Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness

Sleep. 2003 May 1;26(3):287-90. doi: 10.1093/sleep/26.3.287.


Study objective: Myotonic dystrophy type 1 is a multisystem disorder with myotonia, muscle weakness, cataracts, endocrine dysfunction, and intellectual impairment. This disorder is caused by a CTG triplet expansion in the 3' untranslated region of the DMPK gene on 19q13. Myotonic dystrophy type 1 is frequently associated with excessive daytime sleepiness, sharing with narcolepsy a short sleep latency and the presence of sleep-onset rapid eye movement periods during the Multiple Sleep Latency Test. Since narcolepsy is characterized by a dysfunction of the hypothalamic hypocretin system, we investigated whether patients with myotonic dystrophy type 1 with excessive daytime sleepiness have abnormalities in the hypocretin system.

Design/participants: Six patients with myotonic dystrophy type 1 complaining of excessive daytime sleepiness and 13 healthy controls without a sleep disorder were included. The patients with myotonic dystrophy type 1 were evaluated using clinical interviews, nocturnal polysomnograms, and Multiple Sleep Latency Tests. All patients had a confirmed genetic diagnosis for DM1 and were HLA typed. Cerebrospinal fluid hypocretin-1 levels were measured using a direct radioimmunoassay in patients and controls.

Setting: University hospital sleep laboratory.

Interventions: N/A.

Measurement and results: The mean sleep latency on Multiple Sleep Latency Tests was abnormal in all patients (< 5 minutes in 2, < or = 8 in 4) and 2 sleep-onset rapid eye movement periods were observed in 2 subjects. All patients were HLA-DQB1*0602 negative. Hypocretin-1 levels were significantly lower in patients versus controls (p < 0.001); 1 case with 2 sleep-onset rapid eye movement periods had hypocretin-1 levels in the range generally observed in narcolepsy (< 110 pg/mL). Three cases had intermediate levels (110-200 pg/mL). Hypocretin-1 levels did not correlate clinically with disease severity or duration or with subjective or objective sleepiness reports.

Conclusions: A dysfunction of the hypothalamic hypocretin system may mediate sleepiness and abnormal Multiple Sleep Latency Test results in patients with myotonic dystrophy type 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Carrier Proteins / cerebrospinal fluid*
  • Carrier Proteins / genetics
  • Chromosomes, Human, Pair 19 / genetics
  • Disability Evaluation
  • Disorders of Excessive Somnolence / diagnosis
  • Disorders of Excessive Somnolence / epidemiology
  • Disorders of Excessive Somnolence / etiology*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Middle Aged
  • Myotonic Dystrophy / cerebrospinal fluid*
  • Myotonic Dystrophy / complications*
  • Myotonic Dystrophy / genetics
  • Myotonin-Protein Kinase
  • Neuropeptides / cerebrospinal fluid*
  • Neuropeptides / genetics
  • Orexins
  • Polysomnography / instrumentation
  • Protein Serine-Threonine Kinases / genetics
  • Severity of Illness Index


  • Carrier Proteins
  • DMPK protein, human
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Myotonin-Protein Kinase
  • Protein Serine-Threonine Kinases

Associated data

  • OMIM/160900