Unit of Neurology and Unit of Clinical Neurophysiology, Department of Neuroscience, University of Padua, Padua, Italy.
Unit of Neurology and Unit of Clinical Neurophysiology, Department of Neuroscience, University of Padua, Padua, Italy; Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland.
Epilepsy Behav. 2024 Jul;156:109826. doi: 10.1016/j.yebeh.2024.109826. Epub 2024 May 17.
Status epilepticus (SE) is a medical emergency associated with a significant risk of disability and death. The treatment of SE follows a step-wise approach, with limited data on ideal antiseizure medications (ASMs) for refractory and super refractory SE (RSE/SRSE). Perampanel (PER), an AMPA receptor antagonist, has shown promise in animal models but still has limited data in humans. This study tried to evaluate optimal dosage and safety of PER in RSE and SRSE patients.
We retrospectively analysed 17 adult patients with RSE (1) or SRSE (16) treated with PER. Demographic and clinical data, including EEG patterns, ASMs administered, PER dosages, and PER plasma concentrations, were collected. For patients receiving a 24 mg PER loading dose (full dose group), the following treatment regimen was applied: 24 mg per day for 48 h following by 16 mg per day. The response to PER was assessed based on electroencephalographic (EEG) improvement from high to low epileptiform activity or from low to the absence of epileptiform activities. Safety was evaluated monitoring hepatic and renal function.
A response rate of 58.82 % was observed, with significantly higher responses in the full dose group (81.82 %) compared to those receiving PER doses below 24 mg (low dose group) (16.67 %) (p-value = 0.004; OR 0.044, 95 % CI 0.003 to 0.621, p = 0.021). No other clinical factors significantly influenced treatment response. Hepatic enzymes become elevated in most patients (70.59 %) but spontaneously decreased.
Our findings suggest that a 24 mg PER dose administered for 48 h may be more effective in managing RSE and SRSE compared to doses below 24 mg, potentially due to pharmacokinetic factors.
More robust data on PER in RSE and SRSE, including standardized dosing procedures and plasma level monitoring are needed. PER's potential benefits should be explored further, particularly in patients with RSE and SRSE.
癫痫持续状态（SE）是一种与残疾和死亡风险显著相关的医疗紧急情况。SE 的治疗遵循逐步治疗方法，对于难治性和超难治性 SE（RSE/SRSE），理想的抗癫痫药物（ASM）的数据有限。AMPA 受体拮抗剂吡仑帕奈（PER）在动物模型中显示出前景，但在人类中数据仍然有限。本研究试图评估 PER 在 RSE 和 SRSE 患者中的最佳剂量和安全性。
我们回顾性分析了 17 名接受 PER 治疗的 RSE（1）或 SRSE（16）成年患者。收集了人口统计学和临床数据，包括 EEG 模式、给予的 ASM、PER 剂量和 PER 血浆浓度。对于接受 24mg PER 负荷剂量（全剂量组）的患者，采用以下治疗方案：24mg 持续 48 小时，然后 16mg 持续 48 小时。根据脑电图（EEG）从高到低癫痫样活动或从低到无癫痫样活动的改善来评估 PER 的反应。通过监测肝肾功能评估安全性。
观察到 58.82%的反应率，全剂量组（81.82%）的反应率明显高于接受低于 24mg PER 剂量的患者（低剂量组）（16.67%）（p 值=0.004；比值比 0.044，95%CI 0.003 至 0.621，p=0.021）。没有其他临床因素对治疗反应有显著影响。大多数患者（70.59%）的肝酶升高，但自发性下降。
我们的研究结果表明，与低于 24mg 的剂量相比，24mg PER 剂量持续 48 小时给药可能更有效地治疗 RSE 和 SRSE，这可能与药代动力学因素有关。
需要更多关于 PER 在 RSE 和 SRSE 中的数据，包括标准化的给药程序和血浆水平监测。PER 的潜在益处需要进一步探索，特别是在 RSE 和 SRSE 患者中。
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