Background

Entrapment neuropathies of the upper extremities are the most common peripheral neuropathies. They are caused by compression or traction of the peripheral nerves as they travel through a narrow anatomical site. The etiology of entrapment neuropathies is not fully understood. The multifactorial etiology may contribute to the heterogeneity of patients’ symptoms [1].

The pathophysiological changes that take place in entrapment neuropathies due to chronic compression include intraneural ischemia which compromises the blood-nerve interface resulting in nerve edema manifested as enlargement of the nerve segment distal to the site of compression. Eventually, extra-neural and intra-neural fibrotic changes occur due to prolonged edema. Demyelination is the hallmark of entrapment neuropathies with subsequent axonal degeneration due to prolonged ischemia. Additionally, central sensitization and structural changes in the somatosensory cortex have been reported in patients with severe prolonged entrapment neuropathies which may contribute to widespread hypersensitivity and altered pain modulation [2]. It is debatable whether central changes are dependent on peripheral causes or can drive symptoms on their own.

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. CTS is caused by compression of the median nerve under the transverse carpal ligament. The classical symptoms of CTS are nocturnal pain, paresthesia, weakness, and loss of function in the distribution of the median nerve [3]. However, extra-median symptoms involving the medial hand and one and a half fingers supplied by the ulnar nerve were frequently noticed, raising the assumption of possible concomitant ulnar nerve entrapment at the wrist or Guyon's canal syndrome (GCS) [4].

Several theories were hypothesized to explain these whole-hand symptoms; one of them was increased central sensitization [5, 6]. Another theory was built on the assumption of possible structural or functional changes that may take place in the ulnar nerve in patients with CTS due to the close contiguity between the carpal tunnel and Guyon canal (GC) at the wrist [7]. The volar carpal ligament constitutes the floor of the GC and the roof of the carpal tunnel. Therefore, increased pressure in the carpal tunnel may affect the ulnar nerve at the wrist level, and this may explain the extra-median spread of symptoms [8].

There is still controversy regarding ulnar nerve abnormalities at the wrist in idiopathic CTS and their possible role in the development of extra-median symptoms; therefore, the aim of the study was to assess possible early functional and structural changes that might take place in the ulnar nerve in patients with idiopathic mild to moderate carpal tunnel syndrome before central changes take place.

Subjects and methods

This retrospective case–control study included 40 patients with CTS diagnosed according to the criteria of the American Association of Electrodiagnostic Medicine (AAEM) [9], and only those with CTS of a mild to moderate degree according to the scale of Padua et al. [10] were included in the study. Forty healthy subjects of matched age, sex, and body mass index constituted the control group. The study was approved by the local ethical committee, and written consent was signed by all the participants.

A detailed history was taken, and a careful clinical examination was performed to exclude the presence of other diseases that could be related to CTS. The exclusion criteria were (1) history of any potentially confounding conditions such as neurologic, orthopedic, rheumatologic, or endocrine diseases, renal failure, diabetes mellitus, and pregnancy; (2) previous surgery for CTS; (3) proximal median or ulnar nerve affection; (4) history of a previous injury or fracture to the upper limb; (5) peripheral neuropathy; (6) cervical radiculopathy; (7) edema of the upper limb; (8) CTS related to occupational injuries; and (9) patients previously treated with local corticosteroid injection. Additionally, the asymptomatic contralateral upper limb was not included as a control due to the possibility of subclinical CTS.

Patient assessment

Hand symptoms were classified according to a self-administered hand symptoms diagram regarding the distribution of sensory symptoms derived from the original diagram of Katz et al. [11]. Patients were asked to indicate the distribution of their paresthesia by marking areas of discomfort on the hand diagram. They were not asked to distinguish in the diagram between numbness and tingling. The diagram was graded into median (MED) and extra-median (EXTRAMED) patterns.

Neurophysiological examination

The neurophysiological evaluation was done for all the participants by an experienced physiatrist, using Viking Quest electrodiagnostic apparatus (Nicolet ViaSys Healthcare, USA). Nerve conduction studies were performed using AAEM-recommended nerve conduction techniques [12]. The following nerves were studied:

  • Antidromic sensory conduction studies for the median and ulnar nerves were recorded from the 2nd and 5th digits, respectively, with a fixed distance of 14 cm. The following parameters were recorded: peak sensory latency (PSL), onset to peak amplitude (OPA) of sensory nerve action potentials (SNAP), and sensory conduction velocity.

  • Sensory conduction study of the superficial radial and dorsal ulnar cutaneous branch of the ulnar nerve.

  • Motor conduction studies of the median nerve stimulating the median nerve at the wrist, recording from abductor pollicis brevis muscle (APB), and motor conduction studies of the ulnar nerve stimulating the ulnar nerve at the medial wrist adjacent to the flexor carpi ulnaris tendon, recording from abductor digiti-minimi muscle (ADM) as well as first dorsal interosseus muscle (DI). The distance between the stimulating electrode and the active recording electrode was 8 cm. The following parameters were recorded: distal motor latency (DML), compound muscle action potential (CMAP) amplitude, and motor conduction velocity at the forearm segment (MCV). Measuring u-MCV at the elbow segment was done to exclude entrapment of the ulnar nerve across the elbow region.

Ultrasonographic examination

The ultrasonographic examination was carried out for all the participants on the same day of electrodiagnostic evaluation using a 12-MHz linear array transducer (GE Logiq S6 Ultrasound System) by a radiologist experienced in neuromuscular ultrasound who was blinded regarding the patients and their electrophysiological evaluation. The sonographic examination of the median and ulnar nerves was done with the upper limb placed in the supine position and palm up, at the distal wrist crease, with the transducer placed perpendicular to the nerve to obtain a transverse view. The probe was applied cautiously to avoid additional pressure on the nerves. The following parameters were measured:

  • Median nerve cross-sectional area (m-CSA) and ulnar nerve cross-sectional area (u-CSA) at the pisiform level. The area was calculated using the continuous trace method by outlining the perimeter just inside the hyperechoic epineurium [13,14,15]. The CSA of the bifid median nerve was calculated by adding the individual CSAs of its two components.

  • Median nerve flattening ratio (m-FR), which is defined as the ratio of the transverse diameter to the anteroposterior diameter of the median nerve at the level of the hook of the hamate [16].

  • Median nerve swelling ratio (m-SR): m-CSA was measured 4 cm proximal to the distal end of the radius. The m-SR was calculated as m-CSA at the pisiform/m-CSA 4 cm proximal to the distal end of the radius [17].

  • The difference between m-CSA at the inlet of the carpal tunnel and m-CSA at the distal third of the pronator quadratus (Δ m-CSA) was calculated by subtracting the cross-sectional area at the level of the pronator quadratus from the cross-sectional area at the carpal tunnel inlet, reflecting the swelling of the median nerve distally [18].

Statistical analysis

Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp.). The sample size was estimated using the PASS Version 20 program. A minimal total hypothesized sample size of 80 eligible participants (40 per group) was needed to assess the possibility of distal ulnar involvement with carpal tunnel syndrome of mild to moderate degree by electrodiagnostic and ultrasonographic evaluation, taking into consideration a 95% confidence level and 80% power using the chi-square test.

Qualitative data were described using numbers and percentages. The Shapiro–Wilk test was used to verify the normality of the distribution. Quantitative data were described using range (minimum and maximum), mean, standard deviation, median, and interquartile range (IQR). The chi-square test was used for categorical variables to compare different groups. Student t-test was used for normally distributed quantitative variables to compare the two studied groups, while the Mann–Whitney test was used to compare the studied groups for abnormally distributed quantitative variables. Pearson coefficient test was used to correlate normally distributed quantitative variables. The Bonferroni test was used for statistical correction of multiple tests.

Results

This study included 40 right-handed female patients with clinical and electrophysiological features suggestive of carpal tunnel syndrome. The mean duration of their hand symptoms was 2.23 ± 0.6 years. Forty right-handed asymptomatic females of comparable age, weight, height, and body mass index constituted the control group. The symptomless contralateral side of some patients was not considered a control due to the possibility of subclinical CTS. 95% of the patients as well as the control group were housewives (Table 1). Among the patients, 72.5% (n = 29) had right CTS, while left CTS was reported in 37.5% (n = 11). According to the scale of Padua et al., 9 patients (22.5%) had mild CTS and 31 patients (77.5%) had CTS of moderate degree. Regarding the control group, evaluation was done on 40 hands (29 right hands and 11 left hands).

Table 1 Comparison between the two studied groups according to occupation, age, and anthropometric measurements
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Clinically, paresthesia of the hand was the major complaint of all the patients. According to the hand diagram of Katz et al., all the patients had hand paresthesia in the distribution of the median nerve, while extra-median or whole-hand paresthesia was observed in 55% (n = 22) of them. A motor deficit involving the thenar muscles (grade 4 +  − 4 on the Motor Research Council scale) was noted in 70% of the patients (n = 28), while no motor affection of the muscles supplied by the ulnar nerve was detected clinically.

An electrophysiological study revealed no statistically significant differences between both groups regarding the motor conduction parameters of the ulnar nerve. However, sensory conduction parameters of the ulnar nerve were significantly abnormal in the patient group compared to the control group (Table 2).

Table 2 Comparison between the two studied groups according to motor and sensory conduction studies of the ulnar nerve
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Ultrasonographic evaluation of all the participants revealed a significant enlargement of the m-CSA at the level of the pisiform bone (p < 0.001) among the patient group. Additionally, m-SR and ∆m-CSA were significantly higher in the patient group. Similarly, the u-CSA of the patients was significantly higher than the control group (Table 3). Figure 1 demonstrates axial sonograms at the level of pisiform bone in a case of left CTS of moderate degree.

Table 3 Comparison between the two studied groups according to ultrasonographic parameters
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Fig. 1
figure 1

Axial sonograms at the level of pisiform bone in a case of left CTS of moderate degree. A m-CSA: 11 mm2. B u- CSA: 6 mm2

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Although no significant relationship was detected between u-CSA and ulnar electrophysiological parameters nor between u-CSA and m-CSA in the patient group, a statistically significant relationship was demonstrated between u-CSA at the level of the pisiform bone and the motor conduction parameters of the median nerve, where a significant positive correlation was detected between u-CSA and median DML (p < 0.001), while a significant negative correlation was reported between median CMAP amplitude, median MCV, and u-CSA (p = 0.001 and p < 0.001, respectively) (Fig. 2).

Fig. 2
figure 2

Correlation between median motor conduction parameters u-CSA. A Correlation between median DML (ms) and u-CSA (mm2). B Correlation between median CMAP amplitude (mv) and u-CSA (mm2). C Correlation between median MCV (m/s) and u-CSA (mm2)

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Discussion

Considerable debate exists in the literature about the possibility of ulnar nerve involvement at the wrist in idiopathic CTS. Entrapment of the ulnar nerve at the wrist, or Guyon’s canal syndrome (GCS), is a relatively uncommon type of peripheral ulnar neuropathy that involves injury to the distal part of the ulnar nerve as it travels across the wrist. The hypothesis of possible structural and functional changes that may take place in the ulnar nerve in conjunction with CTS was based on clinical observations of the disappearance of hand paresthesia in ulnar nerve distribution after carpal tunnel release.

In our study, selected patients had mild to moderate CTS with symptoms duration ranging from 1 to 3 years. Whole-hand paresthesia was perceived in 55% of the patients with no motor deficit in the distribution of the ulnar nerve. This was in concordance with the studies conducted by Kang et al., Yemisci et al., and Mansiz-Kaplan et al., which found that around 50% of the patients with idiopathic CTS had paresthesia involving the whole hand [8, 19, 20].

Many studies were conducted to evaluate functional changes in the ulnar nerve in conjunction with idiopathic CTS. In the current study, the electrophysiological parameters of the ulnar nerve in the patient group were within the normal range; however, sensory conduction parameters of the ulnar nerve were significantly abnormal in the patients relative to the control group. In agreement with our findings, several studies, including one conducted on the same population [19, 21,22,23,24,25,26,27], documented significant changes in sensory parameters of ulnar nerve conduction in patients with idiopathic CTS. The most frequent abnormality noted was a slowed u-SCV, followed by a reduction in u-SNAP amplitude. Moreover, two studies found a significant delay in u-SL [22, 28]. On the contrary, other studies did not find any ulnar sensory conduction abnormalities in association with carpal tunnel syndrome [8, 29,30,31].

We did not report significant changes in motor conduction parameters in the patients relative to the controls. Several studies agreed with our findings [8, 24, 28, 30, 32,33,34,35]. On the other hand, three studies documented ulnar motor conduction abnormalities mainly in DML and CMAP amplitude relative to the control [19, 25, 36].

The variability in the results may be due to differences in sample size, population characteristics, electrodiagnostic techniques, and the degree of CTS among the recruited patients. Some studies did not exclude patients with diabetes mellitus who may be affected by subtle peripheral neuropathy or a symptomless contralateral hand that may be affected subclinically. Additionally, a lack of selection of matched controls in terms of anthropometric measures and working activities may have an impact on the electrophysiological evaluation. It is worth mentioning that some studies evaluate the ulnar conduction parameters qualitatively in terms of normal versus abnormal rather than quantitative electrophysiological values.

Sonographic evaluation was carried out using a 12-MHz probe. We evaluated the median nerve sonographically by several parameters, such as m-CSA, m-FR, m-SR, as well as ∆m-CSA. Except for the m- FR, all ultrasonographic parameters were significantly higher in the patients relative to the control group. Most of the studies that measured the median nerve sonographic parameters in CTS reported the same findings [37,38,39,40].

In the current study, normal u-CSA at the level of the pisiform bone was 3.28 ± 0.64 mm2. Several studies of normal u-CSA values on sonographic evaluation have been reported. In a study conducted on Asian patients, the normal value was 3.6 ± 5.0 mm2 [41]. Similarly, in the study conducted by Kang et al. on Korean patients [7], u-CSA among the control group was 3.56 ± 0.52 mm2 (1), while another study from the USA determined the mean normal u-CSA value to be 5.9 ± 1.1 mm2 [42]. This study is the first to document normal values of distal u-CSA in our population It seems that differences in age, sex, ethnicity, and anthropometric measures affect the normal u-CSA.

Regarding the ultrasonographic data of the ulnar nerve in conjunction with CTS, a smaller number of studies were published. We demonstrated a significant enlargement of u-CSA relative to the control group, which agreed with the study conducted by Kang et al. [8]. On the contrary, other studies reported a significant reduction in u-CSA relative to the control group [28, 43], and one study by Eom et al. did not show any abnormality in u-CSA [44] in patients with CTS. These conflicting results may reflect the fact that ultrasonography is an operator-dependent diagnostic modality with considerable interobserver variability and different scanning techniques. Moreover, most of these studies used low probe frequencies (< 12 MHz), which warrant caution as the resolution of the image is low, with subsequent less sharp nerve boundaries, making it difficult to accurately measure nerve CSA [45].

It seems reasonable that the long-term increase in pressure in the carpal tunnel and its transmission to the nearby Guyon’s canal is likely to result in nerve edema and thus an increase in m-CSA as well as u-CSA. Our explanation is supported by two studies that reported a significant increase in the intraductal pressure of both the carpal and Guyon’s tunnels in patients with idiopathic CTS, with a subsequent significant reduction in their pressure after a surgical section of the transverse carpal ligament (TCL) [46, 47]. Moreover, morphological evaluation by magnetic resonance imaging (MRI) demonstrated that Guyon’s canal, which had a triangular shape before surgery, turned into an oval or rounded shape after the surgical release of CTS [48, 49]. Unfortunately, no studies were available to demonstrate abnormal sonographic findings of the ulnar nerve secondary to its entrapment in Guyon’s canal due to the rarity of such a condition.

Our study has some limitations. First, the study aimed at reporting early changes that take place in the ulnar nerve in conjunction with idiopathic mild to moderate CTS; however, more studies are needed to evaluate ulnar nerve involvement in longstanding severe cases of CTS. Additionally, since the study included only female patients, it will be more informative to conduct future studies on male patients with idiopathic CTS. Moreover, most of the examined hands in our study were dominant hands (72.5%), in the context of the increased cortical presentation of dominant hands. Additional studies on non-dominant hands may give a better insight into possible concomitant changes in the ulnar nerve in patients with idiopathic CTS.

Conclusion

The current study demonstrated functional and structural changes that took place in the ulnar nerve in cases of mild to moderate CTS. Although the electrophysiological parameters of the ulnar nerve were within the normal ranges, we reported statistically significant differences in ulnar sensory electrophysiological parameters in the patients relative to the control group. Additionally, the CSAs of both median and ulnar nerves were larger at the level of the pisiform bone in those with CTS. Moreover, we demonstrated a significant correlation between u-CSA and median motor conduction parameters. Our findings highlighted the potential importance of neuromuscular ultrasonography in the detection of distal ulnar neuropathy in those patients, even before evident functional changes could be detected by electrodiagnostic evaluation. Finally, more precise sonographic parameters for measuring distal ulnar neuropathy are needed due to the lack of standardized cut-off values for normal u-CSA at this site and the scarcity of available studies on distal ulnar neuropathy due to the relative rarity of this condition.