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2003 Fiscal Year Final Research Report Summary

Low hypocretin levels depend on narcolepsy or hypersomnia?

Research Project

Project/Area Number 14570907
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

SHIMIZU Tetsuo  Akita University, School of Medicine, Professor, 医学部, 教授 (90170977)

Project Period (FY) 2002 – 2003
Keywordshypocretin / orexin / narcolepsy / idiopathic hypersomnia / sleep apnea syndrome / Niemann-pick type C / GBS / HLA
Research Abstract

We have conducted two parts of research (1)hypocretin levels with hypersomnia patients and (2)the autoimmune hypothesis of narcolepsy.
(1)Hypocretin levels with hypersomnia patients.
It is not clear whether the low hypocretin levels depend on narcolepsy or hypersomnia. In order to clear this question, we measured the samples of patients with narcolepsy-cataplexy (N/C), narcolepsy without cataplexy (N/noC), essential hypersomnia (EHS), idiopathic hypersomnia (IHS), sleep apnea syndrome (SAS), Niemann-pick type C (NPC) and neurological disorders.
In 25 patients with N/C, 20 patients with N/C and DR2+ had low hypocretin levels. While 5 patients with N/C and DR2-had normal levels. In 10 patients with N/noC, 4 patients with N/noC and DR2+ had low levels and remaining 6 patients had normal levels. The patients with EHS (n=6), IHS (n=8) and SAS (n=16) had normal levels. In 2 patients with NPC, one patient with cataplexy had intermediate level and the other without cataplexy had normal level. In … More 200 patients with neurological disorders, only several patients with Guillain-Barre syndrome (GBS) had low levels.
Low hypocretin levels only depends on the disease of N/C and DR2+, not the condition of hypersomnia On the other hand, we found some patients with hypersomnia and hypothalamic lesion due to tumor or demyelinating disorders.
(2)The autoimmune hypothesis of narcolepsy.
Human narcolepsy has been shown to be closely associated with a specific HLA. Because most diseases associated with a specific HLA are autoimmune in nature, the finding suggests that autoimmunity is involved in the pathophysiology of narcolepsy. However, at present, all attempts to demonstrate that human narcolepsy is an autoimmune disease have failed. Thus, it is important to know whether hypocretin changes are found in any definite neuroimmunological diseases (NID).
Samples of CSF were obtained from 52 Japanese patients with NID (GBS, n=28, Fisher syndrome n=12, CIDP, n=12) and 48 patients with non-NID.
Levels of CSF hypocretin-1 did not differ between the non-NID patients and the healthy controls previously reported (280pg/ml). In the 28 patients with GBS, 7 patients had lower levels and 5 patients had intermediate levels. Five out of 12 patients with Fisher syndrome and 1 out of 12 patients with CIDP had intermediate levels. Seven GBS patients with low hypocretin-1 levels were clinically severe cases (tetraplegia, dyspnea). Antibodies to gangliosides can be seen in the plasma and CSF of approximately 25% of patients. Sixteen of 21 GBS subjects tested had anti-ganglioside antibodies. There was also no correlation between hypocretin-1 levels and anti-ganglioside antibodies. The mechanism for low hypocretin-1 in GBS is unclear but may involve immune-mediated hypothalamic dysfunction. A subset of GBS and Fisher syndrome may be a good model for studying possible autoimmune damage to the hypocretin system in narcolepsy. Less

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kanbayashi T (a), Shimizu T et al.: "CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia."J Sleep Res. 11(1). 91-93 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanbayashi T (b), Shimizu T et al.: "CSF Hypocretin Concentrarion in Various Neurological Disorders and Sleep Apnea Syndrome."Sleep. 25A. A497-A498 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小林由佳, 清水徹男ほか: "カタプレキシーと睡眠麻痺を主徴とし早期の診断が困難であったナルコレプシー 非典型例における髄液ヒポクレチン1(オレキシンA)定量の有用性について"臨床神経学. 42(3). 233-236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanbayashi T (a), Shimizu T et al.: "Hypocretin Deficiency in Niemann-Pick type C with Cataplexy"Neuropediatrics. 34(1). 52-53 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kubota H, Shimizu T et al.: "Decreased cerebrospinal fluid hypocretin-1 levels near the onset of narcolepsy in two prepuberal children"Sleep. 26(5). 555-557 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arii J, Shimizu T et al.: "The significance of CSF hypocretin-1 (orexin-A) measurements in pediatric and adolescent neurologic disorders"Sleep. 26A. A129-A130 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka Y, Shimizu T et al.: "Decreased CSF Hypocretin-1 (Orexin-A) Level In Narcolepsy Without Cataplexy"Sleep. 26A. A282 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kato T, Shimizu T et al.: "Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions."Intern Med.. 42(8). 743-745 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanbayashi T (b), Shimizu T et al.: "CSF hypocretin measures in patients with obstructive sleep apnea."J Sleep Res.. 12(4). 339-341 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishino S, Shimizu T et al.: "CSF hypocretin levels in Guillain-Barre syndrome and other inflammatory neuropathies."Neurology. 61(6). 823-825 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Abe M, Shimizu T et al.: "Secondary hypersomnia cases due to hypocretin-deficiency."SLEEP. 27A(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "CSF Hypocretin-1 (Orexin-A) Measurement in Pediatric and Teenager Patients with Hypersomnia and/or Cataplexy."SLEEP. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oka Y, Shimizu T et al.: "Low CSF hypocretin-1/orexin-A in hypersomnia secondary to multiple sclerosis with hypothalamic lesion"J Neurology. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia."J Sleep Res. 11(1). 91-93 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "CSF Hypocretin Concentrarion in Various Neurological Disorders and Sleep Apnea Syndrome."Sleep. 25A. A497-A498 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi Y, Miyamoto M, Miyamoto T, Yamazaki K, Hirata K, Kanbayashi T, Shimizu T.: "Nacrolepsy manifesting initially as cataplexy and sleep paralysis : usefulness of CSF hypocretin-1 examination for early diagnosi"Rinsho Shinkeigaku. 42(3). 233-236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "Hypocretin Deficiency in Niemann-Pick type C with Cataplexy"Neuropediatrics. 34(1). 52-53 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kubota H, Shimizu T et al.: "Decreased cerebrospinal fluid hypocretin-1 levels near the onset of narcolepsy in two prepuberal children"Sleep. 26(5). 555-557 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Arii J, Shimizu T et al.: "The significance of CSF hypocretin-1 (orexin-A) measurements in pediatric and adolescent neurologic disorders"Sleep. 26A. A129-A130 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka Y, Shimizu T et al.: "Decreased CSF Hypocretin-1 (Orexin-A) Level In Narcolepsy Without Cataplexy"Sleep. 26A. A282 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kato T, Shimizu T et al.: "Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions."Intern Med.. 42(8). 743-745 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "CSF hypocretin measures in patients with obstructive sleep apnea"J Sleep Res. 12(4). 339-341 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishino S, Shimizu T et al.: "CSF hypocretin levels in Guillain-Barre syndrome and other inflammatory neuropathies."Neurology. 61(6). 823-825 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Abe M, Shimizu T et al.: "Secondary hypersomnia cases due to hypocretin-deficiency."Sleep. 27A(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanbayashi T, Shimizu T et al.: "CSF Hypocretin-1 (Orexin-A) Measurement in Pediatric and Teenager Patients with Hypersomnia and/or Cataplexy"Sleep. 27A(in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oka Y, Shimizu T et al.: "Low CSF hypocretin-1/orexin-A in hypersomnia secondary to multiple sclerosis with hypothalamic lesion"J Neurology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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