International Journal of Rheumatic Diseases 2014
ORIGINAL ARTICLE
The diagnostic value of ultrasound compared with nerve conduction velocity in carpal tunnel syndrome Ahad AZAMI,1 Nasrollah MALEKI,1 Hassan ANARI,2 Manouchehr IRANPARVAR ALAMDARI,3 Mohammadreza KALANTARHORMOZI4 and Zahra TAVOSI5 1
Departments of Internal Medicine, 2Radiology, 3Endocrinology, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, 4Department of Endocrine and Metabolic Diseases, The Persian Gulf Tropical Medicine Research Center, University of Medical Sciences, and 5Department of Internal Medicine, Shohadaye Khalije Fars Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
Abstract Objective: Carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy. The use of sonography for investigation and diagnosis of musculoskeletal conditions has been rapidly increasing over the past few decades. The purpose of this study was to determine whether sonography can be an alternative method to nerve conduction study (NCS) in the diagnosis of CTS. Methods: Individuals with electrodiagnostically proven CTS and healthy control subjects were enrolled prospectively. Median nerve cross-sectional area (CSA) and flattening ratio (FR) at three different levels, proximal to tunnel inlet, at tunnel inlet and tunnel outlet, and flexor retinaculum thickness, were measured. Then, comparisons between ultrasonography and NCS were made. Results: We assessed 180 wrists, of which 120 were electrophysiologically confirmed as CTS diseased hands and 60 nondiseased hands in 90 patients (83 women and seven men). The mean median nerve CSA at the tunnel inlet was 13.31 3.23 mm2 in CTS diseased hands and 8.57 0.82 mm2 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the CSA at various levels of the median nerve were significantly greater in the CTS diseased hands than the nondiseased hands (P = 0.001). CSA at the tunnel inlet with a threshold of 9.15 mm2 gave the best diagnostic accuracy with a sensitivity and specificity of 99.2% and 88.3%, respectively. The difference in cross-sectional area of the median nerve in mild, moderate and severe CTS was statistically significant. Conclusion: Ultrasonographic measurement of the CSA of the median nerve at the carpal tunnel inlet is useful in diagnosing and grading CTS. Key words: carpal tunnel syndrome, diagnosis, nerve conduction velocity, ultrasonography.
INTRODUCTION Carpal tunnel syndrome (CTS) or compression neuropathy of the median nerve at the wrist is the most
Correspondence: Dr Nasrollah Maleki, Resident of Internal Medicine, Department of Internal Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Email: [email protected]
common form of peripheral entrapment neuropathy.1 The pathophysiology of CTS is multifactorial. Increased pressure in the intracarpal canal plays a key role in the development of clinical CTS.2 The estimated annual incidence of CTS per 100 000 population ranges from 324 to 542 for women, and 125 to 303 for men.3,4 Depending on its definition, the estimated prevalence of CTS in the general population is 1–5%.5,6 CTS is more frequent in women (0.7–9.2%) than in men
© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
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(0.4–2.1%).1,5,7 The prevalence of CTS appears to be highest in obese women, and lowest in thin and normal-sized men.8 The frequency of CTS may be higher in the industrial setting than in the general population, as illustrated by prevalence estimates of 5–15% in the workplace.2–10 A number of conditions have been associated with CTS, including: obesity, female gender, pregnancy, diabetes, rheumatoid arthritis and other connective tissue diseases, hypothyroidism, acromegaly, genetic predisposition, use of aromatase inhibitors and workplace factors. The hallmark of classic CTS is pain or paresthesia (numbness and tingling) in a distribution that includes the median nerve territory, with involvement of the first three digits and the radial half of the fourth digit. The symptoms of CTS are typically worse at night and often awaken patients from sleep. Some patients react to these symptoms by shaking or wringing their hands or by placing them under warm running water.11 Bilateral CTS is common at first presentation, affecting up to 65% of patients.12 CTS is a clinical diagnosis. The diagnosis is suspected when the characteristic symptoms and signs are present. The most important of these are nocturnal pain or paresthesia in the distribution of the median nerve.2 Provocative maneuvers for CTS include the Phalen, Tinel, manual carpal compression and hand elevation tests. These can be helpful when interpreted in the proper clinical context. However, the sensitivity and specificity of these provocative tests is moderate at best.13,14 Meta-analyses have shown an average sensitivity of 68% and specificity of 73% for a positive Phalen’s test.14 A positive Tinel sign may be less sensitive (50%) than the Phalen sign, but has similar specificity (77%).14 Nerve conduction studies (NCS) and electromyography (EMG) are a standard part of the evaluation for CTS. They are useful to support the diagnosis of CTS, to assess severity and to rule out other abnormalities.15 The diagnosis is primarily dependent on results from the NCS. The main utility of EMG is to exclude other conditions, such as polyneuropathy, plexopathy, and radiculopathy.11 Although physiologic information is obtained based on nerve conduction studies (NCS), it has a specificity of 95% and a low sensitivity that ranges from 49% to 86%.16 Imaging studies are not routinely employed in the evaluation for possible CTS. Several studies using ultrasonography have shown that patients with CTS have significantly increased cross-sectional area of the median nerve compared with controls.17–19 However, the optimal cross-sectional area cutoff for the diagnosis, as
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well as the sensitivity and specificity of this technique, has varied in these reports.20,21 In a systematic review of the literature published through May 2011, the four highest-quality studies used cutoffs of 8.5–10 mm2 for the diagnosis.21 The sensitivities ranged from 65–97% and the specificities ranged from 73–98%. In comparison with NCS, ultrasonography has many advantages, such as availability, lower cost, noninvasiveness and shorter examination time. The purpose of the present study was to assess the value of ultrasound compared with nerve conduction velocity in CTS.
MATERIALS AND METHODS Patients and controls This was a prospective cross-sectional study. Between December 2012 and September 2013, patients with suspected CTS who were referred to the outpatient clinic of the Department of Rheumatology at the University Hospital in Ardabil, Iran, routinely underwent standardized nerve conduction studies and subsequent sonographic evaluation. Consecutive patients with suspected CTS gave their written informed consent and were prospectively enrolled. Patients were excluded if they had undergone surgery or if there were traumatic lesions at the target wrist, if there was a history of surgery to the wrist or any permanently placed shunts or objects in the hand or wrist, or if there was a known history of other systemic neurologic disorders. The diagnostic criteria of CTS were according to the American Academy of Neurology, which included clinical history, symptoms and evidence of slowing of distal median nerve conduction.22 The clinical diagnosis of CTS was based on signs and symptoms of median nerve distribution, such as: (i) paresthesia, pain, swelling, weakness or clumsiness of the hand provoked or worsened by sleep, sustained hand or arm position or repetitive action of the hand or wrist that is mitigated by a change in posture or by shaking of the hand; (ii) sensory deficits in the median nerveinnervated regions of the hand; (iii) motor deficit or hypotrophy of the median nerve-innervated thenar muscles; and (iv) positive provocative clinical tests (positive Phalen’s maneuver and/or Tinel’s sign). The clinical diagnosis of CTS was made when criterion 1 and one or more of criteria 2–4 were fulfilled.15,22 Anthropometric and demographic data included age, height, body mass index (BMI), sex, occupation, medication history, hand dominance and underlying disorders associated with CTS, such as diabetes mellitus,
International Journal of Rheumatic Diseases 2014
US and nerve conduction velocity in CTS
rheumatoid arthritis, pregnancy, acromegaly or hypothyroidism. Ninety patients (83 women and seven men) with 120 diseased hands were examined within 10 days following NCS. Sixty patients had unilateral CTS (42 cases right hand and 18 cases left hand) and 30 patients were diagnosed with bilateral CTS. We assessed both the right and left hands of all 90 patients blinded to the electrophysiologic study. From unilateral CTS, only those patients were enrolled in the study who had normal hands, which were both clinically and electrophysiologically negative for CTS. Patients with positive clinical symptoms of CTS and a negative NCS result were excluded. In our study, all patients with unilateral CTS had negative clinical and electrophysiological results in their normal hands.
Nerve conduction studies All patients underwent NCS on a Medelec Synergy Electromyography machine (Oxford Instruments, Old Woking, Surrey, UK). Standardized nerve conduction studies were performed by an electrodiagnostician with 21 years experience, using surface electrodes and adjustment for skin temperature, which was kept above 33°C. The antidromic sensory median nerve conduction velocity, the distal motor latency, and the median motor compound muscle action potential were determined. Diagnosis of CTS was made if median sensory nerve conduction velocity (SNCV) was < 40 m/s when the ulnar SNCV was normal, median distal motor latency (DML) more than 4.5 m/s and/or median versus ulnar palm to wrist mixed nerve conduction velocity difference was more than 10 m/s. Our patients were divided into three groups on the basis of electrophysiological severity:1
(Samsung Medical Systems, Seoul, Korea) with a 14 MHz linear-array transducer was used in the study. The sonographic examination was performed with the patient seated in a comfortable position facing the sonographer, with the forearm resting on the table and the palm facing up in the neutral position. The volar wrist crease was used as an initial external reference point, with subsequent modifications during scanning using carpal bony landmarks and internal reference points. The full course of the median nerve in the carpal tunnel was assessed in both transverse and longitudinal planes. The median nerve is located superficial to the echogenic flexor tendons and its size, shape, echogenicity and relationship to the surrounding structures and overlying retinaculum were noted. The mean cross-sectional area (CSA) of the median nerve was measured at the proximal to tunnel, tunnel inlet and outlet (Fig. 1). The ‘tunnel inlet’ referred to the level immediately deep to the proximal edge of the flexor retinaculum. The ‘tunnel outlet’ referred to the level immediately deep to the distal edge of the flexor retinaculum. The mean flattening ratio (defined as the ratio of the major axis of the median nerve to its minor axis) was also assessed at the proximal to tunnel, tunnel inlet and outlet. The thickness of the flexor retinaculum was measured as close to the midline as possible in the midportion of the carpal tunnel (Fig. 2). Median nerve
1 mild: prolonged sensory distal latency SNAP (sensory nerve action potential) amplitude reduction; 2 moderate: prolongation of both median motor and sensory distal latencies; and 3 severe: electrodiagnostic criteria of moderate type of CTS, with either an absence of SNAP, or low amplitude or absent thenar CMAP (compound muscle action potential), or findings compatible with axonal injury in electromyography.
Ultrasonography Ultrasonography of the carpal tunnel was carried out by a musculoskeletal radiologist who was blinded to the NCS results. A MEDISON V20 ultrasound machine
International Journal of Rheumatic Diseases 2014
Figure 1 Receiver operating characteristics (ROC) curve for ultrasonographic assessments of median nerve cross-sectional area (CSA) at the carpal tunnel.
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RESULTS
Figure 2 Graph shows the difference between mean crosssectional area of normal and mild, moderate and severe forms of CTS at the carpal tunnel inlet.
measurements were taken for both patients and control groups.
Statistical analysis Statistical analyses were performed using the SPSS software for Windows, version 21 (SPSS Inc., Chicago, IL, USA); arithmetic mean values and standard deviations (SD) of the data were calculated. Then we carried out an unpaired two sample t-test and chi-squared test comparing age and sex between CTS and non-CTS groups. A repeated measure of analysis of variance (ANOVA) was applied to compare dichotomous and continuous variables between the non-CTS group and three CTS subgroups. The level of confidence was taken at a P-value of 0.05 or less. Relationships of CSA (at the proximal to tunnel, tunnel inlet and outlet), flattening ratio (at the proximal to tunnel, tunnel inlet and outlet), and flexor retinaculum thickness with age, gender, body mass index (BMI) and the electrodiagnostic testing measurements of the nerve conduction velocity were calculated with Spearman’s coefficient. Receiver operating characteristics (ROC) curves were configured to establish the cut-off points of median nerve CSA, flattening ratio, flexor retinaculum thickness with optimal sensitivity and specificity for establishing a diagnosis of CTS. ROC curves are plots of the true positive rate (sensitivity) against the false positive rate (1-specificity) for the different possible cut-off points of a diagnostic test; they show how sensitivity and specificity of a test change as the cut-off point changes.
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We assessed 180 wrists, of which 120 were electrophysiologically confirmed as CTS diseased hands and 60 nondiseased hands in 90 patients (83 women and seven men). All were examined bilaterally. From 120 diseased hands, 42 hands were related to patients with right-handed CTS and 18 hands were related to patients with left-handed CTS. A total of 30 patients had bilateral CTS. Of the 120 symptomatic hands, 57 (47.5%) were mild, 29 (24.2%) moderate and 34 (28.3%) had severe CTS. The mean age of patients was 56.8 10.6 years. In diseased hands, six (5%) showed sensory loss and 29 (24.2%) showed thenar atrophy. A positive Phalen’s sign was present in 119 hands (99.2%) while Tinel’s test was positive in 93 patients (77.5%). Table 1 shows the baseline characteristics of the diseased and nondiseased hands included in this study. Table 2 shows the mean ultrasonographic measurements of cross-sectional areas at various levels of the median nerve in both diseased and nondiseased hands. The mean median nerve CSA at the proximal to tunnel was 11.75 2.56 mm2 in diseased hands with CTS, 7.56 0.77 mm2 in nondiseased hands. The mean median nerve CSA at the tunnel inlet was 13.31 3.23 mm2 in diseased hands with CTS, 8.57 0.82 mm2 in nondiseased hands. The mean Table 1 Baseline characteristics of the patients and control subjects included in this study Variable Age (years), mean SD Gender (male : female) Weight (kg), mean SD Height (cm), mean SD BMI (kg/m2), mean SD Night awakening, n (%) Tinel’s test, n (%) Phalen’s test, n (%) Compression’s test, n (%) Thenar atrophy, n (%) Sensory loss, n (%)
Patients (n = 120)
Controls (n = 60)
Pvalue*
56.8 10.6
54.8 7.8
0.192
5 : 55
2 : 28
0.259
77.8 4.7
71.2 4.9
0.001
162.5 5.8
162.9 4.9
0.681
29.5 2.4
26.8 1.8
0.001
0 (0)
0.001
118 (98.3) 93 (77.5) 119 (99.2) 119 (99.2) 29 (24.2) 6 (5)
11 (18.3) 7 (11.7) 6 (10) 0 (0) 0 (0)
0.034 0.001 0.001 0.001 0.084
*Statistically significant (P < 0.05). BMI, body mass index.
International Journal of Rheumatic Diseases 2014
US and nerve conduction velocity in CTS
0.82 0.1 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the FR at various levels of the median nerve were significantly greater in the diseased hands with CTS than the nondiseased hands (P = 0.001) (Table 2). The mean flexor retinaculum thickness was 2.33 0.61 mm in diseased hands with CTS, 1.25 0.16 mm in nondiseased hands, which was statistically significant (P = 0.001) (Table 2). Table 3 shows the mean ultrasonographic measurements of cross-sectional areas at various levels of the median nerve in diseased hands with CTS. Post hoc comparisons between the CTS subgroups (mild, moderate and severe) and nondiseased hands demonstrated that the cross-sectional area at various levels of the median nerve (at the proximal to tunnel, tunnel inlet and outlet) and flexor retinaculum thickness were significantly greater in the severe CTS group than the other three groups (P = 0.001). Furthermore, a significant difference of this mean ultrasonographic measurements (CSA, FR, flexor retinaculum thickness) was also noted between these subgroups when compared with each other (P = 0.001) (Table 3). ROC curves were used to determine optimal discriminatory threshold values for CSA (at all three levels), FR (at all three levels) and flexor retinaculum thickness (Figs 1,2). When the ROC curve was fitted for sonography using clinical criteria as the reference standard, the area under the curve was 0.85 (95% CI, 0.80–0.91) for the CSA at the proximal to carpal tunnel, 0.78 (95% CI, 0.72–0.85) for the CSA at the tunnel inlet and 0.74 (95% CI, 0.66–0.82) for the CSA at the tunnel outlet. CSA at the tunnel inlet with a threshold of 9.15 mm2 gave the best diagnostic accuracy with a sensitivity and specificity of 99.2% and 88.3%, respectively, followed by CSA at the proximal to carpal tunnel with a threshold of 8.25 mm2 which gave a sensitivity and specificity of 99.2% and 78.3%, respectively. CSA at the tunnel
Table 2 Mean ultrasonographic measurements at various levels of the median nerve in both carpal tunnel syndrome (CTS) patients and controls Ultrasonographic Patients with CTS measurements (mean SD) CSA proximal to tunnel (mm2) CSA at tunnel inlet (mm2) CSA at tunnel outlet (mm2) FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
Control P(mean SD) value*
11.75 2.56
7.56 0.77
0.001
13.31 3.23
8.57 0.82
0.001
11.11 2.29
7.43 0.67
0.001
1.83 0.71
0.88 0.08
0.001
2.21 0.84
1 0.1
0.001
2.01 0.78
0.82 0.1
0.001
2.33 0.61
1.25 0.16
0.001
*Statistically significant (P < 0.05). CSA, median nerve cross sectional area; FR, flattening ratio of median nerve.
median nerve CSA at the tunnel outlet was 11.11 2.29 mm2 in diseased hands with CTS, 7.43 0.67 mm2 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the CSA at various levels of the median nerve were significantly greater in the diseased hands with CTS than the nondiseased hands (P = 0.001) (Table 2). The mean flattening ratio (FR) of median nerve at the proximal to tunnel was 1.83 0.71 in diseased hands, 0.88 0.08 in nondiseased hands. The mean FR of median nerve at the tunnel inlet was 2.21 0.84 in diseased and hands with CTS, 1 0.1 in nondiseased hands. The mean FR of median nerve at the tunnel outlet was 2.01 0.78 in diseased hands with CTS,
Table 3 Mean ultrasonographic measurements of cross-sectional area and flattening ratio at different levels of the median nerve and flexor retinaculum thickness across groups Ultrasonographic measurements CSA proximal to tunnel (mm2) CSA at tunnel inlet (mm2) CSA at tunnel outlet (mm2) FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
No CTS 7.56 8.57 7.43 0.88 1 0.82 1.25
0.77 0.82 0.67 0.08 0.1 0.1 0.16
Mild CTS 9.79 10.66 9.38 1.23 1.48 1.35 1.88
1.09 0.8 1.43 0.2 0.29 0.22 0.30
Moderate CTS 12.29 13.79 11.80 1.97 2.33 2.12 2.45
0.81 0.82 0.91 0.32 0.32 0.32 0.36
Severe CTS 14.58 17.35 13.46 2.73 3.33 3.02 2
2.45 2.62 1.87 0.42 0.31 0.49 0.52
CTS (total)
P-value*
0.001 0.001 0.001 0.001 0.001 0.001 0.001
11.75 13.31 11.11 1.83 2.21 2.01 2.33
2.56 3.23 2.29 0.71 0.84 0.78 0.61
*Statistically significant (P < 0.05). CSA, median nerve cross sectional area; FR, flattening ratio of median nerve; CTS, carpal tunnel syndrome.
International Journal of Rheumatic Diseases 2014
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outlet, with a threshold of 8.15 mm2 yielded a sensitivity of 96.7% but a lower specificity of 55%. With a cut-off point of 1.02 for the FR at the proximal to carpal tunnel, the sensitivity and specificity of ultrasonography was 98.3% and 46.7%, respectively (95% CI, 0.691–0.859). With a cut-off point of 1.01 for the FR at the tunnel inlet, the sensitivity and specificity of ultrasonography was 94.2% and 55%, respectively (95% CI, 0.799–0.924). FR of 0.94 at the tunnel outlet gave a sensitivity and specificity of 99.2% and 75%, respectively (95% CI, 0.662–0.823). Finally, with a cutoff point of 1.26 mm in the flexor retinaculum thickness, the sensitivity and specificity of ultrasonography was 99.2% and 66.7%, respectively (95% CI, 0.666– 0.853) (Table 4).
DISCUSSION Accurate diagnosis of CTS and its differentiation from other causes of hand morbidity is essential, particularly if the patient is a candidate for surgery. Currently, ultrasonography is a reliable method for the diagnosis of CTS. In comparison with NCS, ultrasonography does not evaluate the physiologic condition of the median nerve but may show swallowing and flattening of the median nerve.23 Many authors believe that ultrasonography can be an alternative method in comparison with NCS for the primary evaluation of CTS in daily practice. In the present study, the efficacy of ultrasound for the diagnosis of CTS was evaluated. Electrodiagnostic studies were used as gold standard diagnostic procedures.24 Previous studies showed that ultrasonography is a feasible and reliable diagnostic procedure. Buchberger et al.25 were the first researchers who assessed the cross sectional area of the median nerve using a high resolution ultrasonography machine with a 7 MHz transducer
to confirm previously reported magnetic resonance imaging of the carpal tunnel. Compression of the median nerve in the canal may increase diagnostic yield of the ultrasound. The ultrasonographic measurement used in CTS diagnosis is the CSA of the nerve at various levels of the carpal canal, the flattening ratio, the swelling ratio and the increased palmar bowing of the flexor retinaculum. The sensitivity and specificity of ultrasonographic measures vary widely among studies. Many authors demonstrated that the increase in CSA at the tunnel inlet had the highest sensitivity and specificity;24,26 moreover, the measurement at this level was easier to perform. There was also disagreement about the exact localization of tunnel inlet. Most authors considered the proximal edge of the flexor retinaculum, approximately at the level of the distal – radioulnar joint, as the tunnel inlet, while others considered the pisiform bone and tubercle of the navicular bone as the landmarks.27 The sensitivity of the CSAs ranged from 48% to 89% and the CSA cutoff at which the value was considered abnormal varied from 9 to 15 mm2.26,28 Sensitivities of increased palmar bowing of the flexor retinaculum varied from 40% to 81%29,30 and sensitivities of flattening ratio ranged from 37% to 100%.29,31 These discrepancies result from many factors: selection criteria of patients and controls, gold standard for diagnosis of CTS, electrodiagnostic methods, levels of CSA measurement and ultrasonographic cut-off values. A bias of the results may also be due to incorrect selection of the control group. For example, sometimes the asymptomatic wrist of CTS cases was included in the control group. In almost all studies the gold standard of CTS diagnosis was based on clinical and abnormal electrodiagnostic tests. In contrast, only a few studies used clinical findings only as the gold standard.24,32 Only this type of study is able to
Table 4 Optimal discriminatory threshold, sensitivity and specificity of ultrasonographic criteria for carpal tunnel syndrome Measurements
CSA at proximal to tunnel (mm2) CSA at tunnel inlet mm2 CSA at tunnel outlet mm2 FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
Optimal discriminatory threshold
Sensitivity (%)
Specificity (%)
Area under the curve
P-value
8.25 9.15 8.15 1.02 1.01 0.93 1.26
99.2 99.2 96.7 98.3 94.2 99.2 99.2
78.3 83.3 55 46.7 55 75 66.7
0.852 0.783 0.739 0.775 0.862 0.743 0.76
0.001 0.001 0.001 0.001 0.001 0.001 0.001
CSA, median nerve cross sectional area; FR, flattening ratio of median nerve.
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compare ultrasonography specificity and sensitivity with those of the electrodiagnostic tests. The few literature data reported different results on NCV specificity.32 In particular, Swen et al.24 reported a very low NCV specificity (19%). They used as the gold standard patients with ≥ 90% relief of symptoms after surgery and received many criticisms on their selection criteria of CTS cases. Wong et al.26 measured cross-sectional areas of the median nerve at three different levels: immediately proximal to the carpal tunnel inlet, at the carpal tunnel inlet and at the carpal tunnel outlet. Using a classification and regression tree, they determined optimal threshold values for each of these levels and suggested diagnostic algorithms based on a combination of fixed cut-offs at two levels of the median nerve that differed for the left and right hands. Mean normal values of median nerve CSA at the carpal tunnel inlet have varied among reports, ranging from 6.1 to 10.4 mm2.24–26 In our healthy control group, mean value of median nerve CSA at the carpal tunnel inlet was 8.57 0.82 mm2. Some studies considered that differing demographic and biometric features, such as older age, male gender, body mass index and handedness, may contribute to the range of normal values. However, the debate still remains; another study found no significant association between biometric characteristics of subjects and median nerve CSA at wrist and forearm in their well-matched case controls.32 Thus, it can be said that the range of normal values for median nerve CSA in the literature more likely reflects variations in study design and ultrasonographic technique. Our results are consistent with previous studies of ultrasound in CTS in showing enlargement of the median nerve in CTS hands.25 There were significant differences in median nerve CSA between CTS and controls hands at all levels measured – proximal to the tunnel inlet, at the inlet and outlet, as well as in the FR. In our population, ROC curves estimated the optimal CSA thresholds to be 9.15 mm2 at the tunnel inlet with a sensitivity and specificity of 99.2% and 88.3%, respectively. Wang et al.33 demonstrated that the median nerve CSA at the pisiform level was most predictive of CTS; the optimal cut-off value was ≥ 9.875 mm2, yielding 82% sensitivity and 87.5% specificity. Yazdchi et al.34 demonstrated that median nerve ultrasonography cannot replace the gold standard test (nerve conduction velocity) for the diagnosis of CTS because of low overall sensitivity and specificity, although it might provide useful information in some patients. Tsai
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et al.35 reported that the CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both diabetes mellitus (DM) and non-DM patients compared to normal hands. Shim et al.36 demonstrated that the median nerve CSA at the level of carpal tunnel inlet was most predictive of CTS; the optimal cut-off value was ≥ 9 mm2, yielding 86.7% sensitivity and 88.9% specificity. Keles et al.30 demonstrated that thickness of the flexor retinaculum can be used in the diagnosis of CTS. In this study, flexor retinaculum thickness > 3.7 mm (sensitivity 71.4% and specificity 55%) was considered significant in the evaluation of CTS patients.30 Mondelli et al.37 demonstrated that in mild cases of CTS, ultrasonography did not detect more anomalies than NCV and vice versa, and no anomalies were detected with either diagnostic instrument in 23.5% of mild cases. Mohammadi et al.38 demonstrated that the CSA at the tunnel inlet and outlet was most predictive of CTS; the best cut-off value was ≥ 8.5 mm2, yielding 97–100% sensitivity and 98–100% specificity. In this study, the difference in CSA of the median nerve in mild, moderate and severe CTS was not statistically significant (P = 0.2) either in the carpal tunnel inlet or outlet.38 Moghtaderi et al.39 suggested that ultrasound is a good diagnostic modality for patients referred to tertiary care centers with categorization as moderate CTS. In this study, they accepted cut-off points of 11.5 and 13.5 mm² for CSA of the proximal and distal portions of the carpal canal, respectively. The sensitivity, specificity, positive and negative predictive values for the proximal inlet were 83%, 90.7%, 65.5% and 55.7%; and for the distal outlet were 36.1%, 93%, 81.2% and 63.4%, respectively.39 Kwon et al.40 demonstrated that the best cut-off value of CSA at the tunnel inlet was 10.7 mm2, which had a sensitivity of 66% and a specificity of 63%. In this study, NCS showed a sensitivity of 78% and a specificity of 83%. Sensitivity was similar between sonography and NCS (P = 0.27), whereas specificity was significantly lower in sonography than in NCS (P = 0.02).40
CONCLUSION This study affirms previous studies in demonstrating the usefulness of ultrasonography in diagnosing CTS. The best cut-off value of CSA at the tunnel inlet was 9.15 mm2, which had a sensitivity of 99.2% and a specificity of 88.3%. In addition to being of high diagnostic accuracy, ultrasonography is a reliable test in assessing the severity of CTS.
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syndrome. AAEM Quality Assurance Committee. Muscle Nerve 16, 1392–414. Ashraf AR, Jali R, Moghtaderi AR, Yazdani AH (2009) The diagnostic value of ultrasonography in patients with electrophysiologicaly confirmed carpal tunnel syndrome. Electromyogr Clin Neurophysiol 49, 3. Pinilla I, Martın-Hervas C, Sordo G, Santiago S (2008) The usefulness of ultrasonography in the diagnosis of carpal tunnel syndrome. J Hand Surg Eur 33, 435. Wiesler ER, Chloros GD, Cartwright MS et al. (2006) The use of diagnostic ultrasound in carpal tunnel syndrome. J Hand Surg Am 31, 726. Descatha A, Huard L, Aubert F et al. (2012) Meta-analysis on the performance of sonography for the diagnosis of carpal tunnel syndrome. Semin Arthritis Rheum 41, 914. Cartwright MS, Hobson-Webb LD, Boon AJ et al. (2012) Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 46, 287. You H, Simmons Z, Freivalds A, Kothari MJ, Naidu SH (1999) Relationships between clinical symptom severity scales and nerve conduction measures in carpal tunnel syndrome. Muscle Nerve 22, 497–501. Iannicelli E, Almberger M, Chianta GA et al. (2005) High resolution ultrasonography in the diagnosis of the carpal tunnel syndrome. Radiol Med 110, 623–9. Swen WA, Jacobs JW, Bussemaker FE, de Ward JW, Bijlsma JW (2001) Carpal tunnel sonography by the rheumatologist versus nerve conduction study by the neurologist. J Rheumatol 28, 62–9. Buchberger W, Judmaier W, Birbamer G, Lener M, Schmidauer C (1992) Carpal tunnel syndrome: diagnosis with high-resolution sonography. AJR Am J Roentgenol 159 (4), 793–8. Wong SM, Griffith JF, Hui AC, Lo SK, Fu M, Wong KS (2004) Carpal tunnel syndrome: diagnostic usefulness of sonography. Radiology 232, 93–9. Hammer HB, Hovden IA, Haavardsholm EA, Kvien TK (2006) Ultrasonography shows increased cross-sectional area of the median nerve in patients with arthritis and carpal tunnel syndrome. Rheumatology (Oxford) 45, 584–8. Lee D, van Holsbeeck MT, Janevski PK, Ganos DL, Ditmars DM, Darian VB (1999) Diagnosis of carpal tunnel syndrome: ultrasound versus electromyography. Radiol Clin North Am 37, 859–72. Mallouhi A, Pulzl P, Trieb T, Piza H, Bodner G (2006) Predictors of carpal tunnel syndrome: accuracy of gray-scale and color Doppler sonography. AJR Am J Roentgenol 187, 266. Keles I, Karagulle Kendi AT, Aydin G, Zog SG, Orkun S (2005) Diagnostic precision of ultrasonography in patients with carpal tunnel syndrome. Am J Phys Med Rehabil 84, 443–50.
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31 Keberle M, Jenett M, Kenn W et al. (2000) Technical advances in ultrasound and MR imaging of carpal tunnel syndrome. Eur Radiol 10, 1043–50. 32 El Miedany YM, Aty SA, Ashour S (2004) Ultrasonography versus nerve conduction study in patients with carpal tunnel syndrome: substantive or complementary tests? Rheumatology (Oxford) 43, 887–95. 33 Wang LY, Leong CP, Huang YC, Hung JW, Cheung SM, Pong YP (2008) Best diagnostic criterion in high-resolution ultrasonography for carpal tunnel syndrome. Chang Gung Med J 31 (5), 469–76. 34 Yazdchi M, Tarzemani MK, Mikaeili H, Ayromlu H, Ebadi H (2012) Sensitivity and specificity of median nerve ultrasonography in diagnosis of carpal tunnel syndrome. Int J Gen Med 5, 99–103. 35 Tsai NW, Lee LH, Huang CR et al. (2013) The diagnostic value of ultrasonography in carpal tunnel syndrome: a comparison between diabetic and non-diabetic patients. BMC Neurol 13, 65.
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36 Shim JH, Doh JW, Lee KS, Shim JJ, Yoon SM, Bae HG (2013) The diagnostic value of ultrasonography in Korean carpal tunnel syndrome patients. Korean J Neurotrauma 9, 1–5. 37 Mondelli M, Filippou G, Gallo A, Frediani B (2008) Diagnostic utility of ultrasonography versus nerve conduction studies in mild carpal tunnel syndrome. Arthritis Rheum 59, 357–66. 38 Mohammadi A, Afshar A, Etemadi A, Masoudi S, Baghizadeh A (2010) Diagnostic value of cross-sectional area of median nerve in grading severity of carpal tunnel syndrome. Arch Iran Med 13 (6), 516–21. 39 Moghtaderi A, Sanei-Sistani S, Sadoughi N, Hamed-Azimi H (2012) Ultrasound evaluation of patients with moderate and severe carpal tunnel syndrome. Prague Med Rep 113, 23–32. 40 Kwon BC, Jung KI, Baek GH (2008) Comparison of sonography and electrodiagnostic testing in the diagnosis of carpal tunnel syndrome. J Hand Surg Am 33, 65–71.
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ORIGINAL ARTICLE
The diagnostic value of ultrasound compared with nerve conduction velocity in carpal tunnel syndrome Ahad AZAMI,1 Nasrollah MALEKI,1 Hassan ANARI,2 Manouchehr IRANPARVAR ALAMDARI,3 Mohammadreza KALANTARHORMOZI4 and Zahra TAVOSI5 1
Departments of Internal Medicine, 2Radiology, 3Endocrinology, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, 4Department of Endocrine and Metabolic Diseases, The Persian Gulf Tropical Medicine Research Center, University of Medical Sciences, and 5Department of Internal Medicine, Shohadaye Khalije Fars Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
Abstract Objective: Carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy. The use of sonography for investigation and diagnosis of musculoskeletal conditions has been rapidly increasing over the past few decades. The purpose of this study was to determine whether sonography can be an alternative method to nerve conduction study (NCS) in the diagnosis of CTS. Methods: Individuals with electrodiagnostically proven CTS and healthy control subjects were enrolled prospectively. Median nerve cross-sectional area (CSA) and flattening ratio (FR) at three different levels, proximal to tunnel inlet, at tunnel inlet and tunnel outlet, and flexor retinaculum thickness, were measured. Then, comparisons between ultrasonography and NCS were made. Results: We assessed 180 wrists, of which 120 were electrophysiologically confirmed as CTS diseased hands and 60 nondiseased hands in 90 patients (83 women and seven men). The mean median nerve CSA at the tunnel inlet was 13.31 3.23 mm2 in CTS diseased hands and 8.57 0.82 mm2 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the CSA at various levels of the median nerve were significantly greater in the CTS diseased hands than the nondiseased hands (P = 0.001). CSA at the tunnel inlet with a threshold of 9.15 mm2 gave the best diagnostic accuracy with a sensitivity and specificity of 99.2% and 88.3%, respectively. The difference in cross-sectional area of the median nerve in mild, moderate and severe CTS was statistically significant. Conclusion: Ultrasonographic measurement of the CSA of the median nerve at the carpal tunnel inlet is useful in diagnosing and grading CTS. Key words: carpal tunnel syndrome, diagnosis, nerve conduction velocity, ultrasonography.
INTRODUCTION Carpal tunnel syndrome (CTS) or compression neuropathy of the median nerve at the wrist is the most
Correspondence: Dr Nasrollah Maleki, Resident of Internal Medicine, Department of Internal Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Email: [email protected]
common form of peripheral entrapment neuropathy.1 The pathophysiology of CTS is multifactorial. Increased pressure in the intracarpal canal plays a key role in the development of clinical CTS.2 The estimated annual incidence of CTS per 100 000 population ranges from 324 to 542 for women, and 125 to 303 for men.3,4 Depending on its definition, the estimated prevalence of CTS in the general population is 1–5%.5,6 CTS is more frequent in women (0.7–9.2%) than in men
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(0.4–2.1%).1,5,7 The prevalence of CTS appears to be highest in obese women, and lowest in thin and normal-sized men.8 The frequency of CTS may be higher in the industrial setting than in the general population, as illustrated by prevalence estimates of 5–15% in the workplace.2–10 A number of conditions have been associated with CTS, including: obesity, female gender, pregnancy, diabetes, rheumatoid arthritis and other connective tissue diseases, hypothyroidism, acromegaly, genetic predisposition, use of aromatase inhibitors and workplace factors. The hallmark of classic CTS is pain or paresthesia (numbness and tingling) in a distribution that includes the median nerve territory, with involvement of the first three digits and the radial half of the fourth digit. The symptoms of CTS are typically worse at night and often awaken patients from sleep. Some patients react to these symptoms by shaking or wringing their hands or by placing them under warm running water.11 Bilateral CTS is common at first presentation, affecting up to 65% of patients.12 CTS is a clinical diagnosis. The diagnosis is suspected when the characteristic symptoms and signs are present. The most important of these are nocturnal pain or paresthesia in the distribution of the median nerve.2 Provocative maneuvers for CTS include the Phalen, Tinel, manual carpal compression and hand elevation tests. These can be helpful when interpreted in the proper clinical context. However, the sensitivity and specificity of these provocative tests is moderate at best.13,14 Meta-analyses have shown an average sensitivity of 68% and specificity of 73% for a positive Phalen’s test.14 A positive Tinel sign may be less sensitive (50%) than the Phalen sign, but has similar specificity (77%).14 Nerve conduction studies (NCS) and electromyography (EMG) are a standard part of the evaluation for CTS. They are useful to support the diagnosis of CTS, to assess severity and to rule out other abnormalities.15 The diagnosis is primarily dependent on results from the NCS. The main utility of EMG is to exclude other conditions, such as polyneuropathy, plexopathy, and radiculopathy.11 Although physiologic information is obtained based on nerve conduction studies (NCS), it has a specificity of 95% and a low sensitivity that ranges from 49% to 86%.16 Imaging studies are not routinely employed in the evaluation for possible CTS. Several studies using ultrasonography have shown that patients with CTS have significantly increased cross-sectional area of the median nerve compared with controls.17–19 However, the optimal cross-sectional area cutoff for the diagnosis, as
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well as the sensitivity and specificity of this technique, has varied in these reports.20,21 In a systematic review of the literature published through May 2011, the four highest-quality studies used cutoffs of 8.5–10 mm2 for the diagnosis.21 The sensitivities ranged from 65–97% and the specificities ranged from 73–98%. In comparison with NCS, ultrasonography has many advantages, such as availability, lower cost, noninvasiveness and shorter examination time. The purpose of the present study was to assess the value of ultrasound compared with nerve conduction velocity in CTS.
MATERIALS AND METHODS Patients and controls This was a prospective cross-sectional study. Between December 2012 and September 2013, patients with suspected CTS who were referred to the outpatient clinic of the Department of Rheumatology at the University Hospital in Ardabil, Iran, routinely underwent standardized nerve conduction studies and subsequent sonographic evaluation. Consecutive patients with suspected CTS gave their written informed consent and were prospectively enrolled. Patients were excluded if they had undergone surgery or if there were traumatic lesions at the target wrist, if there was a history of surgery to the wrist or any permanently placed shunts or objects in the hand or wrist, or if there was a known history of other systemic neurologic disorders. The diagnostic criteria of CTS were according to the American Academy of Neurology, which included clinical history, symptoms and evidence of slowing of distal median nerve conduction.22 The clinical diagnosis of CTS was based on signs and symptoms of median nerve distribution, such as: (i) paresthesia, pain, swelling, weakness or clumsiness of the hand provoked or worsened by sleep, sustained hand or arm position or repetitive action of the hand or wrist that is mitigated by a change in posture or by shaking of the hand; (ii) sensory deficits in the median nerveinnervated regions of the hand; (iii) motor deficit or hypotrophy of the median nerve-innervated thenar muscles; and (iv) positive provocative clinical tests (positive Phalen’s maneuver and/or Tinel’s sign). The clinical diagnosis of CTS was made when criterion 1 and one or more of criteria 2–4 were fulfilled.15,22 Anthropometric and demographic data included age, height, body mass index (BMI), sex, occupation, medication history, hand dominance and underlying disorders associated with CTS, such as diabetes mellitus,
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rheumatoid arthritis, pregnancy, acromegaly or hypothyroidism. Ninety patients (83 women and seven men) with 120 diseased hands were examined within 10 days following NCS. Sixty patients had unilateral CTS (42 cases right hand and 18 cases left hand) and 30 patients were diagnosed with bilateral CTS. We assessed both the right and left hands of all 90 patients blinded to the electrophysiologic study. From unilateral CTS, only those patients were enrolled in the study who had normal hands, which were both clinically and electrophysiologically negative for CTS. Patients with positive clinical symptoms of CTS and a negative NCS result were excluded. In our study, all patients with unilateral CTS had negative clinical and electrophysiological results in their normal hands.
Nerve conduction studies All patients underwent NCS on a Medelec Synergy Electromyography machine (Oxford Instruments, Old Woking, Surrey, UK). Standardized nerve conduction studies were performed by an electrodiagnostician with 21 years experience, using surface electrodes and adjustment for skin temperature, which was kept above 33°C. The antidromic sensory median nerve conduction velocity, the distal motor latency, and the median motor compound muscle action potential were determined. Diagnosis of CTS was made if median sensory nerve conduction velocity (SNCV) was < 40 m/s when the ulnar SNCV was normal, median distal motor latency (DML) more than 4.5 m/s and/or median versus ulnar palm to wrist mixed nerve conduction velocity difference was more than 10 m/s. Our patients were divided into three groups on the basis of electrophysiological severity:1
(Samsung Medical Systems, Seoul, Korea) with a 14 MHz linear-array transducer was used in the study. The sonographic examination was performed with the patient seated in a comfortable position facing the sonographer, with the forearm resting on the table and the palm facing up in the neutral position. The volar wrist crease was used as an initial external reference point, with subsequent modifications during scanning using carpal bony landmarks and internal reference points. The full course of the median nerve in the carpal tunnel was assessed in both transverse and longitudinal planes. The median nerve is located superficial to the echogenic flexor tendons and its size, shape, echogenicity and relationship to the surrounding structures and overlying retinaculum were noted. The mean cross-sectional area (CSA) of the median nerve was measured at the proximal to tunnel, tunnel inlet and outlet (Fig. 1). The ‘tunnel inlet’ referred to the level immediately deep to the proximal edge of the flexor retinaculum. The ‘tunnel outlet’ referred to the level immediately deep to the distal edge of the flexor retinaculum. The mean flattening ratio (defined as the ratio of the major axis of the median nerve to its minor axis) was also assessed at the proximal to tunnel, tunnel inlet and outlet. The thickness of the flexor retinaculum was measured as close to the midline as possible in the midportion of the carpal tunnel (Fig. 2). Median nerve
1 mild: prolonged sensory distal latency SNAP (sensory nerve action potential) amplitude reduction; 2 moderate: prolongation of both median motor and sensory distal latencies; and 3 severe: electrodiagnostic criteria of moderate type of CTS, with either an absence of SNAP, or low amplitude or absent thenar CMAP (compound muscle action potential), or findings compatible with axonal injury in electromyography.
Ultrasonography Ultrasonography of the carpal tunnel was carried out by a musculoskeletal radiologist who was blinded to the NCS results. A MEDISON V20 ultrasound machine
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Figure 1 Receiver operating characteristics (ROC) curve for ultrasonographic assessments of median nerve cross-sectional area (CSA) at the carpal tunnel.
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RESULTS
Figure 2 Graph shows the difference between mean crosssectional area of normal and mild, moderate and severe forms of CTS at the carpal tunnel inlet.
measurements were taken for both patients and control groups.
Statistical analysis Statistical analyses were performed using the SPSS software for Windows, version 21 (SPSS Inc., Chicago, IL, USA); arithmetic mean values and standard deviations (SD) of the data were calculated. Then we carried out an unpaired two sample t-test and chi-squared test comparing age and sex between CTS and non-CTS groups. A repeated measure of analysis of variance (ANOVA) was applied to compare dichotomous and continuous variables between the non-CTS group and three CTS subgroups. The level of confidence was taken at a P-value of 0.05 or less. Relationships of CSA (at the proximal to tunnel, tunnel inlet and outlet), flattening ratio (at the proximal to tunnel, tunnel inlet and outlet), and flexor retinaculum thickness with age, gender, body mass index (BMI) and the electrodiagnostic testing measurements of the nerve conduction velocity were calculated with Spearman’s coefficient. Receiver operating characteristics (ROC) curves were configured to establish the cut-off points of median nerve CSA, flattening ratio, flexor retinaculum thickness with optimal sensitivity and specificity for establishing a diagnosis of CTS. ROC curves are plots of the true positive rate (sensitivity) against the false positive rate (1-specificity) for the different possible cut-off points of a diagnostic test; they show how sensitivity and specificity of a test change as the cut-off point changes.
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We assessed 180 wrists, of which 120 were electrophysiologically confirmed as CTS diseased hands and 60 nondiseased hands in 90 patients (83 women and seven men). All were examined bilaterally. From 120 diseased hands, 42 hands were related to patients with right-handed CTS and 18 hands were related to patients with left-handed CTS. A total of 30 patients had bilateral CTS. Of the 120 symptomatic hands, 57 (47.5%) were mild, 29 (24.2%) moderate and 34 (28.3%) had severe CTS. The mean age of patients was 56.8 10.6 years. In diseased hands, six (5%) showed sensory loss and 29 (24.2%) showed thenar atrophy. A positive Phalen’s sign was present in 119 hands (99.2%) while Tinel’s test was positive in 93 patients (77.5%). Table 1 shows the baseline characteristics of the diseased and nondiseased hands included in this study. Table 2 shows the mean ultrasonographic measurements of cross-sectional areas at various levels of the median nerve in both diseased and nondiseased hands. The mean median nerve CSA at the proximal to tunnel was 11.75 2.56 mm2 in diseased hands with CTS, 7.56 0.77 mm2 in nondiseased hands. The mean median nerve CSA at the tunnel inlet was 13.31 3.23 mm2 in diseased hands with CTS, 8.57 0.82 mm2 in nondiseased hands. The mean Table 1 Baseline characteristics of the patients and control subjects included in this study Variable Age (years), mean SD Gender (male : female) Weight (kg), mean SD Height (cm), mean SD BMI (kg/m2), mean SD Night awakening, n (%) Tinel’s test, n (%) Phalen’s test, n (%) Compression’s test, n (%) Thenar atrophy, n (%) Sensory loss, n (%)
Patients (n = 120)
Controls (n = 60)
Pvalue*
56.8 10.6
54.8 7.8
0.192
5 : 55
2 : 28
0.259
77.8 4.7
71.2 4.9
0.001
162.5 5.8
162.9 4.9
0.681
29.5 2.4
26.8 1.8
0.001
0 (0)
0.001
118 (98.3) 93 (77.5) 119 (99.2) 119 (99.2) 29 (24.2) 6 (5)
11 (18.3) 7 (11.7) 6 (10) 0 (0) 0 (0)
0.034 0.001 0.001 0.001 0.084
*Statistically significant (P < 0.05). BMI, body mass index.
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0.82 0.1 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the FR at various levels of the median nerve were significantly greater in the diseased hands with CTS than the nondiseased hands (P = 0.001) (Table 2). The mean flexor retinaculum thickness was 2.33 0.61 mm in diseased hands with CTS, 1.25 0.16 mm in nondiseased hands, which was statistically significant (P = 0.001) (Table 2). Table 3 shows the mean ultrasonographic measurements of cross-sectional areas at various levels of the median nerve in diseased hands with CTS. Post hoc comparisons between the CTS subgroups (mild, moderate and severe) and nondiseased hands demonstrated that the cross-sectional area at various levels of the median nerve (at the proximal to tunnel, tunnel inlet and outlet) and flexor retinaculum thickness were significantly greater in the severe CTS group than the other three groups (P = 0.001). Furthermore, a significant difference of this mean ultrasonographic measurements (CSA, FR, flexor retinaculum thickness) was also noted between these subgroups when compared with each other (P = 0.001) (Table 3). ROC curves were used to determine optimal discriminatory threshold values for CSA (at all three levels), FR (at all three levels) and flexor retinaculum thickness (Figs 1,2). When the ROC curve was fitted for sonography using clinical criteria as the reference standard, the area under the curve was 0.85 (95% CI, 0.80–0.91) for the CSA at the proximal to carpal tunnel, 0.78 (95% CI, 0.72–0.85) for the CSA at the tunnel inlet and 0.74 (95% CI, 0.66–0.82) for the CSA at the tunnel outlet. CSA at the tunnel inlet with a threshold of 9.15 mm2 gave the best diagnostic accuracy with a sensitivity and specificity of 99.2% and 88.3%, respectively, followed by CSA at the proximal to carpal tunnel with a threshold of 8.25 mm2 which gave a sensitivity and specificity of 99.2% and 78.3%, respectively. CSA at the tunnel
Table 2 Mean ultrasonographic measurements at various levels of the median nerve in both carpal tunnel syndrome (CTS) patients and controls Ultrasonographic Patients with CTS measurements (mean SD) CSA proximal to tunnel (mm2) CSA at tunnel inlet (mm2) CSA at tunnel outlet (mm2) FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
Control P(mean SD) value*
11.75 2.56
7.56 0.77
0.001
13.31 3.23
8.57 0.82
0.001
11.11 2.29
7.43 0.67
0.001
1.83 0.71
0.88 0.08
0.001
2.21 0.84
1 0.1
0.001
2.01 0.78
0.82 0.1
0.001
2.33 0.61
1.25 0.16
0.001
*Statistically significant (P < 0.05). CSA, median nerve cross sectional area; FR, flattening ratio of median nerve.
median nerve CSA at the tunnel outlet was 11.11 2.29 mm2 in diseased hands with CTS, 7.43 0.67 mm2 in nondiseased hands. Post hoc comparisons between the diseased and nondiseased hands demonstrated that the CSA at various levels of the median nerve were significantly greater in the diseased hands with CTS than the nondiseased hands (P = 0.001) (Table 2). The mean flattening ratio (FR) of median nerve at the proximal to tunnel was 1.83 0.71 in diseased hands, 0.88 0.08 in nondiseased hands. The mean FR of median nerve at the tunnel inlet was 2.21 0.84 in diseased and hands with CTS, 1 0.1 in nondiseased hands. The mean FR of median nerve at the tunnel outlet was 2.01 0.78 in diseased hands with CTS,
Table 3 Mean ultrasonographic measurements of cross-sectional area and flattening ratio at different levels of the median nerve and flexor retinaculum thickness across groups Ultrasonographic measurements CSA proximal to tunnel (mm2) CSA at tunnel inlet (mm2) CSA at tunnel outlet (mm2) FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
No CTS 7.56 8.57 7.43 0.88 1 0.82 1.25
0.77 0.82 0.67 0.08 0.1 0.1 0.16
Mild CTS 9.79 10.66 9.38 1.23 1.48 1.35 1.88
1.09 0.8 1.43 0.2 0.29 0.22 0.30
Moderate CTS 12.29 13.79 11.80 1.97 2.33 2.12 2.45
0.81 0.82 0.91 0.32 0.32 0.32 0.36
Severe CTS 14.58 17.35 13.46 2.73 3.33 3.02 2
2.45 2.62 1.87 0.42 0.31 0.49 0.52
CTS (total)
P-value*
0.001 0.001 0.001 0.001 0.001 0.001 0.001
11.75 13.31 11.11 1.83 2.21 2.01 2.33
2.56 3.23 2.29 0.71 0.84 0.78 0.61
*Statistically significant (P < 0.05). CSA, median nerve cross sectional area; FR, flattening ratio of median nerve; CTS, carpal tunnel syndrome.
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outlet, with a threshold of 8.15 mm2 yielded a sensitivity of 96.7% but a lower specificity of 55%. With a cut-off point of 1.02 for the FR at the proximal to carpal tunnel, the sensitivity and specificity of ultrasonography was 98.3% and 46.7%, respectively (95% CI, 0.691–0.859). With a cut-off point of 1.01 for the FR at the tunnel inlet, the sensitivity and specificity of ultrasonography was 94.2% and 55%, respectively (95% CI, 0.799–0.924). FR of 0.94 at the tunnel outlet gave a sensitivity and specificity of 99.2% and 75%, respectively (95% CI, 0.662–0.823). Finally, with a cutoff point of 1.26 mm in the flexor retinaculum thickness, the sensitivity and specificity of ultrasonography was 99.2% and 66.7%, respectively (95% CI, 0.666– 0.853) (Table 4).
DISCUSSION Accurate diagnosis of CTS and its differentiation from other causes of hand morbidity is essential, particularly if the patient is a candidate for surgery. Currently, ultrasonography is a reliable method for the diagnosis of CTS. In comparison with NCS, ultrasonography does not evaluate the physiologic condition of the median nerve but may show swallowing and flattening of the median nerve.23 Many authors believe that ultrasonography can be an alternative method in comparison with NCS for the primary evaluation of CTS in daily practice. In the present study, the efficacy of ultrasound for the diagnosis of CTS was evaluated. Electrodiagnostic studies were used as gold standard diagnostic procedures.24 Previous studies showed that ultrasonography is a feasible and reliable diagnostic procedure. Buchberger et al.25 were the first researchers who assessed the cross sectional area of the median nerve using a high resolution ultrasonography machine with a 7 MHz transducer
to confirm previously reported magnetic resonance imaging of the carpal tunnel. Compression of the median nerve in the canal may increase diagnostic yield of the ultrasound. The ultrasonographic measurement used in CTS diagnosis is the CSA of the nerve at various levels of the carpal canal, the flattening ratio, the swelling ratio and the increased palmar bowing of the flexor retinaculum. The sensitivity and specificity of ultrasonographic measures vary widely among studies. Many authors demonstrated that the increase in CSA at the tunnel inlet had the highest sensitivity and specificity;24,26 moreover, the measurement at this level was easier to perform. There was also disagreement about the exact localization of tunnel inlet. Most authors considered the proximal edge of the flexor retinaculum, approximately at the level of the distal – radioulnar joint, as the tunnel inlet, while others considered the pisiform bone and tubercle of the navicular bone as the landmarks.27 The sensitivity of the CSAs ranged from 48% to 89% and the CSA cutoff at which the value was considered abnormal varied from 9 to 15 mm2.26,28 Sensitivities of increased palmar bowing of the flexor retinaculum varied from 40% to 81%29,30 and sensitivities of flattening ratio ranged from 37% to 100%.29,31 These discrepancies result from many factors: selection criteria of patients and controls, gold standard for diagnosis of CTS, electrodiagnostic methods, levels of CSA measurement and ultrasonographic cut-off values. A bias of the results may also be due to incorrect selection of the control group. For example, sometimes the asymptomatic wrist of CTS cases was included in the control group. In almost all studies the gold standard of CTS diagnosis was based on clinical and abnormal electrodiagnostic tests. In contrast, only a few studies used clinical findings only as the gold standard.24,32 Only this type of study is able to
Table 4 Optimal discriminatory threshold, sensitivity and specificity of ultrasonographic criteria for carpal tunnel syndrome Measurements
CSA at proximal to tunnel (mm2) CSA at tunnel inlet mm2 CSA at tunnel outlet mm2 FR at proximal to tunnel FR at tunnel inlet FR at tunnel outlet Flexor retinaculum thickness (mm)
Optimal discriminatory threshold
Sensitivity (%)
Specificity (%)
Area under the curve
P-value
8.25 9.15 8.15 1.02 1.01 0.93 1.26
99.2 99.2 96.7 98.3 94.2 99.2 99.2
78.3 83.3 55 46.7 55 75 66.7
0.852 0.783 0.739 0.775 0.862 0.743 0.76
0.001 0.001 0.001 0.001 0.001 0.001 0.001
CSA, median nerve cross sectional area; FR, flattening ratio of median nerve.
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compare ultrasonography specificity and sensitivity with those of the electrodiagnostic tests. The few literature data reported different results on NCV specificity.32 In particular, Swen et al.24 reported a very low NCV specificity (19%). They used as the gold standard patients with ≥ 90% relief of symptoms after surgery and received many criticisms on their selection criteria of CTS cases. Wong et al.26 measured cross-sectional areas of the median nerve at three different levels: immediately proximal to the carpal tunnel inlet, at the carpal tunnel inlet and at the carpal tunnel outlet. Using a classification and regression tree, they determined optimal threshold values for each of these levels and suggested diagnostic algorithms based on a combination of fixed cut-offs at two levels of the median nerve that differed for the left and right hands. Mean normal values of median nerve CSA at the carpal tunnel inlet have varied among reports, ranging from 6.1 to 10.4 mm2.24–26 In our healthy control group, mean value of median nerve CSA at the carpal tunnel inlet was 8.57 0.82 mm2. Some studies considered that differing demographic and biometric features, such as older age, male gender, body mass index and handedness, may contribute to the range of normal values. However, the debate still remains; another study found no significant association between biometric characteristics of subjects and median nerve CSA at wrist and forearm in their well-matched case controls.32 Thus, it can be said that the range of normal values for median nerve CSA in the literature more likely reflects variations in study design and ultrasonographic technique. Our results are consistent with previous studies of ultrasound in CTS in showing enlargement of the median nerve in CTS hands.25 There were significant differences in median nerve CSA between CTS and controls hands at all levels measured – proximal to the tunnel inlet, at the inlet and outlet, as well as in the FR. In our population, ROC curves estimated the optimal CSA thresholds to be 9.15 mm2 at the tunnel inlet with a sensitivity and specificity of 99.2% and 88.3%, respectively. Wang et al.33 demonstrated that the median nerve CSA at the pisiform level was most predictive of CTS; the optimal cut-off value was ≥ 9.875 mm2, yielding 82% sensitivity and 87.5% specificity. Yazdchi et al.34 demonstrated that median nerve ultrasonography cannot replace the gold standard test (nerve conduction velocity) for the diagnosis of CTS because of low overall sensitivity and specificity, although it might provide useful information in some patients. Tsai
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et al.35 reported that the CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both diabetes mellitus (DM) and non-DM patients compared to normal hands. Shim et al.36 demonstrated that the median nerve CSA at the level of carpal tunnel inlet was most predictive of CTS; the optimal cut-off value was ≥ 9 mm2, yielding 86.7% sensitivity and 88.9% specificity. Keles et al.30 demonstrated that thickness of the flexor retinaculum can be used in the diagnosis of CTS. In this study, flexor retinaculum thickness > 3.7 mm (sensitivity 71.4% and specificity 55%) was considered significant in the evaluation of CTS patients.30 Mondelli et al.37 demonstrated that in mild cases of CTS, ultrasonography did not detect more anomalies than NCV and vice versa, and no anomalies were detected with either diagnostic instrument in 23.5% of mild cases. Mohammadi et al.38 demonstrated that the CSA at the tunnel inlet and outlet was most predictive of CTS; the best cut-off value was ≥ 8.5 mm2, yielding 97–100% sensitivity and 98–100% specificity. In this study, the difference in CSA of the median nerve in mild, moderate and severe CTS was not statistically significant (P = 0.2) either in the carpal tunnel inlet or outlet.38 Moghtaderi et al.39 suggested that ultrasound is a good diagnostic modality for patients referred to tertiary care centers with categorization as moderate CTS. In this study, they accepted cut-off points of 11.5 and 13.5 mm² for CSA of the proximal and distal portions of the carpal canal, respectively. The sensitivity, specificity, positive and negative predictive values for the proximal inlet were 83%, 90.7%, 65.5% and 55.7%; and for the distal outlet were 36.1%, 93%, 81.2% and 63.4%, respectively.39 Kwon et al.40 demonstrated that the best cut-off value of CSA at the tunnel inlet was 10.7 mm2, which had a sensitivity of 66% and a specificity of 63%. In this study, NCS showed a sensitivity of 78% and a specificity of 83%. Sensitivity was similar between sonography and NCS (P = 0.27), whereas specificity was significantly lower in sonography than in NCS (P = 0.02).40
CONCLUSION This study affirms previous studies in demonstrating the usefulness of ultrasonography in diagnosing CTS. The best cut-off value of CSA at the tunnel inlet was 9.15 mm2, which had a sensitivity of 99.2% and a specificity of 88.3%. In addition to being of high diagnostic accuracy, ultrasonography is a reliable test in assessing the severity of CTS.
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