Division of Pediatric Neurology, David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States.
Division of Pediatric Neurology, David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States.
Epilepsy Behav. 2021 Feb;115:107624. doi: 10.1016/j.yebeh.2020.107624. Epub 2020 Dec 16.
Epileptic spasms are often preceded by focal (or multifocal) seizures. Based on a series of case reports suggesting that carbamazepine and oxcarbazepine may induce epileptic spasms, we set out to rigorously evaluate the potential association between exposure to voltage-gated sodium channel blockade and latency to epileptic spasms.
We identified 50 cases (children with focal seizures and evolution to epileptic spasms) and 50 controls (children with focal seizures without evolution to epileptic spasms). For each patient, we reviewed all sequential neurology encounters between onset of epilepsy and emergence of epileptic spasms. For each encounter we recorded seizure-frequency and all anti-seizure therapy exposures. Using multivariable Cox proportional hazards regression, we evaluated the association between voltage-gated sodium channel exposure (carbamazepine, oxcarbazepine, lacosamide, or phenytoin) and latency to epileptic spasms onset, with adjustment for etiology and seizure-frequency.
Latency to epileptic spasms onset was independently associated with exposure to sodium channel blockade (hazard ratio = 2.4; 95% CI 1.1-5.2; P = 0.03) and high-risk etiology (hazard ratio = 2.8; 95% CI 1.5-5.1; P = 0.001). With assessment for interaction between sodium channel blockade and etiology, we identified an estimated 7-fold increased risk of epileptic spasms with the combination of sodium channel blockade and high-risk etiology (hazard ratio = 7.0, 95% CI 2.5-19.8; P < 0.001).
This study suggests that voltage-gated sodium channel blockade may induce epileptic spasms among children at risk on the basis of etiology. Further study is warranted to replicate these findings, ascertain possible drug- and dose-specific risks, and identify potential mechanisms of harm.
癫痫发作常伴有局灶性（或多灶性）发作。基于一系列病例报告表明卡马西平和奥卡西平可能诱发癫痫发作，我们着手严格评估电压门控钠通道阻断与癫痫发作潜伏期之间的潜在关联。
我们确定了 50 例（局灶性发作并发展为癫痫发作的儿童）和 50 例对照（局灶性发作未发展为癫痫发作的儿童）。对于每位患者，我们回顾了癫痫发作开始至癫痫发作发作之间的所有连续神经学就诊。对于每次就诊，我们记录了发作频率和所有抗癫痫治疗的暴露情况。使用多变量 Cox 比例风险回归，我们评估了电压门控钠通道暴露（卡马西平、奥卡西平、拉考沙胺或苯妥英）与癫痫发作潜伏期之间的关联，调整了病因和发作频率。
癫痫发作潜伏期与钠通道阻断的暴露独立相关（风险比=2.4；95%CI 1.1-5.2；P=0.03）和高风险病因（风险比=2.8；95%CI 1.5-5.1；P=0.001）。在评估钠通道阻断和病因之间的相互作用时，我们发现钠通道阻断和高风险病因的组合使癫痫发作的风险增加了约 7 倍（风险比=7.0，95%CI 2.5-19.8；P<0.001）。
这项研究表明，在病因的基础上，电压门控钠通道阻断可能在有风险的儿童中诱发癫痫发作。需要进一步研究来复制这些发现，确定可能的药物和剂量特异性风险，并确定潜在的危害机制。
