Surgical anatomy of the recurrent laryngeal nerve: a systematic review and meta-analysis of variants

Background: Injury to the recurrent laryngeal nerve (RLN) remains a significant concern in thyroid surgery. The inferior thyroid artery (ITA) is frequently used as a landmark. Yet, the RLN-ITA relationship shows substantial anatomical variability, and the non-recurrent laryngeal nerve (NRLN) represents a rare but high-risk variant. This systematic review and meta-analysis quantified the prevalence of RLN-ITA topographic patterns and NRLN occurrence. Materials and methods: A PRISMA-compliant search was performed across major databases up to May 1, 2025. Eligible studies included intraoperative, cadaveric, or mixed anatomical series reporting extractable numerical data on RLN-ITA relationships (anterior, posterior, interposed) and/or NRLN prevalence, using the hemisoma as the unit of analysis. Study quality was assessed with the AQUA tool. Proportions were pooled using Freeman-Tukey double arcsine transformation under a random-effects model with REML estimation. Heterogeneity was quantified with I², τ², and Cochran's Q, and prespecified subgroup analyses were conducted by study setting. Results: Sixty studies (1973-2025) comprising 9,032 patients and 14,820 hemisomas were included. Fifty-seven studies contributed 14,169 hemisomas to the RLN-ITA synthesis. Crude proportions were posterior 54.43% (7,712/14,169), anterior 27.11% (3,841/14,169), and interposed 18.46% (2,616/14,169). Random-effects pooling confirmed a posterior course as the most frequent configuration (~ 52%, 95% CI ~ 46-58%), followed by anterior (~ 30%, 95% CI ~ 24-36%) and interposed (~ 18%, 95% CI ~ 15-21%), with very high heterogeneity (I² > 97%). Subgroup analyses of intraoperative (30 studies; 10,376 hemisomas) and cadaveric (25 studies; 3,589 hemisomas) series yielded similar distributions, with persistently high heterogeneity (I² > 94%). Across all studies, 39 NRLNs were identified, all on the right side, corresponding to a prevalence of 0.78% among right hemisomas (n = 4,974); no left-sided NRLNs were reported. Conclusion: The RLN most commonly courses posterior to the ITA, but anterior and interposed variants are sufficiently frequent to mandate systematic intraoperative verification before vessel ligation. The NRLN is rare and exclusively right-sided in available data, yet clinically significant due to its high injury risk. Marked between-study heterogeneity highlights the need for standardized definitions and side-specific reporting in future anatomical research.