Diagnostic Yield and Therapeutic Impact of Etiologic Investigations After Status Epilepticus: Insights From the ICTAL Registry.

Background

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Objectives

Status epilepticus (SE) is a critical neurologic emergency requiring prompt symptomatic and etiologic treatment. However, the diagnostic yield of etiologic investigations remains poorly characterized. We aimed to evaluate the diagnostic yield and therapeutic impact of etiologic investigations in SE, using pretest probability strata.

Methods

This prospective multicenter cohort study based on the ICTAL registry was conducted in 26 university-affiliated intensive care units (ICUs) in France (2018-2025). All adults (≥18 years) admitted for SE were included. Participants underwent a predefined diagnostic protocol including brain imaging (CT scan/MRI), laboratory investigations, lumbar puncture, toxicology screening, antiseizure medication (ASM) assays, and paraneoplastic/autoimmune disease workup. The primary outcome was the diagnostic yield of each test, defined as confirmation, codiagnosis, or reclassification of SE etiology. The secondary outcome was management changes directly attributable to test results.

Results

Among 1,123 patients (64% male; median age 60 years), SE was motor-predominant in 90%. Across high pretest probability strata, first-line investigations confirmed the suspected etiology in 8.5%-44.5% of cases and reclassified it in 22.1%-35.1%. Confirmation rates were the highest for toxicology screening in alcohol/toxic/iatrogenic causes (44.5%), ASM assays in precipitating factors (44.0%), paraneoplastic/autoimmune workup in noninfectious encephalitis (40.0%), brain CT in vascular causes (28.0%) and brain tumor (27.7%), laboratory investigations in metabolic causes (21.4%), and lumbar puncture in CNS infection (17.2%). Reclassification was most evident for brain MRI (27.8%-35.1%) across CNS infection, metabolic, noninfectious encephalitis, and sequelae strata, with the highest rate in noninfectious encephalitis (35.1%); brain CT contributed similarly (22.1%-27.9%). Toxicology screening reclassified 32.4% of high pretest probability metabolic presentations. Management changes were most frequent following brain MRI (up to 58.3%), brain CT (up to 56.9%), lumbar puncture (39.4%), paraneoplastic/autoimmune workup (33.3%), and ASM assays (up to 35.1%).

Discussion

Diagnostic yield and therapeutic impact of investigations in SE are strongly influenced by pretest clinical probability. Stratified diagnostic strategies may optimize etiologic identification and guide timely, targeted interventions. TRIAL REGISTRATION INFORMATION The study is registered with ClinicalTrials.gov, number NCT03457831.