Download PDF
Schlaf 2015; 04(04): 199-204
DOI: 10.1055/s-0038-1626150
Review
Schattauer GmbH

Narkolepsie – Aktuelles zur Pathophysiologie

ULF KALLWEIT
1   Schlaf-Wach-Epilepsie-Zentrum, Universitätsklinik für Neurologie, Inselspital Bern, Freiburgstrasse 18 3010 Bern, Schweiz Tel. +41 (0)31/632 3066, Email: ulf.kallweit@insel.ch
› Author Affiliations
Further Information

Publication History

Publication Date:
12 February 2018 (online)

    Permissions and Reprints

Narkolepsie ist eine seltene neurologische Erkrankung mit den Hauptsymptomen Tagesschläfrigkeit und Kataplexie. Es wird eine immunvermittelte Pathogenese postuliert, bei der sowohl genetische Faktoren (HLA-DQB1*06:02) wie auch Umweltfaktoren (Streptokokken, H1N1-Virus bzw. -Impfung) von Bedeutung sind und an deren Ende der Untergang von Hypokretin-produzierenden Zellen im Hypothalamus steht. Die aktuellen neuroimmunologischen Erkenntnisse helfen bei der Entwicklung innovativer therapeutischer Strategien.

 

  • Literatur

  • 1 Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva P. Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology 2002; 58: 1826-1833.
    CrossrefPubMedGoogle Scholar
  • 2 Dauvilliers Y, Montplaisir J, Molinari N. et al. Age at onset of narcolepsy in two large populations of patients in France and Quebec. Neurology 2001; 57: 2029-2033.
    CrossrefPubMedGoogle Scholar
  • 3 Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369: 499-511.
    CrossrefPubMedGoogle Scholar
  • 4 Luca G, Haba-Rubio J, Dauvilliers Y. et al. Clinical, polysomnographic and genome- wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study. J Sleep Res 2013; 22: 482-495.
    CrossrefPubMedGoogle Scholar
  • 5 Tafti M, Hor H, Dauvilliers Y. et al., DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep 2014; 37: 19-25.
    CrossrefPubMedGoogle Scholar
  • 6 Mignot E, Lin L, Rogers W. et al. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet 2001; 68: 686-699.
    CrossrefPubMedGoogle Scholar
  • 7 Mignot E, Lammers GJ, Ripley B. et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002; 59: 1553-1562.
    CrossrefPubMedGoogle Scholar
  • 8 Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev 2005; 9: 269-310.
    CrossrefPubMedGoogle Scholar
  • 9 Mathis J, Hess CW, Bassetti C. Isolated mediotegmental lesion causing narcolepsy and rapid eye movement sleep behaviour disorder: a case evidencing a common pathway in narcolepsy and rapid eye movement sleep behaviour disorder. J Neurol Neurosurg Psychiatry 2007; 78: 427-429.
    PubMedGoogle Scholar
  • 10 American Academy of Sleep Medicine. International classification of sleep disorders. 3rd. ed. Darien, IL: American Academy of Sleep Medicine; 2014
    Google Scholar
  • 11 Sakurai T. Orexin deficiency and narcolepsy. Curr Opin Neurobiol 2013; 23: 760-766.
    CrossrefPubMedGoogle Scholar
  • 12 Mueller-Eckhardt G, Meier-Ewert K, Schendel DJ, Reinecker FB, Multhoff G, Mueller-Eckhardt C. HLA and narcolepsy in a German population. Tissue Antigens 1986; 28: 163-169.
    PubMedGoogle Scholar
  • 13 Mignot E. Genetic and familial aspects of narcolepsy. Neurology 1998; 50: S16-22.
    CrossrefPubMedGoogle Scholar
  • 14 Gough SCL, Simmonds MJ. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr Genomics 2007; 8: 453-465.
    CrossrefPubMedGoogle Scholar
  • 15 Pelin Z, Guilleminault C, Risch N. et al. HLA- DQB1*06:02 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. Tissue Antigens 1998; 51: 96-100.
    CrossrefPubMedGoogle Scholar
  • 16 Hallmayer J, Faraco J, Lin L. et al. Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 2009; 41: 708-711.
    CrossrefPubMedGoogle Scholar
  • 17 Aran A, Lin L, Nevsimalova S. et al. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 2009; 32: 979-983.
    CrossrefPubMedGoogle Scholar
  • 18 Nohynek H, Jokinen J, Partinen M. et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One 2012; 7: e33536
    CrossrefPubMedGoogle Scholar
  • 19 Wijnans L, Lecomte C, de Vries C. et al. The incidence of narcolepsy in Europe: before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine 2013; 31: 1246-1254.
    CrossrefPubMedGoogle Scholar
  • 20 Oberle D, Drechsel-Bäuerle U, Schmidtmann I, Mayer G, Keller-Stanislawski B. Incidence of Narcolepsy in Germany. Sleep 2015; Mar 14 ii sp-00656–14. [Epub ahead of print]
    Google Scholar
  • 21 Jacob L, Leib R, Ollila HM, Bonvalet M, Adams CM, Mignot E. Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development. Brain Behav Immun 2015; 47: 44-57.
    CrossrefPubMedGoogle Scholar
  • 22 Winstone AM, Stellitano L, Verity C. et al. Clinical features of narcolepsy in children vaccinated with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in England. Dev Child. 2013
    PubMedGoogle Scholar
  • 23 Dauvilliers Y, Montplaisir J, Cochen V. et al. Post-H1N1 narcolepsy-cataplexy. Sleep 2010; 33: 1428-1430.
    CrossrefPubMedGoogle Scholar
  • 24 Pizza F, Peltola H, Sarkanen T, Moghadam KK, Plazzi G, Partinen M. Childhood narcolepsy with cataplexy: comparison between post-H1N1 vaccination and sporadic cases. Sleep Med 2014; 15: 262-265.
    CrossrefPubMedGoogle Scholar
  • 25 Han F, Lin L, Warby SC. et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol 2011; 70: 410-417.
    CrossrefPubMedGoogle Scholar
  • 26 Han F, Lin L, Li J, Dong XS, Mignot E. Decreased incidence of childhood narcolepsy 2 years after the 2009 H1N1 winter flu pandemic. Ann Neurol 2013; 73: 560.
    CrossrefPubMedGoogle Scholar
  • 27 Carlander B, Puech-Cathala AM, Jaussent I. et al. Low vitamin D in narcolepsy with cataplexy. PLoS One 2011; 6: e20433.
    CrossrefPubMedGoogle Scholar
  • 28 Ahmed SS, Volkmuth W, Duca J. et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med. 2015 7. 294ra105.
    PubMedGoogle Scholar
  • 29 Cvetkovic-Lopes V, Bayer L, Dorsaz S. et al. Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. J Clin Invest 2010; 120: 713-719.
    CrossrefPubMedGoogle Scholar
  • 30 Juji T, Satake M, Honda Y, Doi Y. HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive. Tissue Antigens 1984; 24: 316-319.
    CrossrefPubMedGoogle Scholar
  • 31 Thannickal TC, Moore RY, Nienhuis R. et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27: 469-474.
    CrossrefPubMedGoogle Scholar
  • 32 Partinen M, Kornum B, Plazzi G, Jennum P, Julkunen I, Vaarala O. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurology 2014; 13: 600-613.
    CrossrefPubMedGoogle Scholar
  • 33 Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL. Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss?. Brain 2010; 133: 1300-1311.
    CrossrefPubMedGoogle Scholar
  • 34 Liblau RS, Vassalli A, Seifinejad A, Tafti M. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy. Lancet Neurol 2015; 14: 318-328
    CrossrefPubMedGoogle Scholar
  • 35 Dauvilliers Y, Bassetti C, Lammers GJ. et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol 2013; 12: 1068-1075.
    CrossrefPubMedGoogle Scholar
  • 36 Alshaikh MK, Tricco AC, Tashkandi M, Mamdani M, Straus SE, BaHammam AS. Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. J Clin Sleep Med 2012; 8: 451-458.
    CrossrefPubMedGoogle Scholar
  • 37 Weinhold SL, Seeck-Hirschner M, Nowak A. et al. The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res 2014; 262: 8-13.
    CrossrefPubMedGoogle Scholar
  • 38 Valko PO, Khatami R, Baumann CR, Bassetti CL. No persistent effect of intravenous immunoglobulins in patients with narcolepsy with cataplexy. J Neurol 2008; 255: 1900-1903.
    CrossrefPubMedGoogle Scholar
  • 39 Dauvilliers Y, Abril B, Mas E, Michel F, Tafti M. Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment. Neurology 2009; 73: 1333-1334.
    CrossrefPubMedGoogle Scholar
  • 40 Knudsen S, Biering-Sørensen B, Kornum BR. et al. Early IVIg treatment has no effect on post-H1N1 narcolepsy phenotype or hypocretin deficiency. Neurology 2012; 79: 102-103.
    CrossrefPubMedGoogle Scholar