What is narcolepsy?

What is Narcolepsy

Narcolepsy is a chronic neurological disorder of sleep-wake cycle regulation characterized by excessive daytime sleepiness (EDS) occurring daily for at least 3 months, often accompanied by cataplexy (sudden muscle weakness triggered by emotion), sleep paralysis, hypnagogic/hypnopompic hallucinations, and disrupted nocturnal sleep. 1, 2

Core Clinical Features

Primary Symptom: Excessive Daytime Sleepiness

• EDS must occur daily for a minimum of 3 months and represents the cardinal feature present in all narcolepsy patients 1
• Patients experience brief involuntary sleep episodes and an overwhelming urge to sleep during the day despite adequate nighttime sleep opportunity 3, 4
• The sleepiness is pathological—not simply feeling tired—and involves unintentional sleep attacks that can occur during activities requiring attention 5

Cataplexy: The Pathognomonic Feature

• Cataplexy consists of sudden bilateral loss of muscle tone triggered by strong emotions, most commonly laughter or anger 1, 6
• Episodes manifest as leg/arm weakness, knee buckling, jaw dropping, or dropping objects while consciousness remains completely preserved 6
• Patients have no amnesia for cataplexy episodes and can recall everything that occurred 6
• When cataplexy is present alongside daytime sleepiness, it establishes the diagnosis of narcolepsy Type 1 (formerly "narcolepsy with cataplexy") 2, 6
• Approximately 60-90% of narcolepsy patients experience cataplexy, though only 15% manifest all narcolepsy symptoms together 7

REM Sleep Intrusion Phenomena

• Sleep paralysis: Brief inability to move or speak occurring at sleep onset or upon awakening, representing REM sleep atonia intruding into wakefulness 1, 8
• Hypnagogic/hypnopompic hallucinations: Vivid, often frightening visual hallucinations at sleep onset (hypnagogic) or upon awakening (hypnopompic) 1, 3
• Disrupted nocturnal sleep: Frequent awakenings and fragmented nighttime sleep despite excessive daytime sleepiness 2, 5

Classification System

Type 1 Narcolepsy (with Cataplexy)

• Characterized by EDS plus definite cataplexy 2
• Associated with very low or undetectable cerebrospinal fluid (CSF) hypocretin-1 levels (≤110 pg/mL or <1/3 of normal) 9, 1
• Results from loss of hypocretin/orexin-producing neurons in the hypothalamus 5, 7

Type 2 Narcolepsy (without Cataplexy)

• Features EDS without cataplexy but may include other narcolepsy symptoms like automatic behaviors, hypnagogic hallucinations, and sleep paralysis 2
• CSF hypocretin levels are typically normal or only mildly reduced 2

Underlying Pathophysiology

• Narcolepsy Type 1 results from dysfunction of the hypocretin/orexin system, specifically loss of hypothalamic neurons that produce these wake-promoting neuropeptides 5, 7
• Substantial evidence supports an autoimmune mechanism targeting hypocretin neurons, likely triggered by environmental factors in genetically susceptible individuals 4, 7
• The disorder represents impaired expression of wakefulness and abnormal REM sleep regulation, causing REM sleep phenomena to intrude into wakefulness 8

Epidemiology and Natural History

• Symptom onset typically occurs between ages 10-35 years, though presentation can occur at any age 5
• Nearly half of patients first present for diagnosis after age 40 years due to diagnostic delays 8
• Only 15-30% of individuals with narcolepsy are ever diagnosed or treated, reflecting significant underrecognition 8
• The disorder appears lifelong but not progressive, though mild disease severity and long delays in cataplexy expression often cause intervals of years between symptom onset and diagnosis 8

Diagnostic Approach

Clinical History Requirements

• Document onset, frequency, duration, and response to napping of EDS for minimum 3 months 1
• Assess for emotional triggers of muscle weakness (particularly laughter or anger) to identify cataplexy 1, 6
• Evaluate for auxiliary REM-sleep symptoms including hallucinations, sleep paralysis, and disturbed nocturnal sleep 1
• Obtain comprehensive medication review, as sedating agents (benzodiazepines, opioids, antihistamines, certain antidepressants) frequently mimic narcolepsy symptoms in older adults 1, 2

Objective Testing

• Overnight polysomnography (PSG) must precede diagnostic testing to rule out other sleep disorders (obstructive sleep apnea, periodic limb movements, restless legs syndrome) and ensure adequate sleep before MSLT 1, 2
• Multiple Sleep Latency Test (MSLT) involves 4-5 daytime nap opportunities at 2-hour intervals measuring sleep latency and sleep type 1
• MSLT diagnostic criteria for narcolepsy: Mean sleep latency ≤8 minutes PLUS ≥2 sleep-onset REM periods (SOREMPs) 2
• CSF hypocretin-1 testing can confirm Type 1 narcolepsy when levels are ≤110 pg/mL, and this result cannot be falsely positive from sleep deprivation 9, 1

Secondary Causes to Exclude

• Neurological disorders: Parkinson's disease, traumatic brain injury, stroke, multiple sclerosis, myotonic dystrophy 1, 2
• Endocrine/metabolic: Hypothyroidism, hepatic encephalopathy 2
• Medication-induced: Current use or recent discontinuation of sedating medications or stimulants 1, 2
• Other sleep disorders: Insufficient sleep syndrome, circadian rhythm disorders, severe restless legs syndrome 2

Critical Diagnostic Pitfalls

• Medication-induced hypersomnia is the most frequently overlooked cause in older adults who commonly take multiple sedating medications 1, 2
• The critical distinction between narcolepsy and idiopathic hypersomnia is the number of SOREMPs: ≥2 SOREMPs indicate REM dysregulation characteristic of narcolepsy, while <2 SOREMPs with mean sleep latency ≤8 minutes suggests idiopathic hypersomnia 2
• Cataplexy can be misdiagnosed as epilepsy, but unlike seizures, cataplexy preserves consciousness with no post-ictal confusion 6
• In children, cataplexy presents atypically with profound facial hypotonia, tongue/perioral movements, and hyperkinetic movements that may resemble seizures but occur without loss of consciousness 6

Referral Indications

• The American Academy of Sleep Medicine recommends referring patients to a sleep specialist when narcolepsy or idiopathic hypersomnia is suspected, as sleep specialists have expertise to differentiate narcolepsy from other causes of excessive sleepiness and manage complex pharmacological treatment 1