Sleep and Biological Rhythms

, Volume 17, Issue 1, pp 123–140 | Cite as

Clinical characteristics of symptomatic narcolepsy or hypersomnia: an analysis of 182 consecutive cases with neurological disorders associated with hypersomnolence

  • H. OnoEmail author
  • T. Kanbayashi
  • A. Imanishi
  • T. Ayabe
  • Y. Sagawa
  • K. Tsutsui
  • Y. Ohmori
  • M. Takeshima
  • S. Nishino
  • T. Shimizu
Original Article



Symptomatic narcolepsy is characterized as low orexin (hypocretin) levels (≤ 110 pg/ml) due to neurological diseases. However, we have experienced the cases that show symptoms similar to narcolepsy, complaining of pathological sleepiness even in cases with intermediate orexin levels (110–200 pg/ml). Therefore, we reevaluated the previously reported cases to make the concept of disease to the group in which the orexin concentration is intermediate.


Although orexin-deficient symptomatic narcolepsy has been reported worldwide, facilities that are capable of measuring orexin are still limited. Currently, our laboratory handles with almost all the CSF samples from Asian countries for determining orexin levels. We measured over 2500 cases including 182 cases suspected of symptomatic narcolepsy/hypersomnolence. Therefore, we subdivided these cases into three groups according to CSF orexin levels, low orexin group (≤ 110 pg/ml), intermediate orexin group (110–200 pg/ml), and normal orexin group (> 200 pg/ml). We defined “symptomatic hypersomnia” for hypersomnolence cases with intermediate CSF orexin levels. MSLT was recommended but not necessary. Short sleep latency (< 8 min) without SOREMPs should be observed on MSLT when performed. We compared symptoms (excessive daytime sleepiness and cataplexy) and objective measures (mean sleep latency and number of SOREMPs in MSLT) among the three groups, attempting to characterize the “symptomatic hypersomnia” group.


Among the 182 cases with clinical hypersomnolence, there were 32 cases of symptomatic narcolepsy (16%) and 14 cases of symptomatic hypersomnia (8%). Causative diseases of symptomatic narcolepsy cases consist of immune-mediated demyelinating disorders (34%) and neurodegenerations (19%), whereas those of symptomatic hypersomnia are immune-mediated demyelinating disorders (43%) and encephalopathies (14%). Significant differences were not found between orexin levels and the existence of cataplexy, SOREMPs, and short sleep latency among three hypersomnolence groups. From these results, we found that it is difficult to estimate orexin concentration from subjective symptoms and PSG/MSLT findings.


We identified that 32 symptomatic narcolepsy and 14 cases of symptomatic hypersomnolence with intermediate CSF orexin levels. We proposed these latter cases as a novel category of “symptomatic hypersomnia”. Currently, symptomatic hypersomnia cases with intermediate orexin levels or short sleep latency (< 8 min) without SOREMPs were not classified as a specific entity. However, symptomatic hypersomnia had similar severity of hypersomnolence symptoms to symptomatic narcolepsy. Therefore, these cases including equivalent pathophysiology are enough to make a comparable category as “symptomatic hypersomnia”. Since it is difficult to estimate the orexin concentration from subjective symptoms and physiological findings (PSG/MSLT), further studies for the characterization of “symptomatic hypersomnia” and understanding its pathophysiology are necessary.


Hypersomnolence Narcolepsy Hypersomnia Orexin Sleep disorder 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This study was approved by ethical committees at Akita University and it is conformed to the provisions of the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Japanese Society of Sleep Research 2018

Authors and Affiliations

  1. 1.Department of Systems Pharmacology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of NeuropsychiatryAkita University Graduate School of MedicineAkitaJapan
  3. 3.International Institute for Integrative Sleep Medicine (WPI-IIIS)University of TsukubaTsukubaJapan
  4. 4.Division of Allergy, Department of Medical SpecialtiesNational Center for Child Health and DevelopmentTokyoJapan
  5. 5.Sleep and Circadian Neurobiology LaboratoryStanford University School of MedicinePalo AltoUSA

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