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West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri

Yıl 2022, Cilt: 22 Sayı: 1, 30 - 37, 18.05.2022
https://doi.org/10.26650/jchild.2022.947220

Öz

Amaç: West sendromu en sık görülen süt çocukluğu epileptik ensefalopati tablosu olup, tedavisinde sıklıkla ACTH veya oral kortikosteroidler kullanılmaktadır. West sendromu tanısı alan bir grup çocukta ACTH tedavisinin etkinliğinin ve subakut-kronik dönemde kemik metabolizması ve adrenal yolak üzerine etkilerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: West sendromuyla izlenen 35 çocuk, tanı sonrası 4-68 ay arasında değişen sürelerde çalışmaya alındı. Toplam 25 hastaya sentetik ACTH tedavisi uygulandı. ACTH tedavisi alan ve almayan gruplar nöbet kontrolü, EEG bulgularındaki düzelme ve nörolojik prognoz açısından değerlendirildi. Ayrıca ACTH tedavisi alan ve almayan gruplar, kemik metabolizması değişiklikleri ve adrenal yolak işlevleri açısından karşılaştırıldı. Bulgular: West sendromu tanısıyla izlenen 35 çocuktan 31’i semptomatik (%88,6) 4’ü kriptojenik (%11,4) gruptaydı. Semptomatik gruptakilerin üçte ikisinde etyolojide yapısal beyin anomalileri (11 olgu) ve hipoksik-iskemik ensefalopati (9 olgu) saptandı. Semptomatik gruptan 22, kriptojenik gruptan 3 olguya ACTH tedavisi uygulandı. Tedavi sonrası semptomatik grupta 15 olguda tam (%68,2), 4 olguda kısmi (%18,2) nöbet kontrolü sağlanırken, kriptojenik grupta 2 olguda tam, 1 olguda kısmi nöbet kontrolü sağlandı. Semptomatik grupta ACTH ile nöbet kontrolü ve EEG bulgularında düzelme yüksek oranda (%68,2) saptanmasına karşın, nörolojik gelişimde beklenen düzelmenin gerçekleşmediği gözlendi. ACTH uygulanan ve uygulanmayan olgularda kemik metabolizması ve adrenal yolak tetkikleri arasında anlamlı fark bulunmadı, hiçbir olguda adrenal yetersizlik saptanmadı. Sonuç: West sendromunda etiyolojiden bağımsız olarak ACTH tedavisi etkindir ancak, semptomatik grupta nöbet kontrolüne karşın nörolojik gelişimde ağır gerilik devam etmiştir. ACTH tedavisi sonrası subakut-kronik dönemde kemik metabolizması ve adrenal işlev bozukluğu açısından bir risk olmadığı ortaya konmuştur.

Destekleyen Kurum

Bu araştırma herhangi bir kiş, kurum ya da kuruluş tarafından mali olarak desteklenmemiştir.

Kaynakça

  • 1. Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, et al. Infantile spasms: A U.S. consensus report. Epilepsia 2010;51(10):2175-89. google scholar
  • 2. Riikonen R. Long-term outcome of patients with West syndrome. Brain and Development 2001;23:7:683-87. google scholar
  • 3. D’Alonzo R, Rigante D, Mencaroni E, Esposito S. West syndrome: A review and guide for paediatricians. Clin Drug Investig 2018;38:113-24. google scholar
  • 4. Bistritzer J, Noyman I, Hazan G, Hershkovitz E, Haim A. Adrenal function following ACTH therapy for infantile spasms: A retrospective study. Clin Neurol Neurosurg 2020;195:105901. google scholar
  • 5. Weinstein RS. Glucocorticoid-induced osteoporosis and asteonecrosis. Endocrinol Metab Clin North Am 2012;41(3): 595611. google scholar
  • 6. Krasner AS. Glucocorticoid-Induced Adrenal Insufficiency. JAMA. 1999;282(7):671-6. google scholar
  • 7. LoCascio V, Bonucci E, Imbimbo B, Ballanti P, Adami S, Milani S, et al. Bone loss in response to long-term glucocorticoid therapy. Bone Miner 1990;8(1):39-51. google scholar
  • 8. Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004;15(4):301-10. google scholar
  • 9. Adami G, Saag KG. Glucocorticoid-induced osteoporosis: 2019 concise clinical review. Osteoporos Int 2019;30(6):1145-56. google scholar
  • 10. Osborne JP, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, et al. The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS). Epilepsia 2019;60(9):1861-9. google scholar
  • 11. Nasiri J, Kachuei M, Kermani R, Samaninobandegani Z. Neurodevelopmental outcomes of the West syndrome in pediatric patients: The first report from the Middle-East. Res Dev Disabil 2019;89:114-9. google scholar
  • 12. Singhi P, Ray M. Profile of West syndrome in North Indian children. Brain and Development 2005;27(2):135-40. google scholar
  • 13. Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2013;5(6):CD001770 google scholar
  • 14. Yilmaz S, Tekgul H, Serdaroglu G, Akcay A, Gokben S. Evaluation of ten prognostic factors affecting the outcome of West syndrome. Acta Neurol Belg 2016;116(4):519-27. google scholar
  • 15. Romero MC, Portillo EA, Lobato ML, Cabello BM, Martmez BB, Garrido MM et al. Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors. Anales de pediatria 2018;89(3):176-82. google scholar
  • 16. Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshe SL, Shinnar S. Treatment Outcomes of West Syndrome in Infants With Down Syndrome. Pediatr Neurol 2013;48(1):42-7. google scholar
  • 17. Riikonen R. Infantile Spasms: Outcome in Clinical Studies. Pediatr Neurol 2020;108:54-64. google scholar
  • 18. Demarest ST, Shellhaas RA, Gaillard WD, Keator C, Nickels KC, Hussain SA, et al. The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia 2017;58(12):2098-103. google scholar
  • 19. Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, et al. Response to Treatment in a Prospective National Infantile Spasms Cohort. Ann Neurol 2016;79(3):475-84. google scholar
  • 20. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EAS, Mullins LJ, Mullins JJ, et al. Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics 2010;40(3):158-66. google scholar
  • 21. Rausch HP, Hanefeld F, Kaufmann HJ. Medullary nephrocalcinosis and pancreatic calcifications demonstrated by ultrasound and CT in infants after treatment with ACTH. Radiology 1984;153(1):105-7. google scholar
  • 22. Miyahara H, Akiyama T, Hasegawa K, Akiyama M, Oka M, Kobayashi K, et al. Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions. Pediatr Int 2020;62(5):587-92. google scholar
  • 23. Lorente-Ramos R, Azpeitia-Armân J, Munoz-Hernândez A, Garda-Gomez JM, D^ez-Mart^nez P, Grande-Bârez M. Dual-Energy X-Ray Absorptiometry in the Diagnosis of Osteoporosis: A Practical Guide. Am J Roentgenol 2011;196(4):897-904. google scholar
  • 24. Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol 2017;69(8):1521-37. google scholar
  • 25. Eidlitz-Markus T, Kivity S, Goldberg-Stern H, Haimi-Cohen Y, Zeharia A. Effect of high-dose glucocorticosteroid treatment for infantile spasms on quantitative bone parameters later in life. J Child Neurol 2012;27(1):74-9. google scholar
  • 26. Mytinger JR, Bowden SA. Adrenal Function Testing Following Hormone Therapy for Infantile Spasms: Case Series and Review of Literature. Front Neurol 2015;8;6:259. google scholar

The Effectiveness of Acth Therapy According to Etiology in Patients with West Syndrome and Its Long-Term Effects on Bone Mineral Metabolism and Adrenal Pathway

Yıl 2022, Cilt: 22 Sayı: 1, 30 - 37, 18.05.2022
https://doi.org/10.26650/jchild.2022.947220

Öz

Objective: West syndrome is the most common infantile epileptic encephalopathy, and ACTH or oral corticosteroids are frequently used in its treatment. The aim of this study was to evaluate the efficacy of ACTH therapy and its effects on bone metabolism and adrenal pathway in the subacute-chronic period in a group of children diagnosed with West syndrome. Materials and Methods: Thirty-five children followed up with West syndrome were included in the study for a period ranging from 4 to 68 months after diagnosis. A total of 25 patients were treated with synthetic ACTH. The groups that received and did not receive ACTH treatment were evaluated in terms of seizure control, improvement in EEG findings and neurological prognosis. In addition, the groups that received and did not receive ACTH therapy were compared in terms of bone metabolism changes and adrenal pathway functions. Results: Of the 35 children followed up with the diagnosis of West syndrome, 31 (88.6%) were in the symptomatic group and 4 (11.4%) were in the cryptogenic group. Structural brain anomalies (11 cases) and hypoxic-ischemic encephalopathy (9 cases) were found in the etiology in two-thirds of those in the symptomatic group. ACTH treatment was applied to 22 patients from the symptomatic group and 3 patients from the cryptogenic group. After treatment, complete seizure control was achieved in 15 cases (68.2%) and partial seizure control in 4 cases (18.2%) in the symptomatic group, while complete seizure control was achieved in 2 cases and partial seizure control in 1 case in the cryptogenic group. Although a high rate of improvement in seizure control and EEG findings with ACTH was detected in the symptomatic group (68.2%), it was observed that the expected improvement in neurological development did not occur. There was no significant difference between bone metabolism and adrenal pathway examinations in cases with and without ACTH, and adrenal insufficiency was not detected in any of the cases. Conclusion: ACTH treatment was effective for West syndrome regardless of the etiology, but severe retardation in neurological development continued despite seizure control in the symptomatic group. It was demonstrated that there is no risk in terms of bone metabolism and adrenal dysfunction in the subacute-chronic period after ACTH treatment.

Kaynakça

  • 1. Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, et al. Infantile spasms: A U.S. consensus report. Epilepsia 2010;51(10):2175-89. google scholar
  • 2. Riikonen R. Long-term outcome of patients with West syndrome. Brain and Development 2001;23:7:683-87. google scholar
  • 3. D’Alonzo R, Rigante D, Mencaroni E, Esposito S. West syndrome: A review and guide for paediatricians. Clin Drug Investig 2018;38:113-24. google scholar
  • 4. Bistritzer J, Noyman I, Hazan G, Hershkovitz E, Haim A. Adrenal function following ACTH therapy for infantile spasms: A retrospective study. Clin Neurol Neurosurg 2020;195:105901. google scholar
  • 5. Weinstein RS. Glucocorticoid-induced osteoporosis and asteonecrosis. Endocrinol Metab Clin North Am 2012;41(3): 595611. google scholar
  • 6. Krasner AS. Glucocorticoid-Induced Adrenal Insufficiency. JAMA. 1999;282(7):671-6. google scholar
  • 7. LoCascio V, Bonucci E, Imbimbo B, Ballanti P, Adami S, Milani S, et al. Bone loss in response to long-term glucocorticoid therapy. Bone Miner 1990;8(1):39-51. google scholar
  • 8. Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004;15(4):301-10. google scholar
  • 9. Adami G, Saag KG. Glucocorticoid-induced osteoporosis: 2019 concise clinical review. Osteoporos Int 2019;30(6):1145-56. google scholar
  • 10. Osborne JP, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, et al. The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS). Epilepsia 2019;60(9):1861-9. google scholar
  • 11. Nasiri J, Kachuei M, Kermani R, Samaninobandegani Z. Neurodevelopmental outcomes of the West syndrome in pediatric patients: The first report from the Middle-East. Res Dev Disabil 2019;89:114-9. google scholar
  • 12. Singhi P, Ray M. Profile of West syndrome in North Indian children. Brain and Development 2005;27(2):135-40. google scholar
  • 13. Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2013;5(6):CD001770 google scholar
  • 14. Yilmaz S, Tekgul H, Serdaroglu G, Akcay A, Gokben S. Evaluation of ten prognostic factors affecting the outcome of West syndrome. Acta Neurol Belg 2016;116(4):519-27. google scholar
  • 15. Romero MC, Portillo EA, Lobato ML, Cabello BM, Martmez BB, Garrido MM et al. Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors. Anales de pediatria 2018;89(3):176-82. google scholar
  • 16. Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshe SL, Shinnar S. Treatment Outcomes of West Syndrome in Infants With Down Syndrome. Pediatr Neurol 2013;48(1):42-7. google scholar
  • 17. Riikonen R. Infantile Spasms: Outcome in Clinical Studies. Pediatr Neurol 2020;108:54-64. google scholar
  • 18. Demarest ST, Shellhaas RA, Gaillard WD, Keator C, Nickels KC, Hussain SA, et al. The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium. Epilepsia 2017;58(12):2098-103. google scholar
  • 19. Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, et al. Response to Treatment in a Prospective National Infantile Spasms Cohort. Ann Neurol 2016;79(3):475-84. google scholar
  • 20. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EAS, Mullins LJ, Mullins JJ, et al. Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics 2010;40(3):158-66. google scholar
  • 21. Rausch HP, Hanefeld F, Kaufmann HJ. Medullary nephrocalcinosis and pancreatic calcifications demonstrated by ultrasound and CT in infants after treatment with ACTH. Radiology 1984;153(1):105-7. google scholar
  • 22. Miyahara H, Akiyama T, Hasegawa K, Akiyama M, Oka M, Kobayashi K, et al. Laboratory changes during adrenocorticotropic hormone therapy associated with renal calcified lesions. Pediatr Int 2020;62(5):587-92. google scholar
  • 23. Lorente-Ramos R, Azpeitia-Armân J, Munoz-Hernândez A, Garda-Gomez JM, D^ez-Mart^nez P, Grande-Bârez M. Dual-Energy X-Ray Absorptiometry in the Diagnosis of Osteoporosis: A Practical Guide. Am J Roentgenol 2011;196(4):897-904. google scholar
  • 24. Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol 2017;69(8):1521-37. google scholar
  • 25. Eidlitz-Markus T, Kivity S, Goldberg-Stern H, Haimi-Cohen Y, Zeharia A. Effect of high-dose glucocorticosteroid treatment for infantile spasms on quantitative bone parameters later in life. J Child Neurol 2012;27(1):74-9. google scholar
  • 26. Mytinger JR, Bowden SA. Adrenal Function Testing Following Hormone Therapy for Infantile Spasms: Case Series and Review of Literature. Front Neurol 2015;8;6:259. google scholar
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Çocuk Sağlığı ve Hastalıkları
Bölüm Araştırma Makaleleri
Yazarlar

Mesut Güngör 0000-0003-1594-0006

Mine Düzgöl Bu kişi benim 0000-0002-3190-2950

Hülya Maraş Genç 0000-0001-8869-0277

Emek Uyur Yalçın 0000-0001-6071-6375

Filiz Mine Çizmecioğlu Jones Bu kişi benim 0000-0001-7340-6368

Bülent Kara 0000-0003-3780-6596

Yayımlanma Tarihi 18 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 22 Sayı: 1

Kaynak Göster

APA Güngör, M., Düzgöl, M., Maraş Genç, H., Uyur Yalçın, E., vd. (2022). West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri. Journal of Child, 22(1), 30-37. https://doi.org/10.26650/jchild.2022.947220
AMA Güngör M, Düzgöl M, Maraş Genç H, Uyur Yalçın E, Çizmecioğlu Jones FM, Kara B. West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri. Journal of Child. Mayıs 2022;22(1):30-37. doi:10.26650/jchild.2022.947220
Chicago Güngör, Mesut, Mine Düzgöl, Hülya Maraş Genç, Emek Uyur Yalçın, Filiz Mine Çizmecioğlu Jones, ve Bülent Kara. “West Sendromlu Olgularda Acth Tedavisinin Etkinliği Ve Kemik Mineral Metabolizması Ve Adrenal Yolak Üzerine Uzun Dönem Etkileri”. Journal of Child 22, sy. 1 (Mayıs 2022): 30-37. https://doi.org/10.26650/jchild.2022.947220.
EndNote Güngör M, Düzgöl M, Maraş Genç H, Uyur Yalçın E, Çizmecioğlu Jones FM, Kara B (01 Mayıs 2022) West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri. Journal of Child 22 1 30–37.
IEEE M. Güngör, M. Düzgöl, H. Maraş Genç, E. Uyur Yalçın, F. M. Çizmecioğlu Jones, ve B. Kara, “West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri”, Journal of Child, c. 22, sy. 1, ss. 30–37, 2022, doi: 10.26650/jchild.2022.947220.
ISNAD Güngör, Mesut vd. “West Sendromlu Olgularda Acth Tedavisinin Etkinliği Ve Kemik Mineral Metabolizması Ve Adrenal Yolak Üzerine Uzun Dönem Etkileri”. Journal of Child 22/1 (Mayıs 2022), 30-37. https://doi.org/10.26650/jchild.2022.947220.
JAMA Güngör M, Düzgöl M, Maraş Genç H, Uyur Yalçın E, Çizmecioğlu Jones FM, Kara B. West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri. Journal of Child. 2022;22:30–37.
MLA Güngör, Mesut vd. “West Sendromlu Olgularda Acth Tedavisinin Etkinliği Ve Kemik Mineral Metabolizması Ve Adrenal Yolak Üzerine Uzun Dönem Etkileri”. Journal of Child, c. 22, sy. 1, 2022, ss. 30-37, doi:10.26650/jchild.2022.947220.
Vancouver Güngör M, Düzgöl M, Maraş Genç H, Uyur Yalçın E, Çizmecioğlu Jones FM, Kara B. West Sendromlu Olgularda Acth Tedavisinin Etkinliği ve Kemik Mineral Metabolizması ve Adrenal Yolak Üzerine Uzun Dönem Etkileri. Journal of Child. 2022;22(1):30-7.