Epidemiology of Narcolepsy around the World

First created | 05/04/2007

Last edited   | 05/11/2012

Adapted by Maurice M. Ohayon, MD, DSc, PhD

Reference to cite: Ohayon Mm. Epidemiology of Narcolepsy. In: Bassetti C, Mignot E, Billard M (Eds). Narcolepsy and Hypersomnia. 2007, New York: Informa Health Care USA. pp. 125-132

 

Narcolepsy, a lifelong neurological disorder, has been known for more than a century (1). Its prevalence has been estimated from clinical samples in different parts of the world. Consequently, the findings have varied partly because different methodologies were used and partly because estimates were done using clinical populations and rarely general populations.

 

Prevalence in the United States

Four studies have been undertaken in the United States (Table 1):

- The first study (2) was performed among young black naval recruits. This early study reported a prevalence of narcolepsy with cataplexy at 0.02% (2 subjects on 10,000) and 3 on 100,000 among white individuals. 

- Two other studies (3,4) recruited participants through advertisement in newspapers (3) or television broadcasts and then through telephone interviews assessed the presence of narcolepsy. Afterward, the prevalence of narcolepsy was extrapolated to the general population with rates of 0.05% and 0.067%, respectively.

- A recent study (5) used the records-linkage system of the Rochester Epidemiology Project to review all medical records entered in that system between 1960 and 1989. All patients were living in Olmsted County. Each medical record was coded into the system using the International Classification of Diseases. Medical records were then classified as “Definite Narcolepsy,” “Probable Narcolepsy (laboratory confirmation)” or “Probable Narcolepsy (clinical).” Prevalence of narcolepsy (with or without cataplexy), extrapolated to the 1985 Olmsted County population, was set at 0.056% and prevalence of narcolepsy with cataplexy was set at 0.035%. This is the only study that calculated the incidence of narcolepsy. They found an incidence of 1.37/100,000 per year (1.72 for men, 1.05 for women). Moreover the incidence rate was the highest in the second decade, followed in descending order by the third, fourth and first decades.

 

 

Prevalence in Europe

Six studies have been conducted in European populations:

 

- The oldest study was performed in 1957 by Roth (6). Based on a review of his patient material, he extrapolated that the prevalence of narcolepsy in Czechoslovakia was between 0.02% and 0.03%.  This estimate also included “monosymptomatic” patients.  When only patients with narcolepsy with cataplexy were included, the prevalence was between 0.013% and 0.02%.

 

- A study of excessive daytime sleepiness reviewed the charts of 2,518 unselected patients, aged 6-92 years, admitted to an Italian general hospital during a one-year period.  A review of case histories, and clinical and polysomnographic data, revealed one case of narcolepsy.  The authors extrapolated the prevalence of narcolepsy at 0.04% in this population (7).

- Another study was performed with 58,162 young men recruited for military service in Vincennes and Tarascon (France) (8). Based on the answers to a questionnaire, narcolepsy, defined as more than two daytime sleep episodes per day accompanied by cataplexy and sleeping difficulties, was found in 0.055% of the sample.

- A study examined the prevalence of narcolepsy inside the Finnish Twin Cohort (9), 16,179 twin individuals were contacted and 12,504 returned the questionnaire (77.3% response rate). The postal questionnaire included the Ullanlinna Narcolepsy Scale (UNS). Based on the answers to that questionnaire, 75 participants were further interviewed by telephone and then invited to a clinical evaluation, including polygraphic recording and HLA blood typing. Five were strongly suspected of narcolepsy but only three were confirmed by sleep laboratory. This indicates a prevalence of narcolepsy in the Finnish population of 0.026% (95% confidence interval, 0.0-0.06).

- Ondzé et al. (10) distributed 38,527 structured questionnaires to all the physicians (general practitioners, specialists, hospital physicians, company physicians and army medical officers) in the Gard department (South of France). The questionnaires were displayed in the waiting rooms and filled out by patients 15 years of age or older; 14,195 questionnaires of patients living in the Gard department were analyzed. A total of 29 subjects were classified as possible narcoleptics and were further interviewed by telephone. Four of them were identified as probable narcoleptics and were HLA- typed. Three of them were confirmed by polysomnography and HLA typing (DRB, 1501 and DQB 0602) leading to a prevalence of narcolepsy equal to 3 / 14,195 = 0.021 % in the Gard « département ».

- Another study investigated the prevalence of narcolepsy in five European countries (The United Kingdom, Germany, Italy, Portugal and Spain). These five countries represent 205 million Europeans aged 15 years and over. The study was conducted using telephone interview with the Sleep-EVAL System to administer the questionnaires.  The system contained all the questions necessary to validate the criteria required by the ICSD classification for the diagnosis of narcolepsy. Minimal criteria for narcolepsy were defined as the presence of recurrent daytime naps occurring at least twice daily or lapses into sleep for a minimum of three months and the presence of cataplexy (the sudden bilateral loss of postural muscle tone associated with intense emotion). Based on that definition, the prevalence of narcolepsy was 0.047%  (95% confidence interval, 0.016% to 0.078%).

 

Prevalence in Asia

Five studies have been performed in Asia (Japan and China):

- The two oldest studies were conducted in Japan (12,13) and yielded the highest prevalence of narcolepsy.

The first study, a questionnaire-based survey of 12,469 adolescents from Fujisawa, estimated a prevalence of 0.16% for narcolepsy with cataplexy (12). 

Another study of 4,559 Japanese employees, aged between 17 and 59 years, used a questionnaire, followed by an interview of subjects suspected of having narcolepsy, and polysomnographic examination if appropriate (13). This study reported a prevalence of 0.18%.

 

- Three studies performed in China estimated the prevalence of narcolepsy between 0.001% and 0.04% in adults (14) and at 0.04% in a sample of 70,000 children and adolescents (15).

Subsequently, Wing et al. (16) performed another study using a general population sample of 9,851 adults aged between 18 and 65 years. They administered by telephone a validated Chinese version of the Ullanlinna Narcolepsy Scale. Twenty-eight subjects who had positive scores on the Ullanlinna Narcolepsy Scale were invited to a clinical interview and further testing (MSLT and HLA typing). Three subjects refused supplemental evaluation. Three subjects were found to have narcolepsy. This set the prevalence of narcolepsy at 0.034% (95% CI: 0.021%-0.154%).

 

 

 

Prevalence in Middle-East

 

Two studies were conducted in the Middle-East: one in Israel (17) and one in South Arabia (18):

- The lowest narcolepsy frequency was observed among Israeli Jews.  In a study of 1,526 patients (2/3 of the subjects were Jewish and 1/3 Arabs) complaining of excessive daytime sleepiness and who were clinically interviewed and polysomnographically recorded, narcolepsy was diagnosed in only six.  This sets the prevalence of narcolepsy at 0.002% in the general Israeli Jewish population, a group known for its low rate of human leukocyte antigen (HLA-DR2) (17).

 

- Another study was conducted with 23,227 individuals aged 1 year or older living in South Arabia. Interviewers administered a questionnaire in face-to-face interviews. A neurologist subsequently evaluated all participants with abnormal responses in the questionnaire. Narcolepsy was found in 0.04% of the sample (18).

 

Conclusions

Studies that have investigated the prevalence of narcolepsy have reported a prevalence ranging between 0.02% and 0.067% in North America, Europe, Asia and the Middle-East, with the exception of the two Japanese studies, where the prevalences were clearly higher than in the other studies.

Whether this is a particularity of the Japanese population or a bias due to the methodology remains to be further investigated. The major weakness of these two studies remains the assessment of cataplexy based on a single question assessing muscle weakness during a strong emotion. Questionnaire-based studies have shown that episodes of muscle weakness triggered by emotions are reported by up to 30% of the general population (8,9,11,12).  These episodes are generally not genuine cataplexy. Further investigation is needed to determine which muscles are involved, which emotions triggered the episode, and what were the frequency and last occurrence of episodes.  Furthermore, it should be stressed that epidemiological surveys completed with polysomnography yield lower prevalences than studies based only on questionnaires.

 

The importance of genetic factors in narcolepsy has been addressed for more than 60 years (19). However, the results varied from six to 40 percent of narcoleptic individuals who have a close relative with the disease (20-24).

The risk for narcolepsy was estimated to be between 10 to 40 times higher among families with a narcoleptic member than in the general population (20). However, other factors were also cited as playing a role in the appearance of narcolepsy. This was further illustrated in twin studies (25-27). Among 20 pairs of narcoleptic monozygotic twins, only 25-30% were concordant for narcolepsy-cataplexy (28).

Limitations from existing classifications pose serious difficulties in studying narcolepsy in the general population. The use of too large criteria inflates the prevalence. With the exception of cataplexy, the other narcolepsy symptoms (automatic behavior, sleep paralysis, hypnagogic hallucinations) are too poorly defined to be useful in epidemiology. Furthermore, recurrent intrusions of elements of REM sleep into the transition between sleep and wakefulness are highly prevalent in the general population: 6.2% for sleep paralysis and 24.1% for hypnagogic hallucinations (11). This indicates that these symptoms are not specific to narcolepsy (29,30).

References

 

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2.        Solomon P. Narcolepsy in negroes. Dis Nerv Syst 1945;6:176-183.

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5.        Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep 2002;25:197-202.

6.        Roth B, Eng. Trans. Broughton R. Narcolepsy and Hypersomnia. Chapter 10. London 1980.

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9.        Hublin C, Kaprio J, Partinen M, Koskenvuo M, Heikkila K, Koskimies S, Guilleminault C. The prevalence of narcolepsy: an epidemiological study of the Finnish Twin Cohort. Ann Neurol 1994;35:709-716.

10.      Ondzé B, Lubin S, Lavendier B, Kohler F, Mayeux D, Billiard M.  Frequency of narcolepsy in the population of a French “département”. J Sleep Res1998; 7: 193.

11.      Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva T. Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology 2002;58:1826-1833.

12.      Honda Y. Census of narcolepsy, cataplexy and sleep life among teenagers in Fujisawa city. Sleep Res 1979; 8:191.

13.      Tashiro T, Kanbayashi T, Iijima S, Hishikawa Y. An epidemiological study on prevalence of narcolepsy in Japanese. J Sleep Res 1992; 1(suppl):228.

14.      Wing YK, Chiu HF, Ho CK, Chen CN. Narcolepsy in Hong Kong Chinese--a preliminary experience. Aust N Z J Med 1994;24:304-306.

15.      Han F, Chen E, Wei H, Dong X, He Q, Ding D, Strohl KP. Childhood narcolepsy in North China. Sleep  2001; 24(3):321-324.

16.      Wing YK, Li RH, Lam CW, Ho CK, Fong SY, Leung T. The prevalence of narcolepsy among Chinese in Hong Kong. Ann Neurol 2002;51:578-584.

17.      Lavie P, Peled, R. Letter to the Editor: Narcolepsy is a Rare Disease in Israel. Sleep 1987; 10:608-609.

18.      al Rajeh S, Bademosi O, Ismail H, Awada A, Dawodu A, al-Freihi H, Assuhaimi S, Borollosi M, al-Shammasi S. A community survey of neurological disorders in Saudi Arabia: the Thugbah study. Neuroepidemiology 1993;12(3):164-178.

19.      Krabbe E, Magnussen G. Familial aspects of narcolepsy. Tran Am Neurol Ass 1942; 17:149-173.

20.      Nevsimalova S, Mignot E, Sonka K, Arrigoni JL. Familial aspects of narcolepsy-cataplexy in the Czech Republic. Sleep 1997;20:1021-1026.

21.      Billiard M, Pasquie-Magnetto V, Heckman M, Carlander B, Besset A, Zachariev Z, Eliaou JF, Malafosse A. Family studies in narcolepsy. Sleep 1994;17(8 Suppl):S54-S59.

22.      Hayduk R, Flodman P, Spence MA, Erman MK, Mitler MM. HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy. Sleep 1997;20:850-857.

23.      Guilleminault C, Mignot E, Grumet FC. Familial patterns of narcolepsy. Lancet 1989; 2(8676):1376-1379.

24.      Baraitser M, Parkes JD. Genetic study of narcoleptic syndrome. J Med Genet 1978;15:254-259.

25.      Honda M, Honda Y, Uchida S, Miyazaki S, Tokunaga K. Monozygotic twins incompletely concordant for narcolepsy. Biol Psychiatry  2001;49:943-947.

26.      Pollmacher T, Schulz H, Geisler P, Kiss E, Albert ED, Schwarzfischer F. DR2-positive monozygotic twins discordant for narcolepsy. Sleep 1990;13:336-343.

27.      Partinen M, Hublin C, Kaprio J, Koskenvuo M, Guilleminault C. Twin studies in narcolepsy. Sleep 1994;17(8 Suppl):S13-S16.

28.      Mignot E. Genetics of narcolepsy and other sleep disorders. Am J Hum Genet 1997;60:1289-1302.

29.      Ohayon MM, Zulley J, Guilleminault C, Smirne S. Prevalence and pathological associations of sleep paralysis in the general population. Neurology 1999;52:1194-1200.

30.      Ohayon MM, Priest RG, Caulet M, Guilleminault C. Hypnagogic and hypnopompic hallucinations: pathological phenomena? Br J Psychiatry 1996;169: 459-467.

More Information

Dyssomnias
Dyssomnias are sleep disorders characterized by abnormalities in the quantity, quality or timing of sleep

 

Breathing Disorders
Sleep disordered breathing encompasses a spectrum of conditions whose common feature is intermittent loss of upper airway patency associated with sleep

 

Hypersomnia (disabled)

 

Insomnia
More than fifty studies of insomnia based on data collected in various representative community-dwelling samples or populations were published with highly variable rates

 

Excessive Daytime Sleepiness
Prevalence of daytime sleepiness has been reported to range from 0.5% to about 40%

 

Narcolepsy
This syndrome is characterized by an imperative need to sleep suddenly and for brief periods, recurring at more or less close intervals

 

Periodic Limb Movement
This syndrome is characterized by periodic episodes of repetitive limb movements caused by contractions of the muscles during sleep

 

Restless Legs Syndrome
Restless legs syndrome, initially reported by Ekbom (1944), is characterized by disagreeable leg sensations occurring most often at sleep onset that provoke an urge to move the legs