婴儿痉挛新型药物治疗的研究进展_Journal of Epilepsy

Authors：

刘力 ,  谭李红

湖南省儿童医院神经内科（长沙 410007）;

Corresponding author：

谭李红, Email: Tanlihong118@163.com

Keywords：

婴儿痉挛; 新型药物治疗; 雷帕霉素; 氟桂利嗪; 大麻二酚

DOI：

10.7507/2096-0247.202201005

Video：

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Abstract Full text Figures/Tables Video References Cited by

婴儿痉挛是婴儿最常见的癫痫性脑病之一，早期诊断和治疗可以改善患儿神经发育的预后。促肾上腺皮质激素（Adrenocorticotropic hormone，ACTH）及氨己烯酸是目前临床首选的一线治疗方案。此外还有一些具有动物实验或临床研究价值但尚未大范围用于临床治疗的新型药物，如雷帕霉素、氟桂利嗪、非氨酯、褪黑素及大麻二酚等，为这一难治性癫痫提供了新的治疗见解。本综述阐述了婴儿痉挛新型药物治疗的最新进展及实际应用。

Citation： 刘力, 谭李红. 婴儿痉挛新型药物治疗的研究进展. Journal of Epilepsy, 2022, 8(5): 436-441. doi: 10.7507/2096-0247.202201005 Copy

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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.	刘占利. 促肾上腺皮质激素治疗婴儿痉挛症作用机制研究进展. 国际儿科学杂志, 2010, 37(4): 413-415.
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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.	张利利, 周浩, 路通, 等. 25例结节性硬化患儿氨己烯酸治疗效果分析. 癫痫杂志, 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.
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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.
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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.	王艳艳. 天麻素注射液联合卡马西平、氟桂利嗪治疗癫痫合并偏头痛患者的疗效评价. 首都食品与医药, 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.
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44.	Hurst DL. The use of felbamate to treat infantile spasms. Journal of Child Neurology, 1995, 10(2): 421-426.
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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.
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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. 刘占利. 促肾上腺皮质激素治疗婴儿痉挛症作用机制研究进展. 国际儿科学杂志, 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. 张利利, 周浩, 路通, 等. 25例结节性硬化患儿氨己烯酸治疗效果分析. 癫痫杂志, 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. 王杨阳. mTOR抑制剂西罗莫司治疗儿童结节性硬化症相关癫痫的疗效及安全性评估. 中国人民解放军医学院, 博士学位论文, 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, Gröppel 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. 王艳艳. 天麻素注射液联合卡马西平、氟桂利嗪治疗癫痫合并偏头痛患者的疗效评价. 首都食品与医药, 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. 唑尼沙胺添加治疗儿童难治性癫痫的短期疗效及安全性分析. 重庆医科大学, 硕士学位论文, 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. 万林. 婴儿痉挛症褪黑素及相关激素与昼夜节律因子表达水平的研究. 中国人民解放军医学院, 硕士学位论文, 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.
59. Costa-Lotufo LV, Fonteles MM, Lima IS, et al. Attenuating effects of melatonin on pilocarpine-induced seizures in rats. Comp Biochem Physiol C Toxicol Pharmacol, 2002, 131(4): 521-529.
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