Department of Pharmacology, University of Oxford, Oxford, UK.
Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Nat Rev Neurol. 2022 Jul;18(7):428-441. doi: 10.1038/s41582-022-00664-3. Epub 2022 May 10.
Status epilepticus is a life-threatening neurological emergency that affects both adults and children. Approximately 36% of episodes of status epilepticus do not respond to the current preferred first-line treatment, benzodiazepines. The proportion of episodes that are refractory to benzodiazepines is higher in low-income and middle-income countries (LMICs) than in high-income countries (HICs). Evidence suggests that longer episodes of status epilepticus alter brain physiology, thereby contributing to the emergence of benzodiazepine resistance. Such changes include alterations in GABA receptor function and in the transmembrane gradient for chloride, both of which erode the ability of benzodiazepines to enhance inhibitory synaptic signalling. Often, current management guidelines for status epilepticus do not account for these duration-related changes in pathophysiology, which might differentially impact individuals in LMICs, where the average time taken to reach medical attention is longer than in HICs. In this Perspective article, we aim to combine clinical insights and the latest evidence from basic science to inspire a new, context-specific approach to efficiently managing status epilepticus.
癫痫持续状态是一种危及生命的神经系统急症，可影响成人和儿童。大约 36%的癫痫持续状态发作对目前首选的一线治疗药物苯二氮䓬类药物没有反应。在中低收入国家（LMICs），苯二氮䓬类药物难治性癫痫持续状态发作的比例高于高收入国家（HICs）。有证据表明，癫痫持续状态发作时间延长会改变大脑生理机能，从而导致苯二氮䓬类药物耐药性的出现。这些变化包括 GABA 受体功能的改变和氯离子跨膜梯度的改变，这两者都削弱了苯二氮䓬类药物增强抑制性突触信号传递的能力。目前的癫痫持续状态管理指南往往没有考虑到这些与持续时间相关的病理生理学变化，这可能会对 LMICs 中的个体产生不同的影响，因为在 LMICs 中，到达医疗机构的平均时间长于 HICs。在这篇观点文章中，我们旨在结合临床见解和基础科学的最新证据，为有效地管理癫痫持续状态提供一种新的、特定于背景的方法。
