Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis: new neurochemical and immunological implications

Arch Neurol. 2009 Dec;66(12):1563-6. doi: 10.1001/archneurol.2009.264.


Objective: To characterize factors that contribute to symptomatic narcolepsy and excessive daytime sleepiness in neuromyelitis optica and multiple sclerosis.

Setting: Japanese university hospitals.

Design: Case study.

Patients: Seven Japanese patients whose initial diagnoses were multiple sclerosis and who were exhibiting excessive daytime sleepiness.

Main outcome measures: Lesions on magnetic resonance imaging, cerebrospinal fluid hypocretin-1 levels, and serum anti-aquaporin 4 (AQP4) antibody titer.

Results: Bilateral and symmetrical hypothalamic lesions associated with marked or moderate hypocretin deficiency were found in all 7 cases. Four of these patients met the International Classification of Sleep Disorders 2 narcolepsy criteria. Three patients, including 2 patients with narcolepsy, were seropositive for anti-AQP4 antibody and diagnosed as having neuromyelitis optica-related disorder.

Conclusion: 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 hypocretin deficiency in narcolepsy/excessive daytime sleepiness associated with autoimmune demyelinating diseases.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aquaporin 4 / blood
  • Case-Control Studies
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / cerebrospinal fluid
  • Male
  • Middle Aged
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism*
  • Narcolepsy / complications
  • Narcolepsy / immunology*
  • Narcolepsy / metabolism*
  • Neuromyelitis Optica / complications
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / metabolism*
  • Neuropeptides / cerebrospinal fluid
  • Orexins
  • Young Adult


  • AQP4 protein, human
  • Aquaporin 4
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins