Voice Alterations Associated with Implanted Vagus Nerve Stimulation in Epilepsy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Implanted vagus nerve stimulation (VNS) is an established treatment for drug-resistant epilepsy. However, stimulation-related voice disturbances are among the most frequently reported adverse effects. This systematic review and meta-analysis synthesized available evidence regarding voice outcomes associated with implanted VNS in patients with epilepsy. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of PubMed, Scopus, and Web of Science was conducted following PRISMA guidelines. Studies evaluating acoustic, perceptual, aerodynamic, phonatory, laryngeal, or patient-reported voice outcomes associated with implanted VNS in epilepsy were eligible. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools and ROBINS-I. Evidence certainty was evaluated using the GRADE approach. Random-effects meta-analyses were performed for outcomes reported in controlled studies. RESULTS: Thirteen studies published between 1993 and 2024 met the inclusion criteria, comprising case reports, case series, observational studies, and two controlled comparative studies. Qualitative synthesis consistently demonstrated increased jitter and shimmer during active stimulation, reduced maximum phonation time (MPT), perceptual voice deterioration, and greater voice-related handicap. Quantitative synthesis demonstrated shorter MPT in participants with implanted VNS than in healthy controls (MD = -8.66 s, 95% CI -11.31 to -6.01; P < 0.00001). Participants with VNS also showed significantly higher scores in the functional (MD = 6.58, 95% CI 4.13-9.04; P < 0.00001) and physical (MD = 8.49, 95% CI 3.40-13.58; P = 0.001) domains of the Voice Handicap Index. Evidence certainty ranged from low to very low. CONCLUSIONS: Implanted VNS appears to be associated with alterations in voice function, including reduced phonatory efficiency, increased acoustic perturbation, and greater self-perceived vocal handicap. Although evidence certainty remains limited, the consistency of findings and meta-analytic results support clinically relevant VNS-related voice effects. Routine voice monitoring should be considered as part of the long-term clinical management of patients receiving implanted VNS for drug-resistant epilepsy.