Characteristics and the clinical prognosis of epilepsy in patients with a diagnosis of tuberous sclerosis complex

Abstract

Aim: Epilepsy is the most common neurological problem in tuberous sclerosis complex TSC The aim of this study is to investigate the clinical features and prognosis of epilepsy associated with TSC and to determine the factors that may affect the course of epilepsy in TSC patients Material and Method: Our study included 21 TSC patients 11 10: M F aged between 1 14 years 7 5 plusmn;4 2 and followed up for 9 months 10 years because of epileptic seizures After epileptic seizures were classified as seizures with good and poor prognosis they were were statistically compared in terms of age at seizure onset history of status and infantile spasms initial treatment with vigabatrin initial EEG findings presence of autism or mental retardation or cognitive impairment the number of cortical tubers and presence of astrocytoma Results: The age at seizure onset ranged between 3 days and 2 5 years The most common seizure type in our patients was partial seizure and eight patients had infantile spasms and status epilepticus As a result of follow up the prognosis was evaluated as poor in 11 and good in 10 patients No statistical relationship was found between seizure prognosis and age at seizure onset younger and older than 1 age the history of status and infantile spasms initial EEG findings use of vigabatrin as the first drug the presence of autism or mental retardation or cognitive impairment the number and localization of cortical tubers and the presence of astrocytoma p gt;0 05 Conclusions: The prognosis of epilepsy in patients with TSC varies in each patient depending on several factors For this reason close follow up of these patients with clinical evaluation and EEG is required Turk Arch Ped 2013; 48: 123 30

Keywords

• Epilepsy, prognosis, tuberous sclerosis complex

Tüberoskleroz kompleksi tanılı hastalarda epilepsinin özellikleri ve klinik seyri

Öz

Amaç: Tüberoskleroz kompleksinde en sık görülen nörolojik sorun epilepsidir Bu çalışma epileptik tüberoskleroz kompleksi tanılı hastaların epilepsi özeliklerini ve klinik seyrini incelemek epilepsi seyrini etkileyebilecek etmenleri araştırmak amacıyla planlandı.

Gereç ve Yöntem: Çocuk Nörolojisi Kliniği rsquo;mizde epilepsi nedeniyle 9 ay 10 yıl izlenen 1 14 7 5 plusmn;4 2 yaşları arasında 21 tüberoskleroz kompleksi tanılı hasta 11 10: E K çalışmaya alındı Hastalara ait aşağıdaki bilgiler elde edildi: epileptik nöbet özellikleri muayene bulguları zeka veya bilişsel gelişim düzeyleri antiepileptik tedavi kraniyal manyetik rezonans görüntüleri ve elektroansefalogram bulguları Epileptik nöbet seyri iyi ve kötü olarak gruplandırıldıktan sonra ilk nöbet yaşı öyküde status infantil spazm varlığı ilk tedavi seçeneğinin vigabatrin olması ilk elektroansefalogram bulguları elektroansefalogramda epileptik aktivite yeri hastalarda otizm veya zeka ve bilişsel gelişim geriliği varlığı kortikal tüberlerin sayı ve yerleşimleri astrositom varlığı açısından istatiksel olarak karşılaştırıldı.

Bulgular: Hastaların nöbet başlama yaşı üç gün ile 2 5 yaş arasında olup 16 hastada 76 bir yaş ve altındaydı Hastalarımızın en sık nöbet tipi 95 kısmi nöbet olup sekizer hastada 38 infantil spazm ve status epileptikus saptandı İzlemleri sonucunda nöbet seyri 11 rsquo;inde kötü 10 rsquo;unda iyi olarak değerlendirildi Nöbet başlangıç yaşı bir yaş altı ve üstü status veya infantil spazm öyküsü ilk elektroansefalogram bulguları ilk ilaç olarak vigabatrin kullanılması hastada otizm veya zeka ve gelişim geriliği varlığı kraniyal manyetik rezonans görüntülemede kortikal tüber sayısı yerleşimi ve astrositom varlığının nöbet seyri ile ilişkisi saptanmadı.

Çıkarımlar: Tüberoskleroz kompleksi tanılı hastalarda epilepsinin klinik seyrinin her hasta özelinde çeşitli etmenlere bağlı değişkenlik gösterebilmesi nedeniyle bu hastaların klinik ve elektroansefalogram ile yakın izlemi gereklidir.

Anahtar Kelimeler

• Epilepsi
• seyir
• tüberoskleroz kompleksi

References

1. Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci 1991; 615: 125–7.
2. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006; 355(13): 1345-56.
3. Schwartz RA, Fernández G, Kotulska K, Jóźwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol 2007; 57: 189-202.
4. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet 2008; 372: 657-68.
5. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 1998; 13(12): 624-8.
6. Weiner DM, Ewalt DH, Roach ES, Hensle TW. The tuberous sclerosis complex: a comprehensive review. J Am Coll Surg 1998; 187(5): 548-61.
7. Holmes GL, Stafstrom CE; Tuberous Sclerosis Study Group. Tuberous sclerosis complex and epilepsy: recent developments and future challenges. Epilepsia 2007; 48(4): 617-30.
8. Samir H, Ghaffar HA, Nasr M. Seizures and intellectual outcome: clinico-radiological study of 30 Egyptian cases of tuberous sclerosis complex. Eur J Paediatr Neurol 2011; 15(2): 131-7.

9. Goodman M, Lamm SH, Engel A, Shepherd CW, Houser OW, Gomez MR. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol 1997; 12(2): 85-90.
10. Roach ES, Williams DP, Laster DW. Magnetic resonance imaging in tuberous sclerosis. Arch Neurol 1987; 44(3): 301-3.
11. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision [DSM–IV-TR]. Washington, DC: American Psychiatric Association, 2000.
12. Culberton FM, Feral CH, Gabby S. Pattern analysis of Wechsler Intelligence Scale for children-revised profiles of delinquent boys. J Clin Psychol 1989; 45(4): 651-60.
13. Savaşır I, Şahin N. Wechsler çocuklar için zeka ölçeği (WISC-R) el kitabı. Ankara Türk Psikologlar Derneği Yayınları, 1995: 13-52.
14. Anlar B, Yalaz K. Denver II gelişimsel tarama testi Türk çocuklarına uyarlanması ve standardizasyonu el kitabı. Ankara Meteksan Matbası, 1996.
15. Sparagana SP, Delgado MR, Batchelor LL, Roach ES. Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex. Arch Neurol 2003; 60(9): 1286-9.
16. Cross JH. Neurocutaneous syndromes and epilepsy-issues in diagnosis and management. Epilepsia 2005; 46(Suppl 10): 17-23. Devlin LA, Shepherd CH, Crawford H, Morrison PJ. Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland. Dev Med Child Neurol 2006; 48(6): 495-9. Józwiak S, Schwartz RA, Janniger CK, Bielicka-Cymerman J. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol 2000; 15(10): 652-9.
17. Webb DW, Fryer AE, Osborne JP. On the incidence of fits and mental retardation in tuberous sclerosis. J Med Genet 1991; 28(6): 395-7.
18. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol 1996; 38(2): 146-55.
19. Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 2010; 51(7): 1236-41.
20. Gomez MR. Natural history of cerebral tuberous sclerosis. In: Gomez MR, Sampson JR, Whittemor VH, (eds). Tuberous sclerosis complex: Developmental perspectives in psychiatry. New York: Oxford University Press, 1999: 29-46.
21. Riikonen R, Simell O. Tuberous sclerosis and infantile spasms. Dev Med Child Neurol 1990; 32(3): 203-9.
22. Thiele EA. Managing epilepsy in tuberous sclerosis complex. J Child Neurol 2004; 19(9): 680-6.
23. O’Callaghan FJ, Harris T, Joinson C, et al. The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex. Arch Dis Child 2004; 89(6): 530-3.
24. Pampiglione G, Moynahan EJ. The tuberous sclerosis syndrome: clinical and EEG studies in 100 children. J Neurol Neurosurg Psychiatry 1976; 39(7): 666-73.
25. Westmoreland B. The electroencephalogram in tuberous sclerosis. In: Gomez MR, Sampson JR, Whittemore VH, (eds). Tuberous sclerosis complex: developmental perspectives in psychiatry. 3th ed. New York: Oxford University Press, 1999: 63-74.
26. Mizuguchi M, Takashima S. Neuropathology of tuberous sclerosis. Brain Dev 2001; 23(7): 508-15.
27. Ridler K, Suckling J, Higgins N, Bolton P, Bullmore E. Standardized whole brain mapping of tubers and subependymal nodules in tuberous sclerosis complex. J Child Neurol 2004; 19(9): 658-65.
28. Baron Y, Barkovich AJ. MR imaging of tuberous sclerosis in neonates and young infants. AJNR Am J Neuroradiol 1999; 20(5): 907Goh S, Butler W, Thiele EA. Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 2004; 63(8): 1457-61.
29. O’Callaghan FJ, Martyn CN, Renowden S, Noakes M, Presdee D, Osborne JP. Subependymal nodules, giant cell astrocytomas and the tuberous sclerosis complex: a population-based study. Arch Dis Child 2008; 93(9): 751-4.
30. 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.
31. Kassiri J, Snyder TJ, Bhargava R, Wheatley BM, Sinclair DB. Cortical tubers, cognition, and epilepsy in tuberous sclerosis. Pediatr Neurol 2011; 44(5): 328-32.
32. Smalley SL, Tanguay PE, Smith M, Gutierrez G. Autism and tuberous sclerosis. J Autism Dev Disord 1992; 22(3): 339-55.
33. Wiznitzer M. Autism and tuberous sclerosis. J Child Neurol 2004; 19(9): 675-9.
34. Park SM, Lee YJ, Son YJ, Kim YO, Woo YJ. Clinical progress of epilepsy in children with tuberous sclerosis: prognostic factors for seizure outcome. Chonnam Med J 2011; 47(3): 150-4.
35. Curatolo P, Moavero R. Can we change the course of epilepsy in tuberous sclerosis complex? Epilepsia 2010; 51(7): 1330-1.
36. Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology 2008; 70(12): 916-23.
37. White R, Hua Y, Scheithauer B, Lynch DR, Henske EP, Crino PB. Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers. Ann Neurol 2001; 49(1): 67-78.
38. Wong M, Ess KC, Uhlmann EJ, et al. Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model. Ann Neurol 2003; 54(2): 251-6.
39. Doherty C, Goh S, Young PT, Erdag N, Thiele EA. Prognostic significance of tuber count and location in tuberous sclerosis complex. J Child Neurol 2005; 20(10): 837-41.