Child's Nervous System

, Volume 35, Issue 3, pp 463–468 | Cite as

Factors affecting epilepsy prognosis in patients with tuberous sclerosis

  • Gülen Gül MertEmail author
  • Şakir Altunbaşak
  • Özlem Hergüner
  • Faruk İncecik
  • Hilal Cansever Övetti
  • Neslihan Özcan
  • Duygu Kuşçu
  • İlker Ünal
Original Article



We aimed to determine the characteristics of epileptic seizures that significantly affect the cognitive functions of 83 patients followed with tuberous sclerosis complex (TSC), their resistance to treatment and risk factors causing this resistance.


In order to determine the prognosis, the seizure-free/seizure-controlled group and the group with refractory seizures were compared. In addition, risk factors affecting cognitive functions in the patients were determined.


There was a statistical significance between the presence of a history of seizures in the neonatal period, the age of onset of seizures being less than 2 years of age, autism, status epilepticus, Lennox-Gastaut syndrome (LGS), presence of infantile spasm, generalization of the electroencephalography (EEG) findings, the number of tubers in cerebral imaging being more than three and refractory seizures (p < 0.05). Statistically significant relationship was found between presence of a history of seizures in the neonatal period, the age of onset of seizures, autism, LGS, presence of infantile spasm, presence of status epilepticus history, history of using more than three antiepileptic drugs, generalization of EEG findings, presence of SEGA in cerebral imaging, number of tubers being more than three and the patient’s mental retardation (p < 0.05).


In logistic regression analysis, the age of the seizure onset being less than 2 years of age, the presence of autism and number of tubers being more than three in cerebral magnetic resonance imaging (MRI) are determined to be the risk factors that most likely to increase the seizures to be more resistant.


Tuberous sclerosis Epilepsy Prognosis 


Compliance with ethical standards

On June 1, 2018, under the decree no 72, ethic committee approval of the study from Cukurova University Faculty of Medicine Non-Interventional Clinical Trials Ethics Committee and consent from the families of the patients to participate in the study were obtained

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Curatolo P, Bombardieri R, Jozwiak S (2008) Tuberous sclerosis. Lancet 372:657–668CrossRefGoogle Scholar
  2. 2.
    Hallett L, Foster T, Liu Z, Blieden M, Valentim J (2011) Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. Curr Med Res Opin 27:1571–1583CrossRefGoogle Scholar
  3. 3.
    Kwiatkowski DJ, Manning BD (2014) Molecular basis of giant cells in tuberous sclerosis complex. N Engl J Med 371:778–780CrossRefGoogle Scholar
  4. 4.
    Child ND, Benarroch EE (2014) mTOR: its role in the nervous system and involvement in neurologic disease. Neurology 83:1562–1572CrossRefGoogle Scholar
  5. 5.
    Yates JR, Maclean C, Higgins JN et al (2011) The tuberous sclerosis 2000 study: presentation, initial assessments and implications for diagnosis and management. Arch Dis Child 96:1020–1025CrossRefGoogle Scholar
  6. 6.
    Chu-Shore CJ, Major P, Camposano S et al (2010) The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 51:1236–1241CrossRefGoogle Scholar
  7. 7.
    Northrup H, Krueger DA (2013) International tuberous sclerosis complex consensus group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 49:243–254CrossRefGoogle Scholar
  8. 8.
    Shinnar S (2010) The new ILAE classification. Epilepsia 51:715–717CrossRefGoogle Scholar
  9. 9.
    Vignoli A, La Briola F, Turner K, Scornavacca G, Chiesa V, Zambrelli E et al (2013) Epilepsy in TSC: certain etiology does not mean certain prognosis. Epilepsia 54:2134–2142CrossRefGoogle Scholar
  10. 10.
    Jozwiak S, Shwarz RA, Janniger CK, Bielicka-Cymerman J (2000) Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol 15:652–659CrossRefGoogle Scholar
  11. 11.
    Sparagana SP, Delgado MR, Batchelor LL, Roach ES (2003) Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex. Arch Neurol 60:1286–1289CrossRefGoogle Scholar
  12. 12.
    Wang S, Fallah A (2014) Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options. Neuropsychiatr Dis Treat 23:2021–2030Google Scholar
  13. 13.
    Shehata H, AbdelGhaffar HM, Nasreldin M, Elmazny A, Abdelalim A, Sabbah A, Shalaby N (2017) Clinical patterns and outcomes of status epilepticus in patients with tuberous sclerosis complex. Ther and Clin Risk Manag 13:779–785CrossRefGoogle Scholar
  14. 14.
    Saxena A, Sampson JR (2015) Epilepsy in tuberous sclerosis: phenotypes, mechanisms, and treatments. Semin Neurol 35:269–276CrossRefGoogle Scholar
  15. 15.
    Primec ZR, Stare J, Neubauer D (2006) The risk of lower mental outcome in infantile spasms increases after three weeks of hypsarrhythmia duration. Epilepsia 47:2202–2205CrossRefGoogle Scholar
  16. 16.
    Camposano S, Greenberg E, Kwiatkowski D, Thiele EA (2009) Distinct clinical characteristics of tuberous sclerosis complex patients with no mutation identified. Ann Hum Genet 73:141–146CrossRefGoogle Scholar
  17. 17.
    Mizuguchi M, Takashima S (2001) Neuropathology of tuberous sclerosis. Brain and Development 23:508–515CrossRefGoogle Scholar
  18. 18.
    Goh S, Butler W, Thiele EA (2004) Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 63:1457–1461CrossRefGoogle Scholar
  19. 19.
    Chou IJ, Wong A, Wang HS, Chou ML, Hung PC, Hsieh MY, Chang MY (2008) Neuroimaging correlation with neurological severity in tuberous sclerosis complex. Eur J Paediatr Neurol 12:108–112CrossRefGoogle Scholar
  20. 20.
    Soo MP, Yong JL, Yong JS, Yong OK, Yong JW (2011) Clinical progress of epilepsy in children with tuberous sclerosis: prognostic factors for seizure outcome. Chonnam Med J 47:150–154CrossRefGoogle Scholar
  21. 21.
    Goodman M, Lamm SH, Engel A, Shepherd CW, Houser OW, Gomez MR (1997) Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol 12:85–90CrossRefGoogle Scholar
  22. 22.
    Kopp CM, Muzykewicz DA, Staley BA et al (2008) Behavior problems in children with tuberous sclerosis complex and parental stress. Epilepsy Behav 13:505–510CrossRefGoogle Scholar
  23. 23.
    Bolton PF, Park RJ, Higgins JN et al (2002) Neuroepileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 125:1247–1255CrossRefGoogle Scholar
  24. 24.
    Bolton PF, Griffiths PD (1997) Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 349:392–395CrossRefGoogle Scholar
  25. 25.
    Walz NC, Byars AW, Egelhoff JC, Franz DN (2002) Supratentorial tuber location and autism in tuberous sclerosis complex. J Child Neurol 17:830–832CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Gülen Gül Mert
    • 1
    Email author
  • Şakir Altunbaşak
    • 1
  • Özlem Hergüner
    • 1
  • Faruk İncecik
    • 1
  • Hilal Cansever Övetti
    • 1
  • Neslihan Özcan
    • 1
  • Duygu Kuşçu
    • 2
  • İlker Ünal
    • 3
  1. 1.Department of Pediatrics, Division of Pediatric NeurologyCukurova UniversityAdanaTurkey
  2. 2.Department of PsychologyCukurova UniversityAdanaTurkey
  3. 3.Department of BiostatisticsCukurova UniversityAdanaTurkey

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