Di Vito Lidia, Matteo Eleonora, Meletti Stefano, Zenesini Corrado, Bernabè Giorgia, Bomprezzi Chiara, Casadio Maria Chiara, Castioni Carlo Alberto, Cesnik Edward, Coniglio Carlo, Currò-Dossi Marco, De Massis Patrizia, Fallica Elisa, Florindo Irene, Giovannini Giada, Guarino Maria, Marchesi Elena, Marudi Andrea, Merli Elena, Monti Giulia, Orlandi Niccolò, Pasini Elena, Passarelli Daniela, Rinaldi Rita, Rizzi Romana, Romoli Michele, Santangelo Mario, Tontini Valentina, Turchi Giulia, Volpini Mirco, Zini Andrea, Zinno Lucia, Michelucci Roberto, Vignatelli Luca, Tinuper Paolo, Bisulli Francesca
IRCCS Istituto Delle Scienze Neurologiche di Bologna, full member of the European Reference Network for Rare and Complex Epilepsies (EpiCARE), Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Epilepsia. 2025 Mar;66(3):753-767. doi: 10.1111/epi.18227. Epub 2024 Dec 21.
The STEPPER (Status Epilepticus in Emilia-Romagna) study aimed to investigate the clinical characteristics, prognostic factors, and treatment approaches of status epilepticus (SE) in adults of the Emilia-Romagna region (ERR), Northern Italy.
STEPPER, an observational, prospective, multicentric cohort study, was conducted across neurology units, emergency departments, and intensive care units of the ERR over 24 months (October 2019-October 2021), encompassing incident cases of SE. Patients were followed up for 30 days.
A total of 578 cases were recruited (56% female, mean age = 70 years, 32% with previous diagnosis of epilepsy, 43% with in-hospital onset, 35% stuporous/comatose, 46% with nonconvulsive SE). Etiology was known in 87% (acute 43%, remote 24%, progressive 17%, definite epileptic syndrome 3%). The mean pre-SE Rankin Scale score was 2, the Status Epilepticus Severity Score was ≥4 in 33%, the Epidemiology-Based Mortality Score in Status Epilepticus score was ≥64 in 61%, and 34% were refractory. The sequence of treatments followed current clinical practice guidelines in 63%. Benzodiazepines (BDZs) were underused as first-line therapy (71%), especially in in-hospital onset cases; 15% were treated with continuous intravenous anesthetic drugs. Mortality was 24%; 63% of survivors had functional worsening. At the two-step multivariable analysis, incorrect versus correct treatment sequence with correct BDZ dose was the strongest predictor of failure to resolve SE in the in-hospital group (odds ratio [OR] = 4.42, 95% confidence interval [CI] = 1.86-10.5), with a similar trend in the out-of-hospital group (OR = 2.22, 95% CI = .98-5.02). In turn, failure to resolve was the strongest predictor of 30-day mortality (OR = 11.3, 95% CI = 4.16-30.9, out-of-hospital SE; OR = 6.42, 95% CI = 2.79-14.8, in-hospital SE) and functional worsening (OR = 5.83, 95% CI = 2.05-16.6, out-of-hospital SE; OR = 9.30, 95% CI 2.22-32.3, in-hospital SE).
The STEPPER study offers insights into real-world SE management, highlighting its significant morbidity and functional decline implications. Although nonmodifiable clinical factors contribute to SE severity, modifiable factors such as optimized first-line therapies and adherence to guidelines can potentially influence prognosis.
STEPPER（艾米利亚-罗马涅地区癫痫持续状态研究）旨在调查意大利北部艾米利亚-罗马涅地区（ERR）成年癫痫持续状态（SE）患者的临床特征、预后因素及治疗方法。
STEPPER是一项观察性、前瞻性、多中心队列研究，在ERR的神经内科、急诊科和重症监护病房开展，为期24个月（2019年10月至2021年10月），纳入SE新发病例。对患者进行30天随访。
共招募578例患者（56%为女性，平均年龄70岁，32%既往有癫痫诊断，43%在医院发病，35%呈昏睡/昏迷状态，46%为非惊厥性SE）。87%的患者病因明确（急性病因占43%，既往病因占24%，进行性病因占17%，明确的癫痫综合征占3%）。SE发作前的平均Rankin量表评分为2分，33%的患者癫痫持续状态严重程度评分≥4分，61%的患者癫痫持续状态基于流行病学的死亡率评分≥64分，34%的患者为难治性癫痫。63%的治疗顺序遵循当前临床实践指南。苯二氮䓬类药物（BDZs）作为一线治疗用药未得到充分使用（71%），尤其是在医院发病的病例中；15%的患者接受了持续静脉麻醉药物治疗。死亡率为24%；63%的幸存者功能恶化。在两步多变量分析中，在医院组中，治疗顺序不当与正确使用BDZ剂量且顺序正确相比，是SE未能缓解的最强预测因素（比值比[OR]=4.42，95%置信区间[CI]=1.86-10.5），院外组也有类似趋势（OR=2.22，95%CI=0.98-5.02）。反过来，未能缓解是30天死亡率（院外SE的OR=11.3，95%CI=4.16-30.9；院内SE的OR=6.42，95%CI=2.79-14.8）和功能恶化（院外SE的OR=5.83，95%CI=2.05-16.6；院内SE的OR=9.30，95%CI 2.22-32.3）的最强预测因素。
STEPPER研究为SE的实际管理提供了见解，突出了其显著的发病率和功能下降影响。尽管不可改变的临床因素会导致SE严重程度增加，但优化一线治疗和遵循指南等可改变因素可能会影响预后。
