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

Comprehensive Summary

This systematic review and meta-analysis evaluated the efficacy of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS, ≤1 Hz) on cognitive function and epileptiform discharges (EDs) in patients with epilepsy. Twelve randomized controlled trials (n = 1,289 participants) were included. The analysis demonstrated that LF-rTMS significantly improved cognitive function (SMD = 1.22) and significantly reduced epileptiform discharges (SMD = −0.68) compared with sham stimulation or conventional pharmacotherapy alone. Subgroup analyses identified protocol-dependent effects. Greater cognitive improvement was observed in patients aged 45–60 years, with 1 Hz stimulation, session durations >20 minutes, intervention periods >4 weeks, ≤7 sessions per week, stimulation targeted at the epileptogenic focus, and when combined with levetiracetam therapy. In contrast, reduction in epileptiform discharges was more pronounced in patients under 45 years of age and with shorter intervention durations (≤1 week). Methodological quality was moderate to good (mean PEDro score 6.3). Evidence certainty was rated high for cognitive outcomes and moderate for ED reduction. Although heterogeneity was substantial for cognition outcomes, subgroup analyses suggested that stimulation parameters, age, and medication use accounted for much of the variability. No significant publication bias was detected. Overall, LF-rTMS appears to exert clinically meaningful effects on both cortical excitability and cognitive performance in epilepsy, with therapeutic efficacy strongly influenced by stimulation protocol characteristics.

Outcomes and Implications

This study supports LF-rTMS as a viable adjunctive neuromodulation strategy in epilepsy management, particularly for patients experiencing cognitive impairment alongside seizure activity. Because cognitive dysfunction is a major contributor to reduced quality of life in epilepsy, the demonstrated high-certainty benefit in cognition has significant clinical relevance. The findings suggest that treatment protocols must be individualized. For cognitive rehabilitation, longer-duration stimulation (>4 weeks) at 1 Hz targeting the epileptogenic focus appears optimal, particularly when combined with levetiracetam. Conversely, short-term LF-rTMS may provide rapid suppression of epileptiform discharges, indicating potential utility in acute cortical hyperexcitability control. Mechanistically, LF-rTMS likely reduces pathological cortical excitability, modulates excitatory–inhibitory balance, and promotes synaptic plasticity, thereby addressing both electrophysiological abnormalities and network-level cognitive dysfunction. These dual effects position LF-rTMS as a promising noninvasive intervention that may complement antiseizure medications without adding systemic pharmacologic burden. However, given moderate evidence certainty for ED outcomes and variability in stimulation parameters, further large-scale, well-blinded multicenter trials with longer follow-up are required before widespread protocol standardization can be recommended.