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1、 难治性癫痫持续状态难治性癫痫持续状态 的预后及处理的预后及处理四川省医学科学院四川省医学科学院四川省人民医院四川省人民医院神经内科神经内科孙红斌孙红斌2012-112012-11现状现状癫痫持续状态是神经内科的急重症，多数国家癫痫持续状态是神经内科的急重症，多数国家癫痫持续状态均需进入癫痫持续状态均需进入NICUNICU进行处理，经过适进行处理，经过适当的药物治疗和病因治疗，近当的药物治疗和病因治疗，近80%80%病例均可获病例均可获得满意的疗效。生命体征稳定，神经元得到保得满意的疗效。生命体征稳定，神经元得到保护，脑电图痫样放电停止，并发症得到良好控护，脑电图痫样放电停止，并发症得到良好控
2、制。制。但仍有但仍有9-22%9-22%的病例癫痫发作和并发症难以控的病例癫痫发作和并发症难以控制，并成为难治性癫痫持续状态制，并成为难治性癫痫持续状态( ( refractory refractory status epilepticusstatus epilepticus， RSE)RSE)。诊诊 断断 二种以上药物治疗维持一小时以上，未能二种以上药物治疗维持一小时以上，未能有效控制。有效控制。*Jan Novy, yGiancarlo Logroscino, Refractory status epilepticus: A prospective *Jan Novy, yGiancarl
3、o Logroscino, Refractory status epilepticus: A prospective observational studyobservational study。 Epilepsia, 2010Epilepsia, 2010，51(2):25151(2):251256256Status epilepticus (SE) that is resistant to Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as two antiepilep
4、tic compounds is defined as refractory status epilepticus (RSE). refractory status epilepticus (RSE). In the few available retrospective studies, In the few available retrospective studies, estimated RSE frequency is between 31% and estimated RSE frequency is between 31% and 43% of patients presenti
5、ng an SE episode; 43% of patients presenting an SE episode; almost all seem to require a coma induction almost all seem to require a coma induction for treatment. for treatment. We prospectively assessed RSE frequency, We prospectively assessed RSE frequency, clinical predictors, and outcome in a cl
6、inical predictors, and outcome in a tertiary clinical setting. tertiary clinical setting. *Jan Novy, yGiancarlo Logroscino, Refractory status epilepticus: A prospective *Jan Novy, yGiancarlo Logroscino, Refractory status epilepticus: A prospective observational studyobservational study。 Epilepsia, 2
7、010Epilepsia, 2010，51(2):25151(2):251256256Twenty-nine of 128 SE episodes (22.6%) were Twenty-nine of 128 SE episodes (22.6%) were refractory to first- and second-line refractory to first- and second-line antiepileptic treatments. Severity of antiepileptic treatments. Severity of consciousness impai
8、rment and de novo consciousness impairment and de novo episodes were independent predictors of episodes were independent predictors of RSE. RSE. RSE showed a worse outcome than non-RSE RSE showed a worse outcome than non-RSE (39% vs. 11% for mortality; 21% vs. 63% for (39% vs. 11% for mortality; 21%
9、 vs. 63% for return to baseline clinical conditions). return to baseline clinical conditions). Only 12 patients with RSE (41%) required Only 12 patients with RSE (41%) required coma induction for treatment. coma induction for treatment. 非惊厥性癫痫持续状态（非惊厥性癫痫持续状态（NCSENCSE）长程视频脑）长程视频脑电可明显提高诊断率和监测治疗效果电可明显提
10、高诊断率和监测治疗效果Eric J. Ericson, Elizabeth E. GerardEric J. Ericson, Elizabeth E. Gerard，Aphasic status epilepticus: Electroclinical Aphasic status epilepticus: Electroclinical correlationcorrelation，Epilepsia, 52(8):1452Epilepsia, 52(8):14521458, 2011 1458, 2011 All nine patients were right-handed with
11、subacute or All nine patients were right-handed with subacute or chronic left hemispheric lesions on magnetic chronic left hemispheric lesions on magnetic resonance imaging (MRI). resonance imaging (MRI). All patients had mixed aphasia, three presenting All patients had mixed aphasia, three presenti
12、ng with persistent aphasia from onset and six with with persistent aphasia from onset and six with episodic speech impairment, which became persistent episodic speech impairment, which became persistent in five of the six. in five of the six. The initial 30-min EEG demonstrated electrographic The in
13、itial 30-min EEG demonstrated electrographic seizure in only five patients (56%), despite the seizure in only five patients (56%), despite the presence of aphasia during the recording. presence of aphasia during the recording. Left hemispheric periodic lateralized epileptiform Left hemispheric perio
14、dic lateralized epileptiform discharges (PLEDS) were seen in two patients, and discharges (PLEDS) were seen in two patients, and left hemispheric slowing in two patients.left hemispheric slowing in two patients.ERIC J. ERICSON, ELIZABETH E. GERARDERIC J. ERICSON, ELIZABETH E. GERARD，APHASIC STATUS E
15、PILEPTICUS: ELECTROCLINICAL APHASIC STATUS EPILEPTICUS: ELECTROCLINICAL CORRELATIONCORRELATION，EPILEPSIA, 52(8):1452EPILEPSIA, 52(8):14521458, 20111458, 2011 Continuous video-EEG monitoring confirmed Continuous video-EEG monitoring confirmed electrographic seizure activity in all nine patients. elec
16、trographic seizure activity in all nine patients. Peak electrographic seizure frequency varied from Peak electrographic seizure frequency varied from continuous to once every 2h and was not associated continuous to once every 2h and was not associated with fluctuations in the speech deficit. with fl
17、uctuations in the speech deficit. EEG seizures resolved abruptly in three patients EEG seizures resolved abruptly in three patients and gradually over up to 4 days in six patients. and gradually over up to 4 days in six patients. Clinical improvement was delayed in eight of the Clinical improvement
18、was delayed in eight of the nine patients, and four patients retained some aphasia nine patients, and four patients retained some aphasia at discharge, 2at discharge, 24 days after EEG seizure resolution. 4 days after EEG seizure resolution. 8Eric J. Ericson, Elizabeth E. GerardEric J. Ericson, Eliz
19、abeth E. Gerard，Aphasic status epilepticus: Aphasic status epilepticus: Electroclinical correlationElectroclinical correlation，Epilepsia, 52(8):1452Epilepsia, 52(8):14521458, 20111458, 2011Standard EEG is sensitive for detection of Standard EEG is sensitive for detection of abnormalities in the domi
20、nant hemisphere abnormalities in the dominant hemisphere in patients with ASE. in patients with ASE. However, continuous EEG is necessary to However, continuous EEG is necessary to confirm the diagnosis and monitor confirm the diagnosis and monitor treatment, since clinical symptoms do not treatment
21、, since clinical symptoms do not correlate with electrographic seizure correlate with electrographic seizure activity and do not provide sufficient activity and do not provide sufficient information to guide treatment decisions. information to guide treatment decisions. 预后预后*Jan Novy, yGiancarlo Log
22、roscino, Refractory status epilepticus: A prospectiveobservational study，Epilepsia, 51(2):251256, 2010*Jan Novy, yGiancarlo Logroscino, Refractory status epilepticus: A prospectiveobservational study，Epilepsia, 51(2):251256, 2010*Jan Novy, yGiancarlo Logroscino, Refractory status epilepticus: A pros
23、pectiveobservational study，Epilepsia, 51(2):251256, 2010处理流程处理流程保持呼吸道通畅或建立人工辅助呼吸保持呼吸道通畅或建立人工辅助呼吸积极寻找病因，对可能的病因进行处理积极寻找病因，对可能的病因进行处理维持水电解质及酸碱平衡维持水电解质及酸碱平衡药物治疗药物治疗（1 1）戊巴比妥：）戊巴比妥：是目前治疗难治性癫痫持续状态的标准疗法，对其是目前治疗难治性癫痫持续状态的标准疗法，对其中多数病例有效，有作者研究提示使用标准剂量治中多数病例有效，有作者研究提示使用标准剂量治疗疗120min120min可使可使75%75%的病例停止发作，的病例停
24、止发作，123min123min内可使内可使80%80%的病例停止发作。初始负荷剂量的病例停止发作。初始负荷剂量5mg/kg5mg/kg静脉注射，静脉注射，再以再以0.5-3mg/kg0.5-3mg/kgh h连续静脉输注，直至发作停止或连续静脉输注，直至发作停止或见暴发抑制脑电图。见暴发抑制脑电图。低血压，呼吸抑制，复苏延迟是其主要副作用。但低血压，呼吸抑制，复苏延迟是其主要副作用。但需特别注意的是多项临床研究证实，用戊巴比妥停需特别注意的是多项临床研究证实，用戊巴比妥停药后，如癫痫复发死亡率接近药后，如癫痫复发死亡率接近30%30%，原因尚不清楚。，原因尚不清楚。因而认为使用戊巴比妥后癫痫
25、复发是预后不良的独因而认为使用戊巴比妥后癫痫复发是预后不良的独立危险因素。立危险因素。（2 2）咪达唑仑）咪达唑仑 ：是一种作用很强的苯二氮卓药物，对不是一种作用很强的苯二氮卓药物，对不同年龄段的同年龄段的RSERSE都有效。近年来广泛用来都有效。近年来广泛用来代替戊巴比妥。常用剂量，首剂静注，代替戊巴比妥。常用剂量，首剂静注，然后然后 0.2-0.4mg/kg 0.2-0.4mg/kgh h静脉输注静脉输注1-31-3天。天。对血压、呼吸影响较小。对血压、呼吸影响较小。（3 3）普鲁泊福（）普鲁泊福（propofolpropofol）是一种非巴比妥类的麻醉药，能够增强是一种非巴比妥类的麻醉药
26、，能够增强GABAGABA神经递神经递质的释放。多个开放性试验证实起效时间为质的释放。多个开放性试验证实起效时间为2-6min2-6min。部分研究者建议。部分研究者建议RSERSE应首先考虑普鲁泊福或者咪应首先考虑普鲁泊福或者咪达唑仑，而不是戊巴比妥治疗。建议剂量是达唑仑，而不是戊巴比妥治疗。建议剂量是1-2mg1-2mg静脉注射，然后以静脉注射，然后以2-10mg/kg2-10mg/kgh h持续静脉输注射。持续静脉输注射。PropofolPropofol可能的副作用包括诱导癫痫发作，但并不可能的副作用包括诱导癫痫发作，但并不常见，且在低于推荐剂量时出现。还可能出现中枢常见，且在低于推荐剂
27、量时出现。还可能出现中枢系统的兴奋状态，如强直、角弓反张、手足徐动症。系统的兴奋状态，如强直、角弓反张、手足徐动症。儿童使用儿童使用24h24h，有出现横纹肌溶解，难治性低氧，有出现横纹肌溶解，难治性低氧症，酸中毒，心衰等副作用的报道。症，酸中毒，心衰等副作用的报道。（4 4）大剂量地西泮静脉滴注：）大剂量地西泮静脉滴注：地西泮是治疗地西泮是治疗SESE的首选，但传统剂量对的首选，但传统剂量对RSERSE无效，可静脉给药达无效，可静脉给药达0.01-0.01-0.03mg/kg0.03mg/kgminmin，平均起效时间，平均起效时间40min40min，持续用药时间持续用药时间120-226
28、h120-226h，平均，平均68h68h，83%83%的患者有效。的患者有效。可出现低血压，可出现低血压，20%20%以上的病例需要机械以上的病例需要机械通气。通气。（5 5）利多卡因）利多卡因（6 6）丙戊酸注射）丙戊酸注射（7 7）电休克治疗）电休克治疗对部分可能有效，可试探性的观察治疗。对部分可能有效，可试探性的观察治疗。Refractory status epilepticus (SE) is a current Refractory status epilepticus (SE) is a current daily therapeutic challenge. Electroco
29、nvulsive daily therapeutic challenge. Electroconvulsive therapy (ECT), which is frequently used to treat therapy (ECT), which is frequently used to treat psychiatric disorders, is known to raise the psychiatric disorders, is known to raise the seizure threshold. As such, ECT could be of seizure thre
30、shold. As such, ECT could be of major interest in refractory SEmajor interest in refractory SE。In this paper, we provide a brief overview of In this paper, we provide a brief overview of ECT in refractory SE. Although no placebo-ECT in refractory SE. Although no placebo-controlled or open-label stud
31、y has been controlled or open-label study has been published on the efficacy or safety of ECT in published on the efficacy or safety of ECT in refractory SE, eight case reports have been refractory SE, eight case reports have been identified.identified.Virginie Lambrecq a,b,*, Frede ric Villega c, R
32、efractory status epilepticus: Electroconvulsive therapy as a possible therapeutic strategy。Eur J Epilepsy (2012)VIRGINIE LAMBRECQ A,B,*, FREDE RIC VILLEGA C, REFRACTORY STATUS EPILEPTICUS: VIRGINIE LAMBRECQ A,B,*, FREDE RIC VILLEGA C, REFRACTORY STATUS EPILEPTICUS: ELECTROCONVULSIVE THERAPY AS A POS
33、SIBLE THERAPEUTIC STRATEGYELECTROCONVULSIVE THERAPY AS A POSSIBLE THERAPEUTIC STRATEGY。EUR J EPILEPSY (2012)EUR J EPILEPSY (2012) SE cessation was obtained in 80% of cases, and SE cessation was obtained in 80% of cases, and complete recovery was achieved in 27% of patients. complete recovery was ach
34、ieved in 27% of patients. Despite the heterogeneity of the ECT parameters used Despite the heterogeneity of the ECT parameters used in these articles, we identified some common features in these articles, we identified some common features that may be recommended for the use of ECT in that may be re
35、commended for the use of ECT in refractory SE.refractory SE. ECT might be a viable therapeutic strategy for ECT might be a viable therapeutic strategy for the most resistant and severe cases of SE, the most resistant and severe cases of SE, particularly after the failure of two inductions of particu
36、larly after the failure of two inductions of anesthetic coma. This potential indication highlights anesthetic coma. This potential indication highlights the urgent need for clinical trials that assess the the urgent need for clinical trials that assess the usefulness of ECT in refractory SE.usefulness of ECT in refractory SE.20（8 8）全身麻醉治疗）全身麻醉治疗常见并发症常见并发症1. 1.感染感染2. 2.心肺功能不全心肺功能不全3. 3.电解质失调电解质失调4. 4.卒死卒死5. 5.肺栓塞肺栓塞
