明、白石一浩、中村龍文、松永晶子、原誠ら
  • Total Pages: 928
  • Publisher: 日本臨床社
• [Book] 今日の診断指針 第7版 (2015)
  • Author(s): 小池春樹、石塚達夫、平本淳、秋山暢、平家俊男、釜田康行、辻貞俊、桃井眞里子、島津岳士、児玉亘弘、丹羽公一郎、木村守次、五十嵐隆、増山理、藤井秀壯、永井宏和、高田徹、渡辺晋一、宮地良樹、冨山桂昭ら
  • Total Pages: 2144
  • Publisher: 医学書院
• [Book] 神経疾患最新の治療2015-2017 (2015)
  • Author(s): 小池春樹、 祖父江元、陣上直人、高橋良輔、松本慎一、高尾洋之、村上雄一、鈴木謙介、兵頭明夫、矢坂正弘、小坂憲司、松井真、竹島多賀夫、武田篤、伊藤秀文、松尾秀徳、荒木信夫、伊藤康夫、城倉健、中島健一ら
  • Total Pages: 310
  • Publisher: 南光堂
• [Book] Handbook of Clinical Neurology (2013)
  • Author(s): Koike H, Sobue G.
  • Publisher: Elsevier