Narcolepsy

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.

Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. "Sleep attacks" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.

Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.

Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.

Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Narcolepsy probably results from a combination of genetic and environmental factors, some of which have been identified, but many of which remain unknown.

In most cases of narcolepsy with cataplexy, and in some cases without cataplexy, sleep abnormalities result from a loss of particular brain cells (neurons) in a part of the brain called the hypothalamus. These cells normally produce chemicals called hypocretins (also known as orexins), which have many important functions in the body. In particular, hypocretins regulate the daily sleep-wake cycle. It is unclear what triggers the death of hypocretin-producing neurons in people with narcolepsy, although evidence increasingly points to an abnormality of the immune system.

Researchers have identified changes in several genes that influence the risk of developing narcolepsy. The most well-studied of these genes is HLA-DQB1, which provides instructions for making part of a protein that plays an important role in the immune system. The HLA-DQB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-DQB1 gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in people who also have cataplexy and a loss of hypocretins. Most people with narcolepsy have the HLA-DQB1*06:02 variation, and many also have specific versions of other, closely related HLA genes. It is unclear how these genetic changes influence the risk of developing the condition.

Variations in several additional genes have also been associated with narcolepsy. Many of these genes are thought to play roles in immune system function. However, variations in these genes probably make only a small contribution to the overall risk of developing narcolepsy. Other genetic and environmental factors are also likely to influence a person's chances of developing this disorder. For example, studies suggest that bacterial or viral infections such as strep throat (streptococcus), colds, and influenza may be involved in triggering narcolepsy in people who are at risk.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of narcolepsy are sporadic, which means they occur in people with no history of the disorder in their family. A small percentage of all cases have been reported to run in families; however, the condition does not have a clear pattern of inheritance. First-degree relatives (parents, siblings, and children) of people with narcolepsy with cataplexy have a 40 times greater risk of developing the condition compared with people in the general population.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Narcolepsy affects about 1 in 2,000 people in the United States and Western Europe. However, the disorder is likely underdiagnosed, particularly in people with mild symptoms. Worldwide, narcolepsy appears to be most common in Japan, where it affects an estimated 1 in 600 people.

Which doctor should you see?

The suggested department for discussing Narcolepsy is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.