Narcolepsy

This article is about the medical condition. For other uses, see Narcolepsy (disambiguation).

Narcolepsy
The concentration of orexin-A neuropeptides in the cerebrospinal fluid of narcoleptic individuals is usually very low
Pronunciation
SpecialtySleep medicine, neurology
SymptomsExcessive daytime sleepiness, involuntary sleep episodes, sudden loss of muscle strength, hallucinations[1]
ComplicationsMotor vehicle collisions, falls[1]
Usual onsetAdolescence[1]
DurationLifelong[1]
CausesOrexin deficiency[1]
Risk factorsFamily history, brain injury[1]
Diagnostic methodBased on the symptoms and sleep studies[1]
Differential diagnosisSleep apnea, major depressive disorder, anemia, heart failure, drinking alcohol, idiopathic hypersomnia, sleep deprivation[1]
TreatmentMedication, regular short naps, sleep hygiene[1]
MedicationStimulants (modafinil, pitolisant, solriamfetol, methylphenidate, amphetamine), sodium oxybate, mixed oxybate salts, serotonin reuptake inhibitors[1]
Frequency0.2 to 600 per 100,000[2]

Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep.[1] The pentad symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS), and cataplexy.[1] People with narcolepsy tend to sleep about the same number of hours per day as people without it, but the quality of sleep is typically compromised.[1]

There are two recognized forms of narcolepsy, narcolepsy type 1 and type 2.[3] Narcolepsy type 1 (NT1) can be clinically characterized by symptoms of EDS and cataplexy, and/or will have CSF orexin levels of less than 110 pg/ml. Cataplexy are transient episodes of aberrant tone, most typically loss of tone, that can be associated with strong emotion.[4] In pediatric-onset narcolepsy, active motor phenomena are not uncommon.[5] Cataplexy may be mistaken for syncope, tics, or seizures.[1] Narcolepsy type 2 (NT2) does not have features of cataplexy and CSF orexin levels are normal. Sleep-related hallucinations, also known as hypnogogic (going to sleep) and hypnopompic (on awakening) are vivid hallucinations that can be auditory, visual, or tactile and may occur independent of or in combination with an inability to move (sleep paralysis). Narcolepsy is a clinical syndrome of hypothalamic disorder,[6] but the exact cause of narcolepsy is unknown, with potentially several causes.[7] A leading consideration for the cause of narcolepsy type 1 is that it is an autoimmune disorder.[8] Proposed pathophysiology as an autoimmune disease suggest antigen presentation by DQ0602 to specific CD4+ T cells resulting in CD8+ T-cell activation and consequent injury to orexin producing neurons.[9] Familial trends of narcolepsy are suggested to be higher than previously appreciated. Familial risk of narcolepsy among first degree relatives is high. Relative risk for narcolepsy in a first degree relative has been reported to be 361.8.[10] However, there is a spectrum of symptoms found in this study, including asymptomatic abnormal sleep test findings to significantly symptomatic.[11]

The autoimmune process is thought to be triggered in genetically susceptible individuals by an immune provoking experience, such as infection with H1N1 influenza.[12] Secondary narcolepsy can occur as a consequence of another neurological disorder. Secondary narcolepsy can be seen in some individuals with traumatic brain injury, tumors, Prader–Willi syndrome or other diseases affecting the parts of the brain that regulate wakefulness or REM sleep. Diagnosis is typically based on the symptoms and sleep studies, after excluding alternative causes of EDS. EDS can also be caused by other sleep disorders such as insufficient sleep syndrome, sleep apnea, major depressive disorder, anemia, heart failure, and drinking alcohol.

While there is no cure, behavioral strategies, lifestyle changes, social support and medications may help. Lifestyle and behavioral strategies can include identifying and avoiding or desensitizing emotional triggers for cataplexy, dietary strategies that may reduce sleep inducing foods and drinks, scheduled or strategic naps and maintaining a regular sleep wake schedule. Social support, social networks, and social integration are resources[13] that may lie in the communities related to living with narcolepsy. Medications used to treat narcolepsy are primarily targeting EDS and/or cataplexy. These medications include alerting agents (e.g., modafinil, armodafinil, pitolisant, solriamfetol), oxybate medications (e.g., twice nightly sodium oxybate, twice nightly mixed oxybate salts, and once nightly extended-release sodium oxybate), and other stimulants (e.g., methylphenidate, amphetamine). There is also the use of antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and serotonin–norepinephrine reuptake inhibitors (SNRIs) for the treatment of cataplexy.[1]

Estimates of frequency range from 0.2 to 600 per 100,000 people in various countries.[2] The condition often begins in childhood, with males and females being affected equally. Untreated narcolepsy increases the risk of motor vehicle collisions and falls.[1]

Narcolepsy generally occurs anytime between early childhood and 50 years of age, and most commonly between 15 and 36 years of age. However, it may also rarely appear at any time outside of this range.[14]

  1. ^ a b c d e f g h i j k l m n o p "Narcolepsy Fact Sheet". NINDS. NIH Publication No. 03-1637. Archived from the original on 27 July 2016. Retrieved 19 August 2016.
  2. ^ a b Goswami M, Thorpy MJ, Pandi-Perumal SR (2016). Narcolepsy: A Clinical Guide (2nd ed.). Springer. p. 39. ISBN 9783319237398. Archived from the original on 23 August 2016. Retrieved 19 August 2016.
  3. ^ American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed.; American Academy of Sleep Medicine: Darien, CT, USA, 2014.
  4. ^ Moscovitch, A.; Partinen, M.; Guilleminault, C. The positive diagnosis of narcolepsy and narcolepsy’s borderland. Neurology 1993, 43, 55–60.
  5. ^ Postiglione, E.; Antelmi, E.; Pizza, F.; Lecendreux, M.; Dauvilliers, Y.; Plazzi, G. The clinical spectrum of childhood narcolepsy. Sleep Med. Rev. 2018, 38, 70–85
  6. ^ Kim H, Ayele GM, Atalay RT, Hussien S, Tewoldemedhin B, Michael MB, Scharf SM (July 2022). "What Works for One May Not Work for Another: A New Warning for Modafinil". Cureus. 14 (7): e27287. doi:10.7759/cureus.27287. PMC 9413809. PMID 36043022.
  7. ^ "Narcolepsy Information Page". NINDS. Archived from the original on 7 January 2017. Retrieved 7 January 2017.
  8. ^ "Narcolepsy with cataplexy". Autoimmune Registry Inc. Retrieved 13 June 2022.
  9. ^ Ollila, H.M., Sharon, E., Lin, L., Sinnott-Armstrong, N., Ambati, A., Yogeshwar, S.M., Hillary, R.P., Jolanki, O., Faraco, J., Einen, M. and Luo, G., 2023. Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy. Nature communications, 14(1), p.2709.
  10. ^ Wing, Y.K., Chen, L., Lam, S.P., Li, A.M., Tang, N.L., Ng, M.H., Cheng, S.H., Ho, C.K., Mok, V., Leung, H.W. and Lau, A., 2011. Familial aggregation of narcolepsy. Sleep medicine, 12(10), pp.947-951.
  11. ^ Wing, Y.K., Chen, L., Lam, S.P., Li, A.M., Tang, N.L., Ng, M.H., Cheng, S.H., Ho, C.K., Mok, V., Leung, H.W. and Lau, A., 2011. Familial aggregation of narcolepsy. Sleep medicine, 12(10), pp.947-951.
  12. ^ Cite error: The named reference mignot2018 was invoked but never defined (see the help page).
  13. ^ Gottlieb, B.H. and Bergen, A.E., 2010. Social support concepts and measures. Journal of psychosomatic research, 69(5), pp.511-520.
  14. ^ Cite error: The named reference :1 was invoked but never defined (see the help page).