Prognostic factors and impact of management strategies for status epilepticus: The STEPPER study in the Emilia-Romagna region, Italy

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Significance: 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.

Keywords: EEG; antiseizure medications; cohort studies; natural history studies; status epilepticus.

FIGURE 1

Conceptual framework of the statistical plan for prognosis analysis of status epilepticus (SE). Prognostic factors are categorized as pre‐onset factors (sex, age, comorbidities assessed by the comorbidity subsection of the Epidemiology‐Based Mortality Score in Status Epilepticus scale, modified Rankin Scale score pre‐SE [functional status], antiseizure medications [ASMs]), onset factors (SE etiology, SE classification [phenomenology], electroencephalographic [EEG] activity), first‐level dynamic factors (general management, pharmacological treatment), and second‐level dynamic factors (resolution). Prognostic outcomes are failure to resolve (intermediate outcome), functional worsening (according to modified Rankin Scale score), and survival at 30 days.

FIGURE 2

Pharmacological treatment of status epilepticus (SE) in the four groups: convulsive SE (CSE), SE with prominent motor symptoms not CSE, nonconvulsive SE (NCSE) in coma, NCSE without coma. Each bar represents the percentage of patients receiving each drug class (antiseizure medications [ASMs]/benzodiazepines [BDZs]/continuous intravenous anesthetic drugs [CIVADs]) at each therapeutic attempt, from the first to the last in temporal order. The total number of patients treated at each therapeutic attempt is indicated below the bars.

FIGURE 3

Status epilepticus (SE) outcome is shown in the two groups: in‐hospital and out‐of‐hospital onset.