What is Narcolepsy Type 1?
Narcolepsy Type 1, also called Narcolepsy with Cataplexy, is an incurable sleep disorder where there is a reduction of hypocretin (HCRT) producing neurons in the brain. This neurotransmitter functions to control the circadian rhythm of the brain and the loss of these neurons causes Narcolepsy Type 1 which is a REM (rapid eye movement) sleep disorder. This form of narcolepsy occurs in approximately 14 per 100,000 individuals and is 50% more common in women.[1]
What are the symptoms of Narcolepsy Type 1?
- Excessive uncontrollable daytime sleepiness [2]
- Cataplexy: “Sudden loss of muscle tone while a person is awake leads to weakness and a loss of voluntary muscle control. It is often triggered by sudden, strong emotions such as laughter, fear, anger, stress, or excitement.” [3]
- Difficulty staying awake throughout the day
- Difficulty staying asleep throughout the night
- Sleep attacks
- Sleep paralysis [4]
Testing and Diagnosis
Polysomnogram - A polysomnogram is done to rule out other sleep conditions such as sleep apnea or restless leg syndrome. This test tracks breathing, eye movement, muscle movement, and brain activity and is used to quantify the amount of quality sleep the patient is receiving overnight. [5]
Multiple Sleep Latency - This exam measures how fast the patient reaches rapid eye movement (REM) sleep. During this exam patients are given 5, 15-minute opportunities to nap 2 hours apart from each other. If a patient falls asleep with a mean time of below 8 minutes with 2 or more naps where REM sleep was reached the patient can be clinically diagnosed with narcolepsy. [6]
Multiple Sleep Latency - This exam measures how fast the patient reaches rapid eye movement (REM) sleep. During this exam patients are given 5, 15-minute opportunities to nap 2 hours apart from each other. If a patient falls asleep with a mean time of below 8 minutes with 2 or more naps where REM sleep was reached the patient can be clinically diagnosed with narcolepsy. [6]
Management of the condition
Narcolepsy Type 1 is managed with a variety of medications. The goal of prescribed medications are typically either to aid in wakefulness during the day or to aid in keeping one asleep fully throughout the night.
Wakefulness promoting medications
|
Sleep aid medications
|
What causes Narcolepsy Type 1
Loss of function mutations in HCRT gene - Narcolepsy is not typically caused by a loss of function of the HCRT gene itself. Although a few cases of familial inheritance of narcolepsy have been documented, narcolepsy caused by loss of function in the HCRT gene has only been studied in canine and mouse models of the disease. [7]
Autoimmunity - It is believed that narcolepsy type 1 is linked to an autoimmune attack on neurons that produce hypocretin which is expressed by the HCRT gene. Scientists have found that 95% of narcolepsy type 1 patients belong to HLA haplotype DQB1*0602 Which suggests that immune function plays a key role in the development of the disease. Furthermore, infections from, Streptococcus pyogenes, Epstein Barr virus, H1N1 Flu and Pandemrix (a vaccine against H1N1) have all been linked to having a higher likelihood of developing this disease. [1]
Autoimmunity - It is believed that narcolepsy type 1 is linked to an autoimmune attack on neurons that produce hypocretin which is expressed by the HCRT gene. Scientists have found that 95% of narcolepsy type 1 patients belong to HLA haplotype DQB1*0602 Which suggests that immune function plays a key role in the development of the disease. Furthermore, infections from, Streptococcus pyogenes, Epstein Barr virus, H1N1 Flu and Pandemrix (a vaccine against H1N1) have all been linked to having a higher likelihood of developing this disease. [1]
Gaps in knowledge
Considering the strong links between immune type and past pathogen infections, scientists are unsure how these factors function in the development of Narcolepsy Type 1. Scientists hypothesize that there is an autoimmune reaction that selectively targets neuronal cells that express HCRT. The differentiation in how these neurons develop and the immunological pathology of what makes these neurons a target of an autoimmune attack is also unknown.
Organizations
|
References:
[1] Slowik JM, Collen JF, Yow AG. Narcolepsy. [Updated 2023 Jun 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459236/
[2] Mayo Foundation for Medical Education and Research. (2023, January 14). Narcolepsy. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/narcolepsy/symptoms-causes/syc-20375497?utm_source=Google&utm_medium=abstract&utm_content=Narcolepsy&utm_campaign=Knowledge-panel
[3] U.S. Department of Health and Human Services. (n.d.). Narcolepsy. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/narcolepsy
[4] NHS. (2022, December 30). Symptoms -Narcolepsy. NHS choices. https://www.nhs.uk/conditions/narcolepsy/symptoms/#:~:text=Sleep%20attacks%2C%20where%20you%20fall,vary%20from%20person%20to%20person.
[5] Hwang, J., Lee, T., Lee, H., & Byun, S. (2022). A clinical decision support system for sleep staging tasks with explanations from artificial intelligence: User-centered design and evaluation study. Journal of Medical Internet Research, 24(1). https://doi.org/10.2196/28659
[6] Multiple sleep latency test (MSLT). Stanford Health Care. (n.d.). https://stanfordhealthcare.org/medical-conditions/sleep/narcolepsy/diagnosis/multiple-sleep-latency-test.html#:~:text=A%20positive%20MSLT%20is%20obtained,where%20REM%20sleep%20was%20reached.
[7] Chen, L., Brown, R., McKenna, J., & McCarley, R. (2009). Animal models of narcolepsy. CNS & Neurological Disorders - Drug Targets, 8(4), 296–308. https://doi.org/10.2174/187152709788921717
[1] Slowik JM, Collen JF, Yow AG. Narcolepsy. [Updated 2023 Jun 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459236/
[2] Mayo Foundation for Medical Education and Research. (2023, January 14). Narcolepsy. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/narcolepsy/symptoms-causes/syc-20375497?utm_source=Google&utm_medium=abstract&utm_content=Narcolepsy&utm_campaign=Knowledge-panel
[3] U.S. Department of Health and Human Services. (n.d.). Narcolepsy. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/narcolepsy
[4] NHS. (2022, December 30). Symptoms -Narcolepsy. NHS choices. https://www.nhs.uk/conditions/narcolepsy/symptoms/#:~:text=Sleep%20attacks%2C%20where%20you%20fall,vary%20from%20person%20to%20person.
[5] Hwang, J., Lee, T., Lee, H., & Byun, S. (2022). A clinical decision support system for sleep staging tasks with explanations from artificial intelligence: User-centered design and evaluation study. Journal of Medical Internet Research, 24(1). https://doi.org/10.2196/28659
[6] Multiple sleep latency test (MSLT). Stanford Health Care. (n.d.). https://stanfordhealthcare.org/medical-conditions/sleep/narcolepsy/diagnosis/multiple-sleep-latency-test.html#:~:text=A%20positive%20MSLT%20is%20obtained,where%20REM%20sleep%20was%20reached.
[7] Chen, L., Brown, R., McKenna, J., & McCarley, R. (2009). Animal models of narcolepsy. CNS & Neurological Disorders - Drug Targets, 8(4), 296–308. https://doi.org/10.2174/187152709788921717
This page was produced as an assignment for Genetics 564, a capstone course at UW-Madison.