| Summary: | Abstract Background Median nerve cross-sectional area (CSA) is the primary sonographic parameter for assessing and diagnosing median nerve pathology, such as carpal tunnel syndrome. However, variability in the sensitivity of diagnostic thresholds exists, which may be due to a lack of standardized normative reference values. Current estimates of normal median nerve CSA stem largely from small studies using a local pool of healthy controls. A systematic review and meta-analysis will be conducted to identify all available data for median nerve CSA in healthy, asymptomatic individuals to create a comprehensive set of normative reference values. Methods Articles that include sonographic measures of median nerve CSA will be identified through a rigorous search of published evidence, a hand search through tables of contents of key journals, and the gray literature, including ClinicalTrials.gov and conference abstracts. Each abstract and full text will be reviewed by multiple raters to identify studies from 2000 to present that include original data. Any study that provides median nerve CSA values from healthy individuals will be included (e.g., reference value study, control participants in a diagnostic study). Studies will be assessed for quality using a modified version of the National Institute of Health Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, with primary focus on the use of a detailed and acceptable image acquisition and analysis protocol. Using data from included studies, reference values will be calculated for median nerve CSA by anatomical regions, including the distal forearm, wrist, and carpal tunnel at the level of the pisiform. Reference values will be stratified by gender, ethnicity, and age based upon the specificity of the data provided by the included articles. Discussion A comprehensive set of normative reference values of median nerve CSA will reduce variability across studies, allowing future research to more accurately evaluate and establish diagnostic thresholds. Additionally, normative values can serve as a reference for evaluating treatment outcomes and provide a means to investigate and understand minor nuances in CSA changes that may be indicative of preclinical stages of median nerve pathology. Systematic review registration PROSPERO 2016 CRD42016037286
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