The hypocretin neurotransmission system in myotonic dystrophy type 1.
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.
Ciafaloni
E
E
University of Rochester, Department of Neurology, 601 Elmwood Avenue, Box 673, Rochester, NY 14642, USA. Emma_Ciafaloni@urmc.rochester.edu
Mignot
E
E
Sansone
V
V
Hilbert
J E
JE
Lin
L
L
Lin
X
X
Liu
L C
LC
Pigeon
W R
WR
Perlis
M L
ML
Thornton
C A
CA
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D015331:Cohort Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009223:Myotonic Dystrophy / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000503:physiopathology; D009479:Neuropeptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D064446:Orexin Receptors; D000068797:Orexins; D017286:Polysomnography; D011446:Prospective Studies; D011863:Radioimmunoassay; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000235:genetics; D012893:Sleep Wake Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics
D005819:Genetic Markers; C578630:HCRTR1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide