Narcolepsy historical perspective
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Narcolepsy is a long term neurological sleep disorder, which was first reported in Germany by Westphal and Fisher (1877-1878). French physician Jean-Baptiste-Édouard Gélineau (1880) first named this disorder as narcolepsy and identified it as a specfic clinical entity, while Loëwenfeld (1902) and Kinnier Wilson (1928) subsequently named the terms, cataplexy and sleep paralysis, respectively. Hypocretins (orexins) were first identified by DeLecea and Sakurai in 1990s but association between Hypocretin deficiency and human narcolepsy was established by Nishino and Ripley later in 2000.
- The earliest account of narcolepsy was described by Thomas Willis (1621-1675) in patients, "with a sleepy disposition who suddenly falls fast asleep."
- The term narcolepsy is derived by combining the Greek narke numbness, stupor and lepsis attack, to seize.
- The first-ever convincing descriptions of narcolepsy and cataplexy were reported by Westphal (1877) and Fisher (1878) in Germany. Both descriptions observed a hereditary factor in narcolepsy; the mother of Westphal's patient and a sister of Fisher's patient had similar clinical features. They also reported the unique association of excitement and sleepiness triggering episodes of muscle weakness.
- French physician Jean-Baptiste-Édouard Gélineau (1880) described this condition in a wine merchant as neurosis or a functional condition. Gélineau gave narcolepsy its name, which is the English form of the French word narcolepsie, and recognized narcolepsy as a specific clinical entity. Although Gélineau named this distinct clinical entity he did not differentiate episodes of muscle weakness and sleep attacks triggered by emotions as he proposed common physiology for these two distinct symptoms of narcolepsy.
- Cataplexy from the Greek kataplexis (fixation of the eyes), was first named by Loëwenfeld (1902) as he was the first to name brief episodes of muscle weakness triggered by emotions.
- Kinnier Wilson (1928) first coined the term, "sleep paralysis."
- Large case series of narcolepsy with cataplexy was published by Addie (1926), Wilson (1927), and Daniels (1934). Review of narcolepsy-cataplexy by Daniels is considered by many as one of the most insightful clinical reviews published.
- Various causes or lesions were proposed for narcolepsy. Tumors situated in relation to the third ventricle were suggested as a possible cause of narcolepsy by Wilson. The association of oculomotor paralysis and somnolence led to the pioneering work of Von Economo (1930) who first recognized the posterior hypothalamus as a critical region for the promotion of wakefulness and correctly proposed that a region in the posterior hypothalamus was lesioned in human narcolepsy. He specifically wrote: “it is very probable, though not proved, that the narcolepsy of Redlich, Westphal, and Gélineau has its primary cause in a yet unknown disease of that region”.
- The classic description of narcolepsy tetrad was possible due to further work by Yoss and Daly at the Mayo clinic in 1957 and Bedrich Roth in Prague.
- REM sleep at the onset of sleep attack in narcoleptic patients was first ever recorded and reported by Vogel (1960), an observation extended by Rechschaffen and Dement in 1967. Hishikawa (1968) studied the EEG of narcoleptic patients. These authors together first articulated the now classical hypothesis of dissociated REM sleep and explained some symptoms of narcolepsy. Their discovery established a multiple sleep latency test as a standard diagnostic test for narcolepsy in 1970.
- The first epidemiological studies of narcolepsy were performed by Roth (1980) and Dement (1972-73), revealing a prevalence of 0.02-0.05% for narcolepsy with cataplexy. 
- Canine narcolepsy in various breeds of dogs was identified and described in 1973, by Knecht and Mitler.
- Dr. Honda (1981), together with Drs. Asaka and Juji, initiated a research study on narcolepsy and observed a significant increase in the frequency of HLA-B35 in patients with narcolepsy, which lead to discovery in 1983 that all patients with narcolepsy were HLA-DR2 positive, while only 30% healthy controls had similar HLA-DR2. This discovery was subsequently confirmed in research studies conducted by Langdon N (1984), Billiard M (1985), Mueller-Eckhardt G (1986), and Poirier G (1986).
- Link with the HLA-DQB1*0602 gene on chromosome 6 was established in 1980s. As many HLA associated disorders are also autoimmune in nature, it raised the possibility that narcolepsy may be an autoimmune disorder.
- Hypocretins (orexins) were identified in 1990s. In 1998, DeLecea and Sakurai identified hypocretins/orexins almost simultaneously with a difference of a few weeks. Sakurai (1998) also identified and mapped associated receptors with these peptides, including Hypocretin (orexin) receptor 1 (HCRT1) and Hypocretin (orexin) receptor 2 (HCRT2).
- Hypocretin deficiency was associated with human narcolepsy by Nishino and Ripley in 2000.
Landmark Events in the Development of Treatment Strategies
- Various methods were initially proposed in the treatment of narcolepsy until Prinzmetal and Bloomberg introduced amphetamines in 1935.
- After the discovery of tricyclic antidepressants in 1957, Akimoto, Honda, and Takahashi used imipramine in the treatment of cataplexy in humans.
- Methylphenidate was introduced by Yoss and Daly in the 1960s.
The following are a few famous cases of narcolepsy:
- Sir Winston Leonard Spencer Churchill, former Prime Minister of the United Kingdom, is one of the most famous sufferers from narcolepsy
- Thomas Alva Edison, the greatest American inventor, was thought to suffer from narcolepsy because he was photographed sleeping in his lab
- Jimmy Kimmel, American late-night talk show host, actor, producer, comedian, and writer
- Harold M. Ickes, former deputy White House chief of staff for President Bill Clinton and a leading figure in the His administration's healthcare reform initiative
- Harriet Tubman, an underground railroad pioneer, an American abolitionist, and political activist suffered from head inury and later developed narcolepsy and epilepsy
- Arthur Lowe, a British actor who played iconic Captain Mainwaring in the British sitcom Dad's Army
- Nastassja Aglaia Kinski, German actress, and former model
- Lenny Bruce, controversial American stand-up comedian and satirist, suffered from narcolepsy and took medication to treat his condition
- George M. Church, molecular geneticist, molecular engineer, and chemist, who is a Professor of Genetics and Professor of Health Sciences at Harvard
- Teresa Nielsen Hayden, American science fiction editor, fanzine writer, and essayist who has a famous weblog, named Making Light
- Franck Bouyer, French former road racing cyclist who was unable to compete or train without treatment with Modafinil
- Gabe Barham, former Drummer for American post-hardcore band Sleeping With Sirens
- Kurt Cobain, former front-man for American rock band Nirvana, claimed in interviews that he suffered from narcolepsy
- Jinkx Monsoon (real name is Jerick Hoffer), Seattle Drag Queen, stage performer, comedian and singer who is the winner of the fifth season of RuPaul's Drag Race
- Aaron Flahavan, former English (Portsmouth) football Goalkeeper
- Paul Gonsalves, Jazz tenor saxophonist
Milestones in Narcolepsy
- Fischer, Franz (1878). "Epileptoide Schlafzustände". Archiv für Psychiatrie und Nervenkrankheiten. 8 (1): 200–203. doi:10.1007/BF01791317. ISSN 0003-9373.
- Westphal C. Eigenthümliche mit Einschläfen verbundene Anfälle. Arch. Psychiat., 7: 631-635 1877.
- Schenck CH, Bassetti CL, Arnulf I, Mignot E (2007). "English translations of the first clinical reports on narcolepsy and cataplexy by Westphal and Gélineau in the late 19th century, with commentary". J Clin Sleep Med. 3 (3): 301–11. PMC 2564780. PMID 17561602.
- Janković S, Susić V, Sokić D, Lević Z (1996). "[Dr. John Baptiste Edouard Gélineau]". Srp Arh Celok Lek. 124 (11–12): 331–5. PMID 9132972.
- Gélineau J. De la narcolepsie. Gazette des hôpitaux,. 53: 626-628, 1880.
- Gélineau JBE. De la narcolepsie. Surgères, Charente-Inférieure: Imprimerie de Surgères, 64, 1881.
- Löwenfeld L. Uber Narkolepsie. Munch. Med. Wochenschr., 49: 1041-1045, 1902.
- Addie W. IdIopathic narcolepsy: a disease sui generis; with remarks on the mechanism of sleep. Brain, 49: 257-306, 1926.
- Wilson SAK. The narcolepsies. Annual Congress Assoc. Phys., June 3: 63-109, 1927.
- Daniels LE. Narcolepsy. Medicine, 13(1): 1-122, 1934.
- Van Economo C. Sleep as a problem of localization. J. Nerv. Ment. Disease, 71(3): 249-259, 1930.
- . doi:10.1159/isbn.978-3-318-05312-8. Missing or empty
- YOSS RE, DALY DD (1957). "Criteria for the diagnosis of the narcoleptic syndrome". Proc Staff Meet Mayo Clin. 32 (12): 320–8. PMID 13441766.
- Vogel, Gerald (1960). "Studies in Psychophysiology of Dreams". Archives of General Psychiatry. 3 (4): 421. doi:10.1001/archpsyc.1960.01710040091011. ISSN 0003-990X.
- Rechtschaffen A, Dement W (1967). "Studies on the relation of narcolepsy, cataplexy, and sleep with low voltage random EEG activity". Res Publ Assoc Res Nerv Ment Dis. 45: 488–505. PMID 6083200.
- Hishikawa Y, Nan'no H, Tachibana M, Furuya E, Koida H, Kaneko Z (1968). "The nature of sleep attack and other symptoms of narcolepsy". Electroencephalogr Clin Neurophysiol. 24 (1): 1–10. doi:10.1016/0013-4694(68)90060-6. PMID 4169745.
- Richardson GS, Carskadon MA, Flagg W, Van den Hoed J, Dement WC, Mitler MM (1978). "Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects". Electroencephalogr Clin Neurophysiol. 45 (5): 621–7. doi:10.1016/0013-4694(78)90162-1. PMC 2391074. PMID 81764.
- Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S (1986). "Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness". Sleep. 9 (4): 519–24. doi:10.1093/sleep/9.4.519. PMID 3809866.
- Roth, Bedrich, and Roger J. Broughton. Narcolepsy and hypersomnia. Basel New York: Karger, 1980. Print.
- Dement WC, Zarcone V, Varner V. The prevalence of narcolepsy. Sleep Res., 1: 148-149 1972.
- Dement WC, Carskadon M, Ley R. The prevalence of narcolepsy II. Sleep Res., 2: 147, 1973.
- Knecht CD, Oliver JE, Redding R, Selcer R, Johnson G (1973). "Narcolepsy in a dog and a cat". J Am Vet Med Assoc. 162 (12): 1052–3. PMID 4736237.
- Mitler MM, Boysen BG, Campbell L, Dement WC (1974). "Narcolepsy-cataplexy in a female dog". Exp Neurol. 45 (2): 332–40. doi:10.1016/0014-4886(74)90122-8. PMC 2391078. PMID 4472992.
- Honda Y, Asake A, Tanaka Y, Juji T. Discrimination of narcolepsy by using genetic markers and HLA. Sleep Res.,1 2: 254, 1983.
- Honda Y. Introduction to " HLA in Narcolepsy". 1-10. In: Honda Y, Juji T (Eds.). HLA in Narcolepsy. 1988.
- Juji T, Satake M, Honda Y, Doi Y (1984). "HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive". Tissue Antigens. 24 (5): 316–9. doi:10.1111/j.1399-0039.1984.tb02144.x. PMID 6597978.
- Matsuki, K.; Honda, Y.; Satake, M.; Juji, T. (1988). "HLA in Narcolepsy in Japan": 58–75. doi:10.1007/978-3-642-83387-8_4.
- Mueller-Eckhardt, Gertrud; Meier-Ewert, K.; Schendel, Dolores J.; Reinecker, F. B.; Multhoff, Gabriele; Mueller-Eckhardt, C. (2008). "HLA and narcolepsy in a German population". Tissue Antigens. 28 (3): 163–169. doi:10.1111/j.1399-0039.1986.tb00476.x. ISSN 0001-2815.
- Langdon, Nicola; Dam, MiekeVan; Welsh, KenI.; Vaughan, RobertW.; Parkes, David (1984). "GENETIC MARKERS IN NARCOLEPSY". The Lancet. 324 (8413): 1178–1180. doi:10.1016/S0140-6736(84)92742-9. ISSN 0140-6736.
- "Extraordinary association between HLA-DR2 and narcolepsy". Lancet. 1 (8422): 226–7. 1985. PMID 2857308.
- Poirier G, Montplaisir J, Décary F, Momège D, Lebrun A (1986). "HLA antigens in narcolepsy and idiopathic central nervous system hypersomnolence". Sleep. 9 (1 Pt 2): 153–8. doi:10.1093/sleep/9.1.153. PMID 3486443.
- Matsuki, Kazumasa; Grumet, F.Carl; Lin, Xiaoyan; Gelb, Michael; Guilleminault, Christian; Dement, WilliamC.; Mignot, Emmanuel (1992). "DQ (rather than DR) gene marks susceptibility to narcolepsy". The Lancet. 339 (8800): 1052. doi:10.1016/0140-6736(92)90571-J. ISSN 0140-6736.
- Mignot, E.; Kimura, A.; Lattermann, A.; Lin, X.; Yasunaga, S.; Mueller-Eckhardt, G.; Rattazzi, C.; Lin, L.; Guilleminault, C.; Grumet, F. C.; Mayer, G.; Dement, W. C.; Underhill, P. (1997). "Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with cataplexy". Tissue Antigens. 49 (4): 329–341. doi:10.1111/j.1399-0039.1997.tb02761.x. ISSN 0001-2815.
- Mignot, E.; Lin, X.; Arrigoni, J.; Macaubas, C.; Olive, F.; Hallmayer, J.; Underhill, P.; Guilleminault, C.; Dement, W. C.; Grumet, F. C. (1994). "DQB1*0602 and DQA1*0102 (DQ1) Are Better Markers Than DR2 for Narcolepsy in Caucasian and Black Americans". Sleep. 17 (suppl_8): S60–S67. doi:10.1093/sleep/17.suppl_8.S60. ISSN 1550-9109.
- Mignot E, Hayduk R, Black J, Grumet FC, Guilleminault C (November 1997). "HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients". Sleep. 20 (11): 1012–20. PMID 9456467.
- Carlander, B; Eliaou, JF; Billiard, M (1993). "Autoimmune hypothesis in narcolepsy". Neurophysiologie Clinique/Clinical Neurophysiology. 23 (1): 15–22. doi:10.1016/S0987-7053(05)80279-5. ISSN 0987-7053.
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- Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H; et al. (1998). "Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior". Cell. 92 (4): 573–85. doi:10.1016/s0092-8674(00)80949-6. PMID 9491897.
- Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000). "Hypocretin (orexin) deficiency in human narcolepsy". Lancet. 355 (9197): 39–40. doi:10.1016/S0140-6736(99)05582-8. PMID 10615891.
- Prinzmetal, Myron (1935). "THE USE OF BENZEDRINE FOR THE TREATMENT OF NARCOLEPSY". Journal of the American Medical Association. 105 (25): 2051. doi:10.1001/jama.1935.02760510023006. ISSN 0002-9955.
- AKIMOTO H, HONDA Y, TAKAHASHI Y (1960). "Pharmacotherapy in narcolepsy". Dis Nerv Syst. 21: 704–6. PMID 13681922.
- Yoss, R. E.; Daly, D. (1959). "Treatment of narcolepsy with Ritalin". Neurology. 9 (3): 171–171. doi:10.1212/WNL.9.3.171. ISSN 0028-3878.
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