• Investigation of the Functional Impact of Narcolepsy Type 1 including Persistent Orexin Deficiency on REM Sleep Behavior Disorder (RBD)
  • Rojin Ehsan,1 Ali Ahmadi,2,*
    1. M.Sc. Student of Genetics, Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
    2. M.Sc. Student of Genetics, Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.


  • Introduction: Rapid eye movement (REM) sleep behavior disorder is a REM sleep parasomnia first described in the mid-1980s in the United States and in 1995 in the United Kingdom. This disease is a movement control disorder due to the loss of REM-related muscle atony and is characterized by complex, intense and often violent sleep behaviors during REM sleep. This behavior can lead to damage to the patient and cause fracture, dislocation and even subdural hematoma. Clinical features during sleep include abnormal sounds, abnormal motor behavior, and changes in dream mentality. Narcolepsy is a debilitating neurological disorder characterized by instability of sleep or wakefulness states and pathological intrusion of REM sleep-related events into wakefulness. It affects approximately 1 in 2,000 people in the United States. Narcolepsy type 1 (NT1) is a group of sleep disorders that have benefited from great scientific advances in the last two decades. Deficiency of orexin, a neurotransmitter involved in the regulation of rapid eye movement sleep, is responsible for the main symptoms of NT1, which include: drowsiness, including cataplexy, nocturnal sleep disturbances, sleep-related hallucinations, and sleep paralysis. The onset of this disease usually occurs during adolescence. According to studies, the association of non-sleep-related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular complications, has subsequently been recognized. Diagnostic tools have improved, but sleep-onset rapid eye movement episodes in polysomnography and multiple sleep latency testing are key measures. The pathogenic mechanisms of narcolepsy type 1 have been partially elucidated after the discovery of a strong association of HLA class II and orexin or hypocretin deficiency. In addition, new technologies, such as the use of deep learning analysis of electroencephalographic signals, reveal a complex pattern of sleep abnormalities in human narcolepsy. The aim of this study is the functional impact of narcolepsy type 1 on persistent orexin deficiency in REM sleep behavior disorder (RBD).
  • Methods: This review study was conducted in 2024 by searching keywords such as: Narcolepsy type 1, Orexin Deficiency, REM, RBD in reliable databases such as: PubMed, Scopus and Web of Science.
  • Results: Much progress has been made since the first description of narcolepsy at the end of the 19th century. Today, this disease is distinguished as type 1 and type 2 narcolepsy. The discovery that NT1 is caused by hypocretin or orexin deficiency, along with neurochemical studies of this system, has helped determine how this neuropeptide regulates sleep-wake organization in humans. Current analyzes suggest that the main functions of the hypocretin/orexin system are (1) maintaining wakefulness in the face of moderate sleep deprivation; (2) promotion of passive wakefulness, especially in the evening, driven by the circadian clock; (3) inhibition of REM sleep, with possible differential modulatory effects on different components of the sleep stage, explaining REM sleep dissociation events in NT1; Narcolepsy is also associated with an inability to stabilize sleep, a more complex phenotype that may result from secondary alterations or the central role of hypocretin in coordinating the activity of other sleep-wake promoting systems. In addition, in the 1960s, the discovery of rapid eye movement sleep at the onset of sleep led to a better understanding of the main sleep-related symptoms of this disease. This condition may be violent and lead to harm to oneself or others without any conscious awareness. After waking up, the patient can remember the contents and information of his dream. Most patients with REM behavior disorder eventually develop neurodegenerative diseases such as Parkinsonism, dementia with Lewy bodies, or multiple system atrophy. There are also secondary causes of RBD associated with Parkinsonism, narcolepsy, or the use of antidepressants. The patient may be warned about the future development of these neurological disorders. Its medicinal and therapeutic measures are also such that in severe cases, melatonin or clonazepam may be prescribed for the patient. RBD is usually idiopathic or secondary to neurological problems such as Parkinson's disease. Also, in the absence of lumbar puncture, the diagnosis based on neurophysiological tests (day and night) and the presence of cataplexy is a pathognomonic symptom.
  • Conclusion: Also, since orexin is a potent arousal-enhancing agent, it is reasonable to assume that orexin receptor antagonists will be effective as drugs for the treatment of insomnia. To date, several orexin receptor antagonists with different pharmacological properties have been developed.
  • Keywords: Narcolepsy Type 1, Orexin Deficiency, REM, RBD