Surgical Management in Patients With Drug-Resistant Epilepsy: A Summary of Four Systematic Reviews and Meta-Analyses

Abstract

Drug-resistant epilepsy (DRE) may lead to substantial morbidity, impaired quality of life (QoL), and increased mortality. Clinicians increasingly use surgical interventions to manage DRE, but uncertainty remains regarding their comparative benefits and harms across epilepsy syndromes. We conducted 4 systematic reviews and meta-analyses to inform the American Epilepsy Society (AES) and Congress of Neurological Surgeons (CNS) guidelines on surgical management of DRE. We searched MEDLINE, Embase, and CENTRAL from inception to August 2024 for randomized controlled trials (RCTs) and nonrandomized studies (NRS). We evaluated (1) resective or ablative surgery versus medical therapy in drug-resistant mesiotemporal lobe epilepsy (DR-MTLE); (2) resective or ablative surgery versus medical therapy in drug-resistant neocortical epilepsy (DR-NE); (3) callosotomy versus vagus nerve stimulation (VNS) in developmental and epileptic encephalopathies (DEEs) with drop attacks; and (4) ablative versus resective surgery in hypothalamic hamartoma (HH). The panel prioritized the following critical outcomes: seizure freedom, QoL, neuropsychological, neuropsychiatric, and social outcomes, and serious adverse events. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. We included 47 studies comprising 4868 participants. In DR-MTLE, moderate-certainty evidence from RCTs showed that anterior temporal lobectomy (ATL), compared with medical therapy, probably increases seizure freedom and improves QoL. The evidence was very uncertain regarding the effects of selective amygdalohippocampectomy, laser interstitial thermal therapy (LITT), and radiosurgery in patients with DRE. In DR-NE, very low-certainty evidence suggested that seizure freedom may occur after resective surgery. However, we did not identify any eligible studies evaluating ablative surgery in this population. In DEE, very low-certainty evidence suggested that, when compared to VNS, callosotomy may improve seizure outcomes but may also increase serious adverse events. In HH, evidence for LITT and radiosurgery was found to be very uncertain. Across reviews, the most common reason for downgrading the certainty of evidence was risk of bias and imprecision. Moderate-certainty evidence supports ATL in selected patients with DR-MTLE. For other surgical approaches and epilepsy syndromes, the evidence remains very uncertain, highlighting the need for better comparative studies.