Elsevier

The Lancet Neurology

Volume 19, Issue 9, September 2020, Pages 748-757
The Lancet Neurology

Articles
Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study

https://doi.org/10.1016/S1474-4422(20)30220-9Get rights and content

Summary

Background

Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.

Methods

In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.

Findings

9147 patients were included, of whom seizure outcomes were available for 8191 (89·5%) participants at 2 years, and for 5577 (61·0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77·5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74·0% (328 of 443) for vascular malformation, and 71·5% (2108 of 2948) for hippocampal sclerosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50·0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52·3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53·5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0–14% at 1 year and increased to 14–51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.

Interpretation

Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered.

Funding

None.

Introduction

Epilepsy is one of the most prevalent and severe neurological disorders with around 70 million individuals affected worldwide.1 Antiepileptic drugs (AEDs) are effective in approximately 70% of patients,2, 3 but often have side-effects4 and merely suppress seizures rather than modifying the disease course. Approximately 60% of patients who are drug-resistant with focal epilepsy have been reported to become seizure-free 1 year after surgery5 and elective surgery is increasingly recognised as a curative treatment option.6 The reported range for the proportion of individuals who are seizure-free remains large, varying from 15% to 93%. The range depends on—among other factors—the number of seizures, MRI findings, localisation of the epileptogenic zone, need for invasive diagnostics, definition of seizure freedom, duration of follow-up, and underlying pathology.6, 7, 8, 9, 10 The study of postoperative seizure outcomes in relation to the large spectrum of brain lesions and duration of follow-up, while adjusting for many different determinants of outcome, is a particular challenge and requires large numbers of patients in a multicentre approach. We have described the spectrum of histopathological diagnoses in 9523 European patients who underwent epilepsy surgery between 1990 and 2014,5 confirming a large variation in the proportion of patients within the different histopathological categories between children and adults.5 Seizure outcomes were reported for the main categories of pathology only at 1 year after surgery. In the current study, we aimed to substantiate the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, and the effects of age at surgery and duration of epilepsy among different histopathological diagnoses on outcome, in a cohort of patients undergoing epilepsy surgery in Europe.

Research in context

Evidence before this study

We searched PubMed from database inception until Feb 18, 2019, for original cohort studies describing outcomes of epilepsy surgery related to histopathology or cause, using the terms “epilepsy surgery”, “outcome OR seizure”, and “histopathology OR histopathological OR etiology OR aetiology”, without language restrictions. Cohorts focusing on specific pathologies or brain regions were excluded because direct comparison of outcomes between pathologies would not be possible, as were studies without a comparison in surgery outcomes between different causes. The search yielded 252 results. Only five identified studies had sample sizes of more than 500 patients. The largest cohort sample size was 1995. None of these studies included all pathological categories, including encephalitis and vascular malformations. Only one study included a category consistent with a brain scar. The only cause included in all five studies was hippocampal sclerosis, four looked at either focal cortical dysplasia or the total group of malformations of cortical development, and only three looked at outcomes for tumours. The identified studies did not provide detailed information on expected surgical outcomes for all classes of histopathological diagnoses, nor for specific diagnoses. Postoperative drug freedom was not reported in any of the studies. None studied the effect of duration of epilepsy in the separate diagnoses.

Added value of this study

This study provides epilepsy surgery outcomes up to 5 years after surgery, for all major classes of histopathological diagnosis and specific sub-diagnoses, for 9147 patients. For the first time, to our knowledge, evidence for a correlation between long-term seizure and drug outcomes and cause, age, and epilepsy duration was provided.

Implications of all the available evidence

Epilepsy surgery should be considered in every person with drug-resistant focal and (presumed) lesional epilepsy. Surgery renders most selected patients free from disabling seizures. Histopathology is an important determinant of seizure outcome. Other independent determinants of seizure and drug outcomes are age at surgery, location of surgery, and duration of epilepsy. Longer duration of epilepsy is associated with poorer outcomes.

Section snippets

Study design and participants

We did a retrospective, multicentre, longitudinal, cohort study. The European Epilepsy Brain Bank is an EU-funded open collaboration of specialised epilepsy centres in 18 countries (Austria, Belgium, Croatia, Czech Republic, Finland, France, Germany, Greece, Italy, Netherlands, Portugal, Russia, Serbia, Spain, Sweden, Switzerland, Turkey, and the UK). Histopathological diagnoses of resected brain tissue were made at local centres or the German Neuropathology Reference Center for Epilepsy

Results

Information regarding histopathological diagnosis was available for 9601 epilepsy surgeries from 37 centres. Re-operations (n=77) and patients without clinical follow-up (n=377) were excluded, leaving a total cohort of 9147 patients, of whom 5462 (59·7%) had an age at onset of epilepsy of younger than 18 years, and 2952 (32·3%) were younger than 18 years at time of surgery. Age at surgery ranged between younger than 1 year and 75 years, 4429 (48·4%) were female, and 6014 (66·5%) of surgeries

Discussion

In this large, multicentre, cohort study of 9147 patients who underwent epilepsy surgery across 18 European countries, histopathological diagnosis was an important and independent determinant of outcome. The proportion of patients who were Engel class 1 was 68% at 2 years post-surgery, varying from 78% in patients with LEAT to 50% in those classified as FCD type I or mild MCD. From 1 to 5 years after surgery, these rates dropped in the range of 2% to 9%, depending on the underlying brain lesion

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    Members and affiliations of the writing group are listed at the end of the Article

    Members of the study group are listed at the end of the Article

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