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|TOPIC OF THE ISSUE - MINI REVIEW
|Year : 2012 | Volume
| Issue : 1 | Page : 66-67
Narcolepsy: Past, present and future
Department of Neurology, Sleep Disorders Center and Sleep Medicine Fellowship Program, University of Missouri, School of Medicine, Colombia
|Date of Submission||15-Feb-2012|
|Date of Decision||15-Feb-2012|
|Date of Acceptance||15-Feb-2012|
|Date of Web Publication||7-Mar-2012|
Department of Neurology and Sleep Disorders Center and Sleep Medicine Fellowship Program, University of Missouri, School of Medicine
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sahota P. Narcolepsy: Past, present and future. Neurol India 2012;60:66-7
Narcolepsy is a debilitating life-long disorder characterized by excessive sleepiness and an abnormal tendency to transition from wakefulness into rapid eye movement (REM) sleep. Gélineau, a French physician, was the first to use this term and describe it as a distinct entity.  The International Classification of Sleep Disorders includes two forms: narcolepsy with cataplexy and narcolepsy without cataplexy.  The clinical features are characterized by the classic tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations.  Other symptoms such as automatic behavior and disrupted nocturnal sleep can be seen in these patients. The clinical impression is usually confirmed by polysomnographic evidence (overnight sleep study followed by the Multiple Sleep Latency Test (MSLT).
The discovery that narcolepsy with cataplexy is caused by loss of the orexineregic hypothalamic neurons is most important in understanding the pathophysiology of narcolepsy. In fact, documented low cerebrospinal fluid (CSF) orexin in patients with narcolepsy with cataplexy has begun to offer another diagnostic tool. This questions the pathophysiology of narcolepsy without cataplexy where low CF orexin levels may not be present. Sleep paralysis and hypnagogic hallucinations are also more prevalent in narcolepsy with cataplexy in comparison to narcolepsy without cataplexy. Thus, in place of one specific entity, narcolepsy may have a spectrum of clinical presentations.
Very limited literature is available on narcolepsy from the Indian subcontinent. However, the accompanying article in this issue begins the effort to address this deficiency. In the article, Gupta et al.  describe the clinical and polysomnographic features of 20 patients with narcolepsy from North India. This study shows a significant male preponderance (9:1), which is significantly different from the other studies, which have shown only a slight male preponderance. Gupta et al. attribute this to either the small number of patients in their study or a possibility of the underestimation of symptoms by female patients in their population. Eight of these patients had narcolepsy with cataplexy (40%), while 12 had narcolepsy without cataplexy (60%). Previous studies have shown that 60 to 70% of the patients with narcolepsy have cataplexy. The onset of symptoms of daytime sleepiness typically occurs between 15 and 25 years of age. In this study, only half of the patients fell in this age group. Cataplexy, a unique and pathognomonic feature of narcolepsy, is often misdiagnosed as another disorder. It is characterized by a sudden loss of bilateral muscle tone, provoked by strong, positive emotions. Gupta et al. describe a patient with cataplexy, who was misdiagnosed as having epilepsy. They also describe a patient who expressed having supernatural premonitions during his dreams.
On MSLT, a mean sleep latency of less than or equal to eight minutes, and a presence of two or more sleep onset rapid eye movement periods (SOREMP) following sufficient nocturnal sleep during the night prior to the test, was required for the diagnosis of narcolepsy without cataplexy, and should, whenever possible, be used in patients with narcolepsy with cataplexy, for confirmation of the diagnosis.  Gupta et al.  described a mean sleep onset latency of 1.30 minutes in their group of patients. Their patients had a high percentage of REM sleep. None of their patients had periodic limb movements in their sleep, which was stated to occur in 45 to 65% of the patients with narcolepsy.
Given that only one previous case report on narcolepsy has been described from India, we commend Gupta et al. for this study. In a country with a population of over a billion people, a greater awareness about narcolepsy and hypersomnolence will help many patients with this disorder, especially those who have not been evaluated or diagnosed yet. Patients with narcolepsy, without treatment, are at risk for various sorts of accidents and a comprehensive treatment is critical for the safety of these patients and those around them. 
Looking to the future, there are pathophysiological, etiological, therapeutic, and genetic implications. Pathophysiologically, the role of histamines, in addition to orexins, is under investigation. Etiologically, the mechanism of loss of orexin neurons still needs to be fully understood. At the end of the treatment, wake promoting agents and gamma-hydroxybutyrate have been important additions. Limited clinical trials of immune therapies, with the use of intravenous immunoglobulins (IVIG) have shown benefit in some cases.  In genetics, if the cause of narcolepsy is due to lack of orexin, caused by the loss of orexin neurons, then we must consider all possible means to replace that loss. Intranasal orexin is available, but is too expensive and has not been tried, to address sleepiness and other symptoms of narcolepsy. Finally gene therapy to replace orexins opens another window of opportunity to treat narcolepsy.
| » References|| |
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|2.||American Academy of Sleep Medicine. The international classification of sleep disorders: diagnostic and coding manual. 2 nd ed.West?chester, IL: American Academy of Sleep Medicine, 2005. |
|3.||Daniels LE. Narcolepsy. Medicine 1934;13:1-122. |
|4.||Gupta A, Shukla G, Goyal V, Srivastava A, Behari M. Clinical and polysomnographic characteristics in 20 North Indian patients with narcolepsy - 7 year experience from a neurology service sleep clinic. Neurol India 2012;60:75-8. |
|5.||Richey SM, Guilleminault, C. Acute issues in narcolepsy and hypersomnia. In: Chokroverty S, Sahota P, editors. Acute and Emergent in Sleep Disorders. New York: Oxford University Press; 2011. p. 33-47. |
|6.||Dauvilliers Y, Abril B, Mas E, Michel F, Tafti M. Normalization of hypocretin-1 in narcolepsy after intravenous immunoglobulin treatment. Neurology 2009;73:1333-4. |