Supplementary Material for: Neuromodulation in Refractory Bitemporal Lobe Epilepsy in Adults: A Systematic Review and Meta-Analysis.

Objective
Bilateral temporal lobe epilepsy represents a subset of patients with medically intractable epilepsy that is particularly difficult to treat. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of three neuromodulation techniques—Vagus Nerve Stimulation (VNS), Responsive Neurostimulation (RNS), and Deep Brain Stimulation (DBS)—in refractory BTLE.

Methods
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a thorough electronic literature search using Ovid MEDLINE, Ovid Embase, and PubMed databases. Data from the selected studies were extracted, analyzed, and a quality assessment was performed. Meta-analysis was performed comparing mean seizure reduction rates in VNS, RNS, and DBS.

Results
Twenty studies (4 VNS, 7 RNS, 9 DBS) involving 142 BTLE patients were included in the systematic review. Meta-analysis of 12 studies (2 VNS, 5 RNS, 5 DBS) revealed comparable efficacy between VNS (61.69%), RNS (67.51%), and DBS (66.68%), with no statistically significant difference (p = 0.932) between the modalities. All three techniques demonstrated efficacy in seizure reduction. Additionally, complication rates did not significantly differ between VNS, RNS, and DBS. (p = 0.85).

Conclusion
This study provides a comprehensive assessment of existing data regarding the use of neuromodulation in refractory BTLE. VNS, RNS, and DBS demonstrated comparable efficacy, supporting their consideration in treatment planning. Clinical decision-making should weigh factors such as surgical candidacy, patient preferences, comorbidities, and side effect profiles. Further research, including standardized reporting and head-to-head trials, is vital for optimizing treatment protocols and expanding our understanding of neuromodulation's impact on seizure reduction, quality of life, and cognitive outcomes in patients with BTLE.