Not all that glitters is gold: A guide to surgical trials in epilepsy

Epilepsy surgery is often the only effective treatment in appropriately selected patients with drug-resistant epilepsy, a disease affecting about 30% of those with epilepsy. We review the evidence supporting the use of epilepsy surgery, with a focus on randomized controlled trials (RCTs). Second, we identify gaps in knowledge about the benefits of epilepsy surgery for certain populations, the challenges of individualizing the choice of surgery, and our lack of understanding of the mechanisms of surgical outcomes. We conducted a search (MEDLINE, Embase, Cochrane, Clinicaltrials.gov) on March 2, 2016, to identify epilepsy surgery RCTs, systematic reviews, or health technology assessments (HTAs). Abstracts were screened to identify resective, palliative (e.g., corpus callosotomy, multiple subpial transection [MST]), ablative (e.g., Laser interstitial thermal therapy [LITT], gamma knife radiosurgery [RS]), and neuromodulation (e.g., cerebellar stimulation [CS], hippocampal stimulation [HS], repetitive transcranial magnetic stimulation [rTMS], responsive neurostimulation [RNS], thalamic stimulation [TS], trigeminal nerve stimulation [TNS], and vagal nerve stimulation [VNS]) RCTs. Study characteristics and outcomes were extracted. Knowledge gaps were identified. Of 1,205 abstracts, 20 RCTs were identified (resective surgery including corpus callosotomy [n = 7], MST [n = 0], RS [n = 1, 3 papers], LITT [n = 0], CS [n = 1], HS [n = 2], RNS [n = 1], rTMS [n = 1], TNS [n = 1], TS [n = 1], and VNS [n = 5]). Most studies targeted patients with temporal lobe epilepsy (TLE) and none examined the effectiveness of resective surgical therapies in patients with extra-TLE (ETLE) or with specific lesions aside from mesial temporal lobe sclerosis. No pediatric surgical RCTs were identified except for VNS. Few RCTs address the effectiveness of surgery in epilepsy and most are of limited generalizability. Future studies are needed to compare the effectiveness of different surgical strategies, better understand the mechanisms of surgical outcomes, and define the ideal surgical approaches, particularly for patients with high or very low cognitive function, normal imaging, or ETLE.