Role of High Resolution Ultrasound in Assessment of Abnormalities of Median Nerve in Carpal Tunnel Syndrome

Background: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and consists of the compression of the median nerve as it courses through the carpal tunnel. Carpal tunnel syndrome was diagnosed by history and physical examination, electrodiagnostic studies (EDX) were used to confirm the diagnosis. However, these studies are painful for most of the patients with high incidence of false positive or false negative results. Ultrasound is a low cost, short time and non-invasiveness technique that could be used to assess a number of parameters of the median nerve (MN) in cases of CTS. Objective: To assess the utility of high resolution ultrasound (HRUS) in assessment of median nerve in carpal tunnel syndrome through different ultrasound diagnostic criteria in patients with clinical and electrodiagnostic evidence of CTS. Patients and Methods: This study included a total of 60 participants divided into 2 groups; group A, the patients group included 30 patients with a clinical diagnosis of carpal tunnel syndrome (CTS) and group B, the control group who included 30 sex and age-matched healthy individuals. All the included cases were subjected to full history taking, full general and general examination. Nerve conduction studies were performed using a Caldwell Sierra Wave and the NCS consisted of sensory median nerve conduction tests using standard techniques. High resolution US was performed by using an Aplio 400 Ultrasound System. The following measurement was recorded in each of the included subjects including cross sectional area (CSA) of the median nerve, flattening ratio (FR) of median nerve and palmar bowing (PB) of the flexor retinaculum. Results: There was high statistically significant difference in the mean CSA and mean PB between the cases with CTS and healthy control. No statistically significant difference in the mean FR between the cases with CTS and healthy control. Optimal CSA cut-off How to cite this paper: Agag, M.F., Elsharkawy, M.M.K. and Ahmed, A.K. (2020) Role of High Resolution Ultrasound in Assessment of Abnormalities of Median Nerve in Carpal Tunnel Syndrome. Open Journal of Medical Imaging, 10, 73-88. https://doi.org/10.4236/ojmi.2020.102007 Received: March 12, 2020 Accepted: April 17, 2020 Published: April 20, 2020 Copyright © 2020 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and consists of the compression of the median nerve as it courses through the carpal tunnel, it is estimated to occur in 2% of the adult population [1].
It is the most prevalent type of peripheral entrapment neuropathy that accounts for about 90% of all entrapment neuropathies [2].
It is defined by American Academy of Orthopedic Surgeons AAOS as a symptomatic compression neuropathy of the median nerve at the level of the wrist characterized physiologically by evidence of increased pressure in the carpal tunnel and decreased function of the nerve at that level (American Academy of Orthopedic Surgeons).
Carpal tunnel syndrome was diagnosed by history and physical examination, electrodiagnostic studies (EDX) were used to confirm the diagnosis [3].
Electrodiagnostic studies (EDX) are known to be painful or unpleasant, have false negative and false positive results [4]. The utility of ultrasound in the diagnosis has been reported in a number of studies showing that sensitivity and specificity are approaching that of EDX studies [5].
There are many advantages to ultrasound as low cost, short study time, noninvasiveness, immediacy, and dynamic imaging and can be used to assess a number of parameters of the median nerve (MN) such as size, vascularity (using power Doppler) and mobility (using dynamic imaging), anatomical variations of The measurement of cross-sectional area (CSA) of the median nerve at the wrist is the most widely used ultrasonography method in CTS diagnosis [9].
Grading the severity of CTS is important for treatment planning and follow-up. Many researchers have classified CTS severity based on the clinical features and electrophysiological findings [9].
The purpose of this study is to assess the utility of high resolution ultrasound (HRUS) in assessment of median nerve in carpal tunnel syndrome through different ultrasound diagnostic criteria in patients with clinical and electrodiagnostic evidence of CTS.

Study design
This study is a case control one.

Study settings and duration
This study was conducted in radiology department, Al Hussein Hospital, Al The cut-off point used in the NCS was the median nerve distal sensory latency of 3.5 milliseconds and NCS results were considered supportive of CTS when median nerve distal sensory latency was more than 3.5 milliseconds. Wrists with CTS were divided into three groups on the basis of the severity of CTS to mild, moderate, and severe.
High-resolution US was performed by using an Aplio 400 Ultrasound System  -The palmar bowing (PB) of the flexor retinaculum is displacement (measured in mm) of the retinaculum from its attachments to the carpal bones and was measured at the trapezium-hamate level. Once the trapezium and hamate bones are identified, a line was drawn tangential to them. Then, the distance between this line and the most anterior portion of the flexor retinaculum was measured.

Statistical Analysis
The collected data were coded, processed and analyzed using the SPSS (Statistical Package for Social Sciences) version 22 for Windows® (IBM SPSS Inc, Chicago, IL, USA).
Data were tested for normal distribution using the Shapiro Walk test. Qualitative data were represented as frequencies and relative percentages. Chi-square test (χ 2 ) was used to calculate difference between qualitative variables as indicated. Quantitative data were expressed as mean ± SD (Standard deviation). Independent samples t-test was used to compare between two independent groups of normally distributed variables (parametric data) and one way analysis of the variance (ANOVA) was used to compare more than two groups with normally distributed variables (parametric data).
The receiver operating characteristic (ROC) curve was used to find out cut-off points, sensitivity, specificity, positive and negative predictive values. The shape of a ROC curve and the area under the curve (AUC) helps us estimate how high the discriminative power of a test is. For all tests, P values < 0.05 are considered significant.

Results
In the patient group, 30 patients (50 wrists) were included in the study. Out of the 30 patients, 20 patients had bilateral CTS and 10 patients had unilateral CTS (right 6, left 4). In the control group, 30 healthy subjects (50 wrists) ( Table 1).
The mean age (p = 0.121) and BMI (p = 0.523) didn't reveal statistically significant difference between the two groups (p = 0.523). there were females (60%) females and 40% males in the cases group while there were 53.3% females and 46.7% males in the control, with no statistically significant difference between the two groups (p = 0.822). The mean BMI also didn't reveal statistically significant difference between the two groups (p = 0.523). These data are shown in Table 2.
According to the severity of CTS, there were 28 wrists (56%) with mild CTS, 10 wrists (20%) with moderate CTS and 12 wrists (24%) with severe CTS. These data are shown in Table 4. Ultrasonographic measurements: Correlation of the ultrasonographic measurements in CTS patients and control group: In this study, the mean CSA of the median nerve of the cases in the CTS group was 18.98 ± 5.66 mm 2 and in the control group was 7.6 ± 1.32 mm 2 with high statistically significant difference between the two groups (p < 0.001   The diagnostic accuracy of Ultrasonographic measurements in CTS: CSA cut-off value of 8 mm 2 yielded a sensitivity of 96% and specificity of 66%, cut-off value of 9 mm 2 yielded a sensitivity of 96% and a specificity of 90%, cut-off value of 10 mm 2 yielded sensitivity of 92% and a specificity of 98% and Open Journal of Medical Imaging cut off value of 11 mm 2 yielded 97% sensitivity and 100% specificity ( Table 6, Figure 1). PB cut-off value of (3 mm) yielded a sensitivity of 94% and specificity of 80%, cut-off value of (3.2 mm) yielded a sensitivity of 88% and a specificity of 84% and cut-off value of (3.4 mm) yielded sensitivity of 82% and a specificity of 88%. (Table 7, Figure 2).
Optimal cut-off value of CSA and PB for diagnosis of CTS: Optimal CSA cut-off value was (10.2 mm 2 ) which yielded 98.3% sensitivity, 98.3% specificity, and 98.2% positive predictive value and 93.6% negative predictive value (Table 8).

Discussion
Carpal tunnel syndrome (CTS) is the most frequent nerve entrapment neuropathy; it occurs secondary to compression of the median nerve under the flexor retinaculum of wrist joint and leads to an enlargement of its cross-sectional area (CSA) just proximal to the site of entrapment [10]. CTS is considered an idiopathic condition, however, characteristic anatomical variations may participate in development of CTS, such as persistent median artery, or a bifid median nerve [11]. It may also result from traumatic injury, inflammatory arthritis such as rheumatoid arthritis, or in association with hypothyroidism, diabetes mellitus, or pregnancy [12].
Early diagnosis is essential to alleviate permanent nerve damage and functional disability. The diagnosis of CTS is usually based on clinical and neurophysiological studies [9].
US is a diagnostic imaging modality is being used more often in daily clinical practice not only to confirm the diagnosis of CTS but also it can detect anatomical variations, nerve shape and space-occupying lesions as tenosynovitis and ganglion cysts [17].
Modern US equipment allows freehand tracing of the circumference of the median nerve proximal to the site of entrapment and calculation of the crosssectional area (CSA) [18] [19]. Klauser et al. assessed the CSA of median nerve distally at the region of maximal enlargement, usually just proximal to the carpal tunnel, and proximally at the level of pronator quadratus muscle, thereby using the same nerve as its own control, to improve the precision of CTS diagnosis [24].
The aim of this study was to assess the utility of high resolution ultrasound (HRUS) in assessment of median nerve in carpal tunnel syndrome through different ultrasound diagnostic criteria in patients with clinical and electro diagnostic evidence of CTS. This study included a total of 60 participants divided into 2 groups; group A, the patients group included 30 patients with a clinical diagnosis of carpal tunnel syndrome (CTS) and confirmed by the nerve conduction studies (NCS) and group B, the control group who included 30 sex and age-matched healthy individuals who were free of symptoms or clinical signs of neuropathy.
There was no statistically significant difference in the basic demographic criteria between the cases with CTS and the control group. Open Journal of Medical Imaging In this study, there were 24 cases (80%) with idiopathic CTS, 4 cases (13.3%) with DM, 1 case (3.3%) with rheumatoid arthritis and 1 case (3.3%) with hypothyroidism.
Although studies had investigated median nerve CSA at the wrist in CTS patients exclusively with diabetes and hypothyroidism, a comparison of different US parameters, especially the CSA, in patients with idiopathic CTS versus those with CTS associated with diabetes and hypothyroidism has not been compared in the same study [25] [26] [27].
In this study, the mean CSA of the median nerve of the cases in the CTS group was 18.98 ± 5.66 mm 2 and in the control group was 7.6 ± 1.32 mm 2 with high statistically significant difference between the two groups (p < 0.001). The mean PB of the flexor retinaculum of the cases in the CTS group was 4.31 ± 0.85 mm and in the control group was 2.6 ± 0.62 mm with high statistically significant difference between the two groups (p < 0.001). The mean FR of the median nerve of the cases in the CTS group was 2.89 ± 0.68 and in the control group was 2.76 ± 0.55 with no statistically significant difference between the two groups (p = 0.243). This is in accordance with Mohamed et al. (2018) who showed that in the healthy control group included in their study, median nerve CSA at the carpal tunnel inlet ranged from 5 to 9 mm 2 with a mean of 7.85 ± 1.08 mm 2 . They also reported that FR and PB were significantly increased in the CTS group than the control group [28]. These data were found to be in concordance with previous data [15] [29] [30].
Regarding PB of flexor retinaculum, the present study revealed that PB of flexor retinaculum significantly increased in the CTS group compared to control group which went in concordance with studies performed by Rayegani et al. PB of the flexor retinaculum was attributed to increase the pressure inside the carpal tunnel described in the pathogenesis of CTS [31].
Previous studies attempted to ascertain a universal cutoff value of CSA for the diagnosis of CTS, however until now there was no standard universal cutoff range, being mainly dependent on the ethnicity of the group studied [14] [41], with sensitivity of 82% and specificity of 87% (which were almost equal to those of electrodiagnostic values) with a cutoff CSA of more than 12 mm 2 considered as excellent to diagnose CTS [14]. In this study, Optimal CSA cut-off value to differntaite between CTS cases and control was (10.2 mm 2 ) which yielded 98.3% sensitivity, 98.3% specificity, and 98.2% positive predictive value and 93.6% negative predictive value.
This came in agreement with Elnady et al. (2019) who showed that the cutoff value of CSA at the level of carpal tunnel to diagnose CTS in Saudi population was 13 mm 2 with 90% sensitivity and 95% specificity [17]. Mohamed et al. (2018) showed 84% sensitivity and 100% specificity at a 9.5 mm 2 cut-off value for the mean CSA at the inlet [28].
The study of  showed higher sensitivity (88.5%) probably due to the less number of their control (30 vs. 100 wrists in our study) and higher sample size (246 wrists) and showed a higher specificity (90%) probably due to a higher cut-off value (10 mm 2 ) [29].
This also came in accordance with other studies cutoff threshold that ranged between 12 and 13 mm 2 in CTS as compared with the control [24] [42] [43].
Elnady and his colleagues showed that the mean CSAdp of 9.5 showed sensitivity of 82% and 95% specificity to diagnose CTS, however ∆CSA of 2.5 mm 2 was associated with 97% sensitivity and 100% specificity, with much higher sensitivity and specificity than using CSAd and mean CSAdp [17].
In another study, the ∆CSA of 2 mm 2 or greater was considered diagnostic for CTS with sensitivity of 99% and a specificity of 100% [24].
In this study, PB cut-off value of (3 mm) yielded a sensitivity of 94% and specificity of 80%, cut-off value of (3.2 mm) yielded a sensitivity of 88% and a specificity of 84% and cut-off value of (3.4 mm) yielded sensitivity of 82% and a specificity of 88%. Sonbol et al. (2017) showed that the recorded optimal cut-off value of PB for diagnosis of CTS in current study was 3.3 mm with a sensitivity and specificity of 90% and 85% respectively. Positive and negative predictive values were recorded as 85.7% and 89.5% respectively [31].
In previous studies, PB values have ranged between 2.5 and 4 mm [44]. In our study, there was a statistically significant increase in the CSA of the media nerve with the severity of CTS. There were 28 wrists out of 50 (56%) classified as mild CTS, mean CSA in this group was (17.15 ± 3.58 mm 2 ), 10 out of 50 wrists (20%) were classified as moderate CTS with mean CSA of (20.16 ± 4.42 mm 2 ), the remaining 12 patients (24%) were classified as severe CTS with mean CSA of (27.26 ± 7.37 mm 2 ).
This came in agreement with Elnady et al. (2019) who showed that the CSAd was statistically correlated to the severity of CTS with neurophysiologic assessment, the higher the value the more severe the CTS [17].
US is advantageous in that it is noninvasive, less painful (and therefore more acceptable to patients), more readily available and less expensive. According to our results, US is highly sensitive and specific, so that it may be used as an early tool to assess CTS in patients that may have negative or borderline electrophysiologic studies since negative electrophysiologic studies may occur in up to 30% of CTS patients [48] [49].
Despite the results of this study, there were some limitations such as it is a single center study and the relatively small sample size of the cases included in the study. Also, the design of the study is a case control study which decreases the power of the results.

Conclusions
This study revealed that there was Carpel tunnel syndrome (CTS) which is the most prevalent form of nerve entrapment. CTS is common in middle age group with higher risk in females. Idiopathic form is the most common form of CTS followed by endocrinal and metabolic abnormalities mostly diabetes mellitus (DM).
Electrophysiological studies are the most utilized diagnostic methods for diagnosing nerve entrapment including median nerve in CTS. Hugh resolution ultrasound (HRUS) is non-invasive sensitive diagnostic tool in diagnosing CTS. Different parameters measured by HRUS revealed high sensitivity and specificity in diagnosing CTS such as (cross sectional area, palmer bowing and flattening ratio).