Narcolepsy

Article Author:
Jennifer Slowik
Article Editor:
Allison Yow
Updated:
5/5/2019 4:35:53 PM
PubMed Link:
Narcolepsy

Introduction

Narcolepsy is a disorder of rapid onset rapid eye movement (REM) sleep characterized by daily uncontrollable sleep attacks and can be associated with cataplexy, sleep paralysis, and hypnagogic hallucinations. There are two types: narcolepsy type 1 (formerly narcolepsy with cataplexy) and narcolepsy type 2 (formerly narcolepsy without cataplexy).

Etiology

Narcolepsy type 1 occurs when the neurons that contain hypocretin (also called orexin) are lost. [1] The reason for this is not fully understood, but it is thought to be an autoimmune process possibly triggered by an infection. HLA haplotype DQB1*0602 is present in 95% of narcolepsy type 1 patients, but this is also present in about 20% of the general population without narcolepsy. The cause of narcolepsy type 2 is not entirely clear. Current hypotheses include less destruction of hypocretin cells, impaired hypocretin receptor signaling, or an unknown mechanism. Some patients initially diagnosed with narcolepsy type 2 will develop cataplexy indicating disease progression.

Epidemiology

Prevalence is 25 to 50 per 100,000 people for narcolepsy type 1 and 20 to 34 per 100,000 people for narcolepsy type 2. Age of onset peaks at 15 and again at 35 years with a 1.6:1 male predominance.

Pathophysiology

Hypocretin containing neurons are found in the hypothalamus where they normally stimulate the reticular activating system (RAS) and inhibit REM sleep during wakefulness. In patients with narcolepsy type 1, these neurons are lost, and REM sleep is no longer inhibited during wakefulness. Loss of hypocretin may allow REM sleep phenomenon such as cataplexy, sleep paralysis, and hypnagogic hallucinations to intrude during periods of wakefulness.

History and Physical

Patients present with moderate to severe daytime sleepiness. The typical patient with narcolepsy will begin experiencing symptoms in either their mid-teens or mid-thirties with a progressive increase of symptoms. The average time from onset of symptoms to diagnosis is about 15 years.[2][3] The only required symptom for the diagnosis of narcolepsy is daily irrepressible, rapid lapses into REM sleep known as “sleep attacks” that are present for at least 3 months. [4]

Cataplexy is a sudden, often bilateral muscle weakness lasting a few seconds to a couple of minutes in response to increased emotion (typically laughter) during which patients remain conscious. Cataplexy can also be brought on by excitement, anger, grief, or any strong emotional feeling. It is pathognomonic for the disorder if it is present but is not required for the diagnosis of narcolepsy type 2. Sleep paralysis occurs when waking from sleep when patients can hear what is occurring around them but are unable to open their eyes or move. They often describe a sensation of suffocating due to the paralysis of the intercostal muscles despite the diaphragm continuing to function normally. It can be associated with narcolepsy but also occurs at least once in up to 50% of the normal population.

Hypnagogic hallucinations are visual, auditory, or tactile dream-like experiences that occur as patients are falling asleep or just waking up. They can typically see human faces or experience a feeling like someone else is in the room. Additionally, these patients have significantly fragmented nighttime sleep. Unlike some other disorders with excessive daytime sleepiness, patients with narcolepsy typically find naps to be refreshing. It is also important to do a complete physical exam to rule out other possible causes of hypersomnia.

Evaluation

The first step is ensuring that the patient is regularly getting at least 6 hours of sleep per night for at least 2 weeks. Although this can be done with a patient-reported sleep log alone and still be considered valid for additional testing, patients often overestimate their total sleep time. Two weeks of actigraphy with a sleep log before additional testing is recommended. If the patient is getting less than 6 hours of sleep per night averaged over 2 weeks, they cannot be diagnosed with narcolepsy. [5]

If the patient is getting a minimum of 6 hours of sleep per night, then a reasonable next step is a polysomnogram (PSG) to rule out other possible sleep disorders such as sleep apnea. Following the PSG a Multiple Sleep Latency Test (MSLT) is conducted during the day as long as there were at least 6 hours of sleep during the PSG and no other sleep disorders are found. The patient is given four to five 20-minute nap opportunities at 2-hour intervals. A positive test will show rapid onset of REM sleep (less than 15 minutes) at least twice during the test, and a shortened mean sleep latency averaged across all trials (less than 8 minutes). One of the sleep onset REM periods (SOREMPs) can occur during the PSG with only one during the MSLT and still meet diagnostic criteria. If the MSLT is negative, but there is strong clinical suspicion for narcolepsy, the test should be repeated.

When conducting the MSLT, it is important that the patient is allowed to sleep until they wake up on their own from the PSG the night before the test to prevent a possible false positive. If the patient doesn’t get enough sleep the night before the test or it is started too early in the morning, SOREMPs may be present of the first couple of naps even in a patient without narcolepsy. Those with chronic insufficient sleep can also have SOREMPs on MSLT if they are not screened appropriately with actigraphy and sleep logs before testing.

Narcolepsy type 1 can also be diagnosed if hypocretin-1 is low in the cerebrospinal fluid. This testing could be helpful to confirm or exclude the diagnosis in uncertain cases but is no longer available as of January 2017. Although HLA DQB1*0602 is present in most narcolepsy type 1 patients, there is no common diagnostic utility in testing for it.

Treatment / Management

Behavior modification can be effective with 15 to 20 minutes long naps strategically scheduled throughout the day and maintaining an adequate nighttime sleep schedule. First-line pharmacologic treatment for excessive daytime sleepiness is modafinil (twice daily dosing) or armodafinil (once daily dosing). Second-line treatment would be amphetamines. First-line treatment for cataplexy is sodium oxybate, is a form of gamma-hydroxybutyrate, or GHB.  The medication is taken while in bed due to the short onset of sleepiness, usually 5 to 15 minutes. A second dose is given 2.5 to 4 hours later. Xyrem is a restricted medication being distributed from a central pharmacy. While there are concerns about abuse, dependence and illegal use of Xyrem post-market research has not proven these concerns to be valid. Tricyclic antidepressants (protriptyline, clomipramine) and SNRI/SSRIs (venlafaxine, fluoxetine) have also been used with some success in treating cataplexy. [6][7]

Pearls and Other Issues

Narcolepsy symptoms can be improved with behavioral modifications and medications, but some patients may never be able to maintain a normal state of alertness consistently. While most narcoleptic patients are safe to drive, each patient will have a differing degree of symptoms. Driving safety must be discussed with patients. If a patient has a car accident related to sleepiness, a Maintenance of Wakefulness Test (MWT) may help to ensure he/she can stay awake during mundane circumstances. The test consists of four to five 40-minute testing periods during which they will be asked to sit still in a quiet room.

Enhancing Healthcare Team Outcomes

Narcolepsy is a rare sleep disorder that has no cure and is difficult to manage. The condition needs lifelong monitoring by a multidisciplinary team that includes a social workers, sleep specialist, neurologist, psychiatrist, mental health nurse, primary care giver and the primary provider. The condition is managed by both medications and behavior modifications. Not everyone has a good response to medications and most people have a poor quality of life. Many patients remain home bound, are not able to drive or perform daily living activities for fear of injuring themselves during the sudden bouts of sleep which cause falls.[8][9] 

Narcoleptic patients may face difficulties with work-related issues and psychosocial support. They may have difficulty with work or social engagements and struggle with misconceptions regarding their disease. Patients may benefit from a support group.[10]


References

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[3] Delayed diagnosis of narcolepsy: characterization and impact., Thorpy MJ,Krieger AC,, Sleep medicine, 2014 May     [PubMed PMID: 24780133]
[4] Challenges in diagnosing narcolepsy without cataplexy: a consensus statement., Baumann CR,Mignot E,Lammers GJ,Overeem S,Arnulf I,Rye D,Dauvilliers Y,Honda M,Owens JA,Plazzi G,Scammell TE,, Sleep, 2014 Jun 1     [PubMed PMID: 24882898]
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[8] Szakács A,Chaplin JE,Tideman P,Strömberg U,Nilsson J,Darin N,Hallböök T, A population-based and case-controlled study of children and adolescents with narcolepsy: Health-related quality of life, adaptive behavior and parental stress. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2019 Mar;     [PubMed PMID: 30711365]
[9] Raggi A,Plazzi G,Ferri R, Health-Related Quality of Life in Patients With Narcolepsy: A Review of the Literature. The Journal of nervous and mental disease. 2019 Feb;     [PubMed PMID: 30672873]
[10] Vignatelli L,Antelmi E,Ceretelli I,Bellini M,Carta C,Cortelli P,Ferini-Strambi L,Ferri R,Guerrini R,Ingravallo F,Marchiani V,Mari F,Pieroni G,Pizza F,Verga MC,Verrillo E,Taruscio D,Plazzi G, Red Flags for early referral of people with symptoms suggestive of narcolepsy: a report from a national multidisciplinary panel. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2019 Mar;     [PubMed PMID: 30539345]