Tendon injury produces changes in SSCT and nerve physiology similar to carpal tunnel syndrome in an in vivo rabbit model

Background  

The etiology of carpal tunnel syndrome (CTS) remains idiopathic in many cases. Noninflammatory fibrosis of the subsynovial connective tissue (SSCT) within the carpal tunnel is common in CTS, and some clinicians have hypothesized that this fibrosis might be a cause rather than an effect of CTS. An animal model in which to test this hypothesis would be useful. The principal objective of this study was to investigate the effect of a surgical injury on SSCT fibrosis and median nerve function within the carpal tunnel in an in vivo rabbit model.     

Dextrose-Induced Subsynovial Connective Tissue Fibrosis in the Rabbit Carpal Tunnel: A Potential Model to Study Carpal Tunnel Syndrome?

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of saline in the contralateral paw, to serve as a control. The animals were killed at 1, 2, 4, 8, or 12 weeks. While the saline side showed minimal changes at any time period, the hypertonic dextrose side showed progressive noninflammatory SSCT fibrosis, with vascular proliferation and thickening of collagen bundles. Demyelination of the median nerve developed at 12 weeks after the injection on the dextrose side. These findings are similar to the progression of pathology noted in humans with CTS.     

High-resolution ultrasound analysis of subsynovial connective tissue in human cadaver carpal tunnel.

The carpal tunnel contains the median nerve, nine flexor tendons, two synovial bursae, and peritendinous subsynovial connective tissue (SSCT). Fibrosis of the SSCT is the most consistent pathological finding in patients with carpal tunnel syndrome. We investigated the anatomy and gliding characteristics of the flexor digitorum superficialis tendon and its adjacent SSCT with high-resolution ultrasound (15 MHz). Our hypotheses were that tendon and SSCT are distinguishable by ultrasound and that their velocities during tendon excursion are different. Qualitative ultrasound analysis of a flexor tendon and its SSCT was performed on five cadaver wrists and correlated to respective findings after anatomical study of the same cadavers. Quantitative Doppler velocity analysis of eight cadaver wrists was done to assess the sliding movement of the tendon and its SSCT within the carpal tunnel. No significant difference was found between the thickness of SSCT measured by ultrasound and that measured directly after dissection. The SSCT moved slower than its flexor tendon. The SSCT velocities were statistically different from the tendon velocities (t-test, p>0.001). High-resolution ultrasound is a very precise method to display the anatomy of the tendon and SSCT within the carpal tunnel, and their different velocities can be detected with Doppler. Noninvasive assessment of the thickness and velocity of the tenosynovium in carpal tunnel syndrome by high-resolution sonography might be a new diagnostic tool for disorders affecting the SSCT, especially carpal tunnel syndrome.     

The effect of time after shear injury on the subsynovial connective tissue and median nerve within the rabbit carpal tunnel

Background

The most prominent nonneurological finding in the common compression neuropathy carpal tunnel syndrome (CTS) is fibrosis of the subsynovial connective tissue (SSCT). Recently, a rabbit model of CTS has been developed, based on the hypothesis that SSCT injury and subsequent fibrosis cause nerve compression. The purpose of this study was to evaluate the effects in this model at earlier and later time points than have heretofore been reported.

Methods

Sixty rabbits were operated on and observed at two different time periods: 6 and 24 weeks. Nerve electrophysiology (EP), SSCT histology, and SSCT mechanical properties were assessed.

Results

There was no significant difference in median motor nerve amplitude or latency at either time point. The total cell density in the SSCT was significantly higher at 6 and 24 weeks compared to controls. The mean size of the collagen fibrils in the SSCT was higher 6 and 24 weeks after surgery compared to controls. Both the ultimate load and the total energy absorption of the SSCT were significantly higher at 6 and 24 weeks compared to controls.

Conclusions

In this model, there were signs of SSCT fibrosis and histology changes at 6 weeks, which persist after 24 weeks. Thus, this model leads to sustained SSCT fibrosis, which is one characteristic of human CTS. However, no significant EP changes were found at these two time points, which is in contrast to the findings reported previously for this model at 12 weeks. The significance of the differences in EP findings will be the subject of future studies.     

Subsynovial connective tissue is sensitive to surgical interventions in a rabbit model of carpal tunnel syndrome

The most common histological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) in the tunnel. While the cause of SSCT fibrosis and the relationship of SSCT fibrosis and CTS are unknown, one hypothesis is that SSCT injury causes fibrosis, and that the fibrosis then leads to CTS. We investigated the sensitivity of the SSCT to injuries. Two types of surgical interventions were performed in a rabbit model: A skin incision with tendon laceration and SSCT stretching sufficient to damage the SSCT, and skin incision alone. Twelve weeks after surgery, the rabbit carpal tunnel tissues were studied with immunochemistry for TGF-β receptors 1, 2, and 3, collagen III, and collagen VI. All TGF-β receptors were expressed. The percentages of the TGF-β receptors' expressions were less in the control SSCT fibroblasts than in the fibroblasts from rabbits with surgical interventions. The surgical interventions did not result in any alteration of collagen III expression. However, both surgical interventions resulted in a significant decrease in collagen VI expression compared to the control group. The two surgical interventions achieved similar expression of TGF-β receptors and collagens. Our results provide evidence that the SSCT is sensitive to surgical interventions, even when these are modest. Since SSCT fibrosis is a hallmark of CTS, these data also suggest that such fibrosis could result from relatively minor trauma.     

The effect of tendon excursion velocity on longitudinal median nerve displacement: Differences between carpal tunnel syndrome patients and controls

The subsynovial connective tissue (SSCT) is a viscoelastic structure connecting the median nerve (MN) and the flexor tendons in the carpal tunnel. Increased strain rates increases stiffness in viscoelastic tissues, and thereby its capacity to transfer shear load. Therefore, tendon excursion velocity may impact the MN displacement. In carpal tunnel syndrome (CTS) the SSCT is fibrotic and may be ruptured, and this may affect MN motion. In this study, ultrasonography was performed on 14 wrists of healthy controls and 25 wrists of CTS patients during controlled finger motions performed at three different velocities. Longitudinal MN and tendon excursion were assessed using a custom speckle tracking algorithm and compared across the three different velocities. CTS patients exhibited significantly less MN motion than controls (p ≤ 0.002). While in general, MN displacement increased with increasing tendon excursion velocity (p ≤ 0.031). These findings are consistent with current knowledge of SSCT mechanics in CTS, in which in some patients the fibrotic SSCT appears to have ruptured from the tendon surface. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:483–487, 2015.     

The response of the rabbit subsynovial connective tissue to a stress-relaxation test

The subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in the etiology of carpal tunnel syndrome (CTS), yet the material properties of the SSCT remain unclear. Thus, we investigated the mechanical response of the SSCT in a rabbit model. Twenty‐four rabbit cadaver paws were used for mechanical testing; two paws were used for scanning electron microscopy (SEM) imaging. After testing normal tendon excursion, the divided third digit flexor digitorum superficialis (FDS) tendon was pulled to displacements of 2, 3.5, 5, or 8 mm, maintained at that position until force decay, and then the process was repeated. Normal excursion of the FDS averaged 4.8 mm. The ratio of the second peak force to the first peak force in the 2 mm group was 0.98 (SD = 0.16), which was significantly higher than the other groups (3.5 mm: 0.74, 5 mm, 0.63, and 8 mm: 0.59; p < 0.05). SEM showed ruptured fibrils in the displaced specimen. The declining force ratio with displacements >2 mm suggests damage to the SSCT within the physiological tendon excursion. These data may be useful in understanding SSCT mechanics in CTS, which is associated with SSCT fibrosis. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:443–447, 2012     

Multidimensional ultrasound imaging of the wrist: Changes of shape and displacement of the median nerve and tendons in carpal tunnel syndrome

Dynamics of structures within the carpal tunnel may alter in carpal tunnel syndrome (CTS) due to fibrotic changes and increased carpal tunnel pressure. Ultrasound can visualize these potential changes, making ultrasound potentially an accurate diagnostic tool. To study this, we imaged the carpal tunnel of 113 patients and 42 controls. CTS severity was classified according to validated clinical and nerve conduction study (NCS) classifications. Transversal and longitudinal displacement and shape (changes) were calculated for the median nerve, tendons and surrounding tissue. To predict diagnostic value binary logistic regression modeling was applied. Reduced longitudinal nerve displacement (p≤ 0.019), increased nerve cross‐sectional area (p≤ 0.006) and perimeter (p≤ 0.007), and a trend of relatively changed tendon displacements were seen in patients. Changes were more convincing when CTS was classified as more severe. Binary logistic modeling to diagnose CTS using ultrasound showed a sensitivity of 70–71% and specificity of 80–84%. In conclusion, CTS patients have altered dynamics of structures within the carpal tunnel. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1332–1340, 2015.     

Median nerve deformation and displacement in the carpal tunnel during index finger and thumb motion

The purpose of this study was to investigate the deformation and displacement of the normal median nerve in the carpal tunnel during index finger and thumb motion, using ultrasound. Thirty wrists from 15 asymptomatic volunteers were evaluated. Cross‐sectional images during motion from full extension to flexion of the index finger and thumb were recorded. On the initial and final frames, the median nerve, flexor pollicis longus (FPL), and index finger flexor digitorum superficialis (FDS) tendons were outlined. Coordinate data were recorded and median nerve cross‐sectional area, perimeter, aspect ratio of the minimal‐enclosing rectangle, and circularity in extension and flexion positions were calculated. During index finger flexion, the tendon moves volarly while the nerve moves radially. With thumb flexion, the tendon moves volarly, but the median nerve moves toward the ulnar side. In both motions, the area and perimeter of the median nerve in flexion were smaller than in extension. Thus, during index finger or thumb flexion, the median nerve in a healthy human subject shifts away from the index finger FDS and FPL tendons while being compressed between the tendons and the flexor retinaculum in the carpal tunnel. We are planning to compare these data with measurements in patients with carpal tunnel syndrome (CTS) and believe that these parameters may be useful tools for the assessment of CTS and carpal tunnel mechanics with ultrasound in the future. Published by Wiley Periodicals, Inc. J Orthop Res 28:1387–1390, 2010     

正中神经返支的解剖及临床研究

目的　研究正中神经返支的解剖特点 ,提高腕管综合征的手术疗效。方法　通过应用解剖观察正中神经返支在走行过程中存在的易卡因素。 2 0 0 2 -2 0 0 4年 ,对 2 3例 3 4侧腕管综合征 ,在作正中神经松解时 ,同时探查及松解正中神经返支 ,并切除对返支形成卡压的拇短屈肌尺侧缘腱纤维束和致密的纤维弓。结果　 3 4侧术中均发现正中神经返支存在易卡压解剖因素 ,其中 8侧受到纤维弓及腱纤维束的明显卡压。全部病例获得 2个月～ 1年随访。功能评定 :优 17侧 ,良 7侧 ,可 10侧 ,优良率为 70 .6%。结论　中、重度腕管综合征在松解正中神经时 ,应同时行返支松解术。     

Repetitive differential finger motion increases shear strain between the flexor tendon and subsynovial connective tissue

Non‐inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) are characteristic in carpal tunnel syndrome (CTS) patients. These pathological changes have been linked to repetitive hand tasks that create shear forces between the flexor tendons and SSCT. We measured the relative motion of the flexor digitorum superficialis tendon and SSCT during two repetitive finger tasks using color Doppler ultrasound. Twelve participants performed flexion?extension cycles for 30 min with the long finger alone (differential movement) and with all four fingers together (concurrent movement). Shear strain index (SSI, a relative measure of excursion in flexion and extension) and maximum velocity ratio (MVR, the ratio of SSCT versus tendon during flexion and extension) were used to represent shear. A linear effect of exertion time was significant and corresponded with larger tendon shear in differential motion. The flexion SSI increased 20.4% from the first to the 30th minute, while MVR decreased 8.9% in flexion and 8.7% in extension. No significant changes were found during concurrent motion. These results suggest that exposure to repetitive differential finger tasks may increase the risk of shear injury in the carpal tunnel. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1533–1539, 2013.

     

Carpal tunnel syndrome caused by a giant cell tumour of the flexor tendon sheath

Abstract

A 76-year-old woman developed right carpal tunnel syndrome after being conservatively treated for tenosynovitis of the flexor tendons with associated mild carpal tunnel syndrome. A magnetic resonance imaging scan showed a tumour in the carpal tunnel. Re-exploration showed that the median nerve was being compressed by a giant cell tumour of the flexor tendon sheaths. Appropriate imaging is advised in patients with additional findings (such as swelling) or in patients with secondary carpal tunnel syndrome and incomplete response to conservative treatment, to exclude a space-occupying lesion.     

Anatomical variations of the carpal tunnel structures

There are many anatomical variations in and around the carpal tunnel that affect the nerves, tendons and arteries in this area. Awareness of these variations is important both during the clinical examination and during carpal tunnel release. The purpose of the present review is to highlight recognized anatomical variations within the carpal tunnel including variation in nerve anatomy, tendon anatomical variants, vascular anatomical variations and muscle anatomical variations.     

Current concepts of carpal tunnel syndrome: pathophysiology, treatment, and evaluation

The current concepts of carpal tunnel syndrome (CTS) with respect to its pathophysiology, treatment, and evaluation are discussed. With regard to the pathophysiology of idiopathic CTS, biomechanical studies to determine the kinematics of the flexor tendon, and the median nerve inside the carpal tunnel may provide valuable insights. Different degrees of excursion between the flexor tendons and the median nerve could cause strain and microdamage to the synovial tissue; this has been microscopically observed. A biomechanical approach for elucidating the events that trigger the development of CTS seems interesting; however, there are limitations to its applications. Endoscopic carpal tunnel release (ECTR) is a useful technique for achieving median nerve decompression. However, it is not considered superior to conventional open carpal tunnel release in terms of fast recovery of hand function. Unless the effect of inserting a cannula into the diseased carpal tunnel on the median nerve function is quantitatively elucidated, ECTR will not be regarded as a standard procedure for relieving the median nerve from chronic compression. The treatment of CTS should be evaluated on the basis of patient-oriented questionnaires as well as conventional instruments because these questionnaires have been validated and found to be highly responsive to the treatment. It should be noted that nerve conduction studies exclusively evaluate the function of the median nerve, whereas patient-oriented questionnaires take into account not only the symptoms of CTS but other accompanying pathologies as well, such as flexor tenosynovitis. In Japan, the number of CTS patients is expected to rise; this may be attributed to a general increase in the life-span of the Japanese and increase in the number of diabetic patients. Thus, more efforts should be directed toward elucidating the pathophysiology of so-called idiopathic CTS, so that new treatment strategies can be established for CTS of different pathologies.     

Bifid median nerve as a determinant of carpal tunnel syndrome recurrence after endoscopic procedures. A case report

A number of complications have been associated with endoscopic technique in treating carpal tunnel syndrome (CTS). We observed a female patient who had previously undergone endoscopic surgery for CTS. Shortly after surgery, this patient complained of pain, numbness and strength deficiency, as severe as it was before the operation. A new, open, surgical procedure was performed. During this second-look surgery, we found a bifid median nerve, which divided into two branches at the second third of the forearm, proximal to the flexor retinaculum. We strongly suggest a careful exploration of the median nerve in the carpal tunnel. Moreover, we believe that an extensive preoperative assessment of median nerve morphology and function is mandatory prior to endoscopic approach in treating CTS.     

Carpal tunnel syndrome caused by cysticercosis

We present a case of carpal tunnel syndrome (CTS) due to compression of the median nerve within the carpal tunnel, caused by cysticercosis. Nerve conduction studies revealed severe CTS. Magnetic resonance imaging suggested an inflammatory mass compressing the median nerve in carpal tunnel. The histological diagnosis was consistent with cysticercosis. The case resolved with conservative treatment. Such solitary presentation of entrapment median neuropathy as CTS caused by cysticercosis is extremely rare. To our knowledge, this is the only case of its kind reported in literature till date.     

External Compression and Partial Ischemia Decrease Human Finger Flexor Tendon and Subsynovial Connective Tissue Relative Motion

Cumulative shear strain of the subsynovial connective tissue (SSCT) surrounding finger flexor tendons plays a significant role in the development and progression of carpal tunnel syndrome. Biomechanical risk factors can alter tendon-SSCT shear strain but the effects of external mechanical compression and localized ischemia have yet to be investigated. In a laboratory study with 19 healthy participants, color Doppler ultrasound imaging was used to quantify relative motion between the flexor digitorum superficialis tendon and SSCT during repetitive finger flexion–extension under various conditions of external mechanical compression (palmar and forearm compression), ischemia and different movement speeds (0.75 and 1.25 Hz). Forearm compression reduced tendon displacement (baseline = 28.5 ± 4.1 mm vs. forearm = 27.0 ± 4.6 mm; p = 0.043) and showed a trend for reduced SSCT displacement, while palmar compression had no significant effects on tendon-SSCT motion. Compared with baseline, partial ischemia decreased SSCT displacement (baseline = 22.9 ± 3.3 mm vs. ischemia = 22.0 ± 3.3 mm; p = 0.015), while tendon displacement remained unchanged. In all experimental conditions, faster movements elicited greater tendon-SSCT relative motion. Our findings suggest that palmar compression may not negatively impact tendon-SSCT relative motion, but forearm compression may require further investigation. Localized ischemia in the forearm may alter the gliding conditions within the carpal tunnel and affect tendon-SSCT relative motion, which bridges an important gap between blood flow in the carpal tunnel and shear injury risk. These findings contribute to the growing body of literature, supporting the role that cumulative tendon-SSCT shear injury may have on the pathomechanics of carpal tunnel syndrome. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1038-1044, 2020     

Gliding resistance of flexor tendon associated with carpal tunnel pressure: A biomechanical cadaver study

The purpose of this study was to investigate the effect of carpal tunnel pressure on the gliding characteristics of flexor tendons within the carpal tunnel. Eight fresh human cadaver wrists and hands were used. A balloon was inserted into the carpal tunnel to elevate the pressure. The mean gliding resistance of the middle finger flexor digitorum superficialis tendon was measured with the following six conditions: (1) as a baseline, before balloon insertion; (2) balloon with 0 mmHg pressure; (3) 30 mmHg; (4) 60 mmHg; (5) 90 mmHg; (6) 120 mmHg. The gliding resistance of flexor tendon gradually increased as the carpal tunnel pressure was elevated. At pressures above 60 mmHg, the increase in gliding resistance became significant compared to the baseline condition. This study helps us to understand the relationship between carpal tunnel pressure, which is elevated in the patient with carpal tunnel syndrome (CTS) and tendon gliding resistance, which is a component of the work of flexion. These findings suggest that patients with CTS may have to expend more energy to accomplish specific motions, which may in turn affect symptoms of hand pain, weakness and fatigue, seen commonly in such patients. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:58–61, 2011     

Diagnosis and staging of carpal tunnel syndrome: Comparison of magnetic resonance imaging and intra-operative findings

Summary Purpose: In order to determine the reliability of magnetic resonance imaging (MRI) in the diagnosis and staging of carpal tunnel syndrome (CTS), the most common entrapment neuropathy, the following prospective study has been performed.Methods: We compared clinical and electrophysiological studies in 58 cases of CTS with MRI investigations and confirmed the reliability by exact correspondence with intra-operative findings.Results: Typical MRI characteristics of the median nerve in CTS have been established. There is a significant difference in flattening (p < 0.05), swelling (p < 0.01) and signal intensity (p < 0.05) of the median nerve between early and advanced CTS. Comparison of MRI and intra-operative findings revealed that median nerve compression was diagnosed correctly in 91% of cases. Additional lesions in the carpal tunnel, which are a primary cause of nerve compression, were established by MRI in 25 cases and confirmed by surgery.Conclusion: MRI is a reliable diagnostic tool for assessing as well as staging of CTS. Morphological changes following chronic nerve compression can be visualized. It is particularly useful in cases of suspected lesions within the carpal tunnel as a cause of CTS. The information provided may support the choice of adequate treatment modality.