Tuberoskleroz kompleks tanılı çocuk hastalarda epileptogenezis
Küçük Resim Yok
Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Tuberoskleroz kompleksi (TSK), tedaviye dirençli epilepsiye ve gelişimsel problemlere neden olan genetik, multisistemik bir hastalıktır. Hastaların çoğunda nöbetler erken yaşta başlayabilir ve dirençli seyredebilmektedir. Tedavi edilmeyen erken başlangıçlı epilepsi, otizm ve entelektüel yetersizlik de dahil olmak üzere nörogelişimsel gerilik riski ile ilişkilidir. Bu geriye dönük çalışmada TSK tanısıyla takip edilen hastalarımızın klinik, laboratuvar ve görüntüleme bulgularını, uygulanan tedavi modalitelerini gözden geçirerek epilepsinin seyrini etkileyebilecek klinik faktörleri belirlemek amaçlanmaktadır. GEREÇ ve YÖNTEM Çalışmada Ege Üniversitesi Tıp Fakültesi Çocuk Nörolojisi Bilim Dalı'nda TSK tanısı ile takip edilen 55 hastanın demografik verileri, laboratuvar bulguları, klinik ve psikiyatrik bulguları retrospektif olarak değerlendirildi. Hastaların nöbet özellikleri, seyri ve uygulanan farmakolojik (antinöbet ilaçlar, mTOR inhibitörleri) ve nonfarmakolojik (ketojenik diyet, vagal sinir stimülasyonu, cerrahi) tedaviler ve elde edilen tedavi yanıtları değerlendirildi. Dirençli epilepsi gelişimi ve nöbet kontrolu ile nöbet başlangıç yaşı, nöbet tipi, otizm ve DEHB varlığı, bilişsel düzeyleri arasındaki ilişki incelendi. Prognoza etki eden faktörler saptanarak, iyi ve kötü prognostik faktörler saptandı. BULGULAR (1) Hastaların yaş ortalaması 129,3 ±74,6 ay olup, 28'i (%50,9) erkek, 27'si (%49,1) kız idi. Tanı yaşı ortalaması 30±43,4ay olarak saptandı. Nöbet %70,9 oranı ile en sık başvuru yakınmasıydı. (2) Hastaların %89,1 epilepsi nedeniyle takip edilmekteydi. İlk nöbet geçirme yaşı 20,7± 38,6 (10 gün-192 ay) ay idi. İlk başvuru esnasındaki nöbet tipleri incelendiğinde, 35 (%71,4) hastada fokal nöbet, 14 (%28,6) hastada infantil spazm tipi nöbet olduğu görüldü. (3) Genetik inceleme yapılan 18 hastanın 5'inde (%27,7) TSK 1 mutasyonu, 9'unda (%50) TSK 2 mutasyonu saptandı. TSK1 mutasyonu pozitif saptanan hastaların %80'inde, TSK2 mutasyonu saptanan hastaların %88,9'unda nöbet görüldü. (4) Antinöbet ilaç olarak en sık kullanılan ajanlar; vigabatrin (%75.5), valproik asit (%63,3), levetirasetam(%49) idi. Etkinlik açısından değerlendirildiğinde; vigabatrin ile 6 (%12,2) hastada, valproik asit ile 4 (% 8,2) hastada, okskarbazepin ile 2 (%4,1) hastada ve fenobarbital, karbamazepin ve levetirasetam ile birer (%2) hastada nöbet kontrolü sağlandığı görüldü. (5) Epilepsi ile takip edilen hastaların 23/49'u (%46,9) izlemde dirençli epilepsi tanısı aldı. Dirençli epilepsi tanılı hastaların 6/23'ünde (%42,8) mTOR inhibitörü, 2/23'ünde (%8,6) VNS ve 4/23'ünde (%17,3) ketojenik diyet uygulandı. (6) mTOR inhibitörü everolimus kullanan hastaların %33,3'ünde (2/6) tam yanıt, %50'sinde (3/6) kısmi yanıt elde edilirken, bir hastada nöbet sıklığında değişiklik olmadı. (7) Psikometrik değerlendirme ile 35 (%63,6) hastada mental düzeyde etkilenim, 9 (%16,4) hastada otizm, 26 hastada (%47,3) DEHB saptandı. Zeka düzeyinde ağır etkilenimi olan hastaların nöbetinin bir yaşından önce başladığı saptandı. İnfantil spazm tipi nöbetleri olan hastalarda otistik spektrum bozukluğunun daha sık olduğu görüldü SONUÇ Epilepsinin erken tanı ve tedavisi, tuberoskleroz kompleksi tanılı hastaların zeka düzeyindeki etkilenimlerin önlenebilmesi açısından önemlidir. Dirençli epilepsi gelişen hastalarda, antinöbet ilaçların yanısıra antiepileptojenik etkinlik gösteren m TOR inhibitörleri umut verici moleküler tedavi görülmektedir.
Introductıon and Aim: Tuberous sclerosis complex (TSC) is a genetic, multisystemic disease that causes severe and drug-resistant epilepsy. In most of the cases, the seizures start at an early age and can be resistant. Untreated early-onset epilepsy is associated with an increased risk of neurodevelopmental retardation, including autism and intellectual disability. In this study, it is aimed to determine the factors that may affect the course of epilepsy, to evaluate the seizure profile, treatment process and results by retrospectively reviewing the clinical, laboratory and imaging findings and treatment modalities of our cases followed up with the diagnosis of TSC. Materıals and Methods: In the study, demographic data, laboratory findings, clinical and psychiatric findings of 55 cases followed up with the diagnosis of TSC at the Department of Pediatric Neurology at Ege University Faculty of Medicine were evaluated retrospectively. Seizure characteristics, course, pharmacological (anti-seizure drugs, mTOR inhibitors) and non-pharmacological (ketogenic diet, vagal nerve stimulation, epilepsy surgery) treatments and treatment responses of the cases were evaluated. The relationship between the development of resistant epilepsy, seizure control and seizure onset age, seizure type, presence of autism and attention deficit hyperactivity disorder (ADHD), and cognitive levels were investigated. Results: (1) The mean age of the cases was 129,3 ± 74,6 months. The study group consisted of 28 (50,9%) boys and 27 (49,1%) girls. The mean age at diagnosis was 30±43,4 months. Seizure was the most common complaint of admission with a rate of 70,9%. (2) Epilepsy was defined in 89,1% of the cases. Age at seizure onset was 20,7±38,6 (10 days-1992 months) months. Analysis of the seizure types at the first admission indicated 35 (71,4%) cases had focal motor seizures and 14 (28,6%) cases had infantile spasms. (3) Among the cases that genetic analysis was performed, TSC 1 mutation was found in 5 (9,1%) of 18 cases, and TSC 2 mutation was found in 9 (16,4%). Seizures were present in 80% of cases with TSC 1 mutation and in 88,9% of cases with TSC 2 mutation. (4) The most commonly used agents as anti-seizure drugs were: vigabatrin (75,5%), valproic acid (63,3%), levetiracetam (49%). In terms of effectiveness, seizure control was provided in six (12,2%) cases with vigabatrin, in four (8,2%) cases with valproic acid , in two (4,1%) cases with oxcarbazepine, and in three single one (2%) cases with one of phenobarbital, carbamazepine and levetirasetam. (5) Twenty-three (46,9%) of 49 patients followed up with epilepsy were diagnosed with resistant epilepsy. Of 23 cases diagnosed with resistant epilepsy; mTOR inhibitor was used in five (21,7%), vagus nerve stimülation (VNS) in two (8,6%) and ketogenic diet in four (17,3%) patients as add-on therapy. (6) Of six patients using the mTOR inhibitor everolimus; partial response was obtained in 33,3% (2/6) and seizure-freedom in 50% (3/6) patient. One patient was considered unresponsive to treatment. (7) Psychometric evaluation revealed intellectual disability in 35 (63,6%) cases, autism in 9 (16,4%), and ADHD in 26 (47,3%) cases. It was determined that seizures started before the age of one in all cases with severe intellectual disability. Autistic spectrum disorder was found more common in cases with infantile spasm-type seizures. Conclusıons: Early diagnosis and treatment of epilepsy is important in terms of preventing the negative impact on the intelligence level of patients with tuberous sclerosis complex. In patients with resistant epilepsy, mTOR inhibitors are a promising molecular therapy option, which have antiepileptogenic activity, in addition to anti-seizure drugs.
Introductıon and Aim: Tuberous sclerosis complex (TSC) is a genetic, multisystemic disease that causes severe and drug-resistant epilepsy. In most of the cases, the seizures start at an early age and can be resistant. Untreated early-onset epilepsy is associated with an increased risk of neurodevelopmental retardation, including autism and intellectual disability. In this study, it is aimed to determine the factors that may affect the course of epilepsy, to evaluate the seizure profile, treatment process and results by retrospectively reviewing the clinical, laboratory and imaging findings and treatment modalities of our cases followed up with the diagnosis of TSC. Materıals and Methods: In the study, demographic data, laboratory findings, clinical and psychiatric findings of 55 cases followed up with the diagnosis of TSC at the Department of Pediatric Neurology at Ege University Faculty of Medicine were evaluated retrospectively. Seizure characteristics, course, pharmacological (anti-seizure drugs, mTOR inhibitors) and non-pharmacological (ketogenic diet, vagal nerve stimulation, epilepsy surgery) treatments and treatment responses of the cases were evaluated. The relationship between the development of resistant epilepsy, seizure control and seizure onset age, seizure type, presence of autism and attention deficit hyperactivity disorder (ADHD), and cognitive levels were investigated. Results: (1) The mean age of the cases was 129,3 ± 74,6 months. The study group consisted of 28 (50,9%) boys and 27 (49,1%) girls. The mean age at diagnosis was 30±43,4 months. Seizure was the most common complaint of admission with a rate of 70,9%. (2) Epilepsy was defined in 89,1% of the cases. Age at seizure onset was 20,7±38,6 (10 days-1992 months) months. Analysis of the seizure types at the first admission indicated 35 (71,4%) cases had focal motor seizures and 14 (28,6%) cases had infantile spasms. (3) Among the cases that genetic analysis was performed, TSC 1 mutation was found in 5 (9,1%) of 18 cases, and TSC 2 mutation was found in 9 (16,4%). Seizures were present in 80% of cases with TSC 1 mutation and in 88,9% of cases with TSC 2 mutation. (4) The most commonly used agents as anti-seizure drugs were: vigabatrin (75,5%), valproic acid (63,3%), levetiracetam (49%). In terms of effectiveness, seizure control was provided in six (12,2%) cases with vigabatrin, in four (8,2%) cases with valproic acid , in two (4,1%) cases with oxcarbazepine, and in three single one (2%) cases with one of phenobarbital, carbamazepine and levetirasetam. (5) Twenty-three (46,9%) of 49 patients followed up with epilepsy were diagnosed with resistant epilepsy. Of 23 cases diagnosed with resistant epilepsy; mTOR inhibitor was used in five (21,7%), vagus nerve stimülation (VNS) in two (8,6%) and ketogenic diet in four (17,3%) patients as add-on therapy. (6) Of six patients using the mTOR inhibitor everolimus; partial response was obtained in 33,3% (2/6) and seizure-freedom in 50% (3/6) patient. One patient was considered unresponsive to treatment. (7) Psychometric evaluation revealed intellectual disability in 35 (63,6%) cases, autism in 9 (16,4%), and ADHD in 26 (47,3%) cases. It was determined that seizures started before the age of one in all cases with severe intellectual disability. Autistic spectrum disorder was found more common in cases with infantile spasm-type seizures. Conclusıons: Early diagnosis and treatment of epilepsy is important in terms of preventing the negative impact on the intelligence level of patients with tuberous sclerosis complex. In patients with resistant epilepsy, mTOR inhibitors are a promising molecular therapy option, which have antiepileptogenic activity, in addition to anti-seizure drugs.
Açıklama
Anahtar Kelimeler
Tuberoskleroz Kompleksi, Epilepsi, Anti Nöbet İlaç, mTOR İnhibitörü, Zihinsel Yetersizlik, Tuberous Sclerosis Complex, Epilepsy, Antiseizure Drugs, mTOR Inhibitor, Intellectual Disability
