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Carpal tunnel syndrome is the most common peripheral nerve entrapment encountered worldwide. The aetiology can be related to repetitive exposure to vibrations or forceful angular motions, genetic predisposition, injury and specific conditions, such as diabetes, pregnancy and morbid obesity. This entity is observed with increased frequency in females and the elderly. The diagnosis is largely clinical and suspected when patients present with typical symptoms such as numbness, tingling, nocturnal paraesthesia and/or neuritic “pins-and-needles” pain in the radial 3.5 digits. Certain provocative manoeuvres can be employed to evoke the symptoms of the disease to guide the diagnosis. Further testing such as electrodiagnostic studies, ultrasound or magnetic resonance imaging is required in the case of diagnostic uncertainty or if there is a need for objective evaluation whether or not more invasive surgical intervention is required. If the presenting symptoms are mild and discontinuous, non-surgical measures are indicated. However, if the symptoms are moderate to severe, further testing modalities such as nerve conduction studies or needle electromyography are used to determine whether carpal tunnel syndrome is acute or chronic. If significant evidence of axonal injury is identified, surgical treatment may be indicated. Surgical release of the carpal tunnel has evolved over time to become the most common hand surgery procedure.

Background Between 2001 and 2010, five research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries and collected detailed subject-level exposure information with follow-up of symptoms, electrophysiological measures and job changes. Objective This analysis examined the associations between workplace biomechanical factors and incidence of dominant-hand CTS, adjusting for personal risk factors. Methods 2474 participants, without CTS or possible polyneuropathy at enrolment, were followed up to 6.5 years (5102 person-years). Individual workplace exposure measures of the dominant hand were collected for each task and included force, repetition, duty cycle and posture. Task exposures were combined across the workweek using time-weighted averaging to estimate job-level exposures. CTS case-criteria were based on symptoms and results of electrophysiological testing. HRs were estimated using Cox proportional hazard models. Results After adjustment for covariates, analyst (HR=2.17; 95% CI 1.38 to 3.43) and worker (HR=2.08; 95% CI 1.31 to 3.39) estimated peak hand force, forceful repetition rate (HR=1.84; 95% CI 1.19 to 2.86) and per cent time spent (eg, duty cycle) in forceful hand exertions (HR=2.05; 95% CI 1.34 to 3.15) were associated with increased risk of incident CTS. Associations were not observed between total hand repetition rate, per cent duration of all hand exertions, or wrist posture and incident CTS. Conclusions In this prospective multicentre study of production and service workers, measures of exposure to forceful hand exertion were associated with incident CTS after controlling for important covariates. These findings may influence the design of workplace safety programmes for preventing work-related CTS.

BackgroundWork-related musculoskeletal disorders (WMSDs) are a growing and probably undervalued concern for neurosurgeons and spine surgeons, as they can impact their quality of life and career length. This systematic review aims to ascertain this association and to search for preventive measures.MethodsWe conducted a PRISMA-P-based review on ergonomics and WMSDs in neurosurgery over the last 15 years. Twelve original articles were included, of which 6 focused on spine surgery ergonomics, 5 cranio-facial surgery (mainly endoscopic), and one on both domains.ResultsWe found a huge methodological and content diversity among studies with 5 surveys, 3 cross-sectional studies, 2 retrospective cohorts, and 2 technical notes. Spine surgeons have sustained neck flexion and neglect their posture during surgery. In a survey, low back pain was found in 62% of surgeons, 31% of them with a diagnosed lumbar disc herniation, and 23% of surgery rate. Pain in the neck (59%), shoulder (49%), finger (31%), and wrist (25%) are more frequent than in the general population. Carpal tunnel syndrome showed a linear relationship with increasing cumulative hours of spine surgery practice. Among cranial procedures, endoscopy was also significantly related to shoulder pain while pineal region surgery received some attempts to optimize ergonomics.ConclusionsErgonomics in neurosurgery remains underreported and lack attention from surgeons and authorities. Improvements shall target postural ergonomics, equipment design, weekly schedule adaptation, and exercise.

To study the association between occupational co-exposure to biomechanical risk factors, potentially neurotoxic chemicals and carpal tunnel syndrome (CTS) in a large cohort of French workers, using two methods to estimate chemical exposure: job-exposure matrices (JEM) and self-reported exposure. A randomly selected sample of adults were included between 2012 and 2018 in the French cohort CONSTANCES. Self-reported CTS was assessed using the first self-administered follow-up questionnaire, sent out approximately one year after baseline. Occupational exposure to biomechanical risk factors was assessed using self-administered questionnaire completed at inclusion. Lifetime occupational exposure to chemicals was assessed using two different methods: with JEMs and with a self-administered questionnaire completed at inclusion. Multivariate logistic regression models were used to evaluate the association between co-exposure to biomechanical risk factors and chemicals and CTS, adjusted for personal and medical factors and stratified by gender. For the analysis using JEM assessment, 35,941 workers (16,920 men and 19,021 women) were included: 261 men (1.5%) and 469 women (2.5%) declared having CTS at follow-up. There was an association between CTS and the co-exposure group: OR=2.37 [1.60-3.44] in men and OR=2.09 [1.55-2.77] in women, compared to the non-exposed group. For the self-reported chemicals analysis, 42,168 workers (20,877 men and 21,291 women) were included: 338 men (1.6%) and 532 women (2.5%) declared having CTS at follow-up. There was an association between CTS and the co-exposure group: OR=3.07 [2.28-4.08] in men and OR=2.68 [1.91-3.66] in women, compared to the non-exposed group. The study showed an association between self- reported CTS and co-exposure to biomechanical risk factors and chemicals. This finding should be confirmed using more objective case definition of CTS, e.g. carpal tunnel release surgery.

ObjectivesTo prospectively determine the association between occupational biomechanical exposures and the incidence of surgically treated carpal tunnel syndrome (CTS) in Swedish male construction workers.MethodsA cohort of 203 866 Swedish male construction workers who participated in a national occupational health surveillance programme between 1971 and 1993 were followed for CTS surgery between 2001 and 2019. Age, height, weight, smoking status and construction trade were obtained from programme records. CTS surgery cases were defined using the diagnostic code for CTS and surgical procedure code for peripheral median nerve decompression in the Swedish National Patient Register. Biomechanical exposure estimates were assigned by trade from a job-exposure matrix. The relative risk (RR) of CTS surgery for each biomechanical exposure was assessed with multivariable negative binomial regression modelling.ResultsThe study included 3851 cases and the total incidence rate of CTS surgery was 137.6 cases per 100 000 person-years. Associations were found for upper extremity load (RR 2.6; 95% CI 2.2 to 3.0), repetitive wrist flexion and extension (RR 2.6; 95% CI 2.2 to 3.0), full wrist extension (RR 2.3; 95% CI 1.9 to 2.6), power grip (RR 2.5; 95% CI 2.2 to 2.9), pinch grip (RR 2.0; 95% CI 1.7 to 2.4), handheld tool use (RR 2.3; 95% CI 2.0 to 2.7) and hand-arm vibration exposure (RR 2.3; 95% CI 1.9 to 2.7).ConclusionsOccupational upper extremity load and postural exposures were associated with increased risk for surgical treatment for CTS in this large construction worker cohort. Preventive actions and consideration of occupation on assessment are warranted.

This systematic review summarizes the evidence on associations between physical and psychosocial work-related exposures and the development of carpal tunnel syndrome (CTS). Relevant databases were searched up to January 2020 for cohort studies reporting associations between work-related physical or psychosocial risk factors and the incidence of CTS. Two independent reviewers selected eligible studies, extracted relevant data, and assessed risk of bias (RoB). We identified fourteen articles for inclusion which reported data from nine cohort studies. Eight reported associations between physical exposure and the incidence of CTS and five reported associations between psychosocial exposures and the incidence of CTS. Quality items were generally rated as unclear or low RoB. Work-related physical exposure factors including high levels of repetition, velocity, and a combination of multiple physical exposures were associated with an increased risk of developing CTS. No other consistent associations were observed for physical or psychosocial exposures at work and CTS incidence.

ObjectivesThe aim was to examine exposure–response relations between occupational hand exposures and carpal tunnel syndrome (CTS) and to compare the relation between surgery-treated and non-surgery-treated CTS. The secondary aim was to study sex-specific differences in exposure–response relations.MethodsWe conducted a nationwide register-based cohort study of all persons born in Denmark (1945–1994). During follow-up (2010–2013), we identified first-time events of CTS. Occupational hand exposure estimates the year before each follow-up year were obtained by linking individual occupational codes with a job exposure matrix. We used multivariable logistic regression equivalent to discrete survival analysis based on sex and surgery. The excess fraction of cases was calculated.ResultsFor both sexes, exposure–response relations were found for all occupational hand exposures. Among men, we found ORadj of 3.6 (95% CI 3.2 to 3.8) for hand-related force, 2.9 (95% CI 2.5 to 3.2) for repetitive hand movements, 3.8 (95% CI 2.7 to 5.2) for non-neutral hand posture and 2.5 (95% CI 2.2 to 2.7) for hand-arm vibration in the highest exposure groups. For combined exposure (hand load), ORadj was 3.5 (95% CI 3.1 to 4.0). Slightly higher ORsadj were generally found for surgery-treated CTS compared with non-surgery-treated CTS for both sexes. When comparing sex, somewhat higher ORsadj were found among men. The excess fraction was 42%.ConclusionsOccupational hand exposures carried a 3-5-fold increased risk of CTS with slightly higher risks for surgery-treated compared with non-surgery-treated CTS. Even though CTS occurs more frequently among women, somewhat higher exposure–response relations were found for men compared with women. In the general working population, a substantial fraction of first-time CTS could be related to occupational hand exposures.

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. Familial carpal tunnel syndrome (CTS) is common, but causal genes are not characterized. Here the authors report two CTS-related mutations in two large families that impair secretion of COMP in tenocytes, leading to ER stress-induced unfolded protein response, inflammation and fibrosis in patients and mouse models.

BackgroundAlthough recent studies have identified important risk factors associated with incident carpal tunnel syndrome (CTS), risk factors associated with its severity have not been well explored.ObjectiveTo examine the associations between personal, workplace psychosocial and biomechanical factors and incident work disability among workers with CTS.MethodsBetween 2001 and 2010 five research groups conducted coordinated prospective studies of CTS and related work disability among US workers from various industries. Workers with prevalent or incident CTS (N=372) were followed for up to 6.4 years. Incident work disability was measured as: (1) change in work pace or work quality, (2) lost time or (3) job change following the development of CTS. Psychosocial factors were assessed by questionnaire. Biomechanical exposures were assessed by observation and measurements and included force, repetition, duty cycle and posture. HRs were estimated using Cox models.ResultsDisability incidence rates per 100 person-years were 33.2 for changes in work pace or quality, 16.3 for lost time and 20.0 for job change. There was a near doubling of risk for job change among those in the upper tertile of the Hand Activity Level Scale (HR 2.17; 95% CI 1.17 to 4.01), total repetition rate (HR 1.75; 95% CI 1.02 to 3.02), % time spent in all hand exertions (HR 2.20; 95% CI 1.21 to 4.01) and a sixfold increase for high job strain. Sensitivity analyses indicated attenuation due to inclusion of the prevalent CTS cases.ConclusionPersonal, biomechanical and psychosocial job factors predicted CTS-related disability. Results suggest that prevention of severe disability requires a reduction of both biomechanical and organisational work stressors.

BackgroundAlthough carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy, its pathogenesis remains largely unknown. An estimated heritability index of 0.46 and an increased familial occurrence indicate that genetic factors must play a role in the pathogenesis.Methods and resultsWe report on a family in which CTS occurred in subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons resulting in toe walking in childhood. Using exome sequencing, we identified a heterozygous variant (c.5009T>G; p.Phe1670Cys) in the fibrillin-2 (FBN2) gene that co‐segregated with the phenotype in the family. Functional assays showed that the missense variant impaired integrin-mediated cell adhesion and migration. Moreover, we observed an increased transforming growth factor-β signalling and fibrosis in the carpal tissues of affected individuals. A variant burden test in a large cohort of patients with CTS revealed a significantly increased frequency of rare (6.7% vs 2.5%–3.4%, p<0.001) and high-impact (6.9% vs 2.7%, p<0.001) FBN2 variants in patient alleles compared with controls.ConclusionThe identification of a novel FBN2 variant (p.Phe1670Cys) in a unique family with early onset CTS, together with the observed increased frequency of rare and high-impact FBN2 variants in patients with sporadic CTS, strongly suggest a role of FBN2 in the pathogenesis of CTS.