Hypnagogic Research Articles

Genetic association, seasonal infections and autoimmune basis of narcolepsy

In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebsky's criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers.

Dream imagery, rapid eye movement sleep behavior disorder, and hallucinations

Rapid eye movement (REM) sleep behavior disorder (RBD) and hypnagogic hallucinations are salient symptoms of abnormal and dissociated REM sleep that are frequently associated in serious neurological diseases. RBD is a strong, independent risk factor for hallucinations in narcolepsy (odds ratio: 4.3) and in Parkinson's disease (odds ratio: 2.7). In Parkinson's disease, RBD also predicts incident hallucinations and psychosis in prospective cohorts. Status dissociatus (a mixture of hallucinations, RBD, and dissociated sleep–wake states) is observed in patients with Guillain-Barré when hallucinating, but also in Lewy bodies dementia, delirium tremens, fatal familial insomnia, and Morvan's chorea. This co-occurrence of RBD and visual hallucinations suggests a common, extensive lesion within REM sleep executive systems.

Narcolepsy-Characteristics of those in the Borderland-We Need a Better Diagnostic Tool

Narcolepsy-Characteristics of those in the Borderland-We Need a Better Diagnostic Tool Purpose: The criteria for the diagnosis of narcolepsy changed when the 2nd edition of the International Classification of Sleep Disorders supplanted the first edition (ICSD-1). The impact of using the updated criteria is unknown. We thus compared the characteristics of a population of patients diagnosed using ICSD- 2 with those that only met ICSD-1 criteria. Minimum criteria for narcolepsy in ICSD-1 are sleepiness with cataplexy, sleep paralysis, or hypnogogic hallucinations plus sleep latency <10 minutes or REM latency <20 min on polysomnography. ICSD-2 requires sleepiness with cataplexy or a positive MSLT (MSLT-SL ≤ 8 min and SOREMPs ≥ 2). Methods: The records of 148 subjects with suspected narcolepsy were reviewed. Seventy subjects were excluded because of other diagnoses or use of REM suppressants. 59 patients were diagnosed on the basis of cataplexy (54%) or positive MSLT (55%). The remaining 19 patients without cataplexy or positive MSLT fulfilled the minimal criteria using ICSD-1. Results: The anthropometrics, narcolepsy symptoms including refreshing naps, Epworth sleepiness scores and sleep bioparameters were comparable between patient with and without cataplexy.

2638 – Successful treatment of narcolepsy with methylphenidate (concerta)

Background Narcolepsy is a disorder characterized by diurnal somnolence and episodes of short duration sleep. It can occur in 0.02–0.16% of adults, generally before the age of 30. Objective The aim of this work is to present tolerability and treatment response of Concerta in one adult suffering from narcolepsy. Methods We report the case of a 28 years adult female with narcolepsy. One year ago, after a strong social stress, she manifested some symptoms of narcolepsy: excessive daytime sleepiness, cataplexy, and visual hypnogogic hallucinations. There was no family history of sleep disorders and not experienced premorbid seizure or sleep disorder. Diagnosis of narcolepsy is based on DSM-IV criteria, polysomnography and Multiple Sleep Latency Test. Sleep latency, rapid eye movement sleep latency, and mean multiple sleep latency were 2.9, 70.1 and 1.5 min, respectively. Twenty-four hour EEG monitoring, MRI imaging of the brain and serum chemistries were normal. At the beginning because of the misdiagnosis the patient was treated with lithium and olanzapine. Patient started Concerta treatment after 1 year with 9 mg/day at the morning. Dose was increased maximum to 18 mg twice daily over a 2-weeks period. Results Treatment of narcolepsy with Concerta lasted 6 month. Visual hypnogogic hallucinations and cataplexy started to improve 3 weeks after adjustments in methylphenidate dosing. Three months after the initiation of therapy, the patient is completely asymptomatic. Side effects included faster heart rate and nervousness. Conclusion This case support results from recent studies that methylphenidate is well tolerated and effective in narcolepsy.

Decreased incidence of childhood narcolepsy 2 years after the 2009 H1N1 winter flu pandemic

increased several fold in China following the H1N1 winter flu pandemic (pH1N1). 1 In parallel with this report, increased incidence was also reported in several countries in Northern Europe, with many children developing the disease following administration of Pandemrix, an adjuvanted pH1N1 vaccine. Studies in Sweden, Finland, and Norway have shown a 4- to 13fold increased risk of developing childhood narcolepsy following Pandemrix (only 1 of 16,000 vaccinated children developed narcolepsy, however). 2–4 These results bolster the claim that narcolepsy, an autoimmune disease caused by hypocretin cell loss, could be triggered by H1N1 vaccination or infection. Further evidence of causality may come from studying narcolepsy incidence following the 2009 pandemic, as H1N1 infections decreased in subsequent seasons. In the Figure, we report on the evolution of new onset cases at Beijing University People’s Hospital. For better comparison, we only present data on cases diagnosed within 1 year of onset, so that data are comparable to prior years. Data from 2012 are also included, although curtailed after September, so that a few cases with onset in the first 3 months of 2012 will still be identified (denoted with a star and not used in any statistical analysis). As can be seen, a return to baseline is evident, suggesting that the 2009–2010 winter was a unique event. We next examined whether patients identified following the pH1N1 pandemic season differed clinically. As before, to avoid issues pertaining to evaluation time since onset, we only compared subjects diagnosed within 1 year of onset. In 1998–2009, 2010, and 2011 respectively, 187, 201, and 49 subjects were identified (mean 6 standard error of the mean delay to diagnosis: 4.7 6 0.3, 4.4 6 0.2, and 4.6 6 0.4 months). Sex, body mass index, age at diagnosis, occurrence and age of onset of each narcolepsy symptom (ie, sleepiness, cataplexy, sleep paralysis, hypnagogic hallucination, and disturbed nocturnal sleep), and sleep recording findings (Multiple Sleep Latency Test, Apnea Hypopnea Index) were next compared across the 3 groups. Remarkably few differences were found. First, although mean age of onset in subjects diagnosed in 2010 was younger than in those diagnosed before and after 2010, differences were not statistically significant (8.7 6 0.4 years in 2010 vs 10.0 6 0.7 years before and 10.1 6 1.7 years in 2011, p ¼ 0.2). Second, sleep-onset rapid eye movement periods during the multiple latency tests were more numerous in cases diagnosed in 2010 versus others, whether or not controlled with age (4.65 6 0.05 in 2010 vs 4.32 6 0.05 before and 4.00 6 0.18 years in 2011, p < 0.001), suggesting increased severity. All other parameters were similar across groups. We conclude that pH1N1 infections during the 2009–2010 season have likely played a role in triggering narcolepsy in children, but that the phenotypes of these cases is not distinguishable from prior cases.

Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep.

One hypnagogic dream and the I Ching: an interpretation.

In this paper I report about one very simple but deeply intriguing hypnagogic dream which potential meanings were subsequently unfolded and analysed by means of the I Ching, and instrument that has been reputed to have the capacity to disclose hidden meanings in the situations that are scrutinized with its help. The paper concludes for the possibility of amplifying the hermeneutics of one dream through the I Ching.

Sleepiness that cannot be overcome: Narcolepsy and cataplexy

Narcolepsy-cataplexy syndrome is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. It is strongly associated with the genetic marker, human leucocyte antigen (HLA) DQB1*06:02. A deficit in the endogenous hypocretin/orexin system due to neuronal degeneration in the lateral hypothalamus, induced by an autoimmune-mediated process, is the primary pathophysiology associated with the human disease. The important finding of an association with hypocretin genes in animal models of narcolepsy has led to the establishment of cerebrospinal fluid hypocretin measurements as a new diagnostic test for human narcolepsy. This is a fascinating story of translation of basic science research into clinical practice in sleep medicine during the past decade. Recent advances have shed light on the associations between respiratory medicine and narcolepsy-cataplexy research. The first is that upper airway infections, including H1N1 and/or streptococcal infections, may initiate or reactivate an immune response that leads to loss of hypocretin-secreting cells and narcolepsy in genetically susceptible individuals. The second is that an increased incidence of sleep disordered breathing among narcoleptic subjects may relate to the impairment of central control of breathing, linked to hypocretin deficiency or carriage of HLADQB1*06:02, in animals and human subjects with narcolepsy, respectively, indicating neural dysfunction in an area where respiratory and sleep-wake systems are closely interrelated.

What Has Been Going on With My Sleep After My Car Accident?

INTRODUCTION: Hypnagogic hallucinations are hallucinatory experiences that accompany the onset of awakening, they can occur in certain states, such as sleep deprivation and conditions such as narcolepsy. Main neural structures responsible for muscle atonia in REM sleep are dorsolateral portions of the pons and brainstem, cholinergic and cholinoceptive REM sleep-on neurons, monoaminergic REM sleep-off neurons. Generalized atonia originates in dorsolateral portions of the pontine reticular formation and descend to the medulla and spinal cord to bring postural atonia. Muscle atonia characteristic of REM sleep produces both cataplexy and sleep paralysis. Disruptions induced experimentally of these neurons can cause REM sleep without atonia. Reports on narcolepsy following traumatic brain injury have been previously described in the literature.CASE PRESENTATION: We report a case of a 25 year old woman referred to Sleep Clinic with complaints of episodes of drifting off and suffocating while in bed for about 2 years, with visual hallucinations of a figure in the room or the surroundings, feeling paralyzed during these episodes, that occur approximately 3 to four times per week, sometimes occuring more than once per night. Sleep paralysis, nightmares were described. Excessive daytime sleepiness was observed, with propensity to naps that could last 3 to 4 hours and were refreshing. Epworth Sleepiness scale was 6. There was no family history of parasomnias. She denied snoring or sleep attacks. She noticed the symptoms described occurred two years ago after a car accident, when she suffered a concussion. She had reported a recent 15 Lbs weight gain. On Physical exam she had an airway Mallampati class II and was obese (BMI 32) without any neurological findings. Polysomnography results were as follows: Total sleep time: 494 min (efficiency 93%), Sleep latency: 13 min and REM latency: 5 min. Sleep disordered breathing was not observed. Multiple Sleep Latency Test results were: Mean sleep latency of 10 min with mean REM latency of 7.7 min and 3 SOREMPs.DISCUSSION: We describe a case of Narcolepsy without cataplexy presenting after a concussion following a car accident. Prior associations with multiple sclerosis, encephalitis and had trauma have been reported, but the temporal relationship between these and the onset of symptoms were not clearly established. Hypnagogic hallucinations, sleep paralysis and nightmares are often present in the general population and may not warrant additional testing.CONCLUSIONS: In our patient, her excessive daytime sleepiness and temporal relationship with the diagnosis of concussion were helpful elucidating her final diagnosis of Narcolepsy.1) Castriotta R, Murthy J. Sleep disorders in patients with traumatic brain injury: A Reveiw. CNS Drugs; 2011, 25175-852) Clavelou P, Tournilhac M, Vidal C, et al. Narcolepsy associated with arteriovenous malformation of the diencephalon. Sleep; 1995, 18:202-5DISCLOSURE: The following authors have nothing to disclose: Veronica Brito, Chrisoula Politis, Shalinee ChawlaNo Product/Research Disclosure InformationWinthrop University Hospital, Mineola, NY. Language: en

Late-Onset Obsessive-Compulsive Disorder With Comorbid Narcolepsy After Perfect Blend of Thalamo-Striatal Stroke and Post-Streptococcal Infection

Late-Onset Obsessive-Compulsive Disorder With Comorbid Narcolepsy After Perfect Blend of Thalamo-Striatal Stroke and Post-Streptococcal Infection

Effectiveness and safety of sodium oxybate in narcolepsy-cataplexy syndrome

BackgroundNarcolepsy is a chronic neurological disease characterised by excessive daytime somnolence, cataplexy, hypnagogic or hypnopompic hallucinations, sleep paralysis and fragmented night-time sleep. The most severe symptom is cataplexy. Because no...

Unique sleep disorders profile of a population-based sample of 747 Hmong immigrants in Wisconsin

Concerns regarding sleep disorders in Hmong immigrants in the US emerged when an astonishingly high mortality rate of Sudden Unexplained Nocturnal Death Syndrome (SUNDS) was documented in Hmong men. Stress, genetics, and cardiac abnormalities interacting with disordered sleep were hypothesized as contributing factors to SUNDS. Most recently, sleep apnea has been implicated in nighttime deaths of Brugada Syndrome. This syndrome is thought to comprise a spectrum of sudden cardiac death disorders, including SUNDS. However, little research since has placed SUNDS in its context of Hmong cultural beliefs, health, or the prevalence of other sleep disorders. Because the epidemiology of sleep disorders and terrifying nighttime experiences in Hmong is poorly documented, we investigated the prevalence and correlates of sleep apnea, rapid eye movement (REM) sleep stage related disorders, and insomnia in 3 population-based samples (collected from 1996 to 2001) comprising 747 Hmong immigrants in Wisconsin. Participants were questioned on sleep problems, cultural beliefs, health, and other factors. A random subsample (n = 37) underwent in-home polysomnography to investigate sleep apnea prevalence. Self-report and laboratory findings were compared with similarly collected data from the Wisconsin Sleep Cohort (WSC) study (n = 1170), a population-based longitudinal study of sleep. The results inform a unique Hmong sleep disorder profile of a high prevalence of sleep apnea, sleep paralysis, and other REM-related sleep abnormalities as well the interaction of culturally related nighttime stressors with these sleep problems. For example, experiences of dab tsog (frightening night spirit pressing on chest) was prevalent and related to sleep apnea indicators, sleep paralysis, nightmares, hypnogogic hallucinations, and insomnia. Understanding the role of sleep disorders and the cultural mechanisms that may trigger or condition response to them could ultimately provide a basis for screening and intervention to reduce the adverse health and emotional consequences of these conditions in Hmong.

Narcolepsy in the Pediatric Population

Narcolepsy is characterized by excessive daytime sleepiness, with or without cataplexy. Associated features include sleep paralysis, hypnagogic or hypnopompic hallucinations, and disturbed nocturnal sleep. Narcolepsy is strongly associated with the HLA DQB1*0602 allele, and its symptoms stem from destruction of hypocretin-secreting neurons in the hypothalamus. Recently identified autoantibodies to Tribbles homologue 2 in some patients, as well as cases associated with H1N1 vaccination, support an autoimmune mechanism. There are many challenges in diagnosing and treating pediatric narcolepsy. Caution must also be used in interpreting polysomnography and multiple sleep latency test results in children. HLA testing is nonspecific, and no commercial test exists to measure cerebrospinal fluid hypocretin levels. Neuroimaging has not yet proven useful in primary narcolepsy. Treatment of sleepiness and cataplexy in children requires extrapolating from adult studies. Hopefully, further insights into the pathophysiology of narcolepsy will allow for new therapeutics to manage the symptoms and modify the course of the disease.

Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

BackgroundNarcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles.MethodsThe study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT).ResultsThe 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci.ConclusionsThe clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.

Ring the Bell for Matins: Circadian Adaptation to Split Sleep by Cloistered Monks and Nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39 ± 4:30 h (median ± 95% interval), plateau or rise of temperature at 22:35 ± 00:23 h (while asleep) lasting 296 ± 39 min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85 ± 15 min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05 ± 00:59 h vs. 00:00 ± 00:54 h, median ± 95% confidence interval, p = .0001) and offset (06:27 ± 0:22 h, vs. 07:37 ± 0:33 h, p = .0001), as well as a shorter sleep time (6.5 ± 0.6 vs. 7.6 ± 0.7 h, p = .05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time. (Author correspondence: isabelle.arnulf@psl.aphp.fr)

Current and Future Therapeutic Approaches In Narcolepsy

Narcolepsy with cataplexy (NC) is a disabling orphan sleep disorder characterized by excessive daytime sleepiness, cataplexy and other dissociated manifestations of rapid eye movement sleep (hypnagogic hallucinations and sleep paralysis), as well as frequent movement and awakening during night-time sleep. In this article, we will describe the main symptoms and the current and future treatments of NC. Pathophysiological studies have shown that NC is caused by the early loss of neurons in the hypothalamus that produce hypocretin/orexin, a wakefulness-associated neurotransmitter present in cerebrospinal fluid. The cause of neural loss could be autoimmune since most patients have the human leukocyte antigen DQB1*0602 allele that predisposes individuals to NC. The treatment of narcolepsy has evolved over the past few years with the widespread use of modafinil for daytime sleepiness, antidepressants for cataplexy and γ-hydroxybutyrate (sodium oxybate) for both symptoms. Potential development of new wake-promoting drugs, anticataplectic medications, slow-wave sleep-enhancing treatments, hypocretin-replacement therapy and immunotherapy at early stages of the disease needs to be evaluated in the near future.

Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities.

Immunological and Genetic Aspects of Narcolepsy

Narcolepsy is an increasingly recognized sleep disorder characterized by excessive daytime sleepiness, symptoms of dissociated/abnormal rapid eye movement (REM) sleep, disrupted nocturnal sleep, and cataplexy. Although daytime sleepiness is the most disabling symptom, significantly disrupted sleep at night results in a similar total amount of sleep over 24 hours compared to controls. Many of the hallmark symptoms of narcolepsy [sleep paralysis, hypnagogic hallucinations, sleep-onset REM periods (SOREMPs)] are also seen in the general population, especially in the context of sleep deprivation, however cataplexy (brief episodes of bilateral muscle weakness triggered by emotions) is highly specific to narcolepsy. The most typical triggers for cataplexy are joking, laughter, and to a lesser extent, anger. Attacks may vary in severity ranging from jaw sagging or head dropping, to knees buckling, or total body paralysis lasting up to several minutes, with consciousness preserved throughout the episode. The unifying feature of these symptoms is that they all reflect a fundamental dysregulation of normal transitions between sleep and wake. Disease onset is most often in childhood, peaking between 10 and 25 years of age, and once established, the disease is life-long. Recent work has resulted in substantial insights on key genetic factors contributing to susceptibility and how these relate to the immunological processes underlying the pathophysiology of the disease. Narcolepsy-cataplexy occurs with a fairly consistent prevalence of approximately 0.02-0.03% in various Caucasian groups throughout the world, with a somewhat higher prevalence in Japanese (0.16%) and individuals of African descent, and a lower prevalence in Israeli Jews (0.002%).1,2 These prevalence rates partially correspond with higher frequency of the susceptibility factor DQB1*06:02 (discussed below). This factor has a high frequency in African Americans (38%) and lower frequency in Ashkenazi Jews (3-6%), although not in Japanese (12%). The prevalence of narcolepsy without cataplexy has been difficult to characterize, as the diagnosis lacks specificity (relying primarily on the presence of SOREMPs), and patients are likely to be underdiagnosed or misdiagnosed. Population based studies indicate that 1-3% of the population report sleepiness with multiple SOREMPs detected by mean sleep latency test (MSLT) testing.3,4 Familial occurrence of narcolepsy-cataplexy was reported in the initial 1887 report by Westphal,5 and until recently, it has been considered to be a familial disorder. Many previously reportReceived: July 23, 2011 Accepted: July 23, 2011 Correspondence Emmanuel Mignot, MD, PhD Department of Psychiatry, Stanford University Center for Sleep Sciences and Medicine, 1050 Arastradero Road, Building A Floor 2, Palo Alto, CA 94304, USA Tel +1-650-725-6517 Fax +1-650-725-4913 E-mail mignot@stanford.edu Immunological and Genetic Aspects of Narcolepsy

Experience‐dependent induction of hypnagogic images during daytime naps: a combined behavioural and EEG study

This study characterizes hypnagogic hallucinations reported during a polygraphically recorded 90-min daytime nap following or preceding practice of the computer game Tetris. In the experimental group (N = 16), participants played Tetris in the morning for 2 h during three consecutive days, while in a first control group (N = 13, controlling the effect of experience) participants did not play any game, and in a second control group (N = 14, controlling the effect of anticipation) participants played Tetris after the nap. During afternoon naps, participants were repetitively awakened 15, 45, 75, 120 or 180 s after the onset of S1, and were asked to report their mental content. Reports content was scored by three judges (inter-rater reliability 85%). In the experimental group, 48 out of 485 (10%) sleep-onset reports were Tetris-related. They mostly consisted of images and sounds with very little emotional content. They exactly reproduced Tetris elements or mixed them with other mnemonic components. By contrast, in the first control group, only one report out of 107 was scored as Tetris-related (1%), and in the second control group only three reports out of 112 were scored as Tetris-related (3%; between-groups comparison; P = 0.006). Hypnagogic hallucinations were more consistently induced by experience than by anticipation (P = 0.039), and they were predominantly observed during the transition of wakefulness to sleep. The observed attributes of experience-related hypnagogic hallucinations are consistent with the particular organization of regional brain activity at sleep onset, characterized by high activity in sensory cortices and in the default-mode network.

Daily stress interacts with trait dissociation to predict sleep-related experiences in young adults.

Building on the previously documented effects of stress and dissociation on sleep and dreaming, we examined their interactive role in general sleep-related experiences (GSEs; e.g., nightmares, falling dreams, hypnagogic hallucinations; see Watson, 2001). Stress, sleep quality, and GSEs were assessed daily for 14 days among young adults. Baseline assessment included life stress, sleep quality, psychopathology, dissociation, and related dimensions. Multilevel analyses indicated that daily stress brings about GSEs among highly dissociative young adults. Additionally, baseline trait dissociation predicted within-subject elevation in GSEs when daily stress was high. Flawed sleep-wake transitions, previously linked to dissociation and sleep-related experiences, might account for this effect.