Narcolepsy

1R02 crystallography[1]

Narcolepsy is a chronic neurological disorder characterized by the classic tetrad of excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. The first descriptions of narcolepsy-cataplexy were reported in Germany by Westphal and Fisher in 1877/1878.

The disorder is related to the following process: endocrine.

Presentation

The classic tetrad of narcolepsy consists of excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. In very few cases it is seen that a child presents with all 4 symptoms [13].

EDS is the primary symptom of narcolepsy and must be present for at least 3 months to justify the diagnosis. In persons with narcolepsy, severe EDS leads to involuntary somnolence during activities that normally need attention, like driving, eating, or talking. Narcoleptic patient can suffer from severe and constant sleepiness, with bouts of falling asleep without any warning (i.e. sleep attacks).

Patients with narcolepsy tend to take short and refreshing naps (i.e. rapid eye movement (REM)-type naps) during the day. Sometimes dreams also accompany the daytime naps.

A significant number of narcolepsy patients have trouble sleeping at night [14]. In addition, patients may have nocturnal compulsive habits like, eating disorder in relation with sleep and smoking at night [15]. Obesity is commonly seen with narcolepsy.

Cataplexy is a brief and sudden loss of muscle tone and represents REM sleep intrusion during wakefulness. The most characteristic feature of cataplexy is that it usually is triggered by emotions (especially laughter and anger). Cataplexy is seen in about 70% of patients with narcolepsy. The presence of cataplexy along with EDS is strongly suggestive of narcolepsy.

Patients with narcolepsy may experience sleep paralysis, in which the patient is not able to move when he/she wakes up and sometimes when asleep with consciousness intact. Often hallucinations accompany it. Sleep paralysis occurs less frequently when patients sleep in uncomfortable positions. The person can be rescued from this condition by sensory stimuli, like touch or talking with that person.

Sleep-related hallucinations may be either hypnagogic (i.e. occurring at sleep onset) or hypnopompic (i.e. occurring at awakening). These hallucinations are usually vivid (dreamy) either tactile, visual or auditory in character.

At disease onset, children with narcolepsy and cataplexy may display a wide range of motor disturbances that do not corroborate with cataplexy as it is classically. The motor disturbances, can be negative (hypotonia) or active (e.g. perioral movements, dyskinetic-dystonic movements, or stereotypic movements), and are seen to settle later during the course of disease [16].

In children aged 5-10 years, inattentiveness is the most common initial complaint, followed by recurring sleepiness and later on by difficulty in morning arousal associated with aggressive behavior and abrupt falls in school [17]. These children often were misdiagnosed as having attention deficit hyperactivity disorder (ADHD), learning disability, depression, or another neurological disorder. In children aged 10-12 years, poor academic performance is a common complaint [17].

Physically, narcoleptic patients are normal.

Workup

Sleep studies are an essential part of the evaluation of patients with probable chances narcolepsy. An overnight polysomnogram (PSG) followed by a multiple sleep latency test (MSLT) can provide strongly suggestive evidence of narcolepsy while excluding other sleep disorders.

Human leukocyte antigen (HLA) typing may provide collateral data, but it is more useful for excluding the diagnosis by documenting that the patient does not have either DQB1*0602 or DQA1*0602.

Measurement of hypocretin (orexin) levels in the cerebrospinal fluid (CSF) may help establish the diagnosis [9]. CSF hypocretin levels lower than 110 pg/mL are included in the diagnostic criteria for narcolepsy in the second edition of the International Classification of Sleep Disorders (ICSD-2).

Imaging studies such as MRI are useful for excluding rare causes of symptomatic narcolepsy. Idiopathic narcolepsy may be seen in cases where there are structural abnormalities of the brainstem and diencephalon. MRI of brain in patients suffering from secondary narcolepsy, may show different abnormalities that can be related to the underlying cause.

Treatment

Treatment of narcolepsy has two components i.e medical and auxiliary management. Good sleep hygiene is a must. Improvement is seen when the patients have a regular sleep schedule, which is generally 7.5-8 hours of sleep every night. Scheduled naps during the day also may help [18].

Pharmacologic treatment of narcolepsy involves the use of central nervous system (CNS) stimulants such as amphetamine, methylphenidate, modafinil, methamphetamine, and dextroamphetamine sulfate. With the help of these medicines daytime sleepiness can be reduced, thereby improving the symptoms in 65-85% of patients.

Tricyclic antidepressants such as protriptyline, imipramine and clomipramine, are effective for cataplexy. Sodium oxybate is highly effective for cataplexy, as it helps in improving night time sleep, which is often poor in narcolepsy. Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) suppress REM sleep, thus helping to alleviate the symptoms of cataplexy, hypnotic hallucinations and sleep paralysis. They include fluoxetine and venlafaxine.

Prognosis

If the disease is managed and treated properly, then patients suffering from narcolepsy can have good life at home and work too. But if not treated, then it can be psychosocially disastrous [12].

Narcoleptic children may suffer from bad performance in school, social impairment, mocked by the colleagues, and there would be flaws in various activities seen in normal childhood development.

Etiology

The exact cause of narcolepsy isn't known. Narcolepsy has a genetic component and tends to run in families. An estimated 8 to 10% of people with narcolepsy have a close relative who has the disorder. Narcolepsy most likely involves a combination of genetics and one or more environmental provoking factors like infection, trauma, hormonal changes, immune system disorders, or stress.

Epidemiology

Narcolepsy affects about 1 in 2,000 people. The prevalence of narcolepsy in the US is 0.02-0.18%, which is comparable to that of multiple sclerosis [2] [3]. The frequency among first-degree relatives is 1-2%. Narcolepsy with cataplexy affects 0.02% of adults worldwide [4].

The male-to-female ratio in narcolepsy is 1.64:1. The disease has highest peak of occurrence at 15 years and a less marked peak at 36 years.

Sex distribution
Age distribution

Pathophysiology

Narcolepsy is considered to be an outcome of susceptible genes, defective neurotransmitter functioning and sensitivity, and aberrant immune modulation. Recent studies blame some human leukocyte antigen (HLA) subtypes and abnormal hypocretin (orexin) neurotransmission, that causes unexpected changes in monoamine and acetylcholine synaptic transmissions, and more accurately in the reticular activating system of the pons [5] [6].

The centrality of hypocretin transmission in the pathophysiology of narcolepsy was demonstrated when hypocretin knockout mice displayed cataplexy and sleepiness [7] [8]. Further evidence for impaired hypocretin functioning in humans was found with the discovery of low levels of hypocretin in the cerebrospinal fluid (CSF) of narcoleptic patients [9].

Subsequently, abnormal immune modulation was associated with the clinical development of narcolepsy in children in Scandinavia and Finland. It was found that the chances of narcolepsy increased to 8-12 folds in Finnish children after vaccination against the H1N1 influenza virus with a vaccine that used a potent ASO3 adjuvant. Every affected child who went through HLA typing was seen having the HLA DQB*0602 allele [10] [11].

Prevention

Narcolepsy cannot be prevented but the frequency of the narcolepsy episodes can be reduced in those suffering from it by avoiding the triggering factors or the conditions that causes the attack.

Summary

Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden bouts of sleep. It is difficult for a person suffering from narcolepsy to stay awake for long periods of time, whatever be the circumstances. It is characterized by the classic tetrad of excessive sleepiness during the daytime, cataplexy, hypnotic hallucinations, and sleep paralysis. It is also known as hypnolepsy, defined as a chronic neurological disorder caused by autoimmune destruction of hypocretin-producing neurons inhibiting the brain's ability to regulate sleep-wake cycles normally.[1]

Patient Information

Narcolepsy is a medical disorder characterized by excessive, sudden bouts of uncontrollable sleep during the day. These patients cannot sleep well at night and a polysomnogram is used to diagnose the condition.

The condition cannot be prevented as the exact cause is not understood but the symptoms can be controlled very well lifelong with medications like antidepressants, and stimulants. It is not a fatal condition but it can lead to accidents that are life-threatening.

Patients with narcolepsy should avoid heavy meals and alcohol. Patients should take scheduled short naps and participate in an exercise programs. They must avoid driving, operating heavy machinery, or any other activity that can have detrimental effect when sleepy. In one survey, almost 75% of patients with narcolepsy reported falling asleep while driving, and 56% reported nearly having accidents. In addition to these accidents, there are various other accidents that associated with narcolepsy like burns due to coming in close contact with hot objects, cuts from handling sharp objects, and breaking things. Patients with narcolepsy with cataplexy should wear a life preserver when engaged in water activities. They should not do water activities all by themselves. They should inform and also educate others about their cataplectic attacks.

People with narcolepsy have problems with memory, thinking, and attention. They suffer from emotional and social difficulties caused by their uncontrollable sleep episodes and cataplexy. They are prone to suffer from depression, severe emotional and social dysfunction in all areas, be it work, relationships or any relaxing activity. Generally it is seen that men with narcolepsy suffer from sexual problems.

Self-assessment

References

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  11. Nohynek H, Jokinen J, Partinen M, Vaarala O, et al. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One. 2012;7(3):e33536.
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  13. Vendrame M, Havaligi N, Matadeen-Ali C, Adams R, Kothare SV. Narcolepsy in children: a single-center clinical experience. Pediatr Neurol. 2008 May;38(5):314-20.
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Media References

  1. 1R02 crystallography, Public Domain
Self-assessment