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Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor-β (TGF-β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF-β and connective tissue growth factor (CTGF), a downstream mediator of TGF-β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF-β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-β1 (p < 0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF-β1 and CTGF, (R(2) = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF-β1 (R(2) = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF-β and CTGF, a TGF-β regulated protein, and that this TGF-β activation may be responsible for SSCT fibrosis in CTS patients., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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., (Copyright © 2013 Orthopaedic Research Society.)

We investigated morphological changes of a released carpal tunnel in response to variations of carpal tunnel pressure. Pressure within the carpal tunnel is known to be elevated in patients with carpal tunnel syndrome and dependent on wrist posture. Previously, increased carpal tunnel pressure was shown to affect the morphology of the carpal tunnel with an intact transverse carpal ligament (TCL). However, the pressure-morphology relationship of the carpal tunnel after release of the TCL has not been investigated. Carpal tunnel release (CTR) was performed endoscopically on cadaveric hands and the carpal tunnel pressure was dynamically increased from 10 to 120 mmHg. Simultaneously, carpal tunnel cross-sectional images were captured by an ultrasound system, and pressure measurements were recorded by a pressure transducer. Carpal tunnel pressure significantly affected carpal arch area (p < 0.001), with an increase of >62 mm(2) at 120 mmHg. Carpal arch height, length, and width also significantly changed with carpal tunnel pressure (p < 0.05). As carpal tunnel pressure increased, carpal arch height and length increased, but the carpal arch width decreased. Analyses of the pressure-morphology relationship for a released carpal tunnel revealed a nine times greater compliance than that previously reported for a carpal tunnel with an intact TCL. This change of structural properties as a result of transecting the TCL helps explain the reduction of carpal tunnel pressure and relief of symptoms for patients after CTR surgery., (Copyright © 2012 Orthopaedic Research Society.)

Carpal tunnel mechanics is relevant to our understanding of median nerve compression in the tunnel. The compliant characteristics of the tunnel strongly influence its mechanical environment. We investigated the distensibility of the carpal tunnel in response to tunnel pressure. A custom balloon device was designed to apply controlled pressure. Tunnel cross sections were obtained using magnetic resonance imaging to derive the relationship between carpal tunnel pressure and morphological parameters at the hook of hamate. The results showed that the cross-sectional area (CSA) at the level of the hook of hamate increased, on average, by 9.2% and 14.8% at 100 and 200 mmHg, respectively. The increased CSA was attained by a shape change of the cross section, displaying increased circularity. The increase in CSA was mainly attributable to the increase of area in the carpal arch region formed by the transverse carpal ligament. The narrowing of the carpal arch width was associated with an increase in the carpal arch. We concluded that the carpal tunnel is compliant to accommodate physiological variations of the carpal tunnel pressure, and that the increase in tunnel CSA is achieved by increasing the circularity of the cross section., (Copyright © 2011 Orthopaedic Research Society.)

This study investigated the effects of loading and posture on mechanical properties of the transverse carpal ligament (TCL). Ten fresh-frozen cadaver arms were dissected to expose the TCL and positioned in the load frame of a servo-hydraulic testing machine, equipped with a load cell and custom made indenters. Four cylindrical indenters (5, 10, 20, and 35 mm) loaded the TCL in three wrist postures (30° extension, neutral and 30° flexion). Three loading cycles with a peak force of 50 N were applied at 5 N/s for each condition. The flexed wrist posture had significantly greater TCL stiffness (40.0 ± 3.3 N/mm) than the neutral (35.9 ± 3.5 N/mm, p = 0.045) and extended postures (34.9 ± 2.8 N/mm, p = 0.025). TCL stiffness using the 10 and 20 mm indenters was larger than the 5 mm indenter. Stiffness was greatest with the 20 mm indenter, which had the greatest indenter contact area on the TCL. The 35 mm indenter covered the carpal bones, compressed the carpal tunnel and produced the lowest stiffness. The complexity of the TCL makes it an important part of the carpal tunnel and the mechanical properties found are essential to understanding mechanisms of carpal tunnel syndrome. , (Copyright © 2011 Orthopaedic Research Society.)

Data on the outcome predictors of surgical result of carpal tunnel syndrome (CTS) is sparse and often conflicting. The purpose of this prospective comparative study was to evaluate the neurophysiologic findings and histological characteristics of the flexor tenosynovium in patients with CTS, assessing possible associations between these findings and preoperative patient status or surgical outcome. We evaluated 30 consecutive patients with a diagnosis of idiopathic CTS who were referred for surgery. Demographic data, subjective and objective data, and responses on an expanded assessment set, were collected before and 6 months after surgery. All patients underwent diagnostic neurophysiological testing prior to surgery, and histological analysis of tenosynovium specimens that were removed during surgery. Ten fresh-frozen cadavers served as controls. There was significant improvement in most of the disease specific (Boston questionnaire and Hi-Ob scale) and health generic (SF-36 questionnaire) evaluation tools used in the study at the 6-month follow-up. Vascular changes were noted in the tenosynovium of the flexor tendon of patients with CTS when compared with controls. Greater synovial vascularization was negative predictor of the SF-36's physical summary score before surgery. Bilateral presentation of symptoms and low nerve conduction velocity were negative predictors of the quality of life of patients after surgery for CTS. These findings have to be considered when discussing with patients as for the expected and desired outcomes of CTS surgery. The increased vascularization of flexor tenosynovium is associated with patients' functional status., (Copyright © 2011 Orthopaedic Research Society.)

Objective: This study investigated the effects of different doses of hypertonic dextrose injection on the carpal tunnel subsynovial connective tissue (SSCT) and median nerve in a rabbit model., Methods: Thirty-eight New Zealand white rabbits weighing 4.0-4.5 kg were used. One forepaw carpal tunnel was randomly injected with one of five different treatments: saline-single injection; saline-two injections 1 week apart; 10% dextrose-single injection; 20% dextrose-single injection; or 10% dextrose-two injections 1 week apart. Animals were sacrificed at 12 weeks after the initial injection and were evaluated by electrophysiology (EP), SSCT mechanical testing and histology., Results: There were significant increases in the energy absorption of the SSCT in the 10% dextrose-double injection group compared to the saline injection groups. SSCT stiffness was also significantly increased in the 10% dextrose-double injection group compared to the other groups. There was a significant increase in the thickness of the SSCT in the 10% dextrose-double injection group compared to the saline-single injection group and a significant decrease in the nerve short-long diameter ratio in the 10% dextrose-double injection group compared to the saline-single injection group. There were no changes in EP among the groups., Conclusions: SSCT fibrosis is present for up to 12 weeks after dextrose injection; multiple injections have bigger effects, including what appears to be a secondary change in nerve flattening. This model may be useful to study the effects of external fibrosis on nerve morphology and physiology, such as occurs clinically in carpal tunnel syndrome., (Copyright © 2011 Orthopaedic Research Society.)

The purpose of this study was to measure the compliance of the carpal tunnel in candidate animal models of carpal tunnel syndrome (CTS), by measuring the resistance when passing a tapered metal rod through the carpal tunnel. Forepaws from 10 dogs, 10 rabbits, and 10 rats with intact carpal tunnels, and 10 fresh frozen human wrist cadavers were used. The slopes of the linear part of the force-displacement curve (a measure of stiffness), normal force, and increasing area ratio (InAR) were significantly different among the four species (p<0.05). Post hoc analysis indicated that the mean slopes for the human carpal tunnel were the largest, indicating the least compliance, whereas those of the rat were the least (p<0.05). The features of the compliance for the dog carpal tunnel were closest to the human. The development of animal models of CTS should consider the compliance of the carpal tunnel, as it will be more difficult to increase pressure in a more compliant tunnel., (Copyright (c) 2009 Orthopaedic Research Society.)

The purpose of this study was to investigate the gliding characteristics of flexor tendons within the carpal tunnel with varied wrist positions and tendon motion styles, which may help us to understand the relationship between carpal tunnel syndrome (CTS) and repetitive hand motion. Eight fresh human cadaveric wrists and hands were used. The peak (PGR) and mean (MGR) gliding resistance of the middle finger flexor digitorum superficialis tendon were measured with the wrist in 0, 30, and 60 degrees of flexion and extension. While moving all three fingers together, the PGR at 60 degrees flexion was significantly higher than that at 0, 30, or 60 degrees extension. While moving the middle finger alone, the PGR at 60 and 30 degrees flexion was significantly higher than the PGR at 60 degrees extension. The PGR moving the middle finger FDS alone was significantly greater than that for all three digits moving together in 0, 30, and 60 degrees flexion. Differential finger motion with wrist flexion elevated the tendon gliding resistance in the carpal tunnel, which may be relevant in considering the possible role of wrist position and activity in the etiology of CTS.

The tenosynovium within the carpal tunnel consists of a single layer of synovial cells, which lines the bursae within the carpal tunnel, and the subsynovial connective tissue (SSCT), which contains the tendon vasculature and other structural elements. In this study, we used immunogold labeling to localize collagen types within the SSCT in three cadaver specimens and three patients with carpal tunnel syndrome. Positive labeling for collagen types I, III and VI was found with immunoelectron microscopy. Collagen types I and III were codistributed within the SSCT. Type VI was primarily located in microfibrillar structures between collagen bundles, between elastin and collagen bundles and between collagen bundles and cells. There was no difference in the distribution of collagen types when comparing cadaver specimens and carpal tunnel patients.

We used the Verhoeff-van Gieson stain method to identify histopathology and to localize elastin in the subsynovial connective tissue of the tendon sheath (SSCT) of the middle finger flexor digitorum superficialis (FDS) within the carpal tunnel in 10 carpal tunnel syndrome (CTS) patients and 10 control cadaver specimens. Normal SSCT stained for elastin abundantly around blood vessels and within vessel walls. The typical pathologic findings of CTS patients SSCT included vascular proliferation, vascular hypertrophy, and vascular obstruction with wall thickening. There was a decreased amount of elastin in the blood vessel walls and around the vessels in the CTS patients as well. The changes in the carpal tunnel patients were particularly remarkable in that the patients were younger than the controls, yet showed findings more characteristic of chronic degeneration.