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. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Clin Biomech (Bristol). 2021 Jul 24;88:105440. doi: 10.1016/j.clinbiomech.2021.105440

Carpal tunnel syndrome treatment and the subsequent alterations in tendon and connective tissue dynamics

Mohammad Hosseini-Farid 1,2, Verena JMM Schrier 1,3, Julia Starlinger 1,4, Chunfeng Zhao 1, Peter C Amadio 1,*
PMCID: PMC8490321  NIHMSID: NIHMS1730485  PMID: 34329857

Abstract

Background

Carpal tunnel syndrome patients demonstrate diminished motion of the median nerve and fibrotic changes in the subsynovial connective tissue within the carpal tunnel. Currently, there are few prognostic factors to help predict the outcome of commonly performed treatments including surgical carpal tunnel release and corticosteroid injections. This study aimed to non-invasively assess the changes in the dynamic response of the subsynovial tissue relative to tendon motion after the intervention and to correlate this with disease severity.

Methods

A total of 145 patients with carpal tunnel syndrome were recruited into this study. Clinical and demographic data, electrophysiological severity and dynamic ultrasound images were collected before and after treatment, either by injection or surgery. The relative motion of the subsynovial tissue with the underlying middle finger flexor digitorum superficialis tendon was measured using a speckle tracking algorithm and was expressed as a shear index (SI). Baseline and follow-up data, the association between change in SI and severity, and the role of treatment modality were analyzed and statistically compared.

Findings

Overall, there was a significant increase (more relative motion) after treatment in the mean shear index from 79.9% (±15.4% SD) to 82.9% (±14.8% SD) (p=0.03). Secondary analyses showed that this change was mostly present in those with mild disease severity undergoing surgery (p=0.01).

Interpretation

This study shows that the relative subsynovial tissue movement increases in patients after intervention. The present study lays a foundation for future studies to non-invasively assess the role of carpal tunnel dynamics in response to treatment.

Keywords: Carpal tunnel, CTS, subsynovial connective tissue, ultrasound imaging, Speckle tracking

1. Introduction

Carpal tunnel syndrome (CTS) has been recognized as the most common median nerve (MN) entrapment syndrome worldwide (Padua et al., 2016). In the United States alone, 500,000 carpal tunnel releases are performed annually, with an associated cost of over $2 billion (Milone et al., 2019). Varying treatment protocols, which include surgical and non-surgical options, are used depending on institutional and professional preferences. Overall, corticosteroid injections are considered to be more likely to be effective for early stage of CTS or mild cases, with the possibility of a repeat injection with the return of symptoms. The relatively high percentage of patients requiring additional treatment (Evers et al., 2017), and low satisfaction rates (Jenkins et al., 2012; Surgeons, 2016) has caused the role of corticosteroids to be a topic of debate. Carpal tunnel release (CTR) surgery is widely perceived as the only definitive solution, and is recommended for severe cases to prevent irreversible nerve damage and subsequent loss of strength, dexterity, and sensation. Interestingly, it has been shown that, when studies are pooled together, CTR surgery success rates vary in a wide range, from 27% to 100% (Bland, 2007). Additionally, there is no clear patient-based treatment algorithm, since only a limited number of pre-intervention factors (e.g. co-morbid conditions such as diabetes, poor health status, thoracic outlet syndrome, double crush, alcohol and smoking), have been shown to correlate directly with outcome (Turner et al., 2010).

Limited motion of carpal tunnel structures, as measured with ultrasound, has been noted in CTS patients (Ellis et al., 2017). One pathophysiological model links this finding to the non-inflammatory thickening and fibrotic character of the subsynovial connective tissue (SSCT) in the carpal tunnel, as has been found histologically in CTS patients (Ettema et al., 2004). The mechanical characteristics such as shear modulus and gliding function of the SSCT are changed due to fibrotic alterations of this tissue in CTS patients, compared to normal subjects (Ettema et al., 2004; Ettema et al., 2007; Ketchum, 2004; Osamura et al., 2007). In CTS, the SSCT moves less smoothly and is more adherent to the adjacent flexor tendons (Ettema et al., 2008; Ettema et al., 2007), a feature subsequently described as directly correlated to the severity of symptoms (Filius et al., 2015a).

Recent developments have led to improved accuracy of dynamic ultrasound image processing, allowing the SSCT to be visualized more reliably (Bandaru et al., 2018; Schrier et al., 2019a). With a need for more prognostic parameters and only limited data availability on the effect of treatment on the dynamic behavior of the SSCT, this study aimed to: (1) investigate whether there is a change in SSCT/tendon relative motion after the CTS intervention (2) determine whether this change is associated with the electrophysiological severity of the CTS, and (3) explore if the prospective change is associated with the intervention method.

2. Methods

2.1. CTS Participants

A total of 145 hands were enrolled in the study. 48 of these hands were treated with a corticosteroid injection (20 mg of triamcinolone acetate) and 97 subjects had open CTR surgery. The patients’ ages ranged from 21 to 84 years, with a mean of 54 years.

2.2. Data collection

Patients clinically diagnosed with CTS were recruited at a specialized hand clinic. The Institutional Review Board (IRB) approved the study and written informed consent was obtained from all participants prior to participation. The diagnosis and choice of intervention (i.e., surgery or injection) were determined based on a combination of clinical tests, symptoms at presentation, and the results of electro-diagnostic (EDS) tests. All patients underwent EDS using the Viking EDZ EMG machine (CareFusion, San Diego (CA), USA), and the test was performed according to the guidelines of the American Association of Neuromuscular and Electro-diagnostic Medicine (Medicine, 2002). Based on the results from this test, the patients were categorized by severity as normal, mild, moderate, severe or very severe CTS (Witt et al., 2004).

The inclusion criteria were: clinical diagnosis of CTS, symptoms of numbness or tingling in the median nerve distribution for at least 4 weeks, and recommendation for treatment by either injection or surgical release. Patients who had a previous surgical release, tumor, mass or deformity in hand or wrist, or were diagnosed with pregnancy-induced CTS, cervical radiculopathy, peripheral nerve disease, thyroid disease, rheumatoid arthritis or other inflammatory arthritis, osteoarthritis in wrist, diabetes, renal failure, sarcoidosis, amyloidosis or major trauma to ipsilateral hand or wrist, were excluded from this study. Patients were allowed to enroll both hands, but only if each hand was treated differently (i.e., one hand having surgery and the other hand, injection). Additionally, conversion to surgery after unsuccessful injection was allowed, in which case patients could be approached to enroll that hand in the surgical group (provided that the contralateral hand had not already been enrolled in the surgery arm). 135 participants (53 males and 82 females) with a total of 145 hands were enrolled.

2.3. Imaging protocol

The dynamic ultrasound images for all 145 CTS cases were captured by a standard protocol by a trained sonographer, both prior to and either one month (injection) or three months (surgery, to minimize surgical artifact) after the therapeutic intervention. Patients were rested supine and the forearm of the affected hand was stretched out on a Plexiglas board in 70–80° abduction. As depicted in Figure 1-a, b, to ensure isolated middle finger flexion-extension, the forearm and the second and fourth digit were constrained using a strap. All images were captured by a linear array transducer (L15–7io) using a Philips iE33 ultrasound machine (Royal Philips Electronics, Amsterdam, the Netherlands). The probe was positioned over the proximal wrist crease in the sagittal plane, using copious gel to prevent excessive pressure. In this configuration, the probe was able to capture longitudinal images of the middle finger flexor digitorum superficialis tendon (confirmed by patient activation of isolated middle finger proximal interphalangeal joint flexion), including the overlying SSCT. After a training period, participants performed full flexion and extension of the middle finger at a rate of fifty beats per minute, guided by a metronome. The metronome assisted the participants in identifying the start moment of each cycle and the transition time between flexion and extension. Three cycles of active middle finger flexion-extension were collected in each subject.

Fig. 1.

Fig. 1.

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The flexion-extension performance of the third digit demonstrating the finger motion at the (a) start and (b) end position (Schrier et al., 2019a). Note that the distal interphalangeal joint is not flexed, confirming isolated flexor superficialis activation. (c) The ultrasound B-mode images with selected areas indicating tendon and SSCT were recorded for three cycles of the finger motion. Figure 2. The pre and post-intervention value of shear indices for the study cohort of CTS patients. A significant difference (p < 0.05) was found between the before and after treatment. These Box plots are generated by JMP and illustrate the distribution of the data, mean, median and the outlier at each group. Figure 3. The shear indices based on different EDS categories. A significant difference (p < 0.01) was found between the pre and post-intervention SI for CTS patients with mild EDS. Figure 4. The shear indices based on different EDS groups and intervention methods. The calculated pre and post-intervention SI display a significant difference (p < 0.05) for mild EDS patients who had carpal tunnel release surgery.

2.4. Ultrasound Image assessment

The captured ultrasound images were processed by a custom written MATLAB code (Korstanje et al., 2010). This speckle tracking algorithm was originally created to capture tendon motion and later enhanced and validated with a singular value decomposition (SVD) technique to track the SSCT (Bandaru et al., 2017; Bandaru et al., 2018; Schrier et al., 2019a). The whole clip was reviewed and the median nerve, the flexor digitorum superficialis III (FDS), the flexor digitorum profundus III (FDP) and the SSCT were identified. Then, the region of interest (ROI) for the tendon was manually placed, covering the main width in the middle of the tendon. The detailed sequences and procedure of the applied speckle tracking have been described in the earlier study (Bandaru et al., 2018). Finally, the averaged displacement vectors calculated from frame-to-frame displacement vector of all ultrasound images were evaluated and reported.

2.5. Data analysis

The assessments of all sonographic images were done in Matlab (R2019a, The MathWorks Inc., Natick, MA, 2000) and the total displacements of tendon and SSCT at three cycles of middle finger flexion-extension were measured. To obtain a consistent comparison for the relative motion between tendon and SSCT, Yoshii et al. (Yoshii et al., 2009b) introduced the concept of the SSCT/tendon shear index (SI), as the ratio of displacement change for these structures. The index is defined as the difference in the motion of these two tissues divided by the tendon excursion. The tendon-SSCT SI has been widely used to study the relative dynamic behavior between these tissues (Filius et al., 2015a; Schrier et al., 2019a; Tat et al., 2015; Van Doesburg et al., 2012; Yoshii et al., 2009a) and is expressed as:

Shear IndexSI%=Tendon Excursion−SSCT ExcursionTendon Excursion×100

By this definition, when the SI=100 the tendon moves completely independently from the SSCT, and when SI=0 the tendon and SSCT move identically. Based on the measured total displacements for tendon and SSCT at 3 flexion-extension cycles of the third digit, the SI of all CTS patients were calculated.

2.6. Statistical analysis

The SI of both pre and post-intervention cohorts were visually assessed, and determined to be not normally distributed. Hence, in order to test the overall difference in shear index for all groups, a Wilcoxon signed-rank test was used. For the secondary analyses, the data was categorized by disease severity and subsequently by treatment type and sex. Significance was set with a p-value = 0.05, and the statistical analyses were done using JMP Statistical Package (JMP, Version 14. SAS Institute Inc., Cary, NC, USA 2019).

3. Results

3.1. Change in relative motion

The mean SI values of all studied CTS patients before the intervention was 79.9% (±15.4% SD), and this value increased to 82.9% (±14.8% SD) after the intervention (p=0.030). Figure 2 demonstrates the shear indices assessed for the CTS patients before and after the treatments were performed. In the patients treated by injection, the shear index changed from 77.6% (±19.9% SD) to 81.2% (±16.1% SD, p=0.250). The surgery cohort values changed from 81% (±12.5% SD) to 83.7% (±14.1% SD, p=0.076). Hence, both treatment methods demonstrated an increase in SI, denoting higher relative motion occurred after the intervention.

Fig. 2.

Fig. 2.

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The pre and post-intervention value of shear indices for the study cohort of CTS patients. A significant difference (p < 0.05) was found between the before and after treatment. These Box plots are generatead by JMP and illustrate the distribution of the data, mean, median and the outlier at each group.

3.2. Shear Index and disease severity

Data were also stratified by disease severity, as measured by electrodiagnostic studies and mean SI of each group. This data is presented in Table 1. As depicted in Figure 3 and also reported in Table 1, except for the patients identified as normal in EDS, all other groups with different EDS severity (i.e. mild, moderate, and severe) attained higher SI after the intervention, but only the patients who identified with mild severity were found to have significant differences (p = 0.007) in their shear index after the intervention.

Table 1.

Summary of the measured shear index (SI) of CTS patients and for both intervention methods and different EDS groups.

All subjects Injection Surgery EDS_Normal EDS_Mild EDS_Moderate EDS_Severe
N 145 48 97 32 37 42 34
SI Pre mean (SD) 79.9 (15) 77.6 (20) 81 (13) 81.8 (14) 75.6 (17) 80.7 (15) 80.9 (15)
SI Post mean (SD) 82.9 (15) 81.2 (16) 83.7 (14) 80.5 (17) 84.2 (13) 83 (14) 83.6 (17)
SI Change +3 +3.6 +2.7 −1.3 +8.5 +2.3 +2.7
P-value 0.030 0.250 0.076 0.956 0.007 0.405 0.475
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Fig. 3.

Fig. 3.

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The shear indices based on different EDS categories. A significant difference (p < 0.01) was found between the pre and post-intervention SI for CTS patients with mild EDS.

3.3. Shear Index, severity and treatment

The SI data for different EDS based groups was then stratified according to intervention method to investigate how either injection or surgery would have affected the relative motion between tendon and SSCT. Table 2 provides the calculated mean value and the changes in SI for different EDS categories based on the treatment method patients received. The mean SI for normal EDS patients who had the injection therapy was decreased after the intervention (−5.3%). A slight reduction was also observed for the patients with severe EDS who had surgery. That implies that the relative motion for these cohorts was reduced, or the SSCT is more adherent to the tendon after the intervention. The shear indices for the other patient groups were relatively increased, suggesting that the SSCT obtained slightly higher mobility in compare to the tendon. Finally, figure 4 illustrates the shear indices of each group pre and post-intervention. The SI for patients with mild EDS who had surgery was significantly higher (p = 0.014) after treatment.

Table 2.

Summary of the shear index (SI) measured for different EDS groups of CTS patients based on two intervention method.

EDS group Normal Mild Moderate Severe
Intervention method Injection Surgery Injection Surgery Injection Surgery Injection Surgery
N 14 18 14 23 11 31 9 25
SI Pre mean 82.4 81.4 76.3 75.1 77.0 82.0 73.0 84.9
SI Post mean 77.1 83.1 83.4 84.7 83.5 82.8 81.6 84.4
SI Change −5.3 +1.7 +7.1 +9.6 +6.5 +0.8 +8.6 −0.5
P-value 0.761 0.865 0.241 0.014 0.637 0.419 0.250 0.948
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Fig. 4.

Fig. 4.

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The shear indices based on different EDS groups and intervention methods. The calculated pre and post-intervention SI display a significant difference (p < 0.05) for mild EDS patients who had carpal tunnel release surgery.

4. Discussion

A reduced mobility in the carpal tunnel structures (i.e. median nerve and flexor tendon) in both transverse (Filius et al., 2015a; Nanno et al., 2017; Nanno et al., 2015) and longitudinal planes (Hough et al., 2007; Korstanje et al., 2012; Liong et al., 2014; Wang et al., 2014) has been reported for patients with CTS (Ellis et al., 2017). Additionally, synovial biopsies from CTS patients consistently show fibrosis of the SSCT (Ettema et al., 2006; Kerr et al., 1992; Ketchum, 2004; Nakamichi and Tachibana, 1998; Neal et al., 1987). Incorporating these two observations, it has been concluded that the SSCT could play an important role in the dynamic behavior of the carpal tunnel structures and in the progression of CTS (Festen-Schrier and Amadio, 2018; Lluch, 1992; Werthel et al., 2014). Hence, in this manuscript, we concentrated on the mobility of the SSCT, and implicitly associated the severity of CTS pathology with the abnormalities in the SSCT. In this regard, the relative motion of the FDS III tendon and its associated SSCT was investigated as a potential representation for intervention efficiency.

Non-invasive measurement and visualization of SSCT behavior are challenging due to its small thickness, quick and non-linear motion, and viscoelastic properties. We found that the mean shear index of CTS patients was increased after both interventions, but only significantly in the patients with mild severity disease undergoing surgery. Also, no differences in pre-post change was found when accounting for sex. As stated earlier, the increase in the post-intervention SI denotes that the SSCT is less adherent to the tendon, as one might expect if fibrosis were reduced. In a prior study (Schrier et al., 2019a), with the same test procedure and analysis method, normal subjects had a higher SI compared to CTS patients. In the current study, results showed that the mean of these indices increased from 79.9% before intervention to 82.9% after intervention. The increase in the post-intervention shear indices (3%) was not as high as the previously reported difference between the healthy and CTS patients (5%); however, the change direction shows the interventions were successful in modifying the dynamic behavior of these tissues in the patient’s carpal tunnel more toward the direction of more normal function. This finding is also in accordance with the results of a recent ultrasound assessment for CTS patients that reported a grow in transverse median nerve mobility after intervention (Schrier et al., 2019b).

Among all CTS patients with different EDS severity, we found a significant increase in the shear index only for CTS patients with mild EDS severity. Although the means of shear indices for moderate and severe CTS patients were increased after intervention, no significant association (improvement) was noted between the pre and post-intervention shear index. This observation suggests that the SSCT in the mild CTS patient may be less fibrotic and thus more responsive to treatment, especially in the relatively short term, and would therefore be more likely to recover its normal structure and gliding characteristics compared to other EDS categories. In contrast, as the severity increased in moderate and severe groups one could hypothesize that a more fibrotic SSCT might be more resistant to improvement post intervention. Further investigation shows that generally there was no association between SSCT motion changes and the intervention methods, but it is important to remember that each intervention had a different follow-up interval, 1 month for injection and 3 months for surgery. These time points were selected based on anticipated time to see clinical improvement after these interventions, but the longer time frame after surgery as well as the more invasive intervention might be expected to have a greater impact on SSCT function as well.

In the CTS literature , many studies have used the SI as an indicator of pathological change in the carpal tunnel (Filius et al., 2015b; Korstanje et al., 2012; Schrier et al., 2019a; Schrier et al., 2020; Tat et al., 2015; Van Doesburg et al., 2012). Tat et al. (2015) examined eleven self-reported CTS patients and reported a higher Doppler-based shear index (30.2% versus 21.7%, p=0.016) in comparison to healthy volunteers. This finding agreed with the published data by Van Doesburg et al. (2012), who reported a shear index of 48% in 18 CTS patients, which was higher compared to the shear index of 22 healthy participants (36%, p<0.05) (Van Doesburg et al., 2012). Two other studies have demonstrated an increase in absolute SSCT excursion and also shown the majority of CTS patients had higher SI in compare to the healthy groups (Filius et al., 2015a; Korstanje et al., 2012). Interestingly the majority of our shear index values ranged between 77–82% and 80–85% for before and after the intervention, respectively. It is unclear why the shear indicis were relatively high compared to those four published studies. A possible reason could be the sample size. In the current study, we tested 145 patients, and we found some patients with a relatively low SI (<50%) as well as some who had lower relative motion after the intervention (Figure 4). Also, various measurement techniques could cause differences in the reported SI values. For instance, Tat et al., (2015) used Doppler approach, Van Doesburg et al., (2012) and Yoshii et al., (2009a) used commercial non-adjustable speckle tracking software (SyngoVVI, Siemens Corp, Munich, Germany), while Korstanje et al., (2012) and Filius et al., (2015b) used a custom design speckle tracking code similar to the one that has been used in current study. Another possible explanation for this discrepancy might be due to our speckle tracking protocol. For instance, in this study, great consideration was taken to select an ROI for the SSCT, exactly parallel and volar to the ROI of the tendon. In contrast, in some of the other studies an area dorsal to the tendon was chosen as the ROI (Tat et al., 2015). Our approach was previously tested and validated in cadavers (Korstanje et al., 2010), and recently enhanced with a singular value decomposition (SVD) noise filter that avoids overestimation of motion detection to improve the speckle tracking algorithm. It was shown that after applying the SVD filter the noise caused by stationary tissue was removed from the ultrasound signal, leading to a more reliable representation of SSCT and tendon motion in a lab based setting (Bandaru et al., 2018). With the noise reduction included, SSCT displacement decreased, leading to the higher shear indices presented here. Although tested in an artificial setting, one of the main limitations of this study was the absence of live validation of the algorithm since we felt that (intra-operative) marking of the SSCT would not adequately represent the in vivo setting and would likely lead to disturbance of the tissue’s integrity, altering the post-intervention follow-up measurements. The inter- and intra-rater reliability of our speckle tracking procedure has been found to be quite good (Schrier et al., 2019a), so we do not think that a difference in observers explains the differences between studies.

As a limitation, the current ultrasound resolution was not sufficient to characterize the SSCT in detail, but we are optimistic that further improvement in imaging resolution will facilitate capturing more aspects of its structural change.

5. Conclusions

In conclusion, we showed the change in SI suggests that the treatment may have an effect on SSCT mechanical properties, most predominantly in patients with mild CTS severity. Also, it should be noted that the sample size in the subdivided groups was relatively small, and that might question the accuracy of our conclusions. The findings of this study need further clinical correlation to validate any association with clinical outcomes, and with other dynamic measures of carpal tunnel mechanics, such longitudinal and transverse motion of the median nerve. Finally, the results of this study imply that the dynamic sonographic assessment of the carpal tunnel structures can potentially be correlated with CTS therapy outcomes.

Highlights.

  • Carpal tunnel syndrome patients have a reduced motion of the subsynovial connective tissue

  • The suggested shear index is able to measure and indicate this relative motion between the tissues

  • Surgical release of the carpal tunnel results in a significant increase of the shear index

  • This change was mostly present in those with mild disease severity

Acknowledgement

The authors would like to acknowledge the National Institutes of Health/NIAMS (Grant AR62613) for providing funding for this work.

Footnotes

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Conflict of Interest Statement

None of the authors have any commercial associations that might pose or create a conflict of interest with information presented in the submitted manuscript. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay and direct, funds to Mayo Clinic or any other charitable or nonprofit organization with which the authors are affiliated or associated.

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