Altered brain function and structure in carpal tunnel syndrome: a systematic review and meta-analysis of structural and functional brain imaging.

This systematic review with a meta-analysis aimed to identify the altered brain structure and function in carpal tunnel syndrome (CTS) by summarizing the literature about magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) outcomes compared to healthy controls (HC). CTS is the most common nerve entrapment in the arm associated with altered peripheral and central nociceptive system. PRISMA guidelines were used to report the outcomes. Six databases were searched for relevant literature (Web of Science, Scopus, PubMed, Sage, EBSCO host, and Cochrane). Eligible studies comparing MRI, fMRI, and MEG findings in people with CTS (present for at least 2 months) and HC through the following parameters: (1) interdigit cortical separation distance, (2) white and grey matter changes, (3) peak latency of M20 wave and recovery function of N20 from the somatosensory cortex (SI), and (4) surface area of activated digit cortical representation. The results from different studies were pooled and a meta-analysis was done. From 17 included, there was a significant reduction of interdigit cortical separation distance of index-middle and index-little fingers in the CTS (SMD = - 0.869, 95% CI (- 1.325, - 0.413), p-value = 0.000) and (SMD = - 0.79, 95% CI (- 1.217, - 0.364), p-value = 0.000), respectively. Middle-little fingers interdigit separation showed no difference (SMD = - 0.2, 95% CI (- 0.903, 1.309), p-value = 0.718). There is evidence supporting the altered brain structure and function in CTS as evidenced by reduction of interdigit cortical separation distance, and excessive blurring and disinhibition of SI, with low resting state functional connectivity. Thus, centrally directed therapeutic approaches might complement peripheral treatments.

Evaluation of ultrasound as diagnostic tool in patients with clinical features suggestive of carpal tunnel syndrome in comparison to nerve conduction studies: Study protocol for a diagnostic testing study.

BACKGROUND: Carpal Tunnel Syndrome (CTS) is the most common compressive neuropathy, accounting for 90% of all neuropathies. Its prevalence ranges from 3.8%-7.8% in the population. The gold standard for its diagnosis is the neurophysiological study (85% sensitivity and 95% specificity), with the disadvantage of being invasive, complex and expensive, which means an increase in cost and time for the diagnosis of the disease. The main objective of this diagnostic test evaluation study is to investigate the value of ultrasound in the diagnosis of CTS, and among the secondary objectives, to establish the ultrasound parameters that are predictors of CTS in comparison with neurophysiological studies, attempting to standardize a protocol and reference values that determine the presence or absence of CTS. METHODS: Prospective, cross-sectional study. The reference test with which we compared the ultrasound is the neurophysiological test (NPT). Patients will come consecutively from the Neurophysiology Department of the Virgen Macarena Hospital, with clinical suspicion of CTS and fulfilling the inclusion/exclusion criteria. To calculate the sample size (EPIDAT program) we proposed a sensitivity of 78% and specificity of 87% with a confidence level of 95%, requiring 438 patients (264 NPT positive, 174 NPT negative). We followed an ultrasound study protocol that included the ultrasound variables: cross-sectional area at the entrance and exit of the tunnel, range of nerve thinning, wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and the existence of adjacent wrists or masses. We propose a timeline for the study to be performed between 2020 and 2023. Finally, we propose a cost-effectiveness analysis. DISCUSSION: Ultrasound not only allows to objectify the alterations of the median nerve but also the underlying pathological mechanisms in CTS. A multitude of ultrasound parameters have been described that should be regarded in syndrome's study, among which we included the cross-sectional area, the range of nerve thinning, the wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and assessment of anatomical alterations. The use of ultrasound as a diagnostic tool in CTS has many advantages for both doctors and the patients, as it is a non-invasive, convenient, and fast tool increasingly accessible to professionals. TRIAL REGISTRATION: Trials registry number: NCT05556278.

Comparison of the Mean Cross-sectional Area of the Median Nerve between Pregnant and Non-Pregnant Women Using Ultrasonography in a Tertiary Level Hospital, Nepal.

Background The median nerve is subjected to compression in the carpal tunnel giving rise to a constellation of symptoms known as carpal tunnel syndrome. It is the most frequent form of peripheral entrapment neuropathies and is most prevalent in the middle age females. The most common cause of this syndrome is idiopathic. One of the known secondary causes is pregnancy. Objective To compare the mean cross sectional area of median nerve using ultrasound in pregnant and non-pregnant females at carpal tunnel inlet and its variations with different trimesters. Method The study was conducted during a period of one year (October 2014 to September 2015). A total of 204 participants were evaluated among which 102 were nonpregnant and 102 were pregnant. Among the 102 pregnant participants, 34 females each were in the first, second, and third trimesters. A convenience sampling technique was used for the selection of the participants. The mean cross-sectional area of the median nerve was calculated in both of these groups in both hands by using the direct method. The mean cross-sectional area of non-pregnant female was used as the reference value to which that of pregnant female were compared. Data obtained were compiled and analyzed using Statistical Package for Social Sciences Version 16. Result The overall mean cross-sectional area of the median nerve in non-pregnant females was 6.76 ± 1.05 mm2 and in pregnant females was 6.84 ± 1.09 mm. No statistically significant difference was noted in the mean cross-sectional area of the median nerve in either hand in both pregnant and non-pregnant females. No statistically significant difference was noted in the overall mean cross-sectional area between the non-pregnant and pregnant females. There was no significant difference in the mean cross-sectional area within the different trimesters in both hands on intergroup comparisons. Conclusion Ultrasound examination of the median nerve and measurement of its crosssectional area is a useful diagnostic tool in the evaluation of carpal tunnel syndrome. Ultrasound has the advantage of easy availability, low cost, quick scan time, able to scan a long segment of nerve and examine the structures in both static and dynamic states. Besides, it also helps in the identification of various anatomic variants and pathologies within or adjacent to carpal tunnel.

Can Diffusion Tensor Imaging Apparent Diffusion Coefficient Diagnose Carpal Tunnel Syndrome? A Systematic Review and Meta-Analysis.

Magnetic resonance diffusion tensor imaging (DTI) can detect microstructural changes in peripheral nerves. Studies have reported that the median nerve apparent diffusion coefficient (ADC), a quantification of water molecule diffusion direction, is sensitive in diagnosing carpal tunnel syndrome (CTS). Five databases were searched for studies using ADC to investigate CTS. Apparent diffusion coefficient (measured in mm2/s) were pooled in random-effects meta-analyses. Twenty-two studies met criteria yielding 592 patients with CTS and 414 controls. Median nerve ADC were measured at the level of the distal radioulnar joint (CTS ADC: 1.11, 95% CI: 1.07-1.15, I2 = 54%; control ADC: 1.04, 95% CI: 1.01-1.07, I2 = 57%), pisiform (CTS ADC: 1.39, 95% CI: 1.37-1.42, I2 = 0%; control ADC: 1.27, 95% CI: 1.23-1.31, I2 = 59%), hamate (CTS ADC: 1.40, 95% CI: 1.36-1.43, I2 = 58%; control ADC: 1.27, 95% CI: 1.25-1.28, I2 = 47%), and as an combination of several measurements (CTS ADC: 1.40, 95% CI: 1.37-1.47, I2 = 100%; control ADC: 1.39, 95% CI: 1.24-1.53, I2 = 100%). Median nerve ADC is decreased in individuals with CTS compared to controls at the levels of the hamate and pisiform. ADC cut-offs to diagnose CTS should be established according to these anatomic levels and can be improved through additional studies that include use of a wrist coil.

A unique bilateral accessory forearm flexor muscle.

Muscular and neurovascular variations in the upper extremity are of utmost clinical significance. Here we report a unique bilateral accessory muscle in the forearm and palm of an 89-year-old male cadaver. The accessory muscle presented two bellies on the right side, one in the forearm, innervated by the anterior interosseous nerve, and the other in the palm, innervated by a branch of the median nerve. A long tendon interconnected the two bellies. On the left side, the muscle had a single belly in the palm, which began at the end of a long tendon that extended from the forearm. However, on both sides, the muscle originated from the posterior surface of the flexor digitorum superficialis belly and inserted along with the first lumbrical muscle into the dorsal digital expansion of the index finger. The proximal parts of the variant muscles were sandwiched between the flexor digitorum muscles. The palmar bellies coursed distally through the carpal canal and lay deep to the superficial palmar arch, and superficial to the first lumbrical, between the thenar muscles and the lateral-most tendon of the flexor digitorum superficialis. Arguably, the accessory muscle might be a variant of a lumbrical muscle, as reported before, but innervation of the proximal belly by the anterior interosseous nerve suggests that the muscle may well be a deep accessory muscle at the forearm, probably appeared as a diverted part of the flexor digitorum profundus. Its space-occupying course through the forearm and palm, especially through the carpal canal, might be clinically significant as it might contribute to nerve compression pathologies in the upper extremity. This accessory muscle also indicates the complex nature of individual muscle formation and evolution of the upper extremity with constant changes in the morphology of muscles based on their changing functions.

[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.

A new diagnostic morphological parameter for the Carpal tunnel syndrome: The palmaris longus tendon cross-sectional area.

Carpal tunnel syndrome (CTS) is correlated with increased intracarpal canal pressure (ICP). The effect of palmaris longus tendon (PLT) loading on ICP is documented in previous researches. PLT loading induces the greatest absolute increase in ICP. Therefore, to analyze the connection between the PLT and CTS, we newly made the measurement of the PLT cross-sectional area (PLTCSA). We assumed that PLTCSA is a reliable diagnostic parameter in the CTS. PLTCSA measurement data were acquired from 21 patients with CTS, and from 21 normal subjects who underwent wrist magnetic resonance imaging (W-MRI). We measured the PLTCSA at the level of pisiform on W-MRI. The PLTCSA was measured on the outlining of PLT. The two different cutoff values in the analysis were determined using receiver operating characteristic (ROC) analysis. The mean PLTCSA was 2.34 ± 0.82 mm2 in the normal group and 3.97 ± 1.18 mm2 in the CTS group. ROC curve analysis concluded that the best cutoff point for the PLTCSA was 2.81 mm2, with 76.2% sensitivity, 71.4% specificity, and area under the curve of 0.88 (95% CI, 0.78-0.98). PLTCSA is a sensitive, new, objective morphological parameter for evaluating CTS.

A deep learning approach to median nerve evaluation in ultrasound images of carpal tunnel inlet.

Ultrasound (US) imaging is recognized as a useful support for Carpal Tunnel Syndrome (CTS) assessment through the evaluation of median nerve morphology. However, US is still far to be systematically adopted to evaluate this common entrapment neuropathy, due to US intrinsic challenges, such as its operator dependency and the lack of standard protocols. To support sonographers, the present study proposes a fully-automatic deep learning approach to median nerve segmentation from US images. We collected and annotated a dataset of 246 images acquired in clinical practice involving 103 rheumatic patients, regardless of anatomical variants (bifid nerve, closed vessels). We developed a Mask R-CNN with two additional transposed layers at segmentation head to accurately segment the median nerve directly on transverse US images. We calculated the cross-sectional area (CSA) of the predicted median nerve. Proposed model achieved good performances both in median nerve detection and segmentation: Precision (Prec), Recall (Rec), Mean Average Precision (mAP) and Dice Similarity Coefficient (DSC) values are 0.916 ± 0.245, 0.938 ± 0.233, 0.936 ± 0.235 and 0.868 ± 0.201, respectively. The CSA values measured on true positive predictions were comparable with the sonographer manual measurements with a mean absolute error (MAE) of 0.918 mm2. Experimental results showed the potential of proposed model, which identified and segmented the median nerve section in normal anatomy images, while still struggling when dealing with infrequent anatomical variants. Future research will expand the dataset including a wider spectrum of normal anatomy and pathology to support sonographers in daily practice.

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.

Deep CTS: a Deep Neural Network for Identification MRI of Carpal Tunnel Syndrome.

Carpal tunnel syndrome (CTS) is a common peripheral nerve disease in adults; it can cause pain, numbness, and even muscle atrophy and will adversely affect patients' daily life and work. There are no standard diagnostic criteria that go against the early diagnosis and treatment of patients. MRI as a novel imaging technique can show the patient's condition more objectively, and several characteristics of carpal tunnel syndrome have been found. However, various image sequences, heavy artifacts, small lesion characteristics, high volume of imagine reading, and high difficulty in MRI interpretation limit its application in clinical practice. With the development of automatic image segmentation technology, the algorithm has great potential in medical imaging. The challenge is that the segmentation target is too small, and there are two categories of images with the proximal border of the carpal tunnel as the boundary. To meet the challenge, we propose an end-to-end deep learning framework called Deep CTS to segment the carpal tunnel from the MR image. The Deep CTS consists of the shape classifier with a simple convolutional neural network and the carpal tunnel region segmentation with simplified U-Net. With the specialized structure for the carpal tunnel, Deep CTS can segment the carpal tunnel region efficiently and improve the intersection over union of results. The experimental results demonstrated that the performance of the proposed deep learning framework is better than other segmentation networks for small objects. We trained the model with 333 images, tested it with 82 images, and achieved 0.63 accuracy of intersection over union and 0.17 s segmentation efficiency, which indicate great promise for the clinical application of this algorithm.

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.

Prediction of carpal tunnel syndrome using the thenar muscle cross-sectional area by magnetic resonance imaging.

ABSTRACT: Carpal tunnel syndrome (CTS) is a common neuropathy. Although CTS progression is known to be associated with thenar muscle (TM) atrophy, the diagnostic value of TM atrophy for CTS has not been established. In this research, the thenar muscle cross-sectional area (TMCSA) was evaluated to analyze the relationship between the TMCSA and CTS. We assumed that TMCSA is a major diagnostic parameter in the CTS.Both TMCSA and thenar muscle thickness (TMT) samples were acquired from 18 CTS patients, and from 18 control subjects who underwent wrist magnetic resonance imaging with no evidence of CTS. T2-weighted transverse magnetic resonance imaging images were obtained. We measured the TMCSA and TMT at the level of first carpometacarpal joint.The average TMCSA was 296.98 ±â€Š49.39 mm2 in the normal group and 203.36 ±â€Š72.13 mm2 in the CTS group. The average TMT was 8.54 ±â€Š1.45 mm in the normal group and 7.38 ±â€Š1.14 mm in the CTS group. CTS group had significantly lower TMCSA and TMT. Receiver operator characteristics curve analysis showed that the best cutoff point for the TMCSA was 260.18 mm2, with 77.8% sensitivity, 77.8% specificity. The best cutoff point of the TMT was 7.70 mm, with 61.1% sensitivity, 66.7% specificity.Although the TMCSA and TMT were both significantly associated with CTS, the TMCSA was a much more sensitive measurement parameter. Thus, to evaluate CTS patients, the physician should more carefully inspect the TMCSA than TMT.

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.

Effects of diabetes mellitus on the rate of carpal tunnel release in patients with carpal tunnel syndrome.

The objective of this study was to evaluate the effects of diabetes mellitus (DM) on the rate of carpal tunnel release (CTR) using a large nationwide cohort in Korea and to identify risk factors, including comorbidities and socioeconomic status (SES), associated with CTR. Patients with a primary or secondary diagnosis of carpal tunnel syndrome (CTS; ICD-10 code: G560) were selected and divided into two groups according to the presence of DM. A Cox proportional hazard model was used to assess the rate of CTR between the two groups. To evaluate the influence of demographic factors, comorbidities, and SES on CTR, multivariate Cox proportional hazard regression models were used to adjust for confounding variables. In total, 12,419 patients with CTS were included in the study: 2487 in DM cohort and 9932 in non-DM cohort. DM duration was negatively related with the rate of CTR (HR = 0.89, 95% CI 0.87-0.91) in CTS patients with DM. The rate of CTR was decreased in patients with DM compared to those without DM in the unadjusted model; however, after adjusting for comorbidities, DM had no significant effect on the rate of CTR. Female sex (HR = 1.50, 95% CI 1.36-1.67) correlated with the rate of CTR, and an inverse relationship between the number of comorbidities and CTR was found (p < 0.001) irrespective of DM. Diabetic polyneuropathy (DPN) was not associated with CTR, and we did not find any factors correlating with CTR in DPN patients. We found that CTS patients with more comorbidities or combined with a longer duration of DM were undertreated in real-word practice. Actual outcomes of CTR in CTS patents with various comorbidities should be investigated in future studies for optimal management of CTS.

Sonographic pattern of median nerve enlargement in Hansen's neuropathy.

OBJECTIVES: Median nerve enlargement in leprosy seems to be more proximal than in carpal tunnel syndrome (CTS), but this feature has not been studied systematically. The aim of the study was to compare the sites of median nerve enlargement in patients with leprosy with that of patients with CTS. MATERIALS AND METHODS: Transverse sections of the median nerve were recorded from wrist to the mid-forearm (at distal wrist crease and at 2-cm: M1, 4-cm: M2, 6-cm: M3, 8-cm: M4 and 10-cm: M5, proximal to the distal wrist crease in the forearm) in patients with leprosy, CTS and healthy subjects using high-resolution ultrasound. RESULTS: Twenty-six patients each with leprosy and CTS were compared with healthy controls. Patients with leprosy included 6 (23.1%), 7 (26.9%), 7 (26.9%) and 6 (23.1%) patients with borderline tuberculoid, borderline-borderline, borderline lepromatous and lepromatous leprosy, respectively. Cross-sectional area (CSA) of median nerve was increased in all patients with leprosy as compared to healthy controls at all points of measurement. CSA was higher among patients with leprosy as compared to CTS at all points except at the wrist. In patients with leprosy, the maximal enlargement was noted 2-cm (M1) proximal to the wrist crease with gradual tapering of the CSA proximally (p < .05). In contrast, in patients with CTS the median nerve was maximally enlarged at the distal wrist crease (p<.05). CONCLUSIONS: Median nerve enlargement 2-cm proximal to the distal wrist crease distinguishes leprosy from CTS. This important discriminating sign can be used at point-of-care to identify patients with leprosy.

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.

The Effect of Hamatum Curvature Angle on Carpal Tunnel Volumetry: A Mathematical Simulation Model.

In carpal tunnel volume measurements, the angle of the hamatum curvature is not considered a variable, and its effect on carpal tunnel volume has not been investigated. We hypothesize that a change in the anatomical angle of the hamatum curvature changes the carpal tunnel volume. To prove our hypothesis, we used a mathematical simulation model considering the carpal tunnel as a truncated cone. We reviewed the wrist CT scans of 91 adults (>18 years of age), including 51 men and 40 women. We measured the angle of the hamatum curvature in the CT scans. We measured cross-sectional areas at the outlet of the carpal tunnel at the level of the trapezium and hook of hamate (r1) and at the inlet at the level of the scaphoid and pisiform (r2) and the length (h) of the carpal tunnel. We attempted to calculate the effect of 2 degree by 2-degree changes in the angle of the hamatum curvature between the angles of 98° and 140° on the carpal tunnel volume. The mean angle of the hook of hamatum of the subjects was 122.55° ± 8.20° (range, 97.20° - 139.31°). No suitable cutoff point was found for the angle values. There was no difference between the gender groups according to the angle value. The data clearly show that there is a high correlation between carpal tunnel volume and the angle of hamatum curvature. The results of our study emphasize the importance of taking into account the anatomical features of the hamatum bone, especially the angle of curvature, which may play a predisposing role in idiopathic carpal tunnel syndrome.

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.

Subsynovial connective tissue thickness in carpal tunnel syndrome: A systematic review.

BACKGROUND: Non-inflammatory thickening of the subsynovial connective tissue is a common histological finding in carpal tunnel syndrome. This subsynovial connective tissue thickening may precede changes in electrodiagnostic testing. Therefore, measuring subsynovial connective tissue thickness may help in detecting early changes in carpal tunnel syndrome. METHODS: To provide an overview of subsynovial connective tissue thickness characteristics in subjects with and without carpal tunnel syndrome, a systematic review of articles, assessing human subsynovial connective tissue, was performed using MEDLINE, CENTRAL and EMBASE. FINDINGS: Seven studies were included for qualitative analysis. Measurements were done ex vivo (laser (n = 3), photographic (n = 1), micrometric (n = 1)) and in vivo (ultrasound (n = 3)). All four case-control studies showed a significant difference in subsynovial connective tissue thickness between subjects with and without carpal tunnel syndrome. One study showed good correlation between ultrasound and anatomical measurements. No correlation was found between subsynovial connective tissue thickness and symptom duration, electrodiagnostic changes, age and sex. INTERPRETATION: Subsynovial connective tissue thickness may be a valuable aid in diagnosing carpal tunnel syndrome. No factors influencing subsynovial connective tissue thickness are identified, although they are not well investigated.