Sage Journals: Discover world-class research

Abstract

Objective:

Establish median nerve cross-sectional area (CSA) reference values and identify patient-level factors impacting diagnostic thresholds.

Materials and Methods:

Studies were identified through a robust search of multiple databases, and quality assessment was conducted using a modified version of the National Institute of Health Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A meta-analysis was performed to identify normative values stratified by anatomic location. A meta-regression was conducted to examine heterogeneity effects of age, sex, and laterality.

Results:

The meta-analysis included 73 studies; 41 (56.2%) were high quality. The median nerve CSA [95% confidence interval, CI] was 6.46 mm² [6.09–6.84], 8.68 mm² [8.22–9.13], and 8.60 mm² [8.23–8.97] at the proximal forearm, the carpal tunnel inlet, and the proximal carpal tunnel, respectively. Age was positively associated with CSA at the level of proximal carpal tunnel (β = 0.03 mm², P = .047). Men (9.42 mm² [8.06–10.78]) had statistically larger proximal tunnel CSA (P = .03) as compared with women (7.71 mm² [7.01–8.42]). No difference was noted in laterality.

Conclusion:

A reference value for median nerve CSA in the carpal tunnel is 8.60 mm². Adjustments may be required in pediatrics or older adults. The diagnostic threshold of 10.0 mm² for male patients should be cautiously applied as the upper limit of normative averages surpasses this threshold.

Keywords

ultrasonography median nerve reference values meta-analysis

Sonographic imaging is becoming widely used for the examination of peripheral nerves, particularly in the diagnosis of carpal tunnel syndrome (CTS), where a growing body of literature is examining the diagnostic accuracy of sonography for CTS.^1–3 Research and clinical approaches primarily compare median nerve cross-sectional area (CSA) to a diagnostic threshold (e.g., 10 mm²) or use a within-arm comparison of the CSA in the carpal tunnel to the CSA in the forearm.^4–6 Sonography has been shown to demonstrate a better false-positive rate at 23% compared with the “gold standard” of nerve conduction at 43%.¹ Recent expert consensus suggests that combining sonography with other clinical measures⁷ can increase diagnostic accuracy⁸ and may be able to differentiate severity of CTS.⁹

Most researchers examining diagnostic accuracy or developing diagnostic thresholds for sonographic measurements enroll a unique sample of healthy individuals to serve as reference values, in their individual studies. These comparative samples are often substantially small and purposefully recruited to match the patient population of the primary study. Although a few studies have been conducted to report normative values within specific populations^10–12 and across different demographic factors,^13,14 these studies do not provide the substantially large, heterogeneous samples necessary to serve as stand-alone reference values, for all clinical patients or research protocols.

With the proliferation of sonographic measurement of the median nerve in diagnostic studies and clinical trials, along with the increasing clinical use of sonography for screening and prevention of CTS, there is a need to establish a robust set of normative reference values for these measures across various populations, ages, and sexes. Thus, the purpose of this meta-analysis was to locate all published data on median nerve CSA measurements in healthy participants, statistically combine the data to establish references values, and identify patient-level factors that may impact how diagnostic thresholds are considered within clinical practice and research.

Materials and Methods

Search Strategy

This review was designed to meet the criteria of the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses.¹⁵ The study protocol was registered with the International Prospective Register of Systematic Reviews (CRD42016037286) and the detailed search and selection methodology has been previously published.¹⁶ An initial bibliographic search was completed by a clinical and research librarian on March 20, 2017, and an updated search was conducted on May 31, 2019. Searches were conducted in Ovid MEDLINE, Embase, Cochrane Library, CINAHL, and SPORTDiscus using a combination of subject headings (when available) and keywords for concepts of peripheral nerves, reference values, or carpal tunnel and ultrasonography to capture articles published since the year 2000. The detailed search strategies for each database are included (see Supplemental Table 1). Additional searches were conducted in ClinicalTrials.gov, the tables of contents of journals within related medical (e.g., imaging, neurology) and injury prevention fields (e.g., human factors and industrial engineering), and the reference lists of relevant review articles identified in the search process.

Study Selection

A review team with varied training in sonographic imaging, rehabilitation, and medicine followed a standardized protocol to complete the study selection process.¹⁶ Following removal of duplicates, all abstracts were imported into Covidence (Veritas Health Innovation Ltd; Melbourne, Australia) and independently screened by two reviewers. Full texts were obtained for any article that at least one reviewer indicated used sonography to examine the peripheral nerves of the upper extremity in healthy individuals. All full texts were independently reviewed for eligibility by two reviewers to identify studies that measured median nerve CSA in healthy participants using sonography. A registered musculoskeletal sonographer with more than 10 years of experience examined articles with discrepancies between the primary reviewers, and final inclusion was determined by consensus among the reviewers. Studies that used a transducer <10 MHz, a measurement technique other than direct trace around the internal hyperechoic border of the nerve, or a primary measurement of CSA in cm² rather than mm² were excluded. When units of measurement were not reported in the methods, studies were excluded if cm² appeared in figures or whole numbers were used to report CSA. Studies that lacked a clear anatomical description or combined measures from different locations across participants (e.g., largest CSA measured across the carpal tunnel region) were also excluded.

Data Extraction and Quality Assessment

For each study, the number, average age, and distributions of sex and handedness of participants were extracted. Central tendency and variance for each sonographic CSA measurement of the median nerve were entered into the data set across nine anatomic locations from the axilla to the distal carpal tunnel (see Table 1). To obtain missing data, the corresponding authors were contacted when articles did not report both centrality and variance of CSA for healthy participants. Because the purpose of this review was limited to measures of the median nerve in healthy participants, additional information related to overall study (e.g., design, diagnosis, intervention) were not extracted or reported.

Table 1.

Parameters Used to Categorize Median Nerve Measures Reported Across the Included Studies Into Anatomical Regions for Analysis.

Region	Descriptions of Anatomical Regions Reported Across Studies
Axilla	Axillary fossa
Humerus	Midpoint of the upper arm, mid humerus, or midpoint between medial epicondyle and axillary fossa
Elbow	Antecubital fossa to the pronator teres
Proximal forearm	At the pronator teres to 10 cm proximal to the distal wrist crease
Distal forearm	Between 4 and 10 cm proximal to distal wrist crease
Carpal tunnel inlet	Less than 4 cm proximal to or at the distal wrist crease, distal radioulnar joint, lunate, pronator quadratus, proximal scaphoid
Proximal carpal tunnel	At the pisiform, distal scaphoid, or under the flexor retinaculum
Distal carpal tunnel	At the hook of hamate or trapezium
Carpal tunnel outlet	Over the metacarpal bones or in the palm

Quality assessment was conducted using a modified version of the National Institute of Health Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.¹⁷ Studies were scored as having fully met (1 point), partially met (0.5 points), or not met (0 points) eight quality criteria related to the imaging of healthy participants in the study.¹⁶ Studies that did not report enough detail to determine whether a criterion was met received no points, and studies that included only healthy participants received full points for criteria that required differentiation between groups (e.g., blinding of raters to participant status). Two reviewers individually scored each article, and a third reviewer resolved any differences. Average quality across the included studies was calculated, and individual articles were categorized into three quality levels: (1) high quality: > 6.0 points; (2) fair quality: 4.5–6.0 points; and (3) poor quality: < 4.5 points.

Statistical Analysis

A meta-analysis was performed to identify normative values for sonographic measurement of median nerve CSA stratified by anatomic location. Weighted averages were calculated for each anatomic location using random-effects models specifying the mean value of each study-specific median nerve CSA as an effect size. Standard errors for each study mean were obtained (in order of preference): (1) using directly reported standard errors, (2) calculated from standard deviation (SD) and sample size, or (3) using the sample range to compute an SD. Overall measures, study-specific effect sizes, and 95% confidence intervals (CIs) were displayed in forest plots by anatomic location, and the I² test statistic was used to evaluate heterogeneity of CSA means across studies. A meta-regression was conducted to examine heterogeneity effects of age (i.e., mean study age) and sex (i.e., % male in study) at the two most clinically used anatomical locations (i.e., proximal forearm, proximal carpal tunnel). Finally, means were reported by subgroups of sex and hand dominance using studies that reported CSA values in these two locations by these subgroups or that had a homogeneous sample (e.g., all females, all dominant hands); differences in CSA means by sex and hand dominance were tested. Meta-analyses were conducted using Stata V17 (College Station, TX).

Results

Study Selection

The flow of records through the study selection process is presented in Figure 1. Screening was conducted for 18 592 unique records. A total of 418 full-text articles were reviewed for eligibility due to abstracts indicating that sonographic measurement of the median nerve was conducted in the study. Articles were excluded that did not evaluate median nerve CSA (n = 75), did not include healthy participants (n = 34), or did not use an appropriate measurement technique (n = 166). In addition, 69 articles were excluded due to missing data or re-reporting of healthy participant data that had been used in previous studies already included in the review. One study was identified as an outlier and excluded; this study reported an average CSA of approximately twice the size reported by the 20 other studies within the same anatomical region.¹⁸ Data from the remaining 73 articles were included in the meta-analysis.

Figure 1.

Flow chart of studies through the search, screening, eligibility, and inclusion process.

Study Characteristics and Quality

The proximal carpal tunnel (47/73, 64.4%), carpal tunnel inlet (35/73, 47.9%), and proximal forearm (20/73, 27.4%) were the most common anatomical locations of CSA measurement among the included studies. The meta-analytic average age of healthy participants across all articles in the sample was 43.6 years. The average quality rating across the included studies was 6.1 of 8.0, with 41 of 73 (56.2%) studies identified as high quality, 28 of 73 (38.4%) fair quality, and 5 of 73 (6.8%) poor quality (see Table 2). Quality of the image acquisition process was the criterion most often partially or not met based on the description in the articles (i.e., only 37.8% fully met this criterion). Only half of the studies indicated the qualifications of the individuals obtaining or measuring the sonographic data.

Table 2.

A Quality Assessment of Included Published Studies, Sorted By Their Quality Score.

Study	Rating	Score	Criterion
Study	Rating	Score	1	2	3	4	5	6	7	8
Ajeena et al.¹⁹	Good	8
Ghasemi-Esfe et al.²⁰	Good	8
Horng et al.²¹	Good	8
Kwon et al.²²	Good	8
Tajika et al.²³	Good	8
Boehm et al.²⁴	Good	7.5
Junck et al.²⁵	Good	7.5
Kerasnoudis et al.²⁶	Good	7.5
Mansiz Kaplan et al.²⁷	Good	7.5
Rahmani et al.²⁸	Good	7.5
Woo et al.²⁹	Good	7.5
Cartwright et al.³⁰	Good	7
Cartwright et al.³¹	Good	7
Ghasemi-Esfe et al.³²	Good	7
Kang et al.³³	Good	7
Kantarci et al.³⁴	Good	7
Kim et al.³⁵	Good	7
Lai et al.³⁶	Good	7
Loh and Muraki³⁷	Good	7
Loh et al.³⁸	Good	7
Mohammadi et al.³⁹	Good	7
Ooi et al.⁴⁰	Good	7
Roll et al.⁴¹	Good	7
Şahin Şenocak et al.⁴²	Good	7
Toosi et al.⁴³	Good	7
Werner et al.⁴⁴	Good	7
Won et al.⁴⁵	Good	7
Chen et al.⁴⁶	Good	6.5
Choo et al.⁴⁷	Good	6.5
Kasius et al.⁴⁸	Good	6.5
Kaymak et al.⁴⁹	Good	6.5
Lee et al.⁵⁰	Good	6.5
Loh et al.⁵¹	Good	6.5
Loh and Muraki⁵²	Good	6.5
Ng et al.⁵³	Good	6.5
Noto et al.⁵⁴	Good	6.5
Pitarokoili et al.⁵⁵	Good	6.5
Toosi et al.⁵⁶	Good	6.5
Yang et al.⁵⁷	Good	6.5
Yurdakul et al.⁵⁸	Good	6.5
Atan and Günendi⁵⁹	Fair	6
Kang et al.⁶⁰	Fair	6
Nodera et al.⁶¹	Fair	6
Su et al.⁶²	Fair	6
Borire et al.⁶³	Fair	5.5
De Kleermaeker et al.⁶⁴	Fair	5.5
El Miedany et al.⁶⁵	Fair	5.5
Jang et al.⁶⁶	Fair	5.5
Kotb et al.⁶⁷	Fair	5.5
Lee et al.⁶⁸	Fair	5.5
Mohamed et al.⁶⁹	Fair	5.5
Mori et al.⁷⁰	Fair	5.5
Mulroy et al.⁷¹	Fair	5.5
Wang et al.⁷²	Fair	5.5
Watanabe et al.⁷³	Fair	5.5
Agirman et al.⁷⁴	Fair	5
Borire et al.⁷⁵	Fair	5
Cartwright et al.⁷⁶	Fair	5
Fujimoto et al.⁷⁷	Fair	5
Lopes et al.⁷⁸	Fair	5
Moon et al.⁷⁹	Fair	5
Park⁸⁰	Fair	5
Scheidl et al.⁸¹	Fair	5
Schreiber et al.⁸²	Fair	5
Borire et al.⁸³	Fair	4.5
Koyuncuoglu et al.⁸⁴	Fair	4.5
Miwa and Miwa⁸⁵	Fair	4.5
Pelosi et al.⁸⁶	Fair	4.5
Schreiber et al.⁸⁷	Poor	4
van Doesburg et al.⁸⁸	Poor	4
Arumugam et al.⁸⁹	Poor	3.5
Hammer et al.⁹⁰	Poor	3.5
Niu et al.⁹¹	Poor	2

Green plus = satisfactorily met the criterion; yellow plus = partially met the criterion; red minus = did not meet criterion; gray question mark = did not report on the criterion. Quality assessment was conducted using a modified version of the National Institute of Health Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies¹⁷ using the eight criteria as previously described.¹⁶

Meta-analysis of Healthy Median Nerve CSA

The weighted averages and CIs for median nerve CSA across the nine anatomic regions are presented in Table 3. The median nerve CSA was approximately 8–9 mm² in the upper arm, elbow, and wrist, with a smaller CSA noted in forearm. In the most frequently measured regions, CSA was 6.46 mm² (95% CI: 6.09–6.84) in the proximal forearm, 8.60 mm² (95% CI: 8.23–8.97) at the level of the pisiform in the proximal carpal tunnel, and 8.68 mm² (95% CI: 8.22–9.13) at inlet to the carpal tunnel (see Figures 2 and 3). Most CIs for the weighted means were approximately ±0.5 mm²; however, these intervals were larger for measurements in the upper arm, the distal carpal tunnel, and the carpal tunnel outlet indicating either wider variability in nerve size or increased measurement error in these locations. The I² values indicated heterogeneity across the included studies suggesting potential moderating effects within the individual study designs or samples and confirming the need for further meta-regression and moderator analyses. Forest plots for the additional anatomical regions are provided and these give a quick graphic summary and direction of the data (see Supplemental Figures 1–6).

Table 3.

Meta-Analytic Averages for Cross-Sectional Area (CSA) of the Median Nerve Within Healthy Individuals Across Anatomical Regions of the Upper Extremity.

Anatomical Region	N	Weighted Mean	95% CI	I ²
Axilla	1	7.90	7.53–8.27	–
Humerus	12	9.27	8.50–10.05	97.1
Elbow	6	8.32	7.69–8.95	88.7
Proximal forearm	20	6.46	6.09–6.84	99.3
Distal forearm	9	6.20	5.87–6.53	92.9
Carpal tunnel inlet	35	8.68	8.22–9.13	98.6
Proximal carpal tunnel	47	8.60	8.23–8.97	99.1
Distal carpal tunnel	15	8.43	7.62–9.25	98.6
Carpal tunnel outlet	2	11.12	9.77–12.47	86.7

Abbreviation: CI, confidence interval.

Figure 2.

Forest plot of meta-analysis results showing the direction and magnitude of the weighted averages of median nerve cross-sectional area (CSA) in the proximal forearm 10 cm or greater from the wrist across individual studies. CI, confidence interval.

Figure 3.

Forest plot of meta-analysis results showing the direction and magnitude of the weighted averages of median nerve cross-sectional area (CSA) at the inlet to the carpal tunnel (CT) up to 4cm proximal to the radial carpal joint (i.e., distal wrist crease; (a)) and proximal CT at the level of the pisiform (b) across individual studies. CI, confidence interval.

Meta-regression and Moderator Analysis of Study Factors Related to CSA

Five studies were excluded from the meta-regression due to missing data for average age or sex distribution (i.e., % male). Among the remaining studies, there was no significant effect of sex distribution or age in proximal forearm CSA (sex, P = .809; age, P = .418) and no effect of sex distribution on proximal carpal tunnel CSA (sex, P = .112). There was a statically significant effect of age on proximal carpal tunnel CSA (P = .047), such that, assuming a linear trend, each year of increase or decrease from the average age of the sample (i.e., 43.6 years) would result in a subsequent increase or decrease in CSA by 0.03 mm² [95% CI: 0.00–0.07]. Thus, assuming a linear trend, the estimated range of normal CSA at the pisiform for adults aged 18–65 years would be 7.83–9.24 mm².

Only three studies reported stratified data by either sex or hand dominance at the proximal forearm, so that, further evaluation of these factors at this location was not completed. Ten studies provided proximal carpal tunnel CSA values stratified by sex (see Figure 4). The weighted average CSA of these 10 studies was equal to the overall weighted average of the 47 studies measuring CSA at this location (i.e., approximately 8.60 mm²); however, men (9.42 mm² [8.06–10.78]) had statistically larger weighted average CSA (P = .03) as compared with women (7.71 mm² [7.01–8.42]). Eighteen studies reported CSA values at the proximal carpal tunnel stratified by hand dominance and 16 studies reported values based on laterality of right versus left wrist (see Figure 5). The weighted averages were nearly identical with no significant differences between nerves measured in a dominant wrist (8.51 mm² [7.72–9.29]) and a non-dominant wrist (8.57 mm² [7.62–9.52]), and in nerves measured in the right (7.71 mm² [7.03–8.40]) versus left wrist (7.93 mm² [7.46–8.76]). Similarly, there was no significant difference (P = .81) among eleven studies that reported laterality for CSA of the median nerve in the proximal formal between the right (6.92 mm² [6.30–7.54]) and left (6.87 mm² [6.49–7.26]).

Figure 4.

Forest plots showing group differences for weighted averages of median nerve cross-sectional area (CSA) in the proximal carpal tunnel (CT) among studies that provided data stratified by sex demonstrating significantly larger CSA (P = .03) in men (9.42 mm²) than in women (8.58 mm²). CI, confidence interval.

Figure 5.

Forest plots showing group differences for weighted averages of median nerve cross-sectional area (CSA) in the proximal carpal tunnel (CT) among studies that provided data stratified by hand dominance (a) or side (b) demonstrating no differences based on laterality (P = .92, P = .41). CI, confidence interval.

Discussion

Without accounting for age, sex, or laterality, healthy median nerve CSA values measured at the inlet to or in the proximal carpal tunnel all fall below the commonly used diagnostic threshold of 10 mm² and are well below meta-analytic values reported for patients with various severities of CTS.^5,92 Reference values for median nerve CSA in healthy individuals change slightly as the nerve travels from proximal to distal, being of similar size in the wrist and upper arm regions and slightly smaller in the forearm. Specifically, healthy median nerve CSA should be about 8.60 mm² in the proximal carpal tunnel, approximately 2.0 mm² larger than in the forearm with a wrist-to-forearm ratio of approximately 1.3. Although using either a difference of 2.0 mm² or a wrist-to-forearm ratio of greater than 1.4 as suggested by commonly cited literature,^93,94 these measures may lead to false positives and might be best considered as general “rules of thumb” rather than singular diagnostic threshold. That is, when considering CIs of healthy measures of the nerve between the proximal forearm and carpal tunnel, the potential difference in a healthy individual could be as large as 2.88 mm² (i.e., 8.97–6.09 mm²) with a corresponding wrist-to-forearm ratio of 1.5. Definitive diagnosis of CTS may require adoption of these more conservative thresholds or a combination of multiple clinical measures.^9,95

When accounting for linear changes by age, the estimated range of CSA within the carpal tunnel in healthy adults (18–65) is 7.83–9.24 mm², falling well below a diagnostic threshold of 10 mm². Given a small effect of age on CSA measures, adjusting normative values is only necessary when evaluating pediatric or older adults; however, sex and laterality may require attention in clinical practice and research. Although there were no differences in median nerve CSA when considering percent male versus female across 47 studies, among 10 studies that exclusively stratified data by sex, men had significantly larger CSA than women. Given that these studies had the same weighted average as the full sample when compiling men and women together, research with mixed-sex samples could confidently use 8.60 mm² as a valid reference for median nerve CSA at the level of the pisiform. Alternatively, for studies with higher representation of men or women and for individual patients, researchers or clinicians should consider using the sex-normed reference values of 7.71 mm² for women and 9.42 mm² for men. Importantly, caution should be used when applying the diagnostic threshold of 10.0 mm² in men as the upper limit of the 95% CI for male CSA surpasses this threshold in the aggregate data within this meta-analysis.

In healthy individuals, median nerve CSA in the proximal carpal tunnel is likely highly similar between dominant and non-dominant sides. Thus, studies that consider bilateral CSA as independent data points could have increased risk of erroneous statistical findings. Alternatively, accounting for within-subject differences between wrists as a diagnostic assessment may have significant validity. Current primary sonographic diagnostic criteria for CTS rely on an absolute threshold (i.e., 10.0 mm²) or a within-arm comparison (e.g., wrist-to-forearm ratio). Adding a bilateral comparison criterion would mirror electrodiagnostic approaches that consider bilateral differences in conduction velocities along with an absolute threshold and a within-arm comparison with the ulnar nerve.

Methodological concerns require attention to improve rigor in the clinical or research use of median nerve CSA measurements. One previously identified issue that remains pervasive is the wide variability how anatomical locations of CSA measurements are identified and described.⁶ Two issues arose in attempting to categorize study findings using the heterogeneous descriptions across the studies. First, the same term was often used to represent different anatomical regions, such as the word “inlet” used to indicate a location immediately proximal to the carpal ligament in some studies and a location under the most proximal portion of the carpal ligament in other studies. Second, there was variability in how much detail was used to describe where a measure was taken and disparate use of surface landmarks versus sonographically identified anatomical landmarks to identify the measurement location. For example, the “carpal tunnel inlet” was sometimes mentioned as generally being measured from an image taken at the wrist crease, while measurements in the proximal forearm were sometimes completed at a specific distance from the elbow or wrist and other times completed at the location where the nerve emerged between the heads of the pronator teres muscle. The only consistent description noted across the studies was using the pisiform as a landmark for measuring the median nerve in the proximal carpal tunnel. Developing additional standardized nomenclature that avoids gross, external landmarks and uses clear sonographic anatomical landmarks for the acquisition and analysis of median nerve CSA will improve clarity across research studies and consistency in clinical diagnostics.

In addition to adopting standardized nomenclature, there is a significant need for studies to clearly describe how individual patients versus individual wrists are included or excluded from final data samples. It was often challenging to determine whether one or both wrists were included among individual participants and even more challenging to know when or why data from some wrists were either not collected or were excluded when the number of wrists was not equal between sides or did not match the total number of participants in the sample. Importantly, if both wrists of an individual participant are included, data from this meta-analysis suggest a need to account for the dependent nature of nerves when conducting within-subject analyses. Finally, although most studies now measure CSA using a direct trace within the hyperechoic epineurium, multiple studies were eliminated due to measurement using less sensitivity or accurate techniques (e.g., ellipse).

Limitations

The reliance on reported summary data rather than using primary data, combined with inconsistencies in reporting of methodological details across studies introduces some error in the meta-analytic means. First, individual studies obtained and reported data either by individual or by wrist, and it was often unclear when data were from left or right wrists, from dominant or non-dominant sides, or averaged across a mixture of both upper extremities. Furthermore, some studies reported inconsistencies between the number of included wrists or individuals and the final sample size used in the analysis. Second, despite efforts to obtain missing data, many studies were excluded, and inconsistent reporting of race and ethnicity resulted in the inability to examine CSA based on these factors. Finally, definitions of “healthy” varied greatly across studies or were generally undefined, which potentially resulted in inclusion of some data from individuals with pathologies. Despite these limitations, consistency of CSA means within similar ranges across the included studies increases confidence in reporting the meta-analytic averages as normative reference values within the general population.

Conclusion

Using data from 73 studies, normative reference values for the CSA of the median nerve in healthy individuals were identified. The reference value for the most common measurement site within the carpal tunnel at the level of the pisiform is 8.60 mm². Adjustment for age in a clinical setting or age-matching in research samples may only be necessary when examining pediatric or older adult patients. Men generally have larger CSA in the proximal carpal tunnel than women, and caution is required when applying a diagnostic threshold of 10.0 mm² for male patients as the upper limit of normative averages surpasses this threshold. Finally, evidence of no difference between dominant and non-dominant wrists is important. Researchers should avoid considering bilateral CSA measures from one individual as independent data points, while within-patient differences between wrists may be useful as a clinical diagnostic assessment. In addition to normative values, this meta-analysis illuminated numerous issues in the quality of study reporting, variations in the use of anatomical landmarks, and a lack of standard nomenclature.

Supplemental Material

sj-docx-2-jdm-10.1177_87564793231176009 – Supplemental material for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals

Supplemental material, sj-docx-2-jdm-10.1177_87564793231176009 for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals by Shawn C. Roll, Sandy C. Takata, Buwen Yao, Lynn Kysh and Wendy J. Mack in Journal of Diagnostic Medical Sonography

Supplemental Material

sj-docx-3-jdm-10.1177_87564793231176009 – Supplemental material for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals

Supplemental material, sj-docx-3-jdm-10.1177_87564793231176009 for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals by Shawn C. Roll, Sandy C. Takata, Buwen Yao, Lynn Kysh and Wendy J. Mack in Journal of Diagnostic Medical Sonography

Supplemental Material

sj-pdf-1-jdm-10.1177_87564793231176009 – Supplemental material for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals

Supplemental material, sj-pdf-1-jdm-10.1177_87564793231176009 for Sonographic Reference Values for Median Nerve Cross-sectional Area: A Meta-analysis of Data From Healthy Individuals by Shawn C. Roll, Sandy C. Takata, Buwen Yao, Lynn Kysh and Wendy J. Mack in Journal of Diagnostic Medical Sonography

Footnotes

Acknowledgements

The authors would like to acknowledge the assistance in reviewing abstracts and studies provided by Joyce Ho and Nina Wakayama.

Key Takeaways

A healthy median nerve cross-sectional area reference at the pisiform is 8.60 mm².

Age adjustments for median nerve reference values are not indicated in adults.

Healthy men have larger nerves that may exceed common diagnostic thresholds.

Healthy nerves do not differ in size between wrists.

Differences in nerve area between wrists may be a viable diagnostic indicator.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by grant number R01 OH010665 from the Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health, and by grant number F31 AR074894 from the National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the CDC or the NIH.

Peer Reviewer Guarantee Statement

The Editor/Associate Editor of JDMS is an author of this article; therefore, the peer review process was managed by alternative members of the Board and the submitting Editor/Associate Editor had no involvement in the decision-making process.

ORCID iDs

Shawn C. Roll

Sandy C. Takata

Buwen Yao

Supplemental Material

Supplemental material for this article is available online. Scan the QR code with your smart device to view the online supplemental videos available at .

References

Fowler

Byrne

Pan

Goitz

: False-positive rates for nerve conduction studies and ultrasound in patients without clinical signs and symptoms of carpal tunnel syndrome. J Hand Surg Am 2019;44(3):181–185.

Wang

Buterbaugh

Kadow

Goitz

Fowler

: A prospective comparison of diagnostic tools for the diagnosis of carpal tunnel syndrome. J Hand Surg Am 2018;43(9):833–836.e2.

Cartwright

Hobson-Webb

Boon

, et al: Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012;46(2):287–293.

Ibrahim

Khan

Goddard

Smitham

: Suppl 1: carpal tunnel syndrome: a review of the recent literature. Open Orthop J 2012;6:69.

Fowler

Gaughan

Ilyas

: The sensitivity and specificity of ultrasound for the diagnosis of carpal tunnel syndrome: a meta-analysis. Clin Orthop Relat Res 2011;469:1089–1094.

Roll SC, Case-Smith J, Evans KD: Diagnostic accuracy of ultrasonography vs. electromyography in carpal tunnel syndrome: a systematic review of literature. Ultrasound Med Biol 2011;37:1539–1553.

Pelosi

Arányi

Beekman

, et al: Expert consensus on the combined investigation of carpal tunnel syndrome with electrodiagnostic tests and neuromuscular ultrasound. Clin Neurophysiol 2022;135:107–116. doi:10.1016/j.clinph.2021.12.012.

Wang

Hanson

Fowler

: A comparison of 6 diagnostic tests for carpal tunnel syndrome using latent class analysis. Hand 2020;15:776–779.

Roll

Volz

Fahy

Evans

: Carpal tunnel syndrome severity staging using sonographic and clinical measures. Muscle Nerve 2015;51(6):838–845.

10.

Bathala

Kumar

Shaik

Visser

: Normal values of median nerve cross-sectional area obtained by ultrasound along its course in the arm with electrophysiological correlations, in 100 Asian subjects. Muscle Nerve 2014;49(2):284–286.

11.

Burg

Bathala

Visser

: Difference in normal values of median nerve cross-sectional area between Dutch and Indian subjects. Muscle Nerve 2014;50(1):129–132.

12.

Qrimli

Ebadi

Breiner

, et al: Reference values for ultrasonograpy of peripheral nerves. Muscle Nerve 2016;53(4):538–544.

13.

Cartwright

Mayans

Gillson

Griffin

Walker

: Nerve cross-sectional area in extremes of age. Muscle Nerve 2013;47(6):890–893.

14.

Guillen-Astete

Muñoz Martinez-De-Castilla

Zurita-Prada

Urrego-Laurín

García-Casado

: Relationship between anthropometric variables and the cross-sectional area of the median nerve by ultrasound assessment in healthy subjects. Acta Reumatol Port 2020;45(2):104–110.

15.

Moher

Liberati

Tetzlaff

Altman

: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–269, W264.

16.

Takata

Kysh

Mack

Roll

: Sonographic reference values of median nerve cross-sectional area: a protocol for a systematic review and meta-analysis. Syst Rev 2019;8:2.

17.

National Heart, Lung, and Blood Institute: Quality assessment tool for observational cohort and cross-sectional studies. Date unknown. Accessed January 11, 2022. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.

18.

Karmakar

: Age-related differences in the quantitative echo texture of the median nerve. J Ultrasound Med 2015;34(5):797–804.

19.

Ajeena

Al-Saad

Al-Mudhafar

Hadi

Al-Aridhy

: Ultrasonic assessment of females with carpal tunnel syndrome proved by nerve conduction study. Neural Plast 2013;2013: 754564.

20.

Ghasemi-Esfe

Khalilzadeh

Mazloumi

, et al: Combination of high-resolution and color Doppler ultrasound in diagnosis of carpal tunnel syndrome. Acta Radiol 2011;52:191–197.

21.

Horng

Hsieh

Lin

Chang

Lee

Liang

: Ultrasonographic median nerve changes under tendon gliding exercise in patients with carpal tunnel syndrome and healthy controls. J Hand Ther 2014;27(4):317–323; quiz 324.

22.

Kwon

Jung

Baek

: Comparison of sonography and electrodiagnostic testing in the diagnosis of carpal tunnel syndrome. J Hand Surg Am 2008;33(1):65–71.

23.

Tajika

Kobayashi

Yamamoto

Kaneko

Takagishi

: Diagnostic utility of sonography and correlation between sonographic and clinical findings in patients with carpal tunnel syndrome. J Ultrasound Med 2013;32(11):1987–1993.

24.

Boehm

Scheidl

Bereczki

Schelle

Arányi

: High-resolution ultrasonography of peripheral nerves: measurements on 14 nerve segments in 56 healthy subjects and reliability assessments. Ultraschall Med 2014;35(5):459–467.

25.

Junck

Escobedo

Lipa

, et al: Reliability assessment of various sonographic techniques for evaluating carpal tunnel syndrome. J Ultrasound Med 2015;34(11):2077–2088.

26.

Kerasnoudis

Pitarokoili

Behrendt

Gold

Yoon

: Cross sectional area reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol 2013;124(9):1881–1888.

27.

Mansiz Kaplan

Yağci Akdeniz

Leblebicier

: Ultrasonographic assessment of the shoulder in patients with carpal tunnel syndrome. Marmara Med J 2016;29:102–109.

28.

Rahmani

Ghasemi Esfe

Vaziri-Bozorg

Mazloumi

Khalilzadeh

Kahnouji

: The ultrasonographic correlates of carpal tunnel syndrome in patients with normal electrodiagnostic tests [Erratum appears in Radiol Med 2011;116(3):503. Note: Bozorg SM [corrected to Vaziri-Bozorg SM]]. Radiol Med (Torino) 2011;116:489–496.

29.

Woo

EHC

White

Lai

CWK

: Morphological changes of the median nerve within the carpal tunnel during various finger and wrist positions: an analysis of intensive and nonintensive electronic device users. J Hand Surg Am 2019;44(7):610.e1–610.e15.

30.

Cartwright

Shin

Passmore

Walker

: Ultrasonographic reference values for assessing the normal median nerve in adults. J Neuroimaging 2009;19(1):47–51.

31.

Cartwright

Baute

Caress

Walker

: Ultrahigh-frequency ultrasound of fascicles in the median nerve at the wrist. Muscle Nerve 2017;56(4):819–822.

32.

Ghasemi-Esfe

Khalilzadeh

Vaziri-Bozorg

, et al: Color and power Doppler US for diagnosing carpal tunnel syndrome and determining its severity: a quantitative image processing method. Radiology 2011;261(2):499–506.

33.

Kang

Yang

Yoon

Kang

Won

: Effect of carpal tunnel syndrome on the ulnar nerve at the wrist: sonographic and electrophysiologic studies. J Ultrasound Med 2016;35(1):37–42.

34.

Kantarci

Ustabasioglu

Delil

, et al: Median nerve stiffness measurement by shear wave elastography: a potential sonographic method in the diagnosis of carpal tunnel syndrome. Eur Radiol 2014;24(2):434–440.

35.

Kim

Joo

Han

Kim

: The nerve/tunnel index: a new diagnostic standard for carpal tunnel syndrome using sonography: a pilot study. J Ultrasound Med 2012;31(1):23–29.

36.

Lai

Chiu

Law

: The deformation and longitudinal excursion of median nerve during digits movement and wrist extension. Man Ther 2014;19(6):608–613.

37.

Loh

Muraki

: Effect of wrist angle on median nerve appearance at the proximal carpal tunnel. PLoS ONE 2015;10(2):e0117930.

38.

Loh

Nakashima

Muraki

: Median nerve behavior at different wrist positions among older males. PeerJ 2015;3:e928.

39.

Mohammadi

Afshar

Masoudi

Etemadi

: Comparison of high resolution ultrasonography and nerve conduction study in the diagnosis of carpal tunnel syndrome: diagnostic value of median nerve cross-sectional area. Iran J Radiol 2009;6:147–152.

40.

Ooi

Wong

Tan

, et al: Diagnostic criteria of carpal tunnel syndrome using high-resolution ultrasonography: correlation with nerve conduction studies. Skeletal Radiol 2014;43(10):1387–1394. doi:10.1007/s00256-014.

41.

Roll

Evans

Freimer

Sommerich

: Screening for carpal tunnel syndrome using sonography. J Ultrasound Med 2011;30(12):1657–1667.

42.

Şahin

Şenocak

Üzüm

Kıyan

Çoğalgil

: Ultrasonographic evaluation of median nerve in tennis training athletes. Erciyes Tıp Dergisi 2010;32:247–252.

43.

Toosi

Impink

Baker

Boninger

: Effects of computer keyboarding on ultrasonographic measures of the median nerve. Am J Ind Med 2011;54(11):826–833.

44.

Werner

Jacobson

Jamadar

: Influence of body mass index on median nerve function, carpal canal pressure, and cross-sectional area of the median nerve. Muscle Nerve 2004;30(4):481–485.

45.

Won

Kim

Park

Yoon

Choi

: Reference values for nerve ultrasonography in the upper extremity. Muscle Nerve 2013;47(6):864–871.

46.

Chen

Huang

, et al: Ultrasonographic median nerve cross-section areas measured by 8-point “inching test” for idiopathic carpal tunnel syndrome: a correlation of nerve conduction study severity and duration of clinical symptoms. BMC Med Imaging 2011;11:1–9.

47.

Choo

Lee

Park

Kim

: Distally extended muscle belly of the flexor digitorum within the carpal tunnel: is it a risk factor for carpal tunnel syndrome? Acta Radiol 2017;58(10):1269–1275.

48.

Kasius

Claes

Meulstee

Verhagen

: Bifid median nerve in carpal tunnel syndrome: do we need to know? Muscle Nerve 2014;50(5):835–843.

49.

Kaymak

Ozçakar

Cetin

Candan Cetin

Akinci

Hasçelik

: A comparison of the benefits of sonography and electrophysiologic measurements as predictors of symptom severity and functional status in patients with carpal tunnel syndrome. Arch Phys Med Rehabil 2008;89(4):743–748.

50.

Lee

Kim

: Relationship between electrodiagnosis and various ultrasonographic findings for diagnosis of carpal tunnel syndrome. Ann Rehabil Med 2016;40(6):1040–1047.

51.

Loh

Nakashima

Muraki

: Effects of grip force on median nerve deformation at different wrist angles. PeerJ 2016;4: e2510.

52.

Loh

Muraki

: Effect of wrist deviation on median nerve cross-sectional area at proximal carpal tunnel level. Iran J Pub Health 2014;43:180–185.

53.

Griffith

Lee

Tse

Wong

: Ultrasound carpal tunnel syndrome: additional criteria for diagnosis. Clinical Radiology 2018;73:214.e11–214.e18.

54.

Noto

Garg

, et al: Comparison of cross-sectional areas and distal-proximal nerve ratios in amyotrophic lateral sclerosis. Muscle Nerve 2018;58(6):777–783.

55.

Pitarokoili

Kerasnoudis

Behrendt

, et al: Facing the diagnostic challenge: nerve ultrasound in diabetic patients with neuropathic symptoms. Muscle Nerve 2016;54(1):18–24.

56.

Toosi

Hogaboom

Oyster

Boninger

: Computer keyboarding biomechanics and acute changes in median nerve indicative of carpal tunnel syndrome. Clin Biomech (Bristol, Avon) 2015;30(6):546–550.

57.

Yang

Kang

Yoon

Won

Seo

Koh

: Is median nerve enlargement at the wrist associated with tremor in Parkinson disease? J Ultrasound Med 2014;33(12):2079–2083.

58.

Yurdakul

Mesci

Çetinkaya

Geler Külcü

: Diagnostic significance of ultrasonographic measurements and median-ulnar ratio in carpal tunnel syndrome: correlation with nerve conduction studies. J Clin Neurol 2016;12(3):289–294.

59.

Atan

Günendi

: Diagnostic utility of the sonographic median to ulnar nerve cross-sectional area ratio in carpal tunnel syndrome. Turk J Med Sci 2018;48:110–116.

60.

Kang

Kim

Yang

Yoon

: Sonographic features of peripheral nerves at multiple sites in patients with diabetic polyneuropathy. J Diabetes Complications 2016;30(3):518–523.

61.

Nodera

Takamatsu

Shimatani

, et al: Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography. Clin Neurophysiol 2014;125(9):1906–1911.

62.

Chen

Wang

Liang

: Correlation between subclinical median neuropathy and the cross-sectional area of the median nerve at the wrist. Ultrasound Med Biol 2013;39(6):975–980.

63.

Borire

Arnold

Pussell

, et al: Effects of hemodialysis on intraneural blood flow in end-stage kidney disease. Muscle Nerve 2018;57(2):287–293.

64.

De Kleermaeker

FGCM

Meulstee

Verhagen

WIM

: The controversy of the normal values of ultrasonography in carpal tunnel syndrome: diagnostic accuracy of wrist-dependent CSA revisited. Neurol Sci 2019;40(5):1041–1047.

65.

El Miedany

Aty

Ashour

: Ultrasonography versus nerve conduction study in patients with carpal tunnel syndrome: substantive or complementary tests? Rheumatology (Oxford) 2004;43:887–895.

66.

Jang

Cho

Yang

Seok

Kim

: Pattern analysis of nerve enlargement using ultrasonography in chronic inflammatory demyelinating polyneuropathy. Clin Neurophysiol 2014;125(9):1893–1899.

67.

Kotb

Bedewi

Aldossary

Mahmoud

Naguib

: Sonographic assessment of carpal tunnel syndrome in diabetic patients with and without polyneuropathy. Medicine (Baltimore) 2018;97(24):e11104.

68.

Lee

Kim

, et al: Ultrasonography and electrophysiological study of median nerve in patients with essential tremor. PLoS ONE 2019;14(4):e0215750.

69.

Mohamed

Amin

Aboelsafa

Elsayed

: Contribution of power Doppler and gray-scale ultrasound of the median nerve in evaluation of carpal tunnel syndrome. Egypt J Radiol Nucl Med 2014;45:191–201.

70.

Mori

Nodera

Takamatsu

, et al: Focal nerve enlargement is not the cause for increased distal motor latency in ALS: sonographic evaluation. Clin Neurophysiol 2015;126:1632–1637.

71.

Mulroy

Pelosi

Leadbetter

, et al: Peripheral nerve ultrasound in Friedreich ataxia. Muscle Nerve 2018;57(5):852–856.

72.

Wang

Leong

Huang

Hung

Cheung

Pong

: Best diagnostic criterion in high-resolution ultrasonography for carpal tunnel syndrome. Chang Gung Med J 2008;31(5):469–476.

73.

Watanabe

Sakakibara

Sugimori

, et al: Effect of long-term physical exercise of peripheral nerve: comparison of nerve conduction study and ultrasonography. J Sports Med Phys Fitness 2012;52(2):212–220.

74.

Agirman

Yagci

Leblebicier

Ozturk

Akyuz

: Is ultrasonography useful in the diagnosis of the polyneuropathy in diabetic patients? J Phys Ther Sci 2016;28(9):2620–2624.

75.

Borire

Issar

Kwai

, et al: Correlation between markers of peripheral nerve function and structure in type 1 diabetes. Diabetes Metab Res Rev 2018;34(7):e3028.

76.

Cartwright

Walker

Griffin

Caress

: Peripheral nerve and muscle ultrasound in amyotrophic lateral sclerosis. Muscle Nerve 2011;44(3):346–351.

77.

Fujimoto

Kanchiku

Kido

Imajo

Funaba

Taguchi

: Diagnosis of Severe Carpal tunnel syndrome using nerve conduction study and ultrasonography. Ultrasound Med Biol 2015;41(10):2575–2580.

78.

Lopes

Lawson

Scott

Keir

: Tendon and nerve excursion in the carpal tunnel in healthy and CTD wrists. Clin Biomech (Bristol, Avon) 2011;26(9):930–936.

79.

Moon

Kwon

Kim

Lee

: Ultrasonography of palm to elbow segment of median nerve in different degrees of diabetic polyneuropathy. Clin Neurophysiol 2014;125(4):844–848.

80.

Park

: Ultrasonography of the transverse movement and deformation of the median nerve and its relationships with electrophysiological severity in the early stages of carpal tunnel syndrome. PM R 2017;9(11):1085–1094.

81.

Scheidl

Böhm

Simó

Bereznai

Bereczki

Arányi

: Different patterns of nerve enlargement in polyneuropathy subtypes as detected by ultrasonography. Ultrasound Med Biol 2014;40(6):1138–1145.

82.

Schreiber

Oldag

Kornblum

, et al: Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP. Muscle Nerve 2013;47(3):385–395.

83.

Borire

Arnold

Pussell

, et al: Haemodialysis alters peripheral nerve morphology in end-stage kidney disease. Clin Neurophysiol 2017;128(1):281–286.

84.

Koyuncuoglu

Kutluhan

Yesildag

Oyar

Guler

Ozden

: The value of ultrasonographic measurement in carpal tunnel syndrome in patients with negative electrodiagnostic tests. Eur J Radiol 2005;56(3):365–369.

85.

Miwa

: Ultrasonography of carpal tunnel syndrome: clinical significance and limitations in elderly patients. Intern Med 2011;50(19):2157–2161.

86.

Pelosi

Mulroy

Leadbetter

, et al: Peripheral nerves are pathologically small in cerebellar ataxia neuropathy vestibular areflexia syndrome: a controlled ultrasound study. Eur J Neurol 2018;25(4):659–665.

87.

Schreiber

Abdulla

Debska-Vielhaber

, et al: Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes. Muscle Nerve 2015;51(5):669–675.

88.

van Doesburg

Henderson

Yoshii

, et al: Median nerve deformation in differential finger motions: ultrasonographic comparison of carpal tunnel syndrome patients and healthy controls. J Orthop Res 2012;30(4):643–648.

89.

Arumugam

Razali

Vethakkan

Rozalli

Shahrizaila

: Relationship between ultrasonographic nerve morphology and severity of diabetic sensorimotor polyneuropathy. Eur J Neurol 2016;23(2):354–360.

90.

Hammer

Hovden

Haavardsholm

Kvien

: Ultrasonography shows increased cross-sectional area of the median nerve in patients with arthritis and carpal tunnel syndrome. Rheumatology (Oxford) 2006;45(5):584–588.

91.

Niu

Cui

Liu

: Multiple sites ultrasonography of peripheral nerves in differentiating charcot–marie–tooth type 1A from chronic inflammatory demyelinating polyradiculoneuropathy. Front Neurol 2017;8:181.

92.

Roomizadeh

Eftekharsadat

Abedini

, et al: Ultrasonographic assessment of carpal tunnel syndrome severity: a systematic review and meta-analysis. Am J Phys Med Rehabil 2019;98(5):373–381.

93.

Klauser

Halpern

De Zordo

, et al: Carpal tunnel syndrome assessment with US: value of additional cross-sectional area measurements of the median nerve in patients versus healthy volunteers. Radiology 2009;250(1):171–177.

94.

Hobson-Webb

Massey

Juel

Sanders

: The ultrasonographic wrist-to-forearm median nerve area ratio in carpal tunnel syndrome. Clin Neurophysiol 2008;119:1353–1357.

95.

Wang

Hanson

Fowler

: A comparison of 6 diagnostic tests for carpal tunnel syndrome using latent class analysis. Hand (N Y) 2020;15(6):776–779.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.44 MB

0.02 MB

0.05 MB