脑血管疾病继发癫痫：实验回顾和临床危险因素的荟萃分析_Journal of Epilepsy

Authors：

FerlazzoE , GaspariniS , BeghiE , 迟潇洒 , 慕洁

Corresponding author：

Keywords：

动物模型; 抗癫痫药物; 脑白质疏松症; 痫性发作; 卒中

DOI：

10.7507/2096-0247.20170039

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癫痫发作可能发生在刚刚卒中发生以后或在很久以后。此外，癫痫也常发生在患有脑白质疏松的患者。尽管卒中后早期痫性发作被广泛研究，卒中后癫痫(Post-stroke epilepsy，PSE)和与脑白质疏松相关癫痫(Epilepsy associated with leukoaraiosis，EAL)研究较少。文章目的是回顾PSE和EAL相关病理生理学，预后和治疗情况。并进行了广泛的文献检索，以筛选关于PSE和EAL的动物实验和临床文章。同时，还对纳入研究中PSE和EAL发生的风险因素进行了系统的回顾分析。PSE是由于瘢痕组织内和其附近神经元兴奋性增加引起的。白质改变在EAL中的作用尚待阐明。荟萃分析显示皮质受累[ OR=3.71，95% CI (2.34, 5.90)，P < 0.001]，脑出血[ OR=2.41，95% CI (1.57, 3.70)，P < 0.001]和早期痫性发作[ OR=4.43，95% CI (2.36, 8.32)，P < 0.001]显著增加PSE发生风险。关于EAL，没有前瞻性、基于人群的研究评估不同变量对癫痫发作风险的影响。关于PSE治疗的研究相对有限。PSE药物控制效果通常良好。有关危险因素、预后和EAL治疗的资料较缺乏。PSE的病理生理学和危险因素是明确的，但在EAL中仍需进一步阐明。PSE和EAL的治疗依赖于临床医生的判断，并应在个人基础上进行调控。

Citation： FerlazzoE, GaspariniS, BeghiE, 迟潇洒, 慕洁. 脑血管疾病继发癫痫：实验回顾和临床危险因素的荟萃分析. Journal of Epilepsy, 2017, 3(3): 248-256. doi: 10.7507/2096-0247.20170039 Copy

1.	Menon B, Shorvon SD. Ischaemic stroke in adults and epilepsy. EpilepsyRes, 2009, 87(2):1-11.
2.	Hesdorffer DC, Benn EKT, Cascino GD, et al. Is a first acute symptomaticseizure epilepsy Mortality and risk for recurrent seizure.Epilepsia, 2009, 50(11):1102-1108.
3.	Fisher RS, Acevedo C, Arzimanoglou A, et al. A practical clinical definitionof epilepsy. Epilepsia, 2014, 55(8):475-482.
4.	Gasparini S, Ferlazzo E, Beghi E, et al. Epilepsy associated withLeukoaraiosis mainly affects temporal lobe: a casual or causal relationship. Epilepsy Res, 2015, 109(2):1-8.
5.	Pantoni L. Cerebral small vessel disease: from pathogenesis and clinicalcharacteristics to therapetic challenges. Lancet Neurol, 2010, 9(2): 689-701.
6.	Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiologyand Prognosis, International League Against Epilepsy.Epilepsia, 1993, 34(5):592-596.
7.	Cuomo O, Rispoli V, Leo A, et al. The antiepileptic drug levetiracetamsuppresses non-convulsive seizure activity and reduces ischemic braindamage in rats subjected to permanent middle cerebral artery occlusion.PLoS ONE, 2013, 8(6):e80852.
8.	Watson BD, Dietrich WD, Busto R, et al. Induction of reproduciblebrain infarction by photochemically initiated thrombosis. Ann Neurol, 1985, 17(5):497-504.
9.	Karhunen H, Bezvenyuk Z, Nissinen J, et al. Epileptogenesis after corticalphotothrombotic brain lesion in rats. Neuroscience 2007, 48(10):314-324.
10.	Kessler KR, Schnitzler A, Classen J, et al. Reduced inhibition withinprimary motor cortex in patients with posts-troke focal motor seizures.Neurology, 2002, 59(7):1028-1033.
11.	Kim JH, Lee HW, Cohen LG, et al. Motor cortical excitability inpatients with post-stroke epilepsy. Epilepsia, 2008, 49(10):117-124.
12.	Kaiser D, Weise G, Meoller K, et al. Spontaneous white matter damage, cognitive decline and neuro-inflammation in middle-aged hypertensiverats: an animal model of early-stage cerebral small vessel disease. ActaNeuropatholCommun, 2014, 2(3):169.
13.	Tchekalarova J, Georgiev V. Angiotensin peptides modulatory system:how is it implicated n the control of seizure susceptibility. Life Sci, 2005, 76(9):955-970.
14.	Tchekalarova J, Loyens E, Smolders I. Effects of AT1 receptor antagonismon kainate-induced seizures and concomitant changes in hippocampalextracellular noradrenaline, serotonin, and dopamine levelsin Wistar-Kyoto and spontaneously hypertensive rats. Epilepsy Behav, 2015, 46(8):66-71.
15.	Arganaraz GA, Konno AC, Perosa SR, et al. The renin-angiotensinsystem is up-regulated in the cortex and hippocampus of patients withtemporal lobe epilepsy related to mesial temporal sclerosis. Epilepsia, 2008, 49(11):1348-1357.
16.	Ng SK, Hauser WA, Brust JC, et al. Hypertension and the risk of newonsetunprovoked seizures. Neurology, 1993, 43(2):425-428.
17.	Hesdorffer DC, Hauser WA, Annegers JF, et al. Severe, uncontrolledhypertension and adult-onset seizures: a case-control study in Rochester, Minnesota. Epilepsia, 1996, 37(2):736-741.
18.	Li X, Breteler MM, deBruyne MC, et al. Vascular determinants of epilepsy:the Rotterdam Study. Epilepsia, 1997, 38(4):216-220.
19.	Maxwell H, Hanby M, Parkes LM, et al. Prevalence andsubtypes of radiological cerebrovascular disease in late-onset isolatedseizures and epilepsy. ClinNeurolNeurosurg, 2013, 115(10):591-596.
20.	Okroglic S, Widmann CN, Urbach H, et al. Clinical symptoms and riskfactors in cerebral microangiopathy patients. PloS ONE, 2013, 8(4):e53455.
21.	De Reuck J, Van Maele G. Cognitive impairment and seizures inpatients with lacunar strokes. EurNeurol, 2009, 61(4):159-163.
22.	Smith EE, Schneider JA, Wardlaw JM, et al. Cerebral microinfarcts:the invisible lesions. Lancet Neurol, 2012, 11(7):272-282.
23.	Keller L, Hobohm C, Zeynalova S, et al. Does treatment with t-PAincrease the risk of developing epilepsy after stroke. J Neurol, 2015, 262(4):2364-2372.
24.	Serafini A, Gigli GL, Gregoraci G, et al. Are early seizures predictiveof epilepsy after a stroke Results of a population-based study Neuroepidemiology, 2015, 45(4):50-58.
25.	Zhang C, Wang X, Wang Y, et al. Risk factors for post-strokeseizures:a systematic review and meta-analysis. Epilepsy Res, 2014, 108(7):1806-1816.
26.	De Reuck J, Nagy E, Van Maele G. Seizures and epilepsy in patientswith lacunar strokes. J NeurolSci, 2007, 263(10):75-78.
27.	Ferlazzo E, Sueri C, Gasparini S, et al. Challenges in the pharmacologicalmanagement of epilepsy and its causes in the elderly. PharmacolRes, 2016, 106(4):21-26.
28.	Semah F, Picot MC, Adam C, et al. Is the underlying cause of epilepsya major prognostic factor for recurrence Neurology, 1998, 51(4):1256-1262.
29.	Stephen LJ, Kwan P, Brodie MJ. Does the cause of localisation-relatedepilepsy influence the response to antiepileptic drug treatment.Epilepsia, 2001, 42(7):357-362.
30.	Gilad R, Boaz M, Dabby R, et al. Are post intracerebral hemorrhageseizures prevented by antiepileptic treatment. Epilepsy Res, 2011, 95(6):227-231.
31.	Gilad R, Sadeh M, Rapoport A, et al. Monotherapy of lamotrigine versuscarbamazepine in patients with poststroke seizure. ClinNeuropharmacol, 2007, 30(5):189-195.
32.	Kutlu G, Gomceli YB, Unal Y, et al. Levetiracetam monotherapy forlate post-stroke seizures in the elderly. Epilepsy Behav, 2008, 13(4):542-544.
33.	Belcastro V, Costa C, Galletti F, et al. Levetiracetam in newly diagnosedlate-onset post-stroke seizures: a prospective observationalstudy. Epilepsy Res, 2008, 82(1):223-226.
34.	Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepinein patients with late poststroke seizures: a multicenterprospective randomized open-label study (EpIC Project). CerebrovascDis, 2012, 34(8):282-289.
35.	Huang YH, Chi NF, Kuan YC, et al. Efficacy of phenytoin, valproicacid, carbamazepine and new antiepileptic drugs on control of lateonsetpost-stroke epilepsy in Taiwan. Eur J Neurol, 2015, 22(7):1459-1468.
36.	Brodie MJ, Overstall PW, Giorgi L. Multicenter, double-blind, randomizedcomparison between lamotrigine and carbamazepine inelderly patients with newly diagnosed epilepsy. Epilepsy Res, 1999, 37(2):81-87.
37.	Rowan AJ, Ramsay RE, Collins JF, et al. New onset geriatric epilepsy:a randomized study of gabapentin, lamotrigine, and carbamazepine.Neurology, 2005, 64(6):1868-1873.
38.	Marson AG, Al-Kharusi AM, Alwaidh M, et al. SANAD study ofeffectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblendedrandomized controlled trial. Lancet, 2007, 369(11):1000-1015.
39.	Saetre E, Perucca E, Isojarvi J, et al. An international multicenter randomizeddouble-blind controlled trial of lamotrigine and sustainedreleasecarbamazepine in the treatment of newly diagnosed epilepsy inthe elderly. Epilepsia, 2007, 48(2):1292-1302.
40.	Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, doubleblindcomparison of antiepileptic drug treatment in the elderly withnew-onset focal epilepsy. Epilepsia, 2015, 56(5):450-459.

1. Menon B, Shorvon SD. Ischaemic stroke in adults and epilepsy. EpilepsyRes, 2009, 87(2):1-11.
2. Hesdorffer DC, Benn EKT, Cascino GD, et al. Is a first acute symptomaticseizure epilepsy Mortality and risk for recurrent seizure.Epilepsia, 2009, 50(11):1102-1108.
3. Fisher RS, Acevedo C, Arzimanoglou A, et al. A practical clinical definitionof epilepsy. Epilepsia, 2014, 55(8):475-482.
4. Gasparini S, Ferlazzo E, Beghi E, et al. Epilepsy associated withLeukoaraiosis mainly affects temporal lobe: a casual or causal relationship. Epilepsy Res, 2015, 109(2):1-8.
5. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinicalcharacteristics to therapetic challenges. Lancet Neurol, 2010, 9(2): 689-701.
6. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiologyand Prognosis, International League Against Epilepsy.Epilepsia, 1993, 34(5):592-596.
7. Cuomo O, Rispoli V, Leo A, et al. The antiepileptic drug levetiracetamsuppresses non-convulsive seizure activity and reduces ischemic braindamage in rats subjected to permanent middle cerebral artery occlusion.PLoS ONE, 2013, 8(6):e80852.
8. Watson BD, Dietrich WD, Busto R, et al. Induction of reproduciblebrain infarction by photochemically initiated thrombosis. Ann Neurol, 1985, 17(5):497-504.
9. Karhunen H, Bezvenyuk Z, Nissinen J, et al. Epileptogenesis after corticalphotothrombotic brain lesion in rats. Neuroscience 2007, 48(10):314-324.
10. Kessler KR, Schnitzler A, Classen J, et al. Reduced inhibition withinprimary motor cortex in patients with posts-troke focal motor seizures.Neurology, 2002, 59(7):1028-1033.
11. Kim JH, Lee HW, Cohen LG, et al. Motor cortical excitability inpatients with post-stroke epilepsy. Epilepsia, 2008, 49(10):117-124.
12. Kaiser D, Weise G, Meoller K, et al. Spontaneous white matter damage, cognitive decline and neuro-inflammation in middle-aged hypertensiverats: an animal model of early-stage cerebral small vessel disease. ActaNeuropatholCommun, 2014, 2(3):169.
13. Tchekalarova J, Georgiev V. Angiotensin peptides modulatory system:how is it implicated n the control of seizure susceptibility. Life Sci, 2005, 76(9):955-970.
14. Tchekalarova J, Loyens E, Smolders I. Effects of AT1 receptor antagonismon kainate-induced seizures and concomitant changes in hippocampalextracellular noradrenaline, serotonin, and dopamine levelsin Wistar-Kyoto and spontaneously hypertensive rats. Epilepsy Behav, 2015, 46(8):66-71.
15. Arganaraz GA, Konno AC, Perosa SR, et al. The renin-angiotensinsystem is up-regulated in the cortex and hippocampus of patients withtemporal lobe epilepsy related to mesial temporal sclerosis. Epilepsia, 2008, 49(11):1348-1357.
16. Ng SK, Hauser WA, Brust JC, et al. Hypertension and the risk of newonsetunprovoked seizures. Neurology, 1993, 43(2):425-428.
17. Hesdorffer DC, Hauser WA, Annegers JF, et al. Severe, uncontrolledhypertension and adult-onset seizures: a case-control study in Rochester, Minnesota. Epilepsia, 1996, 37(2):736-741.
18. Li X, Breteler MM, deBruyne MC, et al. Vascular determinants of epilepsy:the Rotterdam Study. Epilepsia, 1997, 38(4):216-220.
19. Maxwell H, Hanby M, Parkes LM, et al. Prevalence andsubtypes of radiological cerebrovascular disease in late-onset isolatedseizures and epilepsy. ClinNeurolNeurosurg, 2013, 115(10):591-596.
20. Okroglic S, Widmann CN, Urbach H, et al. Clinical symptoms and riskfactors in cerebral microangiopathy patients. PloS ONE, 2013, 8(4):e53455.
21. De Reuck J, Van Maele G. Cognitive impairment and seizures inpatients with lacunar strokes. EurNeurol, 2009, 61(4):159-163.
22. Smith EE, Schneider JA, Wardlaw JM, et al. Cerebral microinfarcts:the invisible lesions. Lancet Neurol, 2012, 11(7):272-282.
23. Keller L, Hobohm C, Zeynalova S, et al. Does treatment with t-PAincrease the risk of developing epilepsy after stroke. J Neurol, 2015, 262(4):2364-2372.
24. Serafini A, Gigli GL, Gregoraci G, et al. Are early seizures predictiveof epilepsy after a stroke Results of a population-based study Neuroepidemiology, 2015, 45(4):50-58.
25. Zhang C, Wang X, Wang Y, et al. Risk factors for post-strokeseizures:a systematic review and meta-analysis. Epilepsy Res, 2014, 108(7):1806-1816.
26. De Reuck J, Nagy E, Van Maele G. Seizures and epilepsy in patientswith lacunar strokes. J NeurolSci, 2007, 263(10):75-78.
27. Ferlazzo E, Sueri C, Gasparini S, et al. Challenges in the pharmacologicalmanagement of epilepsy and its causes in the elderly. PharmacolRes, 2016, 106(4):21-26.
28. Semah F, Picot MC, Adam C, et al. Is the underlying cause of epilepsya major prognostic factor for recurrence Neurology, 1998, 51(4):1256-1262.
29. Stephen LJ, Kwan P, Brodie MJ. Does the cause of localisation-relatedepilepsy influence the response to antiepileptic drug treatment.Epilepsia, 2001, 42(7):357-362.
30. Gilad R, Boaz M, Dabby R, et al. Are post intracerebral hemorrhageseizures prevented by antiepileptic treatment. Epilepsy Res, 2011, 95(6):227-231.
31. Gilad R, Sadeh M, Rapoport A, et al. Monotherapy of lamotrigine versuscarbamazepine in patients with poststroke seizure. ClinNeuropharmacol, 2007, 30(5):189-195.
32. Kutlu G, Gomceli YB, Unal Y, et al. Levetiracetam monotherapy forlate post-stroke seizures in the elderly. Epilepsy Behav, 2008, 13(4):542-544.
33. Belcastro V, Costa C, Galletti F, et al. Levetiracetam in newly diagnosedlate-onset post-stroke seizures: a prospective observationalstudy. Epilepsy Res, 2008, 82(1):223-226.
34. Consoli D, Bosco D, Postorino P, et al. Levetiracetam versus carbamazepinein patients with late poststroke seizures: a multicenterprospective randomized open-label study (EpIC Project). CerebrovascDis, 2012, 34(8):282-289.
35. Huang YH, Chi NF, Kuan YC, et al. Efficacy of phenytoin, valproicacid, carbamazepine and new antiepileptic drugs on control of lateonsetpost-stroke epilepsy in Taiwan. Eur J Neurol, 2015, 22(7):1459-1468.
36. Brodie MJ, Overstall PW, Giorgi L. Multicenter, double-blind, randomizedcomparison between lamotrigine and carbamazepine inelderly patients with newly diagnosed epilepsy. Epilepsy Res, 1999, 37(2):81-87.
37. Rowan AJ, Ramsay RE, Collins JF, et al. New onset geriatric epilepsy:a randomized study of gabapentin, lamotrigine, and carbamazepine.Neurology, 2005, 64(6):1868-1873.
38. Marson AG, Al-Kharusi AM, Alwaidh M, et al. SANAD study ofeffectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblendedrandomized controlled trial. Lancet, 2007, 369(11):1000-1015.
39. Saetre E, Perucca E, Isojarvi J, et al. An international multicenter randomizeddouble-blind controlled trial of lamotrigine and sustainedreleasecarbamazepine in the treatment of newly diagnosed epilepsy inthe elderly. Epilepsia, 2007, 48(2):1292-1302.
40. Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, doubleblindcomparison of antiepileptic drug treatment in the elderly withnew-onset focal epilepsy. Epilepsia, 2015, 56(5):450-459.

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