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

Abstract

SummaryEpilepsy 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.

Localization yield and seizure outcome in patients undergoing bilateral SEEG exploration

“…42 In a patient population with medically intractable focal epilepsy without a curative resective strategy, management options without pursuing further SEEG evaluation would include the following: (a) continued medical management with further AED trials (4%-7% chance of seizure freedom, 51% chance of >50% seizure reduction in this cohort), (b) VNS (0-1% chance of seizure freedom, 16%-21% chance of >50% seizure reduction), and (c) RNS (14%-15% chance of seizure freedom for at least 1 year, 29% chance of >50% seizure reduction). 43 The responder rate in our cohort (80%) was comparatively higher than any of these, suggesting that pursuing a B-SEEG implantation to craft a resective surgery may have greater potential to reduce seizures than continued medical management and traditional “palliative” procedures, even in suspected multifocal epilepsy.…”

Neurostimulation in people with drug‐resistant epilepsy: Systematic review and meta‐analysis from the ILAE Surgical Therapies Commission

“…Prior reviews included either included only randomized controlled trials (RCTs) with limited follow‐up time, or retrospective chart reviews as well as prospective studies 12–16 . We conducted a systematic review and meta‐analysis of VNS, RNS, and DBS in the treatment of DRE to summarize the most up‐to‐date evidence on efficacy and tolerability for these modalities.…”

Factors Associated with Short-Term Seizure Recurrence in Extratemporal Epilepsy Surgery

“…Even so, only one percent of the cases that could probably benefit from this procedure are referred for presurgical evaluation. With an average of 20 years or more from the onset of their disease, on the other hand, about half of the patients who undergo epilepsy surgery in the world continue with seizures [8,9] so it is of utmost importance to better predict the postoperative prognosis. The literature describes different clinical, surgical, electrophysiological, and imaging variables, which behave as prognostic factors.…”