精准医疗在难治性癫痫中的现状_Journal of Epilepsy

Authors：

胡笑月 ^1,2 ,  汤继宏 ¹ , 华颖 ²

1. ;
2. ;

Corresponding author：

汤继宏, Email: tjhzsh@126.com

Keywords：

难治性癫痫; 基因检测; 精准治疗

DOI：

10.7507/2096-0247.20190034

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

癫痫是常见的神经系统疾病，其中高达 30% 的患者为药物难治性癫痫，不仅给患者造成身心的危害，也增加了社会、家庭的负担。而单纯依据临床特征和现行癫痫用药指南的给药方案，难以获得满意的治疗效果。随着基因测序技术的发展，越来越多的癫痫致病基因得以发现，可以精确地帮助医生明确癫痫发生的机制，辅助临床选择适合的个体化治疗方案，把握治疗时机。

Citation： 胡笑月, 汤继宏, 华颖. 精准医疗在难治性癫痫中的现状. Journal of Epilepsy, 2019, 5(3): 192-195. doi: 10.7507/2096-0247.20190034 Copy

1.	Birbeck GL. Epilepsy care in developing countries: part II of II. Epilepsy Curr, 2010, 10(5): 105-110.
2.	Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia, 1979, 20(6): 729-737.
3.	Moshe SL, Perucca E, Ryvlin P, et al. Epilepsy: new advances. Lancet, 2015, 385: 884-898.
4.	姚兰, 孟红梅. 难治性癫痫的临床研究及治疗现状分析. 中华神经科杂志, 2012, 45(6): 434-435.
5.	Lindhout D. Epilepsy treatment: precision medicine at a crossroads. Lancet Neurol, 2015, 14: 1148-1149.
6.	Consortium TE. Epi4K: gene discovery in 4000genomes. Epilepsia, 2012, 53(8): 1457-1467.
7.	Epi4K Consortium. De Novo Mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am J Hum Genet, 2016, 99(2): 287-298.
8.	Appenzeller S, Balling R, Barisic N, et al. Epilepsy phenome/genome project, and Epi4K Consortium. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies, 2014, 95(4): 360-370.
9.	Epi4K Consortium. Phenotypic analysis of 303 multiplex families with common epilepsies. Brain, 2017, 140(8): 2144-2156.
10.	Kearney JA. Epi4K Phase I: Gene discovery in epileptic encephalopathies by exome sequencing. Epilepsy Curr, 2014, 14(4): 208-210.
11.	Epilepsy Phenome/Genome Project Epi4K Consortium. Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy. Ann Neurol, 2015, 78(2): 323-328.
12.	Striano P, Striano S, Minetti C, et al. Refractory, life-threatening status epilepticus in a 3-year-old girl. Lancet Neurol, 2008, 7(3): 278-284.
13.	Maljevic S, Reid CA, Petrou S. Models for discovery of targeted therapy in genetic epileptic encephalopathies. J Neurochemistry, 2017, 143(3): 1-19.
14.	Shi XY, Tomonoh Y, Wang W Z, et al. Efficacy of antiepileptic drugs for the treatment of Dravet syndrome with different genotypes. Brain Dev, 2016, 38(1): 40-46.
15.	Sanders SJ, Campbell AJ, Cottrell JR, et al. Progress in understanding and treating, SCN2A-mediated disorders. Trends Neurosci, 2018, 42(7): 442-456.
16.	Atkin TA, Maher CM, Gerlach AC, et al. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy. Epilepsia, 2018, 59(suppl 2): 802-813.
17.	Wolff M, Johannesen KM, HedrichUBS, et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 2017, 140(5): 1316-1336.
18.	Robertino D, Difrancesco JC, Virginia SM, et al. Early treatment with quinidine in 2 patients with epilepsy of infancy with migrating focal seizures (EIMFS) due to gain-of-function KCNT1 mutations: functional studies, clinical responses, and critical issues for personalized therapy. Neurotherapeutics, 2018, 15(4): 1112-1126.
19.	Chong PF, Nakamura R, Saitsu H, et al. Ineffective quinidine therapy in early onset epileptic encephalopathy with KCNT1 mutation. Ann Neurol, 2016, 79(3): 502-503.
20.	Mikati MA, Jiang YH, Carboni M, et al. Quinidine in the treatment of KCNT1-positive epilepsies. Ann Neurol, 2015, 78(6): 995-999.
21.	Maljevie S, LercheH. Potassium channel genes and benign familial neonatal epilepsy. Prog Brain Res, 2014, 213: 17-53.
22.	Millichap JJ, Park KL, TsuchidaT, et al. KCNQ2 encephalopathy: features, mutational hot spots, and ezogabine treatment of 11 patients. Neurol Genetics, 2016, 2(5): e96.
23.	Pierson TM, Yuan H, Marsh ED, et a1. GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine. Ann Clin Transl Neurol, 2014, 1(3): 190-198.
24.	Li D, Yuan H, Ortiz-Gonzalez XR, et al. GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers. Am J Hum Genet, 2016, 99(4): 802-816.
25.	Zhang Y, Lian Y, Xie N. Early onset epileptic encephalopathy with a novel GABRB3 mutation treated effectively with clonazepam. Medicine, 2017, 96(50): e9273.
26.	Hewson S, Brunga L, Ojeda MF, et al. Prevalence of genetic disorders and GLUT1 deficiency in a ketogenic diet clinic. Can J Neurol Sci, 2017, 45(1): 93-96.
27.	Falsaperla R, CorselloG. Pyridoxine dependent epilepsies: new therapeutical point of view. Ital J Pediatr, 2017, 43(1): 68.
28.	Griffith JL, Michael W. ThemTOR pathway in treatment of epilepsy: a clinical update. Future Neurol, 2018, 13(2): 49-58.
29.	孟曙庆, 张洪. 难治性癫痫的治疗进展. 中华临床医师杂志(电子版), 2013, 7(15): 142-145.
30.	Ara K, Jung DE, Kim SH, et al. The Efficacy of ketogenic diet for specific genetic mutation in developmental and epileptic encephalopathy. Front Neurol, 2018, 9: 530.
31.	Su DJ, Lu JF, Lin LJ, et al. SCN2A, mutation in an infant presenting with migrating focal seizures and infantile spasm responsive to a ketogenic diet. Brain Dev, 2018, 40(8): 724-727.
32.	Schoeler, NE, Leu C, Balestrini S, et al. Genome-wide association study: exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy. Epilepsia, 2018, 59(8): 1557-1566.
33.	Fainberg N, Harper A, Tchapyjnikov D, et al. Response to immunotherapy in a patient with Landau-Kleffner syndrome and GRIN2A mutation. Epileptic Disord, 2016, 18(1): 97-100.
34.	Harvey AS, Cross JH, Shinnar S, et al. Defining the spectrum of international practice in pediatric epilepsy surgery patients. Epilepsia, 2008, 49(1): 146-155.
35.	Benova B, Jacques TS. Genotype-phenotypecorrelations in focalmalformations of corticaldevelopment: a pathway to integratedpathologicaldiagnosis in epilepsysurgery. Brain Pathol, 2018.
36.	Stevelink R, Sanders MW, Tuinman MP, et al. Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review. Epileptic Disord, 2018, 20(2): 99-115.
37.	Shetty AK, Upadhya D. GABA-ergic cell therapy for epilepsy: advances, limitations and challenges. Neurosci. Biobehav Rev, 2016, 62: 35-47.
38.	Rao G, Mashkouri S, Aum D, et al. Contemplating stem cell therapy for epilepsy-induced neuropsychiatric symptoms. Neuropsychiatr Dis Treat, 2017, 13: 585-596.
39.	Hattiangady B, Rao MS, Shetty AK. Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy. Exp Neurol, 2008, 212(2): 468-481.
40.	Upadhya D, Hattiangady B, Shetty GA, et al. Neural stem cell or human induced pluripotent stem cell-derived GABA-ergic progenitor cell grafting in an animal model of chronic temporal lobe epilepsy. Curr Protoc Stem Cell Biol, 2016.
41.	Cunningham M, Cho JH, Leung A, et al. hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell, 2014, 15(5): 559-573.

1. Birbeck GL. Epilepsy care in developing countries: part II of II. Epilepsy Curr, 2010, 10(5): 105-110.
2. Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia, 1979, 20(6): 729-737.
3. Moshe SL, Perucca E, Ryvlin P, et al. Epilepsy: new advances. Lancet, 2015, 385: 884-898.
4. 姚兰, 孟红梅. 难治性癫痫的临床研究及治疗现状分析. 中华神经科杂志, 2012, 45(6): 434-435.
5. Lindhout D. Epilepsy treatment: precision medicine at a crossroads. Lancet Neurol, 2015, 14: 1148-1149.
6. Consortium TE. Epi4K: gene discovery in 4000genomes. Epilepsia, 2012, 53(8): 1457-1467.
7. Epi4K Consortium. De Novo Mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am J Hum Genet, 2016, 99(2): 287-298.
8. Appenzeller S, Balling R, Barisic N, et al. Epilepsy phenome/genome project, and Epi4K Consortium. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies, 2014, 95(4): 360-370.
9. Epi4K Consortium. Phenotypic analysis of 303 multiplex families with common epilepsies. Brain, 2017, 140(8): 2144-2156.
10. Kearney JA. Epi4K Phase I: Gene discovery in epileptic encephalopathies by exome sequencing. Epilepsy Curr, 2014, 14(4): 208-210.
11. Epilepsy Phenome/Genome Project Epi4K Consortium. Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy. Ann Neurol, 2015, 78(2): 323-328.
12. Striano P, Striano S, Minetti C, et al. Refractory, life-threatening status epilepticus in a 3-year-old girl. Lancet Neurol, 2008, 7(3): 278-284.
13. Maljevic S, Reid CA, Petrou S. Models for discovery of targeted therapy in genetic epileptic encephalopathies. J Neurochemistry, 2017, 143(3): 1-19.
14. Shi XY, Tomonoh Y, Wang W Z, et al. Efficacy of antiepileptic drugs for the treatment of Dravet syndrome with different genotypes. Brain Dev, 2016, 38(1): 40-46.
15. Sanders SJ, Campbell AJ, Cottrell JR, et al. Progress in understanding and treating, SCN2A-mediated disorders. Trends Neurosci, 2018, 42(7): 442-456.
16. Atkin TA, Maher CM, Gerlach AC, et al. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy. Epilepsia, 2018, 59(suppl 2): 802-813.
17. Wolff M, Johannesen KM, HedrichUBS, et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 2017, 140(5): 1316-1336.
18. Robertino D, Difrancesco JC, Virginia SM, et al. Early treatment with quinidine in 2 patients with epilepsy of infancy with migrating focal seizures (EIMFS) due to gain-of-function KCNT1 mutations: functional studies, clinical responses, and critical issues for personalized therapy. Neurotherapeutics, 2018, 15(4): 1112-1126.
19. Chong PF, Nakamura R, Saitsu H, et al. Ineffective quinidine therapy in early onset epileptic encephalopathy with KCNT1 mutation. Ann Neurol, 2016, 79(3): 502-503.
20. Mikati MA, Jiang YH, Carboni M, et al. Quinidine in the treatment of KCNT1-positive epilepsies. Ann Neurol, 2015, 78(6): 995-999.
21. Maljevie S, LercheH. Potassium channel genes and benign familial neonatal epilepsy. Prog Brain Res, 2014, 213: 17-53.
22. Millichap JJ, Park KL, TsuchidaT, et al. KCNQ2 encephalopathy: features, mutational hot spots, and ezogabine treatment of 11 patients. Neurol Genetics, 2016, 2(5): e96.
23. Pierson TM, Yuan H, Marsh ED, et a1. GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine. Ann Clin Transl Neurol, 2014, 1(3): 190-198.
24. Li D, Yuan H, Ortiz-Gonzalez XR, et al. GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers. Am J Hum Genet, 2016, 99(4): 802-816.
25. Zhang Y, Lian Y, Xie N. Early onset epileptic encephalopathy with a novel GABRB3 mutation treated effectively with clonazepam. Medicine, 2017, 96(50): e9273.
26. Hewson S, Brunga L, Ojeda MF, et al. Prevalence of genetic disorders and GLUT1 deficiency in a ketogenic diet clinic. Can J Neurol Sci, 2017, 45(1): 93-96.
27. Falsaperla R, CorselloG. Pyridoxine dependent epilepsies: new therapeutical point of view. Ital J Pediatr, 2017, 43(1): 68.
28. Griffith JL, Michael W. ThemTOR pathway in treatment of epilepsy: a clinical update. Future Neurol, 2018, 13(2): 49-58.
29. 孟曙庆, 张洪. 难治性癫痫的治疗进展. 中华临床医师杂志(电子版), 2013, 7(15): 142-145.
30. Ara K, Jung DE, Kim SH, et al. The Efficacy of ketogenic diet for specific genetic mutation in developmental and epileptic encephalopathy. Front Neurol, 2018, 9: 530.
31. Su DJ, Lu JF, Lin LJ, et al. SCN2A, mutation in an infant presenting with migrating focal seizures and infantile spasm responsive to a ketogenic diet. Brain Dev, 2018, 40(8): 724-727.
32. Schoeler, NE, Leu C, Balestrini S, et al. Genome-wide association study: exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy. Epilepsia, 2018, 59(8): 1557-1566.
33. Fainberg N, Harper A, Tchapyjnikov D, et al. Response to immunotherapy in a patient with Landau-Kleffner syndrome and GRIN2A mutation. Epileptic Disord, 2016, 18(1): 97-100.
34. Harvey AS, Cross JH, Shinnar S, et al. Defining the spectrum of international practice in pediatric epilepsy surgery patients. Epilepsia, 2008, 49(1): 146-155.
35. Benova B, Jacques TS. Genotype-phenotypecorrelations in focalmalformations of corticaldevelopment: a pathway to integratedpathologicaldiagnosis in epilepsysurgery. Brain Pathol, 2018.
36. Stevelink R, Sanders MW, Tuinman MP, et al. Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review. Epileptic Disord, 2018, 20(2): 99-115.
37. Shetty AK, Upadhya D. GABA-ergic cell therapy for epilepsy: advances, limitations and challenges. Neurosci. Biobehav Rev, 2016, 62: 35-47.
38. Rao G, Mashkouri S, Aum D, et al. Contemplating stem cell therapy for epilepsy-induced neuropsychiatric symptoms. Neuropsychiatr Dis Treat, 2017, 13: 585-596.
39. Hattiangady B, Rao MS, Shetty AK. Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy. Exp Neurol, 2008, 212(2): 468-481.
40. Upadhya D, Hattiangady B, Shetty GA, et al. Neural stem cell or human induced pluripotent stem cell-derived GABA-ergic progenitor cell grafting in an animal model of chronic temporal lobe epilepsy. Curr Protoc Stem Cell Biol, 2016.
41. Cunningham M, Cho JH, Leung A, et al. hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell, 2014, 15(5): 559-573.

Previous Article
Effects of Tianjiang Niuhuang powder on the epileptic model of pilocarpine rats
Next Article
自身免疫性脑炎继发癫痫风险的研究进展

Journal of Epilepsy

精准医疗在难治性癫痫中的现状

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content