Intravenous ganaxolone in pediatric super-refractory status epilepticus: A single hospital experience.
Intravenous ganaxolone in pediatric super-refractory status epilepticus: A single hospital experience.
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DOI：
10.1016/j.ebr.2022.100567
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发表时间：
2022
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除了连续静脉输注麻醉剂之外，儿科SRSE的治疗选择有限;需要新的治疗选择来降低发病率和死亡率。加奈索酮具有作用于突触内和突触外GABAA受体的独特机制，促进神经元信号传导的紧张性抑制。在我们的两名患者中，加奈索酮辅助剂似乎能有效终止SRSE，使IV麻醉剂能够脱机并最终出院。突触GABAA受体（GABAAR）内化有助于超难治性癫痫持续状态（SRSE）的耐药性。加奈索酮是内源性神经活性类固醇别孕烯醇酮的3β-甲基化合成类似物，对突触和突触外GABAA受体具有正变构调节活性。加奈索酮目前正在临床试验中，用于治疗罕见的儿科癫痫发作疾病和已建立的难治性SE。2例SRSE儿科患者（17岁和7岁）在紧急研究性新药（E-IND）应用下接受静脉（IV）加奈索酮治疗，作为初始推注和维持输注，持续长达4.5天，根据需要间歇IV推注，然后在第5天逐渐减少，并过渡到使用加奈索酮混悬液的长期治疗。加奈索酮辅助剂可有效终止两例患者的SRSE，安全地允许停用IV麻醉剂。在过渡到肠道加奈索酮后，癫痫控制一直保持不变。需要进一步研究加奈索酮作为SRSE的安全有效治疗。
Treatment options for pediatric SRSE beyond continuous IV infusions of anesthetics are limited; novel therapeutic options are warranted to decrease morbidity and mortality. Ganaxolone has a unique mechanism acting on BOTH intrasynaptic AND extrasynaptic GABAA receptors promoting tonic inhibition of neuronal signaling. Adjunctive ganaxolone appeared effective in terminating SRSE in two of our patients, permitting IV anesthetics to be weaned and ultimate discharge. Synaptic GABAA receptor (GABAAR) internalization contributes to the drug resistant nature of super-refractory status epilepticus (SRSE). Ganaxolone is a 3β-methylated synthetic analog of the endogenous neuroactive steroid, allopregnanolone, that has positive allosteric modulatory activity on synaptic and extrasynaptic GABAA receptors. Ganaxolone is currently in clinical trials to treat rare pediatric seizure disorders and established and refractory SE. Two pediatric patients with SRSE (age 17 and age 7) were treated under emergency investigational new drug (E-IND) applications with intravenous (IV) ganaxolone administered as an initial bolus and a maintenance infusion for up to 4.5 days with intermittent IV boluses as-needed followed by taper on day 5 and transitioned to chronic treatment using ganaxolone suspension. Adjunctive ganaxolone was effective in terminating SRSE in both patients, safely permitting IV anesthetics to be weaned. Seizure control has been maintained after transitioning to enteric ganaxolone. Further investigation of ganaxolone as a safe and effective treatment for SRSE is warranted.