Abstract Drug-refractory epilepsy (DRE), defined by the International League Against Epilepsy (ILAE) as failure of two appropriately chosen antiepileptic drugs, affects roughly 30% of the 65 million people with epilepsy worldwide and places patients at increased risk of sudden unexpected death in epilepsy (SUDEP), cognitive decline, and psychiatric comorbidity. Although conventional resective surgery produces seizure freedom in 60 to 80% of well-selected patients, many remain ineligible because of eloquent cortex involvement, diffuse seizure networks, or medical contraindications to craniotomy. Minimally invasive ablative techniques such as laser interstitial thermal therapy/stereotactic laser ablation (LITT/SLA), stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC), stereotactic radiosurgery (SRS), MR-guided focused ultrasound (MRgFUS), and LITT corpus callosotomy have gained ground as less invasive alternatives. We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searching PubMed/MEDLINE, Google Scholar, SciSpace, and ArXiv for English-language studies published between January 2014 and December 2025 that enrolled at least five patients with ILAE-confirmed DRE, used one of the above modalities, and reported seizure outcomes at 6 months or longer. We appraised methodological quality with the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. A total of 19 studies met our inclusion criteria, covering an estimated 2,000 or more unique patients drawn primarily from retrospective cohorts and meta-analyses. Pooled seizure freedom ranged from 18.9% for LITT corpus callosotomy (reflecting its palliative intent) to approximately 77% for LITT or RFTC directed at hypothalamic hamartoma. Responder rates (≥50% seizure reduction) were 62 to 84%, depending on the modality and underlying pathology. Complication rates ranged from 12.9 to 17.6%, with permanent neurological deficits in 1.3 to 4.7% of cases. ROBINS-I risk of bias was serious or critical in 63% of studies, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality of evidence was low to very low for most reported outcomes. Epilepsy etiology was the strongest predictor of outcome: hypothalamic hamartoma achieved the highest seizure freedom, while MRI-negative epilepsy consistently showed the poorest results across all modalities. These ablative procedures appear effective and reasonably safe in carefully selected patients with DRE, particularly those with lesional epilepsy in surgically difficult locations. However, the evidence remains limited by retrospective designs, short follow-up rarely exceeding 24 months, and the complete absence of randomized trials. Prospective multicenter registries with standardized outcome measures and etiology-stratified comparative studies should be research priorities going forward.
Nandam et al. (Thu,) studied this question.