Diagnostic potential of ultrasound in carpal tunnel syndrome with different etiologies: correlation of sonographic median nerve measures with electrodiagnostic severity

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 (1).

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 (2). It may also result from traumatic injury, inflammatory arthritis such as rheumatoid arthritis, or in association of hypothyroidism, diabetes mellitus, or pregnancy (3, 4).

Early diagnosis is essential to alleviate permanent nerve damage and functional disability. The diagnosis of CTS is usually based on clinical and neurophysiological studies (1).

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 (5, 6).

Modern US equipment allows freehand tracing of the circumference of the median nerve proximal to the site of entrapment and calculation of the cross-sectional area (CSA). Unfortunately, there is no clear cut and generally accepted cutoff value of a single CSA measurement to diagnose CTS as different studies have producing widely variable results with various cutoff threshold for establishing the diagnosis of CTS which appear to be affected by group ethnicity. (7‐16). Although studies had investigated median nerve CSA at the wrist in CTS patients exclusively with diabetes and hypothyroidism (17‐19), 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.

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 (20).

The aim of this study was to assess the accuracy of ultrasound in diagnosis of CTS in the Saudi population using the method developed by Klauser et al. (i.e. ΔCSA) and also the mean of the proximal and distal (mean CSApd) measurements. The median nerve US measurements were further analyzed to detect any difference in the parameters between idiopathic CTS and CTS associated with diabetes mellitus or hypothyroidism.

42/60(70%) patients were females and 38/50 (76%) controls were females. The mean patient age was 50.2 ± 11.2 years. 89 wrists of the 60 CTS patients and 76 wrists of the 50 healthy controls were scanned by US,

There was no statistical significant difference regarding age, sex and BMI between CTS patients and controls. However there was a highly significant difference between both groups regarding mean ± SD of CSAd, CSAp, ∆ CSA, and mean CSApd (p = 0.0001) (Table 1).

Severe CTS according to neurophysiological assessment was found in 31 wrists with 58 wrists diagnosed as mild to moderate. Cohen’s kappa test showed highly statistical inter-reader agreement regarding both ultrasonography measurements (k = 0.88, p < 0.001). There was a statistical significant difference in CSAd values between mild to moderate CTS (16.4 ± 5.1 mm²) and severe CTS (19.7 ± 5.3 mm²) (P = 0.01), additionally there was a highly statistical significant difference in ∆CSA values between mild to moderate CTS (5.8 ± 3.1 mm²) and severe CTS (11 ± 4.3 mm²) (P = 0.001), furthermore there was a highly statistical significant difference in the mean of CSApd values between mild to moderate CTS (8.8 ± 1.5 mm²) and severe CTS (14.4 ± 4.2 mm²).

A positive significant correlation was also found between the CSAd, ∆ CSA and mean of CSApd measurements with the severity grade based on the neurophysiologic studies (P = 0.001) (Table 2).

To assess the accurate cutoff value and the most sensitive and specific threshold values, a receiver operating characteristic (ROC) curve was done and the area under the curve was calculated. The ultrasound measures of CSAd with area under the curve = 0.978, showed threshold values of 11, 12, and 13 mm², the ∆CSA with area under the curve = 0. 998, showed threshold values of 2, 2.5, 3 mm², and mean CSAdp with area under the curve = 0.925, showed threshold values of 9.5, 10, 10.5 mm² were illustrated in Table 3. The best diagnostic values were achieved by using a ∆CSA threshold of 2.5 mm². Receiver operating characteristic analysis revealed excellent ability to use CSAd, ∆CSA, and Mean CSAdp (Fig. 4, Table 3).

58 scanned CTS wrists were characterized as idiopathic, 18 diabetes-associated CTS and 13 hypothyroidism-associated CTS. There was no significant difference regarding ∆CSA between diabetic, idiopathic and hypothyroidism CTS groups (P > 0.05), however there was statistical significant difference regarding mean CSAdp and CSAd values within groups (P < 0.05), Post Hoc analysis was done showed no significant difference regarding mean CSAdp and CSAd values between idiopathic and hypothyroidism associated CTS or between hypothyroid and diabetes associated CTS. However a significant difference was found between mean CSAdp and CSAd values between diabetes and idiopathic CTS, with higher measurement values in diabetic patients (P < 0.05) (Table 4).

Median nerve entrapment in the wrist joint is the most frequent entrapment neuropathy [1, 28], with high prevalence in females [29]. US is a noninvasive tool that can assess the median nerve in CTS [5, 6]. We investigated the use of US CSA measurements of the median nerve in patients with electrophysiological confirmed CTS and in non-affected normal controls to validate this technique in the Saudi population. We evaluated the difference and average mean of both the proximal, non affected, part of the median nerve at the level of the pronator quadratus muscle and the CSA at the wrist where you would expect to find the maximum enlargement due to distal compression effect, [20]. Furthermore, we calculated the mean of CSA proximal values to omit the individual variability rather than depend on CSA at the level of carpal tunnel only.

We found a statistical significant difference in the US values of CSAd, CSAp, ∆CSA, and mean CSAdp between CTS patients and healthy controls, with these findings was in agreement with Klauser et al. [20].

Although neurophysiologic study is accurate in diagnosis of CTS [1], US has the added value of potentially identifying the underlying pathology causing CTS, such as anatomical variants or space occupying pathology [3‐6]. In the our study, the CSAd was statistically correlated to the severity of CTS with neurophysiologic assessment, the higher the value the more severe the CTS, which were concordant with other studies [20, 30, 31]. However, Mhoon et al. did not find a significant correlation between CSAd and electrophysiologic severity assessment [32]. Klauser et al. also [20] stated that ∆CSA is correlated with neurophysiologic CTS severity, which agreed with our findings related to ∆CSA. In addition, we found that the mean CSAdp also statistically correlated to the severity of CTS which was not assessed in previous studies.

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 [7‐12]. In previous literature, the suggested values of CSAd median nerve abnormality varies between 9 to 14 mm² [27, 28]. Although discrepancies in the accuracy of sonographic criteria of median nerve entrapment have been reported, CSA with cutoff values of more than 9 or 10 mm² at the scapho-pisiform level indicating CTS [12‐15] is still agreed upon as the most reliable and reproducible sonographic criterion indicating CTS [33], 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 mm² considered as excellent to diagnose CTS [11]. In the current work, the cutoff value of CSA at the level of carpal tunnel to diagnose CTS in Saudi population was 13 mm² with 90% sensitivity and 95% specificity which was in agreement with other studies cutoff threshold that ranged between 12 and 13 mm² in CTS with or without diabetes [20, 34, 35]. The mean CSAdp of 9.5 showed sensitivity of 82 and 95% specificity to diagnose CTS, however ∆CSA of 2.5 mm² was associated with 97% sensitivity and 100% specificity, with much higher sensitivity and specificity than using CSAd and mean CSAdp. In another study, the ∆CSA of 2 mm² or greater was considered diagnostic for CTS with sensitivity of 99% and a specificity of 100% [20].

Electrodiagnostic testing is considered the reference standard for CTS diagnosis with sensitivities of 82–94% and specificities of 65–97% [10‐12, 15], even though paresthesia may occur before changes can be measured with nerve conduction tests [36]. 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 [9]. According to our results, ultrasound is highly sensitive and specific, so it may be used as an early tool to assess CTS where patients may have negative or borderline electrophysiologic studies.

In the current study, we also looked at different CTS etiologies. There was a statistical difference regarding CSAd, and mean CSAdp values between CTS patients with idiopathic CTS and diabetes, however, there was no statistical difference between different etiologic groups regarding ∆CSA. A recent meta-analysis on CSA of CTS with diabetes, in spite being not statistically significant (p = 0.52), CSA of median nerve in patients with diabetes and CTS were likely to be larger than patients with idiopathic CTS [17]. A study by Thomsen et al. found focal CSA enlargement of median nerve in diabetic patients without CTS, particularly at the level of the carpal tunnel inlet, they suggested other additional factors which may contribute to such phenomenon, such as a reduction in myelinated nerve fibers and capillary density that may predispose diabetics to develop CTS [37]. Imaging modalities as US and magnetic resonance imaging (MRI) have had a significant role in understanding, assessment and diagnosis of disorders of the peripheral nervous disorders [39].

Our study had several limitations. The assessment of US measurements CSAd, ∆CSA and mean CSAdp in cases with bifid median was not done on our group of patients. In addition, this study is only assessed in one ethnic group with smaller sample size.

Strengths of the current study are that it was designed as a case controlled study involving a less commonly studied ethnic group, the inclusion of disease severity and various etiologies, the correlation of the different US measurements to disease severity, the sub analysis of US measurements in relation to variable etiologies and the establishment of a cutoff diagnostic value of CTS in Saudi population with ultrasound.

Ultrasound assessment in carpal tunnel syndrome is noninvasive diagnostic tool with correlation to the degree of entrapment severity with a ∆CSA greater than 2.5 mm² being considered diagnostic for CTS in Saudi population. Diabetic CTS patients tend to have higher median nerve US measurements values as opposed to idiopathic and hypothyroid CTS in our study group. This study, in our opinion, emphasizes the importance of utilizing US in the diagnosis of early stage CTS to alleviate permanent nerve damage and functional disability, however, large randomized control studies are needed to assess the current study measurements in bifid median nerve with CTS.