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PubMed2002

The prevalence of narcolepsy among Chinese in Hong Kong.

Narcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500-fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical-polysomnographic-HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep-wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010-0.117%). All available narcoleptic subjects were HLA DRB1-1501 positive and 50% were DQB1-0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross-ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.

Adult↗
PubMed2003

Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia?

Does narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical "tetrad"--cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB1*0602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a "chronic psychotic," while in fact they can now be properly diagnosed and treated.

Bipolar Disorder↗
PubMed2002

Diagnoses received by narcolepsy patients in the year prior to diagnosis by a sleep specialist.

STUDY OBJECTIVES: Narcolepsy is a neurological disorder whose clinical features include excessive daytime sleepiness, hypnagogic hallucinations, cataplexy, sleep paralysis, and disrupted nocturnal sleep. It has been shown that there may be quite a long interval between the onset of symptoms, and the correct diagnosis. We tested the hypothesis that given their severe symptomatology, these patients would have been diagnosed more often with a variety of psychiatric and neurologic conditions than controls in the year prior to confirmation of their narcolepsy diagnosis. DESIGN: Using the Province of Manitoba Health database, we compared the diagnoses made in the year prior to initial sleep disorder center evaluation of 77 patients with narcolepsy (33 males, 44 females) and 1,155 matched control subjects from the general population. SETTING: Sleep disorders center in University-based teaching hospital PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Patients were much more likely than controls to be diagnosed with mental disorders (Odds ratio (OR) = 4.0645; 95% confidence limit (CL) = 2.4671-6.6962; p<0.0001) and nervous system disorders (OR= 5.0495; CL = 3.0606 -8.3309; p<0.0001) and there was a trend towards more injuries in these patients (OR =1.6316; CL = 0.9857-2.7007; p=0.0514). We found that cases were statistically much more likely than controls to have received a diagnosis for neurotic disorders (17% of cases), depression (16%), personality disorders (3%) and adjustment reaction (4%). Although the cases had twice as many doctor visits as the controls (9.3 +/- 0.97 (sem) vs. 4.8 +/- 0.17 p<0.0001), only 38% of them had received a diagnosis of narcolepsy in the year prior to sleep specialist evaluation. Neurologists had the highest "success rate" for correct diagnosis: neurologists diagnosed narcolepsy in 55% of the cases they had seen. The other medical practitioners diagnosed narcolepsy in a much smaller percentage of the cases they had seen: 23.5% for internists (excluding neurologists), 21.9% for general practitioners, 11.1% for psychiatrists, and 0% for pediatricians. CONCLUSIONS: In the year prior to documentation of narcolepsy in a sleep disorders center, patients with narcolepsy were diagnosed with a wide variety of mental and neurologic disorders. Our findings are supportive of either the coexistence of these disorders in narcolepsy patients or a high frequency of missed diagnosis by their clinicians. The latter may help explain the very long interval between onset of symptoms and correct diagnosis.

Adjustment Disorders↗
PubMed2004

Schizophrenia and narcolepsy: a review with a case report.

Several reports emphasize the importance of differentiating between psychosis in schizophrenia and the psychotic form of narcolepsy. The failure to identify narcolepsy leads to the labeling of patients as refractory to standard treatments for schizophrenia and retards consideration of intervention for narcolepsy in which psychosis can improve with psychostimulant treatment. Psychosis in patients with narcolepsy can occur in three ways: (i) as the psychotic form of narcolepsy with hypnagogic and hypnopompic hallucinations; (ii) as a result of psychostimulant use in a patient with narcolepsy; and (iii) as the concurrent psychosis of schizophrenia in a patient with narcolepsy. The present case report describes a difficult-to-treat patient who likely had concurrent schizophrenia and narcolepsy. It then summarizes the literature related to the treatment of the three types of patients with psychosis associated with narcolepsy.

Adult↗
PubMed2006

The psychosocial problems of children with narcolepsy and those with excessive daytime sleepiness of uncertain origin.

BACKGROUND: Narcolepsy is a predominantly rapid eye movement sleep disorder with onset usually in the second decade but often in earlier childhood. Classically it is characterized by combinations of excessive sleepiness especially sleep attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The psychosocial effects of this lifelong condition are not well documented, especially in children. This study aims to describe the psychosocial profile of a large group of children with narcolepsy compared with other excessively sleepy children and controls. METHODS: We used an international cross-sectional questionnaire survey of children aged from 4 to 18 years who had received from a physician a diagnosis of narcolepsy compared with age- and gender-matched controls. Assessments were made of behavior, mood, quality of life, and educational aspects. RESULTS: Recruited children were separated into those who met conventional criteria for narcolepsy (n = 42) and those whose primary complaint was excessive daytime sleepiness without definite additional features of narcolepsy (excessive daytime sleepiness group; n = 18). Compared with controls, children with narcolepsy and also those with excessive daytime sleepiness alone showed significantly higher rates of behavioral problems and depression. Again, to a significant extent, their quality of life was poorer and they had more educational problems. The children with narcolepsy and the excessive daytime sleepiness group were indistinguishable from each other on these measures. CONCLUSIONS: A range of psychosocial problems can be identified in children with narcolepsy. The origins of these problems are unclear. The similar profiles of difficulties in the narcolepsy and excessive daytime sleepiness groups suggest that excessive sleepiness is the main cause. Clinicians and others responsible for the care of such children need to be mindful of the importance of early detection, intervention, and, ideally, the prevention of these problems.

Adolescent↗
PubMed2002

Benefits and risks of pharmacotherapy for narcolepsy.

Narcolepsy is a life-long central nervous system (CNS) syndrome characterised by excessive sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed night-time sleep. Unsuccessfully treated narcolepsy confers increased risks on patients and on society due to the patient's increased chance of becoming involved in vehicle crashes and workplace mishaps. The syndrome may be diagnosed by a clinical history positive for cataplexy and excessive daytime sleepiness and negative for other more common sleep disorders such as sleep apnoea and sleep deprivation. Night-time polysomnography and multiple sleep latency testing are helpful in differentiating narcolepsy from other sleep problems. Recent data from canine, murine, and human forms of narcolepsy indicate that genetically or developmentally mediated deficits in the hypocretin neurotransmitter system may cause some, but not all, forms of narcolepsy. Pharmacotherapy for narcolepsy is required to control symptoms and involves the use of CNS stimulants or modafinil to control sleepiness and antidepressant medications or sodium oxybate to control cataplexy. Modafinil and sodium oxybate have been developed and approved specifically for the indication of narcolepsy based on large, double-blind, placebo-controlled, parallel group efficacy and safety studies. The efficacy of drugs in the treatment of narcolepsy is variable from patient to patient and usually associated with adverse effects that can limit patient compliance and, therefore, symptom control. Nevertheless, the benefits of pharmacotherapy are judged to outweigh the risks to the patient. The favourable benefit-risk ratio of pharmacotherapy is greater if one considers the reduced risk to society of vehicle crashes and workplace mishaps that might be precipitated by attentional lapses or sleep attacks in the untreated or under-treated patient with narcolepsy.

Animals↗
PubMed2000

Narcolepsy: genetic predisposition and neuropharmacological mechanisms. REVIEW ARTICLE.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime somnolence (EDS), cataplexy and REM sleep-related abnormalities. It is a frequently-occurring but under-diagnosed condition that affects 0.02 to 0.18% of the general population in various countries. Although most cases occur sporadically, familial clustering may be observed; the risk of a first-degree relative of a narcoleptic developing narcolepsy is 10-40 times higher than in the general population. The disorder is tightly associated with the specific human leukocyte antigen (HLA) allele, DQB1*0602 [most often in combination with HLA-DR2 (DRB1*15)]. Genetic transmission is, however, likely to be polygenic in most cases, and genetic factors other than HLA-DQ are also likely to be implicated. In addition, environmental factors are involved in disease predisposition; most monozygotic twins pairs reported in the literature are discordant for narcolepsy. Narcolepsy was reported to exist in canines in the early 1970s. Both sporadic and familial cases are also observed in this animal species. A highly-penetrant single autosomal recessive gene, canarc-1, is involved in the transmission of narcolepsy in Doberman pinschers and Labrador retrievers. Positional cloning of this gene is in progress, and a human homologue of this gene, or a gene with a functional relationship to canarc-1, might be involved in some human cases. Human narcolepsy is currently treated with central nervous system (CNS) stimulants for EDS and antidepressants for cataplexy and abnormal REM sleep. These treatments are purely symptomatic and induce numerous side effects. These compounds disturb nocturnal sleep in many patients, and tolerance may develop as a result of continuous treatment. The canine model is an invaluable resource for studying the pharmacological and physiological control of EDS and cataplexy. Experiments using canine narcolepsy have demonstrated that increased cholinergic and decreased monoaminergic transmission are likely to be at the basis of the pathophysiology of the disorder. Pharmacological studies have shown that blockade of norepinephrine uptake mediates the anticataplectic effect of currently prescribed antidepressants, while blockade of dopamine uptake and/or stimulation of dopamine release mediates the awake-promoting effect of CNS stimulants. Studies in canine narcolepsy also suggest that mechanisms and brain sites for triggering cataplexy are not identical to those regulating REM sleep. It may thus be possible to develop new pharmacological compounds that specifically target abnormal symptoms in narcolepsy, but do not disturb physiological sleep/wake cycles. (See also postscript remarks).

Journal Article↗
PubMed1989

Narcolepsy without unique MHC class II antigen association: studies in the canine model.

Human narcolepsy is almost exclusively associated with the major histocompatibility complex (MHC) class II antigen HLA-DR2 and is the strongest HLA-disease association described to date. Canine narcolepsy resembles the human disease in its behavioral manifestations and responses to therapeutic drugs. Therefore, mixed leukocyte culture (MLC) was used to study differences in the canine MHC class II (DLA-D) antigens present in narcoleptic dogs to determine whether an analogous, unique DLA-D antigen could be identified in canine narcolepsy. Results show at least five different DLA-D antigens appear in potential narcoleptic haplotypes among the 29 dogs studied. The data demonstrate that, unlike man, in dogs there is no unique D locus antigen associated with narcolepsy and further suggest that linkage disequilibrium with a specific MHC antigen is unlikely to be essential for the manifestation of canine narcolepsy. Because human narcolepsy is thought to be multigenic, the canine narcolepsy-MHC dissociation suggests that the dog model may help elucidate the non-MHC narcolepsy gene(s).

Animals↗
PubMed2004

A putative link between childhood narcolepsy and obesity.

BACKGROUND AND PURPOSE: While there have been anecdotal observations of binge eating in childhood-onset narcolepsy, the possible relationship between increased weight gain and childhood-onset narcolepsy has not been evaluated. PATIENTS AND METHODS: A retrospective, case-control design was used to compare the body mass index (BMI) of 31 narcolepsy children at the time of diagnosis with that of healthy, age- and gender-matched controls. RESULTS: The median BMI in the narcolepsy subjects was 22.93 as compared to that in controls of 20.36 (P=0.001). BMI did not differ significantly between narcolepsy subjects who had received prior psychotropic medications and those who had not. The mean BMI of 22 of 31 narcolepsy subjects who had not received psychotropic medications prior to diagnosis was also significantly higher than that of controls (25.1, SEM 1.53 versus 21.1, SEM 0.56; P=0.008 ). CONCLUSION: The tendency for increased weight gain is intrinsic to childhood narcolepsy and is manifested relatively early in the course of the disorder. Correlation of this finding with hypocretin and leptin metabolism may further understanding of the pathogenesis of narcolepsy.

Adolescent↗
PubMed2001

MAO-A and COMT polymorphisms and gene effects in narcolepsy.

Narcolepsy presents one of the tightest associations with a specific HLA antigen (DQB1*0602) but there is strong evidence that non-HLA genes also confer susceptibility. Recent observations have implicated the hypocretin/orexin system in narcolepsy in both humans and animals. In addition, the implication of monoaminergic systems in the pathophysiology of narcolepsy is well established and a significant association between the monoamine oxydase-A (MAO-A) gene and human narcolepsy has recently provided a possible genetic link. We investigated polymorphisms of MAO-A and catechol-O-methyltransferase (COMT) in 97 Caucasians with well-defined narcolepsy-cataplexy and sought for genotypic effects on disease symptoms. No evidence of association between genotype or allele frequencies of both MAO-A or COMT gene and narcolepsy was found. However, a sexual dimorphism and a strong effect of COMT genotype on disease severity were found. Women narcoleptics with high COMT activity fell asleep twice as fast as those with low COMT activity during the multiple sleep latency test (MSLT) while the opposite was true for men. COMT genotype also strongly affected the presence of sleep paralysis and the number of REM sleep onsets during the MSLT. In agreement with well-documented pharmacological results in canine narcolepsy, this study reports the first genetic evidence for the critical involvement of the dopaminergic and/or noradrenergic systems in human narcolepsy.

Cataplexy↗
PubMed1996

Sleepiness and performance in narcolepsy.

Previous attempts to investigate the relationship between sleepiness and performance for subjects with narcolepsy have been limited by both the ability of narcoleptic subjects to contain their sleepiness for brief testing periods and the potential lack of sensitivity of routine performance tasks to sleepiness induced changes. The present study developed a research protocol which allowed subjects with narcolepsy to express states of sleepiness and non sleepiness and to then compare the performance of subjects with narcolepsy to age, gender and IQ matched controls on tasks evaluating automatic, attentional and complex cognitive functioning. The results indicated that at high arousal subjects with narcolepsy performed as well as controls on automatic tasks suggesting that the capacity to perform for narcolepsy subjects is not restricted by physiological factors but is secondary to the effects of sleepiness. Comparison of both the within subject effects for narcolepsy subjects of the transition between high and low arousal states, and the between subject effects of low arousal for narcolepsy subjects compared to controls indicate that complex cognitive tasks are the most sensitive to arousal fluctuation. This study provides support for the subjective experiences of subjects with narcolepsy of diminished cognitive function associated with the disorder.

Adult↗
PubMed1998

Segregation of HLA genes in multicase narcolepsy families.

In the past 15 years, 411 sporadic narcolepsy patients have been diagnosed in the Hephata Klinik, Schwalmstadt, Germany. They were explored for presence or absence of excessive daytime sleepiness and narcolepsy in their relatives. A subset of 39 patients were explored for presence or absence of parasomnias. Six patients had more than one relative affected by narcolepsy-cataplexy. Forty-seven family members were investigated with the Stanford Center for Narcolepsy Sleep Inventory and a standardized parasomnia questionnaire. Twenty-four relatives had nocturnal polysomnographies and Multiple Sleep Latency Tests. HLA class I typing was performed in all sporadic and familial cases, class II and microsatellite typing was performed in all members of multicase families. Based on the Finnish prevalence study by Hublin et al., 1994, the relative risk for first degree relatives to develop narcolepsy-cataplexy was in our sample 16.5, 34.2 for excessive daytime sleepiness and 426.9 for parasomnias. Cataplexy, excessive daytime sleepiness and single narcoleptic symptoms in the multicase families segregate with the DRBI*1501, CARII:200, CARI: 103, DQBI*0602 haplotype. In two families, members with narcolepsy and isolated symptoms have inherited the DRBI*1501/DQBI*0602 haplotype from the nonaffected parent. The observed segregations in these two families may support the view that narcoleptic symptoms are expressed by DRBI*1501/DQBI*0602 carriers, independent of haplotype origin. Parasomnias do not segregate with a specific haplotype. The frequency of parasomnias in narcolepsy is much higher than in the general population. The empirical risk for first degree family members of narcolepsy patients to develop cataplexy seems to be low, whereas it is higher for EDS and highest for parasomnias.

Adult↗
PubMed1994

Epidemiology of narcolepsy.

The prevalence of narcolepsy is usually presented at about 50/100,000. There are, however, marked differences of about 2,500-fold between the lowest and the highest reported prevalence. This discrepancy is at least partly explained by differences in the study populations and methods. There are, however, no earlier population-based epidemiological studies with polygraphically confirmed diagnoses. We studied the occurrence of symptoms resembling the two main manifestations of narcolepsy, i.e. abnormal sleep tendency and emotion-associated muscular weakness, in an adult twin cohort (n = 16,179) with a questionnaire. A total of 3.2% met the minimal diagnostic criteria of the International Classification of Sleep Disorders for narcolepsy. Eleven questionnaire items assessing the main manifestations of narcolepsy formed a measure called the Ullanlinna Narcolepsy Scale (UNS), which has been validated. The UNS score was calculated for 11,354 subjects. Those (n = 75) having a UNS score equal or higher than the lowest value in a narcolepsy patient group were studied. Thirty-one of them (fulfilling also the minimal diagnostic criteria) were interviewed, and those suspected of having narcolepsy (n = 5) were evaluated in the sleep laboratory. In three subjects the narcolepsy diagnosis was verified (all dizygotic, nonfamilial and human leukocyte antigen DR2/DQB-0602 positive), giving a prevalence of 0.026% in the adult Finnish (Caucasian) population.

Adult↗
PubMed1997

Familial aspects of narcolepsy-cataplexy in the Czech Republic.

A group of 153 probands with narcolepsy included 38 subjects (24.8%) with a familial incidence of excessive daytime sleepiness (EDS). In 15 cases (9.8%), at least one additional family member suffered from narcolepsy-cataplexy; only EDS was present in the remaining 23 cases (15.0%). One thousand eighty-two relatives were evaluated. The percentage of first degree relatives affected with narcolepsy-cataplexy was 2.28% (1.20% if only clinically confirmed cases were accounted); the adequate value for second degree relatives was 1.49%. The occurrence of EDS exceeded these values several times (4.28% in first degree relatives, 6.57% in second degree relatives). The vertical mode of transmission was found in most families. Human leukocyte antigen (HLA) typing was performed in six families with multiple-case incidence of narcolepsy. Forty-one blood samples were analyzed (12 patients with narcolepsy, 7 with only EDS, 2 with sleep apnea syndrome, and 20 healthy relatives). HLA DR2+ and DQB1*0602+ were found in only 8 out of 12 narcoleptic patients with cataplexy and in six out of seven patients with isolated attacks of sleepiness. These findings support the hypothesis that there is a common genetic basis for narcolepsy associated with cataplexy and "monosymptomatic" forms of narcolepsy and suggest the existence of non-major histocompatibility complex (MHC) susceptibility factors for narcolepsy.

Adolescent↗
PubMed2006

EFNS guidelines on management of narcolepsy.

Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.

Advisory Committees↗
PubMed1998

Genetic and familial aspects of narcolepsy.

Narcolepsy-cataplexy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep. The development of human narcolepsy involves environmental factors acting on a specific genetic background. The importance of environmental factors is evidenced by the reported 25 to 31% of monozygotic twins who are concordant for narcolepsy. One of the predisposing genetic factors is located in the MHC DQ region. More than 85% of all narcoleptic patients with definite cataplexy share a specific HLA allele, HLA DQB1*0602 (most often in combination with HLA DR2), compared with 12 to 38% of the general population, as evaluated in various ethnic groups. Genetic factors other than HLA are also likely to be involved. Even if genuine multiplex families are rare, 1 to 2% of the first-degree relatives of narcolepsy patients manifest the disorder, compared with 0.02 to 0.18% in the general population. Studies using a canine model of narcolepsy illustrate the importance of non-MHC genes in disease predisposition. In this model, narcolepsy is transmitted as a single autosomal recessive trait, canarc-1. In spite of an association with immune-related polymorphisms, narcolepsy does not appear to be a classic autoimmune disease. Other pathophysiologic models involving the microglia and the release of specific cytokines in the CNS may be involved and are being explored. This approach, together with positional cloning studies in humans and canines, should reveal the cause of narcolepsy and open new therapeutic avenues.

Animals↗
PubMed2005

Narcolepsy in Singapore: is it an elusive disease?

INTRODUCTION: The aims of the study were to determine the demographic, clinical, and polysomnographic characteristics of narcolepsy, and to address the difficulties in diagnosing narcolepsy and cataplexy, which is a cardinal symptom. We also ventured to investigate the differences between narcolepsy with and without cataplexy. MATERIALS AND METHODS: Data were collected retrospectively from patients diagnosed with narcolepsy at the Sleep Disorder Unit of Singapore General Hospital over 5 years. Each patient had had a detailed clinical evaluation and overnight polysomnography (PSG) followed by a multiple sleep latency test (MSLT). RESULTS: A total of 28 cases were studied. Males made up 85.7% of the total and females, 14.3%. The mean age was 30.9 years. All had excessive daytime sleepiness. Other manifestations were cataplexy (48.1%), sleep paralysis (51.9%), hypnogogic hallucinations (84%), disturbed night sleep (29.2%), automatisms (17.4%) and catnaps (95.8%). The mean duration of symptoms was 7.24 years. In the MSLT, the mean values for mean sleep latency and number of sleep onset rapid eye movement (REM) periods (SOREMP) were 4.3 minutes and 2.7, respectively. Narcolepsy was associated with obstructive sleep apnoea and periodic limb movement disorder (35.7%). All the variables were compared between those who had narcolepsy with cataplexy and without cataplexy. The duration of presenting complaint, REM latency, respiratory disturbance index, number of SOREMPs and the presence of sleep paralysis were significantly different in the 2 groups. CONCLUSIONS: Narcolepsy predominantly affects young males. Concurrence of other sleep disorders is not uncommon. Some differences are evident between those who have narcolepsy with and without cataplexy.

Adolescent↗
PubMed2001

Current concepts in the etiology, diagnosis and treatment of narcolepsy.

Background and purpose: Narcolepsy is the most common neurologic cause of excessive daytime sleepiness. Rapid eye movement (REM) sleep phenomena such as cataplexy, sleep paralysis and hypnagogic hallucinations can also occur. Cataplexy, a sudden bilateral loss of muscle tone usually brought on by emotional reactions such as excitement, is essentially unique to narcolepsy. Narcolepsy, which has a prevalence of 0.02-0.05% in the US, has a profound influence on the quality of life and safety of affected individuals.Patients and methods: The most characteristic and striking physiological abnormality observed in narcolepsy is the sleep-onset REM, or the occurrence of REM sleep at, or within 20 min of, the onset of sleep. The diagnosis is established by nocturnal polysomnography, and the Multiple Sleep Latency Test (MSLT).Results: Familial cases of narcolepsy have been reported, with the risk to first-degree relatives estimated at 1-2%; however, most cases are sporadic and the syndrome is generally believed to involve environmental factors acting on a specific genetic background. The observation of an HLA association in narcolepsy suggests that autoimmunity may play a role in the disorder. However, extensive studies have failed to find convincing evidence of an autoimmune process. Patients with narcolepsy have recently been shown to be deficient in hypocretin, also called orexin, in the cerebrospinal fluid and have a reduction in hypocretin cells in the lateral hypothalamus. This suggests that hypocretins could potentially provide a novel therapeutic approach to the treatment of narcolepsy.Conclusions: Although non-pharmacologic measures can be helpful in treating narcolepsy, most patients require pharmacotherapy that includes psychostimulants or modafinil. Cataplexy is controlled by tricyclic antidepressants or selective serotonin reuptake inhibitors.

Journal Article↗