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


METHODS
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.


METHODS
University hospital sleep laboratory.


METHODS
N/A.


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.
Neurology service, Hospital Clinic i Provincial de Barcelona and Institut d'lnvestigació Biomédica August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 33029jmr@comb.es
Jose E
JE
Martínez-Rodríguez
Ling
L
Lin
Alex
A
Iranzo
David
D
Genis
Maria J
MJ
Martí
Joan
J
Santamaria
Emmanuel
E
Mignot
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002352:Carrier Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004185:Disability Evaluation; D006970:Disorders of Excessive Somnolence / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000235:genetics; D065636:Myotonin-Protein Kinase; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000235:genetics; D000068797:Orexins; D017286:Polysomnography / Q000295:instrumentation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012720:Severity of Illness Index
D002352:Carrier Proteins; C585517:DMPK protein, human; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases