Çocuklarda Epileptik Ensefalopatiler

Yıl 2020, , 538 - 546, 30.11.2020

Aydan Değerliyurt , Özlem Yayıcı Köken

https://doi.org/10.12956/tchd.727161

Öz

Epilepsi çocuklarda en sık karşılaşılan nörolojik sorunlardandır. Özellikle bebeklik ve çocuklukta başlayan bazı epilepsilerde daha sık olarak rastlanan epileptik ensefalopatilerde ise nöbetler ve yoğun epileptiform aktivitelere bağlı olarak nöropsikolojik gelişim olumsuz yönde etkilenir. Bu hastalarda devam eden ağır epileptiform aktivite ve nöbetler, normal nöronal ağların gelişimini engelleyerek epileptik ensefalopatinin ortaya çıkmasında rol oynarlar. Epileptik ensefalopatilere tüm yaş gruplarında rastlansa bile çocukluk gibi gelişimsel açıdan kritik bir dönemde ortaya çıkması sadece kazanılmış fonksiyonları değil, aynı zamanda yaşa bağlı olarak gelişmesi beklenen yeni fonksiyonları da olumsuz olarak etkileyeceği için bu yaş grubunda daha yıkıcı seyreder. Epileptik ensefalopatilerin erken tanı alması ve tedavinin erken dönemde başlanması, ortaya çıkacak gelişimsel sorunların -bazı hastalarda- önlenmesi potansiyelini barındırdığı için önemlidir. Etyolojide diğer nedenlerin yanında gittikçe artan sayılarda gen mutasyonlarının gösterilmesi nedeniyle son yıllarda genetik nedenler öne çıkmaktadır. Bu grup epileptik ensefalopatilerde nöbetler ve epileptiform bozuklukların yanı sıra genetik mutasyonun kendisine bağlı olarak da nörogelişimsel gerilikler bulunduğu için yeni bir kavram olarak gelişimsel ve epileptik ensefalopati terimi önerilmiştir.
Bu yazıda çocuklukta sık görülen West sendromu, Dravet sendromu gibi fenotipler ve konuşma geriliği veya gerilemesi, psikomotor gerileme, otistik semptomlar ile belirti veren ve bu nedenle dikkatli ayırıcı tanı yapılması gereken Landau-Kleffner ve CSWS sendromu başta olmak üzere tüm epileptik ve gelişimsel ve epileptik ensefalopatilerin karakteristik klinik özellikleri ve genetik etyolojiler yönünden yaklaşım amaçlanmıştır.

Anahtar Kelimeler

Epilepsi, , epileptik ensefalopati, , gelişimsel ensefalopati

Pediatric Epileptic Encephalopathies

Öz

Epilepsy is one of the most common neurologic problems encountered in children. Epileptic encephalopathies, which are more common in epilepsies with an onset in infancy and childhood, seizures and frequent epileptiform activities have a negative impact on neuropsychological development. Ongoing severe epileptiform activities and seizures impede the normal development of neural networks and cause epileptic encephalopathies. Although epileptic encephalopathies can be seen at every age, an onset in childhood, which is a critical period for development, can be detrimental since not only acquired functions but also expected new functions will be negatively effected. Early diagnosis and prompt treatment for epileptic encephalopathies is important since developmental problems can be prevented in some patients. In addition to other etiologies, genetic causes are becoming more prevalent secondary to gene mutations which are being detected more frequently. Developmental and epileptic encephalopathy is a new term which is being used to connote the neurodevelopmental retardation caused by the genetic mutation itself in addition to seizures and epileptiform activities.
This manuscript aims to evaluate the clinical features and etiological approach in all epileptic, developmental and epileptic encephalopathies such as mostly seen phenotypes like West syndrome and Dravet syndrome in addition to Landau-Kleffner and CSWS syndromes which require a careful differential diagnosis due to language retardation or deterioration, psychomotor retardation and symptoms of autism.

Anahtar Kelimeler

Epilepsy, Epileptic encephalopathy,, Developmental encephalopathy, Developmental regression

Kaynakça

• Referans1. Cross JH, Guerrini R. The epileptic encephalopathies. Handb Clin Neurol. 2013;111:619–26. Referans2. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51:676–85. Referans3. Kalser J, Cross JH. The epileptic encephalopathy jungle – from Dr West to the concepts of aetiology-related and developmental encephalopathies: Curr Opin Neurol. 2018;31:216–22. Referans4. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58:512–21. Referans5. Howell KB, Harvey AS, Archer JS. Epileptic encephalopathy: Use and misuse of a clinically and conceptually important concept. Epilepsia. 2016;57:343–7. Referans6. McTague A, Howell KB, Cross JH, Kurian MA, Scheffer IE. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016;15:304–16. Referans7. Patel J, Mercimek-Mahmutoglu S. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes. Indian J Pediatr. 2016;83:1164–74. Referans8. Costain G, Cordeiro D, Matviychuk D, Mercimek-Andrews S. Clinical Application of Targeted Next-Generation Sequencing Panels and Whole Exome Sequencing in Childhood Epilepsy. Neuroscience. 2019;418:291–310. Referans9. Helbig I, Tayoun AAN. Understanding Genotypes and Phenotypes in Epileptic Encephalopathies. Mol Syndromol. 2016;7:172–81. Referans10. Lemke JR, Syrbe S. Epileptic Encephalopathies in Childhood: The Role of Genetic Testing. Semin Neurol. 2015;35:310–22. Referans11. Olson HE, Kelly M, LaCoursiere CM, Pinsky R, Tambunan D, Shain C, et al. Genetics and genotype-phenotype correlations in early onset epileptic encephalopathy with burst suppression. Ann Neurol. 2017;81:419–29. Referans12. Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res. 2006;70(Suppl 1):S58-67. Referans13. Beal JC, Cherian K, Moshe SL. Early-onset epileptic encephalopathies: Ohtahara syndrome and early myoclonic encephalopathy. Pediatr Neurol. 2012;47:317–23. Referans14. Shbarou R, Mikati MA. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies. Semin Pediatr Neurol. 2016;23:134–42. Referans15. Cornet MC, Cilio MR. Genetics of neonatal-onset epilepsies. Handb Clin Neurol. 2019;162:415–33. Referans16. Covanis A. Epileptic encephalopathies (including severe epilepsy syndromes). Epilepsia. 2012;53(Suppl 4):114–26. Referans17. Burgess R, Wang S, McTague A, Boysen KE, Yang X, Zeng Q, et al. The Genetic Landscape of Epilepsy of Infancy with Migrating Focal Seizures. Ann Neurol. 2019;86:821–31. Referans18. Gataullina S, Dulac O. From genotype to phenotype in Dravet disease. Seizure. 2017 Jan;44:58–64. Referans19. Gaily E, Anttonen A-K, Valanne L, Liukkonen E, Träskelin A-L, Polvi A, et al. Dravet syndrome: new potential genetic modifiers, imaging abnormalities, and ictal findings. Epilepsia. 2013;54:1577–85. Referans20. Steel D, Symonds JD, Zuberi SM, Brunklaus A. Dravet syndrome and its mimics: Beyond SCN1A. Epilepsia. 2017;58:1807–16. Referans21. Elia M. Myoclonic status in nonprogressive encephalopathies: an update. Epilepsia. 2009;50(Suppl 5):41–4. Referans22. Tassinari CA, Rubboli G. Encephalopathy related to Status Epilepticus during slow Sleep: current concepts and future directions. Epileptic Disord. 2019;21(Suppl 1):82–7. Referans23. Tassinari CA, Rubboli G. Cognition and paroxysmal EEG activities: from a single spike to electrical status epilepticus during sleep. Epilepsia. 2006;47(Suppl 2):40–3. Referans24. Caraballo R, Pavlidis E, Nikanorova M, Loddenkemper T. Encephalopathy with continuous spike-waves during slow-wave sleep: evolution and prognosis. Epileptic Disord. 2019;21(Suppl 1):15–21. Referans25. Hergüner MO, Incecik F, Altunbaşak S, Kiriş N. Clinical characteristics of 10 patients with continuous spikes and waves during slow sleep syndrome. Pediatr Neurol. 2008;38:411–4. Referans26. Yilmaz S, Serdaroglu G, Akcay A, Gokben S. Clinical characteristics and outcome of children with electrical status epilepticus during slow wave sleep. J Pediatr Neurosci. 2014;9:105–9. Referans27. Değerliyurt A, Yalnizoğlu D, Bakar EE, Topçu M, Turanli G. Electrical status epilepticus during sleep: a study of 22 patients. Brain Dev. 2015;37:250–64. Referans28. Arhan E, Serdaroglu A, Aydin K, Hırfanoglu T, Soysal AS. Epileptic encephalopathy with electrical status epilepticus: an electroclinical study of 59 patients. Seizure. 2015;26:86–93. Referans29. Gencpinar P, Dundar NO, Tekgul H. Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) syndrome in children: An electroclinical evaluation according to the EEG patterns. Epilepsy Behav. 2016;61:107–11. Referans30. Fejerman N, Caraballo R, Cersósimo R, Ferraro SM, Galicchio S, Amartino H. Sulthiame add-on therapy in children with focal epilepsies associated with encephalopathy related to electrical status epilepticus during slow sleep (ESES). Epilepsia. 2012;53:1156–61. Referans31. Tassinari CA, Rubboli G, Volpi L, Meletti S, d’Orsi G, Franca M, et al. Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clin Neurophysiol. 2000;111(Suppl 2):S94–102. Referans32. Deonna T, Roulet-Perez E. Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: the continuing debate. Brain Dev. 2010;32:746–52. Referans33. Hirsch E, Caraballo R, Bernardina BD, Loddenkemper T, Zuberi SM. Encephalopathy related to Status Epilepticus during slow Sleep: from concepts to terminology. Epileptic Disord. 2019;21(Suppl 1):5–12. Referans34. Scheltens-de Boer M. Guidelines for EEG in encephalopathy related to ESES/CSWS in children. Epilepsia. 2009;50(Suppl 7):13–7. Referans35. Guerrini R, Pellacani S. Benign childhood focal epilepsies. Epilepsia. 2012;53(Suppl 4):9–18. Referans36. Fejerman N. Atypical rolandic epilepsy. Epilepsia. 2009;50(Suppl 7):9–12. Referans37. De Tiège X, Goldman S, Verheulpen D, Aeby A, Poznanski N, Van Bogaert P. Coexistence of idiopathic rolandic epilepsy and CSWS in two families. Epilepsia. 2006;47:1723–7. Referans38. Sánchez Fernández I, Loddenkemper T, Peters JM, Kothare SV. Electrical status epilepticus in sleep: clinical presentation and pathophysiology. Pediatr Neurol. 2012;47:390–410. Referans39. Rudolf G, Valenti MP, Hirsch E, Szepetowski P. From rolandic epilepsy to continuous spike-and-waves during sleep and Landau-Kleffner syndromes: insights into possible genetic factors. Epilepsia. 2009;50(Suppl 7):25–8. Referans40. Saltik S, Uluduz D, Cokar O, Demirbilek V, Dervent A. A clinical and EEG study on idiopathic partial epilepsies with evolution into ESES spectrum disorders. Epilepsia. 2005;46:524–33. Referans41. Takeoka M, Riviello JJ, Duffy FH, Kim F, Kennedy DN, Makris N, et al. Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome. Neurology. 2004;63:1289–92. Referans42. Tsai M-H, Vears DF, Turner SJ, Smith RL, Berkovic SF, Sadleir LG, et al. Clinical genetic study of the epilepsy-aphasia spectrum. Epilepsia. 2013;54:280–7. Referans43. Scheffer IE, Jones L, Pozzebon M, Howell RA, Saling MM, Berkovic SF. Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with anticipation. Ann Neurol. 1995;38:633–42. Referans44. Kevelam SHG, Jansen FE, Binsbergen E van, Braun KPJ, Verbeek NE, Lindhout D, et al. Copy number variations in patients with electrical status epilepticus in sleep. J Child Neurol. 2012;27:178–82. Referans45. Giorda R, Bonaglia MC, Beri S, Fichera M, Novara F, Magini P, et al. Complex segmental duplications mediate a recurrent dup(X)(p11.22-p11.23) associated with mental retardation, speech delay, and EEG anomalies in males and females. Am J Hum Genet. 2009;85:394–400. Referans46. Broli M, Bisulli F, Mastrangelo M, Fontana E, Fiocchi I, Zucca C, et al. Definition of the neurological phenotype associated with dup (X)(p11.22-p11.23). Epileptic Disord. 2011;13:240–51. Referans47. Nakayama T, Nabatame S, Saito Y, Nakagawa E, Shimojima K, Yamamoto T, et al. 8p deletion and 9p duplication in two children with electrical status epilepticus in sleep syndrome. Seizure. 2012;21:295–9. Referans48. Mefford HC, Yendle SC, Hsu C, Cook J, Geraghty E, McMahon JM, et al. Rare copy number variants are an important cause of epileptic encephalopathies. Ann Neurol. 2011;70:974–85. Referans49. Verhoeven WMA, Egger JIM, Feenstra I, de Leeuw N. A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild intellectual disability and epilepsy. Eur J Med Genet. 2012;55:358–61. Referans50. Conroy J, McGettigan PA, McCreary D, Shah N, Collins K, Parry-Fielder B, et al. Towards the identification of a genetic basis for Landau-Kleffner syndrome. Epilepsia. 2014;55:858–65. Referans51. Reutlinger C, Helbig I, Gawelczyk B, Subero JIM, Tönnies H, Muhle H, et al. Deletions in 16p13 including GRIN2A in patients with intellectual disability, various dysmorphic features, and seizure disorders of the rolandic region. Epilepsia. 2010;51:1870–3. Referans52. Lesca G, Rudolf G, Labalme A, Hirsch E, Arzimanoglou A, Genton P, et al. Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism. Epilepsia. 2012;53:1526–38. Referans53. Lemke JR, Lal D, Reinthaler EM, Steiner I, Nothnagel M, Alber M, et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013;45:1067–72. Referans54. Carvill GL, Regan BM, Yendle SC, O’Roak BJ, Lozovaya N, Bruneau N, et al. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nat Genet. 2013;45:1073–6. Referans55. Lesca G, Rudolf G, Bruneau N, Lozovaya N, Labalme A, Boutry-Kryza N, et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction. Nat Genet. 2013;45:1061–6. Referans56. Lesca G, Møller RS, Rudolf G, Hirsch E, Hjalgrim H, Szepetowski P. Update on the genetics of the epilepsy-aphasia spectrum and role of GRIN2A mutations. Epileptic Disord. 2019;21(Suppl 1):41–7. Referans57. Arzimanoglou A, Resnick T. All children who experience epileptic falls do not necessarily have Lennox-Gastaut syndrome... but many do. Epileptic Disord. 2011;13 (Suppl 1):S3-13. Referans58. Kaminska A, Oguni H. Lennox-Gastaut syndrome and epilepsy with myoclonic-astatic seizures. Handb Clin Neurol. 2013;111:641–52. Referans59. Mastrangelo M. Lennox-Gastaut Syndrome: A State of the Art Review. Neuropediatrics. 2017;48:143–51. Referans60. Tang S, Pal DK. Dissecting the genetic basis of myoclonic-astatic epilepsy. Epilepsia. 2012;53:1303–13. Referans61. Mullen SA, Marini C, Suls A, Mei D, Della Giustina E, Buti D, et al. Glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. Arch Neurol. 2011;68:1152–5. Referans62. Carvill GL, McMahon JM, Schneider A, Zemel M, Myers CT, Saykally J, et al. Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures. Am J Hum Genet. 2015;96:808–15. Referans63. Trivisano M, Striano P, Sartorelli J, Giordano L, Traverso M, Accorsi P, et al. CHD2 mutations are a rare cause of generalized epilepsy with myoclonic-atonic seizures. Epilepsy Behav. 2015;51:53–6.