PRIMEVIEW

NARCOLEPSY
For the Primer, visit doi:10.1038/nrdp.2016.100

Narcolepsy is a chronic sleep disorder MECHANISMS

DIAGNOSIS
that is characterized by excessive
daytime sleepiness. The disorder can be
Diagnosis requires sleep The selective loss of hypocretin neurons in the
subdivided into two subtypes: narcolepsy
The core questionnaires, lateral hypothalamus is speculated to underlie
type 1 (NT1; also known as narcolepsy symptoms of polysomnography the development of NT1. Hypocretin neurons act as
with cataplexy) and narcolepsy type 2 narcolepsy include Patients with (a comprehensive a stabilizing input to inhibitory connections between
(NT2; also known as narcolepsy without excessive daytime recording of the patient
NT1 also develop brain areas that promote wakefulness and those that
cataplexy). sleepiness, disrupted cataplexy — a loss during sleep) and promote sleep. Thus, loss of these neurons could
night‑time sleep, hypnagogic of muscle tone during the multiple sleep lead to uncontrolled transitions between sleep and
hallucinations (that is, wakefulness that is latency test (which wakefulness, resulting in the sleep disturbances that
EPIDEMIOLOGY hallucinations when the usually evoked by is used to quantify are observed in patients. The mechanism underlying
individual is falling asleep) strong emotions daytime sleepiness) the loss of hypocretin neurons is unknown, but the
The main genetic risk factor for narcolepsy and sleep paralysis
most likely hypothesis is that the loss of neurons is
is the HLA-DQB1*06:02 allele, which is These objective electrophysiological mediated by an autoimmune response. Supporting
found in 86–98% of patients with NT1. tests are used to assess the transition evidence for this includes the selective neuronal loss,
Other genetic risk factors include Compared into REM states and the durations of the identification of autoreactive T cells in patients
polymorphisms in several immune- with NT1, the different sleep periods, to better with narcolepsy and the strong association between
related genes, such as those encoding less is known understand the patient’s condition polymorphisms in immune-related genes and NT1.
the T cell receptor, pro-cathepsin H about NT2; this is However, no direct evidence has been reported.
and chemokine receptors. still a poorly defined
Environmental risk factors for NT1 condition and requires Antibodies Cytokines
include certain formulations of the further study
H1N1 influenza vaccination, influenza
virus infection and streptococcal infection.
The
The global prevalence of narcolepsy is 25–50 mechanisms
cases per 100,000 individuals, which probably underlying the Hypocretin
reflects a combination of NT1 and NT2 subtypes development neuron
of cataplexy
are poorly
understood MANAGEMENT
QUALITY OF LIFE
Stimulants (such as modafinil and armodafinil)
Pitolisant,
Patients with narcolepsy have deficits in alertness are the first-line treatments for excessive
a histamine
and attention, which are enhanced when patients daytime sleepiness in patients with narcolepsy.
receptor antagonist,
have to concentrate on demanding, monotonous Sodium oxybate is the only treatment that
has been approved
and prolonged tasks. Several comorbidities are can improve all of the core narcolepsy
for the treatment of
found in patients with narcolepsy, including symptoms, including excessive daytime
OUTLOOK narcolepsy by the
psychiatric conditions, other sleep disorders sleepiness, disrupted night-time sleep and,
European Medicines
(such as sleep apnoea and restless legs syndrome) in patients with NT1, cataplexy.
Agency
and metabolic diseases. Despite a substantial improvement past decade, further questions NT1, more studies
in our understanding of the remain. Although the autoimmune- are required to Non-pharmacological management
Narcolepsy might increase pathophysiology, diagnosis and mediated loss of hypocretin provide direct evidence of narcolepsy includes scheduled
the risk of car accidents treatment of narcolepsy over the neurons is likely in patients with in support of this hypothesis. daytime naps and night-time sleep

Written by Louise Adams; designed by Laura Marshall Article number: 160101; doi:10.1038/nrdp.2016.101; published online 9 Feb 2017
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