[MEDIAN NERVE COMPRESSION BY LIPOMA CAN MIMIC CARPAL TUNNEL SYNDROME].

INTRODUCTION: Lipoma of the nerve is an uncommon tumor, and usually has the highest incidence in the upper limb, especially in the median nerve. When the lesion is large it can cause peripheral neuropathy such as carpal tunnel syndrome. Therefore, a physical examination is paramount for correct surgery and patient preparation. In this article we present a case that was mainly diagnosed by a complete physical examination, which led to the selection of appropriate surgery for the patient.

Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome.

Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as 'regenerators' or 'non-regenerators' based on post-surgical epidermal re-innervation. We demonstrate that patients with CTS have lower GAP-43 positive intra-epidermal nerve fibre density (IENFD) before surgery than healthy controls. However, this difference disappears when normalising for total IENFD. Of note, we found surgery did not change GAP-43 expression in IENF, with no differences both in patients who were classified as regenerators and non-regenerators. We also did not identify pre-post surgical differences in cutaneous GAP-43 gene expression or associations with regeneration. These findings suggest cutaneous GAP-43 may not be a compelling marker for nerve regeneration in humans.

Ultrasound Findings in Patients with Normal Nerve Conduction despite Clinical Signs and Symptoms Consistent with Carpal Tunnel Syndrome.

BACKGROUND: Confirmatory methods such as nerve conduction studies are often performed to support a clinical carpal tunnel syndrome diagnosis and to rule out other upper extremity pathologies. Ultrasonography provides another diagnostic option, especially when nerve conduction studies are discordant with history and physical examination. The authors explored the correlation of ultrasound findings with clinical carpal tunnel syndrome diagnosis in patients with normal nerve conduction study results. METHODS: A database of 220 patients with carpal tunnel syndrome was analyzed retrospectively to reveal 24 patients (28 hands) with a clinical diagnosis and normal nerve conduction study results. Patient demographics and nerve conduction study and ultrasound findings were compared with those of a control group of patients without carpal tunnel syndrome (42 patients, 52 hands). Median nerve cross-sectional area was recorded; values of 10 mm 2 or greater were considered positive for carpal tunnel. Statistical and correlation analyses were performed between control and carpal tunnel groups comparing key measures of interest. RESULTS: Mean cross-sectional area was significantly increased in patients with carpal tunnel syndrome with normal nerve conduction study results compared with controls. The proportion of carpal tunnel-positive, nerve conduction study-negative patients with cross-sectional area measurements greater than 10 mm 2 was significantly greater than the proportion for control patients. Neither age nor body mass index correlated with cross-sectional area measurements. Nerve conduction study latencies and amplitudes did not correlate with ultrasound abnormalities. CONCLUSIONS: Patients diagnosed clinically with carpal tunnel syndrome with normal nerve conduction study results were found to have clinically significant median nerve cross-sectional area on ultrasound (10.1 ±2.1 mm 2 , p < 0.001). Cross-sectional area measurements on ultrasound did not correlate with nerve conduction study measures. These results suggest that ultrasound holds a unique diagnostic utility in the evaluation of carpal tunnel syndrome, especially when nerve conduction studies are negative. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

High-resolution ultrasound in the diagnosis of failed carpal tunnel decompression: a study of 35 cases.

We used high-resolution ultrasound to examine 35 median nerves (35 patients) with failed carpal tunnel decompression to identify the cause of failure. The carpal tunnel was examined before revision surgery, and the results were correlated with surgical findings. The cross-sectional area was measured, and nerve morphology was analysed at the sites of compression. We found persistent median nerve compression in 30 out of 35 patients. In 20 patients, the compression was caused by a residual transverse carpal ligament, in four by perineural fibrosis, in five by both of these causes and in one by tenosynovitis. In four patients, evidence of median nerve injury with an epineural/fascicular lesion was detected; and in one, no abnormalities were found. Surgical findings were consistent with the ultrasound findings except in one patient where tenosynovitis was associated with a giant cell tumour, which was missed by ultrasound. High-resolution ultrasound can provide helpful information in preoperative diagnosis of failed carpal tunnel decompression with good correlation between the ultrasound and surgical findings.Level of evidence: IV.

Cardiac Amyloidosis Screening at Trigger Finger Release Surgery.

Cardiac amyloidosis is often preceded by orthopedic manifestations such as carpal tunnel syndrome, and 10% of patients who underwent idiopathic carpal tunnel release surgery will have biopsy-confirmed amyloid deposits in the tenosynovial sheath. Trigger finger is also commonly reported in patients with amyloidosis and involves the same tendon sheath as carpal tunnel syndrome, but the prevalence of amyloid deposition is unclear. This prospective cross-sectional study enrolled 100 patients aged ≥50 years at the time of surgery for idiopathic trigger finger. Patients underwent release surgery, and a sample of the tenosynovium of the affected finger was excised, stained with Congo red, and subtyped with mass spectrometry if amyloid was demonstrated. Further cardiac evaluation was performed in patients with amyloid deposition. Of the 100 patients (mean age 65.5 ± 8.1 years) enrolled, only 2 demonstrated amyloid deposits on Congo red staining. One patient with previous proteinuric kidney disease had fibrinogen A α-chain amyloidosis, and the other patient had untyped amyloidosis. Neither patient had cardiac involvement. A total of 13 of the 100 patients underwent concomitant carpal tunnel release surgery, and 2 of these patients had amyloid deposits in the carpal tunnel with "false-negative" samples from the trigger finger tenosynovium. In conclusion, biopsy during trigger finger release surgery demonstrated a 2% yield for amyloidosis, which is significantly lower than the previously published yield of 10% during carpal tunnel release surgery. This observation has important implications for the development of diagnostic algorithms to screen patients for amyloidosis during orthopedic operations.

Systemic Amyloidosis Caused by Monoclonal Immunoglobulins: Soft Tissue and Vascular Involvement.

Clinical features of soft tissue amyloid light-chain (AL) amyloidosis include macroglossia, arthropathy, muscle pseudohypertrophy, skin plaques, and carpal tunnel syndrome. Vascular manifestations of AL amyloid include periorbital ecchymosis, jaw or limb claudication, and even myocardial infarction caused by occlusion of small vessel coronary arteries. Some of these features, such as macroglossia, periorbital ecchymosis, and the so-called shoulder-pad sign, are pathognomonic for AL amyloidosis. These findings may be the initial presenting features of the disease, and the recognition of these red flag symptoms is very important for the diagnosis and early intervention on the underlying plasma cell disease.

Mutations in COMP cause familial carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, affecting a large proportion of the general population. Genetic susceptibility has been implicated in CTS, but the causative genes remain elusive. Here, we report the identification of two mutations in cartilage oligomeric matrix protein (COMP) that segregate with CTS in two large families with or without multiple epiphyseal dysplasia (MED). Both mutations impair the secretion of COMP by tenocytes, but the mutation associated with MED also perturbs its secretion in chondrocytes. Further functional characterization of the CTS-specific mutation reveals similar histological and molecular changes of tendons/ligaments in patients' biopsies and the mouse models. The mutant COMP fails to oligomerize properly and is trapped in the ER, resulting in ER stress-induced unfolded protein response and cell death, leading to inflammation, progressive fibrosis and cell composition change in tendons/ligaments. The extracellular matrix (ECM) organization is also altered. Our studies uncover a previously unrecognized mechanism in CTS pathogenesis.

Risk factors for carpal tunnel syndrome or trigger finger following distal radius fracture: a nationwide study.

New-onset carpal tunnel syndrome (CTS) and trigger finger after distal radius fractures (DRFs) with or without open reduction and internal fixation (ORIF) have been reported inconsistently across different studies. This study assessed the incidence of CTS and trigger finger after DRFs using Taiwan National Health Insurance Research Database. In total, 1454 patients in the case (ORIF) cohort and 1454 patients in the control (non-ORIF) cohort were included in this retrospective study. The mean age was approximately 55 years old, and the female to male ratio was approximately 3/2. Nine patients underwent carpal tunnel release (CTR) surgery after diagnosis of CTS in the case group, and no patients did in the control group; whereas 19 cases of CTS were diagnosed without CTR in the case group, and 4 such cases were observed in the control group. Five cases of trigger finger were diagnosed in the case group, and 3 cases were diagnosed in the control group. CTS were significantly associated with ORIF for DRFs within 9 months after the fracture, whereas trigger finger was not significantly different between groups. Diabetes mellitus was a significant risk factor for CTS and trigger finger within 9 months after the incidence of DRFs.

Investigating the effects of Pirfenidone on TGF-ß1 stimulated non-SMAD signaling pathways in Dupuytren's disease -derived fibroblasts.

BACKGROUND: Dupuytren's disease (DD) is a progressive, debilitating condition of the hand that can eventually cause contractures of the affected fingers. Transforming growth factor- ß1 (TGF-ß1) has been reported to play a key role in DD pathology. Increased expression of TGF-ß1 has shown to be the main stimulator of myofibroblast activity and in DD contractures. Pirfenidone (PFD), a small active molecule possess the ability to inhibit TGF-ß1-mediated action in various fibrotic disorders. Our recent published findings show that PFD reduced TGF-ß1-mediated cellular functions implicated in DD through SMAD signaling pathways. In the present study, the effect of PFD on TGF-ß1-mediated non-SMAD signaling pathways were investigated in both carpal tunnel (CT) - and DD-derived fibroblasts. METHODS: Fibroblasts harvested from Dupuytren's disease (DD) and carpal tunnel (CT) tissues were cultured in the presence or absence of TGF-ß1 (10 ng/ml) and/or PFD (800 µg/ml). Cell lysates were analyzed using Western blots. Equal amounts of proteins were loaded to determine the phosphorylation levels of phosphatidylinositol-3 kinase (PI3K/AKT), extracellular regulated kinases (ERK1/2), p38 mitogen-activated protein kinase and Rho family related myosin light chain (MLC). RESULTS: We show that the TGF-ß1-induced phosphorylation of AKT was significantly decreased by the addition of PFD (800 µg/mL) in both CT- and DD-derived fibroblasts. Interestingly, there was no significant difference in the phosphorylation levels of both ERK and p38 on TGF-ß1- induced cells in both CT-and DD-derived fibroblasts. But, PFD significantly decreased the TGF- ß1-induced phosphorylation levels of ERK1/2 in both CT- and DD- cells. In contrast, PFD significantly decreased the basal and TGF- ß1-induced phosphorylation levels of p38 in DD-derived fibroblasts. TGF- ß1-induced phosphorylation levels of MLC was decreased by PFD in DD-derived fibroblasts. CONCLUSIONS: These in-vitro results indicate for the first time that PFD has the potential to inhibit TGF-ß1-induced non-SMAD signaling pathways in both CT- and DD-derived fibroblasts but pronounced statistically significant inhibition on all molecules was observed only in DD-derived fibroblasts. Our previous studies show that PFD can inhibit TGF-ß1- induced SMAD signaling pathway proteins, namely p- SMAD2/SMAD3. These broad and complementary actions suggest PFD as a promising candidate to inhibit the TGF-ß1- mediated molecular mechanisms leading to DD fibrosis.

Carpal tunnel release with versus without flexor retinaculum reconstruction for carpal tunnel syndrome at short- and long-term follow up-A meta-analysis of randomized controlled trials.

BACKGROUND: Carpal tunnel syndrome is a common neuropathy disorder for which surgical treatment consists of release and reconstruction of the flexor retinaculum. Reports of postoperative clinical outcomes after carpal tunnel release with or without flexor retinaculum reconstruction in several studies are controversial. This meta-analysis aimed to compare the efficacy and safety of carpal tunnel release with or without flexor retinaculum reconstruction. METHODS: The PubMed, EMBASE, Web of Science, Ovid, Cochrane Library and Clinical Tri Org databases were searched for randomized controlled trials that compared carpal release with and without transverse carpal ligament reconstruction for carpal tunnel syndrome. Outcomes included postoperative Boston Carpal Tunnel Questionnaire Symptom Severity Scale (SSS), Functional Status Scale (FSS), grip strength and complications. The follow-up time was categorized into short-term (0-3mon) and long-term(>3mon). RESULTS: A total of 7 studies with 613 patients met the inclusion criteria and were analyzed in detail. Statistical analysis showed no significant difference between two groups on postoperative long-term grip strength (MD 5.85, 95% CI -1.05 to 12.76) long-term SSS (MD -0.31, 95% CI -0.75 to 0.13) and occurrence of complications (RR 1.14, 95% CI 0.84 to 1.54), whereas statistically significant difference was found between groups regarding short-term grip strength (MD 1.51, 95% CI 0.86 to 2.17) and long-term FSS (MD -0.34, 95% CI -0.47 to -0.21). CONCLUSION: Carpal tunnel release with flexor retinaculum reconstruction for carpal tunnel syndrome may result in improved long-term functional status while there's no advantage regarding grip strength, symptom severity and safety over individual carpal tunnel release in short- and long-term outcomes.

Ultrasound-Guided Hydroneurolysis of the Median Nerve for Recurrent Carpal Tunnel Syndrome.

BACKGROUND: Recurrent carpal tunnel syndrome is often associated with perineural scarring around the median nerve. Surgical options include relatively invasive procedures, such as fat pad grafting, ligament reconstruction, muscle transfer, and nerve wraps. All have limited success because of the possibility of repeated recurrent scarring postoperatively. METHODS: We discuss a technique involving injection with external hydroneurolysis of the median nerve under ultrasound guidance for recurrent carpal tunnel. Injection enables a gentler dissection of the surrounding tissues compared with open external neurolysis, with less chance of recurrent scarring. This technique is a unique alternative to repeat operative intervention in recurrent carpal tunnel, as well as a prelude to repeat open decompression and salvage procedures. RESULTS: Ultrasound-guided injection with external hydroneurolysis of the median nerve is a safer, more limited procedure compared with repeat open surgery, usually performed in an office setting. This procedure limits risk, anesthesia, and operating/recovery room expenses, offering relief in 70% to 80% of cases. Furthermore, in the 20% to 30% of patients with inadequate relief, surgery remains a viable option. US provides important information on the anatomy of the median nerve and carpal canal and can rule out covert pathology. CONCLUSIONS: We offer an alternative treatment for recurrent carpal tunnel syndrome, a difficult problem for which many surgeons recommend nonoperative treatment. US provides objective data concerning residual nerve compression and allows for dynamic assessment. Theoretically, this also offers a viable solution for surgeons and their patients with recurrent carpal tunnel syndrome before being pressed to consider repeat open surgery.

Carpal Tunnel Syndrome: Evaluation of the Effects of Low-Level Laser Therapy With Ultrasound Strain Imaging.

OBJECTIVES: To evaluate the efficacy of low-level laser therapy on median nerve stiffness by using strain elastography in carpal tunnel syndrome (CTS). METHODS: This study included 37 wrists of 34 patients with mild or moderate CTS between January 2016 and August 2016. The control group comprised 17 patients (18 wrists) with CTS who were treated with wrist splinting for 3 weeks. The low-level laser therapy group included 17 patients (19 wrists) with CTS who were treated with a combination of splinting and low-level laser therapy, which was applied 5 times per week for 3 weeks. Clinical assessment scales, including the Symptom Severity Scale (SSS) and Functional Status Score (FSS), were obtained from our database. The cross-sectional area by ultrasound and strain ratio by elastography were studied. The differences in the strain ratio, cross-sectional area, SSS, and FSS between pretreatment and posttreatment periods in the groups were compared by the paired-sample t test. The correlations between changes in the strain ratio and the cross-sectional area, SSS, and FSS were analyzed by Pearson correlation coefficients. RESULTS: The control group included 13 women and 4 men, and the therapy group included 14 women and 3 men. In the therapy group, the mean values of the strain ratio, cross-sectional area, SSS, and FSS decreased significantly after laser therapy (P < .001) in contrast to the control group. No significant correlation was observed between the decreasing degree of the strain ratio and the cross-sectional area, SSS, and FSS after laser therapy. CONCLUSIONS: The strain ratio and cross-sectional area of the median nerve decrease after low-level laser therapy. These changes may be related to the therapeutic effects of low-level laser therapy, such as nerve regeneration and improvement of the vascular supply.

Histopathologic Evaluation of Flexor Tenosynovium in Recurrent Carpal Tunnel Syndrome.

BACKGROUND: The authors' purpose was to evaluate the histopathology of flexor tenosynovium in true, idiopathic recurrent carpal tunnel syndrome for the presence of abnormal inflammatory or pathologic findings that might explain causation or that differ from those previously described for primary, idiopathic carpal tunnel syndrome. METHODS: Thirty-five patients (19 women and 16 men; mean age, 72 years) underwent open revision carpal tunnel release a mean 13 years (range, 0.5 to 30 years) after primary carpal tunnel release. Recurrence was confirmed by recurrent symptoms, positive provocative tests, and electrodiagnostic testing. All patients underwent tenosynovial biopsy, including Congo red staining for amyloid. RESULTS: Histopathologic findings demonstrated noninflammatory, fibrous connective tissue in 31 of 35 patients (89 percent); and mild, chronic inflammation (without granulomas) in four of 35 patients (11 percent). Nine of 35 patients (26 percent) had positive results for amyloid, with a statistically higher incidence in men (p = 0.03) and advanced age (p = 0.02). Subtyping performed in eight of nine amyloid-positive specimens confirmed seven cases of transthyretin-type amyloid typically seen in localized (senile) amyloidosis and one case of light-chain amyloid in a patient who was subsequently diagnosed with myeloma. CONCLUSIONS: Flexor tenosynovium in patients with recurrent carpal tunnel syndrome does not appear to be substantially different histologically from that previously described in primary idiopathic carpal tunnel syndrome, although a slightly higher prevalence of amyloid was seen in this group (especially older men). No patients have developed systemic amyloidosis. Routine biopsy of tenosynovium in idiopathic, recurrent carpal tunnel syndrome is unnecessary.

Neurophysiological study of the radial nerve variant in the innervation of the dorsomedial surface of the hand.

INTRODUCTION: Sensory innervation of the dorsomedial surface of the hand usually depends on the dorsal ulnar nerve (DUN). Innervation in this area by the superficial radial nerve (SRN) has been described as a normal variant. METHODS: We studied 358 patients using nerve conduction of the DUN and SRN with dorsomedial recording. Each hand was classified into usual innervation (only DUN response), mixed variant (response of both nerves), or complete variant (only SRN response). RESULTS: Mixed innervation was found in 14.2% of hands and complete innervation was found in 6.8% of hands, mostly unilaterally. No statistically significant differences were observed in age, sex, or clinical suspicion between usual and variant innervation. The potential amplitude after SRN stimulation was greater in the complete variant. DISCUSSION: It is important to know the characteristics of this variant in order to avoid diagnostic errors and to prevent iatrogenic lesions in surgery performed on the dorsum of the wrist. Muscle Nerve 58: 732-735, 2018.

Blocking fibrotic signaling in fibroblasts from patients with carpal tunnel syndrome.

Fibrosis of the subsynovial connective tissue (SSCT) in carpal tunnel syndrome (CTS) patients is increasingly recognized as an important aspect of CTS pathophysiology. In this study, we evaluated the effect of blocking profibrotic pathways in fibroblasts from the SSCT in CTS patients. Fibroblasts were stimulated with transforming growth factor ß1 (TGF-ß1), and then treated either with a specific fibrosis pathway inhibitor targeting TGF-ß receptor type 1 (TßRI), platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), or vascular endothelial growth factor receptor (VEGFR). Fibrosis array and quantitative real-time polymerase chain reaction of fibrotic genes were evaluated. Array gene expression analysis revealed significant down-regulation of multiple fibrotic genes after treatment with TßRI, PDGFR, and VEGFR inhibitors. No array fibrotic genes were significantly down-regulated with EGFR inhibition. Further gene expression analysis of known CTS fibrosis markers collagen type I A2 (Col1), collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 showed significantly down-regulation after TßRI inhibition. In contrast, VEGFR inhibition significantly down-regulated CTGF and SERPINE1, whereas, PDGFR and EGFR inhibition significantly down-regulated Col3. Taken together the inhibition of TßRI appears to be the primary mediator of fibrotic gene expression in fibroblasts from CTS patients. TGF-ß/Smad activity was further evaluated, and as expected inhibition of Smad activity was significantly down-regulated after inhibition of TßRI, but not with PDGFR, VEGFR, or EGFR inhibition. These results indicate that local therapies specifically targeting TGF-ß signaling alone or in combination offer the potential of a novel local antifibrosis therapy for patients with CTS.

Ultrasound Imaging of Median Nerve Conduit in a Patient With Persistent Median Nerve Symptoms.

Peripheral nerve injury can be reconstructed using composite polymer nerve autografts, but the sonographic appearance of nerve wraps and conduits have not been well documented. This case report describes the sonographic findings in a 42-year-old woman with bilateral carpal tunnel syndrome status post nerve repair with a conduit. The cross-sectional area of the left median nerve was 24 mm at the carpal tunnel inlet and 5 mm at the forearm. The wrist to forearm ratio was 4.8. There was a hypoechoic space surrounding the nerve that was 1.8 to 1.9 mm thick and bordered by a thin, hyperechoic outer rim. On review of the operative record and consultation with her surgeon (DR), it was determined that this represented the 2-mm nerve wrap used in the last surgery. Inclusion of these structures with the median nerve measured a total area of 52 mm at its maximum. In describing this image, we hope to lay the foundation for describing the sonographic appearance of peripheral nerve repair.

Cross-sectional Area of the Median Nerve Before Revision Carpal Tunnel Release-A Cross-sectional Study.

BACKGROUND: High-resolution ultrasound can be used for diagnosis of carpal tunnel syndrome with an equal accuracy to electrodiagnostic studies. Up to date there has been no investigation published that examined the median nerve in a large patient cohort with recurrent or persistent symptoms. Reference and cutoff values are lacking. OBJECTIVE: To provide reference values for detection of ongoing or recurrent compression in patients with recurring or persisting symptoms in carpal tunnel syndrome. METHODS: One hundred and sixteen patients undergoing revision decompression of the median nerve at the carpal tunnel between January 2010 and October 2015 were studied retrospectively to determine the cross-sectional area of the median nerve at the wrist by the technique of neurosonography. RESULTS: In cases of insufficient primary release, the mean cross-sectional area was 20.0 mm2 preop. In cases of scar or synovitis, the mean cross-sectional area was 17.0 mm2 (significantly less than in cases of insufficient primary release, P = .008). Compared to successfully operated patients with de novo carpal tunnel syndrome (n = 74), a cutoff value of 14.5 mm2 yielded a sensitivity of 78% and a specificity of 97% to diagnose ongoing or recurrent compression in case of a typical clinical presentation of ongoing or recurrent symptoms (tested via comparison of patients who are symptom free vs patients with symptoms). CONCLUSION: For the first time, we provide reference values in patients with recurring or persisting symptoms in carpal tunnel syndrome based on a large patient population. Ultrasound can aid in the evaluation of patients with entrapment neuropathy of the median nerve and recurring or persisting symptoms.