Farias-Moeller Raquel, Hanin Aurélie, Ahsan Sadaf, Brooks John, Caganap Scott D, Czeisler Barry, Cheuret Emmanuel, Cocuzzo Brianna, Hahn Cecil D, Kyureghyan Henrik, Marcoux Marie-Odile, Mohamed Rana, Park Carol, Stern Zimmer Michal, Barun Vivek, Lai Yi Chen, Hirsch Lawrence J
Department of Neurology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, WI, USA.
Department of Neurology, Comprehensive Epilepsy Center, Yale University School of Medicine, New Haven, CT, USA.
Neurocrit Care. 2025 Apr 25. doi: 10.1007/s12028-025-02254-9.
New-onset refractory status epilepticus (NORSE) is a devastating condition with high mortality and poor long-term outcomes. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE, preceded by fever. Intrathecal dexamethasone (IT-DEX) has emerged as a potential treatment, but few cases have been reported. This study aims to describe the use of IT-DEX in NORSE/FIRES, focusing on treatment logistics, dosing strategies, and patient outcomes.
We conducted a retrospective analysis of 12 patients (10 children and 2 adults) with NORSE (including FIRES) enrolled in an international multicenter clinical biorepository who received IT-DEX as part of their treatment. Demographic and clinical data were extracted. IT-DEX pharmacological details and administration logistics were collected by contacting the primary investigators. A descriptive analysis was performed to evaluate treatment timing, dosage, and concurrent management, as well as clinical outcomes and cytokine profiles.
All patients qualified as FIRES. Patients were treated with a median of five doses of IT-DEX, starting a median of 20 days after refractory status epilepticus onset, with a median dose per infusion of 5 mg (0.21 mg/kg/dose). Clinicians reported a perceived favorable effect on seizure control in 83% of cases, with a median delay of 5 days to wean off continuous infusions after the last IT-DEX administration. Cytokine analysis (based on data from four patients with serial cerebrospinal fluid measurements and two patients with serial blood measurements) revealed persistently elevated levels of proinflammatory markers in most patients, with no significant changes following IT-DEX administration. No adverse effects were reported.
Most clinicians perceived a favorable effect of IT-DEX in refractory status epilepticus termination, and its use appears to be safe in patients with FIRES. This study provides a detailed description of administration logistics and dosing strategies from an international multicenter cohort. Additional studies are needed to confirm the safety and efficacy of IT-DEX and determine its impact on long-term outcomes including epilepsy prevention and functional recovery.
新发难治性癫痫持续状态（NORSE）是一种具有高死亡率和不良长期预后的毁灭性疾病。发热感染相关癫痫综合征（FIRES）是NORSE的一个亚型，发病前有发热症状。鞘内注射地塞米松（IT-DEX）已成为一种潜在的治疗方法，但报道的病例很少。本研究旨在描述IT-DEX在NORSE/FIRES中的应用，重点关注治疗流程、给药策略和患者预后。
我们对12例（10例儿童和2例成人）NORSE（包括FIRES）患者进行了回顾性分析，这些患者纳入了一个国际多中心临床生物样本库，接受IT-DEX作为其治疗的一部分。提取了人口统计学和临床数据。通过联系主要研究者收集IT-DEX的药理学细节和给药流程。进行描述性分析以评估治疗时机、剂量和同期管理，以及临床结果和细胞因子谱。
所有患者均符合FIRES标准。患者接受IT-DEX的中位剂量为5剂，在难治性癫痫持续状态发作后中位20天开始，每次输注的中位剂量为5mg（0.21mg/kg/剂量）。临床医生报告，83%的病例在癫痫控制方面有明显效果，最后一次IT-DEX给药后，停止持续输注的中位延迟时间为5天。细胞因子分析（基于4例进行系列脑脊液测量的患者和2例进行系列血液测量的患者的数据）显示，大多数患者的促炎标志物水平持续升高，IT-DEX给药后无显著变化。未报告不良反应。
大多数临床医生认为IT-DEX在终止难治性癫痫持续状态方面有明显效果，并且其在FIRES患者中的使用似乎是安全的。本研究提供了来自国际多中心队列的给药流程和给药策略的详细描述。需要进一步的研究来证实IT-DEX的安全性和有效性，并确定其对包括预防癫痫和功能恢复在内的长期预后的影响。
