Kapur Jaideep
Department of Neurology and Neuroscience Brain Institute University of Virginia, School of Medicine, Health Sciences Center, Box 801330, Charlottesville, VA 22908-1330, USA.
Neurotherapeutics. 2025 Jan;22(1):e00514. doi: 10.1016/j.neurot.2024.e00514. Epub 2024 Dec 18.
Generalized Convulsive status epilepticus (SE) is a neurological emergency because prolonged convulsions can cause respiratory compromise and neuronal injury. Compromised GABA-mediated inhibition is a defining feature of SE, and many current therapies are benzodiazepines, which are allosteric modulators of GABA-A receptors. Many patients with medically refractory epilepsy are at risk for SE. Newly available nasally delivered benzodiazepines: midazolam and diazepam given for seizure clusters may prevent SE. Although three different benzodiazepines, diazepam, lorazepam and midazolam terminate early SE, midazolam is preferred. It is administered via the intramuscular route, which saves time and is at least as practical or more effective than intravenous lorazepam. Unfortunately, many early SE patients are receiving inadequate doses of benzodiazepines. Patients who fail to respond to adequate doses of benzodiazepines are considered to be in established SE. Levetiracetam, fosphenytoin, and valproic acid are equally safe and effective in treating established SE. The rate of cardiovascular complications: cardiac arrhythmias and hypotension were low in patients treated with phenytoin, levetiracetam, or valproic acid. In contrast, overall, 25 % of patients in established SE were intubated, and this was in response to respiratory compromise in many patients. Interestingly, children treated with fosphenytoin were more likely to require intubation than those treated with valproic acid or levetiracetam. Better therapies are needed for the treatment established SE, because all three drugs were effective in less than 50 % of the patients.
全身性惊厥性癫痫持续状态(SE)是一种神经急症,因为长时间惊厥可导致呼吸功能不全和神经元损伤。γ-氨基丁酸(GABA)介导的抑制作用受损是SE的一个决定性特征,目前许多治疗方法都是使用苯二氮䓬类药物,它们是GABA-A受体的变构调节剂。许多药物难治性癫痫患者有发生SE的风险。新上市的经鼻给药苯二氮䓬类药物:用于癫痫发作丛集的咪达唑仑和地西泮可能预防SE。虽然三种不同的苯二氮䓬类药物,即地西泮、劳拉西泮和咪达唑仑可终止早期SE,但咪达唑仑是首选。它通过肌肉注射途径给药,节省时间,至少与静脉注射劳拉西泮一样实用或更有效。不幸的是,许多早期SE患者接受的苯二氮䓬类药物剂量不足。对足量苯二氮䓬类药物无反应的患者被认为处于确立的SE状态。左乙拉西坦、磷苯妥英和丙戊酸在治疗确立的SE方面同样安全有效。接受苯妥英、左乙拉西坦或丙戊酸治疗的患者中心血管并发症(心律失常和低血压)的发生率较低。相比之下,总体而言,确立的SE患者中有25%需要插管,这是许多患者对呼吸功能不全的反应。有趣的是,接受磷苯妥英治疗的儿童比接受丙戊酸或左乙拉西坦治疗的儿童更有可能需要插管。对于确立的SE的治疗需要更好的疗法,因为这三种药物对不到50%的患者有效。