Narcolepsy is a rare and chronic neurological disorder characterized by instability in sleep-wake regulation. marked by chronic excessive daytime drowsiness (EDS) and disrupted nighttime sleep. Individuals with narcolepsy experience sudden sleep attacks that may last from a few seconds to several minutes and can occur multiple times a day. The condition is thought to be autoimmune, involving the destruction of brain cells that produce hypocretin, a peptide critical for regulating sleep and wakefulness. Narcolepsy disrupts the normal sleep cycle, causing REM sleep to begin abnormally early. There are two types of narcolepsy as classified by the International Classification of Sleep Disorders, Third Edition (ICSD-3):
- Narcolepsy Type 1 (NT1): Cataplexy, low levels of hypocretin.
- Narcolepsy Type 2 (NT2): Similar to NT1 but without cataplexy or low hypocretin levels.
The disorder affects approximately 1 in 2,000 people, though many cases remain undiagnosed or misdiagnosed.
Clinical Description and symptoms
| Classification Level | Disorder |
| Prevalence | 1/2000 -1 /5000 |
| Age of Onset | Adolescent, Adult, Childhood |
| Inheritance | Unknown |
Symptoms typically start between ages 10 and 30 and are lifelong. Diagnosis often takes about 10 years from symptom onset. Non-specific signs may include hypnagogic hallucinations, sleep paralysis, disturbed nocturnal sleep, and weight gain in children. The disorder is linked to the loss of orexin/hypocretin neurons in the lateral hypothalamus, resulting in low hypocretin-1 levels in cerebrospinal fluid. An autoimmune origin is suspected, with genetic factors (e.g., the HLA-DQB1*0602 allele) playing a role, though this remains unproven Excessive Daytime Sleepiness (EDS): Overwhelming urge to sleep, particularly in monotonous situations, leading to sudden sleep attacks and lapses in attention. Symptoms include:
- Automatic Behaviors: Unconscious actions performed while drowsy, such as writing meaningless text.
- Disrupted Nighttime Sleep: Frequent awakenings, excessive physical movements, and sleep apnea.
- Sleep Paralysis: Inability to move while falling asleep or waking up.
- Sleep-Related Hallucinations: Vivid visual or sensory experiences occurring while falling asleep (hypnagogic) or waking up (hypnopompic), sometimes with sleep paralysis.
- For Narcolepsy Type 1 (NT1), an additional symptom is:
- Cataplexy: Sudden loss of muscle control triggered by strong emotions, lasting from seconds to minutes, affecting both sides of the body.
Image: Causes, Prevalence and Symptoms of Narcolepsy
Diagnosis and Treatment
To diagnose narcolepsy, clinicians rely on a combination of clinical symptoms, specific findings from polysomnography, and cerebrospinal fluid analysis for hypocretin-1 levels. A diagnostic polysomnography usually reveals at least two sleep onset rapid eye movement episodes SOREMPs) and an average sleep latency of less than eight minutes. Low cerebrospinal fluid hypocretin-1 levels (<110 pg/ml) can confirm the diagnosis. Differential diagnosis involves ensuring that cataplexy is characteristic; without it, other causes of excessive daytime sleepiness, such as chronic sleep deprivation or idiopathic hypersomnia, should be considered. Genetic counseling is rarely needed, as familial cases are uncommon, and inheritance patterns are unclear. Management focuses on symptomatic treatment since the loss of orexin neurons is irreversible. First-line medications include modafinil, pitolisant, and sodium oxybate, with second-line options like methylphenidate and amphetamines. Sodium oxybate is particularly effective for both daytime sleepiness and nighttime disruptions. Good sleep hygiene practices, including regular naps and consistent sleep routines, are also recommended. Although narcolepsy can significantly impact academic and professional performance, the condition often remains stable, with potential improvements in symptoms over time, though nighttime sleep quality may deteriorate with age.
For more on therapeutics against this disease, stay tuned for N for Narcolepsy Part II. Meanwhile, click here for more available resources and support groups for Narcolepsy.
Dr. Malini Gupta, Ph.D.
Sources
- https://www.orpha.net/en/disease/detail/2073
- https://www.sleepfoundation.org/narcolepsy
- https://rarediseases.org/rare-diseases/narcolepsy/
- Figure has elements from – https://project-sleep.com/
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