Carpal Tunnel Syndrome Assessment with US: Value of Additional Cross-sectional Area Measurements of the Median Nerve in Patients versus Healthy Volunteers

Introduction

Carpal tunnel syndrome (CTS) is the most frequent entrapment syndrome of the upper limb; it arises owing to compression of the median nerve at the wrist, which leads to an enlargement of the median nerve cross-sectional area (CSA) (^,1). An early diagnosis based on clinical and electrodiagnostic findings is essential to preventing permanent nerve damage and functional sequelae (^,1). Ultrasonography (US) is a valuable tool for confirming the diagnosis of CTS because it enables one to detect changes in nerve shape and exclude anatomic variants and space-occupying alterations such as ganglion cysts and tenovaginitis (^,2,^,3). CTS is typically associated with a notch sign or an inverted notch sign, and it manifests as an abrupt change in median nerve caliber in the carpal tunnel (^,4).

Several study investigators have attempted to determine the most appropriate median nerve CSA cutoff value (^,4–^,9). However, in the literature, there remains a lack of consensus regarding the most appropriate median nerve CSA threshold for establishing the diagnosis of CTS. In one study (^,4), a cutoff of 15 mm² was advocated for establishing severe disease, but cutoff values ranging from 9 to 12 mm² have been proposed in the majority of studies (^,5–^,11). CSAs larger than 9 mm² (^,10,^,12) and larger than 10 mm² (^,10,^,13,^,14) have been found at the scaphoid-pisiform level in patients with CTS. The purpose of our study was to improve accuracy in the diagnosis of CTS by including an additional cross-sectional measurement of the median nerve more proximally located at the level of the pronator quadratus muscle.

MATERIALS AND METHODS

The study protocol was approved by the university ethics committee of Medical University Innsbruck; written and verbal consent was obtained from all patients and healthy volunteers. Consecutive patients with confirmed CTS were examined. Two patients with a divided median nerve were excluded. One hundred wrists of 68 patients (16 men [mean age, 61.4 years; range, 41–85 years], 52 women [mean age, 56.8 years; range, 25–82 years]; overall mean age, 57.9 years; range, 25–85 years) were examined at US between 2005 and 2007. All patients had the characteristic clinical symptoms, and the results of their electrodiagnostic tests performed within 2 weeks before or after US were positive. CTS severity was classified on the basis of electrophysiologic results as mild or moderate or as severe or extreme according to the modified scoring system of Padua et al (^,15) (^,Table 1).

So that observer bias in the interpretation of our US data could be avoided, the examining radiologist (A.S.K.) was not permitted to ask the volunteers or patients about symptoms. The only information provided to the examining radiologist was a written request from the referring neurologist (W.N.L.) that the patient be examined for the presence of median nerve thickening. US assessment was performed without knowledge of the clinical and electrodiagnostic test results.

The control group comprised 93 wrists of 58 healthy volunteers (16 male [mean age, 58.3 years; range, 26–85 years], 42 female [mean age, 53.9 years; range, 17–78 years]; overall mean age, 55.1 years; range, 17–85 years) with no clinical signs or symptoms of CTS. All control subjects were screened to exclude systemic disorders (ie, diabetes mellitus, connective tissue disorders, and kidney or thyroid abnormalities) that might result in neuropathy (^,1). Both wrists were evaluated in each volunteer in the control group unless there was a bandage or cast that precluded US evaluation. Electrodiagnostic tests were not performed in the healthy volunteers.

US Technique

A musculoskeletal radiologist (A.S.K.) with 5 years of musculoskeletal US experience performed the US examinations by using a 14–8-MHz (LA424, 14-8 MPX; Esaote, Genoa-Firenze, Italy) or 18–6-MHz (LA435, MyLab90; Esaote) linear array transducer. The subjects were seated facing the examiner with their arms extended, their wrists resting on a flat surface, their forearms supine, and their fingers semiextended. Transverse US of the median nerve from the distal forearm to the outlet of the carpal tunnel was performed. Two measurements of the maximal median nerve CSA were obtained: The carpal tunnel cross-sectional area (CSAc) measurement was obtained at the level of maximal nerve shape change from the proximal to the distal carpal tunnel. A more proximal cross-sectional area (CSAp) measurement was obtained in the distal forearm at the level of the proximal third of the pronator quadratus muscle (^,Figs 1, ^,2). The value of the difference between CSAc and CSAp (ΔCSA) was calculated for each wrist.

In keeping with the findings of Ziswiler et al (^,8), the largest CSA was measured at the level of the carpal tunnel, including the entrance under the transverse carpal ligament, the proximal tunnel (scaphoid-pisiform level), and the distal tunnel (trapezium-hamate level). At the level of the distal radius, after the pronator quadratus muscle was visualized, the median nerve was identified between the flexor pollicis longus tendon and the flexor digitorum superficialis tendons. To minimize sampling errors due to differential loads, pressure to the hand was avoided during scanning and measurement. We used the direct measurement technique, tracing a continuous line around the inner hyperechoic rim of the median nerve with electronic calipers. In several other studies (^,4,^,10,^,13), the CSA was calculated by using a formula for an ellipse after the height and width of the nerve were measured. However, according to Hammer et al (^,16), the median nerve may manifest with different configurations, and measurements obtained by performing a continuous boundary trace of the nerves may yield the most correct CSA. Thus, measurements were repeated three times at both (carpal tunnel and proximal) levels, and a median value was used for statistical evaluation.

Statistical Analyses

The sex and age of the patients with CTS and the control subjects and the numbers of right and left wrists examined were tabulated. The two subject groups were compared by using a t test (for age) or χ² test (for subject sex and side), as appropriate. The CSAc and the ΔCSA were compared between the CTS and control subject groups and between the patients with CTS who had a mildly positive nerve conduction velocity and the patients with CTS who had a highly positive nerve conduction velocity. These comparisons were performed by using t tests for unpaired data, with unequal variances in the two groups. The accuracy of US in the diagnosis of CTS was tabulated by using CSAc measurements only (with threshold values of 10, 11, and 12 mm²), as well as by using the ΔCSA (with threshold values of 2 and 3 mm²). To determine whether the ΔCSA rendered a more accurate diagnostic test than the CSAc, receiver operating characteristic analysis was performed. All statistical tests were performed with Stata, version 10.0, statistical software (Stata, College Station, Tex). P < .05 indicated a significant difference.

An important potential issue in our statistical analyses was the lack of statistical independence between the two wrists in any one individual. One hundred symptomatic wrists were evaluated in 68 consecutive patients; both wrists were evaluated in 32 of these patients. Although CTS usually is unilateral and is related to local anatomic changes rather than a systemic process, it is theoretically possible that the observations from one wrist might be correlated with the observations from the other wrist. To reduce possible bias related to observations on the contralateral side, we based our analysis on objective numeric criteria. Pearson correlation coefficients were computed for measurements of CSAc and ΔCSA to determine whether there was any significant correlation between measurements obtained from the right wrist and measurements obtained from the left wrist of patients who had both wrists evaluated. No significant correlation was found between CSAc (correlation coefficient = 0.12, P = .50) and ΔCSA (correlation coefficient = 0.19, P = .32) measurements in the right wrists and these measurements in the left wrists of patients with bilateral CTS. Thus, these measurements were treated as independent observations for the purposes of our analyses.

RESULTS

There was no significant difference in age, sex, or distribution of right versus left wrists between the patients and the healthy volunteers. The mean CSAp was 9.5 mm² ± 1.9 (standard deviation) in the patients with CTS and 8.7 mm² ± 1.6 in the healthy volunteers (P < .01) (^,Table 2). The mean CSAc was 16.8 mm² ± 5.8 in the patients with CTS and 9.0 mm² ± 1.5 in the healthy volunteers (P < .01). The mean ΔCSA was 7.4 mm² ± 5.6 in the CTS group and 0.25 mm² ± 0.43 in the healthy volunteer group (P < .01) (^,Figs 3–^,6^,)^,.

The CTS grade of the 100 affected wrists at electrodiagnostic testing was mildly positive (n = 41) or highly positive (n = 59). The mean CSAp was 9.1 mm² ± 1.6 in the CTS-affected wrists with mildly positive findings and 9.7 mm² ± 2.1 in the CTS-affected wrists with highly positive findings (P = .15) (^,Table 3). The mean CSAc was 14.4 mm² ± 3.3 in the CTS-affected wrists with mildly positive findings and 18.5 mm² ± 6.5 in the CTS-affected wrists with highly positive findings (P < .01). The mean ΔCSA was 5.2 mm² ± 3.1 in the mildly positive group and 8.9 mm² ± 6.4 in the highly positive group (P < .01).

The sensitivities and specificities of US-measured CSAc alone with threshold values of 10, 11, and 12 mm² and of US-measured ΔCSA with threshold values of 2 and 3 mm² for the diagnosis of CTS are presented in ^,Table 4. The best diagnostic discrimination was achieved by using a ΔCSA threshold of 2 mm², with which only one case of CTS with mild abnormality at nerve conduction testing was missed and all asymptomatic wrists were correctly identified. Receiver operating characteristic analysis revealed excellent discriminating ability with use of both CSAc alone (area under receiver operating characteristic curve [A_z] = 0.9896) and ΔCSA (A_z = 0.9988) in the differentiation of patients with CTS from healthy volunteers. According to comparisons of the areas under the receiver operating characteristic curves, the discriminating performance of ΔCSA was significantly superior to that of CSAc (P = .036). In terms of discriminating between CTS-affected wrists with findings mildly positive for CTS at nerve conduction velocity testing and those with highly positive findings, there was no significant difference between CSAc (A_z = 0.7592) and ΔCSA (A_z = 0.7503). Although measurements of both parameters tended to be greater in wrists with highly positive nerve conduction test results, neither parameter was found to facilitate a clear advantage (P = .8).

DISCUSSION

The diagnosis of CTS usually is based on typical clinical signs and symptoms and can be confirmed with electrodiagnostic examinations in most cases (^,1). US has been used as an additional approach for CTS detection during the past 2 decades (^,2,^,4,^,7,^,8). While electrodiagnostic examinations are based on physiologic malfunctions of the median nerve, US depicts structural abnormalities of nerve swelling (^,17). Prior US study investigators have proposed a range of median nerve CSAc cutoff values (4–9). In our study, we investigated the use of an additional measurement—the CSAp—to calculate a new parameter, ΔCSA.

Mean normal median nerve CSA values cited in the literature vary between 6.1 and 10.4 mm²; the difference between these two normal values (4.3 mm²) constitutes 51% of the normal median nerve CSA (8.4 mm²) (^,18). The threshold suggested for median nerve abnormality varies between 9 and 14 mm²; the difference between these two values (5 mm²) constitutes 59% of the normal CSA (8.4 mm²), as recently discussed in a review article (^,18). We hypothesized that if the degree of nerve swelling in the carpal tunnel were compared with the CSAp of the nerve, a ΔCSA measurement would compensate for the interindividual variability in the CSA of the median nerve and yield a more accurate diagnosis of CTS.

In a recent smaller study, Hobson-Webb et al (^,19) calculated a wrist-to-forearm median nerve ratio from the CSA at the wrist and the CSA approximately 12 cm proximal to the wrist. Their study involving 44 patients and 18 control subjects revealed improved diagnoses of CTS with use of this ratio compared with the diagnoses made with use of measurements obtained at the wrist only. It is interesting that they found the CTS-affected patients (6.9 mm² ± 1.6) and control subjects (9.8 mm² ± 2.4) to have widely different mean median nerve areas in the distal forearms. In contrast, we found only a small difference in CSAp between the patients (9.5 mm² ± 1.9) and the control subjects (8.7 mm² ± 1.6) and the proximal nerve to be slightly larger in the patients.

Our study revealed a mean normal CSAc of 9.0 mm², which was significantly smaller than the mean CSAc in the patients (16.8 mm², P < .01). We also observed a smaller mean ΔCSA in the asymptomatic wrists, 0.25 mm², compared with 7.4 mm² in the CTS-affected wrists. In the healthy volunteers, CSAc and CSAp were relatively similar, with a difference of less than 1 mm². According to our sensitivity and specificity tabulations (Table 4), a ΔCSA of 2 mm² or greater represents an optimal test threshold for the diagnosis of CTS: It had a sensitivity of 99% and a specificity of 100%. Receiver operating characteristic analysis revealed a significant diagnostic advantage to using our ΔCSA parameter rather than the CSAc to diagnose CTS.

With respect to CTS severity at electrodiagnostic examination, the mean CSAc was greater in the patients who had results highly positive for CTS (18.5 mm²) than in the patients with mildly positive results (14.4 mm²). The mean ΔCSA was also greater in wrists with results that were highly positive for CTS (8.9 mm² vs 5.2 mm² for wrists with mildly positive results). Unfortunately, neither parameter exhibited excellent performance in the discrimination between wrists with mildly positive CTS findings and wrists with highly positive findings (A_z = 0.7592 for CSAc, A_z = 0.7503 for ΔCSA). Nonetheless, these findings may be helpful for future US grading of CTS.

With use of the ellipse formula, cutoff values of more than 9 mm² and more than 10 mm² at the scaphoid-pisiform level have been described to indicate CTS (^,10–^,12). However, direct tracing of the CSA has been shown to be more accurate (^,16). By using direct tracings, Ziswiler et al (^,8) derived a cutoff value of 10 mm² and achieved sensitivity (82%) and specificity (87%) values that were nearly equal to those of electrodiagnostic tests. A cutoff median nerve area smaller than 8 mm² had satisfactory power to rule out CTS, while a cutoff area larger than 12 mm² had excellent power to rule in (ie, diagnose) CTS, with a fitted-positive likelihood ratio of 19.9 (^,8).

Prior studies to evaluate US imaging of CTS, with electrodiagnostic tests as the reference standard, have revealed sensitivities of 82%–94% and specificities of 65%–97% (^,7–^,9,^,12). The relatively wide range of sensitivity and specificity values in these studies contributes to the variety of opinions regarding the utility of US for the diagnosis of CTS. Seror (^,18) stated that US appears to be of little use in the diagnosis of CTS. In contrast, Wong et al (^,7) proposed an algorithm involving initial US examination of patients suspected of having CTS and secondary electrodiagnostic tests performed only when US results were negative. US is used to detect the space-occupying lesions that cause CTS symptoms, such as ganglia, fibromata, neural tumors, and tenosynovitis, and to identify an increased median nerve CSA in patients with CTS (^,20). Additional US features such as median nerve echogenicity, mobility, flattening ratio in the distal part, and flexor retinaculum bulging also can be helpful in diagnosing CTS (^,1,^,2,^,21). Our study revealed a high degree of accuracy in the US diagnosis of CTS. Given the relatively noninvasive nature of US as compared with electrodiagnostic tests, clinical examination combined with US might be the best approach in the future. The use of US with an additional measurement at the pronator teres level to monitor therapy should be evaluated in future studies.

It is interesting that in patients with CTS, paresthesia has been shown to occur before conduction failure in myelinated sensory fibers, as measured with nerve conduction tests (^,22). A study by Koyuncuoglu et al (^,6) revealed positive US findings in patients who had CTS-positive clinical results, with negative electrodiagnostic findings in 30.5% of these patients, suggesting an advantage to using US—especially during the early stages of CTS, when the median nerve shows no functional impairment at electrodiagnostic examination. The usefulness of the ΔCSA in patients with negative electrodiagnostic test results needs to be evaluated in additional studies.

Our study had several limitations. No US parameters other than median nerve area were evaluated. Other potentially useful parameters include bulging of the transverse carpal ligament, flattening ratio of the median nerve in the distal carpal tunnel, and median nerve echogenicity and mobility. Although these are well-investigated parameters that yield additional information in the diagnosis of CTS (^,23), the focus of this study was the evaluation of a recently developed US approach for measuring the median nerve size. Second, we performed no correlations with the body mass index or hand physiognomies (small or strong wrists), which may influence the median nerve thickness (^,23). Third, US is an operator-dependent test, and appropriate experience is required to ensure reliability and reproducibility. In this study, we collected no data on inter- or intraobserver variability. Fourth, 10%–15% of patients with CTS have an anatomic variation involving a division of the median nerve into two or three parts at the inlet of the carpal tunnel (^,16). Although we considered this variation to be an exclusion criterion, investigators in future studies should investigate whether direct tracing yields CSA measurements that are predictive of the symptoms—even in patients with a divided median nerve.

A strength of our study design was the inclusion of a wide spectrum of disease severities. The results demonstrate that the ΔCSA was useful in patients with both mild and severe CTS. Use of the ΔCSA improves the US-based diagnostic discrimination of CTS by reducing the overlap of measurements obtained in healthy volunteers with those obtained in CTS-affected patients.

ADVANCES IN KNOWLEDGE

IMPLICATION FOR PATIENT CARE

Figure 1:

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Table 1. Definitions of CTS Grades

Table 2. Nerve Measurements in CTS and Healthy Volunteer Groups

Note.—Data are mean values ± standard deviations.

Table 3. Nerve Measurements in Patients with Mild or Moderate CTS versus Severe or Extreme CTS at Nerve Conduction Examination

Note.—Data are mean values ± standard deviations.

Table 4. Sensitivity and Specificity of Nerve Measurements in the Diagnosis of CTS

Note.—Numbers in parentheses are numbers of wrists used to calculate the percentages.