成人癫痫148例临床分析
摘要
目的：通过对148例接受正规药物治疗的成人癫痫病例的研究，分析成人癫痫的临床特点，探讨其病因、发作类型、辅助检查及治疗方面的问题。
方法：回顾性分析148例于2006年2月至2007年2月在山东大学齐鲁医院神经内科门诊及病房确诊为癫痫的患者。患者均接受正规药物治疗至少6个月，最小年龄18岁，采集所有患者的年龄、性别、病因、临床表现、辅助检查结果、口服药物种类及近期发作情况等临床资料，并应用统计学方法分析年龄、病因、发作类型、影像学检查阳性率、药物疗效等方面的差异。
结果：
1．获得较为明确病因的共52例，占全部患者的35.1％；随着年龄的增加病因明确者的比例增大，即症状性癫痫比例增大。
2．症状性癫痫患者的主要病因为颅脑感染、脑血管病、颅脑外伤、先天发育异常、颅脑肿瘤、围产期损伤等，不同年龄阶段具体病因分布不同。
3．120例患者行EEG检查，检出异常者85例；91例患者行颅脑CT检查，检出异常者40例；25例患者行颅脑MRI检查，检出异常者12例。
4．成人癫痫表现为多种发作类型，以全身性强直阵挛发作(GTCS)、复杂部分性发作(CPS)、简单部分性发作(SPS)多见。
5．成人癫痫患者中最常用药物为苯妥英钠(PHT)、卡马西平(CBZ)、丙戊酸钠(VPA)；癫痫药物在非症状性癫痫组控制有效率为81.2％，症状性癫痫组的控制有效率为53.8％，存在统计学差异。
6．新型抗癫痫药物治疗癫痫显示了良好的疗效与耐受性。
结论：
1．发病年龄与病因的关系：不同年龄组症状性癫痫的比例不同，病因不同，随着年龄的增长，症状性癫痫比例增加。
2．感染、脑血管病、外伤、肿瘤、发育畸形等为成人癫痫患者的主要病因。
3．通过辅助检查，本组病例中症状性癫痫占总数的35.1％，非症状性癫痫占64.9％：影像学检查在诊断不明确的病例中应作为常规检查工具。
4．GTCS、CPS、SPS为成人癫痫患者主要发作类型。
5．症状性癫痫与非症状性癫痫患者药物治疗效果存在统计学差异。
6．新型抗癫痫药物治疗癫痫显示了良好的疗效与耐受性。
Objective: to investigate the characteristics of the adult epilepsy, to obtain some knowledge about the etiological factors, auxiliary examination, seizure type and drug therapy.
Method: 148 patients (age>=18years) who were diagnosed epilepsy in QiluHospital of Shandong University from February 2006 to February 2007 were enrolled in the study. The detailed information about these patients were collected and analyzed.
Results: (1) Among 148 patients, 52 patients were diagnosed as symptomaticepilepsy, and the rate of symptomatic epilepsy grows as the age of the patients grows. (2) The main etiologies of adult epilepsy are infection of CNS, CVD, cerebral trauma and so on. (3) 120 patients do the EEG examination and 85 patients have positive finding; 91 patients have CT examination and 40 patients have positive finding; 25 patients have MRI examination and 12 patients have positive finding. (4) GTCS、CPS、SPS are the main seizure types of adult epilepsy.(5)PHT、CBZ、VPA are the most commonly used antiepileptic drugs in adult epilepsy, the drug efficiency is different in symptomatic epilepsy and non-symptomatic epilepsy.(6)New antiepileptic drugs such as TPM、LTG、OXC are efficient.
Conclusion: (1) The rate of the symptomatic epilepsy grows as the age grows.
(2) Infection of the CNS、CVD、trauma、tumor are the main abnormal findings.
(3) CT/MRI should be carried in adult epileptic patients.
(4) GTCS、CPS、SPS are the main seizure types in adult epilepsy.
(5) The efficiency of the drug therapy is better in non-symptomatic epilepsy when compared with symptomatic epilepsy.
(6) New antiepileptic drugs are efficient.
方法：回顾性分析148例于2006年2月至2007年2月在山东大学齐鲁医院神经内科门诊及病房确诊为癫痫的患者。患者均接受正规药物治疗至少6个月，最小年龄18岁，采集所有患者的年龄、性别、病因、临床表现、辅助检查结果、口服药物种类及近期发作情况等临床资料，并应用统计学方法分析年龄、病因、发作类型、影像学检查阳性率、药物疗效等方面的差异。
结果：
1．获得较为明确病因的共52例，占全部患者的35.1％；随着年龄的增加病因明确者的比例增大，即症状性癫痫比例增大。
2．症状性癫痫患者的主要病因为颅脑感染、脑血管病、颅脑外伤、先天发育异常、颅脑肿瘤、围产期损伤等，不同年龄阶段具体病因分布不同。
3．120例患者行EEG检查，检出异常者85例；91例患者行颅脑CT检查，检出异常者40例；25例患者行颅脑MRI检查，检出异常者12例。
4．成人癫痫表现为多种发作类型，以全身性强直阵挛发作(GTCS)、复杂部分性发作(CPS)、简单部分性发作(SPS)多见。
5．成人癫痫患者中最常用药物为苯妥英钠(PHT)、卡马西平(CBZ)、丙戊酸钠(VPA)；癫痫药物在非症状性癫痫组控制有效率为81.2％，症状性癫痫组的控制有效率为53.8％，存在统计学差异。
6．新型抗癫痫药物治疗癫痫显示了良好的疗效与耐受性。
结论：
1．发病年龄与病因的关系：不同年龄组症状性癫痫的比例不同，病因不同，随着年龄的增长，症状性癫痫比例增加。
2．感染、脑血管病、外伤、肿瘤、发育畸形等为成人癫痫患者的主要病因。
3．通过辅助检查，本组病例中症状性癫痫占总数的35.1％，非症状性癫痫占64.9％：影像学检查在诊断不明确的病例中应作为常规检查工具。
4．GTCS、CPS、SPS为成人癫痫患者主要发作类型。
5．症状性癫痫与非症状性癫痫患者药物治疗效果存在统计学差异。
6．新型抗癫痫药物治疗癫痫显示了良好的疗效与耐受性。
Objective: to investigate the characteristics of the adult epilepsy, to obtain some knowledge about the etiological factors, auxiliary examination, seizure type and drug therapy.
Method: 148 patients (age>=18years) who were diagnosed epilepsy in QiluHospital of Shandong University from February 2006 to February 2007 were enrolled in the study. The detailed information about these patients were collected and analyzed.
Results: (1) Among 148 patients, 52 patients were diagnosed as symptomaticepilepsy, and the rate of symptomatic epilepsy grows as the age of the patients grows. (2) The main etiologies of adult epilepsy are infection of CNS, CVD, cerebral trauma and so on. (3) 120 patients do the EEG examination and 85 patients have positive finding; 91 patients have CT examination and 40 patients have positive finding; 25 patients have MRI examination and 12 patients have positive finding. (4) GTCS、CPS、SPS are the main seizure types of adult epilepsy.(5)PHT、CBZ、VPA are the most commonly used antiepileptic drugs in adult epilepsy, the drug efficiency is different in symptomatic epilepsy and non-symptomatic epilepsy.(6)New antiepileptic drugs such as TPM、LTG、OXC are efficient.
Conclusion: (1) The rate of the symptomatic epilepsy grows as the age grows.
(2) Infection of the CNS、CVD、trauma、tumor are the main abnormal findings.
(3) CT/MRI should be carried in adult epileptic patients.
(4) GTCS、CPS、SPS are the main seizure types in adult epilepsy.
(5) The efficiency of the drug therapy is better in non-symptomatic epilepsy when compared with symptomatic epilepsy.
(6) New antiepileptic drugs are efficient.
引文
1. Commission on Epidemiology and prognosis of epilepsy, ILAE. Guidelines for epidemiologic studies on epilepsy. Epilepsia, 1993, 34: 592-596.
2. Pochlmann-Eden B, Cochius JI, Hoch DB, et al. Stroke and epilepsy critical review of literature. Cerebrovasc Dis, 1997, 7(1): 2.
3．翁武昭，王孙，柴莹，等．急性脑血管病的癫痫发作．中国神经精神疾病杂志，1985，11(1)：36．
4．黄如训．动脉硬化性脑梗塞继发癫痫．中华神经精神科杂志，1988，21(3)：149．
5. Pochlmann-Eden B, Cochius JI, Hoch DB, et al. Stroke and epilepsy critical review of literature. Cerebrovasc Dis, 1996, 6(4): 322.
6. Sumer MM, Atasov HT, Unal A, Kalavci M, Mahmutvazicioqlu K, Erdem. Neurol Sci. 2003 Nov, 24(4): 268-271.
7. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation[J]Arch phys med rehabil. 2003 Mar, 84(3): 365-73.
8. Bryniarska D, Zakrzewska E. Etiological spectrum of symptomatic epilepsy in adults. [J] Przegl Lek. 2001, 58(9): 839-42. Polish.
9. Sperling MR, Ko J. Seizures and brain tumors. Semin Oncol. 2006 Jun, 33(3): 333-41.
10. Morris HH, Estes ML, Gilmore R, et al. Chronic intractable epilepsy as the only symptom of primary brain tumor[J]. Epilepsia, 1993, 34(6): 1038-1043.
11. Zaatreh MM, scpencer DD, Thompson JL, et al. Frontal lobe tumoral epilepsy: clinical, neurophysiologic, features and predictors of surgical outcome. Epilepsia, 2002, 43(7): 727-733.
12．朱谱国，阮旭中．老年人迟发性癫痫[J]．国外医学神经病学神经外科学分册，1988，12(1)：24227．
13. Krzyszkowski T, Czepko R, Berlei M. Prognostic value of epileptic seizures in patients with cerebral gliomas. Ann Acad Med Stetin. 2004, 50(1): 35-40.
14. Bonilha L, Rorden C, et al. Gray matter atrophy associater with duration of temporal lobe epilepsy. Neuroimage, 2006 sep, 32(3): 1070-9.
15. Levesque MF, Nakasccto N, et al. Surgical treatment of limbic epilepsy associated with extra hippocampal lesion: the problem of dual pathology[J]. Neurosurgy, 1991, 75(9): 364-370.
16. Chen HX, Roper SN. Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter. J Neurophysiol, 2003 Jan, 89(1): 150-8.
17. Yalcin AD, Oncel C, et al. Evidence against association between arachnoid cysts and epilepsy. Epilepsy Res, 2002 May: 49(3): 255-60.
18. Kobayashi E, Bonilha L, et al. Temporal lobe hypogenesis associated with arachnoid cyst in patients with epilepsy. Arq Neuropsiquiatr, 2003 Jun; 61(2B): 327-9.
19. Christian A Koch, Dieter Voth, Gunter Kracmer. Arachnoid cysts: does surgery improve epileptic seizures and headaches? Neurosurg Rev, 1995, 18: 173-181.
20. Betting LE, Mory. SB, et al. MRI reveals structural abnormalities in patients with idiopathic generalized epilepsy. Neurology, 2006 Sep 12, 6(5): 848-52.
21. Liu RS, Lemieux L, Bell GS, et al. Cerebral damage in epilepsy: a population based longitudinal quantitative MRI study. Epilepsia, 2005 Sep, 46(9): 1482-94.
22. Bryniarska D, Zakrzewska E. Etiological spectrum of symptomatic epilepsy in adults. [J]Przegl Lek, 2001, 58(9): 839-42. Polish.
23．黄远桂，吴声伶．临床脑电图学[M]．西安：陕西科学技术出版社，1984，1242154，195．
24．林晓东，赵丽．癫痫的CT评价[J]．脑与神经疾病杂志，1997，5(1)：60．
25．赵性泉，王春雪等．成人首发癫痫发作的病因学研究[J]．首都医科大学学报，2004，3(1)：100-102．
26. Chabplla DR. Characteristics of the epilepsies. Mayo Clin Proc, 2002 Sep, 77(9): 981-90.
27. K wan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000, 342: 314-19.
28. K wan P, Brodie MJ. epilepsy after the first drug fails: substitution or add-on?Seizure 2000, 9:464-468.
29. Liporace JD, Sperling MR, Dichter MA. Absence seizures and carbamazepine in adults. Epilepsia, 1994, 35:314-19.
30. Perucca E, Gram L, Avanzini G, Dulac O. Antileptic drugs as a cause of worsening seizures. Epilepsia, 1998, 39:5-17.
31. Scottish intercollegiate Guidelines Network. Diagnosis and treatment of epilepsy in adults. A national clinical guideline, April 2003.
32. Nicolsm A, Appleton RE, Chadwick DW, Smith DF. The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalized epilepsies. J Neurol Neurosurg Psychiatry, 2004, 75:75-79.
33. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of new antiepileptic drugs: treatment of new onset epilepsy. Neurology, 2004, 62:1252-60.
34. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of new antiepileptic drugs: treatment of refractory epilepsy. Neurology 2004;62:1261-73
35. Dougall McCorry, David Chadwick, and Anthony Marson. Current drug treatment of epilepsy in adults. Lancet Neurol, 2004, 3:729-35.
36. Beghi E, Gatti G, Tonini C, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug, a multicentre, randomized, pragmatic controlled trial. Epilepsy Res, 2003, 57:1-13.
37. Deckers CL, Czuczwar SJ, Hekster YA, et al. Selection of antiepileptic drug polytherapy based on mechanism of action: the evidence reviewed. Epilepsia, 2000, 41:1364-1374.
38. Pisani F, Oteri G, Russo MF, et al. The efficacy of valprovate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia, 1999, 40:1141-1146.
39. Steven K arceski, Martha J. Morrell, Daniel Carenter. Treatment of epilepsy in adults: experts opinion, 2005. Epilesy&behavior, 7(2005), S1-S64.
1. Scheffer IE, Bhatia KP, Lopes Cendes I, Fish DR, Marsden CD, Andermann E, et al. Autosomal dominant nocturnal frontal epilepsy: a distinctive clinical disorder. Brain 1995;118:61-73
2. Steinlein O, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor a4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet1995;11:201-3.
3. Phillips, H. A. et al. A de novo mutayion in sporadic nocturnal frontal lobe epilepsy. Ann. Neurol 2000;48:264-7.
4. De Fusco MD, Becchetti A, Patrignani A, Annesi G, Gambardella A, Quattrone A, et al. The nicotinic receptor beta2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet 2000;26:275-6.
5. Phillips HA, Favre I, Kirkpatrick M, Zuberi SM, Goudie D, Heron SE, et al. CHRNB2 is the second acetylcholine receotor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy. Am J Hum Genet 2001;68:225-31.
6. Weiland S, Witzemann V, Villarroel A, Propping P, Steinlein O. An amino acid exchange in the second transmembrane segment of a neuronal nicotinic receptor causes partial epilepsy by altering its desensitization kinetics. FEBS Lett 1996;398:91-6.
7. Bertrand D, Picard F, Le Hellard S, Favre I, Phillips H, et al. How mutations in the nAChRs can cause ADNFLE epilepsy. Epilepsia 2002;43:112-22.
8. Dedek K, Fusco L, Teloy N, Steinlein OK. Neonatal convulsion and epileptic encephalopathy in an Italian family with a missense mutation in the fiftj transmembrane region of KCNQ2. Epilepsy Res 2003;54:21-7.
9. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jenrsch TJ, et al. A novel potassium channel mutation in neonatal human epilepsy. Science 1998;279:403-6.
10. Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T, et al. A novel mutation of KCNQ3 in a Japanese family with benign familial neonatal convulsions. Ann Neurol 2000;47:822-6.
11. Dedek K, Kunath B, Kananura C, Reuner U, Jentsch TJ, Steinlein OK. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci USA 2001;9812272-7.
12. Dedek K, Kunath B, et al. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K channel. Proc Natl Acad Sci USA 2001;98:12272-7.
13. Heron SE, Crossland KM Andermann E, Phillips HA, Hall AJ, et al. Sodium-channel defects in benign familial neonatal infantile seizures. Lancet 2002;360:851-2.
14. Okada, M. et al. Age-dependent modulation of hippocampal excitability by KCNQ-channels. Epilepsy Res 2003;53:81-94.
15. Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, et al. Neuronal sodium channel alpha subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet 2001;68:859-65.
16. Sugawara T, Mazaki E, Ito M, Nagafuji H, Fukuma G, Mitsudome A, et al. Navl. 1 mutations cause febrile seizures associated with a febrile seizures. Neurology 2001;57:703-5.
17. Harkin, LA, et al. Truncation of the GABAA receptor r2 subunit is associated with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet 2002;70:530-6.
18. Claes L, Del-Favero J. Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001;68:1327-32.
19. Burgess DL. Neonatal epilepsy syndromes and GEFS+ mechanistic considerations. Epilepsia 2005;46(suppl 10):41-7
20. Winawer, MR. et al. Autosomal dominant partial epilepsy with auditory features: defining the phenotype. Neurology 2000;54:2173-76.
21. Staub E, Perez-Tur J, Siebert R, Nobile C, et al. The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Treris Biochem Sci 2002;27:441-4.
22. A. Ayerdi-Izquierdo, G. Stavrides, et al. Genetic analysis of the LGI/Epitemin gene family in sporadic and familial lateral temporal lobe epilepsy. Epilepsy Research70 (2006) 118-126
23. Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, et al. A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol 2002;52:654-7
24. Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptacek LJ. A novel gene causing a mendelian audiogen. ic mouse epilepsy. Neuron 2001;31:537-44.
25. Greenberg DA, Dumer M, Shinnar S, et al. Association of HLA class alleles in patients with juvenile myoclonic epilepsy compared with patients with other forms of adolescent-onset generalized epilepsy. Neurology, 1996, 47:750-6.
26. Elmslie FV, Rees M, Williamson MP, et al. Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q. Hum mol Genet, 1997;6:1329-34.
27. T. Suzuki, A. V. Delgado-Escueta, K. Aguan, M. E. Alonso, J. Shi, Y. Hara, M. Nishida, T. N umata, M. t. Medina, T. Takeuchi, R. Morita, D. Bai, S. Ganesh, Y. Sugimoto, J, Inazawa, J. N. Bailey, A. Ochoa, A. JaraPrado, A, Rasmussen, J. Ramos-Peek, et al. Mutation in EFHCI cause juvenile myoclonic epilepsy, Nat. Genet 2004;36:842-9.
28. Fong C, Shap P, Gee M Serratosa J, et al. Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4HZ spike and multispike-slow wave complexes:linkage to chromosome 8q24. Am J Hum Genet, 1998;63:1117-29.
29. Wallace RH, Marini C, Pertou S, et al. Mutant GABAA receotor beta-2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet, 2001;28:49-52
30. Lohi H, Ianzano L, Zhao XC, et al. Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy. Hum Mol Genet, 2005; 14(18):2727-36.
31. Chan EM, Bulman DE, Paterson AD, et al. Genetic mapping of a new Lafora progressive myoclonus epilepsy locus(EPM2B) on 6p22. J Med Genet 2003;40(9):671-5.
2. Pochlmann-Eden B, Cochius JI, Hoch DB, et al. Stroke and epilepsy critical review of literature. Cerebrovasc Dis, 1997, 7(1): 2.
3．翁武昭，王孙，柴莹，等．急性脑血管病的癫痫发作．中国神经精神疾病杂志，1985，11(1)：36．
4．黄如训．动脉硬化性脑梗塞继发癫痫．中华神经精神科杂志，1988，21(3)：149．
5. Pochlmann-Eden B, Cochius JI, Hoch DB, et al. Stroke and epilepsy critical review of literature. Cerebrovasc Dis, 1996, 6(4): 322.
6. Sumer MM, Atasov HT, Unal A, Kalavci M, Mahmutvazicioqlu K, Erdem. Neurol Sci. 2003 Nov, 24(4): 268-271.
7. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation[J]Arch phys med rehabil. 2003 Mar, 84(3): 365-73.
8. Bryniarska D, Zakrzewska E. Etiological spectrum of symptomatic epilepsy in adults. [J] Przegl Lek. 2001, 58(9): 839-42. Polish.
9. Sperling MR, Ko J. Seizures and brain tumors. Semin Oncol. 2006 Jun, 33(3): 333-41.
10. Morris HH, Estes ML, Gilmore R, et al. Chronic intractable epilepsy as the only symptom of primary brain tumor[J]. Epilepsia, 1993, 34(6): 1038-1043.
11. Zaatreh MM, scpencer DD, Thompson JL, et al. Frontal lobe tumoral epilepsy: clinical, neurophysiologic, features and predictors of surgical outcome. Epilepsia, 2002, 43(7): 727-733.
12．朱谱国，阮旭中．老年人迟发性癫痫[J]．国外医学神经病学神经外科学分册，1988，12(1)：24227．
13. Krzyszkowski T, Czepko R, Berlei M. Prognostic value of epileptic seizures in patients with cerebral gliomas. Ann Acad Med Stetin. 2004, 50(1): 35-40.
14. Bonilha L, Rorden C, et al. Gray matter atrophy associater with duration of temporal lobe epilepsy. Neuroimage, 2006 sep, 32(3): 1070-9.
15. Levesque MF, Nakasccto N, et al. Surgical treatment of limbic epilepsy associated with extra hippocampal lesion: the problem of dual pathology[J]. Neurosurgy, 1991, 75(9): 364-370.
16. Chen HX, Roper SN. Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter. J Neurophysiol, 2003 Jan, 89(1): 150-8.
17. Yalcin AD, Oncel C, et al. Evidence against association between arachnoid cysts and epilepsy. Epilepsy Res, 2002 May: 49(3): 255-60.
18. Kobayashi E, Bonilha L, et al. Temporal lobe hypogenesis associated with arachnoid cyst in patients with epilepsy. Arq Neuropsiquiatr, 2003 Jun; 61(2B): 327-9.
19. Christian A Koch, Dieter Voth, Gunter Kracmer. Arachnoid cysts: does surgery improve epileptic seizures and headaches? Neurosurg Rev, 1995, 18: 173-181.
20. Betting LE, Mory. SB, et al. MRI reveals structural abnormalities in patients with idiopathic generalized epilepsy. Neurology, 2006 Sep 12, 6(5): 848-52.
21. Liu RS, Lemieux L, Bell GS, et al. Cerebral damage in epilepsy: a population based longitudinal quantitative MRI study. Epilepsia, 2005 Sep, 46(9): 1482-94.
22. Bryniarska D, Zakrzewska E. Etiological spectrum of symptomatic epilepsy in adults. [J]Przegl Lek, 2001, 58(9): 839-42. Polish.
23．黄远桂，吴声伶．临床脑电图学[M]．西安：陕西科学技术出版社，1984，1242154，195．
24．林晓东，赵丽．癫痫的CT评价[J]．脑与神经疾病杂志，1997，5(1)：60．
25．赵性泉，王春雪等．成人首发癫痫发作的病因学研究[J]．首都医科大学学报，2004，3(1)：100-102．
26. Chabplla DR. Characteristics of the epilepsies. Mayo Clin Proc, 2002 Sep, 77(9): 981-90.
27. K wan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000, 342: 314-19.
28. K wan P, Brodie MJ. epilepsy after the first drug fails: substitution or add-on?Seizure 2000, 9:464-468.
29. Liporace JD, Sperling MR, Dichter MA. Absence seizures and carbamazepine in adults. Epilepsia, 1994, 35:314-19.
30. Perucca E, Gram L, Avanzini G, Dulac O. Antileptic drugs as a cause of worsening seizures. Epilepsia, 1998, 39:5-17.
31. Scottish intercollegiate Guidelines Network. Diagnosis and treatment of epilepsy in adults. A national clinical guideline, April 2003.
32. Nicolsm A, Appleton RE, Chadwick DW, Smith DF. The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalized epilepsies. J Neurol Neurosurg Psychiatry, 2004, 75:75-79.
33. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of new antiepileptic drugs: treatment of new onset epilepsy. Neurology, 2004, 62:1252-60.
34. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of new antiepileptic drugs: treatment of refractory epilepsy. Neurology 2004;62:1261-73
35. Dougall McCorry, David Chadwick, and Anthony Marson. Current drug treatment of epilepsy in adults. Lancet Neurol, 2004, 3:729-35.
36. Beghi E, Gatti G, Tonini C, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug, a multicentre, randomized, pragmatic controlled trial. Epilepsy Res, 2003, 57:1-13.
37. Deckers CL, Czuczwar SJ, Hekster YA, et al. Selection of antiepileptic drug polytherapy based on mechanism of action: the evidence reviewed. Epilepsia, 2000, 41:1364-1374.
38. Pisani F, Oteri G, Russo MF, et al. The efficacy of valprovate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia, 1999, 40:1141-1146.
39. Steven K arceski, Martha J. Morrell, Daniel Carenter. Treatment of epilepsy in adults: experts opinion, 2005. Epilesy&behavior, 7(2005), S1-S64.
1. Scheffer IE, Bhatia KP, Lopes Cendes I, Fish DR, Marsden CD, Andermann E, et al. Autosomal dominant nocturnal frontal epilepsy: a distinctive clinical disorder. Brain 1995;118:61-73
2. Steinlein O, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor a4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet1995;11:201-3.
3. Phillips, H. A. et al. A de novo mutayion in sporadic nocturnal frontal lobe epilepsy. Ann. Neurol 2000;48:264-7.
4. De Fusco MD, Becchetti A, Patrignani A, Annesi G, Gambardella A, Quattrone A, et al. The nicotinic receptor beta2 subunit is mutant in nocturnal frontal lobe epilepsy. Nat Genet 2000;26:275-6.
5. Phillips HA, Favre I, Kirkpatrick M, Zuberi SM, Goudie D, Heron SE, et al. CHRNB2 is the second acetylcholine receotor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy. Am J Hum Genet 2001;68:225-31.
6. Weiland S, Witzemann V, Villarroel A, Propping P, Steinlein O. An amino acid exchange in the second transmembrane segment of a neuronal nicotinic receptor causes partial epilepsy by altering its desensitization kinetics. FEBS Lett 1996;398:91-6.
7. Bertrand D, Picard F, Le Hellard S, Favre I, Phillips H, et al. How mutations in the nAChRs can cause ADNFLE epilepsy. Epilepsia 2002;43:112-22.
8. Dedek K, Fusco L, Teloy N, Steinlein OK. Neonatal convulsion and epileptic encephalopathy in an Italian family with a missense mutation in the fiftj transmembrane region of KCNQ2. Epilepsy Res 2003;54:21-7.
9. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jenrsch TJ, et al. A novel potassium channel mutation in neonatal human epilepsy. Science 1998;279:403-6.
10. Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T, et al. A novel mutation of KCNQ3 in a Japanese family with benign familial neonatal convulsions. Ann Neurol 2000;47:822-6.
11. Dedek K, Kunath B, Kananura C, Reuner U, Jentsch TJ, Steinlein OK. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci USA 2001;9812272-7.
12. Dedek K, Kunath B, et al. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K channel. Proc Natl Acad Sci USA 2001;98:12272-7.
13. Heron SE, Crossland KM Andermann E, Phillips HA, Hall AJ, et al. Sodium-channel defects in benign familial neonatal infantile seizures. Lancet 2002;360:851-2.
14. Okada, M. et al. Age-dependent modulation of hippocampal excitability by KCNQ-channels. Epilepsy Res 2003;53:81-94.
15. Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, et al. Neuronal sodium channel alpha subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet 2001;68:859-65.
16. Sugawara T, Mazaki E, Ito M, Nagafuji H, Fukuma G, Mitsudome A, et al. Navl. 1 mutations cause febrile seizures associated with a febrile seizures. Neurology 2001;57:703-5.
17. Harkin, LA, et al. Truncation of the GABAA receptor r2 subunit is associated with generalized epilepsy with febrile seizures plus. Am. J. Hum. Genet 2002;70:530-6.
18. Claes L, Del-Favero J. Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001;68:1327-32.
19. Burgess DL. Neonatal epilepsy syndromes and GEFS+ mechanistic considerations. Epilepsia 2005;46(suppl 10):41-7
20. Winawer, MR. et al. Autosomal dominant partial epilepsy with auditory features: defining the phenotype. Neurology 2000;54:2173-76.
21. Staub E, Perez-Tur J, Siebert R, Nobile C, et al. The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders. Treris Biochem Sci 2002;27:441-4.
22. A. Ayerdi-Izquierdo, G. Stavrides, et al. Genetic analysis of the LGI/Epitemin gene family in sporadic and familial lateral temporal lobe epilepsy. Epilepsy Research70 (2006) 118-126
23. Nakayama J, Fu YH, Clark AM, Nakahara S, Hamano K, Iwasaki N, et al. A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol 2002;52:654-7
24. Skradski SL, Clark AM, Jiang H, White HS, Fu YH, Ptacek LJ. A novel gene causing a mendelian audiogen. ic mouse epilepsy. Neuron 2001;31:537-44.
25. Greenberg DA, Dumer M, Shinnar S, et al. Association of HLA class alleles in patients with juvenile myoclonic epilepsy compared with patients with other forms of adolescent-onset generalized epilepsy. Neurology, 1996, 47:750-6.
26. Elmslie FV, Rees M, Williamson MP, et al. Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q. Hum mol Genet, 1997;6:1329-34.
27. T. Suzuki, A. V. Delgado-Escueta, K. Aguan, M. E. Alonso, J. Shi, Y. Hara, M. Nishida, T. N umata, M. t. Medina, T. Takeuchi, R. Morita, D. Bai, S. Ganesh, Y. Sugimoto, J, Inazawa, J. N. Bailey, A. Ochoa, A. JaraPrado, A, Rasmussen, J. Ramos-Peek, et al. Mutation in EFHCI cause juvenile myoclonic epilepsy, Nat. Genet 2004;36:842-9.
28. Fong C, Shap P, Gee M Serratosa J, et al. Childhood absence epilepsy with tonic-clonic seizures and electroencephalogram 3-4HZ spike and multispike-slow wave complexes:linkage to chromosome 8q24. Am J Hum Genet, 1998;63:1117-29.
29. Wallace RH, Marini C, Pertou S, et al. Mutant GABAA receotor beta-2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet, 2001;28:49-52
30. Lohi H, Ianzano L, Zhao XC, et al. Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy. Hum Mol Genet, 2005; 14(18):2727-36.
31. Chan EM, Bulman DE, Paterson AD, et al. Genetic mapping of a new Lafora progressive myoclonus epilepsy locus(EPM2B) on 6p22. J Med Genet 2003;40(9):671-5.