The Diagnosis and Treatment of Pediatric Narcolepsy
- 1.3k Downloads
Narcolepsy in children is a serious disorder marked by a chronic course and lifelong handicap in school performance and choice of employment, by free time activity limitation, and by behavior and personality changes, all of which constitute a major influence on the quality of life. Increased daytime sleepiness may be the only sign at the disease onset, with attacks of sleep becoming longer and lasting up to hours. Also present may be confusional arousals with features of sleep drunkenness. Paradoxically, preschool and young children may show inattentiveness, emotional lability, and hyperactive behavior. Cataplexy may develop after onset of sleepiness and affect mainly muscles of the face. Hypnagogic hallucinations and sleep paralysis are seldom present. Multiple Sleep Latency Test criteria are not available for children younger than 6 years. The haplotype (HLA-DQB1:0602) can be associated with the disorder; however, the best predictor of narcolepsy–cataplexy is hypocretin deficiency. The treatment generally used in adults is regarded as off-label in childhood, which is why the management of pediatric narcolepsy is difficult .
KeywordsDiagnostic procedure Differential diagnosis Management Treatment
Sona Nevsimalova was supported by PRVOUK-P26/LF1/4 and IGA MZ CR NT 13238-4/2012.
Compliance with Ethics Guidelines
Conflict of Interest
Sona Nevsimalova has received a grant from First Faculty of Medicine, Charles University, and the Grant Agency of the Ministry of Health, Czech Republic.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by the author.
A sleep attack in a 7-year-old girl falling asleep to the ground even while playing with her toys. Her awakening is difficult and prolonged, with features of sleep drunkenness. Cataplectic attacks are evoked by a funny TV story and affect predominantly face muscles. Hypotonia of mimic muscles can be confused for a severe sleepiness (MPG 19793 kb)
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 5.Nevsimalova S, Pretl M, Vankova J, Blazejova K, Sonka K. Narcolepsy in children and adolescents. In: Evrard P, Richelme C, Tardieu M, editors. 3rd EPNS congress. Bologna: Monduzzi; 1999. p. 73–7.Google Scholar
- 6.Einen MA, Aran A, Mignot E, Nishino S. Pre-versus post-pubertal narcolepsy in children. Sleep. 2009;32(Suppl):A249–50.Google Scholar
- 8.••Han F, Lin L, Warby SC, Faraco J, Li J, Dong SX, et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol. 2011;70:410–7. Narcolepsy onset is highly correlated with seasonal and annual patterns of upper airway infections, including H1N1 influenza. In 2010, the peak seasonal onset of narcolepsy was phase-delayed by 6 months relative to winter H1N1 infections, and the correlation was independent of H1N1 vaccination in most of the sample.PubMedCrossRefGoogle Scholar
- 9.••Partinen M, Saarenpää-Heikkilä O, Ilveskoski I, Hublin C, Linna M, Olsén P, et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One. 2012;7:e33723. A sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. Pandemrix vaccination together with other environmental factors likely contributed to this increase in the number of genetically susceptible children.PubMedCentralPubMedCrossRefGoogle Scholar
- 21.••Andlauer O, Moore H, Rico T, Einen M, Kornum BR, Kanbayashi, et al. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. Sleep. 2012;35:1247–55. Objective (HLA typing and sleep studies) but not subjective (symptomatic assessment) features predicted low CSF hcrt-1 levels in patients with narcolepsy without cataplexy.PubMedCentralPubMedGoogle Scholar
- 22.••American Academy of Sleep Medicine. International classification of sleep disorders. Diagnostic and coding manual, Electronic version. 3rd ed. Westchester: American Academy of Sleep Medicine; 2014. The new classification distinguishes between two basic forms of narcolepsy—narcolepsy type 1 (with hcrt-1 deficiency) and narcolepsy type 2 (without hcrt-1 deficiency).Google Scholar
- 25.Challamel MJ. Hypersomnia in children. In: Billiard M, editor. Sleep-physiology, investigation and medicine. New York: Kluwer/Plenum; 2003. p. 457–68.Google Scholar
- 26.Nevsimalova S. Narcolepsy in children and adolescents. In: Bassetti C, Billiard M, Mignot E, editors. Narcolepsy and hypersomnia. New York: Informa Healthcare USA; 2007. p. 67–75.Google Scholar
- 31.••Pizza F, Franceschini C, Peltola H, Vandi S, Finotti E, Ingravallo F, et al. Clinical and polysomnographic course of childhood narcolepsy with cataplexy. Brain. 2013;136:3787–95. Childhood narcolepsy–cataplexy is characterized at onset by an abrupt increase in total sleep over 24 h, and by generalized hypotonia and motor overexcitability. Hypotonic phenomena and selected facial movements decreased over time and, tested against the disease duration and age, appeared as age-dependent.PubMedCentralPubMedCrossRefGoogle Scholar
- 32.••Plazzi G, Pizza F, Palaia V, Franceschini C, Poli F, Moghadam KV, et al. Complex movement disorders at disease onset in childhood narcolepsy with cataplexy. Brain. 2011;134:3480–92. Patients with narcolepsy–cataplexy displayed a complex array of “negative” (hypotonia) and “active” (ranging from perioral movements to dyskinetic-dystonic movements or stereotypes) motor disturbances. A complex movement disorder at the onset may disappear later in the course of the disease.PubMedCrossRefGoogle Scholar
- 35.Nevsimalova S, Roth B, Zouhar A, Zemanova H. The occurrence of narcolepsy-cataplexy and periodic hypersomnia in early childhood. In: Koella WP, Obal F, Schulz H, Wisser P, editors. Sleep ‘86. Stuttgart: Fisher; 1988. p. 399–401.Google Scholar
- 37.Droogleever-Fortuyn H, Lappenschaar M, Nienhuis F, Furer J, Hodiamont P, Rijnders C, et al. Hypnagogic hallucinations and “psychotic” symptoms in narcolepsy: a comparison with control subjects and schizophrenic patients. Sleep. 2009;32(Suppl):A244–5.Google Scholar
- 38.American Academy of Sleep Medicine. International classification of sleep disorders. Diagnostic and coding Manual. 2nd ed. Westchester: American Academy of Sleep Medicine; 2005.Google Scholar
- 41.Nevsimalova S, Vankova J, Pretl M, Bruck D. Narcolepsy in children and adolescents – clinical and psychosocial aspects (in Czech). Ces Slov Neurol Neurochir. 2002;65:169–74.Google Scholar
- 42.••Inocente CO, Gustin MP, Lauvault S, Perret AG, Christol N, et al. Quality of life in children with narcolepsy. CNS Neurosci Ther. 2014. doi: 10.1111/cns.12291. Narcoleptic children and adolescents were at high risk of poor health-related quality of life. Depressive symptoms had a major impact on affected children’s quality of life.
- 45.••Inocente CO, Lavault S, Lecendreux M, Dauvilliers Y, Reimao R, Gustin MP, et al. Impact of obesity in children with narcolepsy. CNS Neurosci Ther. 2013;19:521–8. Obesity affects more than 50 % of narcoleptic children, mostly younger at disease onset, and has a deleterious impact on sleep quality as well as on school attendance.PubMedCrossRefGoogle Scholar
- 56.••Poli F, Pizza F, Mignot E, Ferri R, Pagotto U, Taheri S, et al. High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy. Sleep. 2013;36:175–81. Narcolepsy–cataplexy occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction.PubMedCentralPubMedGoogle Scholar
- 62.Walters AS, Silvestri R, Zucconi M, Chandrashekariah R, Konofal E. Review of the possible relationship and hypothetical links between attention deficit hyperactivity disorder (ADHD) and simple sleep related movement disorders, parasomnias, hypersomnias and circadian rhythm disorders. J Clin Sleep Med. 2008;4:591–600.PubMedCentralPubMedGoogle Scholar
- 66.Bouvier E, Arnulf I, Claustrat B, Kocher L, Bastuji H, Lecendreux M, et al. Do children with idiopathic narcolepsy have a long sleep time? Sleep. 2009;32(Suppl):A97.Google Scholar
- 68.••Han F, Lin L, Li J, Aran A, Dong SX, An P, et al. Presentation of primary hypersomnia in Chinese children. Sleep. 2011;5:627–32. Of children presenting with primary hypersomnia, 86% (361 of 417) met the criteria for narcolepsy–cataplexy. Puberty did not affect positivity on the MSLT as a diagnostic feature. Sleep paralysis was the only symptom that increased with increasing age. The age at onset appeared to be younger than usually reported in other studies.Google Scholar
- 72.Carskadon MA, Harvey K, Duke P, Anders TF, Litt IF, Dement WC. Pubertal change in daytime sleepiness. Sleep. 1980;3:453–60.Google Scholar
- 86.••Lecendreux M, Bruni O, Franco P, Gringras P, Konofal E, Nevsimalova S, et al. Clinical experience suggests that modafinil is an effective and safe treatment for paediatric narcolepsy. J Sleep Res. 2012;21:481–3. Two-hundred five children and adolescents with narcolepsy were treated with modafinil, the age range was 4-18 years, and the prescribed dose varied from 50 to 600 mg. The patients had been treated for more than 10 years. The most frequent side effects were headache (13.7%), nervousness and irritability (6.5%), and loss of appetite (2.2%). No severe hypersensitivity reactions and no severe skin reactions were reported.PubMedCrossRefGoogle Scholar
- 87.••Davies M, Wilton L, Shakir S. Safety profile of modafinil across a range of prescribing indications, including off-label use, in a primary care setting in England. Drug Saf. 2013;36:237–46. More than 2.400 questionnaires (nine patients aged 16 years or younger) with narcolepsy treated with modafinil were evaluated. No serious skin reactions were reported.PubMedCrossRefGoogle Scholar
- 88.Guilleminault C, Fromherz S. Narcolepsy. diagnosis and management. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th ed. Philadelphia: Elsevier Saunders; 2007. p. 780–90.Google Scholar
- 92.••Lecendreux M, Poli F, Oudertte D, Benazzouz F, Donjacour CEHM, Franceschini C, et al. Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study. Sleep. 2012;35:709–11. Twenty-seven children with narcolepsy–cataplexy ranging from 6 to 16 years, evaluated retrospectively, had been treated with off-label sodium oxybate. Good efficacy and tolerability was documented in most of the patients.PubMedCentralPubMedGoogle Scholar
- 93.••Mansukhani MP, Kotagal S. Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: a retrospective study. Sleep Med. 2012;13:606–10. Fifteen children and adolescents with narcolepsy–cataplexy treated with sodium oxybate had a mean age at diagnosis of 11 years (range 3-17). The treatment was effective in alleviating sleepiness and cataplexy, and the therapeutic response was sustained over time and without development of tolerance.PubMedCrossRefGoogle Scholar