Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.
摘要：
背景：癫痫持续状态（SE）是一种与残疾和死亡的重大风险相关的医疗紧急情况。SE的治疗遵循逐步的方法，关于难治性和超难治性SE（RSE/SRSE）的理想抗癫痫药物（ASM）的数据有限。Perampanel(PER),AMPA受体拮抗剂，在动物模型中显示出希望，但在人类中的数据仍然有限。本研究试图评估PER在RSE和SRSE患者中的最佳剂量和安全性。
方法：我们回顾性分析了17例接受PER治疗的RSE（1）或SRSE（16）成人患者。人口统计学和临床数据，包括脑电图模式，管理的ASM，每个剂量,和血浆浓度，被收集。对于接受24mgPER负荷剂量的患者（全剂量组），采用以下治疗方案：每天24mg，持续48h，每天16mg。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对PER的反应。监测肝肾功能评估安全性。
结果：观察到58.82%的反应率，与接受PER剂量低于24mg的患者（低剂量组）（16.67％）相比，全剂量组的反应明显更高（81.82％）（p值=0.004；OR0.044，95％CI0.003至0.621，p=0.021）。没有其他临床因素显着影响治疗反应。大多数患者的肝酶升高（70.59％），但自发降低。
结论：我们的研究结果表明，与低于24mg的剂量相比，24mgPER剂量持续48h可能更有效地管理RSE和SRSE。可能是由于药代动力学因素。
结论：RSE和SRSE的PER数据更可靠，包括标准化的给药程序和血浆水平监测是必要的。PER的潜在好处应该进一步探索，特别是在RSE和SRSE患者中。
方法：我们回顾性分析了17例接受PER治疗的RSE（1）或SRSE（16）成人患者。人口统计学和临床数据，包括脑电图模式，管理的ASM，每个剂量,和血浆浓度，被收集。对于接受24mgPER负荷剂量的患者（全剂量组），采用以下治疗方案：每天24mg，持续48h，每天16mg。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对PER的反应。监测肝肾功能评估安全性。
结果：观察到58.82%的反应率，与接受PER剂量低于24mg的患者（低剂量组）（16.67％）相比，全剂量组的反应明显更高（81.82％）（p值=0.004；OR0.044，95％CI0.003至0.621，p=0.021）。没有其他临床因素显着影响治疗反应。大多数患者的肝酶升高（70.59％），但自发降低。
结论：我们的研究结果表明，与低于24mg的剂量相比，24mgPER剂量持续48h可能更有效地管理RSE和SRSE。可能是由于药代动力学因素。
结论：RSE和SRSE的PER数据更可靠，包括标准化的给药程序和血浆水平监测是必要的。PER的潜在好处应该进一步探索，特别是在RSE和SRSE患者中。
