Narcolepsy and Hypersomnia Waking Up to Orexins | Neurology Grand Rounds (RECORDING)

Tuesday, April 1, 2025, 12:00 AM - Friday, March 31, 2028, 11:59 PM, On Demand

In this recorded Neurology Grand Rounds presentation, Dr. Emmanuel Mignot, Director of Stanford’s Center for Narcolepsy and a globally recognized leader in sleep research, shares a comprehensive talk on the pathophysiology, diagnosis, and treatment of narcolepsy, with broader insights into sleep disorders and brain-autoimmune interactions. Dr. Mignot begins by discussing Narcolepsy origins, from its 19th-century discovery to REM sleep abnormalities, canine models, and ultimately to its autoimmune basis, centered on the loss of orexin-producing neurons in the hypothalamus. He then reviews breakthrough discoveries, in which narcolepsy was traced to a mutation in the orexin receptor 2. Dr. Mignot then moves on to review diagnostic challenges such as the Multiple Sleep Latency Test (MSLT) nad how it has been overused, leading to overdiagnosis of narcolepsy type 2 (without cataplexy), which Dr. Mignot argues is largely a false-positive artifact. He advocates moving beyond MSLT toward machine learning-based EEG analysis that captures more subtle and accurate sleep-wake patterns. Dr. Mignot then addresses Emerging Tools & AI – which his team uses deep learning and hypnodensity modeling to identify narcolepsy-specific EEG signatures and hopes to integrate actigraphy, genetic markers, and survey data into large-scale screening efforts, such as through the UK Biobank. He then moves on to discuss new therapeutics such Sodium oxybate & Orexin receptor agonists (e.g., TAK-861) which show dramatic improvements in wakefulness, surpassing amphetamines in efficacy and offering transformative impact in narcolepsy type 1. He explains how these advances may also help treatment-resistant depression with persistent sleepiness. Dr. Mignot concludes by emphasizing the need to develop physiology-based diagnostics using proteomic markers of sleep deprivation and circadian phase, and to identify the elusive autoreactive T cells or antibodies that cause orexin neuron loss.

  Release Date: April 01, 2025
  Expiration Date: March 31, 2028
  Estimated Time to Complete: 1.0 hours
  Registration Fee: FREE
 *Originally recorded 12/06/2024

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AMA PRA Category 1 Credits™ (1.00 hours), Non-Physician Participation Credit (1.00 hours)

1. Discuss the origins of Narcolepsy.
2. Identify diagnostic challenges such as the Multiple Sleep Latency Test (MSLT)
3. Review breakthrough discoveries in narcolepsy.
4. Discuss emerging tools & AI – such as deep learning and hypnodensity modeling.
5. Discuss new therapeutics which show dramatic improvements in wakefulness.

In support of improving patient care, Stanford Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. 

Credit Designation 
American Medical Association (AMA) 
Stanford Medicine designates this Enduring Material for a maximum of 1.00 AMA PRA Category 1 Credits^TM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity. 

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Cultural and Linguistic Competency
The planners and speakers of this CME activity have been encouraged to address cultural issues relevant to their topic area for the purpose of complying with California Assembly Bill 1195. Moreover, the Stanford University School of Medicine Multicultural Health Portal contains many useful cultural and linguistic competency tools including culture guides, language access information and pertinent state and federal laws.  You are encouraged to visit the Multicultural Health Portal: https://laneguides.stanford.edu/multicultural-health

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Mitigation of Relevant Financial Relationships

Stanford Medicine adheres to the Standards for Integrity and Independence in Accredited Continuing Education.

There are no relevant financial relationships with ACCME-defined ineligible companies for anyone who was in control of the content of this activity, except those listed in the table below. All of the relevant financial relationships listed for these individuals have been mitigated.

Faculty Member Information	Role in activity	Name of commercial interest/Nature of relationship
Kate Therkelsen, MD	Course Director	Nothing to Disclose
Tara Torabi, MD	Planner	Nothing to Disclose
Rachel Walsh, MD	Planner	Nothing to Disclose
Gregory Wong, MD	Planner and Reviewer	Nothing to Disclose
Jose Eduardo Espindola Lima, MD	Planner and Reviewer	Nothing to Disclose
Emmanuel Mignot, MD, PhD	Faculty	Consultant - Takeda, Elsai Inc. Grant/research support - Elsai Inc.