Narcolepsy Type 1
A rare neurologic disease characterized by excessive daytime sleepiness associated with uncontrollable sleep urges and cataplexy (sudden loss of muscle tone while awake, often triggered by pleasant emotions).
Epidemiology
Narcolepsy type 1 prevalence is estimated between 1/2,000 and 1/5,000.
Clinical description
The age of onset varies between 10 and 30 years old and symptoms are lifelong. The average time between the age of appearance of the symptoms and the diagnosis is still very long, 10 years. Other, non specific, clinical signs include hypnagogic hallucinations, sleep paralysis, disturbed nocturnal sleep, and weight gain, especially in children.
Etiology
The disease is due to loss or impairment of the orexin/hypocretin neurons of the lateral hypothalamus that results in decreased hypocretin-1 levels in the cerebrospinal fluid. An autoimmune origin for the disease is highly suspected, particularly environmental factors interacting with susceptibility genes (more than 98% of the patients carry the HLA-DQB1*0602 allele); however, this is unproven.
Diagnostic methods
Definitive diagnosis requires the presence of clinical symptoms, characteristic polysomnography findings and/or low hypocretin-1 levels in cerebral spinal fluid. Nocturnal and daytime polysomnography demonstrate an average sleep latency of under eight minutes with at least two sleep onset rapid eye movement periods (SOREMP) on multiple sleep latency tests. The presence of low hypocretin-1 levels (<110 pg/ml) in the cerebrospinal fluid can confirm the diagnosis with an excellent sensibility and specificity.
Differential diagnosis
Cataplexy must be typical to be confident with the diagnosis. In absence of typical cataplexy, other causes of sleepiness must be considered, such as chronic insufficient sleep, idiopathic hypersomnia or narcolepsy without cataplexy, now called narcolepsy type 2.
Genetic counseling
Rare familial cases have been reported (<2%); however the mode of inheritance is unclear.
Management and treatment
Treatment is nowadays only symptomatic, as the loss of orexin neurons is irreversible. It comprises stimulants (modafinil, methylphenidate, amphetamine, pitolisant, solriamfetol), anticataplectic drugs (antidepressants) or sodium oxybate. First-line treatment of diurnal sleepiness is often with modafinil but it can be also with pitolisant or sodium oxybate. Second-line treatments are methylphenidate, solriamfetol or amphetamines. Sodium oxybate is efficient for sleepiness, cataplexy and disturbed nocturnal sleep. A good sleep hygiene is always recommended, with scheduled short naps, and regular sleep habits.
Prognosis
Narcolepsy can severely disable scholarly and professional performances. The evolution of the disease is often stable with a frequent improvement of sleepiness and cataplexy, but with age there is an aggravation of the poor quality of night sleep.