International evaluation of the SEIZUre Risk in Encephalitis (SEIZURE) score for predicting acute seizure risk

Encephalitis is brain parenchyma inflammation, frequently resulting in seizures which worsens outcomes. Early anti-seizure medication could improve outcomes but requires identifying patients at greatest risk of acute seizures. The SEIZURE (SEIZUre Risk in Encephalitis) score was developed in UK cohorts to stratify patients by acute seizure risk. A 'basic score' used Glasgow Coma Scale (GCS), fever and age; the 'advanced score' added aetiology. This study aimed to evaluate the score internationally to determine its global applicability.

Patients were retrospectively analysed regionally, and by country, in this international evaluation study. Univariate analysis was conducted between patients who did and did not have inpatient seizures, followed by multivariable logistic regression, hierarchical clustering and analysis of the area under the receiver operating curves (AUROC) with 95% CIs.

2032 patients across 13 countries were identified, among whom 1324 were included in SEIZURE score calculations and 970 were included in regression modelling. The involved countries comprised 19 organisations spanning all WHO regions.

The primary outcome was measuring inpatient seizure rates.

Autoantibody-associated encephalitis, low GCS and presenting with a seizure were frequently associated with inpatient seizures; fever showed no association. Globally, the score had limited discriminatory ability (basic AUROC 0.58 (95% CI 0.55 to 0.62), advanced AUROC 0.63 (95% CI 0.60 to 0.66)). The scoring system performed acceptably in western Europe, excluding Spain, with the best performance in Portugal (basic AUROC 0.82 (95% CI 0.69 to 0.94), advanced AUROC 0.83 (95% CI 0.72 to 0.95)).

The SEIZURE score performed best in several countries in Western Europe but performed poorly elsewhere, partly due to differing and unknown aetiologies. In most regions, the score did not reach a threshold to be clinically useful. The Western European results could aid in designing clinical trials assessing primary anti-seizure prophylaxis in encephalitis following further prospective trials. Beyond Western Europe, there is a need for tailored, localised scoring systems and future large-scale prospective studies with optimised aetiological testing to accurately identify high-risk patients.