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Tuberous Sclerosis Complex

  • Tanjala T. GipsonEmail author
Chapter

Abstract

Tuberous sclerosis complex is a genetic neurocutaneous syndrome affecting 1/6000 live births. Neurobiologically, the manifestations have been linked to excessive activity of the protein kinase mammalian target of rapamycin, and treatments to target this aberration are clinically available. Sleep in TSC is a comorbidity that is not often studied; however, review of the literature reveals cases that warrant consideration when treating these patients. Increasing knowledge and study of sleep in TSC is a worthy pursuit as the targeted therapies currently available for tumors in this population may also have utility for sleep disturbances.

Keywords

Tuberous sclerosis Sleep disturbances Vigabatrin Everolimus Mammalian target of rapamycin Clinical trials 

References

  1. 1.
    Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):243–54.PubMedCentralCrossRefGoogle Scholar
  2. 2.
    Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. 1996;38(2):146–55.CrossRefGoogle Scholar
  3. 3.
    Gillberg IC, Gillberg C, Ahlsen G. Autistic behaviour and attention deficits in tuberous sclerosis: a population-based study. Dev Med Child Neurol. 1994;36(1):50–6.CrossRefGoogle Scholar
  4. 4.
    Joinson C, O’Callaghan FJ, Osborne JP, Martyn C, Harris T, Bolton PF. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med. 2003;33(2):335–44.CrossRefGoogle Scholar
  5. 5.
    Jansen AC, Sancak O, D'Agostino MD, Badhwar A, Roberts P, Gobbi G, et al. Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation. Ann Neurol. 2006;60(5):528–39.CrossRefGoogle Scholar
  6. 6.
    Rosner M, Hanneder M, Siegel N, Valli A, Hengstschläger M. The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners. Mutat Res Rev Mutat Res. 2008;658(3):234–46.CrossRefGoogle Scholar
  7. 7.
    Gomez M, Sampson JR, Whittemore VH. Tuberous sclerosis complex. 3rd ed. New York/Oxford: Oxford University Press; 1999.Google Scholar
  8. 8.
    Han JM, Sahin M. TSC1/TSC2 signaling in the CNS. FEBS Lett. 2011;585(7):973–80.PubMedCentralCrossRefGoogle Scholar
  9. 9.
    Crino PB. Molecular pathogenesis of tuber formation in tuberous sclerosis complex. J Child Neurol. 2004;19:716–25.CrossRefGoogle Scholar
  10. 10.
    de Vries PJ, Howe CJ. The tuberous sclerosis complex proteins – a GRIPP on cognition and neurodevelopment. Trends Mol Med. 2007;13(8):319–26.CrossRefGoogle Scholar
  11. 11.
    Krishnan ML, Commonwick O, Jeste SS, Weisenfeld N, Hans A, et al. Diffusion features of white matter in tuberous sclerosis with tractography. Pediatr Neurol. 2010;42:101–6.PubMedCentralCrossRefGoogle Scholar
  12. 12.
    Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci. 2007;27(21):5546–58.CrossRefGoogle Scholar
  13. 13.
    Moavero R, Cerminara C, Curatolo P. Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges. Childs Nerv Syst. 2010;26(11):1495–504.CrossRefGoogle Scholar
  14. 14.
    Napolioni V, Moavero R, Curatolo P. Recent advances in neurobiology of Tuberous Sclerosis Complex. Brain Dev. 2009;31(2):104–13.CrossRefGoogle Scholar
  15. 15.
    Nie D, Di Nardo A, Han JM, Baharanyi H, Kramvis I, Huynh T, et al. Tsc2-Rheb signaling regulates EphA-mediated axon guidance. Nat Neurosci. 2010;13(2):163–72.PubMedCentralCrossRefGoogle Scholar
  16. 16.
    Sweich L, Perycz M, Malik A, Jaworski J. Role of mTOR in physiology and pathology of the nervous system. Biochem Biophys Acta. 2008;1784(1):116–32.Google Scholar
  17. 17.
    Johnston MV, Nishimura A, Harum K, Pekar J, Blue ME. Sculpting the developing brain. Adv Pediatr Infect Dis. 2001;48:1–38.Google Scholar
  18. 18.
    Segal M, Andersen P. Dendritic spines shaped by synaptic activity. Curr Opin Neurobiol. 2000;10(5):582–6.CrossRefGoogle Scholar
  19. 19.
    Auerbach BD, Osterweil EK, Bear MF. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature. 2011;480(7375):63–8.PubMedCentralCrossRefGoogle Scholar
  20. 20.
    Bateup HS, Takasaki KT, Saulnier JL, Denefrio CL, Sabatini BL. Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J Neurosci. 2011;31(24):8862–9.PubMedCentralCrossRefGoogle Scholar
  21. 21.
    Talos DM, Kwiatkowski DJ, Cordero K, Black PM, Jensen FE. Cell-specific alterations of glutamate receptor expression in tuberous sclerosis complex cortical tubers. Ann Neurol. 2008;63(4):454–65.PubMedCentralCrossRefGoogle Scholar
  22. 22.
    Jones AC, Daniells CE, Snell RG, Tachataki M, Idziaszczyk SA, Krawczak M, et al. Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis. Hum Mol Genet. 1997;6(12):2155–61.CrossRefGoogle Scholar
  23. 23.
    Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, et al. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia. 2014;55(7):1025–9.CrossRefGoogle Scholar
  24. 24.
    van Eeghen AM, Black ME, Pulsifer MB, Kwiatkowski DJ, Thiele EA. Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur J Hum Genet. 2012;20(5):510–5.CrossRefGoogle Scholar
  25. 25.
    Krueger DA, Northrup H, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):255–65.PubMedCentralCrossRefGoogle Scholar
  26. 26.
    Gipson TT, Gerner G, Srivastava S, Poretti A, Vaurio R, Hartman A, et al. Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity. Pediatr Neurol. 2014;51(3):398–402.PubMedCentralCrossRefGoogle Scholar
  27. 27.
    Jambaqué I, Cusmai R, Curatolo P, Cortesi F, Perrot C, Dulac O. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings. Dev Med Child Neurol. 1991;33(8):698–705.CrossRefGoogle Scholar
  28. 28.
    Jansen FE, Vincken KL, Algra A, Anbeek P, Braams O, Nellist M, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology. 2008;70(12):916–23.CrossRefGoogle Scholar
  29. 29.
    Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment. AJNR Am J Neuroradiol. 1995;16(1):149–55.Google Scholar
  30. 30.
    O’Callaghan FJ, Harris T, Joinson C, Bolton P, Noakes M, Presdee D, et al. The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex. Arch Dis Child. 2004;89(6):530–3.PubMedCentralCrossRefGoogle Scholar
  31. 31.
    Chou IJ, Lin KL, Wong AM, Wang HS, Chou ML, Hung PC, et al. Neuroimaging correlation with neurological severity in tuberous sclerosis complex. Eur J Paediatr Neurol. 2008;12(2):108–12.CrossRefGoogle Scholar
  32. 32.
    Davoren PM, Epstein MT. Insulinoma complicating tuberous sclerosis. J Neurol Neurosurg Psychiatry. 1992;55(12):1209.PubMedCentralCrossRefGoogle Scholar
  33. 33.
    Gutman A, Leffkowitz M. Tuberous sclerosis associated with hypoglycaemia. BMJ. 1959;ii:1065–8.CrossRefGoogle Scholar
  34. 34.
    Dimario FJ Jr. Brainstem tubers presenting as disordered breathing in tuberous sclerosis complex. J Child Neurol. 1995;10(5):407–9.CrossRefGoogle Scholar
  35. 35.
    Pacheva I, Panov G, Gillberg C, Neville B. A girl with tuberous sclerosis complex presenting with severe epilepsy and electrical status epilepticus during sleep, and with high-functioning autism and mutism. Cogn Behav Neurol. 2014;27(2):88–95.CrossRefGoogle Scholar
  36. 36.
    Ochi A, Hung, Weiss S, Widjaja E, To T, Nawa Y, et al. Lateralized interictal epileptiform discharges during rapid eye movement sleep correlate with epileptogenic hemisphere in children with intractable epilepsy secondary to tuberous sclerosis complex. Epilepsia. 2011;52(11):1986–94.CrossRefGoogle Scholar
  37. 37.
    Van Eeghen AM, Numis AI, Staley BA, Therrien SE, Thibert RL, Thiele EA. Characterizing sleep disorders of adults with tuberous sclerosis complex: a questionnaire-based study and review. Epilepsy Behav. 2011;20(1):68–74.CrossRefGoogle Scholar
  38. 38.
    Bruni O, Cortesi F, Giannotti F, Curatolo P. Sleep disorders in tuberous sclerosis: a polysomnographic study. Brain Dev. 1995;17(1):52–6.CrossRefGoogle Scholar
  39. 39.
    Leaf JB, Leaf R, McEachin J, Taubman M, Ala’i-Rosales S, Ross RK, et al. Applied behavior analysis is a science and, therefore, progressive. J Autism Dev Disord. 2016;46(2):720–31.CrossRefGoogle Scholar
  40. 40.
    Curatolo P, Bombardieri R, Verdecchia M, Seri S. Intractable seizures in tuberous sclerosis complex: from molecular pathogenesis to the rationale for treatment. J Child Neurol. 2005;20(4):318–25.CrossRefGoogle Scholar
  41. 41.
    Cross JH. Neurocutaneous syndromes and epilepsy-issues in diagnosis and management. Epilepsia. 2005;46(Suppl 10):17–23.CrossRefGoogle Scholar
  42. 42.
    Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci. 1991;615:125–7.CrossRefGoogle Scholar
  43. 43.
    Jóźwiak S, Kotulska K, Domańska-Pakiela D, Lojszczyk B, Syczewska M, Chmielewski D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol. 2011;15(5):424–31.CrossRefGoogle Scholar
  44. 44.
    Bombardieri R, Pinci M, Moavero R, Cerminara C, Curatolo P. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol. 2010;14(2):146–9.CrossRefGoogle Scholar
  45. 45.
    Zhang B, McDaniel SS, Rensing NR, Wong M. Vigabatrin inhibits seizures and mTOR pathway activation in a mouse model of tuberous sclerosis complex. PLoS One. 2013;8(2):e57445.PubMedCentralCrossRefGoogle Scholar
  46. 46.
    Fu C, Cawthon B, Clinkscales W, Bruce A, Winzenburger P, Ess KC. GABAergic interneuron development and function is modulated by the Tsc1 gene. Cereb Cortex. 2012;22(9):2111–9.CrossRefGoogle Scholar
  47. 47.
    Mori K, Mori T, Toda Y, Fujii E, Miyazaki M, Harada M, et al. Decreased benzodiazepine receptor and increased GABA level in cortical tubers in tuberous sclerosis complex. Brain Dev. 2012;34(6):478–86.CrossRefGoogle Scholar
  48. 48.
    Curatolo P, Jóźwiak S, Nabbout R, TSC Consensus Meeting for SEGA and Epilepsy Management. Management of epilepsy associated with tuberous sclerosis complex (TSC): clinical recommendations. Eur J Paediatr Neurol. 2012;16(6):582–6.CrossRefGoogle Scholar
  49. 49.
    Friedman D, Bogner M, Parker-Menzer K, Devinsky O. Vigabatrin for partial-onset seizure treatment in patients with tuberous sclerosis complex. Epilepsy Behav. 2013;27(1):118–20.CrossRefGoogle Scholar
  50. 50.
    Jennesson M, van Eeghen AM, Caruso PA, Paolini JL, Thiele EA. Clobazam therapy of refractory epilepsy in tuberous sclerosis complex. Epilepsy Res. 2013;104(3):269–74.CrossRefGoogle Scholar
  51. 51.
    Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9869):817–24.CrossRefGoogle Scholar
  52. 52.
    Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363(19):1801–11.CrossRefGoogle Scholar
  53. 53.
    Novartis Pharmaceuticals. A placebo-controlled study of efficacy & safety of 2 trough-ranges of everolimus as adjunctive therapy in patients with tuberous sclerosis complex (TSC) & refractory partial-onset seizures (EXIST-3) [Internet]. 2012. [cited November 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01713946.
  54. 54.
    U.S. Department of Health and Human Services. FDA approves Rapamune to treat LAM, a very rare lung disease [Internet]. 2015. [cited October 2015]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm448523.htm.
  55. 55.
    Koenig MK. Topical rapamycin to erase angiofibromas in TSC (treatment) [Internet]. 2015. [cited October 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT01526356.
  56. 56.
    de Vries P, Whittemore V, Leclezio L, Byers A, Dunn D, Ess K, et al. TAND checklist [Internet]. 2014. [cited October 2015]. Available from: http://www.tsalliance.org/documents/TAND_checklist%202014%20(USA%20version).pdf.
  57. 57.
    Hancock E, O’Callaghan F, English J, Osborne J. Melatonin excretion in normal children and in tuberous sclerosis complex with sleep disorder responsive to melatonin. J Child Neurol. 2005;20(1):21–5.CrossRefGoogle Scholar
  58. 58.
    De Leersnyder H, Zisapel N, Laudon M. Prolonged-release melatonin for children with neurodevelopmental disorders. Pediatr Neurol. 2011;45(1):23–6.CrossRefGoogle Scholar
  59. 59.
    O’Callaghan F, Clarke A, Hancock E, Hunt A, Osborne J. Use of melatonin to treat sleep disorders in tuberous sclerosis. Dev Med Child Neurol. 1999;41(2):123–6.CrossRefGoogle Scholar
  60. 60.
    Braam W, Smits MG, Didden R, Korzilius H, Van Geijlswik IM, Curfs LM. Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol. 2009;51(5):340–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Tuberous Sclerosis Center of ExcellenceLeBonheur Children’s HospitalMemphisUSA

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