Introduction

Narcolepsy is a disorder of sleep –wake control and is characterized by daytime sleepiness, cataplexy (sudden transient muscle weakness classically triggered by laughter), hypnagogic hallucinations (seeing things or people when going to sleep), and sleep paralysis (inability to move upon awakening from sleep).  There are two forms of narcolepsy which are differentiated from one another based on the presence (Type 1) or absence (Type 2) of cataplexy.  The symptoms of narcolepsy and cataplexy are caused by a deficiency of neurotransmitters in the brain, hypocretin-1 and hypocretin-2, which increase activity in the brain to promote and maintain wakefulness.  The release of these two neurotransmitters also prevents inappropriate transition into REM (rapid eye movement sleep).  Loss of these neurotransmitters is thought to lead to the intrusion of REM sleep phenomena (cataplexy, sleep paralysis, hypnagogic hallucinations) into wakefulness.  Patients with narcolepsy may be misdiagnosed as depressed or anxious, or mischaracterized at “lazy” because of their symptoms which can often lead to a significant delay in confirmation of the diagnosis.  Life impact can be considerable ranging from social embarrassment and poor school and work performance to potentially life-threatening motor vehicle accidents. Correct diagnosis and effective treatment can be life changing

Symptoms

The essential symptom of narcolepsy is daytime sleepiness.  The classic tetrad of chronic daytime sleepiness with varying amounts of cataplexy, hypnagogic hallucinations, and sleep paralysis are only present in one-third of patients.  Patients with narcolepsy type 1 (narcolepsy with cataplexy) typically present with moderate to severe daytime sleepiness, transient facial weakness or falls triggered by joking or laughter (partial or complete cataplexy), or the inability to move for one or two minutes immediately after awakening or just before falling asleep (sleep paralysis).  While cataplexy should prompt immediate consideration of narcolepsy, other symptoms are less specific, including complaints of daytime sleepiness or hallucinations that occur as the patient is falling asleep or awakening. Patients with narcolepsy type 2 do not have cataplexy.

Diagnosis

A comprehensive history and exam is the first step in evaluating and individual with a suspected diagnosis of narcolepsy.  Additionally, two tests are helpful in establishing the diagnosis and guiding therapeutic decisions:

Polysomngram (PSG): This exam evaluates sleep architecture, sleep quality, and other physiological parameters.  Patients who have narcolepsy typically demonstrate spontaneous awakenings, mildly reduced sleep efficiency, and increased light non-REM sleep.  Patients with narcolepsy type 1 and occasionally those with narcolepsy type 2 may show REM sleep within 15 minutes of the onset of sleep.

Multiple Sleep Latency Test (MSLT): This exam is performed the day after an overnight polysomnogram to objectively evaluate daytime sleepiness by documenting how long it takes to fall asleep during a series of scheduled naps as well as the occurrence of REM sleep during these naps. 

Blood work to include HLA testing (human leukocyte antigen) testing for certain genetic factors may be included but are not routinely suggested. 

Treatment

Narcolepsy is a treatable disorder and responds well to behavioral strategies and medication therapy.

Behavioral strategies include:

• Scheduled naps (20 minutes) once or twice daily can improve wakefulness for up to 3-4 hours and reduce the need for stimulant medication.
• Avoidance of sleep deprivation and maintenance of a regular sleep wake schedule.
• Avoidance of sedating medications including benzodiazepines, opiates, and alcohol.

Medications to improve alertness (side effects are included in parentheses):

• Modafinil/Armodafinil (headache, nausea, dry mouth, anorexia, diarrhea, can reduce effectiveness of hormonal contraception)
• Solriamfetol (Sunosi) (headache, nausea, decreased appetite, anxiety, dry mouth, and diarrhea)
• Pitolisant (Wakix) (headache, insomnia, nausea, and anxiety, may cause QT interval prolongation and reduce effectiveness or hormonal contraception)
• Methylphenidate (can lower threshold for seizures, anxiety, insomnia, rapid heart rate, cardiac arrhythmia, high blood pressure, psychosis)
• Amphetamines (can lower threshold for seizures, anxiety, insomnia, rapid heart rate, cardiac arrhythmia, high blood pressure, psychosis)

Medications to manage cataplexy (side effects included in parentheses):

• Pitolisant (Wakix) (see above)
• Venlafaxine (transient nausea, headache, insomnia, increase in blood-pressure when given in higher doses)
• Fluoxetine (mood changes, dry mouth, nausea, insomnia)
• Protriptyline (dry mouth, constipation, sweating, anxiety, disturbed nighttime sleep, orthostatic hypotension)

Medications that manage both cataplexy and daytime sleepiness (side effects included in parentheses):

• Sodium Oxybate (Xyrem and Xywav) (morning sedation, nausea, dizziness, urinary incontinence, sleepwalking)

Useful links:

Narcolepsy Network