Narcolepsy

Narcolepsy is the clinical syndrome of daytime sleepiness with cataplexy, hypnagogic

hallucinations, and sleep paralysis.
Epidemiology
Narcolepsy type 1 (with cataplexy) has a prevalence of 25-50 per 100,000 people and incidence
of 0.74 per 100,000 per year. It is equally common in men and women and usually begins in the
teens and early twenties. Type 2 (without cataplexy) is poorly studied.
Etiology
Loss of orexin (hypocretin) signaling is the most commonly tested cause for narcolepsy. Loss of
neuropeptides orexin-A and orexin-B in the hypothalamus can lead to Narcolepsy. They have
excitatory effects when they bind to post synaptic neurons and create wakefulness in portions of
the brain. This stabilization of wakefulness prevents inappropriate transitions into REM sleep.
Loss of the orexins leads to REM related phenomena (cataplexy, hallucinations, and sleep
paralysis). There is some speculation that narcolepsy could be brought about by an autoimmune
process against orexin peptides. This is currently controversial and not well proven, but an
interesting theory.
Genetic factors in the HLA DQB1*0602 haplotype are related to narcolepsy. Environmental
factors appear to be more important since only 25% of affected monozygotic twins are
concordant for narcolepsy. Narcolepsy shows incomplete penetrance in families.
Rarely narcolepsy can be caused by brain lesions which cause direct injury to orexin neurons.
Clinical Features
Narcolepsy has a classic tetrad of chronic daytime sleepiness with varying amounts of cataplexy,
hypnagogic/hypnopompic hallucinations, and sleep paralysis. Only one-third of the patients
have all three classic findings. Therefore, chronic daytime sleepiness alone should be a symptom
that brings narcolepsy to mind.
Patients with narcolepsy have chronic sleepiness, but they do not end up sleeping more than
normal individuals within a 24 hour period. Often, they will fall asleep at inappropriate times
with little warning: sleep attacks. Patients with narcolepsy usually have Epworth Sleepiness
Scale scores >15.
Cataplexy is emotionally-triggered muscle weakness. These periods are transient and usually
caused by positive emotions, though anger and grief can be triggers in other individuals. Often
these episodes cause collapse.
Hypnagogic hallucinations-vivid, frightening hallucinations that occur right as the patient is
falling asleep. It is thought that these hallucinations are a result of a mixture of wakefulness and
the dreaming of REM sleep. Hypnopompic hallucinations are similar, but occur upon waking.

Sleep paralysis is the complete inability to move for several minutes immediately after
awakening. This is not specific for narcolepsy and can occur with insufficient sleep, irregular
sleep-wake schedules, or rebound REM.
REM patients have a high prevalence of depression and obesity
Diagnostic Criteria
Narcolepsy type 1 is easy to diagnose since it involves cataplexy and cataplexy occurs in almost
no other disorder. Narcolepsy type 2 is more difficult to diagnose because it presents similar to
other sleep disorders.
Narcolepsy has low sleep latency. Multiple sleep latency tests should be done to confirm this
finding and identify sleep onset rapid eye movement periods. Stop stimulants a week before
testing.

Daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at
least 3 months
Cataplexy and a mean sleep latency of < 8 minutes and two or more sleep onset REM
periods on a multiple sleep latency test.
Cerebrospinal fluid hypocretin-1 is low (lumbar tap)

Treatment
Many drugs available to treat narcolepsy target either daytime sleepiness or cataplexy. If a
patient has both symptoms, they may require more than one drug to manage their disease.
The goal of therapy is to improve alertness and safety. Repeat Epworth Sleepiness score or the
Maintenance of Wakefulness Test should be done to determine improvement. Persistently
daytime sleepy patients should be advised against activities like driving.
Modafinil, Methylphenidate, or amphetamines are used to treat sleepiness. Modafinil trial
should be attempted first, because research has shown superior efficacy with this drug.
Psychiatric and cardiovascular side effects should be discussed with patients.
REM sleep-suppressing medication should be used for cataplexy. Venlafaxine, fluoxetine,
atomoxetine. Venlafaxine with extended release is the preferred drug if compatible with patient.
Sodium oxybate may be of benefit for patients whose sleepiness or cataplexy does not improve
with medications.