Early and effective treatment of KCNQ2 encephalopathy
Early and effective treatment of KCNQ2 encephalopathy
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DOI：
10.1111/epi.12984
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发表时间：
2015-05-01
期刊：
影响因子：
5.6
通讯作者：
Cilio, Maria Roberta
中科院分区：
文献类型：
--
作者：
Pisano, Tiziana;Numis, Adam L.;Cilio, Maria Roberta
目的 描述新生儿期和出生后第一年因 KCNQ2 突变导致的早期婴儿癫痫性脑病患者的抗癫痫药物 (AED) 治疗。方法我们确定了 15 例患者，并回顾了电临床、神经影像学和 AED 治疗数据。结果癫痫发作发生在 1 至 4 日龄之间，9 名患者每日出现强直性不对称性、局灶性和阵挛性癫痫发作，其中 1 名患者出现癫痫持续状态。剩下六个。脑电图 (EEG) 显示 9 名患者出现多灶性癫痫样异常，6 名患者出现突发抑制模式。所有患者在达到无癫痫发作之前都接受了每日足够剂量的几种 AED 试验。六名患者 (40%) 在卡马西平 (CBZ) 给药后 2 周内实现了癫痫发作控制，五名 (33%) 患者使用苯妥英 (PHT) 后癫痫发作消失。最后四名患者 (27%) 成功接受了托吡酯 (TPM)（两名患者）、左乙拉西坦 (LEV)（一名）以及 LEV 与 TPM 联合用药（一名）的治疗。大多数患者在生命的第一年内达到无癫痫发作，并在此后保持无癫痫发作。随访时，12 名患者出现中度至重度发育迟缓。然而，两名癫痫发作在发病几天内停止的患者仅表现出轻度认知障碍。 意义我们的研究结果表明，作用于钠通道的药物（包括CBZ和PHT）应被考虑作为KCNQ2脑病患者的一线治疗。电压门控钠通道和钾通道共定位于神经元膜。因此，作为钠通道阻滞剂的药物的功效可能与其对两个通道的调节作用有关。 KCNQ2 突变的类型可能会影响 AED 反应以及发育结果。早期识别 KCNQ2 脑病并随后采取最适当和有效的治疗对于减少与该疾病相关的神经发育障碍可能很重要。
ObjectivesTo describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.MethodsWe identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.ResultsSeizure onset was between 1 and 4days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography (EEG) showed multifocal epileptiform abnormalities in nine patients and a burst-suppression pattern in six. All patients were trialed with adequate daily doses of several AEDs before they reached seizure freedom. Six patients (40%) achieved seizure control within 2weeks of carbamazepine (CBZ) administration and five (33%) were seizure-free with phenytoin (PHT). The last four patients (27%) were successfully treated with topiramate (TPM) (two patients), levetiracetam (LEV) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure-free thereafter. Twelve patients had moderate-to-severe developmental delay at follow-up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment.SignificanceOur findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first-line treatment in patients with KCNQ2 encephalopathy. Voltage-gated sodium and potassium channels co-localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium-channel blockers could be linked to their modulating effect on both channels. The type of KCNQ2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.