热性惊厥相关癫痫患者抗癫痫药物治疗疗效及与电压依赖性钠通道α1亚基基因突变的关系

Efficacy of anti-epileptic drugs in patients with epilepsy with febrile seizures plus and the relation with voltage-gated sodium channel α1-subunit gene mutations

目的 分析抗癫痫药物（AEDs）对热性惊厥相关癫痫（EFS＋）患者发作控制的效果,探讨EFS＋患者早期适宜的药物选择及与电压依赖性钠通道α1亚基（SCN1A）基因突变的关系.方法 回顾性分析2007年1月至2013年6月收集的202例进行SCN1A基因检测的EFS＋患者的AEDs治疗数据,比较不同AEDs对EFS＋患者发作控制的效果,并在EFS＋有或无SCN1A基因突变患者中做进一步比较.结果 EFS＋患者使用大于10例的AEDs共9种,分别为丙戊酸、托吡酯、氯硝安定、苯巴比妥、左乙拉西坦、拉莫三嗪、卡马西平、奥卡西平和苯妥英钠,其中使用比例最高的前3位为丙戊酸、托吡酯、氯硝安定.AEDs联合治疗占多数（166/202,82.2％）.与其他AEDs相比,丙戊酸（169/187,90.4％）、托吡酯（111/120,92.5％）和氯硝安定（69/78,88.5％）的对发作改善的疗效均较好,差异有统计学意义（P =0.000）;苯妥英钠和拉莫三嗪[0和8.9％ （4/45）]效果最差（P＜0.01）.苯巴比妥和左乙拉西坦的发作改善率[58.1％ （25/43）、44.7％ （21/47）]和无变化率[39.5％（17/43）、48.9％ （23/47）]疗效居中并接近,与其他AEDs比较差异有统计学意义（P＜0.01）.拉莫三嗪和卡马西平明显加重发作[57.8％（26/45）、36.7％ （18/49）]最高,苯妥英钠和奥卡西平次之[33.3％（15/45）和26.9％ （7/26）],与其他AEDs比较差异均有统计学意义（P＜0.01）.拉莫三嗪加重SCN1A突变患者发作的效果（13/16,81.3％）较无突变患者（13/29,44.8％）显著,差异有统计学意义（x2=5.607,P=0.018）;卡马西平、奥卡西平和苯妥英钠也可加重SCN1A基因突变患者的发作,但较无突变患者差异无统计学意义.结论 丙戊酸、托吡酯和氯硝安定是EFS＋患者早期治疗的较好药物选择;尽量避免在EFS＋尤其存在SCN1A突变的患者中使用有钠通道阻滞作用的AEDs.左乙拉西坦和苯巴比妥在EFS＋中的疗效尚不确切.

Objective To analyze the efficacy of seizure control by anti-epileptic drugs （AEDs） in patients with epilepsy with febrile seizure plus （EFS ＋）,and explore the proper medication choice in early stage of EFS ＋ and its relation with voltage-gated sodium channel α1-subunit （SCN1A） gene mutations.Methods In 202 patients with EFS ＋,the data of detected voltage-gated SCN1A gene mutations and their treatment history by AEDs were retrospectively reviewed.The comparative analysis of efficacy of seizure control was performed in each AED administrated and further compared between EFS ＋ patients with or without SCN1A gene mutations.Results Nine AEDs were administered in more than 10 cases,including valproate （VPA）,topiramete （TPM）,clonazepam （CNZ）,phenobarbital （PB）,levetiracetam （LEV）,lamotrigine （LTG）,carbamazepine （CBZ）,oxcarbazepine （OXC） and phenytoin （PHT）.Combined therapy was predominant （166/202,82.2%）.Compared with other AEDs,the improvement rates were the highest in VPA （169/187,90.4%）,TPM （111/120,92.5%） and CNZ （69/78,88.5% ;P =0.000）,and were lowest in PHT and LTG （0 and 8.9% （4/45）; P 〈 0.01）.The improvement rate （58.1% （25/43） and 44.7% （21/47）） and no change rate （39.5% （17/43） and 48.9% （23/47）） of PB and LEV were approximately intermediate,without statistically significant difference between them but with statistically significant difference with others （P 〈 0.01）.The aggravation rats of LTG and CBZ were the highest （57.8% （26/45） and 36.7% （18/49）） followed by OXC and PHT（33.3% （15/45） and 26.9% （7/26））.All of them showed statistically significant difference compared with others （P 〈 0.01）.The aggravation rate of LTG in patients with SCN1A mutations （13/16,81.3%） was significantly higher than those without SCN1A mutations （13/29,44.8%）,and there was statistically significant difference between them （x2 =5.607,P =0.018）; similarly,the aggravation rates of CBZ,OXC and PHT showed an increased tendency,but no significant difference compared with other AEDs.Conclusions VPA,TPM and CNZ are relatively recommended AEDs choices in patients with EFS ＋ in early stage.The study suggests avoiding using the AEDs with sodium channel blocking in EFS ＋,especially in the patients with SCN1A mutations.The efficacy of LEV and PB in EFS ＋ is uncertain.