What is narcolepsy with cataplexy?

Narcolepsy with Cataplexy

Narcolepsy with cataplexy (Type 1 narcolepsy) is a chronic neurological sleep disorder defined by the combination of excessive daytime sleepiness and cataplexy—sudden bilateral loss of muscle tone triggered by strong emotions, particularly laughter or anger. 1

Core Diagnostic Features

To establish the diagnosis, you must document both excessive daytime sleepiness AND a definite history of cataplexy. 1

Cataplexy Characteristics

• Cataplexy manifests as sudden muscle weakness in the legs or arms, buckling at the knees, and/or dropping items from the hands, always triggered by emotion (especially laughter or anger). 1

• Consciousness is completely preserved during cataplexy episodes—patients remain awake and aware throughout the attack and have no amnesia for the event. 2

• This preservation of consciousness distinguishes cataplexy from seizures (which alter consciousness) and syncope (which causes loss of consciousness). 2

• In adults, episodes typically last seconds to minutes and resolve spontaneously. 3, 4

Pediatric Presentation Differences

• Children with cataplexy present differently than adults: they may have profound baseline facial hypotonia, active tongue and perioral muscle movements, and cataplexy without clear emotional triggers. 1, 2

• Pediatric cataplexy can resemble clonic, atonic, or myoclonic seizures, but the key distinguishing feature is the absence of loss of consciousness. 1, 2

• Head drops in young children while eating solid food is a common example of cataplexy in this age group. 1

Associated Symptoms (The Classic Tetrad)

Beyond the required excessive daytime sleepiness and cataplexy, patients may experience:

• Hypnagogic hallucinations—most often visual hallucinations occurring at sleep onset. 1

• Sleep paralysis—episodes of immobility occurring at sleep onset or upon awakening. 1

• Disrupted nocturnal sleep with frequent awakenings. 1, 5

• Automatic behaviors—repetitive common behaviors performed during periods of sleepiness that are not remembered afterward. 1

Epidemiology and Risk Factors

• Narcolepsy with cataplexy affects approximately 0.02-0.05% of the population, with a slight male predominance. 1, 5

• Onset typically occurs during teenage years and young adulthood, though all ages can be affected. 5

• Suggested precipitating factors include head trauma, sustained sleep deprivation, or non-specific viral illness, though these are not definitively proven. 1

• Most patients carry the HLA DQB1*0602 allele, suggesting an autoimmune etiology involving loss of hypocretin-producing neurons in the hypothalamus. 6, 5

Pathophysiology

• Type 1 narcolepsy is caused by degeneration of hypothalamic neurons that produce hypocretin (orexin), a wakefulness-associated neurotransmitter. 1, 5

• Cerebrospinal fluid in patients with narcolepsy with cataplexy shows very low or undetectable levels of hypocretin. 1, 2, 5

Diagnostic Testing

• Sleep monitoring demonstrates rapid sleep onset (mean sleep latency <5 minutes) and two or more sleep-onset REM periods (SOREMPs) during Multiple Sleep Latency Testing (MSLT). 7, 5

• Polysomnography shows abnormal, shortened REM sleep latencies and frequent movements and awakenings during sleep. 5

• Cerebrospinal fluid hypocretin testing can confirm the diagnosis but is not routinely necessary when clinical criteria are met. 1, 6

Impact on Morbidity and Quality of Life

• The morbidity associated with narcolepsy with cataplexy is substantial: cognitive impairment with fatigue, impaired memory and concentration, depression, loss of employment due to sleep-related errors, and social withdrawal. 1

• There is significantly increased risk for traffic accidents and work-related injuries due to sleepiness and inattentiveness. 1

• Untreated cataplexy is socially disabling, as attacks can lead to embarrassment and social isolation. 1

• Weight gain and obesity are common, affecting more than half of children who present with narcolepsy. 1

• Approximately one-third of children with narcolepsy also have symptoms of attention-deficit/hyperactivity disorder. 1

• Diagnosis is typically delayed by 10-15 years due to protean manifestations and lack of physician awareness, leading to prolonged poor quality of life. 4

Common Diagnostic Pitfalls

• Failure to recognize cataplexy as distinct from seizures is a major pitfall—remember that consciousness is preserved in cataplexy but altered in seizures. 8, 2

• Narcolepsy is frequently misdiagnosed as chronic fatigue, depression, attention-deficit/hyperactivity disorder, or sleep-disordered breathing. 4

• In children, cataplexy may be mistaken for seizure activity due to the hyperkinetic movements and facial involvement. 1, 2

Management Principles

• Sodium oxybate is the first-line treatment for both cataplexy and excessive daytime sleepiness, as it is FDA-approved for both symptoms. 8

• Pitolisant (histamine-3-receptor inverse agonist) is also effective for cataplexy and has the advantage of not being a controlled substance. 8, 9

• Antidepressants (particularly tricyclic antidepressants, SSRIs, and venlafaxine) are effective second-line agents for cataplexy control. 8, 3

• Stimulants such as modafinil or methylphenidate are used to manage excessive daytime sleepiness. 7, 3, 4

• Behavioral modifications including scheduled naps, good sleep hygiene, and regular sleep-wake schedules are important adjuncts. 8

When to Refer

• Primary care physicians should refer patients to a sleep specialist when narcolepsy with cataplexy is suspected, as specialized testing (MSLT) and complex pharmacological management are required. 8, 10

• Sleep specialists can properly differentiate narcolepsy from other causes of excessive sleepiness such as obstructive sleep apnea, idiopathic hypersomnia, and medication-induced hypersomnia. 10