Estimating the most accurate sonographic measurement in the diagnosis of carpal tunnel syndrome: Which is the best?
On the other hand, there is still no US standard for the identification of CTS. In the present study, we aimed to identify the most accurate method or measurement combination for the diagnosis of the impingement of the nerve.
PATIENTS AND METHODS
Between October 2010 and April 2011, a total of 160 hands of 87 patients (4 males, 83 females; mean age 54.5 years; range, 26 to 84 years) with clinically and electrodiagnostically proven idiopathic CTS and 80 hands of 40 controls (3 males, 37 females; mean age 53.7 years; range, 32 to 77 years) were evaluated by US examination. Inclusion criteria were as follows: age older than 18 years, presence of symptoms for more than one year, having no evidence of arthritis, hypothyroidism, diabetes mellitus, previous trauma or pregnancy, having no history of injection or splinting within the past six months or receiving any surgery at the carpal tunnel. Patients who had pathological changes in the US examination (i.e., tenosynovitis, synovial cysts, arteriovenous malformations, or bifid median nerve) were excluded. Among 160 hands, we detected mild CTS in 105 hands and moderate CTS in 55 hands according to electroneuromyographic findings. The control group consisted of wrists without signs or symptoms of CTS. A written informed consent was obtained from each participant. The study protocol was approved by the institutional Ethics Committee of Gulhane Training and Research Hospital. The study was conducted in accordance with the principles of the Declaration of Helsinki.
In the patient group, 14 patients met the exclusion criteria for one of their extremities; therefore, unilateral extremities of these patients were evaluated and we decided that personal properties were not important, as hands could be affected in different ways and severity in a single patient. The US examination of unilateral extremity of 14 patients and bilateral extremities of 73 patients were performed.
All patients underwent a nerve conduction study including distal motor latency, motor amplitude, sensory latency, sensory amplitude, and sensory velocity. Ultrasonographic examination was performed by a single investigator using a Logic 7 Pro US system a 18-5 MHz linear array transducer. The investigator was blinded to the electrodiagnostic results. The participants were investigated in the supine position. The boundary trace was performed along the circumference of the nerve, excluding the hyperechoic epineurium. The diameters and CSA of the median nerve at the inlet of the tunnel (radioulnar joint level) (Figure 1), at the proximal tunnel (at the level of pisiform) (Figure 2), and at the outlet of the tunnel (at the level of hamate) (Figure 3), also volar bulging (VB: the farthest distance between the flexor retinaculum and an imaginary line tangent to the trapezium and hamate at the level of the distal carpal bones) were measured.
Transverse images of the median nerve were examined at the distal radius, the pisiform, and the hook of the hamate levels. The level of the radius was at the most distal ridge of the radius. It was reached by moving the US probe distally along the wrist until the radius was not seen, at which time the probe was slided proximally until the bony landmark reappeared again.
The anteroposterior (AP), transverse diameter, and cross-sectional area (CSA) of the median nerve were measured in the proximal carpal tunnel (at the level of pisiform) and at distal carpal tunnel (at the level of hamate).
Accordingly, the flattening ratio (FR) of the nerve was calculated by dividing transvers and AP diameters. At the carpal tunnel entrance and proximal carpal tunnel, thickness of retinaculum (RT) were measured. At the proximal carpal tunnel, the area of the tunnel was measured. The swelling ratios were also calculated according the following formula: swelling ratio (SR): CSA at the level of pisiform/CSA at the distal radioulnar level. Longitudinal diameters (LDs) were examined at three different levels (Figure 4): LD1 at the entrance of carpal tunnel (distal of radius), LD2 at the level of scaphoideum to denote the proximal of carpal tunnel, LD3 at the level of capitatum to denote the distal CT.
Statistical analysis was performed using the SPSS for Windows version 11.5 software (SPSS Inc., Chicago, IL, USA). Descriptive data were expressed in mean [+ or -] standard deviation (SD) or number and frequency. The Pearson's correlation coefficient was calculated. The Shapiro-Wilk test was used to analyze normal distribution of continuous variables. The Spearman correlation analysis was performed to examine relationship between continuous variables. The differences of continuous variables between CTS and control hands were analyzed using receiver operating characteristics (ROC) analysis. The ROC curves were used to select the optimal cut-off values for useful US variables. A p value of 0.05 was considered statistically significant.
Electroneuromyographic findings of patients and controls are shown in Table 1. There were no significant differences between the control and patient groups in terms of age, sex, and body mass index (p>0.05). The CSA and transvers diameters of patients at the tunnel inlet and the CSA, diameters, FR at the proximal carpal tunnel, VB and CSA, diameters, SR at the distal tunnel, LD1 and 2 were significantly larger than the control group (p<0.001). In the patient group, LD3 significantly decreased than the control group (p<0.001). The precision of US measurements was evaluated using the optimal cut-off value of the ROC curve. The area under the ROC curve and 95% confidence interval (CI) of sonographic data used to distinguish patients from controls are shown in Table 2.
The area under the curve (AUC) of CSA was 0.961, indicating a sensitivity and specificity of 88.6% and 96%, respectively. The AUC of VB was 0.960, indicating a sensitivity and specificity of 83% and 98%, respectively. The AUC of the proximal transverse diameter was 0.863, indicating a sensitivity and specificity of 72% and 96%, respectively (Table 3).
In addition, the mean CSA at the level of pisiform was 0.15[+ or -]0.03 [cm.sup.2] in the patient group and 0.10[+ or -]0.02 [cm.sup.2] in the control group, indicating a significant difference between the groups (p<0.001). The most accurate US measurement for CTS diagnosis was proximal CSA with 88% sensitivity and 96% specificity in distinguishing patients from controls, and VB was the second most prognostic measurement method with a sensitivity and specificity of 83% and 98%, respectively (p<0.001), followed by the proximal transverse diameter with 72% sensitivity and 96% specificity (p<0.001) (Table 3). The most accurate US measurements which could discriminate patients from healthy controls were evaluated using multiple logistic regression analysis with forward logistic regression method. Odds ratios, 95% CIs, and Wald statistics were also calculated for each US measurement.
Among the combinations of all US measurements, the most optimal combination for the diagnosis of CTS was proximal CSA and VB. When the proximal transverse diameter was added to these two parameters, although the specificity decreased, there was a significant increase in the sensitivity (Table 4).
The differences in true-positive and true-negative ratios between any two of combined US measurements were analyzed using the McNemar test which showed no significant differences (p>0.05). However, according to the third variable, true-positive ratios of the first, second, fourth, fifth, and sixth variables were statistically significant (p<0.001, p=0.004, p<0.001, p<0.001, and p<0.001, respectively). According to the second variable, true-positive ratios of the fourth and sixth variables were statistically significant (p=0.016 and p=0.016, respectively).
The diagnosis of CTS is obtained by electromyography (EMG) which is able to indicate the physiological situation along with the affection of the nerve and also helps to decide appropriate treatment method. However, knowledge and practice of EMG examination is usually restricted to neurologists or physiatrists. In particular, advanced cases which are candidates for surgery need to be referred to these specialties. On the other hand, in general medicine, physicians may need to have some other methods to estimate the suspected cases. Currently, musculoskeletal US is an option and an increasing number of studies has been reported regarding the role of US in CTS. Ultrasonography is useful to demonstrate the nerve inside the canal along with surrounding structures. The changes in volume and structure of the nerve can be detected using this technique. In general, the route of the nerve throughout the canal, its CSA before entering (inlet), entrance and outlet as well the inner tunnel, its swelling and flattening in the inner tunnel, VB are measured.
As the nerve CSA increases at the inlet due to narrowed tunnel, measuring CSA at this level may increase the suspicion. In most studies, the CSA was measured at only one level, at the proximal carpal tunnel, and these studies reported that the increase in the CSA at the tunnel inlet demonstrated the strongest sensitivity and specificity. [5-8] However, to extract the possible compression, CSA of the median nerve at different levels would be more helpful.
Comparing the CSA at the inlet, proximally inside and outlet of the tunnel, may give the opportunity to show the structural changes during its whole passage. In our study, the CSA at all three levels were found to be significantly larger than those in the control group. However, the increase of the CSA at the proximal carpal tunnel proved the highest sensitivity, yielding consistent results with the literature. [9-13]
In their study, Kele et al.  reported that an enlargement of the median nerve in the proximal carpal tunnel in combination with longitudinal compression of the nerve was highly prognostic for CTS. However, Wiesler et al.  did not evaluate the longitudinal scans due to its unreliable results. In our study, the longitudinal measurements showed a good diagnostic precision according to the ROC curves.
Previously, an increased FR at the hook of hamate level has been reported as a diagnostic criterion. Several studies showed increased FRs at the hook of hamate level [16,17] whereas others did not. [8,18,19] Our results also showed increased FRs at the proximal carpal tunnel with lower sensitivity.
Kim et al.  reported that CSA and VB had a high sensitivity and specificity, similar to our study. Also, CSA and VB were found to have relatively higher precision than FR. In another study, CSA of the median nerve at pisiform, hamate bone levels, and at the distal wrist crease and the AP diameter of the median nerve within the carpal tunnel and wrist-to-forearm ratio (WFR) showed significant differences between the patient and control groups. 
Our results showed that proximal CSA was the most appropriate single measurement with higher values than the literature. Volar bulging was the second-line diagnostic measurement. According to our study results, proximal CSA combined with VB gave the most accurate diagnostic results. Also, additional proximal transverse diameter increased its sensitivity. This approach can be considered as a practical modality to differentiate CTS patients from asymptomatic controls. In a meta-analysis, larger CSA of the median nerve at the carpal tunnel inlet and higher FR at the level of the hamate were seen in CTS wrists and CSA at the carpal tunnel inlet was reported as the most optimal, single measure.  In another study, CSA at the outlet and its palm-to-forearm-ratio were significantly larger than the CSA at the inlet and its WFR.  Accordingly, the addition of CSA outlet measurements to inlet measurements increased diagnostic sensitivity and accuracy of US in CTS. Klauser et al.  suggested that the comparison of the median nerve CSA between proximal and distal carpal tunnel could increase the diagnostic precision. However, Junck et al.  reported that CSA measurements at the proximal site had low intra-rater reliability. Therefore, it is critical to combine CSA with other sonographic measurements, as in the present study.
Furthermore, Yurdakul et al.  reported that only pisiform CSA measurements were predictable for the diagnosis of mild severity of CTS. The CSA pisiform/CSA ulnar nerve yielded a poor diagnostic value for the identification. In another study, a 14-mm two CSA were found to be sufficient to distinguish moderate and severe CTS.  Contrast to our study results, Nur Saracgil et al.  found no significant correlation between the parameters of US and EMG. The variations in measurement methods, different properties of study groups, and equipments may cause differences in diagnostic sensitivity and specificity.
The major limitation of this study was that the US examination was performed by a single physiatrist. Thus, no inter- and intra-rater reliability tests were able to be performed.
In conclusion, as the EMG gives the most accurate values, US would not be used to replace it. However, US has an ability to visualize the nerve with its surrounding structures in the canal. In addition to high sensitivity and specificity, US can be used as a valuable diagnostic and estimation method in CTS patients. Even if not used to detect physiological disturbances, it is valuable method to distinguish CTS patients from asymptomatic controls.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
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Ozlem Koroglu (1) [iD], Serdar Kesikburun (1) [iD], Emre Adiguzel (2) [iD], Mehmet Ali Taskaynatan (1) [iD], Ahmet Ozgul (3) [iD]
(1) Department of Physical Medicine and Rehabilitation, Gulhane Medical Faculty, Ankara, Turkey
(2) Department of Physical Medicine and Rehabilitation, Gaziler Physical Therapy and Rehabilitation Training and Research Hospital, Ankara, Turkey
(3) Department of Physical Medicine and Rehabilitation, Girne University Faculty of Medicine, Girne, KKTC
Received: January 12, 2018 Accepted: July 17, 2018 Published online: April 30, 2019
Corresponding author: Ozlem Koroglu, MD. Gulhane Tip Fakultesi Fiziksel Tip ve Rehabilitasyon Anabilim Dali, 06010 Etlik, Ankara, Turkey.
Table 1. Electroneuromyographic findings of patients and controls Variables Mean[+ or -]SD Min-Max Distal motor latency (msn) Patient group 4.3[+ or -]0.8 2.15-6.85 Control group 2.7[+ or -]0.4 2.05-3.65 Motor amplitude (mikroV) Patient group 8.1[+ or -]2.9 2.10-17.10 Control group 4.7[+ or -]1.5 3.00-9.40 Sensory latency (msn) Patient group 3.3[+ or -]0.8 2.05-6.70 Control group 2.5[+ or -]0.3 2.00-2.98 Sensory velocity (m/sn) Patient group 41.2[+ or -]6.2 11.50-49.80 Control group 54.3[+ or -]3.6 50.00-62.50 Sensory amplitude (mikroV) Patient group 26.8[+ or -]14.3 4.40-61.90 Control group 37.5[+ or -]10.7 20.00-67.00 SD: Standard deviation; Min: Minimum; Max: Maximum. Table 2. The area under receiver operating characteristics curve and 95% confidence interval of sonographic measurements Variables Area under the curve p Inlet transverse diameter 0.847 <0.001 Inlet cross-sectional area 0.790 <0.001 Proximal anteroposterior diameter 0.690 <0.001 Proximal transverse diameter 0.863 <0.001 Proximal cross-sectional area 0.961 <0.001 Flattening ratio (proximal) 0.629 <0.001 Thickness of retinaculum (inlet) 0.554 0.171 Thickness of retinaculum (proximal) 0.575 0.057 Volar bulging 0.960 <0.001 Carpal tunnel area 0.526 0.516 Distal anteroposterior diameter 0.693 <0.001 Distal transverse diameter 0.737 <0.001 Distal cross-sectional area 0.658 <0.001 Swelling ratio 0.700 <0.001 Longitudinal diameter (1) 0.754 <0.001 Longitudinal diameter (2) 0.751 <0.001 Inlet anteroposterior diameter 0.509 0.825 Flattening ratio (distal) 0.516 0.679 Longitudinal diameter (3) 0.632 <0.001 Variables Low limit Upper limit Inlet transverse diameter 0.796 0.898 Inlet cross-sectional area 0.734 0.847 Proximal anteroposterior diameter 0.619 0.762 Proximal transverse diameter 0.815 0.910 Proximal cross-sectional area 0.938 0.985 Flattening ratio (proximal) 0.557 0.701 Thickness of retinaculum (inlet) 0.481 0.627 Thickness of retinaculum (proximal) 0.503 0.648 Volar bulging 0.939 0.981 Carpal tunnel area 0.447 0.604 Distal anteroposterior diameter 0.628 0.758 Distal transverse diameter 0.675 0.800 Distal cross-sectional area 0.591 0.724 Swelling ratio 0.633 0.767 Longitudinal diameter (1) 0.694 0.814 Longitudinal diameter (2) 0.691 0.812 Inlet anteroposterior diameter 0.424 0.594 Flattening ratio (distal) 0.444 0.589 Longitudinal diameter (3) 0.563 0.702 Table 3. The optimal cut-off value of ultrasonography and sensitivity and specificity in distinguishing patients from controls Variables Cut-off value Inlet transverse diameter (mm) 4.910 Inlet cross-sectional area ([cm.sup.2]) 0.105 Proximal anteroposterior diameter (mm) 1.895 Proximal transverse diameter (3) (mm) 5.800 Proximal cross-sectional area (1) ([cm.sup.2]) 0.125 Flattening ratio (proximal) 3.540 Volar bulging (2) (mm) 4.750 Distal anteroposterior diameter (mm) 1.885 Distal cross-sectional area ([cm.sup.2]) 0.085 Swelling ratio 1.430 Longitudinal diameter (1) (mm) 2.235 Longitudinal diameter (2) (mm) 2.455 Longitudinal diameter (3) (mm) 1.755 Variables Sensitivity Specificity Inlet transverse diameter (mm) 0.863 0.700 Inlet cross-sectional area ([cm.sup.2]) 0.469 0.950 Proximal anteroposterior diameter (mm) 0.819 0.500 Proximal transverse diameter (3) (mm) 0.725 0.963 Proximal cross-sectional area (1) 0.881 0.962 ([cm.sup.2]) Flattening ratio (proximal) 0.288 0.925 Volar bulging (2) (mm) 0.838 0.988 Distal anteroposterior diameter (mm) 0.469 0.925 Distal cross-sectional area ([cm.sup.2]) 0.519 0.850 Swelling ratio 0.544 0.788 Longitudinal diameter (1) (mm) 0.581 0.838 Longitudinal diameter (2) (mm) 0.563 0.888 Longitudinal diameter (3) (mm) 0.525 0.788 Table 4. Sensitivity and specificity of combinations of sonographic measurements in distinguishing patients from controls Variables Sensitivity Specificity Proximal CSA + volar bulging 96.3 95.0 Proximal CSA + proximal transverse diameter 93.8 92.5 Proximal CSA + inlet transverse diameter 88.1 96.3 Proximal CSA + volar bulging + proximal 98.1 91.3 transverse diameter Proximal CSA + volar bulging + inlet 96.3 95.0 transverse diameter Proximal CSA + volar bulging + proximal 98.1 91.3 transverse diameter + inlet transverse diameter CSA: Cross-sectional area.
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|Title Annotation:||Original Article|
|Author:||Koroglu, Ozlem; Kesikburun, Serdar; Adiguzel, Emre; Taskaynatan, Mehmet Ali; Ozgul, Ahmet|
|Publication:||Turkish Journal of Physical Medicine and Rehabilitation|
|Article Type:||Clinical report|
|Date:||Jun 1, 2019|
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