What Causes Narcolepsy? These Factors May Play a Role, Science Suggests

In many cases, chronic sleepiness is tied to low levels of certain brain chemicals.

When individuals are diagnosed with a new medical condition, their initial question invariably revolves around “how” and “why.” This natural curiosity persists with greater intensity when confronted with a condition as enigmatic as narcolepsy. Narcolepsy is a chronic sleep disorder often shrouded in obscurity and misperception, as highlighted by the nonprofit Project Sleep. While the precise cause of narcolepsy remains elusive to scientists, it is generally associated with diminished levels of a brain chemical crucial for regulating the sleep-wake cycle. Additionally, various factors are believed to contribute to the development of this perplexing disorder.

In this comprehensive exploration, we delve into the intricate landscape of narcolepsy, elucidating the signs and types of narcolepsy, and peering into the complex tapestry of factors that underlie its onset.

Deciphering the Face of Narcolepsy: Recognizing the Symptoms

Before embarking on an expedition through the causative factors of narcolepsy, it is prudent to gain a comprehensive understanding of what this disorder entails.

Narcolepsy manifests itself through a constellation of symptoms, as outlined by experts in the field of sleep medicine. These symptoms encompass excessive daytime sleepiness, hallucinations, sleep paralysis, vivid dreams, and more, according to Dr. Steven Thau, the Division Chief of the Pulmonary and Sleep Medicine Department and Medical Director of the Sleep Center at Phelps Hospital/Northwell Health. Narcolepsy can make its debut at any stage of life, but it predominantly emerges during a person’s adolescence or early adulthood, notes Dr. Thau.

While the presentation of narcolepsy varies from case to case, the initial symptom often encountered is profound daytime sleepiness. Subsequently, individuals may experience hallucinations, sleep paralysis, and cataplexy, though the latter may not manifest for several years, or possibly never, as indicated by Dr. Manjamalai Sivaraman, a specialist in sleep medicine and neurology at the University of Missouri.

Diverse Faces of Narcolepsy: Unraveling the Different Types

Narcolepsy, a multifaceted sleep disorder, is categorized into two primary types: type 1 and type 2. Additionally, there exists a third variant known as secondary narcolepsy, which will be explored in more detail later.

• Type 1 Narcolepsy: This category encompasses individuals who exhibit diminished levels of hypocretin—a pivotal brain chemical governing wakefulness—and concurrently experience cataplexy, which denotes sudden and transient muscle weakness. The Mayo Clinic asserts that type 1 narcolepsy accounts for approximately 70% of all narcolepsy cases. Dr. Richard Bogan, a medical officer at SleepMed, Inc., and an Associate Clinical Professor at the University of South Carolina School of Medicine, elucidates that these individuals endure severe manifestations of the disorder.
  
• Type 2 Narcolepsy: In this subtype, individuals manifest the full array of narcolepsy symptoms, barring cataplexy. The National Institute of Neurological Disorders and Stroke (NINDS) posits that the symptoms in type 2 narcolepsy are generally milder in intensity, and hypocretin levels typically remain within the normal range. Although no definitive methods for preventing or curing type 1 or type 2 narcolepsy are currently available, lifestyle modifications and medications can aid in managing symptoms and sustaining alertness, as emphasized by NINDS.

Unmasking the Enigma: The Underlying Causes of Narcolepsy

While our understanding of narcolepsy continues to evolve, it is essential to elucidate the factors currently known to contribute to this perplexing disorder.

• Genetics: A complex interplay of genetic factors underlies narcolepsy, particularly type 1. A prominent genetic marker is the HLA-DQB106:02 gene variation, found in a significant proportion of individuals with narcolepsy. The HLA-DQB1 gene, a key player in the immune system, exhibits this variation. However, the extent of the risk associated with this genetic variation remains uncertain. As the US National Library of Medicine notes, research is ongoing to comprehend the relationship between this gene variation and narcolepsy. In type 2 narcolepsy, the HLA-DQB106:02 gene variation is present in 50% of cases but only 12-30% of the general population, further emphasizing its significance, as indicated by the New England Journal of Medicine.
  
  Despite these genetic associations, narcolepsy is not predominantly hereditary, and familial occurrence is infrequent. According to NINDS, a mere 10% of individuals with type 1 narcolepsy have close relatives exhibiting similar symptoms. Furthermore, if a parent is afflicted with narcolepsy, the likelihood of transmitting the disorder to their offspring is merely around 1%, according to the Mayo Clinic.
  
• Infections: A compelling link exists between infections and narcolepsy, particularly in individuals harboring the HLA-DQB106:02 gene variation. Exposure to certain triggers, such as infections, may heighten the risk of developing narcolepsy, according to NINDS, based on studies involving individuals who developed narcolepsy after infection. Upper airway infections, including streptococcus pyogenes and influenza A (including H1N1), exhibit a strong association with narcolepsy. This association is especially pronounced when narcolepsy manifests during childhood, as underscored by Dr. Sivaraman.
  
• Autoimmune Reaction: An intriguing theory posits that narcolepsy, particularly type 1, may result from an autoimmune response within the body. In this scenario, the immune system erroneously targets and damages the hypocretin-producing neurons in the hypothalamus region of the brain, as elucidated by Dr. Sivaraman. This aberrant immune reaction leads to a deficit of hypocretin, contributing to sleepiness and disrupted REM sleep. This perspective envisions a scenario where the body’s immune system inadvertently orchestrates the loss of critical brain cells responsible for wakefulness. Dr. Thau succinctly characterizes this as “the cells that control wakefulness are damaged.”

Researchers are currently investigating the application of immunotherapy to reverse this neuron loss, as noted by Dr. Bogan. Preliminary findings from small-scale studies suggest that immunotherapy may enhance symptoms in narcolepsy patients, particularly those recently diagnosed. However, further research is essential to provide conclusive evidence of the treatment’s efficacy, as elaborated upon in a 2020 review published in Current Treatment Options in Neurology. These studies, while promising, lacked controlled methodologies and definitive endpoints, necessitating continued investigation.

Secondary Narcolepsy: A Distinctive Profile

In contrast to narcolepsy types 1 and 2, secondary narcolepsy differs in its underlying cause. In cases of secondary narcolepsy, damage occurs to the hypothalamus region of the brain, as highlighted by Harvard’s Division of Sleep Medicine. Individuals affected by secondary narcolepsy may display identical symptoms to those with the primary forms of the disorder. However, they frequently contend with severe neurological issues and an insatiable need for sleep, often exceeding ten hours.

Secondary narcolepsy arises from specific triggers or conditions that inflict damage upon the hypothalamus. These triggers encompass head injuries, brain tumors, multiple sclerosis, encephalitis (a rare brain inflammation), and other disorders that lead to the destruction of neural pathways responsible for promoting wakefulness. As Dr. Thau emphasizes, adopting a healthy lifestyle, abstaining from smoking, and refraining from illicit drug use can mitigate the risk of conditions that may precipitate secondary narcolepsy.

In conclusion, narcolepsy, a complex and enigmatic sleep disorder, continues to confound researchers and medical professionals. While substantial progress has been made in elucidating its underlying causes, the condition remains a multifaceted puzzle with genetic, infectious, and autoimmune dimensions. Secondary narcolepsy adds yet another layer of intricacy, arising from specific injuries or conditions. The ongoing pursuit of knowledge in this field promises to shed further light on narcolepsy’s origins, potentially opening new avenues for treatment and management of this challenging disorder.