Emmanuel During, MD, is psychiatrist and neurologist with board certification in sleep medicine on Stanford faculty since 2016 as Clinical Assistant Professor with a primary appointment in the Department of Psychiatry – Division of Sleep Medicine, and a secondary appointment in the Department of Neurology. He directs the Stanford Parasomnia Clinic where he evaluates the broad spectrum of parasomnias, including REM sleep behavior disorder (RBD, abnormal dream-enactment) and other parasomnias such as sleepwalking, sleep talking, sleep terrors and confusional arousals. Lying at the interface of psychiatry, neurology and sleep, the Parasomnia Clinic functions as a platform for high-level specialized clinical care and direct enrollment into clinical trials, particularly for patients with RBD, which in a number of cases is an early sign of neurodegeneration such as Parkinson's disease or dementia with Lewy bodies.
Dr. During is receiving federal and industry grant support for conducting research on RBD. He is currently the PI of an investigator-initiated sponsored trial investigating a new drug in treatment-refractory RBD (NCT04006925), and serves as site PI for a NIA grant supporting a nation-wide consortium, the North American Prodromal Synucleinopathy Consortium (NAPS), laying the groundwork for a first neuroprotective trial in the pre-Parkinson's stage of RBD, (NCT03623672). In 2018, he was invited to join a task force group of experts in RBD commissioned by the American Academy of Sleep Medicine (AASM) to issue the upcoming 2020 Clinical Guidelines for the management of RBD. He was invited the same year to join the International RBD Study Group (IRBD-SG), a group of world-experts in RBD ranging from clinicians to basic scientists. His most recent research interest pertains to wearable sleep devices that can potentially monitor RBD activity in patients home environment and facilitate early diagnosis.
- Sleep Medicine
Clinical Assistant Professor, Psychiatry and Behavioral Sciences - Stanford Center for Sleep Sciences and Medicine
Clinical Assistant Professor, Neurology & Neurological Sciences
Honors & Awards
Resident Best Teaching Award, Cedars-Sinai Medical Center, CA (2015)
Medal Award for best Doctoral Thesis defense, Paris 7 University, France (2008)
Psychiatry Resident of the Year Award, Paris 7 University, France (2008)
Boards, Advisory Committees, Professional Organizations
Member, International RBD Study Group (IRBDSG) (2018 - Present)
Member, American Academy of Sleep Medicine (AASM) REM sleep Behavior Disorder (RBD) Task Force (2018 - Present)
Board Member, California Sleep Society (2019 - Present)
Member, American Academy of Sleep Medicine (2016 - Present)
Member, American Academy of Neurology (2015 - Present)
Member, Conseil National de l'Ordre des Medecins - France (2008 - Present)
Board Certification: Sleep Medicine, American Board of Psychiatry and Neurology (2017)
Fellowship, Stanford University, Sleep Medicine (2016)
Board Certification: Neurology, American Board of Psychiatry and Neurology (2015)
Residency, Cedars-Sinai Medical Center, CA, Neurology (2015)
Internship, Banner Good Samaritan Hospital, AZ, Internal Medicine (2012)
Board Certification, Psychiatry, Paris Diderot University, France (2008)
MD, Louis Pasteur University, Medical School, France (2003)
Current Research and Scholarly Interests
Improving diagnostics and therapeutics in RBD, using home ambulatory devices including wearable actigraphy, dry-EEG, to power clinical trials based on objective outcomes of RBD activity.
Controlling symptoms of RBD testing drugs rigorously.
Predicting the course of neurodegeneration using deep phenotyping using clinical and serum biomarkers, measures of autonomic impairment, skin biopsy, microbiome
Natural History Study of Synucleinopathies
Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain. After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson disease. The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA - the most aggressive of the synucleinopathies.
North American Prodromal Synucleinopathy Consortium
This study will enroll participants with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), for the purpose of preparing for a clinical trial of neuroprotective treatments against synucleinopathies.
Once-Nightly Sodium Oxybate for Treatment of Excessive Daytime Sleepiness and Cataplexy in Narcolepsy
The purpose of this study is to determine whether once-nightly FT218 is safe and effective for the treatment of excessive daytime sleepiness and cataplexy in subjects with narcolepsy.
Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate
This study is the first clinical trial using sodium oxybate for the treatment of REM sleep behavior disorder (RBD). Sodium oxybate is a drug approved by FDA for the treatment of narcolepsy which has been used "off label" to treat patients with severe RBD. This drug has shown to be effective and well tolerated in patients with RBD (Shneerson, 2009; Liebenthal, 2016; Moghadam, 2017).
- Factors Hampering the Discovery of New Therapeutics for Rapid Eye Movement Sleep Behavior Disorder. JAMA neurology 2019
Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder.
Autonomic neuroscience : basic & clinical
2019; 220: 102553
Autonomic dysfunction is common in REM-sleep behavior disorder (RBD). Several studies have demonstrated abnormalities in heart rate variability, cardiac scintigraphy, and cardiovascular autonomic reflex testing. In addition, the type and severity of these abnormalities may correlate with rate of phenoconversion from idiopathic RBD (iRBD) to manifest neurodegenerative disease. This article summarizes the current literature on autonomic impairment in iRBD, with specific focus on the role of autonomic impairment as a potential biomarker of disease progression. REM sleep physiology and relevant anatomy is also discussed in relation to the central autonomic network and autonomic neurodegeneration.
View details for DOI 10.1016/j.autneu.2019.05.005
View details for PubMedID 31219036
RESTLESS LEG SYNDROME: DOES IT START WITH A GUT FEELING?
OXFORD UNIV PRESS INC. 2019
View details for Web of Science ID 000471071000011
UPPER AIRWAY STIMULATION: TITRATION BEYOND THE ATTENDED POLYSOMNOGRAPHY
OXFORD UNIV PRESS INC. 2019
View details for Web of Science ID 000471071002121
THE EFFECT OF SLEEPING POSITION ON THE EFFICACY OF HYPOGLOSSAL NERVE STIMULATION
OXFORD UNIV PRESS INC. 2019
View details for Web of Science ID 000471071002125
- Clinical trials in REM sleep behavior disorder: an urgent need for better evidence. Sleep medicine 2019; 63: 1–2
Drug Treatment of Restless Legs Syndrome in Older Adults.
Drugs & aging
Restless legs syndrome (RLS) has a high prevalence in the elderly and can impact sleep quality and sleep quantity, reduce quality of life (QoL), and increase the risk of falls during episodes of night-time ambulation. In patients unable to verbalize their sensory symptoms, certain behavioral cues may help with the diagnosis. A state of brain iron deficiency could play a central role in the pathophysiology of RLS and be upstream to a series of dysfunctions that are not limited to the dopaminergic system. Management should initially emphasize lifestyle modifications and reduction of all possible iatrogenic contributors while maintaining a state of normal-high peripheral iron stores. Oral iron, in patients with ferritin levels < 75 μg/dL, appears to be effective, although iron infusions should be considered when more immediate benefit or oral iron have not been effective. When other attempts fail and patients continue to experience chronic RLS symptoms substantially interfering with QoL, pharmacological agents may present a favorable benefit versus risk profile. Such agents may include α-2-δ drugs or dopaminergic agents, after careful consideration of the risk of RLS augmentation with the latter class. In patients with established RLS augmentation from the use of dopaminergic drugs, the addition of α-2-δ agents or low-dose opioids, with subsequent slow tapering of dopaminergic agents, is recommended. With any of these agents, caution should be made with regard to the risk of drug-drug interactions and altered pharmacokinetics in this fragile population. Although showing excellent long-term safety data in non-elderly adults with RLS, studies are needed to ascertain that such treatments are effective and well tolerated in older adults.
View details for DOI 10.1007/s40266-019-00698-1
View details for PubMedID 31347095
A Case of Narcolepsy Type 2 and Postural Tachycardia Syndrome Secondary to Lesions of the Thalamus and Amygdala
JOURNAL OF CLINICAL SLEEP MEDICINE
2018; 14 (3): 479–81
Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy.
View details for PubMedID 29458703
View details for PubMedCentralID PMC5837851
- Sustained quality-of-life improvements over 10 years after deep brain stimulation for dystonia Movement Disorders 2018; 33 (7): 1160-1167
A case series of REM sleep behavior disorder in pure autonomic failure
Clin Auton Res
2017; 27 (1)
View details for DOI 10.1007/s10286-016-0386-2
- The Epidemic of Sleep Deprivation: A Modern Curse Huffington Post 2017
- Hypersomnia: Etiologies Encyclopedia of Sleep 2017; 2nd
- Sleep and Movement Disorders Sleep and Neurologic Disease Elsevier. 2017; 1st
- The Functions of Sleep Sleep and Neurologic Disease Elsevier. 2017; 1st
- Central Disorders of Hypersomnolence Review of Sleep Medicine 2017; 4th
- Parasomnias Sleepy or Sleepless: A Clinical Approach to the Sleep Patient Springer . 2015; 1st
The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals
NEUROBIOLOGY OF AGING
2014; 35 (6): 1318-1324
Previous studies have suggested a link between sleep disordered breathing (SDB) and dementia risk. In the present study, we analyzed the relationship between SDB severity, cerebrospinal fluid (CSF) Alzheimer's disease-biomarkers, and the ApoE alleles. A total of 95 cognitively normal elderly participants were analyzed for SDB severity, CSF measures of phosphorylated-tau (p-tau), total-tau (t-tau), and amyloid beta 42 (Aβ-42), as well as ApoE allele status. In ApoE3+ subjects, significant differences were found between sleep groups for p-tau (F[df2] = 4.3, p = 0.017), and t-tau (F[df2] = 3.3, p = 0.043). Additionally, among ApoE3+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was positively correlated with p-tau (r = 0.30, p = 0.023), t-tau (r = 0.31, p = 0.021), and Aβ-42 (r = 0.31, p = 0.021). In ApoE2+ subjects, the apnea and/or hypopnea with 4% O2-desaturation index was correlated with lower levels of CSF Aβ-42 (r = -0.71, p = 0.004), similarly to ApoE4+ subjects where there was also a trend toward lower CSF Aβ-42 levels. Our observations suggest that there is an association between SDB and CSF Alzheimer's disease-biomarkers in cognitively normal elderly individuals. Existing therapies for SDB such as continuous positive airway pressure could delay the onset to mild cognitive impairment or dementia in normal elderly individuals.
View details for DOI 10.1016/j.neurobiolaging.2013.12.030
View details for Web of Science ID 000333970800012
View details for PubMedID 24439479
The concept of FDG-PET endophenotype in Alzheimer's disease
2011; 32 (4): 559-569
Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term "endophenotype" has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term "endophenotype" should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD.
View details for DOI 10.1007/s10072-011-0633-1
View details for Web of Science ID 000292706900004
View details for PubMedID 21630036
A Critical Review of Dissociative Trance and Possession Disorders: Etiological, Diagnostic, Therapeutic, and Nosological Issues
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE
2011; 56 (4): 235-242
Although the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition, acknowledges the existence of dissociative trance and possession disorders, simply named dissociative trance disorder (DTD), it asks for further studies to assess its clinical utility in the DSM-5. To answer this question, we conducted the first review of the medical literature.The MEDLINE, CINAHL, and PsycINFO databases were searched from 1988 to 2010, seeking case reports of DTD according to the DSM or the International Classification of Diseases definitions. For each article, we collected epidemiologic and clinical data, explanatory models used by authors, treatments, and information on the outcome.We found 28 articles reporting 402 cases of patients with DTD worldwide. The data show an equal proportion of female and male patients, and a predominance of possession (69%), compared with trance (31%). Amnesia is reported by 20% of patients. Conversely, hallucinatory symptoms during possession episodes were found in 56% of patients and thus should feature as an important criterion. Somatic complaints are found in 34% of patients. Multiple explanatory models are simultaneously held and appear to be complementary.Data strongly suggest the inclusion of DTD in the DSM-5, provided certain adjustments are implemented. DTD is a widespread disorder that can be understood as a global idiom of distress, probably underdiagnosed in Western countries owing to cultural biases, whose incidence could increase given the rising flow of migration. Accurate diagnosis and appropriate management should result from a comprehensive evaluation both of sociocultural and of idiosyncratic issues, among which acculturation difficulties should systematically be considered, especially in cross-cultural settings.
View details for Web of Science ID 000290063000007
View details for PubMedID 21507280
- GREATER RISK OF ALZHEIMER'S DISEASE IN OLDER ADULTS WITH INSOMNIA JOURNAL OF THE AMERICAN GERIATRICS SOCIETY 2011; 59 (3): 559-562