Ochoa Juan G, Dougherty Michelle, Papanastassiou Alex, Gidal Barry, Mohamed Ismail, Vossler David G
University of South Alabama, Mobile, AL, USA.
Neurotech LLC, Waukesha, WI, USA.
Epilepsy Curr. 2021 Mar 10;21(6):1535759721999670. doi: 10.1177/1535759721999670.
Super-refractory status epilepticus (SRSE) presents management challenges due to the absence of randomized controlled trials and a plethora of potential medical therapies. The literature on treatment options for SRSE reports variable success and quality of evidence. This review is a sequel to the 2020 American Epilepsy Society (AES) comprehensive review of the treatment of convulsive refractory status epilepticus (RSE).
We sought to determine the effectiveness of treatment options for SRSE. We performed a structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) for studies on reported treatments of SRSE. We excluded antiseizure medications (ASMs) covered in the 2016 AES guideline on the treatment of established SE and the convulsive RSE comprehensive review of the 2020 AES. Literature was reviewed on the effectiveness of vagus nerve stimulation, ketogenic diet (KD), lidocaine, inhalation anesthetics, brain surgery, therapeutic hypothermia, perampanel, pregabalin (PGB), and topiramate in the treatment of SRSE. Two authors reviewed each therapeutic intervention. We graded the level of the evidence according to the 2017 classification scheme of the American Academy of Neurology.
For SRSE (level U; 39 class IV studies total), insufficient evidence exists to support that perampanel, PGB, lidocaine, or acute vagus nerve stimulation (VNS) is effective. For children and adults with SRSE, insufficient evidence exists to support that the KD is effective (level U; 5 class IV studies). For adults with SRSE, insufficient evidence exists that brain surgery is effective (level U, 7 class IV studies). For adults with SRSE insufficient, evidence exists that therapeutic hypothermia is effective (level C, 1 class II and 4 class IV studies). For neonates with hypoxic-ischemic encephalopathy, insufficient evidence exists that therapeutic hypothermia reduces seizure burden (level U; 1 class IV study). For adults with SRSE, insufficient evidence exists that inhalation anesthetics are effective (level U, 1 class IV study) and that there is a potential risk of neurotoxicity.
For patients with SRSE insufficient, evidence exists that any of the ASMs reviewed, inhalational anesthetics, ketogenic diet, acute VNS, brain surgery, and therapeutic hypothermia are effective treatments. Data supporting the use of these treatments for SRSE are scarce and limited mainly to small case series and case reports and are confounded by differences in patients' population, and comedications, among other factors.
超难治性癫痫持续状态（SRSE）由于缺乏随机对照试验以及大量潜在的药物治疗方法，给治疗带来了挑战。关于SRSE治疗选择的文献报道了不同的成功率和证据质量。本综述是2020年美国癫痫协会（AES）对惊厥性难治性癫痫持续状态（RSE）治疗的全面综述的续篇。
我们试图确定SRSE治疗选择的有效性。我们对已报道的SRSE治疗研究进行了结构化文献检索（MEDLINE、Embase、CENTRAL、CINAHL）。我们排除了2016年AES关于已确诊癫痫持续状态治疗指南以及2020年AES惊厥性RSE全面综述中涵盖的抗癫痫药物（ASM）。对迷走神经刺激、生酮饮食（KD）、利多卡因、吸入麻醉剂、脑手术、治疗性低温、吡仑帕奈、普瑞巴林（PGB）和托吡酯治疗SRSE的有效性进行了文献综述。两位作者对每种治疗干预进行了综述。我们根据美国神经病学学会2017年的分类方案对证据水平进行了分级。
对于SRSE（U级；共39项IV级研究），没有足够的证据支持吡仑帕奈、PGB、利多卡因或急性迷走神经刺激（VNS）是有效的。对于患有SRSE的儿童和成人，没有足够的证据支持KD是有效的（U级；5项IV级研究）。对于患有SRSE的成人，没有足够的证据表明脑手术是有效的（U级，7项IV级研究）。对于患有SRSE的成人，没有足够的证据表明治疗性低温是有效的（C级，1项II级和4项IV级研究）。对于患有缺氧缺血性脑病的新生儿，没有足够的证据表明治疗性低温能减轻癫痫发作负担（U级；1项IV级研究）。对于患有SRSE的成人，没有足够的证据表明吸入麻醉剂是有效的（U级，1项IV级研究），并且存在神经毒性的潜在风险。
对于患有SRSE的患者，没有足够的证据表明所审查的任何ASM、吸入麻醉剂、生酮饮食、急性VNS、脑手术和治疗性低温是有效的治疗方法。支持将这些治疗方法用于SRSE的数据很少，并且主要限于小型病例系列和病例报告，并且受到患者人群差异、合并用药等因素的混淆。
