Risk of seizure recurrence in people with single seizures and early epilepsy – Model development and external validation

Laura J Bonnett,Lois Kim,Anthony Johnson,Josemir W Sander,Nicholas Lawn,Ettore Beghi,Maurizio Leone,Anthony G Marson

doi:10.1016/j.seizure.2021.11.007

Abstract

PurposeFollowing a single seizure, or recent epilepsy diagnosis, it is difficult to balance risk of medication side effects with the potential to prevent seizure recurrence. A prediction model was developed and validated enabling risk stratification which in turn informs treatment decisions and individualises counselling. MethodsData from a randomised controlled trial was used to develop a prediction model for risk of seizure recurrence following a first seizure or diagnosis of epilepsy. Time-to-event data was modelled via Cox's proportional hazards regression. Model validity was assessed via discrimination and calibration using the original dataset and also using three external datasets – National General Practice Survey of Epilepsy (NGPSE), Western Australian first seizure database (WA) and FIRST (Italian dataset of people with first tonic-clonic seizures). ResultsPeople with neurological deficit, focal seizures, abnormal EEG, not indicated for CT/MRI scan, or not immediately treated have a significantly higher risk of seizure recurrence. Discrimination was fair and consistent across the datasets (c-statistics: 0.555 (NGPSE); 0.558 (WA); 0.597 (FIRST)). Calibration plots showed good agreement between observed and predicted probabilities in NGPSE at one and three years. Plots for WA and FIRST showed poorer agreement with the model underpredicting risk in WA, and over-predicting in FIRST. This was resolved following model recalibration. ConclusionThe model performs well in independent data especially when recalibrated. It should now be used in clinical practice as it can improve the lives of people with single seizures and early epilepsy by enabling targeted treatment choices and more informed patient counselling.

Highlights

A first unprovoked seizure is a common presentation with an esti mated incidence of between 50 and 70 per 100,000 in high-income countries [1]
Study used for model development MESS [3] was a UK-based randomised controlled trial that compared immediate or deferred treatment policies in people presenting with a first unprovoked seizure or early onset epilepsy
Plots for Western Australian study (WA) and FIRST showed less satisfactory agreement with the model generally under-predicting risk of seizure recurrence in WA, and over-predicting risk in FIRST until recalibration was under taken to account for the differing underlying baseline survival proba bility in these datasets compared to MESS

Summary

Introduction

A first unprovoked seizure is a common presentation with an esti mated incidence of between 50 and 70 per 100,000 in high-income countries [1]. Half will have a seizure recurrence [2], be diagnosed with epilepsy, and will usually start treatment with an antiseizure medication (ASM) to prevent further seizures. ; ASM, Antiseizure medication; MESS, Multicentre Study of Early Epilepsy and Single Seizures; NGPSE, National general practice study of epilepsy and epileptic seizures; WA, Western Australian study. Whilst for most people diagnosed with epilepsy, the benefits of treat ment will exceed the risks. This benefit-risk ratio is more finely balanced for those who have had a single seizure. The benefit-risk ratio is more tuned for those who have had two or more seizures with minor symptomatology (e.g. focal seizures with retained awareness), or have had long intervals between seizures

Methods

Results

Discussion

Conclusion