Prognostic factors in vagus nerve stimulation for drug-resistant epilepsy. Results from a systematic review and meta-analysis of the literature

The aim of the present study was to conduct a systematic review and meta-analysis evaluating prognostic factors of response to treatment with VNS implantation in patients with drug-resistant epilepsy. We conducted a systematic review following the PRISMA 2020 guidelines to critically analyze relevant studies. The review question was formulated using the PICO framework: "In patients with drug-resistant epilepsy (P) undergoing VNS implantation (I) and subjected to preoperative and postoperative clinical and instrumental evaluations (C), can prognostic factors for therapeutic response (O) be identified?". As outcome variables for metanalysis evaluation, gender, age at epilepsy onset, age at VNS implantation, focal onset of seizures, epilepsy duration and genetic etiology were evaluated. The protocol for this systematic review and meta-analysis was registered in the PROSPERO database (registration number: CRD420261333961). The literature search yielded a total of 900 results. After removing duplicates, 571 papers were screened. Ultimately 39 were deemed relevant. There was a statistically significant association between focal seizures and VNS response (RR 1.31, 95% CI 1.02-1.69, p < 0.05), gender (RR 1.14, 95% CI 1.02-1.26, p < 0.05) and younger age at seizure onset (SMD 0.22, 95% CI 0.02-0.41, p = 0.028), suggesting a slightly higher probability of response in these subgroups. No significant associations were found for genetic etiology, epilepsy duration, or age at VNS implantation. Heterogeneity was generally low across analyses, except for focal seizures (I2 = 49%). Focal seizures and younger age at epilepsy onset are associated with improved response to VNS therapy. These findings support the role of early patient stratification and suggest that VNS should be considered earlier in selected patients. While several promising biomarkers have been identified, further research is needed to establish their clinical utility and develop more accurate patient selection frameworks.