Central Disorders of Hypersomnolence

Abstract

The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassifi cation distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1.Sleepiness can be treated with modafi nil/armodafi nil or sympathomimetic CNS stimulants, which have been shown to be benefi cial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is eff ective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are

▼Pitolisant for narcolepsy

“…Narcolepsy is a rare condition with an estimated prevalence of 0.025% to 0.05% 2,3. It is a chronic neurological disorder in which there is disruption in the usual pattern of the sleep-wake cycle 2.…”

“…The usual age of onset of narcolepsy is in the first two decades of life with a median onset of 16 years, but it often remains undiagnosed until many years after initial symptom onset. The condition is often associated with severely reduced levels, or absence, of hypocretin (orexin), a neuropeptide produced in the lateral hypothalamus that is essential for the regulation of the sleep-wake cycle through its influence on histaminergic, noradrenergic, serotonergic and cholinergic systems 3. Loss of hypocretin secretion and development of narcolepsy is thought to be an autoimmune response in genetically predisposed people 2,3…”

“…Diagnosis is based on clinical features together with the multiple sleep latency test, which consists of four or five 20-minute nap opportunities at 2-hour intervals and measures readiness to fall asleep 3. The severity of narcolepsy is assessed using measures of ability to stay awake in monotonous conditions (e.g.…”

“…Behavioural modifications, such as scheduled naps and regular bedtimes can help patients maintain a regular sleep schedule 2,3. Patients with narcolepsy are often overweight or obese, or have depression, and 25–30% of patients have associated obstructive sleep apnoea that may require specific management to improve sleepiness.…”

“…The amphetamine stimulants dexamfetamine (licensed for the treatment of adults with narcolepsy)9 and methylphenidate (off-label use) have an effect on daytime sleepiness but are contraindicated in adults with cardiovascular disease or glaucoma and have a potential for addiction and abuse 2. Sodium oxybate, a central nervous system depressant is licensed for the treatment of narcolepsy with cataplexy 2,3,10. Antidepressants that suppress REM sleep have also been used to treat cataplexy, hypnagogic hallucinations and sleep paralysis (unlicensed uses); and hypnotics have been used to treat disturbed nighttime sleep 2…”