Narcolepsy and other Hypersomnias of Central Origin

Essentials

• These conditions are very rare causes of excessive sleepiness but should nevertheless be identified as their correct diagnosis and treatment may significantly improve the patient's future.
• They usually emerge in adolescence or early adulthood and often hinder studies and coping in work life.
• Treatment and follow-up should be carried out in specialist centres.

Epidemiology

• The prevalence of narcolepsy with cataplexy among the Finnish adult population is 0.026%. According to literature, narcolepsy without cataplexy may be almost as common. Symptomatic narcolepsy (narcolepsy due to another medical condition) is very rare.
• After the 2010 Pandemrix^® vaccination campaign, the diagnosis of narcolepsy among children and adolescents in Finland increased more than 10-fold from the previous years. The incidence is now returning to previous levels. Also among vaccinated persons aged 20 to 64 years the risk of developing narcolepsy increased 3-to-5-fold compared to non-vaccinated persons. According to current estimate, the risk of developing narcolepsy was increased for two years after the vaccination, and in Sweden the situation is similar.
• Limited data exist on the incidence of other hypersomnias, but at the very least their classic forms are more rare than narcolepsy.

Tiredness and excessive tiredness

• Some degree of daytime tiredness is a common symptom: one in ten Finns experiences it daily or almost daily and in most cases the cause is not linked to a medical condition.
• Tiredness occurring daily or almost daily in situations that require a certain degree of physical activity and/or alertness suggests excessive tiredness.
• Usual causes include sleep deprivation (especially in those who have an inherited tendency to require a lot of sleep), inadequate sleep hygiene, certain medicines, the use of intoxicating substances, shift work, other irregularity in the sleep-wake cycle or a sleep phase shift.
• The most common medical conditions include psychiatric conditions (e.g. depression), respiratory disturbances during sleep (e.g. sleep apnoea syndrome) and sleep-associated motion disturbances (e.g. restless legs syndrome).
• Hypersomnias of central origin are characterised more by sleepiness, i.e. they are associated with an increased tendency to fall asleep.

Narcolepsy

• Excessive tiredness (sleepiness) is the main symptom of narcolepsy: alertness generally fluctuates in cycles lasting for a few hours, and the patient falls asleep in abnormal situations daily or almost daily. The sleepiness of a narcoleptic has been compared to the feeling a healthy individual would have after staying awake for 2-3 consecutive days.
  • Falling asleep is usually preceded by increased tiredness. The patient may be able to postpone falling asleep by, for example, deliberately fighting against it or by walking. After a fairly short period of sleep (< 30 minutes) the patient usually wakes refreshed.
  • Falling asleep when staying still or in stimuli-poor environments can be expected, but a typical character of narcolepsy is the patient falling asleep in unexpected situations (e.g. when talking or eating) when a healthy individual normally would not fall asleep however tired.
• Another main symptom of the classic form (type 1) of narcolepsy is cataplexy, denoting a loss of muscle tone usually triggered by strong (positive) emotions, which is accompanied by, for example, loss of tendon stretch reflexes. An essential feature of this type is lack of hypocretin (orexin).
  • Cataplexy may be partial (e.g. facial muscle twitching, reduced muscle power in the neck and/or upper limbs) or it may lead to a total loss of skeletal muscle tone leading to postural collapse. The loss of strength is usually gradual and it is rare for the patient to hurt himself/herself.
  • An attack of cataplexy usually lasts from seconds to minutes, but may last considerably longer in some patients. The frequency of the attacks may vary from a few during an entire lifetime to dozens every day.
  • It is not always easy to differentiate mild cataplexy from normal feelings, also experienced by healthy individuals, for example, after a bout of intense laughter.
• There is no cataplexy nor lack of hypocretin in type 2 narcolepsy.
• The majority of patients will experience broken night time sleep.
• Sleep paralysis and terrifying hallucinations associated with falling asleep or wakening are common, but their occurrence shows great inter-individual variation.
• Parasomnias are common, and as many as a quarter of the patients will develop sleep apnoea.
• Depression and obesity with associated consequences are common.

Idiopathic hypersomnia

• Idiopathic hypersomnia is a diagnosis of exclusion, and after comprehensive neurological, psychiatric and other investigations it can be diagnosed in those patients with excessive sleepiness whose test results, other than those of a multiple sleep latency test, are normal.
• The following features usually aid the differentiation of the condition from narcolepsy (without cataplexy):
  • night time sleep is continuous and in a typical case clearly longer than normal
  • upon awakening (also after a daytime nap) the patient is drowsy or even confused ("sleep drunkenness")
  • a patient with hypersomnia often does not feel fully awake throughout the day whereas a patient with narcolepsy has phases of alertness (especially following a short nap) despite the strong variation in the level of alertness
  • the need to fall asleep during the daytime is not as overpowering as in narcolepsy, and the sleep periods are longer (> 1 hour).
• In idiopathic hypersomnia (classic, polysymptomatic), the duration of the main nocturnal sleep phase typically ranges from 12 to 14 hours.

Periodic hypersomnias

• Characterized by episodes of excessive tiredness (sleepiness) that recur at least once a year and last from 2 days to 4 weeks. The patient's functional capacity is normal between the symptomatic episodes.
• The patient may sleep up to 18 hours out of 24 hours.
• The best known periodic hypersomnia is the polysymptomatic type (Kleine-Levin syndrome), which may be associated with confusion, aggression, hypersexuality and compulsive overeating.

Diagnosis

• In a specialist sleep disorder clinic.
• Diagnosis is usually based on polysomnography (PSG) studies and on a multiple sleep latency test, which is carried out on the day after the PSG.
• It is also possible to diagnose narcolepsy without sleep studies if hypocretin (orexin) concentration measured from the cerebrospinal fluid is exceptionally low.
• Narcolepsy and idiopathic hypersomnia are demanding diagnoses, which usually mean lifelong medication and may necessitate, for example, significant occupational adjustments.

Treatment Antidepressant Drugs for Narcolepsy

Ability to work and function

• Based on clinical experience the severity of symptoms shows great inter-individual variability as does the patients' ability to adjust to the limitations imposed by the condition.
• In the best case scenario the effects are mild and the patient's functional capacity shows no significant variation from normal. At their worst the symptoms may significantly impair functional capacity so that it is only periodically at the normal level, a few hours at a time, following episodes of falling asleep or naps.
• A patient with narcolepsy may cope almost normally even in fairly demanding occupations, but in many patients the disease impairs the ability to work at least to some degree and should be considered as a limiting factor when making career choices, particularly in safety critical work.
• Data from various sources indicate that, in addition to periods of sleep, 20-80% of patients experience automatic behaviours, associated with impaired alertness due to sleepiness, during which self-control is diminished or absent and, if the activity continues, the patient's functioning becomes inadequate or erroneous, but the patient will not recall the behaviour.
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