譚李紅,
Email: Tanlihong118@163.com
嬰兒痙攣是嬰兒最常見的癲癇性腦病之一，早期診斷和治療可以改善患兒神經發育的預后。促腎上腺皮質激素（Adrenocorticotropic hormone，ACTH）及氨己烯酸是目前臨床首選的一線治療方案。此外還有一些具有動物實驗或臨床研究價值但尚未大范圍用于臨床治療的新型藥物，如雷帕霉素、氟桂利嗪、非氨酯、褪黑素及大麻二酚等，為這一難治性癲癇提供了新的治療見解。本綜述闡述了嬰兒痙攣新型藥物治療的最新進展及實際應用。
Citation： 劉力, 譚李紅. 嬰兒痙攣新型藥物治療的研究進展. Journal of Epilepsy, 2022, 8(5): 436-441. doi: 10.7507/2096-0247.202201005 Copy
Copyright ? the editorial department of Journal of Epilepsy of West China Medical Publisher. All rights reserved
| 1. | Go CY, Mackay MT, Weiss s K, et al. Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology, 2012, 78(24): 1974-1980. |
| 2. | Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol, 1991, 6(4): 355-364. |
| 3. | Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U. S. consensus report. Epilepsia, 2010, 51(10): 2175-2189. |
| 4. | Osborne JP, Lux AL, Edwards SW, et al. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia, 2010, 51(10): 2168-2174. |
| 5. | Paciorkowski AR, Thio LL, Dobyns WB. Genetic and biologic classification of infantile spasms. Pediatr Neurol, 2011, 45(6): 355-367. |
| 6. | Sumanasena SP, Wanigasinghe J, Arambepola C, et al. Developmental profile at initial presentation in children with infantile spasms. Dev Med Child Neurol, 2019, 61(11): 1295-1301. |
| 7. | Kelley SA, Knupp KG. Infantile spasms-have we made progress? Curr Neurol Neurosci Rep, 2018, 18(5): 27. |
| 8. | Riikonen R. Combination therapy for treatment of infantile spasms. The Lancet Neurology, 2017, 16(1): 19-20. |
| 9. | Mao L, Kessi M, Peng P, et al. The patterns of response of 11 regimens for infantile spasms. Sci Rep, 2020, 10(1): 11509. |
| 10. | Lux A, Edwards S, Hancock E, et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet (London, England), 2004, 364(9447): 1773-1778. |
| 11. | Lux AL, Edwards SW, Hancock E, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol, 2005, 4(11): 712-717. |
| 12. | O'Callaghan F, Edwards S, Alber F, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. The Lancet Neurology, 2017, 16(1): 33-42. |
| 13. | Sasaki M, Takenouchi T, Sakaguchi Y, et al. Decisive evidence of direct effect of ACTH treatment in West syndrome: a case report. Seizure, 2021, 91: 49-51. |
| 14. | 劉占利. 促腎上腺皮質激素治療嬰兒痙攣癥作用機制研究進展. 國際兒科學雜志, 2010, 37(4): 413-415. |
| 15. | Knupp k G, Coryell J, Nickels KC, et al. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol, 2016, 79(3): 475-484. |
| 16. | Knupp KG, Leister E, Coryell J, et al. Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia, 2016, 57(11): 1834-1842. |
| 17. | Hara K, Watanabe K, Miyazaki S, et al. Apparent brain atrophy and subdural hematoma following ACTH therapy. Brain Dev, 1981, 3(1): 45-49. |
| 18. | Hussain SA. Treatment of infantile spasms . Epilepsia Open, 2018, 3(Suppl Suppl 2): 143-154. |
| 19. | Roach ES, Kwiatkowski DJ. Seizures in tuberous sclerosis complex: hitting the target. Lancet, 2016, 388(10056): 2062-2064. |
| 20. | Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55(4): 475-482. |
| 21. | Overwater IE, Bindelsde HK, Rietman AB, et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia, 2015, 56(8): 1239-1245. |
| 22. | 張利利, 周浩, 路通, 等. 25例結節性硬化患兒氨己烯酸治療效果分析. 癲癇雜志, 2016, 2(2): 109-113. |
| 23. | Riikonen R. Long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia, 2015, 56(5): 807-809. |
| 24. | Djuric M, Kravljanac R, Tadic B, et al. In response to: long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia, 2015, 56(5): 809-810. |
| 25. | Hussain SA, Tsao J, Li M, et al. Risk of vigabatrin‐associated brain abnormalities on MRI in the treatment of infantile spasms is dose‐dependent. Epilepsia, 2017, 58(4): 701-709. |
| 26. | Vignot S, Faivre S, Aguirre D, et al. mTOR-targeted therapy of cancer with rapamycin derivatives. Annals of oncology, 2005, 16(4): 525-537. |
| 27. | Salussolia CL, Klonowska K, Kwiatkowski DJ, et al. Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex. Annu Rev Genomics Hum Genet, 2019, 20: 217-240. |
| 28. | Blair J, Hockemeyer D, Bateup H. Genetically engineered human cortical spheroid models of tuberous sclerosis. Nature medicine, 2018, 24(10): 1568-1578. |
| 29. | Prentzell M, Rehbein U, Cadena SM, et al. G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 2021, 184(3): 655-674. |
| 30. | 王楊陽. mTOR抑制劑西羅莫司治療兒童結節性硬化癥相關癲癇的療效及安全性評估. 中國人民解放軍醫學院, 博士學位論文, 2019: 14-68. |
| 31. | Raffo E, Coppola A, Ono T, et al. A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis, 2011, 43(2): 322-329. |
| 32. | Akman O, Briggs SW, Mowrey WB, et al. Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions. Epilepsia, 2021, 62(8): 1985-1999. |
| 33. | Samueli S, Dressler A, Gr?ppel G, et al. Everolimus in infants with tuberous sclerosis complex-related West syndrome: first results from a single-center prospective observational study. Epilepsia, 2018, 59(9): e142-e146. |
| 34. | Bitton J, Sauerwein H, Weiss S, et al. A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms. Epilepsia, 2012, 53(9): 1570-1576. |
| 35. | Stafstrom CE, Arnason BG, Baram TZ, et al. Treatment of infantile spasms: emerging insights from clinical and basic science perspectives. J Child Neurol, 2011, 26(11): 1411-1421. |
| 36. | Hasan M, Pulman J, Marson A. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. The Cochrane Database of Systematic Reviews, 2013, 17(3): CD002750. |
| 37. | Bitton JY, Desnous B, Sauerwein HC, et al. Cognitive outcome in children with infantile spasms using a standardized treatment protocol: a five-year longitudinal study. Seizure, 2021, 89: 73-80. |
| 38. | 王艷艷. 天麻素注射液聯合卡馬西平、氟桂利嗪治療癲癇合并偏頭痛患者的療效評價. 首都食品與醫藥, 2020, 27(11): 97. |
| 39. | Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors. Annals of neurology, 1994, 35(2): 229-234. |
| 40. | Pellock JM, Faught E, Leppik IE, et al. Felbamate: consensus of current clinical experience. Epilepsy Res, 2006, 71(2-3): 89-101. |
| 41. | John MP, Douglas RN, Raman S, et al. Pellock's pediatric epilepsy: diagnosis and therapy (Fourth edition). Narnia, 2017, 81(3): 21-65. |
| 42. | Cilio MR, Kartashov AI, Vigevano F. The long-term use of felbamate in children with severe refractory epilepsy. Epilepsy Research, 2001, 47(1): 65-72. |
| 43. | Zupanc ML, Roell WR, Schwabe MS, et al. Efficacy of felbamate in the treatment of intractable pediatric epilepsy. Pediatr Neurol, 2010, 42(6): 396-403. |
| 44. | Hurst DL. The use of felbamate to treat infantile spasms. Journal of Child Neurology, 1995, 10(2): 421-426. |
| 45. | Dozières PB, Nasser H, Bellavoine V, et al. Felbamate for infantile spasms syndrome resistant to first‐line treatments. Developmental Medicine & Child Neurology, 2020, 62(5): 854-859. |
| 46. | Grosso S, Cordelli DM, Coppola G, et al. Efficacy and safety of felbamate in children under 4 years of age: a retrospective chart review. Eur J Neurol, 2008, 15(9): 940-946. |
| 47. | Victor B. Clinical pharmacology and mechanism of action of zonisamide. Clinical neuropharmacology, 2007, 30(4): 611-617. |
| 48. | Suzuki Y, Imai K, Toribe Y, et al. Long-term response to zonisamide in patients with West syndrome. Neurology, 2002, 58(10): 1556-1559. |
| 49. | Yum MS, Ko TS. Zonisamide in West syndrome: an open label study. Epileptic Disord, 2009, 11(4): 339-344. |
| 50. | Angappan D, Sahu JK, Malhi P, et al. Safety, tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome. Eur J Paediatr Neurol, 2019, 23(1): 136-142. |
| 51. | Rajaraman RR, Lay J, Alayari A, et al. Prevention of infantile spasms relapse: Zonisamide and topiramate provide no benefit. Epilepsia, 2016, 57(8): 1221-1226. |
| 52. | Hussain SA, Navarro M, Heesch J, et al. Limited efficacy of zonisamide in the treatment of refractory infantile spasms. Epilepsia Open, 2020, 5(1): 121-126. |
| 53. | 毛振沙. 唑尼沙胺添加治療兒童難治性癲癇的短期療效及安全性分析. 重慶醫科大學, 碩士學位論文, 2015: 7-24. |
| 54. | Shigeru Y, Hirokazu O, Keisuke Y, et al. Zonisamide for West syndrome: a comparison of clinical responses among different titration rate. Brain & development, 2005, 27(4): 701-704. |
| 55. | 萬林. 嬰兒痙攣癥褪黑素及相關激素與晝夜節律因子表達水平的研究. 中國人民解放軍醫學院, 碩士學位論文, 2019: 7-45. |
| 56. | Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron‐induced epileptic discharges in rats by suppressing peroxidation. Epilepsia, 1998, 39(3): 625-629. |
| 57. | Peled N, Shorer Z, Peled E, et al. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia, 2001, 42(9): 1401-1406. |
| 58. | Lin W, Guang Y, Yulin S, et al. Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis. Neuroscience letters, 2021, 748(1): 68-73. |
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| 67. | 林岷濤, 高慧, 慕潔. 大麻二酚在兒童和成人耐藥性癲癇的長期安全性和治療效果評價: 基于擴大受試試驗的結果. 癲癇雜志, 2019, 5(6): 475-481. |
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- 1. Go CY, Mackay MT, Weiss s K, et al. Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology, 2012, 78(24): 1974-1980.
- 2. Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol, 1991, 6(4): 355-364.
- 3. Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U. S. consensus report. Epilepsia, 2010, 51(10): 2175-2189.
- 4. Osborne JP, Lux AL, Edwards SW, et al. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia, 2010, 51(10): 2168-2174.
- 5. Paciorkowski AR, Thio LL, Dobyns WB. Genetic and biologic classification of infantile spasms. Pediatr Neurol, 2011, 45(6): 355-367.
- 6. Sumanasena SP, Wanigasinghe J, Arambepola C, et al. Developmental profile at initial presentation in children with infantile spasms. Dev Med Child Neurol, 2019, 61(11): 1295-1301.
- 7. Kelley SA, Knupp KG. Infantile spasms-have we made progress? Curr Neurol Neurosci Rep, 2018, 18(5): 27.
- 8. Riikonen R. Combination therapy for treatment of infantile spasms. The Lancet Neurology, 2017, 16(1): 19-20.
- 9. Mao L, Kessi M, Peng P, et al. The patterns of response of 11 regimens for infantile spasms. Sci Rep, 2020, 10(1): 11509.
- 10. Lux A, Edwards S, Hancock E, et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet (London, England), 2004, 364(9447): 1773-1778.
- 11. Lux AL, Edwards SW, Hancock E, et al. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol, 2005, 4(11): 712-717.
- 12. O'Callaghan F, Edwards S, Alber F, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. The Lancet Neurology, 2017, 16(1): 33-42.
- 13. Sasaki M, Takenouchi T, Sakaguchi Y, et al. Decisive evidence of direct effect of ACTH treatment in West syndrome: a case report. Seizure, 2021, 91: 49-51.
- 14. 劉占利. 促腎上腺皮質激素治療嬰兒痙攣癥作用機制研究進展. 國際兒科學雜志, 2010, 37(4): 413-415.
- 15. Knupp k G, Coryell J, Nickels KC, et al. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol, 2016, 79(3): 475-484.
- 16. Knupp KG, Leister E, Coryell J, et al. Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia, 2016, 57(11): 1834-1842.
- 17. Hara K, Watanabe K, Miyazaki S, et al. Apparent brain atrophy and subdural hematoma following ACTH therapy. Brain Dev, 1981, 3(1): 45-49.
- 18. Hussain SA. Treatment of infantile spasms . Epilepsia Open, 2018, 3(Suppl Suppl 2): 143-154.
- 19. Roach ES, Kwiatkowski DJ. Seizures in tuberous sclerosis complex: hitting the target. Lancet, 2016, 388(10056): 2062-2064.
- 20. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia, 2014, 55(4): 475-482.
- 21. Overwater IE, Bindelsde HK, Rietman AB, et al. Epilepsy in children with tuberous sclerosis complex: chance of remission and response to antiepileptic drugs. Epilepsia, 2015, 56(8): 1239-1245.
- 22. 張利利, 周浩, 路通, 等. 25例結節性硬化患兒氨己烯酸治療效果分析. 癲癇雜志, 2016, 2(2): 109-113.
- 23. Riikonen R. Long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia, 2015, 56(5): 807-809.
- 24. Djuric M, Kravljanac R, Tadic B, et al. In response to: long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia, 2015, 56(5): 809-810.
- 25. Hussain SA, Tsao J, Li M, et al. Risk of vigabatrin‐associated brain abnormalities on MRI in the treatment of infantile spasms is dose‐dependent. Epilepsia, 2017, 58(4): 701-709.
- 26. Vignot S, Faivre S, Aguirre D, et al. mTOR-targeted therapy of cancer with rapamycin derivatives. Annals of oncology, 2005, 16(4): 525-537.
- 27. Salussolia CL, Klonowska K, Kwiatkowski DJ, et al. Genetic etiologies, diagnosis, and treatment of tuberous sclerosis complex. Annu Rev Genomics Hum Genet, 2019, 20: 217-240.
- 28. Blair J, Hockemeyer D, Bateup H. Genetically engineered human cortical spheroid models of tuberous sclerosis. Nature medicine, 2018, 24(10): 1568-1578.
- 29. Prentzell M, Rehbein U, Cadena SM, et al. G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell, 2021, 184(3): 655-674.
- 30. 王楊陽. mTOR抑制劑西羅莫司治療兒童結節性硬化癥相關癲癇的療效及安全性評估. 中國人民解放軍醫學院, 博士學位論文, 2019: 14-68.
- 31. Raffo E, Coppola A, Ono T, et al. A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis, 2011, 43(2): 322-329.
- 32. Akman O, Briggs SW, Mowrey WB, et al. Antiepileptogenic effects of rapamycin in a model of infantile spasms due to structural lesions. Epilepsia, 2021, 62(8): 1985-1999.
- 33. Samueli S, Dressler A, Gr?ppel G, et al. Everolimus in infants with tuberous sclerosis complex-related West syndrome: first results from a single-center prospective observational study. Epilepsia, 2018, 59(9): e142-e146.
- 34. Bitton J, Sauerwein H, Weiss S, et al. A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms. Epilepsia, 2012, 53(9): 1570-1576.
- 35. Stafstrom CE, Arnason BG, Baram TZ, et al. Treatment of infantile spasms: emerging insights from clinical and basic science perspectives. J Child Neurol, 2011, 26(11): 1411-1421.
- 36. Hasan M, Pulman J, Marson A. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. The Cochrane Database of Systematic Reviews, 2013, 17(3): CD002750.
- 37. Bitton JY, Desnous B, Sauerwein HC, et al. Cognitive outcome in children with infantile spasms using a standardized treatment protocol: a five-year longitudinal study. Seizure, 2021, 89: 73-80.
- 38. 王艷艷. 天麻素注射液聯合卡馬西平、氟桂利嗪治療癲癇合并偏頭痛患者的療效評價. 首都食品與醫藥, 2020, 27(11): 97.
- 39. Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors. Annals of neurology, 1994, 35(2): 229-234.
- 40. Pellock JM, Faught E, Leppik IE, et al. Felbamate: consensus of current clinical experience. Epilepsy Res, 2006, 71(2-3): 89-101.
- 41. John MP, Douglas RN, Raman S, et al. Pellock's pediatric epilepsy: diagnosis and therapy (Fourth edition). Narnia, 2017, 81(3): 21-65.
- 42. Cilio MR, Kartashov AI, Vigevano F. The long-term use of felbamate in children with severe refractory epilepsy. Epilepsy Research, 2001, 47(1): 65-72.
- 43. Zupanc ML, Roell WR, Schwabe MS, et al. Efficacy of felbamate in the treatment of intractable pediatric epilepsy. Pediatr Neurol, 2010, 42(6): 396-403.
- 44. Hurst DL. The use of felbamate to treat infantile spasms. Journal of Child Neurology, 1995, 10(2): 421-426.
- 45. Dozières PB, Nasser H, Bellavoine V, et al. Felbamate for infantile spasms syndrome resistant to first‐line treatments. Developmental Medicine & Child Neurology, 2020, 62(5): 854-859.
- 46. Grosso S, Cordelli DM, Coppola G, et al. Efficacy and safety of felbamate in children under 4 years of age: a retrospective chart review. Eur J Neurol, 2008, 15(9): 940-946.
- 47. Victor B. Clinical pharmacology and mechanism of action of zonisamide. Clinical neuropharmacology, 2007, 30(4): 611-617.
- 48. Suzuki Y, Imai K, Toribe Y, et al. Long-term response to zonisamide in patients with West syndrome. Neurology, 2002, 58(10): 1556-1559.
- 49. Yum MS, Ko TS. Zonisamide in West syndrome: an open label study. Epileptic Disord, 2009, 11(4): 339-344.
- 50. Angappan D, Sahu JK, Malhi P, et al. Safety, tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome. Eur J Paediatr Neurol, 2019, 23(1): 136-142.
- 51. Rajaraman RR, Lay J, Alayari A, et al. Prevention of infantile spasms relapse: Zonisamide and topiramate provide no benefit. Epilepsia, 2016, 57(8): 1221-1226.
- 52. Hussain SA, Navarro M, Heesch J, et al. Limited efficacy of zonisamide in the treatment of refractory infantile spasms. Epilepsia Open, 2020, 5(1): 121-126.
- 53. 毛振沙. 唑尼沙胺添加治療兒童難治性癲癇的短期療效及安全性分析. 重慶醫科大學, 碩士學位論文, 2015: 7-24.
- 54. Shigeru Y, Hirokazu O, Keisuke Y, et al. Zonisamide for West syndrome: a comparison of clinical responses among different titration rate. Brain & development, 2005, 27(4): 701-704.
- 55. 萬林. 嬰兒痙攣癥褪黑素及相關激素與晝夜節律因子表達水平的研究. 中國人民解放軍醫學院, 碩士學位論文, 2019: 7-45.
- 56. Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron‐induced epileptic discharges in rats by suppressing peroxidation. Epilepsia, 1998, 39(3): 625-629.
- 57. Peled N, Shorer Z, Peled E, et al. Melatonin effect on seizures in children with severe neurologic deficit disorders. Epilepsia, 2001, 42(9): 1401-1406.
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