Carpal tunnel syndrome (CTS) is the most common peripheral mononeuropathy with a prevalence ranging from 1 to 6% in the general population (1, 2). CTS is caused by compression of the median nerve as it travels through the carpal tunnel, and can be diagnosed clinically. The symptoms classically include pain and paraesthesia in the territory of the median nerve, increasing during the night, and provocation by flexing or extending the wrist (3). Case history evaluation is the most important part of consultation for the clinical diagnosis of CTS (4). Nevertheless, in The Netherlands, most surgeons require a confirmation by an electrodiagnostic or ultrasound test (5).

As of 2017, ultrasonography (US) is the recommended first diagnostic test in The Netherlands because it is easily accessible and painless. Moreover, US and nerve conduction studies (NCS) have a similar sensitivity and specificity, according to the Dutch CTS guideline (6). In literature, several ultrasonography parameters for confirming the diagnosis CTS are suggested, the most important being (7, 8):

In a previous study we found that a wrist circumference-dependent cut-off value of the CSA could lead to increased diagnostic accuracy (11). In this study we used the increase of the CSA of the median nerve at wrist level as parameter and evaluated which of three ultrasonographic cut-off values can confirm the clinical diagnosis of CTS the most accurately. These three parameters include a cut-off value of the maximum CSA based on (1) a fixed cut-off value, (2) a wrist circumference-dependent cut-off value, and (3) an intraneural flow-dependent cut-off value (the presence or absence of increased nerve vascularisation).

In earlier studies (12) we used more rigid clinical criteria for diagnosing CTS. Patients were included if they experienced paraesthesias and/or pain in the median nerve-innervated territory, and two or more of the following clinical signs: (1) nocturnal paraesthesias, (2) aggravation of paraesthesias by driving, holding a book or telephone, and (3) a positive Flick sign. However, in our experience, confirmation of presumed CTS is often required by the clinician for patients who do not fulfil all these criteria. In this study we analysed data from three large Dutch teaching hospitals with less strict, but in daily practice more commonly used, inclusion criteria for CTS, as mentioned in paragraph Study Population and Sonography Assessment. Compared to earlier studies, waking up at night due to the symptoms was not mandatory in this study and we did not specify the different types of aggravating activities.

The primary goal of this study was to investigate in how many patients clinical CTS conformation could be achieved by using these three cut-off values and compare performance of these cut-off values. The clinical diagnosis, as defined in the inclusion criteria in the next section, was used as the gold standard.

Table 1 shows the patient characteristics. A total number of 175 patients were included. There were no statistically significant differences between the hospitals in gender, age, side of included wrist, height, weight, BMI, or the duration of symptoms. Particularly, wrist circumference did not differ between these patient groups. The CSA of the median nerve at wrist was significantly smaller in the Zuyderland hospital compared with CWZ (p < 0.001) and compared with the Radboudumc (p = 0.042). This value did not differ between CWZ and the Radboudumc (p = 0.318).

In this cross-sectional study a wrist circumference-dependent cut-off value for the upper limit of normal of the CSA at the wrist led to more abnormal US results than either a fixed upper limit of normal of 11 mm² (p = 0.035) or a cut-off value based on intraneural flow (p = 0.001) did.

As shown in an earlier study, a WDC of the CSA may augment diagnostic accuracy of ultrasonography in CTS patients (11). We found that this parameter considered more US to be abnormal than a FC or an IFC did. The mean CSA of the median nerves of the evaluated patients was relatively low in this study. In the Zuyderland hospital the mean CSA was significantly lower than in the Canisius-Wilhelmina hospital (p < 0.001) and the Radboudumc (p = 0.042). This lower mean CSA in the Zuyderland hospital leads to a very low number of abnormal US in the Zuyderland hospital, ranging from 28.2 to 40.8%. Looking at the small subgroup of patients with abnormal US results while using the WCD and normal US results while using the other two cut-off methods, a statistically significantly smaller wrist circumference was noticed, as is shown in Table 6. These results may point out that a cut-off value based on the wrist-circumference adds the most value in people with a smaller wrist circumference when compared with the other analysed US parameters in this study.

The lack of a gold standard is an important problem in the diagnosis of CTS and this complicates research regarding CTS (15). In literature, clinical signs and symptoms, NCS and (surgical) outcome are used as reference standards (15). CTS is a clinical diagnosis and without signs and symptoms an individual cannot be diagnosed with CTS but can have abnormal US/NCS outcomes. False positives as well as false negatives are therefore present in groups of patients with clinically defined CTS but also in groups of patients with e.g., abnormal US and/or abnormal NCS outcomes. A positive effect of surgical treatment is another possible reference standard. However, even sham operations could have a positive (placebo) effect. Furthermore, in a previous study we showed that patients with clinically defined CTS and normal NCS noted a significant reduction of complaints after carpal tunnel release (16). For the examined wrists in this study the same problem of false positives and false negatives exists and the less strict inclusion criteria are probably the cause of the low sensitivity of US in this study.

Several studies suggest that increased nerve vascularisation in the median nerve, as evaluated by colour Doppler sonography, is associated with (severity of) carpal tunnel syndrome (10). However, one study showed an increased median nerve vascularisation prevalence of 36% in 60 healthy individuals (14). Surprisingly, in this study, median nerve vascularisation was only present in 10.9% of the participants and in the Radboudumc absent in all participants. This is not in line with literature where increased nerve vascularisation is reported in 41–95% of CTS patients (10, 17). This may be explained by differences in techniques while performing US (e.g., manual compression) or differences in settings and/or Doppler sensitivity between US devices. A cut-off value based on nerve median nerve vascularisation seemed to be the least favourable cut-off compared with the other investigated parameters in this study.

There are several limitations to this study. Firstly, it is important to bear in mind the possible bias in our data caused by our more liberal inclusion criteria for investigating carpal tunnel syndrome. We did not mean to change the clinical criteria for CTS in any way, but our goal was to investigate a patient population, as may be encountered in daily outpatient clinical practice, as described in the introduction. Secondly, the neurophysiology technicians performing the US were not blinded. The technicians may have expected to find enlargement of the median nerve, however, compared to an earlier Dutch study the median CSA of the median nerve at wrist level seems to be lower in this study, especially in the Zuyderland hospital (13). Concerning ultrasonography, we did not measure intra- or interobserver variability of the measurements. Earlier studies reported good agreement of CSA measurements of the median nerve (18, 19) but we cannot fully exclude interobserver variability due to variation in outlining the nerve contour (20), particularly because of the significantly smaller CSA found in the Zuyderland hospital. Only in the Radboudumc the distal carpal tunnel was visualised, in the other hospitals the median nerve was visualised only in the proximal and middle part of the carpal tunnel. However, in this study the percentage of abnormal US in the Canisius-Wilhelmina hospital and the Radboudumc were comparable. Furthermore, we cannot exclude slight differences in interhospital interpretations concerning the inclusion criteria.

In conclusion, a WDC for the CSA of the median nerve at the wrist appears to have a higher sensitivity than a FC or IFC in CTS patients in clinical practice, who do not always fulfil more rigid clinical criteria for the clinical diagnosis CTS. A cut-off for the CSA of the median nerve based on the wrist-circumference may at present be the most powerful approach in patients with a smaller wrist circumference.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Commissie Mensgebonden Onderzoek regio Arnhem-Nijmegen. The ethics committee waived the requirement of written informed consent for participation.

TO, FD, JM, and WV: conception and design of study. TO, RBe, and JW: acquisition of data. TO, FD, RBe, JW, RBa, JM, and WV: analysis and/or interpretation of data. TO: drafting of manuscript. TO, FD, RBe, JW, RBa, JM, and WV: revising manuscript. All authors read and approved the final version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.