Pisano Tiziana, Numis Adam L, Heavin Sinéad B, Weckhuysen Sarah, Angriman Marco, Suls Arvid, Podesta Barbara, Thibert Ronald L, Shapiro Kevin A, Guerrini Renzo, Scheffer Ingrid E, Marini Carla, Cilio Maria Roberta
Neurology Unit and Laboratories, A. Meyer Children's Hospital, Florence, Italy.
Department of Neurology, University of California, San Francisco, San Francisco, California, U.S.A.
Epilepsia. 2015 May;56(5):685-91. doi: 10.1111/epi.12984. Epub 2015 Apr 16.
To 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.
We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data.
Seizure onset was between 1 and 4 days 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 2 weeks 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.
Our 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.
描述因KCNQ2基因突变导致的早期婴儿癫痫性脑病患者在新生儿期及出生后第一年的抗癫痫药物（AED）治疗情况。
我们确定了15例患者，并回顾了其电临床、神经影像学和AED治疗数据。
癫痫发作始于出生后1至4天，9例患者每日出现强直性不对称、局灶性和阵挛性发作，其余6例出现癫痫持续状态。脑电图（EEG）显示9例患者有多灶性癫痫样异常，6例呈爆发抑制模式。所有患者在达到无癫痫发作前均试用了多种AED的充足日剂量。6例患者（40%）在服用卡马西平（CBZ）2周内实现了癫痫控制，5例（33%）服用苯妥英（PHT）后无癫痫发作。最后4例患者（27%）分别成功接受了托吡酯（TPM）（2例）、左乙拉西坦（LEV）（1例）以及LEV与TPM联合治疗（1例）。大多数患者在出生后第一年内达到无癫痫发作，此后一直无发作。12例患者在随访时有中度至重度发育迟缓。然而，癫痫发作在数天内停止的2例患者仅表现为轻度认知障碍。
我们的研究结果表明，作用于钠通道的药物，包括CBZ和PHT，应被视为KCNQ2脑病患者的一线治疗药物。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疗效可能与其对两种通道的调节作用有关。KCNQ2突变类型可能影响AED反应以及发育结局。早期识别KCNQ2脑病并随后进行最恰当有效的治疗对于减少与此疾病相关的神经发育损害可能很重要。
