Emmanuel During, MD

All Publications

• AUTOMATED DETECTION OF ISOLATED REM SLEEP BEHAVIOR DISORDER (IRBD) DURING SINGLE NIGHT IN-LAB VIDEO-POLYSOMNOGRAPHY (PSG) USING COMPUTER VISION Adaimi, G., Gupta, N., Mottaghi, A., Yeung, S., Mignot, E., Alahi, A., During, E. OXFORD UNIV PRESS INC. 2022: A282

  View details for Web of Science ID 000838094800637

• AT-HOME DETECTION OF REM SLEEP BEHAVIOR DISORDER USING A MACHINE LEARNING APPROACH AND WRIST ACTIGRAPHY Brink-Kjaer, A., Gupta, N., Marin, E., Zitser, J., Sum-Ping, O., Hekmat, A., Bueno, F., Cahuas, A., Jennum, P., Sorensen, H., Mignot, E., During, E. OXFORD UNIV PRESS INC. 2022: A243-A244

  View details for Web of Science ID 000838094800549

• ISOLATED REM SLEEP BEHAVIOR DISORDER IS ASSOCIATED WITH 24-HOUR RHYTHM DISRUPTION Winer, J., Lok, R., Cahuas, A., Bueno, F., Poston, K., Mormino, E., Zeitzer, J., During, E. OXFORD UNIV PRESS INC. 2022: A125

  View details for Web of Science ID 000838094800278

• Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder. Sleep Miglis, M. G., Zitser, J., Schneider, L., During, E., Jaradeh, S., Freeman, R., Gibbons, C. H. 2021

  Abstract

  STUDY OBJECTIVES: To define the clinical implications of cutaneous phosphorylated alpha-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated REM sleep behavior disorder (iRBD).METHODS: Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients.RESULTS: P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use.CONCLUSIONS: In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

  View details for DOI 10.1093/sleep/zsab172

  View details for PubMedID 34244806

• Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder Miglis, M., Zitser-Koren, J., Rajan, S., During, E., Schneider, L., Jaradeh, S., Freeman, R., Gibbons, C. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for Web of Science ID 000729283605330

• Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci. Proceedings of the National Academy of Sciences of the United States of America Ambati, A., Hillary, R., Leu-Semenescu, S., Ollila, H. M., Lin, L., During, E. H., Farber, N., Rico, T. J., Faraco, J., Leary, E., Goldstein-Piekarski, A. N., Huang, Y., Han, F., Sivan, Y., Lecendreux, M., Dodet, P., Honda, M., Gadoth, N., Nevsimalova, S., Pizza, F., Kanbayashi, T., Peraita-Adrados, R., Leschziner, G. D., Hasan, R., Canellas, F., Kume, K., Daniilidou, M., Bourgin, P., Rye, D., Vicario, J. L., Hogl, B., Hong, S. C., Plazzi, G., Mayer, G., Landtblom, A. M., Dauvilliers, Y., Arnulf, I., Mignot, E. J. 2021; 118 (12)

  Abstract

  Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 * 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R 2 = 0.15; P < 2.0 * 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

  View details for DOI 10.1073/pnas.2005753118

  View details for PubMedID 33737391

• Dreem Open Datasets: Multi-Scored Sleep Datasets to Compare Human and Automated Sleep Staging IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING Guillot, A., Sauvet, F., During, E. H., Thorey, V. 2020; 28 (9): 1955–65

  Abstract

  Sleep stage classification constitutes an important element of sleep disorder diagnosis. It relies on the visual inspection of polysomnography records by trained sleep technologists. Automated approaches have been designed to alleviate this resource-intensive task. However, such approaches are usually compared to a single human scorer annotation despite an inter-rater agreement of about 85% only. The present study introduces two publicly-available datasets, DOD-H including 25 healthy volunteers and DOD-O including 55 patients suffering from obstructive sleep apnea (OSA). Both datasets have been scored by 5 sleep technologists from different sleep centers. We developed a framework to compare automated approaches to a consensus of multiple human scorers. Using this framework, we benchmarked and compared the main literature approaches to a new deep learning method, SimpleSleepNet, which reach state-of-the-art performances while being more lightweight. We demonstrated that many methods can reach human-level performance on both datasets. SimpleSleepNet achieved an F1 of 89.9% vs 86.8% on average for human scorers on DOD-H, and an F1 of 88.3% vs 84.8% on DOD-O. Our study highlights that state-of-the-art automated sleep staging outperforms human scorers performance for healthy volunteers and patients suffering from OSA. Considerations could be made to use automated approaches in the clinical setting.

  View details for DOI 10.1109/TNSRE.2020.3011181

  View details for Web of Science ID 000568675100008

  View details for PubMedID 32746326

• Sleep Issues in Parkinson's Disease and Their Management. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Zuzuárregui, J. R., During, E. H. 2020

  Abstract

  Parkinson's disease (PD) is an alpha-synucleinopathy that leads to prominent motor symptoms including tremor, bradykinesia, and postural instability. Nonmotor symptoms including autonomic, neurocognitive, psychiatric symptoms, and sleep disturbances are also seen frequently in PD. The impact of PD on sleep is related to motor and nonmotor symptoms, in addition to the disruption of the pathways regulating sleep by central nervous system pathology. Rapid eye movement sleep behavior disorder is a parasomnia that can lead to self-injury and/or injury to partners at night. Restless legs syndrome is a subjective sensation of discomfort and urge to move the legs prior to falling asleep and can lead to insomnia and reduced sleep quality. Excessive daytime sleepiness is common in PD and exerts a negative impact on quality of life in addition to increasing the risk of falls. Obstructive sleep apnea is a breathing disorder during sleep that can cause frequent awakenings and excessive daytime sleepiness. Circadian rhythm dysfunction can lead to an advanced or delayed onset of sleep in patients and create disruption of normal sleep and wake times. All of these disorders are common in PD and can significantly reduce sleep quantity, sleep quality, or quality of life for patients and caretakers. Treatment approaches for each of these disorders are distinct and should be individualized to the patient. We review the literature regarding these common sleep issues encountered in PD and their treatment options.

  View details for DOI 10.1007/s13311-020-00938-y

  View details for PubMedID 33029723

• Factors Hampering the Discovery of New Therapeutics for Rapid Eye Movement Sleep Behavior Disorder. JAMA neurology During, E. H., Schenck, C. H. 2019

  View details for DOI 10.1001/jamaneurol.2019.2062

  View details for PubMedID 31329218

• AI vs Humans for the diagnosis of sleep apnea. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference Thorey, V., Hernandez, A. B., Arnal, P. J., During, E. H. 2019; 2019: 1596–1600

  Abstract

  Polysomnography (PSG) is the gold standard for diagnosing sleep obstructive apnea (OSA). It allows monitoring of breathing events throughout the night. The detection of these events is usually done by trained sleep experts. However, this task is tedious, highly time-consuming and subject to important inter-scorer variability. In this study, we adapted our state-of-the-art deep learning method for sleep event detection, DOSED, to the detection of sleep breathing events in PSG for the diagnosis of OSA. We used a dataset of 52 PSG recordings with apnea-hypopnea event scoring from 5 trained sleep experts. We assessed the performance of the automatic approach and compared it to the inter-scorer performance for both the diagnosis of OSA severity and, at the microscale, for the detection of single breathing events. We observed that human sleep experts reached an average accuracy of 75% while the automatic approach reached 81% for sleep apnea severity diagnosis. The F1 score for individual event detection was 0.55 for experts and 0.57 for the automatic approach, on average. These results demonstrate that the automatic approach can perform at a sleep expert level for the diagnosis of OSA.

  View details for DOI 10.1109/EMBC.2019.8856877

  View details for PubMedID 31946201

• Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder. Autonomic neuroscience : basic & clinical Zitser, J., During, E. H., Chiaro, G., Miglis, M. G. 2019; 220: 102553

  Abstract

  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? Blum, D. J., During, E., Barwick, F., Davidenko, P., Zeitzer, J. M. OXFORD UNIV PRESS INC. 2019

  View details for Web of Science ID 000471071000011

• UPPER AIRWAY STIMULATION: TITRATION BEYOND THE ATTENDED POLYSOMNOGRAPHY Liu, S., Poomkonsarn, S., Chou, C., During, E. 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 Chou, C., Poomkonsarn, S., Liu, S. Y., Capasso, R., During, E. 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 During, E. H., Miglis, M. G. 2019; 63: 1–2

  View details for DOI 10.1016/j.sleep.2019.06.001

  View details for PubMedID 31600655

• AI vs Humans for the diagnosis of sleep apnea Thorey, V., Hernandez, A., Arnal, P. J., During, E. H., IEEE IEEE. 2019: 1596–1600

  View details for Web of Science ID 000557295302006

• Drug Treatment of Restless Legs Syndrome in Older Adults. Drugs & aging During, E. H., Winkelman, J. W. 2019

  Abstract

  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 Kim, P., During, E., Miglis, M. 2018; 14 (3): 479–81

  Abstract

  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 Hogg, E., During, E., Tan, E., Athreya, K., Eskenazi, J., Wetheimer, J., Mamelak, A., Alterman, R., Tagliati, M. 2018; 33 (7): 1160-1167
• A case series of REM sleep behavior disorder in pure autonomic failure Clin Auton Res Miglis, M., Muppidi, S., During, E., Jaradeh, J. 2017; 27 (1)

  View details for DOI 10.1007/s10286-016-0386-2

• The Epidemic of Sleep Deprivation: A Modern Curse Huffington Post During, E. 2017
• Hypersomnia: Etiologies Encyclopedia of Sleep During, E., Dimitriu, A., Guilleminault, C. 2017; 2nd
• Sleep and Movement Disorders Sleep and Neurologic Disease Ashbrook, L., During, E. Elsevier. 2017; 1st
• The Functions of Sleep Sleep and Neurologic Disease During, E., Kawai, M. Elsevier. 2017; 1st
• Central Disorders of Hypersomnolence Review of Sleep Medicine During, E., Sullivan, S., Mignot, E. 2017; 4th
• Parasomnias Sleepy or Sleepless: A Clinical Approach to the Sleep Patient During, E., Avidan, A. 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 Osorio, R. S., Ayappa, I., Mantua, J., Gumb, T., Varga, A., Mooney, A. M., Burschtin, O. E., Taxin, Z., During, E., Spector, N., Biagioni, M., Pirraglia, E., Lau, H., Zetterberg, H., Blennow, K., Lu, S., Mosconi, L., Glodzik, L., Rapoport, D. M., de Leon, M. J. 2014; 35 (6): 1318-1324

  Abstract

  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

  View details for PubMedCentralID PMC4022140

• The concept of FDG-PET endophenotype in Alzheimer's disease NEUROLOGICAL SCIENCES During, E. H., Osorio, R. S., Elahi, F. M., Mosconi, L., de Leon, M. J. 2011; 32 (4): 559-569

  Abstract

  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

  View details for PubMedCentralID PMC3831649

• A Critical Review of Dissociative Trance and Possession Disorders: Etiological, Diagnostic, Therapeutic, and Nosological Issues CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE During, E. H., Elahi, F. M., Taieb, O., Moro, M., Baubet, T. 2011; 56 (4): 235-242

  Abstract

  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 Osorio, R. S., Pirraglia, E., Agueera-Ortiz, L. F., During, E. H., Sacks, H., Ayappa, I., Walsleben, J., Mooney, A., Hussain, A., Glodzik, L., Frangione, B., Martinez-Martin, P., de Leon, M. J. 2011; 59 (3): 559-562

  View details for DOI 10.1111/j.1532-5415.2010.03288.x

  View details for Web of Science ID 000288215600031

  View details for PubMedID 21391952

  View details for PubMedCentralID PMC3378676