The hypocretin neurotransmission system in myotonic dystrophy type 1.

Abstract

BACKGROUND:

Patients with myotonic dystrophy type 1 (DM1) frequently have symptoms of excessive daytime sleepiness (EDS). Some patients with DM1 show sleep-onset REM, similar to that observed in narcolepsy. Narcolepsy is characterized by impaired hypocretin (Hcrt) neurotransmission.

OBJECTIVE:

To test for dysregulation of Hcrt neurotransmission in a prospective cohort of patients with DM1.

METHODS:

Hcrt levels in CSF were measured by radioimmunoassay. Sleep physiology was assessed by overnight polysomnography (PSG) and a multiple sleep latency test (MSLT). Splicing of Hcrt receptor 1 and 2 (HcrtR1 and HcrtR2) mRNA was examined in postmortem samples of temporal cortex.

RESULTS:

Seventeen of 38 patients with DM1 reported symptoms of EDS. Among patients with DM1 with EDS who underwent PSG/MSLT, 7 of 13 showed reduced sleep latency, sleep-onset REM, or both. However, CSF Hcrt levels in DM1 (mean 277 pg/mL, n = 38) were not different from controls (mean 277 pg/mL, n = 33). Also, splicing of HcrtR1 and HcrtR2 mRNA in patients with DM1 was similar to controls.

CONCLUSIONS:

Excessive daytime sleepiness and dysregulation of REM sleep occur frequently in patients with myotonic dystrophy type 1 (DM1). However, the pathophysiologic basis is distinct from narcolepsy, as patients with DM1 do not have a consistent defect of Hcrt release or receptor splicing.

• Authors: E Ciafaloni, E Mignot, V Sansone, J E Hilbert, L Lin, X Lin, L C Liu, W R Pigeon, M L Perlis, C A Thornton
• Journal: Neurology (Neurology) Vol. 70 Issue 3 Pg. 226-30 (Jan 15 2008) ISSN: 1526-632X [Electronic] United States
• PMID: 18195268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Genetic Markers
• HCRTR1 protein, human
• Intracellular Signaling Peptides and Proteins
• Neuropeptides
• Orexin Receptors
• Orexins
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide

Topics

• Adult
• Aged
• Alternative Splicing (genetics)
• Cohort Studies
• Comorbidity
• DNA Mutational Analysis
• Female
• Genetic Markers
• Genetic Predisposition to Disease (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (analysis, cerebrospinal fluid)
• Male
• Middle Aged
• Mutation (genetics)
• Myotonic Dystrophy (cerebrospinal fluid, complications, physiopathology)
• Neuropeptides (analysis, cerebrospinal fluid)
• Orexin Receptors
• Orexins
• Polysomnography
• Prospective Studies
• Radioimmunoassay
• Receptors, G-Protein-Coupled (genetics)
• Receptors, Neuropeptide (genetics)
• Sleep Wake Disorders (cerebrospinal fluid, diagnosis, genetics)