Narcolepsy

Synonyms: Gelineau's syndrome, sleep epilepsy, paroxysmal sleep

The term "narcolepsy" was first used by Gelineau in 1880 to describe a pathological state of daytime sleepiness and is a term derived from the Greek "seized by somnolence".

• It is a chronic neurological condition producing disruption to the normal sleep pattern.
• This commonly produces a background state of sleepiness, associated with periods when there is an overwhelming desire to sleep.

Narcolepsy may also be associated with cataplexy, or sudden loss of muscle tone and power in response to strong emotion, e.g. elation and anger.¹ It is not usually triggered by stress. Brief periods of total paralysis may also occur at the beginning or end of sleep, as may vivid hallucinations.

The incidence of narcolepsy is not known with any degree of certainty as it often goes unrecognised or unreported.
The prevalence in European populations has been estimated at 3-5 per 10,000, with men and women being equally affected.² It has a higher prevalence in Japan and a lower one in Israel.

Age of onset is typically around adolescence. A smaller number of cases presents at around 35 years.
There is a male predominance.

Rarely, there may be a familial history of the condition, especially in first-degree relatives, and a number of genetic codes are strongly associated with narcolepsy:

• HLA-DQB1*0602 is found in 95% of patients who have both narcolepsy and cataplexy.
• 40% of those with narcolepsy alone.
• 18-35% of the general population.³

It has been suggested that the genetic coding may interfere with the processing of the hyposecretin neurotransmitter.

• Unlike unaffected individuals, people with narcolepsy enter rapid eye movement (REM) sleep within a few minutes of falling asleep.This has led to the belief that narcolepsy occurs as a result of a disease process affecting the part of the brain controlling the REM component of sleep.
• During normal REM sleep a group of neurones in the brainstem ceases activity. This is also seen during cataplectic attacks, strengthening the theory that a disorder of this part of the brain is responsible for narcolepsy.
• Research has shown that brains from people with narcolepsy have reduced numbers of hypocretin producing neurons.⁴Hypocretin appears to be involved in preventing the brain systems required for wakefulness from turning off.⁵ Hypocretin is also involved in the regulation of appetite and feeding behaviour which may play a part in explaining the higher incidence of obesity in people with narcolepsy when compared to those without.

Narcolepsy is often first brought to light as a result of poor or patchy achievement at school or university. It may sometimes contribute to childhood behavioural problems such as attention deficit disorder (ADD).
The symptoms of narcolepsy may increase gradually over a period of time, and it may be many years from the onset of symptoms to the diagnosis being made. More than 50% of patients report important events in the time immediately preceding the onset of symptoms, e.g. head trauma, pregnancy and major psychological stress.⁶Symptoms which may occur include:

• Obstructive sleep apnoea; this is a major cause of daytime sleepiness, occurring in 24% male population
• Insufficient night-time sleep, e.g. due to pain, coughing
• Effects of prescribed medicines
• Hypothalamic tumour
• Chronic fatigue syndrome
• Epilepsy

A thorough history is important with particular reference to:

• Normal sleep pattern
• Sleepiness in unusual situations, e.g. using Epworth Sleepiness Scale⁸
• Other medical conditions
• Social history - alcohol, "recreational" drugs, occupation, shift work
• Drug history, e.g. benzodiazepines, anticonvulsants, antihistamines
• Family history

Examination:

• Exclusion of other causes (no abnormal findings in patients with narcolepsy)
• Sleep studies - overnight polysomnogram followed by multiple sleep latency test
• Genetic studies
• ± MRI scan if doubt remains over the diagnosis

General measures

Pharmacological

• Modafinil and sodium oxybate appear to help the symptom of excessive daytime sleepiness.^9,10
• Methylphenidate and dexamfetamine have fallen from favour because of the potential for abuse.

Modafinil is suggested as first-line management because:

• It is long-acting.
• It has a low potential as a drug of abuse.
• There have been placebo-controlled, double-blind trials showing its efficacy.¹¹

Cataplexy may also be helped by antidepressants; clomipramine, fluoxetine, venlafaxine and others have been used with success in this regard.

Narcolepsy cannot at present be cured and remains a chronic condition, although its symptoms may be controlled by the various measures outlined above.
Narcolepsy does not affect intelligence and performance at school or university can be optimised by controlling the symptoms.