Recent trials for temporal lobe epilepsy (TLE) highlight the challenges of investigating surgical outcomes using randomized controlled trials (RCTs). Although several reviews have examined seizure-freedom outcomes from existing data, there is a need for an overall seizure-freedom rate estimated from level I data as investigators consider other methods besides RCTs to study outcomes related to new surgical interventions.
The authors performed a systematic review and meta-analysis of the 3 RCTs of TLE in adults and report an overall surgical seizure-freedom rate (Engel class I) composed of level I data. An overall seizure-freedom rate was also collected from level II data (prospective cohort studies) for validation. Eligible studies were identified by filtering a published Cochrane meta-analysis of epilepsy surgery for RCTs and prospective studies, and supplemented by searching indexed terms in MEDLINE (January 1, 2012–April 1, 2018). Retrospective studies were excluded to minimize heterogeneity in patient selection and reporting bias. Data extraction was independently reverified and pooled using a fixed-effects model. The primary outcome was overall seizure freedom following surgery. The historical benchmark was applied in a noninferiority study design to compare its power to a single-study cohort.
The overall rate of seizure freedom from level I data was 72.4% (55/76 patients, 3 RCTs), which was nearly identical to the overall seizure-freedom rate of 71.7% (1325/1849 patients, 18 studies) from prospective cohorts (z = 0.134, p = 0.89; z-test). Seizure-freedom rates from level I and II studies were consistent over the years of publication (R2 < 0.01, p = 0.73). Surgery resulted in markedly improved seizure-free outcomes compared to medical management (RR 10.82, 95% CI 3.93–29.84, p < 0.01; 2 RCTs). Noninferiority study designs in which the historical benchmark was used had significantly higher power at all difference margins compared to using a single cohort alone (p < 0.001, Bonferroni’s multiple comparison test).
The overall rate of seizure freedom for temporal lobe surgery is approximately 70% for medically refractory epilepsy. The small sample size of the RCT cohort underscores the need to move beyond standard RCTs for epilepsy surgery. This historical seizure-freedom rate may serve as a useful benchmark to guide future study designs for new surgical treatments for refractory TLE.
ABBREVIATIONSAED = antiepileptic drug; ATL = anterior temporal lobectomy; ERSET = Early Randomized Surgical Epilepsy Trial; RCT = randomized controlled trial; ROSE = Radiosurgery or Open Surgery for Epilepsy; RR = risk ratio; SAH = selective amygdalohippocampectomy; SLATE = Stereotactic Laser Ablation for Temporal Lobe Epilepsy; SRS = stereotactic radiosurgery; TLE = temporal lobe epilepsy.
AdamC, ClemenceauS, SemahF, HasbounD, SamsonS, AboujaoudeN, : Variability of presentation in medial temporal lobe epilepsy: a study of 30 operated cases. 94:1–11, 1996887458610.1111/j.1600-0404.1996.tb00031.x)| false
AlvimMKMMoritaMEYasudaCLDamascenoBPLopesTMCoanAC: Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study. Epilepsia59:410–4192018
BarbaroNM, QuiggM, WardMM, ChangEF, BroshekDK, LangfittJT, : Radiosurgery versus open surgery for mesial temporal lobe epilepsy: the randomized, controlled ROSE trial. 59:1198–1207, 201810.1111/epi.1404529600809)| false
CukiertABuratiniJAMachadoESousaAVieiraJForsterC: Seizure-related outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis evaluated by magnetic resonance imaging alone. Neurosurg Focus13(4):ecp22002
EdelvikA, RydenhagB, OlssonI, FlinkR, KumlienE, KällénK, : Long-term outcomes of epilepsy surgery in Sweden: a national prospective and longitudinal study. 81:1244–1251, 201310.1212/WNL.0b013e3182a6ca7b23966252)| false
GarciaPALaxerKDBarbaroNMDillonWP: Prognostic value of qualitative magnetic resonance imaging hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures. Epilepsia35:520–5241994
GarciaPA, LaxerKD, BarbaroNM, DillonWP: Prognostic value of qualitative magnetic resonance imaging hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures. 35:520–524, 199410.1111/j.1528-1157.1994.tb02471.x8026397)| false
JehiLFriedmanDCarlsonCCascinoGDewarSElgerC: The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. Epilepsia56:1526–15332015
JehiL, FriedmanD, CarlsonC, CascinoG, DewarS, ElgerC, : The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia. 56:1526–1533, 201510.1111/epi.1311626250432)| false
KaiboriboonK, MalkhachroumAM, ZrikA, DaifA, SchiltzNM, LabinerDM, : Epilepsy surgery in the United States: analysis of data from the National Association of Epilepsy Centers. 116:105–109, 20152631096910.1016/j.eplepsyres.2015.07.007)| false
LauT, MillerT, KleinT, BenbadisSR, ValeFL: Temporal lobe surgery in medically refractory epilepsy: a comparison between populations based on MRI findings. 23:20–24, 20142409484910.1016/j.seizure.2013.09.004)| false
PaglioliEPalminiAPortuguezMPaglioliEAzambujaNda CostaJC: Seizure and memory outcome following temporal lobe surgery: selective compared with nonselective approaches for hippocampal sclerosis. J Neurosurg104:70–782006
SwartzBE, TomiyasuU, Delgado-EscuetaAV, MandelkernM, KhonsariA: Neuroimaging in temporal lobe epilepsy: test sensitivity and relationships to pathology and postoperative outcome. 33:624–634, 1992162857510.1111/j.1528-1157.1992.tb02338.x)| false
Téllez-ZentenoJF, Hernández RonquilloL, Moien-AfshariF, WiebeS: Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. 89:310–318, 201010.1016/j.eplepsyres.2010.02.00720227852)| false