Surgical treatment of epilepsy in a teenager with tuberous sclerosis

Tuberous sclerosis is one of the genetically determined neurodermal syndromes, characterized by focal epilepsy, which is resistant to drug therapy in most cases. Tuberous sclerosis has not been surgically treated for a long time due to the multifocal nature of brain damage. However, using new instrumental methods the surgeon can isolate tuber – “drivers”, responsible for epileptic induction, which, therefore, can be a target for surgical removal. The article presents a clinical case of the treatment of pharmacoresistant epilepsy in a 17-year-old girl with tuberous sclerosis and normal neuropsychiatric and cognitive status; the surgeon managed to achieve a complete regression of seizures after the surgical removal of one of the tubers. Using a multimodal complex of examinations, including high-resolution magnetic resonance imaging and invasive electroencephalographic monitoring, the surgeon managed to identify the “inductor” tuber associated with the epileptic initiation zone among multiple cortical tubers. This section of the cerebral cortex was subjected to surgical resection. For the entire postoperative period (16 months) there were no seizures and antiepileptic drugs were canceled; cognitive processes, memory were improved. Thus, active surgical tactics may be effective in more than 50% of patients with tuberous sclerosis and pharmacoresistant epilepsy. This case confirms the need for a multidisciplinary examination prior to the surgery in patients with tuberous sclerosis.

1. National Institute of Neurological Disorders and Stroke. Tuberous sclerosis fact sheet. NIH publication number 071846 2014 [webpage on the Internet]. Bethesda, MD: National Institutes of Health; 2014 [updated April 16, 2014]. Available from: http://www.ninds.nih.gov/ disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm

2. Huang J., Dibble C., Matsuzaki M., Manning B. The TSC1– TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 2008;28:4104–4115. DOI: 10.1128/ MCB.00289-08.

3. Crino P.B., Nathanson K.L., Henske E.P. The tuberous sclerosis complex. N Engl J Med 2006; 355(13): 1345–1356. DOI: 10.1056/NEJMra055323

4. Wang S., Fallah A. Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options. Neuropsychiatr Dis Treat 2014;10:2021–2030. DOI: 10.2147/NDT.S51789

5. Lewis J.C., Thomas H.V., Murphy K.C., Sampson J.R. Genotype and psychological phenotype in tuberous sclerosis. J Med Genet 2004; 41(3): 203–207. DOI: 10.1136/jmg.2003.012757

6. Туберозный склероз. Диагностика и лечение. Монография. Под ред. М.Ю. Дорофеевой. М.: Адаре, 2017; 290. [Tuberous sclerosis. Diagnosis and treatment. Monography. M.Yu. Dorofeeva (ed.). Moscow: Adare, 2017; 290. (in Russ.)]

7. Yates J.R., Maclean C., Higgins J.N., Humphrey A., le Maréchal K., Clifford M. et al. Tuberous Sclerosis 2000 Study Group. The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management. Arch Dis Child 2011; 96(11): 1020–1025. DOI: 10.1136/adc.2011.211995.

8. Joinson C., O’Callaghan F.J., Osborne J.P., Martyn C., Harris T., Bolton P.F. Learning disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychol Med 2003; 33(2): 335–344. DOI: 10.1017/ s0033291702007092

9. Vignoli A., La Briola F., Turner K., Scornavacca G., Chiesa V., Zambrelli E. et al. Epilepsy in TSC: certain etiology does not mean certain prognosis. Epilepsia 2013; 54(12): 2134–2142. DOI: 10.1111/epi.12430

10. Chu-Shore C.J., Major P., Camposano S., Muzykewicz D., Thiele E.A. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 2010; 51(7): 1236–1241. DOI: 10.1111/j.1528-1167.2009.02474.x

11. Riikonen R., Simell O. Tuberous sclerosis and infantile spasms. Dev Med Child Neurol 1990; 32(3): 203–209. DOI: 10.1111/ j.1469-8749.1990.tb16926.x

12. de Vries P.J., Whittemore V.H., Leclezio L., Byars A.W., Dunn D. Ess K.C. et al. Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist. Pediatr Neurol 2015; 52: 25–35. DOI: 10.1016/j.pediatrneurol.2014.10.004

13. Zaroff C.M., Devinsky O., Miles D., Barr W.B. Cogni- tive and behavioral correlates of tuberous sclerosis complex. J Child Neurol 2004; 19: 847–852. DOI: 10.1177/08830738 040190110101

14. de Vries P. Neurodevelopmental, psychiatric and cognitive aspects of tuberous sclerosis complex. In: Kwiatkowsi D.J., Whittemore V.H., Thiele E.A., editors. Tuberous Sclerosis Complex: Genes, Clinical Features. Weinheim: Wiley-Blackwell, 2010; 229–267.

15. Cusmai R., Moavero R., Bombardieri R., Vigevano F., Curatolo P. Longterm neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. Epilepsy Behav 2011; 22(4): 735–739. DOI: 10.1016/j.yebeh.2011.08.037

16. 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): 582–586. DOI: 10.1016/j.ejpn.2012.05.004

17. Krueger D.A., 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): 255–265. DOI: 10.1016/j. pediatrneurol.2013.08.002

18. Camposano S.E., Major P., Halpern E., Thiele E.A. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia 2008; 49(7): 1186–1191. DOI: 10.1111/j.1528-1167.2008.01589.x

19. Elterman R.D., Shields W.D., Bittman R.M., Torri S.A., Sagar S.M., Collins S.D. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol 2010; 25(11): 1340–1347. DOI: 10.1177/0883073810365103

20. Overwater I.E., Bindels-de-Heus K., Rietman A.B., Ten Hoopen L.V., Vergouwe Yv., Moll H.A. et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia 2015; 56:1239–1245. DOI: 10.1111/epi.13050

21. Overwater I.E., Rietman A.B., Bindels-de Heus K., Looman K.W., Rizopoulos D., Sibindi T.M. et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: a randomized controlled trial. Neurology 2016; 87: 1011–1018. DOI: 10.1212/WNL.0000000000003077

22. Curatolo P. Mechanistic target of rapamycin (mTOR) in tuberous sclerosis complex associated epilepsy. Pediatr Neurol 2015; 52: 281–289. DOI: 10.1016/j.pediatrneurol.2014.10.028

23. Miller J.W. Treating epilepsy in tuberous sclerosis with everolimus: getting closer, Epilepsy Curr 2014; 14: 143–144. DOI: 10.5698/1535-7597-14.3.143

24. French J.A., Lawson J.A., Yapici Z., Ikeda H., Polster T., Nabbout R. et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomized, double-blind, placebo-controlled study. Lancet 2016; 388: 2153–2163. DOI: 10.1016/S0140-6736(16)31419-2

25. Overwater I.E., Bindels-De Heus K., Rietman A.B., Ten Hoopen L.W., Vergouwe Y., Moll H.A. et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia 2015; 56: 1239–1245. DOI: 10.1111/epi.13050

26. Fallah A., Guyatt G.H., Snead O.C. III, Ebrahim S., Ibrahim G.M., Mansouri A. et al. Predictors of seizure outcomes in children with tuberous sclerosis complex and intractable epilepsy undergoing resective epilepsy surgery: an individual participant data meta-analysis. PLoS ONE. 2013; 8: e53565. DOI: 10.1371/JOURNAL.PONE.0053565

27. Arya R., Tenney J.R., Horn P.S, Greiner H.M., Holland K.D., Leach J.L. et al. Long-term outcomes of resective epilepsy surgery after invasive presurgical evaluation in children with tuberous sclerosis complex and bilateral multiple lesions. J Neurosurg Pediatr 2015; 15: 26–33. DOI: 10.3171/2014.10. PEDS14107.

28. Elliott R.E., Carlson C., Kalhorn S.P., Moshel Y.A., Weiner H.L., Devinsky O. et al. Refractory epilepsy in tuberous sclerosis: vagus nerve stimulation with or without subsequent resective surgery. Epilepsy Behav 2009; 16(3): 454–460. DOI: 10.1016/j.yebeh.2009.08.018.

29. Holthausen H., Pieper T., Eitel H., Kudernatsch M. Хирургическое лечение эпилепсии у пациентов с туберозным склерозом. Русский журнал детской неврологии 2015; 10(1): 40–46. [Holthausen H., Pieper T., Eitel H., Kudernatsch M. Surgical treatment of epilepsy in patients with tuberous sclerosis. Russkii zhurnal detskoi nevrologii 2015; 10(1): 40–46. DOI: 10.17650/2073-8803-2015-1-40-46. (in Russ.)]