Emmanuel Mignot

Clinical Focus

• Sleep Disorders

Professional Education

Postdoctoral Advisees

Yosef Appelbaum , Minae Kawashima , Birgitte Kornum , Benjamin Scott , Simon Warby , Karin Weiner

Web Site Links

• http://www-med.Stanford.EDU/school/Psychiatry/narcolepsy/

Industry Relationships

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Research Interests

Research interests focus on mechanisms underlying disorders of excessive sleepiness, neurochemical mechanisms of arousal state control, and the genetics of sleep disorders with emphasis on Narcolepsy.

Clinical studies are mostly aimed at better defining the symptoms of narcolepsy (sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep) using questionnnaire based evaluations and sleep recording studies. Blood samples are also collected for human genetic studies. Clinical and genetic data is entered in a database containing more than 500 narcoleptic subjects (family members and control subjects not included). Functional immaging studies are performed in human narcoleptic patients during cataplexy. Genomic studies are performed to identify susceptibility factors. CSF analysis in various clincial subgroups is performed to measure hypocretin levels.

Pharmacological studies are performed in both human narcoleptic patients and in a canine model. Clinical trials are routinely conducted. Canine pharmacology experiments have led to the pharmacological dissection of the mode of action of antidepressants and amphetamine-like stimulants in narcolepsy. EEG analysis, in vivo dialysis, single unit recording and local drug injections are also being performed to identify the neurobiological substatum underlying sleep abnormalities in narcolepsy. Critical neurochemical systems such as the hypothalamic hypocretin/orexin system, the mesolimbic dopaminergic systems and pontine cholinergic systems have also been identified and are being intensively studied.

Genetic and genomic studies are being performed in both humans and dogs. A positional cloning project identified the hypocretin (orexin) receptor 2 mutation as the canine narcolepsy gene. Mutation screening in hypocretin peptide and receptor genes is being performed in human and canine narcolepsy. Functional studies are carried out to study the effect of any potential...

Clinical Trials

• Measured Hypocretin Levels and Recovery After Hip Surgery Enrolling by Invitation

Publications

• Why we sleep: the temporal organization of recovery. Mignot E, PLoS Biol. 2008; 6 (4): e106
• Anomalous hypothalamic responses to humor in cataplexy. Reiss AL, Hoeft F, Tenforde AS, Chen W, Mobbs D, Mignot EJ. PLoS One. 2008; 3 (5): e2225
• CSF hypocretin-1 assessment in sleep and neurological disorders. Bourgin P, Zeitzer JM, Mignot E. Lancet Neurol. 2008; 7 (7): 649-62
• Sleep and EEG features in genetic models of Down syndrome. Colas D, Valletta JS, Takimoto-Kimura R, Nishino S, Fujiki N, Mobley WC, Mignot E. Neurobiol Dis. 2008; 30 (1): 1-7
• Excessive daytime sleepiness: population and etiology versus nosology. Mignot E, Sleep Med Rev. 2008; 12 (2): 87-94