Elsevier

Sleep Medicine

Volume 2, Issue 1, January 2001, Pages 5-17
Sleep Medicine

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

https://doi.org/10.1016/S1389-9457(00)00081-2Get rights and content

Abstract

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.

Section snippets

Clinical description and symptoms

Narcolepsy is the most common neurologic cause of excessive daytime sleepiness (EDS). In addition to EDS and cataplexy, the two most significant symptoms of narcolepsy, other rapid eye movement (REM) sleep phenomena such as sleep paralysis and hypnagogic hallucinations can also occur [1].

The sleepiness associated with narcolepsy often becomes irresistible, and leads to repeated daily episodes of involuntary ‘naps’ or ‘sleep attacks’ that can occur at inappropriate and unpredictable times, such

Genetics

A family history is important in the evaluation of the patient with EDS, and may include genetic testing. The diagnostic value of genetic testing however, is probably overestimated [3]. More than 99% of individuals with either the HLA DQB1*0602 and DQA1*0102 haplotypes do not have narcolepsy, and 1–5% of patients with classic narcolepsy do not have either of these haplotypes. Therefore, the absence of the pre-disposing genetic markers does not exclude the diagnosis of narcolepsy, while their

Diagnostic criteria

Diagnostic criteria for narcolepsy are summarized in Table 1 [8]. Excessive sleepiness (daytime sleepiness and frequent naps) is usually the presenting complaint in patients with narcolepsy. However, it is recognized that there is considerable overlap among the clinical features of narcolepsy and other sleep disorders. For instance, sleep attacks may occur in patients with chronic severe sleepiness as well as in patients with narcolepsy. Additionally, the classic symptoms of narcolepsy-EDS,

Therapeutic options

Although there is no cure for narcolepsy, a number of treatment options are available. Treatment should be individualized based on the severity of symptoms and it might take weeks or months before an optimal regimen is achieved. Even so, complete control of EDS and cataplexy is rarely possible.

Conclusions

Narcolepsy is a chronic neurologic disorder characterized by EDS, cataplexy, hypnagogic hallucinations, and sleep paralysis. Although patients report EDS and cataplexy as the most frequent symptoms of this condition, EDS is generally considered to be the most debilitating. The socioeconomic impact of narcolepsy may be as high as that of epilepsy. However, knowledge about narcolepsy often remains limited even among neurologists, and the disorder is frequently undiagnosed or misdiagnosed for a

References (75)

  • L Ferraro et al.

    Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers

    Biol Psychiatry

    (1997)
  • L Ferraro et al.

    The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor

    Neurosci Lett

    (1996)
  • L Ferraro et al.

    The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade

    Neuropsychopharmacology

    (1999)
  • M.M Mitler et al.

    Long-term efficacy and safety of modafinil (Provigil) for the treatment of excessive daytime sleepiness associated with narcolepsy

    Sleep Med

    (2000)
  • L Scrima et al.

    Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures (see comments)

    Biol Psychiatry

    (1989)
  • J.M Siegel

    Narcolepsy: a key role for hypocretins (orexins) (comment)

    Cell

    (1999)
  • M.S Aldrich et al.

    Narcolepsy and the hypocretin receptor 2 gene

    Neuron

    (1999)
  • M.J Thorpy

    ICSD-International classification of sleep disorders. Diagnostic coding manual

    (1990)
  • P.M Green et al.

    Narcolepsy. signs, symptoms, differential diagnosis, and management

    Arch Fam Med

    (1998)
  • S Anic-Labat et al.

    Validation of a cataplexy questionnaire in 983 sleep-disorders patients

    Sleep

    (1999)
  • M.S Aldrich

    Narcolepsy. New Engl J Med

    (1990)
  • National Institutes of Health. National Heart Lung, and Blood Institute. Narcolepsy. Bethesda: National Institutes of...
  • C Hublin

    Narcolepsy. Current treatment options. CNS Drugs

    (1996)
  • American Sleep Disorders Association. International classification of sleep disorders, revised: diagnostic and coding...
  • P Passouant et al.

    The evolution of narcolepsy with age

  • M.S Wise

    Childhood narcolepsy

    Neurology; 50

    (1998)
  • R.E Yoss et al.

    Narcolepsy in children

    Pediatrics

    (1960)
  • M.J Challamel et al.

    Narcolepsy in children

    Sleep

    (1994)
  • M Goswami

    The influence of clinical symptoms on quality of life in patients with narcolepsy

    Neurology; 50

    (1998)
  • R Broughton et al.

    Life effects of narcolepsy in 180 patients from North America Asia and Europe compared to matched controls

    Can J Neurol Sci

    (1981)
  • R.J Broughton et al.

    Comparison of the psychosocial effects of epilepsy and narcolepsy/cataplexy: a controlled study

    Epilepsia

    (1984)
  • W.A Broughton et al.

    Psychosocial impact of narcolepsy

    Sleep

    (1994)
  • E Mignot

    Genetic and familial aspects of narcolepsy

    Neurology; 50

    (1998)
  • H Kadotani et al.

    Genetic studies in the sleep disorder narcolepsy

    Genome Res

    (1998)
  • E Mignot et al.

    HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients

    Sleep

    (1997)
  • S Nishino et al.

    Neuropharmacology and neurochemistry of canine narcolepsy

    Sleep

    (1994)
  • M.S Aldrich et al.

    Neurochemical studies of human narcolepsy: alpha-adrenergic receptor autoradiography of human narcoleptic brain and brainstem

    Sleep

    (1994)
  • Cited by (0)

    View full text