What is narcolepsy?

What is Narcolepsy

Narcolepsy is a chronic neurological sleep disorder characterized by the brain's inability to properly regulate sleep-wake cycles, resulting in excessive daytime sleepiness and abnormal intrusion of REM sleep phenomena into wakefulness. 1, 2

Core Clinical Features

Narcolepsy manifests through a constellation of symptoms related to disrupted sleep-wake regulation and REM sleep dyscontrol:

Primary Symptom

• Excessive daytime sleepiness (EDS) occurring daily for at least 3 months is the hallmark feature, with patients experiencing irresistible sleep attacks and difficulty maintaining wakefulness despite adequate nighttime sleep 1, 3

REM Sleep Intrusion Symptoms

• Cataplexy - sudden bilateral loss of muscle tone triggered by strong emotions (particularly laughter or anger), manifesting as leg/arm weakness, knee buckling, or dropping objects, while consciousness remains fully preserved throughout the episode 1, 4, 3
• Sleep paralysis - brief episodes of inability to move occurring at sleep onset or upon awakening 1, 3
• Hypnagogic/hypnopompic hallucinations - vivid, typically visual hallucinations occurring at sleep transitions 1, 3
• Disrupted nocturnal sleep with frequent awakenings 1
• Automatic behaviors - episodes occurring during sleepiness that are not subsequently remembered 1

Classification

Type 1 Narcolepsy (Narcolepsy with Cataplexy)

• Requires both excessive daytime sleepiness AND definite cataplexy 3, 5
• Associated with very low or undetectable cerebrospinal fluid hypocretin-1 levels (≤110 pg/mL or <1/3 of normal) 4, 3
• Cataplexy is pathognomonic for narcolepsy when present with daytime sleepiness 4, 3

Type 2 Narcolepsy (Narcolepsy without Cataplexy)

• Features excessive daytime sleepiness without cataplexy 5
• May include other narcolepsy symptoms like automatic behaviors, hallucinations, and sleep paralysis 5
• Requires objective confirmation via Multiple Sleep Latency Test 3

Underlying Pathophysiology

• The pathological hallmark is loss of hypocretin (orexin) neurons in the hypothalamus, likely triggered by environmental factors in genetically susceptible individuals 6, 7
• A large majority of patients with narcolepsy and cataplexy have hypocretin ligand deficiency due to post-natal death of hypocretin neurons 7
• Close association with specific HLA types suggests possible autoimmune mechanisms, though this remains unproven 7

Epidemiology and Natural History

• Overall prevalence is approximately 0.05% with slight male predominance 1
• Excessive sleepiness typically begins in the second or third decade of life, followed by auxiliary symptoms 2
• The disorder appears lifelong but not progressive 2
• Only 15-30% of individuals with narcolepsy are ever diagnosed or treated, with nearly half first presenting after age 40 years due to mild severity, misdiagnoses, or delayed cataplexy expression 2
• Only 15% of patients manifest all classic symptoms together 6

Diagnostic Approach

Clinical Evaluation

• Obtain thorough history documenting onset, frequency, duration of sleepiness, response to napping, and presence of cataplexy with specific emotional triggers (laughter, anger, excitement, surprise) 1, 4, 3
• Document detailed medical, neurologic, psychiatric history and all current/recently discontinued medications 3
• Assess for preserved consciousness during cataplectic episodes and absence of post-ictal confusion to distinguish from epilepsy 4

Objective Testing

• Overnight polysomnography must precede MSLT to rule out other sleep disorders (particularly obstructive sleep apnea, periodic limb movements) and ensure adequate sleep 1, 3
• Multiple Sleep Latency Test (MSLT) involves 4-5 daytime nap opportunities at 2-hour intervals, measuring mean sleep latency and presence of sleep-onset REM periods 3
• Diagnostic MSLT criteria: mean sleep latency ≤8 minutes PLUS ≥2 sleep-onset REM periods 3, 5
• CSF hypocretin-1 levels ≤110 pg/mL definitively confirm Type 1 narcolepsy and can bypass MSLT requirements 1, 3, 5

Additional Testing

• Brain MRI, thyroid function, liver function tests, complete blood count, and serum chemistry to exclude secondary causes 1, 3

Common Pitfalls

• Narcolepsy is frequently misdiagnosed as psychiatric disorders or epilepsy due to overlapping symptoms 6
• Medications commonly used in older adults may cause or worsen hypersomnia and complicate MSLT interpretation 3, 5
• Cataplexy in children presents atypically with facial hypotonia, tongue movements, and hyperkinetic movements that may resemble seizures 4
• Adequate sleep duration for 1-2 weeks prior to MSLT is essential, as sleep deprivation can produce false-positive results 5
• The critical distinction between narcolepsy and idiopathic hypersomnia is the number of sleep-onset REM periods (≥2 indicates narcolepsy), not just mean sleep latency 5

When to Refer

• Refer to a sleep specialist when narcolepsy or idiopathic hypersomnia is suspected, when the cause of sleepiness is unknown, or for management of complex pharmacological treatment 3