Abstract
Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome, and it frequently presents in working-aged adults. Its mild form causes ‘nuisance’ symptoms including dysaesthesia and nocturnal waking. At its most severe, CTS can significantly impair motor function and weaken pinch grip. This review discusses the anatomy of the carpal tunnel and the clinical presentation of the syndrome as well as the classification and diagnosis of the condition. CTS has a profile of well-established risk factors including individual factors and predisposing co-morbidities, which are briefly discussed. There is a growing body of evidence for an association between CTS and various occupational factors, which is also explored. Management of CTS, conservative and surgical, is described. Finally, the issue of safe return to work post carpal tunnel release surgery and the lack of evidence-based guidelines are discussed.
Anatomy of the carpal tunnel
Found at the palmar wrist, the carpal tunnel is defined by the pisiform and hook of the hamate medially and the tuberosities of the scaphoid and trapezium laterally. Thick connective tissue (the flexor retinaculum) covers these four bony prominences, which creates a tunnel for the extrinsic flexor tendons of the digits (flexor digitorum profundus, flexor digitorum superficialis and flexor pollicis longus), maintaining them in place during wrist flexion ( Fig. 1 ). The median nerve is a major peripheral nerve of the upper limb. It runs a course through the lateral and medial cords of the brachial plexus into the anterior compartment of the forearm through the carpal tunnel into the wrist, where it branches to provide motor supply to the thenar muscle group and sensory innervation to the palmar surface of the thumb, index finger, middle finger and lateral half of the ring finger. Carpal tunnel syndrome (CTS) is caused when the tunnel is narrowed or the extrinsic flexor tendons or tendon sheaths swell. Constriction in the carpal tunnel impinges on the median nerve producing symptoms of disturbed sensation in the digits it innervates. Symptoms may progress to wasting and weakness of the thenar muscles, resulting in weakened pinch grip.
Classification and diagnostic criteria
The typical presentation of CTS involves pain and/or dysaesthesia of the fingers (typically the lateral 3½ digits, but it can be diffuse throughout the hand and can radiate proximal to the wrist). Symptoms are often worse at night or in the early morning. Examination in advanced cases may reveal wasting of the thenar eminence and/or weakness of thumb opposition. Provocation tests such as those of Tinel (tapping the flexor retinaculum) and Phalen (full passive flexion of the wrist sustained for 1 min) are widely used as confirmatory tests in clinical practice. The sensitivity and specificity of these tests are excellent (88–100%) in people about to undergo carpal tunnel decompression , but when the same tests are performed among patients with dysaesthesia in the general population , considerably poorer performance is found, at least when the ‘gold standard’ is nerve conduction studies. Similarly, electrophysiological nerve conduction tests have shown good diagnostic sensitivity (60–84%) and specificity of >95% using a standardised cut-off for sensory nerve velocities among patients awaiting decompression where the ‘gold standard’ was operative relief of symptoms . However, nerve conduction testing is not a perfect gold standard; false positives and negatives are well documented and there is currently no consensus as to optimal technique, standardisation or normalisation for factors such as age, sex, height or skin temperature .
Researchers recently proposed a new case definition for diagnosis of CTS refining the traditional ‘cut-off’ approach and suggested using the difference between conduction velocities in the little and index finger at a threshold >8 m/s . In a study of 908 patients with 1806 symptomatic hands, the researchers found that this threshold mean difference was observed most consistently in cases with ‘classical’ distribution of median nerve dysaesthesia according to a Katz hand diagram and positive Tinel’s and Phalen’s tests . Using this threshold and exploring response to carpal tunnel release (CTR) surgery, the same researchers showed that hands with this mean difference in sensory nerve conduction were significantly more likely to have resolution of numbness, tingling and pain after surgery as compared with hands in which this difference was not detected . More research is required to see if this new case definition will eventually replace the traditional ‘cut-off’ approach.
In clinical practice, the diagnosis of CTS is made from the combination of symptoms, signs and nerve conduction testing. However, most studies of risk factors for CTS have taken place in workplace or population settings where cases are likely to be milder, and neither the clinical provocation tests nor the nerve conduction tests (if available) have the same level of performance. The lack of a single valid and reliable diagnostic test has led to considerable heterogeneity in the case definitions used in epidemiological studies, making it difficult to pool results or data to produce confident estimates of risk based upon systematic review or meta-analysis.
Classification and diagnostic criteria
The typical presentation of CTS involves pain and/or dysaesthesia of the fingers (typically the lateral 3½ digits, but it can be diffuse throughout the hand and can radiate proximal to the wrist). Symptoms are often worse at night or in the early morning. Examination in advanced cases may reveal wasting of the thenar eminence and/or weakness of thumb opposition. Provocation tests such as those of Tinel (tapping the flexor retinaculum) and Phalen (full passive flexion of the wrist sustained for 1 min) are widely used as confirmatory tests in clinical practice. The sensitivity and specificity of these tests are excellent (88–100%) in people about to undergo carpal tunnel decompression , but when the same tests are performed among patients with dysaesthesia in the general population , considerably poorer performance is found, at least when the ‘gold standard’ is nerve conduction studies. Similarly, electrophysiological nerve conduction tests have shown good diagnostic sensitivity (60–84%) and specificity of >95% using a standardised cut-off for sensory nerve velocities among patients awaiting decompression where the ‘gold standard’ was operative relief of symptoms . However, nerve conduction testing is not a perfect gold standard; false positives and negatives are well documented and there is currently no consensus as to optimal technique, standardisation or normalisation for factors such as age, sex, height or skin temperature .
Researchers recently proposed a new case definition for diagnosis of CTS refining the traditional ‘cut-off’ approach and suggested using the difference between conduction velocities in the little and index finger at a threshold >8 m/s . In a study of 908 patients with 1806 symptomatic hands, the researchers found that this threshold mean difference was observed most consistently in cases with ‘classical’ distribution of median nerve dysaesthesia according to a Katz hand diagram and positive Tinel’s and Phalen’s tests . Using this threshold and exploring response to carpal tunnel release (CTR) surgery, the same researchers showed that hands with this mean difference in sensory nerve conduction were significantly more likely to have resolution of numbness, tingling and pain after surgery as compared with hands in which this difference was not detected . More research is required to see if this new case definition will eventually replace the traditional ‘cut-off’ approach.
In clinical practice, the diagnosis of CTS is made from the combination of symptoms, signs and nerve conduction testing. However, most studies of risk factors for CTS have taken place in workplace or population settings where cases are likely to be milder, and neither the clinical provocation tests nor the nerve conduction tests (if available) have the same level of performance. The lack of a single valid and reliable diagnostic test has led to considerable heterogeneity in the case definitions used in epidemiological studies, making it difficult to pool results or data to produce confident estimates of risk based upon systematic review or meta-analysis.
Differential diagnosis
The main differential diagnoses of CTS are other neuropathies. Cervical radiculopathies at C6–C7 may mimic the sensory symptoms, although in such cases motor involvement will be in the distribution of the radial nerve, affecting wrist flexion and triceps. Pain itself may be difficult to localise, and the possibility of an ulnar or small fibre neuropathy should be considered for patients with neuropathic palmar digit pain, along with other causes of medial neuropathy. Wasting of the thenar muscles may also be caused by a T1 radiculopathy.
Individual risk factors for CTS
The results of almost all prevalence studies suggest that CTS occurs more commonly in women, with an annual incidence of 1.5 per 1000 compared to 0.5 per 1000 for men . Gender also seems to exert an effect on incidence such that the incidence among women peaks at ages 45–54 years; if a woman has not experienced symptoms by the fifth or sixth decade, she seems to be less likely to experience them for the first time at an older age. By contrast, the incidence in men appears to continue to increase with age. The gender differences may be explained at least partly by hormonal factors as pregnant and breast-feeding women have an increased risk of CTS , as well as those in their first menopausal year, taking the oral contraceptive pill or taking hormone replacement therapy , and oophorectomy appears to reduce the incidence.
Body mass index and obesity are strongly associated with CTS, with every one-unit increase in body mass increasing the risk of the condition by 8% . Some, but only a very small proportion, of the excess cases are associated with endocrine diseases such as hypothyroidism, acromegaly and diabetes mellitus. Narrowing of the carpal tunnel canal (e.g., through trauma or inflammation due to wrist fractures) and inflammatory rheumatic disorders are also risk factors .
CTS and its association with occupation
Over the past 20 years, there have been a vast number of studies investigating the relationship between CTS and occupational activities. The number of studies is now so extensive that there have been a number of published systematic reviews of this literature . In addition to the issues described above with classification criteria for CTS, another difficulty in interpreting the reviews has been the lack of standardisation of exposure classification across the studies. Very few studies have made in-depth analyses of movements involved in work activities as this is necessarily time consuming and expensive and would therefore need to be limited to few individuals. Exposure classification has generally ranged from simple job titles through to self-reported workplace activities (e.g., repetitive bending/straightening the wrist ≥1 h/day).
In 1992, Hagberg et al. published a review of 21 studies including high-quality information on occupational associations, and they reported an increased risk of CTS in a number of jobs believed to involve repetitive and forceful gripping . Later in the 1990s, the US National Institute of Occupational Safety and Health (NIOSH) carried out a large systematic review of musculoskeletal disorders and workplace factors including CTS as an outcome . This also concluded that there was evidence of a positive association with work that involved highly repetitive movements of the hands, and a similar association with work involving forceful movements of the hands. The evidence was stronger if these exposures were combined. However, the reviewers found insufficient evidence that CTS was associated with extreme wrist postures. A third review from the same period (1998) by Abbas et al. also concluded that force and repetition were significant risk factors for CTS.
An updated review by Palmer et al. in 2007 partially addressed the difficulties with exposure classification by analysing the 38 individual study reports on a comparison of either job titles or the physical activities within the job. There were a wide range of occupational titles, including such diverse jobs as forestry workers, stone carvers, slaughterhouse workers, textile workers, dental hygienists and supermarket workers. These could however be divided into three broad classes: jobs entailing the use of vibratory tools, assembly work, and food processing and packing. Many of these occupations involve prolonged or repeated flexion and extension of the wrist. From this review, it was concluded that ‘there is a substantial body of evidence that prolonged and highly repetitious flexion or extension of the wrist materially increases the risk of carpal tunnel syndrome, especially when allied with a forceful grip’. It found reasonable evidence that regular prolonged use of handheld vibratory tools was associated with more than double the risk of CTS. The balance of evidence did not demonstrate an important association with the use of a computer keyboard and mouse. The association between computer work and CTS was further examined in reviews from 2008 by Thomsen et al. and from 2014 by Mediouni et al. Both reviews concluded that there was insufficient epidemiological evidence that computer work causes CTS, although some particular work circumstances involving computer mouse use may be associated with CTS.
A systematic review published by van Rijn et al. in 2009 was conducted with the aim of providing a quantitative assessment of the exposure–response relationships between work-related physical and psychosocial factors and the occurrence of CTS. This examined the following: (a) associations of CTS with type of work, based on job descriptions; (b) associations of CTS with five types of exposure – force, repetitiveness, hand–arm vibration, combined exposure measure and awkward postures; and (c) associations of CTS with psychosocial risk factors. The authors found that jobs with the highest risk of CTS included work in the meat- and fish-processing industry, forestry work with chainsaws and electronic assembly work. Exposure to high levels of hand–arm vibration, prolonged work with flexed or extended wrist and high levels of hand force and repetitiveness were also associated with CTS. They concluded that CTS is associated with an average hand force of >4 kg, repetitiveness at work with a cycle time <10 s, or >50% of cycle time performing the same movements, and a daily 8-h energy-equivalent frequency-weighted acceleration of ≥3.9 m/s 2 . No association was found between any psychosocial risk factor and CTS. Again, no clear association was found between computer work and CTS.
In a subsequent meta-analysis, based upon studies carried out between 1980 and 2009, Barcenilla et al. reviewed many of the studies included in the reviews mentioned earlier and an additional 14 more recent studies. Using a case definition of CTS that included nerve conduction abnormality with symptoms and/or signs, this study found the following risk factors to be significantly associated with an increased risk of CTS among workers:
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vibration (three studies, odds ratio (OR) 5.40, 95% confidence interval (CI) 3.14–9.31)
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hand force (five studies, OR 4.23, 95% CI 1.53–11.68)
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repetition (11 studies, OR 2.26, 95% CI 1.73–2.94)
In addition, an association close to significance was found for the following risk factor:
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combined exposure to both force and repetition (five studies, OR 1.85, 95% CI 0.99–3.45)
The results of this review also suggested a non-significant association between CTS and wrist posture, based on three studies (OR 4.73, 95% CI 0.42–53.32); an association that has been investigated further in a meta-analysis published by You et al., in 2014 . This pooled analysis from nine studies demonstrated a doubling of risk of CTS with increased exposure to wrist extension/flexion (relative risk (RR) 2.01, 95% CI 1.66–2.43).
Compensation for CTS among workers in the UK
In the UK, the Industrial Injuries Disablement Benefit is a no-fault compensation scheme that compensates employed earners in relation to disablement from occupational accidents or a list of ‘prescribed’ diseases. CTS is a prescribed disease under this scheme for people in occupations that involve the use of handheld powered vibratory tools (and whose symptoms started whilst working in this occupation) and/or performance of repeated palmar flexion and dorsiflexion for at least 20 h/week over at least 12 months in the 24 months prior to the onset of symptoms . A range of different compensation schemes and arrangements apply across Europe, and the reader is encouraged to familiarise themselves with the schemes applicable to their practice.
Management of CTS
The initial management of CTS is conservative. A number of options have been tried, including wrist splinting, exercise and mobilisation, local and systemic corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and therapeutic ultrasound.
Wrist splinting
Nocturnal splinting to hold the wrist in a neutral position is widely advocated. Interestingly however, this strategy is relatively poorly evidence based, at least as reported in a 2012 review by the Cochrane Collaboration who found that despite 19 studies including almost 1200 participants overall, there was limited evidence that a nocturnal splint was more effective than no treatment in the short term . They also reported that there was insufficient evidence regarding the effectiveness and safety of one splint design or wearing regimen over others, and of splinting over the use of other non-surgical interventions for CTS. However, in their systematic review published in 2007, Piazzini and colleagues concluded that there was ‘moderate’ evidence for splinting, particularly if used full time . It should, however, be borne in mind that it is difficult to design a trial to rigorously test the effectiveness of splints when traditional ‘blinding’ of participants is so obviously challenging.
Wrist exercise and mobilisation
A 2012 review by the Cochrane Collaboration compared the efficacy and safety of exercise and mobilisation interventions with other non-operative treatments for CTS . The authors identified 16 studies, with a total of 714 patients, and found limited low-quality evidence in favour of a diverse collection of exercise and mobilisation techniques. Further high-quality trials are needed, and the reviewers recommend that use of these interventions should be based on clinician expertise and patient preferences until further evidence is available.
Diuretics and NSAIDs
The evidence does not support the use of NSAIDs or diuretics for primary CTS .
Oral corticosteroids
Short-term oral corticosteroids have been shown to be effective for the symptomatic treatment of CTS over 2 and 4 weeks of follow-up . However, the side effects of oral corticosteroids and their toxicity profile are such that this is not a recommended therapeutic option in all but the rarest clinical circumstances.
Local corticosteroid injection
According to a review by the Cochrane Collaboration including 12 trials involving 651 participants, local corticosteroid injection produced greater clinical improvement in symptoms than placebo did after 1 month . However, they found insufficient evidence of symptom relief beyond 1 month. Local corticosteroid injection provided significantly greater clinical improvement than oral corticosteroid for up to 3 months. When compared with anti-inflammatories over 8 weeks of follow-up, there was no evidence that local corticosteroid injection improved clinical outcome. Two local corticosteroid injections did not provide significant added clinical benefit when compared to one injection.
Ultrasound
Pooled data from two trials involving 63 participants failed to show any significant benefit of ultrasound treatment over 2 weeks of follow-up . However, in another trial, significant symptom improvement was demonstrated after 7 weeks of ultrasound which was maintained at 6 months .
CTR surgery
Surgical release of the carpal tunnel is recommended for severe cases of CTS, for example, when there is thenar muscle wasting or weakness of thumb opposition, or when conservative management has failed . The first open surgical release of the transverse carpal ligament was performed in Canada in 1924 , and CTR surgery became widely adopted from the 1950s . CTR is the most commonly performed hand operation in the UK, with >51,000 procedures being performed in England in 2012 . Surgical success rates of 54–75% are frequently reported , although there is some disagreement about how ‘success’ should best be defined .
In their review of the evidence comparing surgical versus non-surgical management, Verdugo and colleagues found four randomised controlled trials involving 317 participants, which measured improvement after 3 months of follow-up as a primary outcome . They concluded that surgery is more effective than non-surgical treatment at follow-up after 3 and 6 months of treatment . Two trials including 245 participants also showed benefit of surgery versus non-surgery at 6 months of follow-up .
CTR is now performed endoscopically, or as an open procedure with a minimal incision ( Fig. 2 ). A recent Cochrane review found no evidence that endoscopic CTR provides superior long- or short-term symptom relief compared to the standard open procedure, but it concluded that there was some evidence to suggest that the endoscopic procedure may enable patients to return to work sooner (6 days, 95% CI 3–9 days) .
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