Histopathology, age, disease duration influence outcomes in epilepsy surgery

Neurologists should consider evaluating all patients with refractory focal epilepsy that is presumed to be lesional for resective epilepsy surgery, according to findings published in The Lancet Neurology.

Surgery increased the number of patients who were both free from disabling seizures (Engel Class 1) and medication-free at 5 years. The researchers identified histopathological diagnosis, age at the time of surgery and disease duration as important prognostic factors for outcomes of epilepsy surgery.

“Approximately 60% of patients who are drug-resistant with focal epilepsy have been reported to become seizure-free 1 year after surgery and elective surgery is increasingly recognized as a curative treatment option,” the researchers wrote. “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 analyze the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counseling.”

Herm J. Lamberink, MD, of the UMC Utrecht Brain Center, department of neurology and neurosurgery, at the University Medical Center Utrecht and Utrecht University in the Netherlands, and colleagues conducted a retrospective multicenter longitudinal cohort analysis of patients who underwent epilepsy surgery between Jan. 1, 2000, and Dec. 31, 2012, at 37 collaborating tertiary referral centers in 18 European countries who were part of the European Epilepsy Brain Bank consortium. The researchers included patients of all ages for whom information about histopathology after surgery was available.

Freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2 and 5 years after surgery served as the primary outcomes. Lamberink and colleagues obtained information about histopathological diagnoses and clinical variables from existing databases and patient records. They examined the relationship between histopathology, duration of epilepsy and age at surgery and the primary outcomes using random effects multivariable logistic regression to control for confounding.

The analysis included 9,147 patients. Information about seizure outcomes was available for 89.5% of patients at 2 years and for 61% of patients at 5 years. Most patients (59.7%) were younger than 18 years at the time of epilepsy onset; 32.3% were younger than 18 years at the time of surgery. Patients ranged from age less than 1 year to 75 years at the time of surgery; 48.4% were female and 66.5% of surgeries were in the temporal lobe. The largest categories of histopathological diagnoses were hippocampal sclerosis (35.6%), low-grade epilepsy associated neuroepithelial tumor (LEAT; 16.3%) and focal cortical dysplasia type 2 (9.7%).

Outcomes varied “considerably” between the different diagnostic subcategories, according to the study findings. Diagnoses of LEAT, vascular malformation and hippocampal sclerosis correlated with the best seizure outcomes at 2 years after surgery. Freedom from disabling seizures was achieved by 77.5% of patients with LEAT, 74% of patients with vascular malformations and 71.5% of patients with hippocampal sclerosis at this point.

Lamberink and colleagues observed the worst seizure outcomes at 2 years among patients with focal cortical dysplasia type I or mild malformation of cortical development (50%), those with malformation of cortical development-other (52.3%) and those with no histopathological lesion (53.5%).

The researchers also noted several factors that correlated with outcomes, both positive and negative. Children were more likely to achieve drug freedom and patients who had temporal lobe surgeries experienced the best seizure outcomes. Conversely, the chance of favorable seizure outcomes and drug freedom decreased among patients with a longer duration of epilepsy. Lamberink and colleagues observed the effect of duration for all lesions except for hippocampal sclerosis.

“To our knowledge, this study is the largest for histology findings in epilepsy surgery with seizure and drug outcome data available at 1, 2 and 5 years after surgery,” the researchers wrote. “... This patient cohort from the European Epilepsy Brain Bank allowed for comparison of surgery outcomes across all major disease causes. Apart from histopathology, important factors associated with good outcome after surgery are a short duration of epilepsy, young age at surgery, and when the temporal lobe was targeted for surgery.”