结节性硬化症诊断及其相关癫痫的非手术治疗_Journal of Epilepsy

Authors：

丁平 ,  梁树立

解放军总医院神经外科（北京 100853）;

Corresponding author：

梁树立, Email: 301_1sjwk@sina.cn

Keywords：

结节性硬化症; 癫痫; 抗癫痫药物; 哺乳动物雷帕霉素靶蛋白

DOI：

10.7507/2096-0247.20190022

Video：

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Abstract Full text Figures/Tables Video References Cited by

结节性硬化症（Tuberous sclerosiscomplex，TSC）是一种罕见的 TSC 基因突变引起的常染色体显性遗传性神经皮肤综合征，可累及皮肤、神经、眼、心肺肾等多器官，临床表现或基因检测可以诊断。颅内病变为皮质结节、室管膜下巨细胞星形细胞瘤和钙化灶，癫痫是其主要的神经系统表现，且与智力损害及神经心理异常密切相关。TSC 相关癫痫的非手术治疗包括哺乳动物雷帕霉素靶蛋白抑制剂、抗癫痫药物和生酮饮食等，但药物难治性癫痫比率超过 50%；其中 TSC 相关的婴儿痉挛症首选氨己烯酸治疗。

Citation： 丁平, 梁树立. 结节性硬化症诊断及其相关癫痫的非手术治疗. Journal of Epilepsy, 2019, 5(2): 120-124. doi: 10.7507/2096-0247.20190022 Copy

1.	Curatolo P, Nabbout R, Lagae L, et al. Management of epilepsy associated with tuberous sclerosis complex: updated clinical recommendations. Eur J Paediatr Neurol, 2018, 22(5): 738-748.
2.	Wang YY, Pang LY, Ma SF, et al. Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: a retrospective cohort study. Epilepsy Behav, 2017, 77: 13-18.
3.	Roach ES. Applying the lessons of tuberous sclerosis: the 2015 hower award lecture. Pediatr Neurol, 2016, 63: 6-22.
4.	Yang G, Shi ZN, Meng Y, et al. Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex. Clin Genet, 2017, 91(5): 764-768.
5.	van Eeghen AM, Black ME, Pulsifer MB, et al. Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur J Hum Genet, 2012, 20(5): 510-515.
6.	Saxena A, Sampson JR. Epilepsy in Tuberous sclerosis: phenotypes, mechanisms, and treatments. Semin Neurol, 2015, 35(3): 269-276.
7.	Bolton PF, Clifford M, Tye C, et al. Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study. Psychol Med, 2015, 45(11): 2321-2331.
8.	Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol, 2015, 14(7): 733-745.
9.	Welin KO, Carlqvist P, Svensson A, et al. Epilepsy in tuberous sclerosis patients in Sweden - healthcare utilization, treatment, morbidity, and mortality using national register data. Seizure, 2017, 53: 4-9.
10.	Jeong A, Nakagawa JA, Wong M. Predictors of drug-resistant epilepsy in tuberous sclerosis complex. J Child Neurol, 2017, 32(14): 1092-1098.
11.	Gül Mert G, Altunbaşak Ş, Hergüner Ö, et al. Factors affecting epilepsy prognosis in patients with tuberous sclerosis.Childs Nerv Syst, 2019, 35(3): 463-468.
12.	Benova B, Petrak B, Kyncl M, et al. Early predictors of clinical and mental outcome in tuberous sclerosis complex: a prospective study. Eur J Paediatr Neurol, 2018, 22(4): 632-641.
13.	Overwater IE, Verhaar BJ, Lingsma HF, et al. Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex. J Neurol, 2017, 264(1): 161-167.
14.	Fohlen M, Taussig D, Ferrand-Sorbets S, et al. Refractory epilepsy in preschool children with tuberous sclerosis complex: early surgical treatment and outcome. Seizure, 2018, 60: 71-79.
15.	Liang S, Li A, Zhao M, et al. Epilepsy surgery in tuberous sclerosis complex: emphasis on surgical candidate and neuropsychology. Epilepsia, 2010, 51(11): 2316-2321.
16.	Liang S, Zhang J, Yang Z, et al. Long-term outcomes of epilepsy surgery in tuberous sclerosis complex. J Neurol, 2017, 264(6): 1146-1154.
17.	Gipson TT, Johnston MV. New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND). F1000Res, 2017, 6: F1000 Faculty Rev-859.
18.	Wilde L, Eden K, de Vries P, et al. Self-injury and aggression in adults with tuberous sclerosis complex: frequency, associated person characteristics, and implications for assessment. Res Dev Disabil, 2017, 64: 119-130.
19.	Northrup H, Krueger DA, International tuberous sclerosis complex consensus group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational tuberous sclerosis complex consensus conference. Pediatr Neurol, 2013, 49(4): 243-254.
20.	Amin S, Lux A, Calder N, et al. Causes of mortality in individuals with tuberous sclerosis complex. Dev Med Child Neurol, 2017, 59(6): 612-617.
21.	Yang G, Yang L, Yang X, et al. Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric patients with tuberous sclerosis complex: a systematic review and meta-analysis. Exp Ther Med, 2015, 9(2): 626-630.
22.	Samueli S, Abraham K, Dressler A, et al. Efficacy and safety of Everolimus in children with TSC-associated epilepsy - Pilot data from an open single-center prospective study. Orphanet J Rare Dis, 2016, 11(1): 145.
23.	Curatolo P, Franz DN, Lawson JA, et al. Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial. Lancet Child Adolesc Health, 2018, 2(7): 495-504.
24.	Muncy J, Butler IJ, Koenig MK. Rapamycin reduces seizure frequency in tuberous sclerosis complex. J Child Neurol, 2009, 24(4): 477.
25.	邹丽萍, 刘玉洁, 庞领玉, 等. 雷帕霉素治疗儿童结节性硬化症合并癫痫的临床效果及安全性观察. 中华儿科杂志, 2014, 52(11): 812-816.
26.	Zou LP, Liu YT. Letter re: sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology, 2017, 88(10): 1008.
27.	Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: a randomized controlled trial. Neurology, 2016, 87(10): 1011-1018.
28.	Krueger D, Wilfong A, Holland-Bouley K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol, 2013, 74(5): 679-687.
29.	Krueger DA, Wilfong AA, Mays M, et al. Long-term treatment of epilepsy with everolimus in tuberous sclerosis. Neurology, 2016, 87(23): 2408-2415.
30.	Jóźwiak S, Kotulska K, Domańska-Pakieła D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol, 2011, 15(5): 424-431.
31.	Tibussek D, Klepper J, Korinthenberg R, et al. Treatment of infantile Spasms: report of the interdisciplinary guideline committee coordinated by the german-speaking society for neuropediatrics. Neuropediatrics, 2016, 47(3): 139-150.
32.	Elterman RD, Shields WD, Bittman RM, et al. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol, 2010, 25(11): 1340-1347.
33.	Jennesson M, van Eeghen AM, Caruso PA, et al. Clobazam therapy of refractory epilepsy in tuberous sclerosis complex. Epilepsy Res, 2013, 104(3): 269-274.
34.	Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia, 2016, 57(10): 1617-1624.
35.	Geffrey AL, Belt OD, Paolini JL, et al. Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex. Epilepsy Res, 2015, 112: 72-75.
36.	Kossoff EH, Thiele EA, Pfeifer HH, et al. Tuberous sclerosis complex and the ketogenic diet. Epilepsia, 2005, 46(10): 1684-1686.
37.	Park S, Lee EJ, Eom S, et al. Ketogenic diet for the management of epilepsy associated with tuberous sclerosis complex in children. J Epilepsy Res, 2017, 7(1): 45-49.

1. Curatolo P, Nabbout R, Lagae L, et al. Management of epilepsy associated with tuberous sclerosis complex: updated clinical recommendations. Eur J Paediatr Neurol, 2018, 22(5): 738-748.
2. Wang YY, Pang LY, Ma SF, et al. Epilepsy may be the major risk factor of mental retardation in children with tuberous sclerosis: a retrospective cohort study. Epilepsy Behav, 2017, 77: 13-18.
3. Roach ES. Applying the lessons of tuberous sclerosis: the 2015 hower award lecture. Pediatr Neurol, 2016, 63: 6-22.
4. Yang G, Shi ZN, Meng Y, et al. Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex. Clin Genet, 2017, 91(5): 764-768.
5. van Eeghen AM, Black ME, Pulsifer MB, et al. Genotype and cognitive phenotype of patients with tuberous sclerosis complex. Eur J Hum Genet, 2012, 20(5): 510-515.
6. Saxena A, Sampson JR. Epilepsy in Tuberous sclerosis: phenotypes, mechanisms, and treatments. Semin Neurol, 2015, 35(3): 269-276.
7. Bolton PF, Clifford M, Tye C, et al. Intellectual abilities in tuberous sclerosis complex: risk factors and correlates from the Tuberous Sclerosis 2000 Study. Psychol Med, 2015, 45(11): 2321-2331.
8. Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol, 2015, 14(7): 733-745.
9. Welin KO, Carlqvist P, Svensson A, et al. Epilepsy in tuberous sclerosis patients in Sweden - healthcare utilization, treatment, morbidity, and mortality using national register data. Seizure, 2017, 53: 4-9.
10. Jeong A, Nakagawa JA, Wong M. Predictors of drug-resistant epilepsy in tuberous sclerosis complex. J Child Neurol, 2017, 32(14): 1092-1098.
11. Gül Mert G, Altunbaşak Ş, Hergüner Ö, et al. Factors affecting epilepsy prognosis in patients with tuberous sclerosis.Childs Nerv Syst, 2019, 35(3): 463-468.
12. Benova B, Petrak B, Kyncl M, et al. Early predictors of clinical and mental outcome in tuberous sclerosis complex: a prospective study. Eur J Paediatr Neurol, 2018, 22(4): 632-641.
13. Overwater IE, Verhaar BJ, Lingsma HF, et al. Interdependence of clinical factors predicting cognition in children with tuberous sclerosis complex. J Neurol, 2017, 264(1): 161-167.
14. Fohlen M, Taussig D, Ferrand-Sorbets S, et al. Refractory epilepsy in preschool children with tuberous sclerosis complex: early surgical treatment and outcome. Seizure, 2018, 60: 71-79.
15. Liang S, Li A, Zhao M, et al. Epilepsy surgery in tuberous sclerosis complex: emphasis on surgical candidate and neuropsychology. Epilepsia, 2010, 51(11): 2316-2321.
16. Liang S, Zhang J, Yang Z, et al. Long-term outcomes of epilepsy surgery in tuberous sclerosis complex. J Neurol, 2017, 264(6): 1146-1154.
17. Gipson TT, Johnston MV. New insights into the pathogenesis and prevention of tuberous sclerosis-associated neuropsychiatric disorders (TAND). F1000Res, 2017, 6: F1000 Faculty Rev-859.
18. Wilde L, Eden K, de Vries P, et al. Self-injury and aggression in adults with tuberous sclerosis complex: frequency, associated person characteristics, and implications for assessment. Res Dev Disabil, 2017, 64: 119-130.
19. Northrup H, Krueger DA, International tuberous sclerosis complex consensus group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational tuberous sclerosis complex consensus conference. Pediatr Neurol, 2013, 49(4): 243-254.
20. Amin S, Lux A, Calder N, et al. Causes of mortality in individuals with tuberous sclerosis complex. Dev Med Child Neurol, 2017, 59(6): 612-617.
21. Yang G, Yang L, Yang X, et al. Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric patients with tuberous sclerosis complex: a systematic review and meta-analysis. Exp Ther Med, 2015, 9(2): 626-630.
22. Samueli S, Abraham K, Dressler A, et al. Efficacy and safety of Everolimus in children with TSC-associated epilepsy - Pilot data from an open single-center prospective study. Orphanet J Rare Dis, 2016, 11(1): 145.
23. Curatolo P, Franz DN, Lawson JA, et al. Adjunctive everolimus for children and adolescents with treatment-refractory seizures associated with tuberous sclerosis complex: post-hoc analysis of the phase 3 EXIST-3 trial. Lancet Child Adolesc Health, 2018, 2(7): 495-504.
24. Muncy J, Butler IJ, Koenig MK. Rapamycin reduces seizure frequency in tuberous sclerosis complex. J Child Neurol, 2009, 24(4): 477.
25. 邹丽萍, 刘玉洁, 庞领玉, 等. 雷帕霉素治疗儿童结节性硬化症合并癫痫的临床效果及安全性观察. 中华儿科杂志, 2014, 52(11): 812-816.
26. Zou LP, Liu YT. Letter re: sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology, 2017, 88(10): 1008.
27. Overwater IE, Rietman AB, Bindels-de Heus K, et al. Sirolimus for epilepsy in children with tuberous sclerosis complex: a randomized controlled trial. Neurology, 2016, 87(10): 1011-1018.
28. Krueger D, Wilfong A, Holland-Bouley K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol, 2013, 74(5): 679-687.
29. Krueger DA, Wilfong AA, Mays M, et al. Long-term treatment of epilepsy with everolimus in tuberous sclerosis. Neurology, 2016, 87(23): 2408-2415.
30. Jóźwiak S, Kotulska K, Domańska-Pakieła D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol, 2011, 15(5): 424-431.
31. Tibussek D, Klepper J, Korinthenberg R, et al. Treatment of infantile Spasms: report of the interdisciplinary guideline committee coordinated by the german-speaking society for neuropediatrics. Neuropediatrics, 2016, 47(3): 139-150.
32. Elterman RD, Shields WD, Bittman RM, et al. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol, 2010, 25(11): 1340-1347.
33. Jennesson M, van Eeghen AM, Caruso PA, et al. Clobazam therapy of refractory epilepsy in tuberous sclerosis complex. Epilepsy Res, 2013, 104(3): 269-274.
34. Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia, 2016, 57(10): 1617-1624.
35. Geffrey AL, Belt OD, Paolini JL, et al. Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex. Epilepsy Res, 2015, 112: 72-75.
36. Kossoff EH, Thiele EA, Pfeifer HH, et al. Tuberous sclerosis complex and the ketogenic diet. Epilepsia, 2005, 46(10): 1684-1686.
37. Park S, Lee EJ, Eom S, et al. Ketogenic diet for the management of epilepsy associated with tuberous sclerosis complex in children. J Epilepsy Res, 2017, 7(1): 45-49.

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结节性硬化症诊断及其相关癫痫的非手术治疗

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