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2011 Fiscal Year Final Research Report

Evaluation of etiology for symptomatic narcolepsy and CNS iron metabolism in narcolepsy with RLS

Research Project

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Project/Area Number 21591500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionAkita University

Principal Investigator

KANBAYASHI Takashi  秋田大学, 大学院・医学系研究科, 准教授 (50323150)

Project Period (FY) 2009 – 2011
Keywordsナルコレプシー / オレキシン / 2次性過眠症 / 脳内鉄代謝 / むずむず脚症候群
Research Abstract

(1) Narcolepsy occurs during the course of various neurological conditions. A recent meta-analysis indicated that 10 out of 116 symptomatic cases of narcolepsy are associated with multiple sclerosis, a disease of autoimmune demyelination. Symptomatic narcoleptic cases consist of heterogeneous disease conditions, but the orexin systems are often impaired in these narcolepsy/EDS cases. Since, serum anti.aquaporin 4 (AQP4=NMO) antibody titer were positive, seven Japanese patients were diagnosed as neuromyelitis optica (NMO) related disorder. Bilateral and symmetrical hypothalamic lesions associated with marked or moderate orexin deficiency were found in all 7 cases. Four of these patients met the ICSD 2 narcolepsy criteria. Since AQP4 is highly expressed in the hypothalamic periventricular regions, an immune attack on AQP4 may be partially responsible for the bilateral and hypothalamic lesions and orexin deficiency in narcolepsy/EDS associated with autoimmune demyelinating diseases. Gaini … More ng the basic knowledge of symptomatic narcolepsy in immune mediated conditions will not be useful only for selecting the most appropriate treatment and predicting the prognosis of the disease but also for understanding the etiological mechanism of narcolepsy.
(2) Periodic leg movements during sleep (PLMS) are often associated with restless legs syndrome (RLS). Reduced ferritin and elevated transferrin levels (with normal or low iron levels) in CSF (as indicators of low brain iron) are reported in PLMS/RLS subjects. A much higher incidence (25-50% vs.-5% in general population) of PLMS is reported in narcoleptic patients. Since altered dopaminergic neurotransmissions are suggested in both diseases and since iron is a co-factor for dopamine synthesis (thyrosine hydoroxylase), we evaluated CSF ferritin, transferrin and iron in patients with orexin deficient narcolepsy in the study. Patients with orexin deficient narcolepsy had higher CSF transferrin and iron levels compared to control subjects. There was no difference in CSF ferritin levels between the two groups. As seen in RLS subjects, an increase in transferrin was observed in narcoleptic subjects. However, normal ferritin and increased iron levels in these subjects may possibly suggest a higher utilization of iron or a dysregulation of iron metabolites in narcolepsy. It is not known if these findings are direct or indirect (such as a compensatory increase in dopaminergic synthesis) to orexin deficiency, and whether or not this contributes to the high incidence of PLMS in narcolepsy. Less

  • Research Products

    (22 results)

All 2012 2011 2010 2009

All Journal Article (19 results) (of which Peer Reviewed: 18 results) Presentation (2 results) Book (1 results)

  • [Journal Article] A patient with anti-aquaporin 4 antibody presenting hypersomnolence as the initial symptom and symmetrical hypothalamic lesions2012

    • Author(s)
      Deguchi K, Kono S, Deguchi S, Morimoto N, Ikeda M, Kurata T, Ikeda Y, Matsuura T, Kanbayashi T, Takahashi T, Abe K
    • Journal Title

      J Neurol Sci

      Volume: 312巻1-2号 Pages: 18-20

    • Peer Reviewed
  • [Journal Article] A case with anti-galactocerebroside antibody-positive Mycoplasma pneumoniae meningoencephalitis presenting secondary hypersomnia2012

    • Author(s)
      Sugeno N, Kawaguchi N, Hasegawa T, Kuroda T, Nakashima I, Kanbayashi T, Kusunoki S, Aoki M
    • Journal Title

      Epub ahead of print

  • [Journal Article] Possible mechanism of secondary narcolepsy with a long sleep time following surgery for craniopharyngioma2012

    • Author(s)
      Sakuta K, Nakamura M, Komada Y, Yamada S, Kawana F, Kanbayashi T, Inoue Y
    • Journal Title

      Intern Med

      Volume: 51巻4号 Pages: 413-7

    • Peer Reviewed
  • [Journal Article] Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features2012

    • Author(s)
      Ko Tsutsui, Takashi Kanbayashi, Keiko Tanaka, Shuken Boku, Wakako Ito, Jun Tokunaga, Akane Mori, Yasuo Hishikawa, Tetsuo Shimizu, Seiji Nishino
    • Journal Title

      BMC Psychiatry

      Volume: 12(1) Pages: 37

    • Peer Reviewed
  • [Journal Article] Alcohol Has a Dose-Related Effect on Parasympathetic Nerve Activity During Sleep2011

    • Author(s)
      Sagawa Y, Kondo H, Matsubuchi N, Takemura T, Kanayama , Kaneko Y, Kanbayashi T, Hishikawa Y, Shimizu T
    • Journal Title

      Alcohol Clin Exp Res

      Volume: 35巻11号 Pages: 2093-2100

    • Peer Reviewed
  • [Journal Article] Anhidrosis associated with hypothalamic lesions related to anti-aquaporin 4 autoantibody2011

    • Author(s)
      Sekiguchi T, Ishibashi S, Kubodera T, Fukabori J, Uezato A, Kanbayashi T, Takahashi T, Yokota T, Mizusawa H
    • Journal Title

      J Neurol

      Volume: 258巻12号 Pages: 2293-2295

    • Peer Reviewed
  • [Journal Article] The pathophysiologic basis of secondary narcolepsy and hypersomnia2011

    • Author(s)
      Kanbayashi T, Sagawa Y, Takemura F, Ito SU, Tsutsui K, Hishikawa Y, Nishino S
    • Journal Title

      Curr Neurol Neurosci Rep

      Volume: 20巻1号 Pages: 45-49

    • Peer Reviewed
  • [Journal Article] Narcolepsy due to Parkinson's disease with a decrease in cerebrospinal-fluid orexin : a case report2011

    • Author(s)
      WAKAI M, KANBAYASHI T
    • Journal Title

      Sleep and Biological Rhythms

      Volume: 9巻2号 Pages: 127-129

    • Peer Reviewed
  • [Journal Article] Relationship between clinical characteristics of narcolepsy and CSF orexin-A levels2011

    • Author(s)
      Nakamura M, Kanbayashi T, Sugiura T, Inoue Y
    • Journal Title

      J Sleep Res

      Volume: 20巻 Pages: 45-49

    • Peer Reviewed
  • [Journal Article] Hypocretin ligand deficiency in narcolepsy : recent basic and clinical insights2011

    • Author(s)
      Ritchie C, Okuro M, Kanbayashi T, Nishino S
    • Journal Title

      Curr Neurol Neurosci Rep

      Volume: 10巻3号 Pages: 180-189

    • Peer Reviewed
  • [Journal Article] 抗NMDA受容体脳炎と診断された男性例2011

    • Author(s)
      筒井幸, 徳永純, 森朱音, 近藤類, 岩谷光貴, 伏見進, 大川聡, 菅原純哉, 苗村育郎, 神林崇, 清水徹男
    • Journal Title

      精神科治療学

      Volume: 26巻2号 Pages: 235-239

    • Peer Reviewed
  • [Journal Article] Rapid increase to double breathing rate appears during REM sleep in synchrony with REM-a higher CNS control of breathing?2010

    • Author(s)
      Sato S, Kanbayashi T, Kondo H, Matsubuchi N, Ono K, Shimizu T
    • Journal Title

      Adv Exp Med Biol

      Volume: 669巻 Pages: 249-252

    • Peer Reviewed
  • [Journal Article] 精神病様症状を呈した抗NMDA受容体脳炎の1例2010

    • Author(s)
      筒井幸, 大内東香, 手島和暁, 徳永純, 石黒英明, 西成民夫, 武村史, 森朱音, 神林崇, 清水徹男
    • Journal Title

      精神医学

      Volume: 52巻11号 Pages: 1107-1109

    • Peer Reviewed
  • [Journal Article] 経過中にposterior reversible encephalopathy syndrome (PRES)と甲状腺癌を合併した視神経脊髄炎の47歳女性例2010

    • Author(s)
      嶋崎晴雄, 安藤綾子, 中村優子, 神林崇, 田中惠子, 中野今治
    • Journal Title

      日本内科学会雑誌

      Volume: 99巻8号 Pages: 233-235

    • Peer Reviewed
  • [Journal Article] CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome2009

    • Author(s)
      Kanbayashi T, Shimizu T, Nishino S, et al
    • Journal Title

      SLEEP

      Volume: 32巻3号 Pages: 181-7

    • Peer Reviewed
  • [Journal Article] Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson's disease2009

    • Author(s)
      Asai H, Kanbayashi T, Shimizu T, Ueno S, et al
    • Journal Title

      Clin Neurol Neurosurg

      Volume: 111巻4号 Pages: 341-344

    • Peer Reviewed
  • [Journal Article] Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis : new neurochemical and immunological implications2009

    • Author(s)
      Kanbayashi T, Shimizu T, Nishino S, et al
    • Journal Title

      Arch Neurol

      Volume: 66巻2号 Pages: 1563-1566

    • Peer Reviewed
  • [Journal Article] Narcolepsy as an initial manifestation of neuromyelitis optica with anti-aquaporin-4 antibody2009

    • Author(s)
      Baba T, Nakashima I, Kanbayashi T, Itoyama Y, et al
    • Journal Title

      J Neurol

      Volume: 256巻2号 Pages: 287-288

    • Peer Reviewed
  • [Journal Article] A patient with anti-aquaporin 4 antibody who presented with recurrent hypersomnia, reduced orexin (hypocretin) level and symmetrical hypothalamic lesions2009

    • Author(s)
      Nozaki H, Shimohata T, Kanbayashi T, Sagawa Y, Nishizawa M, et al
    • Journal Title

      Sleep Med

      Volume: 10巻2号 Pages: 53-55

    • Peer Reviewed
  • [Presentation] EVALUATION OF CSF HISTAMINE IN THE PATIENTS WITH NARCOLEPSY OR VARIOUS DISEASES2010

    • Author(s)
      Ito W, Kanbayashi T, Kodama T, Kikuchi Y, Arii J, Shimizu K, Aizawa R, Chiba S, Yano T, Shimizu T
    • Organizer
      Annual Meeting of the Associated Professional Sleep Societies
    • Place of Presentation
      San Antonio, TX, USA
    • Year and Date
      2010-06-07
  • [Presentation] Secondary Narcolepsy2009

    • Author(s)
      Kanbayashi T
    • Organizer
      Asia Sleep Research Society Meeting
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-24
  • [Book] Publisher : Springer ; 1 edition2009

    • Author(s)
      Kanbayashi T, Nakamura M, Shimizu T, Nishino S
    • Publisher
      Narcolepsy : A Clinical Guide. Meeta Goswami, S.R. Pandi-Perumal, Michael J. Thorpy, Eds. Symptomatic Narcolepsy or Hypersomnia With and Without Hypocretin (Orexin) Deficiency

URL: 

Published: 2013-07-31  

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