Araştırma Makalesi
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Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

Yıl 2014, Cilt: 6 Sayı: 3, 271 - 283, 06.11.2014
https://doi.org/10.5455/cap.20140115073522

Öz

Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed.

Kaynakça

  • American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Diagnostic and Coding Manual. 2nd ed. Westchester, IL, American Academy of Sleep Medicine, 2005.
  • Kaynak H, Kaynak D. Narkolepsi-katapleksi sendromu. Türkiye Klinikleri J Psychiatry 2001; 2:111–114.
  • Karadağ MG, Aksoy M. Narkolepsi ve oreksinler. Dirim Tıp Gazetesi 2009; 84:75–83.
  • Morrish E, King MA, Smith IE, Shneerson JM. Factors associated with a delay in the diagnosis of narcolepsy. Sleep Med 2004; 5:37–41.
  • Akintomide GS, Rickards H. Narcolepsy: a review. Neuropsychiatr Dis Treat 2011; 7:507–518.
  • Turgut N. Narkolepsi-katapleksi sendromu. Trakya Üniversitesi Tıp Fakültesi Dergisi 2003; 20:47–53.
  • Longstreth WT Jr, Koepsell TD, Ton TG, Hendrickson AF, van Belle G. The epidemiology of narcolepsy. Sleep 2007; 30:13–
  • Ohayon MM, Ferini-Strambi L, Plazzi G, Smirne S, Castronovo V. How age influences the expression of narcolepsy. J Psychosom Res 2005; 59:399–405.
  • Dauvilliers Y, Billiard M, Montplaisir J. Clinical aspects and pathophysiology of narcolepsy. Clin Neurophysiol 2003; 114:2000–2017.
  • Dantz B, Edgar DM, Dement WC. Circadian rhythms in narcolepsy: studies on a 90 minute day. Electroenceph Clin Neurophysiol 1994; 90:24–35.
  • Nobili L, Besset A, Ferrillo F, Rosadini G, Schiavi G, Billiard M. Dynamics of slow wave activity in narcoleptic patients under bed rest condition. Electroenceph Clin Neurophysiol 1995; 95:414–425.
  • Mignot E. Genetic and familial aspects of narcolepsy. Neurology. 1998; 5:16–22.
  • Watson NF, Ton TG, Koepsell TD, Longstreth WT Jr. Birth order and narcolepsy risk among genetically susceptible individuals: a population-based case-control study. Sleep Med 2012; 13:310–313.
  • Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamusspecific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 1998; 95:322–327.
  • Kilduff, T.S. and Peyron, C. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci 2000; 23:359–365.
  • Thorpy M. Therapeutic advances in narcolepsy. Sleep Med 2007; 8: 427–440.
  • Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001; 24:726–731.
  • Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci 2012; 32:12305–12311. John J, Wu MF, Boehmer LN, Siegel JM. Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior. Neuron 2004; 42:619–634.
  • Xi M, Fung SJ, Sampogna S, Chase MH. Excitatory projections from the amygdala to neurons in the nucleus pontis oralis in themrat: an intracellular study. Neuroscience 2011; 197:181–190.
  • Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000; 355(9197):39–40.
  • Thannickal TC, Moore RY, Nienhuis R. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27:469–474.
  • Black JL, Silber MH, Krahn LE. Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602positive narcoleptic subjects with cataplexy. Biol Psychiatry 2005; 58:504–509.
  • Peacock J, Benca RM. Narcolepsy: clinical features, co-morbidities & treatment. Indian J Med Res 2010; 131:338–149.
  • American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM IV-TR). Washington, DC, American Psychiatric Association, 2000.
  • American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5). Washington, DC, American Psychiatric Association, 2013.
  • Aydın H. Narkoleptiklerin uyku örüntüsü üzerine bir araştırma. GATA Bülteni 1990; 32:269-278.
  • Nishino S. Clinical and neurobiological aspects of narcolepsy. Sleep Med 2007; 8:373–399.
  • Guilleminault C, Anagnos A. Narcolepsy. Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep Medicine, 3rd ed. Philadelphia, W. B. Saunders, 2000.
  • Mignot E, Guilleminault C, Bowersox S, Rappaport A, Dement WC. Effect of alpha 1-adrenoceptors blockade with prazosin in canine narcolepsy. Brain Res 1988; 444:184–188.
  • Rosenthal L, Merlotti L, Young D, Zorick F, Wittig R, Roehrs T et al. Subjective and polysomnographic characteristics of patients diagnosed with narcolepsy. Gen Hosp Psychiatry 1990; 12:191–197.
  • Hankey GJ, Wardlaw JM. Clinical Neurology. London, Manson Publishing, 2002.
  • Kok SW, Overeem S, Visscher TL, Lammers GJ, Seidell JC, Pijl H et al. Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity. Obes Res 2003; 11:1147–1154.
  • Benca R. Narcolepsy and excessive daytime sleepiness: Diagnostic considerations, epidemiology, and comorbidities. J Clin Psychiatry 2007; 68 (suppl 13):P5-P8.
  • Billiard M, Bassetti C, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, et al. EFNS guidelines on management of narcolepsy Eur J Neurol 2006; 13:1035–1048.
  • Billard M. Narcolepsy: Current treatment options and future approaches. Neuropsychiatr Dis Treat 2008; 4:557–566.
  • Billiard M, Besset A, Montplaisir J, Laffont F, Goldenberg F, Weill JS et al. Modafinil: a double- blind multicenter study. Sleep 1994; 17:107–112.
  • U.S. Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000; 54:1166–1175.
  • Schwartz JR, Feldman NT, Bogan RK, Nelson MT, Hughes RJ. Dosing regimen of modafinil for improving daytime wakefulness in patients with narcolepsy. Clin Neuropharmacol 2003; 26:252–257.
  • Guilleminault C, Raynal D, Takahashi S, Carskadon M, Dement W. Evaluation of short-term and long-term treatment of the narcolepsy syndrome with clomipramine hydrochloride. Acta Neurol Scand 1976; 54:71–87.
  • Wise MS, Arand DL, Auger RR, Brooks SN, Watson NF. Treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007; 30:1712–1727.
  • Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C. Long-t ermefficacy and safety of modafinil for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 2000; 1:231–243.
  • Multicenter Study Group. A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep 2002; 25:42–49.
  • Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369:499–511.
  • Thorpy M. Therapeutic advances in narcolepsy. Sleep Med 2007; 8:427–440.
  • Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem. Sleep Med 2009; 10:490–493.
  • Thorpy MJ. Short term triazolam use improves nocturnal sleep of narcoleptics. Sleep 1992; 15:212–216.
  • Powell NB, Schechtman K B, Riley RW, Guilleminault C, Chieng RP, Weaver EM. Sleepy driver near-misses may predict accident risks. Sleep 2007; 30:331–342.
  • Lin JS, Dauvilliers Y, Arnulf I. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin–/–mice and patients. Neurobiol Dis 2008; 30:74–83.
  • Fujiki N, Yoshida Y, Ripley B, Mignot E, Nishino S. Effects of IV and ICV hypocretin-1 orexin A in hypo cretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin ligand deficient narcoleptic dog. Sleep 2003; 26:953–959. Pınar Güzel Özdemir,.Yrd.Doç.Dr., Yüzüncü Yıl Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı,Van; Yavuz Selvi, Doç.Dr., Selçuk Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı, Konya; Tezay Çakın Güleç, Uzm. Dr., Türkan Özilhan Bornova Devlet Hastanesi, İzmir; Mustafa Güleç, Doç. Dr., İzmir Katip Çelebi Üniversitesi Tıp Fak. Psikiyatri Anabilim Dalı, İzmir. Yazışma Adresi/Correspondence: Pınar Güzel Özdemir, Yüzüncü Yıl Üniv. Tıp Fak. Psikiyatri ABD, Van, Turkey. E-mail: pguzelozdemir@yahoo.com Yazarlar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemiştir. The authors reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol6/no3/ Çevrimiçi yayım / Published online 15 Ocak/January 15, 2014; doi: 10.5455/cap.20140115073522

Narkolepsinin Fizyopatolojisi, Klinik Görünümü ve Tedavi Yaklaşımları

Yıl 2014, Cilt: 6 Sayı: 3, 271 - 283, 06.11.2014
https://doi.org/10.5455/cap.20140115073522

Öz

Narkolepsi aşırı gündüz uykululuğu, katapleksi, hipnogojik varsanı ve uyku paralizisi ile giden ve ömür boyu devam eden bir uyku bozukluğudur. Kesin nedeni bilinmemektedir ancak hipokretin eksikliğinin önemli rol oynadığına dair önemli kanıtlar vardır. Narkolepsinin patogenezini anlamada ilerlemeler kaydedilmiştir. Hayat kalitesine olumsuz etkisi vardır ve hastaları belirli kariyer ve aktivitelerden de kısıtlayabilir. Tanı hastanın öyküsüne ve polisomnografi ve çoklu uyku latans testi ile toplanan nesnel verilere dayanır. Tedavi medikal, eğitim ve davranış değişikliği ile semptomlarda rahatlamaya odaklanır. Yeni seçeneklerin yanı sıra klasik farmakolojik tedavinin de yan etki ve kötüye kullanma potansiyeli gibi önemli sorunları vardır. Bazı yeni yöntemler tedavi seçenekleri genişletmek için araştırılmaktadır. Bu derlemede, narkolepsinin, patofizyolojik, klinik ve farmakoterapötik yönleri tartışılmıştır.

Kaynakça

  • American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Diagnostic and Coding Manual. 2nd ed. Westchester, IL, American Academy of Sleep Medicine, 2005.
  • Kaynak H, Kaynak D. Narkolepsi-katapleksi sendromu. Türkiye Klinikleri J Psychiatry 2001; 2:111–114.
  • Karadağ MG, Aksoy M. Narkolepsi ve oreksinler. Dirim Tıp Gazetesi 2009; 84:75–83.
  • Morrish E, King MA, Smith IE, Shneerson JM. Factors associated with a delay in the diagnosis of narcolepsy. Sleep Med 2004; 5:37–41.
  • Akintomide GS, Rickards H. Narcolepsy: a review. Neuropsychiatr Dis Treat 2011; 7:507–518.
  • Turgut N. Narkolepsi-katapleksi sendromu. Trakya Üniversitesi Tıp Fakültesi Dergisi 2003; 20:47–53.
  • Longstreth WT Jr, Koepsell TD, Ton TG, Hendrickson AF, van Belle G. The epidemiology of narcolepsy. Sleep 2007; 30:13–
  • Ohayon MM, Ferini-Strambi L, Plazzi G, Smirne S, Castronovo V. How age influences the expression of narcolepsy. J Psychosom Res 2005; 59:399–405.
  • Dauvilliers Y, Billiard M, Montplaisir J. Clinical aspects and pathophysiology of narcolepsy. Clin Neurophysiol 2003; 114:2000–2017.
  • Dantz B, Edgar DM, Dement WC. Circadian rhythms in narcolepsy: studies on a 90 minute day. Electroenceph Clin Neurophysiol 1994; 90:24–35.
  • Nobili L, Besset A, Ferrillo F, Rosadini G, Schiavi G, Billiard M. Dynamics of slow wave activity in narcoleptic patients under bed rest condition. Electroenceph Clin Neurophysiol 1995; 95:414–425.
  • Mignot E. Genetic and familial aspects of narcolepsy. Neurology. 1998; 5:16–22.
  • Watson NF, Ton TG, Koepsell TD, Longstreth WT Jr. Birth order and narcolepsy risk among genetically susceptible individuals: a population-based case-control study. Sleep Med 2012; 13:310–313.
  • Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamusspecific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 1998; 95:322–327.
  • Kilduff, T.S. and Peyron, C. The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci 2000; 23:359–365.
  • Thorpy M. Therapeutic advances in narcolepsy. Sleep Med 2007; 8: 427–440.
  • Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001; 24:726–731.
  • Burgess CR, Scammell TE. Narcolepsy: neural mechanisms of sleepiness and cataplexy. J Neurosci 2012; 32:12305–12311. John J, Wu MF, Boehmer LN, Siegel JM. Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior. Neuron 2004; 42:619–634.
  • Xi M, Fung SJ, Sampogna S, Chase MH. Excitatory projections from the amygdala to neurons in the nucleus pontis oralis in themrat: an intracellular study. Neuroscience 2011; 197:181–190.
  • Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000; 355(9197):39–40.
  • Thannickal TC, Moore RY, Nienhuis R. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27:469–474.
  • Black JL, Silber MH, Krahn LE. Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602positive narcoleptic subjects with cataplexy. Biol Psychiatry 2005; 58:504–509.
  • Peacock J, Benca RM. Narcolepsy: clinical features, co-morbidities & treatment. Indian J Med Res 2010; 131:338–149.
  • American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM IV-TR). Washington, DC, American Psychiatric Association, 2000.
  • American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5). Washington, DC, American Psychiatric Association, 2013.
  • Aydın H. Narkoleptiklerin uyku örüntüsü üzerine bir araştırma. GATA Bülteni 1990; 32:269-278.
  • Nishino S. Clinical and neurobiological aspects of narcolepsy. Sleep Med 2007; 8:373–399.
  • Guilleminault C, Anagnos A. Narcolepsy. Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep Medicine, 3rd ed. Philadelphia, W. B. Saunders, 2000.
  • Mignot E, Guilleminault C, Bowersox S, Rappaport A, Dement WC. Effect of alpha 1-adrenoceptors blockade with prazosin in canine narcolepsy. Brain Res 1988; 444:184–188.
  • Rosenthal L, Merlotti L, Young D, Zorick F, Wittig R, Roehrs T et al. Subjective and polysomnographic characteristics of patients diagnosed with narcolepsy. Gen Hosp Psychiatry 1990; 12:191–197.
  • Hankey GJ, Wardlaw JM. Clinical Neurology. London, Manson Publishing, 2002.
  • Kok SW, Overeem S, Visscher TL, Lammers GJ, Seidell JC, Pijl H et al. Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity. Obes Res 2003; 11:1147–1154.
  • Benca R. Narcolepsy and excessive daytime sleepiness: Diagnostic considerations, epidemiology, and comorbidities. J Clin Psychiatry 2007; 68 (suppl 13):P5-P8.
  • Billiard M, Bassetti C, Dauvilliers Y, Dolenc-Groselj L, Lammers GJ, Mayer G, et al. EFNS guidelines on management of narcolepsy Eur J Neurol 2006; 13:1035–1048.
  • Billard M. Narcolepsy: Current treatment options and future approaches. Neuropsychiatr Dis Treat 2008; 4:557–566.
  • Billiard M, Besset A, Montplaisir J, Laffont F, Goldenberg F, Weill JS et al. Modafinil: a double- blind multicenter study. Sleep 1994; 17:107–112.
  • U.S. Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 2000; 54:1166–1175.
  • Schwartz JR, Feldman NT, Bogan RK, Nelson MT, Hughes RJ. Dosing regimen of modafinil for improving daytime wakefulness in patients with narcolepsy. Clin Neuropharmacol 2003; 26:252–257.
  • Guilleminault C, Raynal D, Takahashi S, Carskadon M, Dement W. Evaluation of short-term and long-term treatment of the narcolepsy syndrome with clomipramine hydrochloride. Acta Neurol Scand 1976; 54:71–87.
  • Wise MS, Arand DL, Auger RR, Brooks SN, Watson NF. Treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007; 30:1712–1727.
  • Mitler MM, Harsh J, Hirshkowitz M, Guilleminault C. Long-t ermefficacy and safety of modafinil for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 2000; 1:231–243.
  • Multicenter Study Group. A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep 2002; 25:42–49.
  • Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369:499–511.
  • Thorpy M. Therapeutic advances in narcolepsy. Sleep Med 2007; 8:427–440.
  • Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem. Sleep Med 2009; 10:490–493.
  • Thorpy MJ. Short term triazolam use improves nocturnal sleep of narcoleptics. Sleep 1992; 15:212–216.
  • Powell NB, Schechtman K B, Riley RW, Guilleminault C, Chieng RP, Weaver EM. Sleepy driver near-misses may predict accident risks. Sleep 2007; 30:331–342.
  • Lin JS, Dauvilliers Y, Arnulf I. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin–/–mice and patients. Neurobiol Dis 2008; 30:74–83.
  • Fujiki N, Yoshida Y, Ripley B, Mignot E, Nishino S. Effects of IV and ICV hypocretin-1 orexin A in hypo cretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin ligand deficient narcoleptic dog. Sleep 2003; 26:953–959. Pınar Güzel Özdemir,.Yrd.Doç.Dr., Yüzüncü Yıl Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı,Van; Yavuz Selvi, Doç.Dr., Selçuk Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı, Konya; Tezay Çakın Güleç, Uzm. Dr., Türkan Özilhan Bornova Devlet Hastanesi, İzmir; Mustafa Güleç, Doç. Dr., İzmir Katip Çelebi Üniversitesi Tıp Fak. Psikiyatri Anabilim Dalı, İzmir. Yazışma Adresi/Correspondence: Pınar Güzel Özdemir, Yüzüncü Yıl Üniv. Tıp Fak. Psikiyatri ABD, Van, Turkey. E-mail: pguzelozdemir@yahoo.com Yazarlar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemiştir. The authors reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol6/no3/ Çevrimiçi yayım / Published online 15 Ocak/January 15, 2014; doi: 10.5455/cap.20140115073522
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sinirbilim
Bölüm Derleme
Yazarlar

Pınar Güzel Özdemir Bu kişi benim

Yavuz Selvi Bu kişi benim

Tezay Çakın Güleç Bu kişi benim

Mustafa Güleç Bu kişi benim

Yayımlanma Tarihi 6 Kasım 2014
Yayımlandığı Sayı Yıl 2014 Cilt: 6 Sayı: 3

Kaynak Göster

AMA Özdemir PG, Selvi Y, Güleç TÇ, Güleç M. Narkolepsinin Fizyopatolojisi, Klinik Görünümü ve Tedavi Yaklaşımları. Psikiyatride Güncel Yaklaşımlar. Eylül 2014;6(3):271-283. doi:10.5455/cap.20140115073522

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