Systematic reviews of low-frequency repetitive transcranial magnetic stimulation on cognition and epileptiform discharge in patients with epilepsy.

Abstract

<h4>Background</h4>This systematic review investigates the efficacy of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in improving cognitive function and reducing epileptiform discharges in patients with epilepsy. It further examines whether patient age moderates the treatment effect. Additionally, the review evaluates whether intervention parameters, including duration, frequency, session time, and stimulation site, positively influence the improvement of cognition and epileptiform discharges.<h4>Methods</h4>Seven databases were searched: Embase, Web of Science, PubMed, The Cochrane Library, Wanfang, VIP, and China National Knowledge Infrastructure. The search period was from database inception to September 2025. Two researchers independently screened the literature to identify randomized controlled trials (RCTs) that investigated the effects of TMS on cognition in patients with epilepsy. Quality assessment was performed using PEDro, and Meta-analysis and publication bias were tested using RevMan 5.4.1 and Stata 17.0, respectively. The quality of evidence for outcome indicators was evaluated using GRADEPro software. The standardized mean difference (SMD) and 95% CI were used as effect size statistics.<h4>Results</h4>This meta-analysis included 12 randomized controlled trials (<i>n</i> = 1,289 patients). Pooled results demonstrated that low-frequency rTMS (LF-rTMS) significantly improved cognitive function (SMD = 1.22, 95% CI [0.87-1.56], <i>P</i> < 0.0001; <i>n</i> = 861) and reduced epileptiform discharges (SMD = -0.68, 95% CI [-0.98 to -0.37], <i>P</i> < 0.00001; <i>n</i> = 428). Subgroup analyses identified key parameters associated with optimal outcomes. For cognitive improvement, greater effect sizes were observed in patients aged 45-60 years, with an LF-rTMS protocol of 1 Hz stimulation targeting the epileptogenic focus, session time >20 min, intervention duration >4 weeks, and frequency of ≤7 sessions/week, particularly when combined with levetiracetam. Conversely, a greater reduction in epileptiform discharges was associated with younger age (<45 years) and shorter intervention duration (≤1 week).<h4>Conclusion</h4>The included studies (average PEDro = 6.3) had moderate quality, limited by incomplete blinding/allocation reporting. Heterogeneity stemmed from intervention parameters (site, duration, frequency, medications). No significant publication bias was observed. Evidence quality was high for cognition and moderate for epileptiform discharge. LF-rTMS effectively improves both outcomes, influenced by treatment protocols, supporting its clinical use in the management and treatment of epilepsy.<h4>Other</h4>This study has been registered on PROSPERO No. CRD42024593502. Registration Platform: www.crd.york.ac.uk.