Clinical features

Classically, the syndrome of CTS comprises sensory and motor features in the median nerve distribution of the hand, together with evidence of delayed nerve conduction. The history is of gradual onset of numbness and tingling in the median nerve distribution of the hand. Pain is also reported. Strenuous use of the hand tends to aggravate symptoms, although this may not become apparent until several hours after activity. Nighttime pain disturbs sleep, and patients often hang the affected hand over the side of the bed to gain relief. Many sufferers complain of progressive weakness and clumsiness in their hands. Tinel’s test (percussion over the flexor retinaculum) and Phalen’s test (sustained complete flexion of the wrist for a minute or so) may provoke parasthesiae over a median nerve distribution.

Compression of the nerve results in damage to the myelin sheath and manifests as delayed latencies and slowed conduction velocities: electrodiagnosis rests upon demonstrating impaired median nerve conduction across the carpal tunnel in the context of normal conduction elsewhere.

Case definitions and diagnosis

Nerve conduction, with its objectivity and relationship to mechanism, is treated as a reference standard. However, diagnosis is less simple in clinical experience (and especially in surveys of general and working populations) than is implied by the foregoing description. Sensory symptoms are common in the absence of obvious pathology (>30% of adults in one British population survey reported sensory symptoms in the digits in the past 7 days) ; patients may forget the distribution of their symptoms; and questions arise as to the interpretation of compatible but non-classical presentations (e.g., whether symptoms confined to only one of the three median digits is indicative of CTS). ‘Classical’ symptoms, and improvement with surgery, occur despite normal nerve conduction; delayed nerve conduction occurs fairly often in asymptomatic individuals; and Tinel’s and Phalen’s signs can be found in the absence of other syndromic features . Thus, the relation between elements of the triad (symptoms, signs and nerve conduction) is inconstant, making for a reference standard that is imperfect.

The ensuing uncertainty contributes to variation in practice, with physicians entertaining differing views about essential diagnostic features. Thus, when Graham et al. (2006) asked 99 physicians and surgeons to score 57 potential criteria on a visual analogue scale, they found remarkably little agreement beyond chance within and between specialities .

In research, the situation – though far from ideal – is rather better. The hand diagrams of Katz et al. represent a standardised, widely used method of collecting patients’ symptom histories. By pre-specifying and agreeing the shading patterns of ‘classical’, ‘probable’ and ‘possible’ distributions of CTS-like symptoms, different observers have reached acceptable agreement over case history. In one workplace study, two observers achieved a 96% agreement over the rating of 255 hand diagrams collected from workers at 12 worksites ; and in another, good agreement was found between three experienced clinicians assessing the hand diagrams of 333 employees . Others, by pre-specifying a combination of symptoms and signs, have shown that research-trained observers can agree reasonably well .

Reproducibility of case history is a useful achievement, although not synonymous with validity of diagnosis (By analogy, badly calibrated weighing scales can offer repeatable but erroneous data.) Nor has disagreement in research been eliminated entirely; rather, it is manifest in debate about interpretation of the hand diagram. Katz and Stirrat have defined symptoms of CTS as “classical,” if they affect at least two of digits 1–3 but not the palm or dorsum of the hand, as “probable,” if the palm is also involved, and as “possible,” if symptoms are reported in only one of digits 1–3. Minor modifications to these criteria have been suggested by Franzblau et al. and Rempel et al. .

The Katz hand diagram (and other features such as Tinel’s and Phalen’s signs) has been assessed for their positive and negative likelihood ratios (LRs), assuming that nerve conduction is sufficient, if imperfect reference standard ( Table 1 ) . LRs assess how much a positive diagnostic test raises (or a negative test lowers) the post-probability of disease, and, hence, offer an appealing framework for judging a test’s influence on clinical decision-making – the higher the positive LR, the better a test will be at ruling in a disease; the lower the negative LR, the better at ruling out a disease. However, by the criteria of Jaeschke et al. (1994) , the LRs in Table 1 do not suggest a ‘significant’ shift in the post-test likelihood.

The failure may be one of case mix among the generally milder cases found in the workplace and the community. Thus, a ‘classical’ distribution of (Katz definition) is reported to be sensitive and specific for delayed median nerve conduction in patients under hospital investigation ; but the criteria have not predicted delayed nerve conduction in community or occupational samples. A community survey by Ferry et al. also explored the relation of delayed nerve conduction to various other symptom patterns, including hand symptoms that excluded the fifth digit, the dorsum or both of these sites, but found the correlation to be similarly poor.

The want of an ideal reference standard, especially beyond the hospital confines, has knock-on effects for the descriptive epidemiology of CTS and for research aimed at prevention and treatment.

Case definitions and diagnosis

Nerve conduction, with its objectivity and relationship to mechanism, is treated as a reference standard. However, diagnosis is less simple in clinical experience (and especially in surveys of general and working populations) than is implied by the foregoing description. Sensory symptoms are common in the absence of obvious pathology (>30% of adults in one British population survey reported sensory symptoms in the digits in the past 7 days) ; patients may forget the distribution of their symptoms; and questions arise as to the interpretation of compatible but non-classical presentations (e.g., whether symptoms confined to only one of the three median digits is indicative of CTS). ‘Classical’ symptoms, and improvement with surgery, occur despite normal nerve conduction; delayed nerve conduction occurs fairly often in asymptomatic individuals; and Tinel’s and Phalen’s signs can be found in the absence of other syndromic features . Thus, the relation between elements of the triad (symptoms, signs and nerve conduction) is inconstant, making for a reference standard that is imperfect.

The ensuing uncertainty contributes to variation in practice, with physicians entertaining differing views about essential diagnostic features. Thus, when Graham et al. (2006) asked 99 physicians and surgeons to score 57 potential criteria on a visual analogue scale, they found remarkably little agreement beyond chance within and between specialities .

In research, the situation – though far from ideal – is rather better. The hand diagrams of Katz et al. represent a standardised, widely used method of collecting patients’ symptom histories. By pre-specifying and agreeing the shading patterns of ‘classical’, ‘probable’ and ‘possible’ distributions of CTS-like symptoms, different observers have reached acceptable agreement over case history. In one workplace study, two observers achieved a 96% agreement over the rating of 255 hand diagrams collected from workers at 12 worksites ; and in another, good agreement was found between three experienced clinicians assessing the hand diagrams of 333 employees . Others, by pre-specifying a combination of symptoms and signs, have shown that research-trained observers can agree reasonably well .

Reproducibility of case history is a useful achievement, although not synonymous with validity of diagnosis (By analogy, badly calibrated weighing scales can offer repeatable but erroneous data.) Nor has disagreement in research been eliminated entirely; rather, it is manifest in debate about interpretation of the hand diagram. Katz and Stirrat have defined symptoms of CTS as “classical,” if they affect at least two of digits 1–3 but not the palm or dorsum of the hand, as “probable,” if the palm is also involved, and as “possible,” if symptoms are reported in only one of digits 1–3. Minor modifications to these criteria have been suggested by Franzblau et al. and Rempel et al. .

The Katz hand diagram (and other features such as Tinel’s and Phalen’s signs) has been assessed for their positive and negative likelihood ratios (LRs), assuming that nerve conduction is sufficient, if imperfect reference standard ( Table 1 ) . LRs assess how much a positive diagnostic test raises (or a negative test lowers) the post-probability of disease, and, hence, offer an appealing framework for judging a test’s influence on clinical decision-making – the higher the positive LR, the better a test will be at ruling in a disease; the lower the negative LR, the better at ruling out a disease. However, by the criteria of Jaeschke et al. (1994) , the LRs in Table 1 do not suggest a ‘significant’ shift in the post-test likelihood.

The failure may be one of case mix among the generally milder cases found in the workplace and the community. Thus, a ‘classical’ distribution of (Katz definition) is reported to be sensitive and specific for delayed median nerve conduction in patients under hospital investigation ; but the criteria have not predicted delayed nerve conduction in community or occupational samples. A community survey by Ferry et al. also explored the relation of delayed nerve conduction to various other symptom patterns, including hand symptoms that excluded the fifth digit, the dorsum or both of these sites, but found the correlation to be similarly poor.

The want of an ideal reference standard, especially beyond the hospital confines, has knock-on effects for the descriptive epidemiology of CTS and for research aimed at prevention and treatment.

Epidemiology

Estimates of the prevalence and incidence of CTS depend critically on the adopted case definition. The partial concordance of the diagnostic triad (earlier) allows for several choices, and a range of plausible cut-points exists for defining electrophysiological abnormality. Different choices generate markedly different estimates of prevalence .

In a large Dutch population survey that defined CTS as sensory disturbance in the median nerve distribution occurring at least twice a week, generally awakening the patient from sleep, and associated with nerve conduction abnormalities, the point prevalence was 0.6% in men and 8% in women .

In a British population survey, estimates were made of sensory symptoms in various anatomical distributions ( Table 2 ) . ‘Classical’ CTS – defined as symptoms extensively affecting the palmar surfaces of the medial three digits and not felt elsewhere – was reported by 1.2% of adults and ‘probable CTS’ (less extensive symptoms, but still restricted to the median nerve distribution) affected a further 2.2% of adults. Symptomatic respondents from the same survey were examined for physical signs, and this resulted in an estimated population prevalence of 0.9%, rising somewhat with age . Table 2 shows that other patterns of sensory involvement in the digits are very common, with 6–7% of respondents shading all of the digits in one or both of their hands as affected: thus, surveys which define cases on ‘soft’ definitions of symptom distribution generate markedly higher estimates of prevalence (14–19% in some investigations) .

Estimates of prevalence and incidence depend on the setting in which inquiries are made. The crude incidence rate is reported to be 1 per 1000 person years in hospital-diagnosed patients and around 2 per 1000 person-years in primary care . In selected working populations, CTS is somewhat more common (1–2%), using clinically based criteria .

The age-adjusted incidence rate of CTS may be increasing in the general population , but exact comparisons between surveys are difficult, as case definitions have changed over time, following the introduction of electrophysiological testing.

Research-driven case definitions

Ferry et al. have developed an instrument to assess the disability from CTS, which incorporates domains such as sleep disturbance, clumsiness and difficulty with writing, dressing and driving . The researchers explored case definitions based on symptoms and nerve conduction in the community, and found consistently higher levels of self-reported disability in those with electrophysiological abnormalities.

This example suggests a research-driven basis for refinement of case definition: ‘more correct’ definitions (those closer to ‘the truth’) should display stronger correlations with prognosis, effective treatments and established causes of disease . This phenomenon arises because the natural gradients between exposure and response are attenuated by diagnostic misclassification; good case definitions involve less misclassification, allowing dose–response effects to shine through. Where stronger associations (risks from exposure or benefits from treatment) are found, two useful conclusions flow – case definition A is more accurate than case definition B, while the magnitude of risk (or benefit) is greater than might be supposed from research with B as the operational case definition.

Table 3 illustrates the principle. The data derive from a survey of workers manufacturing ski equipment , some in jobs with frequent hand–wrist repetition and some in non-repetitive work. Both groups were classified as having CTS by several case definitions. The more specific detailed case definition (delayed nerve conduction with a positive Tinel’s or Phalen’s test) showed a much stronger association with repetition than non-specific symptoms (e.g., nocturnal hand pain), suggesting both that this definition is a better marker of CTS and that risks of the activity are reasonably high.

Analogously, in the British population survey mentioned above, associations were explored between various symptom patterns and risk factors for sensory hand symptoms ( Table 4 ) . Repetitive work activity was associated ‘only’ with the extensive median pattern of sensory symptoms (classical CTS-like symptoms), whereas low vitality and painfully restricted neck movements were associated ‘only’ with non-median symptoms. Studies such as these vindicate textbook clinical teaching, and help to define tools for field research, despite ongoing debate about the optimum reference standard.

Table 4

Association of numbness and tingling in the hands with low vitality, neck pain and occupational activities (adapted from Reading et al. with permission of the publishers).

Pattern of numbness/tingling in past 7 days	PR (95%CI)
	Low vitality	Neck pain + restricted movement	Repeated finger/wrist movements >4 h/day	Bending & straightening the elbow for >1 h/day
Extensive median in one/both hands	0.8 (0.3–3.1)	1.4 (0.2–9.5)	2.6 (1.0–6.8)	3.1 (1.0–9.5)
Limited median in one/both hands	1.2 (0.6–2.7)	3.7 (1.5–8.9)	1.2 (0.6–2.4)	1.1 (0.6–2.3)
Non-median in one/both hands	1.9 (1.3–2.8)	3.2 (1.8–5.7)	1.4 (0.9–2.1)	1.3 (0.9–2.0)
All fingers, both hands	2.5 (1.4–4.3)	4.9 (2.8–8.6)	1.4 (0.8–2.2)	1.3 (0.8–2.1)
All fingers, one hand	1.6 (0.8–2.9)	2.8 (1.2–6.8)	1.1 (0.6–2.0)	1.1 (0.9–2.5)
No symptoms, either hand	1	1	1	1

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