Diseases and Disorders

A Compendium of Narcolepsy

Christian Gonzalez

History of the Disease

     In the late 19th century, French physician Jean-Baptiste-Edouard Gelineau described the curious case of a wine merchant suffering from short yet pronounced sleep attacks. Observing the merchant’s lifelong drowsiness, Gelineau proposed that the man had neurosis and described his findings in two scientific papers in Paris in 1880. Occurring up to 200 times per day but lasting just 1 to 5 minutes, the pattern of occurrence of the attacks resembled in many respects that of epilepsy. Gelineau believed, however, that the case was unique and named it narcolepsy. Before the coining of the term narcolepsy by Gelineau in the 1880s, German physicians had encountered similar cases in the 1870s and observed a correlation between sleep attacks and muscle weakness initiated by emotional stress. The history of narcolepsy stretches even further back, though, with earlier reports of similar situations that were described by English doctor Thomas Willis in the 17th century. Since Gelineau’s findings, the scientific community has achieved a greater understanding of his observations, due to extensive sleep disorder research. Presently, neurologists have a comprehensive understanding of the pathology of narcolepsy and are working towards finding a cure (Todman, 2008).  


Summary and Symptoms

    Characterized by sudden and recurrent attacks of sleepiness, fatigue, and muscle weakness, narcolepsy is a chronic, debilitating neurological disease that affects approximately 1 out of every 2000 people in the US. With a total of nearly 3 million patients suffering from the condition worldwide, narcolepsy is one of the most commonly observed sleep disorders. The symptoms of narcolepsy include abnormal sleep cycles (similar to those experienced by patients with insomnia), excessive daytime sleepiness, loss of muscle tone, and hypnagogic hallucinations, accompanied by episodes of muscle weakness induced by emotional stimuli, also known as cateplexy, in 70% of patients (“Narcolepsy Fact Sheet,” n.d.). The pathology of narcolepsy results in the brain losing the ability to maintain standard regulatory control of the sleep-wakefulness cycle, producing abnormal sleep patterns and persistent daytime sleepiness that can significantly interfere with daily activities such as driving vehicles and functioning at work. The cateplexy that most patients experience in addition causes temporary muscle weakness while a patient maintains full consciousness. These ephemeral incidences typically torment patients for most of their lives, and can be quite devastating, especially in emotional situations that may trigger such reactions.



    While there is currently no known cause for the onset and pathology of narcolepsy, many researchers believe that there are several factors which may contribute to the development of the disease. The most common factor is low levels of the neuropeptide hypocretin in cerebrospinal fluid brought about by hypothalamic dysfunction. This molecule, also known as orexin, is involved in the regulation of the sleep-wakefulness cycle and proper REM sleep. When lower concentrations of hypocretin are present in a patient, the regulation of normal sleep patterns is offset, resulting in narcolepsy (“Narcolepsy: Causes,” n.d.). More specifically, researchers speculate that the immune system mistakenly attacks specific brain parts, such as the lateral hypothalamus, which produces hypocretin to yield the symptoms of narcolepsy. In the case of narcolepsy with cateplexy, over 90% of patients have deficient amounts of hypocretin-1 and hypocretin-2, supporting this conclusion (“Narcolepsy Research - FAQs,” n.d.). Other factors thought to trigger narcolepsy include genetic abnormalities, significant psychological stress, and infections or viruses (“Causes of narcolepsy,” n.d.).



    Diagnosis of narcolepsy is relatively straightforward, as the process is primarily based on symptoms and physical signs. Typically, neurologists can identify narcolepsy when a patient exhibits frequent sleep attacks and muscle weakness caused by cateplexy. Unfortunately, when these signs are less severe, diagnosis of narcolepsy can be more difficult and often requires further testing. Medical and family histories are helpful in diagnosis, and can provide information such as brain injuries and infections, as well as genetic predisposition for autoimmune diseases. The main symptoms of narcolepsy are daytime sleepiness, muscle weakness, fatigue, sleep attacks, and cateplexy. If a patient experiences sleepiness but not attacks of sleep, for example, narcolepsy may be eliminated as a possibility. Doctors usually utilize two medical tests to validate a diagnosis of narcolepsy. The first of these tests is called a polysomnogram (see the research methods section for more information). The other test is a multiple sleep latency test; this technique enables a physician to identify abnormalities in the amount of time it takes a patient to transition from being awake to falling asleep. Additional investigations may also be conducted with the use of a hypocretin test, in which a lumbar puncture is performed to quantify the amount of hypocretin present in a patient’s cerebrospinal fluid. If the concentration is lower than normal, the patient will likely receive a diagnosis of narcolepsy (“How Is Narcolepsy Diagnosed?,” n.d.).


Molecular Underpinnings

     Although narcolepsy with cateplexy is primarily the result of low hypocretin levels in cerebrospinal fluid, the genetics of an individual play a key role in their susceptibility to the disease. Having an immediate family member affected by narcolepsy increases one’s chances of being afflicted by 20-40 times, compared to those without a narcoleptic relative. Still, even having a parent with narcolepsy will only place an individual at a 1-2% risk of developing the condition in their life. Genes that control the human leukocyte antigen (HLA) are speculated to be involved in the autoimmune etiology of narcolepsy, as differences in their alleles have been identified to be predictive markers for the probability of a patient being diagnosed with the disease. Particularly, the most accurate marker in determining hereditary bases of narcoleptic susceptibility is the allele HLA-DQB1*0602 in the HLA-DQB1 gene. With over 90% of patients with narcolepsy-cateplexy carrying this allele, it is by far the most accurate genetic predictor of narcolepsy to date (“Narcolepsy Research – FAQs,” n.d.). Still, while genetics is an accurate measurement of susceptibility, mutations in hypocretin-related genes associated with hypothalmic dysregulation are exceedingly rare in narcoleptic patients. Accordingly, etiology is less understood compared to other stages of narcoleptic pathology. (Taheri, Chabas, Renier, & Mignot, 2003).



    Although there is no cure for the disease, several treatments can be taken to lessen the severity of narcolepsy’s effects on the life of individuals. Some of the most common types of medications include stimulants, SSRIs, tricyclic antidepressants, and sodium oxybate. Stimulants are the leading method used to abate sleep attacks in narcoleptic patients because they are very effective in keeping patients awake during the day. SSRIs are prescribed in order to ease episodes of cateplexy in narcoleptics. Through suppressing REM sleep, SSRIs such as fluoxetine (better known as Prozac) are also effective in treating narcolepsy. Other types of antidepressants besides SSRIs, such as tricyclic antidepressants, may also be used in certain cases, but have adverse side effects such as lightheadedness and dry mouth, and are therefore less attractive. Cateplexy can also be treated with sodium oxybate, sometimes referred to as xyrem. Unfortunately, xyrem has severe side effects including headache, nausea and sleepwalking. Other medication options include the drugs methylphenidate and atomoxetine, which both result in adverse side effects such as irregular heartbeat and psychosis. (“Narcolepsy: Treatments and drugs,” n.d.).


Advocacy and Awareness

     In order to truly improve the lives of patients suffering from narcolepsy, additional efforts beyond research must be taken. Becoming an advocate to help raise public awareness of the disease is an important key in making narcoleptic lives easier to live. If you would like to spread awareness of narcolepsy and get involved in volunteer programs on local, national, and international levels, please contact the following organizations listed below.

Narcolepsy Network - http://narcolepsynetwork.org/get-involved/

Youth Ambassador Program - http://narcolepsynetwork.org/get-involved/youth-ambassador-program

Wake Up Narcolepsy - http://www.wakeupnarcolepsy.org/


Key Terms

Neurosis - Class of mild functional mental disorders that cause distress but not psychosis

Excessive daytime sleepiness- Condition of persistent sleepiness throughout the day

Hypnagogic hallucinations- Hallucinations that occur during the transitional period between wakefulness and sleep

Cateplexy - Temporary weakness or loss of muscle function spurred on by emotional stress

Orexin/Hypocretin - Neuropeptide involved in regulation of sleep-wakefulness cycle and appetite

Cerebrospinal Fluid - Clear liquid that fills the ventricles of the brain and the vertebral column

Lateral Hypothalamus- Orexinergic area of the brain involved in regulation of body temperature, blood pressure, pain perception, and normal sleep functioning

Polysomnography - Method also known as sleep study that is conducted to diagnose disorders based on electronically measuring activities during sleep

Multiple sleep latency test - Test for measuring how long it takes patients to fall asleep

Hypocretin test - Lumbar punctures may be performed to quantify hypocretin levels in cerebrospinal fluid of patients to diagnose narcolepsy more accurately

HLA-DQB1 - Gene whose DQB1*0602 allele can cause a predisposition to narcolepsy in over 90% of patients

Sodium oxybate - Anti-sleep medication; only treatment for narcolepsy approved by the World Anti-Doping Agency

Methylphenidate- Stimulant drug used to treat narcolepsy and ADHD

Atomoxetine- Cognition enhancing medication used to treat narcolepsy and ADHD


  1. Todman, D. (2008). Narcolepsy: A Historical Review. The Internet Journal of Neurology, 9(2). doi:10.5580/10ef

  2. Taheri, S., Chabas, D., Renier, C., & Mignot, E. (2003, June 17). The Genetics of Narcolepsy. Annual Review of Genomics and Human Genetics, 3-10. doi:10.1007/978-3-319-23739- 8_1

  3. Narcolepsy: Treatments and drugs. (n.d.). Retrieved July 21, 2016, from http://www.mayoclinic.org/diseases-conditions/narcolepsy/basics/treatment/con-20027429

  4. Narcolepsy Research - FAQs. (n.d.). Retrieved July 21, 2016, from https://med.stanford.edu/narcolepsy/faq1.html

  5. Narcolepsy Fact Sheet. (n.d.). Retrieved July 21, 2016, from http://www.ninds.nih.gov/disorders/narcolepsy/detail_narcolepsy.htm

  6. Narcolepsy Fast Facts. (n.d.). Retrieved July 21, 2016, from http://narcolepsynetwork.org/about- narcolepsy/narcolepsy-fast-facts/

  7. Narcolepsy: Description. (n.d.). Retrieved July 21, 2016, from http://umm.edu/health/medical/reports/articles/narcolepsy

  8. Narcolepsy: Causes. (n.d.). Retrieved July 21, 2016, from http://www.mayoclinic.org/diseases- conditions/narcolepsy/basics/causes/con-20027429

  9. How Is Narcolepsy Diagnosed? (n.d.). Retrieved July 21, 2016, from https://www.nhlbi.nih.gov/health/health-topics/topics/nar/diagnosis

  10. Causes of narcolepsy. (n.d.). Retrieved July 21, 2016, from http://www.nhs.uk/Conditions/Narcolepsy/Pages/Causes.aspx

Christian Gonzalez

Christian Gonzalez

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