Narcolepsy historical perspective
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Muhammad Waleed Haider, M.D.[2]
Overview
Historical Perspective
Discovery
- 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 two receptors for 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.
Impact on Cultural History
Famous Cases
The following are a few famous cases of [disease name]: