RT Journal Article
SR Electronic
T1 The hypocretin neurotransmission system in myotonic dystrophy type 1
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 226
OP 230
DO 10.1212/01.wnl.0000296827.20167.98
VO 70
IS 3
A1 Ciafaloni, E.
A1 Mignot, E.
A1 Sansone, V.
A1 Hilbert, J. E.
A1 Lin, L.
A1 Lin, X.
A1 Liu, L. C.
A1 Pigeon, W. R.
A1 Perlis, M. L.
A1 Thornton, C. A.
YR 2008
UL http://n.neurology.org/content/70/3/226.abstract
AB 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. AHI=apnea/hypopnea index; DM1=myotonic dystrophy type 1; EDS=excessive daytime sleepiness; ESS=Epworth Sleepiness Scale; Hcrt=hypocretin; MIRS=Muscular Impairment Rating Scale; MSL=mean sleep latency; MSLT=multiple sleep latency test; PLM=periodic limb movement; PSG=polysomnography; SL=sleep onset latency; SOREMP=sleep onset REM periods; UM=University of Milan, Italy; URMC=University of Rochester Medical Center.