Narcolepsy — clinical spectrum, aetiopathophysiology, diagnosis and treatment

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep–wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep–wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the ‘narcoleptic borderland’, including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.In the past 20 years, understanding of the clinical manifestations, aetiopathophysiology, diagnosis and treatment of narcolepsy has greatly advanced. In this Review, Bassetti et al. present these advances, discuss unmet needs and offer future perspectives for the field of narcolepsy.Key pointsNarcolepsy is a rare and often disabling hypothalamic disorder that presents with sleep–wake dysregulation (excessive daytime sleepiness (EDS), cataplexy, hallucinations, sleep paralysis and disturbed sleep) and motor, cognitive, psychiatric, metabolic and autonomic disturbances.Narcolepsy arises from the interaction of genetic and environmental factors, which lead to an immune-mediated selective loss or dysfunction of orexin neurons in the lateral hypothalamus.Patients with narcolepsy type 1 have cataplexy and little or no orexin in cerebrospinal fluid; narcolepsy type 2 is a diagnosis of exclusion requiring ancillary tests ruling out other causes of EDS.Several drugs (including modafinil, sodium oxybate, pitolisant, solriamfetol and methylphenidate) improve narcoleptic symptoms in most patients.More research is needed to understand the clinical spectrum of narcolepsy, the exact mechanisms leading to orexin neuronal loss and the value of new treatments, including orexin agonists and immunomodulation.Awareness of narcolepsy, assessments of treatment efficacy, treatment of children or during pregnancy and management of comorbidities are still suboptimal in narcolepsy and require improvement.

[1]  H. Lassmann,et al.  Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy. , 2013, JAMA neurology.

[2]  R. Rosenberg,et al.  The AWAKEN Survey: Knowledge of Narcolepsy among Physicians and the General Population , 2014, Postgraduate medicine.

[3]  T. Nicholson,et al.  Mnesic imbalance: a cognitive theory about autism spectrum disorders , 2008, Annals of General Psychiatry.

[4]  J. Buitelaar,et al.  Narcolepsy and psychiatry: an evolving association of increasing interest. , 2011, Sleep medicine.

[5]  P. Jennum,et al.  Health, social, and economic consequences of narcolepsy: a controlled national study evaluating the societal effect on patients and their partners. , 2012, Sleep medicine.

[6]  M. Hersberger,et al.  CSF prostaglandin D synthase is reduced in excessive daytime sleepiness , 2006, Journal of Neurology.

[7]  W Bauer,et al.  The other side of the coin. , 1970, IMJ. Illinois medical journal.

[8]  Pedagógia,et al.  Cross Sectional Study , 2019 .

[9]  C. Baumann,et al.  Sleep-Disordered Breathing and Periodic Limb Movements in Narcolepsy with Cataplexy: A Systematic Analysis of 35 Consecutive Patients , 2013, European Neurology.

[10]  F. Fischer.  Epileptoide Schlafzustände , 1878, European Archives of Psychiatry and Neurological Sciences.

[11]  E. Mignot,et al.  Increase of histaminergic tuberomammillary neurons in narcolepsy , 2013, Annals of neurology.

[12]  E. Rüther,et al.  Narcolepsy increased L-PGDS (beta-trace) levels correlate with excessive daytime sleepiness but not with cataplexy. , 2005, Journal of neurology.

[13]  J. Montplaisir,et al.  Periodic leg movements during sleep and wakefulness in narcolepsy , 2007, Journal of sleep research.

[14]  Mahowald,et al.  Presumed REM sleep behavior disorder arising from cataplexy and wakeful dreaming. , 2000, Sleep medicine.

[15]  M. Vidailhet,et al.  Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson's disease. , 2011, Sleep medicine.

[16]  F. Poli,et al.  Olfactory dysfunction in narcolepsy with cataplexy. , 2010, Sleep medicine.

[17]  P M Moodie,et al.  COHORT , 1971, The Medical journal of Australia.

[18]  J. Santamaria,et al.  Hyperkalemic periodic paralysis associated with multiple sleep onset REM periods. , 1999, Sleep.

[19]  I. Jaussent,et al.  Measurement of narcolepsy symptoms , 2017, Neurology.

[20]  M. Edwards,et al.  The distinguishing motor features of cataplexy: a study from video-recorded attacks , 2017, Sleep.

[21]  C. Economo.  SLEEP AS A PROBLEM OF LOCALIZATION , 1930 .

[22]  C. Baumann,et al.  Hypocretins (orexins) and sleep–wake disorders , 2005, The Lancet Neurology.

[23]  S. Stahl,et al.  Continuous cataplexy in a patient with a midbrain tumor , 1980, Neurology.

[24]  C. Bassetti,et al.  Isolated mediotegmental lesion causing narcolepsy and rapid eye movement sleep behaviour disorder: a case evidencing a common pathway in narcolepsy and rapid eye movement sleep behaviour disorder , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  A. Desautels,et al.  HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy. , 2015, American journal of human genetics.

[26]  Sebastiaan Overeem,et al.  Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy , 2010, Nature Genetics.

[27]  T. Kilduff,et al.  Hypocretin-2-Saporin Lesions of the Lateral Hypothalamus Produce Narcoleptic-Like Sleep Behavior in the Rat , 2001, The Journal of Neuroscience.

[28]  Y. Hishikawa,et al.  Anti-NMDA-receptor antibody detected in encephalitis, schizophrenia, and narcolepsy with psychotic features , 2012, BMC Psychiatry.

[29]  A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes , 2012, Neurotherapeutics.

[30]  E. Mignot,et al.  HPLC analysis of CSF hypocretin-1 in type 1 and 2 narcolepsy , 2019, Scientific Reports.

[31]  K. Maski,et al.  Listening to the Patient Voice in Narcolepsy: Diagnostic Delay, Disease Burden, and Treatment Efficacy. , 2017, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[32]  M. N. Pai.  Hypersomnia Syndromes , 1950, British medical journal.

[33]  J. Siegel,et al.  Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy. , 2009, Sleep.

[34]  J. Montplaisir,et al.  Age at onset of narcolepsy in two large populations of patients in France and Quebec , 2001, Neurology.

[35]  J. Mathis,et al.  Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy. , 2016, Sleep.

[36]  J. Buitelaar,et al.  Psychotic symptoms in narcolepsy: phenomenology and a comparison with schizophrenia. , 2009, General hospital psychiatry.

[37]  D. Picchioni,et al.  The month-of-birth pattern in narcolepsy is moderated by cataplexy severity and may be independent of HLA-DQB1*0602. , 2004, Sleep.

[38]  E. Rüther,et al.  [Symptomatology of the narcoleptic syndrome]. , 1972, Der Nervenarzt.

[39]  Sebastiaan Overeem,et al.  Exploring the clinical features of narcolepsy type 1 versus narcolepsy type 2 from European Narcolepsy Network database with machine learning , 2018, Scientific Reports.

[40]  G. Plazzi,et al.  Electroencephalogram paroxysmal θ characterizes cataplexy in mice and children. , 2013, Brain : a journal of neurology.

[41]  Xiao-Li Wang,et al.  Antidepressants for the treatment of narcolepsy: A prospective study of 148 patients in northern China , 2019, Journal of Clinical Neuroscience.

[42]  Y. Hishikawa,et al.  The nature of sleep attack and other symptoms of narcolepsy. , 1968, Electroencephalography and clinical neurophysiology.

[43]  M. Silber,et al.  Comorbidities in a community sample of narcolepsy. , 2017, Sleep medicine.

[44]  N. Dahmen,et al.  Frequency and dependence on body posture of hallucinations and sleep paralysis in a community sample , 2002, Journal of sleep research.

[45]  C. Baird,et al.  The pilot study. , 2000, Orthopedic nursing.

[46]  Allan L. Reiss,et al.  Anomalous Hypothalamic Responses to Humor in Cataplexy , 2008, PloS one.

[47]  G. Lammers,et al.  A remarkable effect of alemtuzumab in a patient suffering from narcolepsy with cataplexy , 2012, Journal of sleep research.

[48]  C. Guilleminault,et al.  Narcolepsy in prepubertal children , 1998, Annals of neurology.

[49]  N Risch,et al.  Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. , 2001, American journal of human genetics.

[50]  E. Mignot,et al.  Primary progressive narcolepsy type 1: The other side of the coin , 2014, Neurology.

[51]  Krahn,et al.  A standardized test for cataplexy. , 2000, Sleep medicine.

[52]  C. Guilleminault,et al.  High Rates of Psychiatric Comorbidity in Narcolepsy: Findings From the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States. , 2014, The Journal of clinical psychiatry.

[53]  T. Roth,et al.  Excessive daytime sleepiness associated with insufficient sleep. , 1983, Sleep.

[54]  S. Carr,et al.  Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior , 1998, Cell.

[55]  J. Siegel,et al.  Cataplexy-related neurons in the amygdala of the narcoleptic dog , 2002, Neuroscience.

[56]  N. Darín,et al.  Psychiatric comorbidity and cognitive profile in children with narcolepsy with or without association to the H1N1 influenza vaccination. , 2015, Sleep.

[57]  U. S. Xyrem,et al.  A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. , 2003, Sleep.

[58]  M. Aldrich,et al.  Idiopathic hypersomnia : A series of 42 patients , 1997 .

[59]  S. Leeder,et al.  A population based study , 1993, The Medical journal of Australia.

[60]  C. Bassetti,et al.  Amygdala dysfunction in narcolepsy‐cataplexy , 2007, Journal of sleep research.

[61]  B. Vaughn,et al.  Symptomatic cataplexy in pontomedullary lesions , 1994, Neurology.

[62]  G. Plazzi,et al.  The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy , 2015, The Journal of Neuroscience.

[63]  E. Mignot,et al.  Decreased incidence of childhood narcolepsy 2 years after the 2009 H1N1 winter flu pandemic , 2013, Annals of neurology.

[64]  K. Ekbom.  Familial multiple sclerosis associated with narcolepsy. , 1966, Archives of neurology.

[65]  E. Mignot,et al.  Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. , 2012, Sleep.

[66]  F. Poli,et al.  Autonomic disturbances in narcolepsy. , 2011, Sleep medicine reviews.

[67]  S. Gammeltoft,et al.  Cerebrospinal Fluid Biomarkers of Neurodegeneration Are Decreased or Normal in Narcolepsy , 2017, Sleep.

[68]  B. Falissard,et al.  Multiple treatment comparison in narcolepsy: a network meta-analysis , 2018, Sleep.

[69]  L. Michel.  Pediatric narcolepsy: clinical and therapeutical approaches. , 2013, Handbook of clinical neurology.

[70]  R. E. Yoss,et al.  Treatment of narcolepsy with Ritalin , 1959, Neurology.

[71]  K. Tokunaga,et al.  Narcolepsy and HLA in the Japanese , 1988, Annals of the New York Academy of Sciences.

[72]  D. Jacome,et al.  Pseudocataplexy , 1984, Neurology.

[73]  S. Maret,et al.  Clinical efficacy of high‐dose intravenous immunoglobulins near the onset of narcolepsy in a 10‐year‐old boy , 2003, Journal of sleep research.

[74]  R G Priest,et al.  Prevalence of narcolepsy symptomatology and diagnosis in the European general population , 2002, Neurology.

[75]  F. Poli,et al.  Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies , 2013, Journal of sleep research.

[76]  E. Mignot,et al.  Genetic association, seasonal infections and autoimmune basis of narcolepsy. , 2013, Journal of autoimmunity.

[77]  C. Good,et al.  Voxel-based morphometry in hypocretin-deficient narcolepsy. , 2002, Sleep.

[78]  J. Harper.  GELINEAU'S NARCOLEPSY RELIEVED BY OPIATES , 1981, The Lancet.

[79]  J. Schwartz,et al.  An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy: Studies in orexin−/− mice and patients , 2008, Neurobiology of Disease.

[80]  B. Feige,et al.  Transient narcolepsy‐cataplexy syndrome after discontinuation of the antidepressant venlafaxine , 2005, Journal of sleep research.

[81]  J. Touchon,et al.  A monozygotic twin pair discordant for narcolepsy and CSF hypocretin-1 , 2004, Neurology.

[82]  F. Poli,et al.  Motor events during REM sleep in patients with narcolepsy-cataplexy: a video-polysomnographic pilot study. , 2011, Sleep medicine.

[83]  N. Guex,et al.  A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. , 2011, American journal of human genetics.

[84]  T. Young,et al.  Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in community adults. , 2006, Brain : a journal of neurology.

[85]  A. Régnault,et al.  Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ? , 2015, Journal of autoimmunity.

[86]  M. Satake,et al.  HLA antigens in Japanese patients with narcolepsy , 1984 .

[87]  H. S. Davis,et al.  A Controlled Study , 1966 .

[88]  D. Waldvogel,et al.  Parkinsonism with excessive daytime sleepiness , 2005, Journal of Neurology.

[89]  E. Mignot,et al.  High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy. , 2013, Sleep.

[90]  J. Buitelaar,et al.  Severe fatigue in narcolepsy with cataplexy , 2012, Journal of sleep research.

[91]  Z. Kutalik,et al.  Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity. , 2016, Sleep.

[92]  C. Bassetti,et al.  Selective REM sleep deprivation in narcolepsy , 2011, Journal of sleep research.

[93]  R. Rappuoli,et al.  Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2 , 2015, Science Translational Medicine.

[94]  C. Guilleminault,et al.  Twin studies in narcolepsy. , 1994, Sleep.

[95]  A. Adamantidis,et al.  Coreleased Orexin and Glutamate Evoke Nonredundant Spike Outputs and Computations in Histamine Neurons , 2014, Cell reports.

[96]  H. Ullum,et al.  CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens , 2019, Nature Communications.

[97]  D. Rye,et al.  Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[98]  S. Nevsimalova,et al.  Narcolepsy in children. , 1994, Sleep.

[99]  V. Pankratz,et al.  Analysis of hypocretin (orexin) antibodies in patients with narcolepsy. , 2005, Sleep.

[100]  M. Ohayon,et al.  Prevalence and consequences of insomnia disorders in the general population of Italy. , 2002, Sleep medicine.

[101]  Damien Gervasoni,et al.  The rat ponto‐medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study , 2002, The European journal of neuroscience.

[102]  T. Scammell,et al.  Loss of hypocretin (orexin) neurons with traumatic brain injury , 2009, Annals of neurology.

[103]  W. J. Adie.  IDIOPATHIC NARCOLEPSY: A DISEASE SUI GENERIS; WITH REMARKS ON THE MECHANISM OF SLEEP , 1926 .

[104]  A. Awada,et al.  A community survey of neurological disorders in Saudi Arabia: the Thugbah study. , 1993, Neuroepidemiology.

[105]  Susumu Tanaka,et al.  Detection of autoantibodies against hypocretin, hcrtrl, and hcrtr2 in narcolepsy: anti-Hcrt system antibody in narcolepsy. , 2006, Sleep.

[106]  S. Carr,et al.  Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. , 1998, Cell.

[107]  J. Schwartz,et al.  Normal cerebrospinal fluid histamine and tele-methylhistamine levels in hypersomnia conditions. , 2012, Sleep.

[108]  C. Saper,et al.  Role of the Medial Prefrontal Cortex in Cataplexy , 2013, The Journal of Neuroscience.

[109]  Poul Jennum,et al.  Neural network analysis of sleep stages enables efficient diagnosis of narcolepsy , 2017, Nature Communications.

[110]  Sebastiaan Overeem,et al.  A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains , 2000, Nature Medicine.

[111]  C. Burgess,et al.  Amygdala Lesions Reduce Cataplexy in Orexin Knock-Out Mice , 2013, The Journal of Neuroscience.

[112]  M. Pressman,et al.  Treatment of narcolepsy with codeine. , 1986, Sleep.

[113]  E. Mignot,et al.  Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation. , 2018, The Lancet. Child & adolescent health.

[114]  S. Nightingale,et al.  The association between narcolepsy and REM behavior disorder (RBD). , 2005, Sleep medicine.

[115]  Manuel Schabus,et al.  Neuroimaging insights into the pathophysiology of sleep disorders. , 2008, Sleep.

[116]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[117]  M. Ohayon,et al.  Increased mortality in narcolepsy. , 2014, Sleep.

[118]  J. Siegel,et al.  Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy , 2018, Science Translational Medicine.

[119]  J. Montplaisir,et al.  Evaluation of Quality of Life in Patients With Narcolepsy Treated With Sodium Oxybate: Use of the 36-Item Short-Form Health Survey in a Clinical Trial , 2016, Neurology and Therapy.

[120]  F E Bloom,et al.  The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[121]  Parkes.  Genetic factors in human sleep disorders with special reference to Norrie disease, Prader–Willi syndrome and Moebius syndrome , 1999, Journal of sleep research.

[122]  G. Plazzi,et al.  A standardized test to document cataplexy. , 2017, Sleep medicine.

[123]  C. Gieger,et al.  Narcolepsy is strongly associated with the TCR alpha locus , 2009, Nature Genetics.

[124]  Mariana Valencia.  Daytime , 2021, TDR: The Drama Review.

[125]  S. le Cessie,et al.  Month of birth is not a risk factor for narcolepsy with cataplexy in the Netherlands , 2011, Journal of Sleep Research.

[126]  B. Högl,et al.  Subjective deficits of attention, cognition and depression in patients with narcolepsy. , 2015, Sleep medicine.

[127]  S. Tufik,et al.  Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study. , 2015, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[128]  N. Feldman,et al.  Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study. , 2016, Sleep.

[129]  E. Werth,et al.  Unusually prolonged rebound cataplexy after withdrawal of fluoxetine , 2005, Neurology.

[130]  E. Mignot,et al.  REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy. , 2007, Sleep medicine.

[131]  J. Klomp,et al.  A review and synthesis , 2010 .

[132]  Jon T. Willie,et al.  Narcolepsy in orexin Knockout Mice Molecular Genetics of Sleep Regulation , 1999, Cell.

[133]  Jon T. Willie,et al.  Involvement of the Lateral Hypothalamic Peptide Orexin in Morphine Dependence and Withdrawal , 2003, The Journal of Neuroscience.

[134]  H. Kraemer,et al.  Stability of cataplexy over several months--information for the design of therapeutic trials. , 1994, Sleep.

[135]  Z. Kutalik,et al.  DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. , 2014, Sleep.

[136]  D. Auer,et al.  Reduced cortical gray matter in narcolepsy: Preliminary findings with voxel-based morphometry , 2002, Neurology.

[137]  E. Mignot,et al.  Narcolepsy is a common phenotype in HSAN IE and ADCA-DN. , 2014, Brain : a journal of neurology.

[138]  M. Edwards,et al.  Complex movement disorders at disease onset in childhood narcolepsy with cataplexy , 2011, Brain : a journal of neurology.

[139]  T. Roth,et al.  Time to response with sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. , 2015, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[140]  M. Yanagisawa,et al.  Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy , 2018, Proceedings of the National Academy of Sciences.

[141]  E. Mignot,et al.  Relationship between CSF hypocretin levels and hypocretin neuronal loss , 2003, Experimental Neurology.

[142]  R. Broughton,et al.  Comparison of the Psychosocial Effects of Epilepsy and Narcolepsy/Cataplexy: A Controlled Study , 1984, Epilepsia.

[143]  C. Saper,et al.  A putative flip–flop switch for control of REM sleep , 2006, Nature.

[144]  J. Hetta,et al.  Autosomal dominant cerebellar ataxia deafness and narcolepsy , 1995, Journal of the Neurological Sciences.

[145]  O. Hassani,et al.  Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle , 2005, The Journal of Neuroscience.

[146]  S. Higgins,et al.  First rapid eye movement sleep periods and sleep-onset rapid eye movement periods in sleep-stage sequencing of hypersomnias. , 2013, Sleep medicine.

[147]  C. Saper,et al.  Concomitant loss of dynorphin, NARP, and orexin in narcolepsy , 2005, Neurology.

[148]  E. Redlich.  Epilegomena zur Narkolepsiefrage , 1931 .

[149]  E. Mignot,et al.  Cataplexy features in childhood narcolepsy , 2008, Movement disorders : official journal of the Movement Disorder Society.

[150]  J. Touchon,et al.  Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset , 2004, Annals of neurology.

[151]  M. Billiard,et al.  CSF immune variables in patients with narcolepsy , 1990, Acta neurologica Scandinavica.

[152]  Sebastiaan Overeem,et al.  The European Narcolepsy Network (EU‐NN) database , 2016, Journal of sleep research.

[153]  C. Shapiro,et al.  A randomized study of solriamfetol for excessive sleepiness in narcolepsy , 2019, Annals of neurology.

[154]  E. Bixler,et al.  Narcolepsy-cataplexy and loss of sphincter control. , 1996, Postgraduate medical journal.

[155]  S. Gammeltoft,et al.  Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency. , 2010, Brain : a journal of neurology.

[156]  P. Jennum,et al.  Morbidity and mortality of middle-aged and elderly narcoleptics. , 2017, Sleep medicine.

[157]  R. Bogan,et al.  Prevalence and Clinical Correlates of a Short Onset REM Period (SOREMP) during Routine PSG. , 2015, Sleep.

[158]  H. Grudden.  Die physiologische und pathologische Schlaftrunkenheit , 1905, Archiv für Psychiatrie und Nervenkrankheiten.

[159]  A. Yamanaka,et al.  Partial ablation of the orexin field induces a sub-narcoleptic phenotype in a conditional mouse model of orexin neurodegeneration , 2018, Sleep.

[160]  E. Mignot,et al.  Late‐onset narcolepsy presenting as rapidly progressing muscle weakness: Response to plasmapheresis , 2005, Annals of neurology.

[161]  M M Mitler,et al.  Treatment of narcolepsy with methamphetamine. , 1993, Sleep.

[162]  D. Fry,et al.  Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy , 1998, Annals of neurology.

[163]  T. Pollmächer,et al.  EFNS guidelines on management of narcolepsy , 2006, European journal of neurology.

[164]  M. Dresler,et al.  Increased lucid dreaming frequency in narcolepsy. , 2015, Sleep.

[165]  T. Roth,et al.  Effect of sodium oxybate on disrupted nighttime sleep in patients with narcolepsy , 2017, Journal of sleep research.

[166]  H. Pijl,et al.  Glucose and fat metabolism in narcolepsy and the effect of sodium oxybate: a hyperinsulinemic-euglycemic clamp study. , 2014, Sleep.

[167]  J. Golmard,et al.  Lucid dreaming in narcolepsy. , 2015, Sleep.

[168]  B. A. Blansjaar,et al.  Isolated Cataplexy of more than 40 Years' Duration , 1991, British Journal of Psychiatry.

[169]  C. Bassetti,et al.  Development of Parkinson and Alzheimer Diseases in Two Cases of Narcolepsy-Cataplexy , 2011, European Neurology.

[170]  M. Ohayon.  Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. , 2013, Sleep medicine.

[171]  C. Bassetti.  Narcolepsy: selective hypocretin (orexin) neuronal loss and multiple signaling deficiencies. , 2005, Neurology.

[172]  I. Jaussent,et al.  Test–Retest Reliability of the Multiple Sleep Latency Test in Central Disorders of Hypersomnolence , 2017, Sleep.

[173]  B. Becher,et al.  T cells in patients with narcolepsy target self-antigens of hypocretin neurons , 2018, Nature.

[174]  E. Mignot,et al.  Diagnostic value of sleep stage dissociation as visualized on a 2-dimensional sleep state space in human narcolepsy , 2017, Journal of Neuroscience Methods.

[175]  J. Schwartz,et al.  Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial , 2013, The Lancet Neurology.

[176]  W. Oertel,et al.  Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. , 2004, Brain : a journal of neurology.

[177]  S. Overeem,et al.  Weak with laughter , 1999, The Lancet.

[178]  R. Hess,et al.  Some results of clinical studies on narcolepsy. , 1955, Schweizer Archiv fur Neurologie und Psychiatrie. Archives suisses de neurologie et de psychiatrie. Archivio svizzero di neurologia e psichiatria.

[179]  Hannah M. Nash,et al.  A systematic review of cognitive function and psychosocial well-being in school-age children with narcolepsy. , 2017, Sleep medicine reviews.

[180]  E. Mignot,et al.  Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic , 2013, PLoS genetics.

[181]  J. Frey,et al.  Fluoxetine suppresses human cataplexy , 1994, Neurology.

[182]  H. Akiyama,et al.  Absence of ubiquitinated inclusions in hypocretin neurons of patients with narcolepsy , 2009, Neurology.

[183]  R. Peraita-Adrados,et al.  Narcolepsy with cataplexy and pregnancy: a case–control study , 2018, Journal of sleep research.

[184]  A. de Laat,et al.  Network meta-analysis. , 2017, Journal of oral rehabilitation.

[185]  P. Bladin.  Narcolepsy - Cataplexy and Psychoanalytic Theory of Sleep and Dreams , 2000, Journal of the history of the neurosciences.

[186]  C. Bassetti,et al.  Coexisting narcolepsy (with and without cataplexy) and multiple sclerosis , 2018, Journal of Neurology.

[187]  Christian Guilleminault,et al.  Multiple sleep latency test in narcolepsy type 1 and narcolepsy type 2: A 5‐year follow‐up study , 2018, Journal of sleep research.

[188]  T. Pollmächer,et al.  Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy , 2001, Annals of neurology.

[189]  M. Tafti,et al.  Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment , 2009, Neurology.

[190]  P. Boesiger,et al.  Abnormal activity in reward brain circuits in human narcolepsy with cataplexy , 2010, Annals of neurology.

[191]  R Broughton,et al.  Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. , 1986, Sleep.

[192]  J. Montaner.  Genetics of intracerebral haemorrhage: a tsunami effect of APOE ɛ2 genotype on brain bleeding size? , 2011, The Lancet Neurology.

[193]  J. Touchon,et al.  Effect of age on MSLT results in patients with narcolepsy–cataplexy , 2004, Neurology.

[194]  M. Hersberger,et al.  Excessive Daytime Sleepiness in Behçet’s Disease with Diencephalic Lesions and Hypocretin Dysfunction , 2010, European Neurology.

[195]  C. Baumann,et al.  Swiss Narcolepsy Scale , 2018, Clinical and Translational Neuroscience.

[196]  S. Overeem,et al.  The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. , 2011, Sleep medicine.

[197]  A. Bizzi,et al.  Pontine lesions in idiopathic narcolepsy , 1996, Neurology.

[198]  H. J. Roberts.  OBESITY DUE TO THE SYNDROME OF NARCOLEPSY AND DIABETOGENIC HYPERINSULINISM: CLINICAL AND THERAPEUTIC OBSERVATIONS ON 252 PATIENTS * , 1967 .

[199]  V. Pankratz,et al.  The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. , 2002, Sleep.

[200]  S. Chokroverty.  Sleep apnea in narcolepsy. , 1986, Sleep.

[201]  S. Schwartz,et al.  Cortical morphometry in narcolepsy with cataplexy , 2012, Journal of sleep research.

[202]  S. Meuth,et al.  Specific T-cell activation in peripheral blood and cerebrospinal fluid in central disorders of hypersomnolence , 2018, Sleep.

[203]  C. Gieger,et al.  ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy , 2013, PLoS genetics.

[204]  Emmanuel Mignot,et al.  The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene , 1999, Cell.

[205]  H. Emsellem.  A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy , 2003 .

[206]  R. Vaughan,et al.  GENETIC MARKERS IN NARCOLEPSY , 1984, The Lancet.

[207]  Christian Gieger,et al.  Common variants in P2RY11 are associated with narcolepsy , 2010, Nature Genetics.

[208]  T. Shimohata,et al.  Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis: new neurochemical and immunological implications. , 2009, Archives of neurology.

[209]  P. Lavie,et al.  Narcolepsy-cataplexy in Israeli Jews is associated exclusively with the HLA DR2 haplotype. A study at the serological and genomic level. , 1988, Human immunology.

[210]  P. Boesiger,et al.  Reduced amygdala activity during aversive conditioning in human narcolepsy , 2009, Annals of neurology.

[211]  J. Siegel,et al.  Greatly increased numbers of histamine cells in human narcolepsy with cataplexy , 2013, Annals of neurology.

[212]  R. Stickgold,et al.  Delusional confusion of dreaming and reality in narcolepsy. , 2014, Sleep.

[213]  E. Mignot,et al.  Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy , 2018, Proceedings of the National Academy of Sciences.

[214]  M. Goswami,et al.  The influence of clinical symptoms on quality of life in patients with narcolepsy , 1998, Neurology.

[215]  G. Mayer,et al.  The MSLT: More objections than benefits as a diagnostic gold standard? , 2014, Sleep.

[216]  C. Symonds.  NARCOLEPSY AS A SYMPTOM OF ENCEPHALITIS LETHARGICA. , 1926 .

[217]  T. Kodama,et al.  CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. , 2009, Sleep.

[218]  Daly Dd,et al.  Criteria for the diagnosis of the narcoleptic syndrome. , 1957 .

[219]  A. Vourdas,et al.  Narcolepsy and psychopathology: is there an association? , 2002, Sleep medicine.

[220]  J. A. Cheyne,et al.  Relations among hypnagogic and hypnopompic experiences associated with sleep paralysis , 1999, Journal of sleep research.

[221]  C. Bassetti.  Transient loss of consciousness and syncope. , 2014, Handbook of clinical neurology.

[222]  I. Daum,et al.  Cognitive deficits in narcolepsy , 2006, Journal of sleep research.

[223]  S. Overeem,et al.  Possible confusion between primary hypersomnia and adult attention-deficit/hyperactivity disorder , 2006, Psychiatry Research.

[224]  G. Plazzi,et al.  Antibodies Against Hypocretin Receptor 2 Are Rare in Narcolepsy , 2017, Sleep.

[225]  E. Mignot,et al.  Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis , 2004, Neurology.

[226]  E. Mignot,et al.  Sulpiride, a D2/D3 Blocker, Reduces Cataplexy but not REM Sleep in Canine Narcolepsy , 2000, Neuropsychopharmacology.

[227]  D. Bechtold,et al.  Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock , 2014, The Journal of Neuroscience.

[228]  C. Burgess,et al.  Narcolepsy: Neural Mechanisms of Sleepiness and Cataplexy , 2012, The Journal of Neuroscience.

[229]  N. Darín,et al.  The development of a health-related quality-of-life instrument for young people with narcolepsy: NARQoL-21 , 2017, Health and Quality of Life Outcomes.

[230]  V. Natale,et al.  Attention impairments and ADHD symptoms in adult narcoleptic patients with and without hypocretin deficiency , 2017, PloS one.

[231]  E. Mignot,et al.  Genetic and familial aspects of narcolepsy , 1998, Neurology.

[232]  Y. Dauvilliers,et al.  CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice , 2016, Proceedings of the National Academy of Sciences.

[233]  Andrea Rodenbeck,et al.  Prostaglandin D synthase (β-trace) in healthy human sleep , 2004 .

[234]  C. Baumann,et al.  No persistent effect of intravenous immunoglobulins in patients with narcolepsy with cataplexy , 2008, Journal of Neurology.

[235]  K. Vogt,et al.  Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models , 2017, Proceedings of the National Academy of Sciences.

[236]  G. Plazzi,et al.  Narcolepsy during Childhood: An Update , 2015, Neuropediatrics.

[237]  B Roth,et al.  Life Effects of Narcolepsy in 180 Patients from North America, Asia and Europe Compared to Matched Controls , 1981, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[238]  Mitler,et al.  Night‐time sleep and daytime sleepiness in narcolepsy , 2000, Journal of sleep research.

[239]  N. B. Atkin,et al.  Chromosomes in Carcinoma of the Cervix , 1965, British medical journal.

[240]  L. Krahn.  Reevaluating spells initially identified as cataplexy. , 2005, Sleep medicine.

[241]  S. Lehmann,et al.  From radioimmunoassay to mass spectrometry: a new method to quantify orexin-A (hypocretin-1) in cerebrospinal fluid , 2016, Scientific Reports.

[242]  S. Pradervand,et al.  Rare missense mutations in P2RY11 in narcolepsy with cataplexy , 2017, Brain : a journal of neurology.

[243]  C. Bassetti,et al.  Patient-Reported Measures of Narcolepsy: The Need for Better Assessment. , 2017, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[244]  S. Antonarakis,et al.  A narcolepsy susceptibility locus maps to a 5Mb region of chromosome 21q , 2004, Annals of neurology.

[245]  G. Mayer,et al.  Motor dyscontrol in sleep of narcoleptic patients (a lifelong development?) , 1993, Journal of sleep research.

[246]  T. Young,et al.  Narcolepsy and predictors of positive MSLTs in the Wisconsin Sleep Cohort. , 2014, Sleep.

[247]  J. Schwartz,et al.  Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial , 2017, The Lancet Neurology.

[248]  Michael Aldrich,et al.  Reduced Number of Hypocretin Neurons in Human Narcolepsy , 2000, Neuron.

[249]  T. Morikawa,et al.  A REAPPRAISAL , 2020, The Eudemian and Nicomachean Ethics.

[250]  T. Pollmächer,et al.  Increased body-mass index in patients with narcolepsy , 2000, The Lancet.

[251]  C. M. Linton.  Narcolepsy without Cataplexy , 2013 .

[252]  D. Daly,et al.  Narcolepsy in children. , 1960, Pediatrics.

[253]  Masaru Mimura,et al.  Neuroimaging correlates of narcolepsy with cataplexy: A systematic review , 2019, Neuroscience Research.

[254]  T. Sakurai,et al.  Orexin neurons suppress narcolepsy via 2 distinct efferent pathways. , 2014, The Journal of clinical investigation.

[255]  A. Régnault,et al.  Narcolepsy Type 1 Is Associated with a Systemic Increase and Activation of Regulatory T Cells and with a Systemic Activation of Global T Cells , 2017, PloS one.

[256]  S. Jego,et al.  Optogenetic Evidence for Inhibitory Signaling from Orexin to MCH Neurons via Local Microcircuits , 2015, The Journal of Neuroscience.

[257]  E. Mignot,et al.  The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. , 2002, Archives of neurology.

[258]  U.S.Xyrem® Multicenter Study Group.  Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. , 2004, Sleep medicine.

[259]  J. Siegel,et al.  Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla. , 1991, Science.

[260]  L. Álvaro,et al.  Cataplexy associated with midbrain lesion , 1995, Neurology.

[261]  Ulrike Held,et al.  Validation of the fatigue severity scale in a Swiss cohort. , 2008, Sleep.

[262]  Yves Dauvilliers,et al.  High-dimensional single-cell analysis reveals the immune signature of narcolepsy , 2016, The Journal of experimental medicine.

[263]  M. Burns,et al.  Case-Control Study , 2020, Definitions.

[264]  Sebastiaan Overeem,et al.  Clinical, polysomnographic and genome‐wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study , 2013, Journal of sleep research.

[265]  A. Harvey,et al.  Hypersomnia across mood disorders: a review and synthesis. , 2009, Sleep medicine reviews.

[266]  D. Vergani,et al.  Immune factors in narcolepsy. , 1986, Sleep.

[267]  C. Bassetti,et al.  Pharmacological management of narcolepsy with and without cataplexy , 2017, Expert opinion on pharmacotherapy.

[268]  C. Guilleminault,et al.  Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. , 2017, Sleep medicine.

[269]  T. Pollmächer,et al.  Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy , 2001 .

[270]  C. Baumann,et al.  Multiple sleep latency measures in narcolepsy and behaviourally induced insufficient sleep syndrome. , 2009, Sleep medicine.

[271]  G. Plazzi,et al.  Emotional information processing in patients with narcolepsy: a psychophysiologic investigation. , 2003, Sleep.

[272]  E. Mignot,et al.  Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. , 2009, Sleep.

[273]  S. Maret,et al.  Monozygotic twins concordant for narcolepsy-cataplexy without any detectable abnormality in the hypocretin (orexin) pathway , 2004, The Lancet.

[274]  V. Natale,et al.  Physical Activity and Sleep/Wake Behavior, Anthropometric, and Metabolic Profile in Pediatric Narcolepsy Type 1 , 2018, Front. Neurol..

[275]  S. Nevsimalova,et al.  Depression in narcolepsy and hypersomnia. , 1977, Activitas nervosa superior.

[276]  Sebastiaan Overeem,et al.  Hypocretin (orexin) deficiency in human narcolepsy , 2000, The Lancet.

[277]  M. Aldrich,et al.  MRI findings in narcolepsy. , 1997, Sleep.

[278]  S Koskimies,et al.  The prevalence of narcolepsy: An epidemiological study of the Finnish Twin Cohort , 1994, Annals of neurology.

[279]  S. Zuberi,et al.  Symptoms of narcolepsy in children misinterpreted as epilepsy. , 2005, Epileptic disorders : international epilepsy journal with videotape.

[280]  E. Werth,et al.  Weak with sex: sexual intercourse as a trigger for cataplexy. , 2009, The journal of sexual medicine.

[281]  K. Tokunaga,et al.  Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach , 2018, Sleep.

[282]  N. Dahmen,et al.  Season of birth effect in narcolepsy , 2003, Neurology.

[283]  C. Drake,et al.  The prevalence of multiple sleep-onset REM periods in a population-based sample. , 2006, Sleep.

[284]  Yves Dauvilliers,et al.  Executive Control of Attention in Narcolepsy , 2012, PloS one.

[285]  W C Dement,et al.  A syndrome of hypersomnia with automatic behavior. , 1975, Electroencephalography and clinical neurophysiology.

[286]  A. Blanks,et al.  Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus , 2004, Nature Neuroscience.

[287]  Peter Boesiger,et al.  Abnormal activity in hypothalamus and amygdala during humour processing in human narcolepsy with cataplexy. , 2008, Brain : a journal of neurology.

[288]  J. Santamaria,et al.  Obstructive sleep apnea in narcolepsy. , 2010, Sleep medicine.

[289]  H. Pijl,et al.  Reduction of plasma leptin levels and loss of its circadian rhythmicity in hypocretin (orexin)-deficient narcoleptic humans. , 2002, The Journal of clinical endocrinology and metabolism.

[290]  J. G. van Dijk,et al.  Comparing Treatment Effect Measurements in Narcolepsy: The Sustained Attention to Response Task, Epworth Sleepiness Scale and Maintenance of Wakefulness Test. , 2015, Sleep.

[291]  C. Tassinari,et al.  A video-polygraphic analysis of the cataplectic attack , 2000, Clinical Neurophysiology.

[292]  H. Moldofsky,et al.  Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy , 1997, Neurology.

[293]  M. Tafti,et al.  Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy , 2015, The Lancet Neurology.

[294]  G. Plazzi,et al.  Pseudocataplexy in narcolepsy with cataplexy. , 2010, Sleep medicine.

[295]  H. Pijl,et al.  Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men. , 2005, American journal of physiology. Endocrinology and metabolism.

[296]  R. Chervin,et al.  Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy. , 1997, Sleep.

[297]  S. Nishino,et al.  Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. , 2005, Sleep medicine reviews.

[298]  R Broughton,et al.  Daytime sleep inertia in narcolepsy-cataplexy. , 1994, Sleep.

[299]  A. Desautels,et al.  Month of birth as a risk factor for narcolepsy. , 2003, Sleep.

[300]  Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. , 2009, Sleep.

[301]  M. Mitler,et al.  The treatment of excessive somnolence with stimulant drugs. , 1993, Sleep.

[302]  A. Lutterotti,et al.  CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1 , 2016, Sleep.

[303]  Neil J. Douglas.  The psychosocial aspects of narcolepsy , 1998, Neurology.

[304]  C. Bassetti,et al.  The clinical spectrum of narcolepsy with cataplexy: a reappraisal , 2004, Journal of sleep research.

[305]  T. Hökfelt,et al.  Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns , 2014, Proceedings of the National Academy of Sciences.

[306]  Markku Partinen,et al.  Narcolepsy Associated with Pandemrix Vaccine , 2018, Current Neurology and Neuroscience Reports.

[307]  G. Dunn,et al.  The clinical diagnosis of the narcoleptic syndrome , 1998, Journal of sleep research.

[308]  J. Santamaria,et al.  A patient with narcolepsy with cataplexy and multiple sclerosis: two different diseases that may share pathophysiologic mechanisms? , 2013, Sleep medicine.

[309]  J. Peever,et al.  GABA Cells in the Central Nucleus of the Amygdala Promote Cataplexy , 2017, The Journal of Neuroscience.

[310]  G. Plazzi,et al.  Restless legs syndrome is frequent in narcolepsy with cataplexy patients. , 2010, Sleep.

[311]  J. Wellman,et al.  Posttraumatic narcolepsy in mild to moderate closed head injury. , 1994, Sleep.

[312]  T. Young,et al.  Reduction of REM sleep latency associated with HLA-DQB1*0602 in normal adults , 1998, The Lancet.

[313]  T. Roth,et al.  Isolated cataplexy: a familial study. , 1988, Henry Ford Hospital medical journal.

[314]  C. Baumann,et al.  Hypocretin (orexin) deficiency predicts severe objective excessive daytime sleepiness in narcolepsy with cataplexy , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[315]  A. Pariente,et al.  Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France. , 2013, Brain : a journal of neurology.

[316]  G. Plazzi,et al.  Persistence of deep-tendon reflexes during partial cataplexy. , 2018, Sleep medicine.

[317]  S. Overeem,et al.  Cataplexy: 'tonic immobility' rather than 'REM-sleep atonia'? , 2002, Sleep medicine.

[318]  R. Manni,et al.  Sleep paralysis in narcolepsy: more than just a motor dissociative phenomenon? , 2012, Neurological Sciences.

[319]  J. Schwartz,et al.  Cerebrospinal fluid histamine levels are decreased in patients with narcolepsy and excessive daytime sleepiness of other origin , 2010, Journal of sleep research.

[320]  D. Daly,et al.  Criteria for the diagnosis of the narcoleptic syndrome. , 1957, Proceedings of the staff meetings. Mayo Clinic.

[321]  G. Plazzi,et al.  Car Crashes and Central Disorders of Hypersomnolence: A French Study , 2015, PloS one.

[322]  R. Kathol,et al.  Schizophrenia and narcolepsy: A review with a case report , 2004, Psychiatry and clinical neurosciences.

[323]  T. Pollmächer,et al.  DR2-positive monozygotic twins discordant for narcolepsy. , 1990, Sleep.

[324]  J. Hobson,et al.  Transient cataplexy after removal of a craniopharyngioma , 1984, Neurology.

[325]  G. Vogel.  Studies in psychophysiology of dreams. III. The dream of narcolepsy. , 1960, Archives of general psychiatry.

[326]  Curt Rosenthal.  Über das Auftreten von halluzinatorisch-kataplektischem Angstsyndrom, Wachanfällen und ähnlichen Störungen bei Schizophrenen , 1939 .

[327]  M. Tafti,et al.  Life events in the year preceding the onset of narcolepsy. , 1994, Sleep.

[328]  M. Hersberger,et al.  Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury , 2005, Neurology.

[329]  H. A. Paskind.  EFFECT OF LAUGHTER ON MUSCLE TONE , 1932 .

[330]  M. Mühlethaler,et al.  Elevated Tribbles homolog 2-specific antibody levels in narcolepsy patients. , 2010, The Journal of clinical investigation.

[331]  Y. Hishikawa,et al.  Treatment of narcolepsy with imipramine (tofranil) and desmethylimipramine (pertofran). , 1966, Journal of the neurological sciences.

[332]  S. Hong,et al.  Cerebral perfusion changes during cataplexy in narcolepsy patients , 2006, Neurology.

[333]  R. Broughton,et al.  Night sleep does not predict day sleep in narcolepsy. , 1994, Electroencephalography and clinical neurophysiology.

[334]  G. Plazzi,et al.  Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination , 2014, The Lancet Neurology.

[335]  S. Vandi,et al.  Stereotyped episodes of aphasia and immobility: how cataplexy mimics stroke in an elderly patient. , 2017, Sleep medicine.

[336]  B. Lowell,et al.  GABAergic Neurons of the Central Amygdala Promote Cataplexy , 2017, The Journal of Neuroscience.

[337]  J. Lin,et al.  Brain structures and mechanisms involved in the control of cortical activation and wakefulness, with emphasis on the posterior hypothalamus and histaminergic neurons. , 2000, Sleep medicine reviews.

[338]  N. Imlah.  NARCOLEPSY IN IDENTICAL TWINS , 1961, Journal of neurology, neurosurgery, and psychiatry.

[339]  R. Cools,et al.  Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1. , 2016, Sleep.

[340]  G. Plazzi,et al.  Parkinsonian tremor persisting during cataplexy. , 2016, Sleep medicine.

[341]  E. Mignot,et al.  Nocturnal Sleep Dynamics Identify Narcolepsy Type 1. , 2015, Sleep.

[342]  K. Johnson.  An Update. , 1984, Journal of food protection.

[343]  A. N. van den Pol,et al.  Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems , 1998, The Journal of Neuroscience.

[344]  G. Plazzi,et al.  Spectral electroencephalography profile of rapid eye movement sleep at sleep onset in narcolepsy type 1 , 2017, European journal of neurology.

[345]  E. Mignot,et al.  Normal CSF Hypocretin-1 (Orexin A) Levels in Dementia with Lewy Bodies Associated with Excessive Daytime Sleepiness , 2004, European Neurology.

[346]  E. Mignot,et al.  Disrupted nighttime sleep in narcolepsy. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[347]  G. Plazzi,et al.  Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus. , 2014, Journal of autoimmunity.