2023年01月16日发布 | 1590阅读

中国成人局灶性癫痫规范化诊治指南(2022)

中华神经外科杂志
肖波
周东
周罗
龙莉莉
冯莉
出处: 中华神经科杂志 2022 年12 月第 55 卷第 12 期
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癫痫是中枢神经系统常见的慢性疾病,在成人癫痫患者中,绝大部分为局灶性癫痫,约占61.7%(国外文献报道该比例高达90%)。成人局灶性癫痫病因众多、病理机制复杂、症状表现差异较大,常给临床医师在制订诊疗策略时带来困惑。

鉴于此,中华医学会神经病学分会脑电图与癫痫学组组织相关专家,参考国内外相关指南、专家共识及最新文献,结合当前国内医疗发展实际情况,讨论并撰写了《中国成人局灶性癫痫规范化诊治指南》,旨在为我国成人局灶性癫痫患者提供更加实用、规范的诊疗方案。

01

局灶性癫痫发作的分类


对于局灶性发作,首先应依据发作时患者意识是否受损进行分类。其次,如果能获取详细的患者发作时的临床表现或主观感受,根据发作最初始的症状,局灶性发作可进一步分为局灶起源运动发作和局灶起源非运动发作。详见表1。


表1 局灶性癫痫发作的分类

image.png


值得注意的是,局灶性癫痫患者致痫灶可包括单灶和多灶,或累及单侧大脑半球。因此,虽然大多有惯常发作,但也可每次局灶性发作的临床表现不完全相同,即同一患者可以有多个致痫网络和多种发作类型,但每种发作类型的异常电活动起源部位和初始临床症状应该一致。

02

局灶性癫痫综合征的临床表现


依据成人局灶性癫痫发作起源进行解剖学定位,可出现特定的一组临床症状,即癫痫综合征。在成人局灶性癫痫中,临床最常见的癫痫综合征为颞叶癫痫和额叶癫痫。


1

颞叶癫痫


颞叶癫痫发作起源于内侧颞叶的海马、杏仁核、海马旁回和颞叶外侧新皮质区域,是临床最常见的成人局灶性癫痫,以成人和青少年多见,患者年幼时可能有热性惊厥史,发作类型包括伴意识受损或保留的局灶性发作,或进展为双侧强直阵挛发作。


颞叶癫痫解剖定位和发作症状特点见表2。绝大部分颞叶癫痫为症状性癫痫,少部分病例有家族史可能为遗传相关特发性癫痫,即家族性颞叶癫痫。结构异常是颞叶癫痫最常见的病因。


表2

颞叶癫痫临床发作症状特点

image.png


2

额叶癫痫


在成人局灶性癫痫中,额叶癫痫患病率仅次于颞叶癫痫,发作时可出现意识受损或保留。


额叶癫痫解剖定位和发作症状特点见表3。成人额叶癫痫常见病因包括肿瘤、脑血管病、动静脉畸形、脑外伤、局灶性皮质发育不良等。

表3

额叶癫痫临床发作症状特点

image.png


3

枕叶癫痫


枕叶癫痫主要表现为视觉障碍突出的局灶感觉发作,常见视幻觉和视错觉,如发作性盲点、偏盲、黑矇或者表现为火花、闪光、光幻觉。若致痫网络累及颞、顶、枕连接区域可出现复杂的视觉感受,如视物的大小和远近的改变、物体倾斜或变形等。致痫网络异常放电也可累及颞叶,出现颞叶癫痫的类似症状。


4

顶叶癫痫


顶叶癫痫主要表现为局灶感觉发作,通常意识保留,以躯体感觉异常为突出表现,可出现部分肢体感觉缺失、麻木、疼痛、灼烧或触电感、躯体失认、幻多肢症等异常表现,顶下小叶受累可产生严重眩晕与空间定向障碍。


5

岛叶癫痫


岛叶位于大脑外侧裂深部,与额叶、颞叶、顶叶以及杏仁核和基底核存在紧密的神经纤维联系,因此岛叶起源的癫痫发作异常电活动可沿致痫网络向临近脑区扩散,其发作表现复杂多变,可出现嗅觉、味觉、听觉、痛温觉等感觉异常,或出现局灶性运动症状及自主神经功能异常,症状学与颞叶癫痫、额叶癫痫、顶叶癫痫较难鉴别。



表4

枕叶、顶叶及岛叶癫痫临床发作症状特点

image.png


03

局灶性癫痫综合征的诊断


详细可靠的发作病史是癫痫发作分类和诊断局灶性癫痫的关键。


依据2017年国际抗癫痫联盟(ILAE)对癫痫诊断的定义,以下三者满足其一即可诊断为癫痫:

(1)间隔超过24 h的至少2次非诱发性癫痫发作;

(2)单次发作但再发风险高(未来10年复发概率大于60%,如既往脑损伤、脑电图结果明显异常、神经影像学异常、夜间发作);

(3)被诊断为癫痫综合征。


在明确患者癫痫发作类型为局灶性发作的基础上,结合体格检查、脑电图、影像学、实验室检查等辅助检查结果,满足上述ILAE癫痫诊断标准时,可诊断为局灶性癫痫。并根据ILAE的推荐进一步明确属于何种癫痫综合征及相关病因。


1

体格检查


局灶性癫痫患者的神经系统体格检查可完全正常,也可能因颅内病变出现相应的神经功能缺损,或合并其他有特征性的非神经系统体征,如颅内肿瘤或脑血管病出现一侧肢体偏瘫、结节性硬化出现血管纤维瘤和色素脱失斑、线粒体病出现身材矮小和认知障碍、中枢神经系统感染出现颈项强直等,应结合患者病史和辅助检查结果有针对性地进行体格检查。


2

脑电图检查


推荐意见:

(1)对怀疑有局灶性癫痫发作的患者应进行头皮脑电图检查,常规脑电图无阳性发现,建议行动态或视频脑电图(Ⅰ级证据,A级推荐);


(2)硬膜下电极脑电图立体定向脑电图临床应用安全,耐受性良好,可用于癫痫外科术前致痫区定位(Ⅲ级证据,B级推荐)。


3

影像学检查


推荐意见:

(1)局灶性癫痫患者应进行头部1.5 T以上磁共振成像检查,考虑钙化或出血性病变时结合头部电子计算机体层扫描,无阳性发现建议行HARNESS癫痫高分辨率结构序列成像(Ⅱ级证据,B级推荐);


(2)若结构影像学结果为阴性,推荐头部氟代脱氧葡萄糖正电子发射体层摄影用于致痫区定位(Ⅱ级证据,B级推荐);


(3)其他功能影像学检查磁共振波谱分析、功能磁共振成像、单光子发射计算机体层摄影及脑磁图可作为辅助手段用于致痫区定位(Ⅳ级证据,C级推荐)。


4

实验室检查及其它辅助检查


局灶性癫痫患者的实验室检查主要包括血液、尿液、脑脊液检查,其可以提供诊断及鉴别诊断信息。此外,怀疑病因为遗传病时,可酌情进行针对性的基因检查。

推荐意见:
(1)血常规、血尿生化、腰椎穿刺脑脊液检查有助于明确局灶性癫痫病因及监测抗癫痫发作药物的不良反应(Ⅳ级证据,C级推荐);

(2)怀疑为遗传相关局灶性癫痫时,可针对性地进行靶向基因测序、全外显子测序等基因检查(Ⅴ级证据,D级推荐);

(3)心电图、心脏彩超及右心声学造影可用于排除心源性发作疾病(Ⅴ级证据,D级推荐)。


5

局灶性癫痫病因分类


与全面性癫痫不同的是,成人局灶性癫痫很大一部分为症状性癫痫,少部分为特发性癫痫,可能与遗传因素相关。

依据2017年ILAE提出的癫痫发作类型和病因分类建议,局灶性癫痫的病因可依次分为结构异常、感染、免疫、代谢、遗传其他未知原因6大类。


04

局灶性癫痫综合征的治疗


药物治疗


目前局灶性癫痫的治疗,在针对病因治疗的基础上,给予抗癫痫发作药物治疗必不可少。若经过足量、足疗程、合理选用的2种或以上的抗癫痫发作药物治疗后,仍不能有效控制癫痫发作,则可能进展为耐药性癫痫。若局灶性癫痫的病因明确,则应积极针对病因治疗,必要时经过多学科联合评估是否手术治疗。


局灶性癫痫的药物治疗应遵循尽可能单药治疗的原则,若单药控制不佳,再选择不同作用机制的抗癫痫发作药物联合治疗(表5),同时兼顾患者的年龄、性别、合并用药、共患病及患者意愿等因素综合考虑。


表5

抗癫痫发作药物及其作用机制

image.png

注:GABA:γ氨基丁酸;AMPA:α-氨基-3-羟基-5-甲基-4-异噁唑丙酸;Sv2a:突触囊泡蛋白2A


表6

成人局灶性癫痫药物治疗推荐

image.png


推荐意见:


(1)拉莫三嗪、卡马西平、左乙拉西坦、唑尼沙胺可作为成人局灶性癫痫的首选单药治疗(Ⅰ级证据,A级推荐);


(2)针对大于65岁的老年局灶性癫痫患者,拉莫三嗪可作为首选单药治疗(Ⅰ级证据,A级推荐);


(3)奥卡西平、丙戊酸、艾司利卡西平、布瓦西坦可用于成人局灶性癫痫的单药治疗(Ⅲ级证据,B级推荐);


(4)吡仑帕奈(Ⅰ级证据,A级推荐),拉考沙胺(Ⅱ级证据,B级推荐),艾司利卡西平、布瓦西坦、唑尼沙胺和托吡酯(Ⅳ级证据,C级推荐)可用于成人耐药局灶性癫痫的添加药物治疗。


外科手术及神经调控治疗


对于短时间内可能导致神经功能迅速恶化的病变如脑肿瘤、脑脓肿、快速进展的Rasmussen脑炎等,可经评估后尽早实施手术,其余患者则遵循以下指征:

(1)明确为耐药性癫痫,病程2年以上,使用2种或2种以上足量、足疗程合理选用的抗癫痫发作药物疗效不佳或无效;

(2)经临床症状、脑电图及影像学等评估有明确致痫灶;

(3)患者和家属有手术治疗意愿。


推荐意见:


(1)对耐药局灶性癫痫患者,建议多学科联合评估手术指征及治疗方案,若致痫灶明确,建议外科手术切除治疗(Ⅱ级证据,B级推荐);


(2)外科手术困难或失败的耐药局灶性癫痫患者,可选择迷走神经刺激(Ⅲ级证据,B级推荐)、反应性神经电刺激、脑深部电刺激(Ⅳ级证据,C级推荐)神经调控术减少癫痫发作;


(3)反应性神经电刺激和脑深部电刺激可能减少患者癫痫的猝死风险(Ⅳ级证据,C级推荐);


(4)无创神经调控术经颅磁刺激、经颅直流电刺激、经皮迷走神经刺激可能减少该类患者的癫痫发作(Ⅴ级证据,D级推荐)。



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文献来源:

中华医学会神经病学分会
中华医学会神经病学分会脑电图与癫痫学组
中国成人局灶性癫痫规范化诊治指南[J].
中华神经科杂志,2022,55(12):1341-1352.


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