Clinical diagnosis of carpal tunnel syndrome: a systematic review

Clinical Diagnosis of Carpal Tunnel Syndrome: A Systematic Review

Joy C. MacDermid, BScPT, PhD School of Rehabilitation Science McMaster University Hamilton, Ontario, Canada Clinical Research Lab Hand and Upper Limb Centre St. Joseph’s Health Centre London, Ontario, Canada Career Scientist of the Ontario Ministry of Health Health Research Personnel Development Program

Jean Wessel, PhD School of Rehabilitation Science McMaster University Hamilton, Ontario, Canada

Carpal tunnel syndrome (CTS) is a common clinical condition1 that is frequently seen by hand therapists.2 Although a variety of diagnostic tests are available, identifying cases of CTS remains a challenge both in the workplace and the clinic. Clinical tests may focus on the nature of the symptoms, provocation of symptoms, or sensorimotor nerve evaluation. Some of these tests and their variations are listed in Tables 1–3. A number of issues could contribute to disagreements between studies on the relative value of clinical tests. These include differences across studies in the way tests are performed (Tables 2 and 3), in examiner skills, in study populations, or in elements of data collection and analysis. Sackett and colleagues3 defined criteria for conducting and critically appraising diagnostic tests. They emphasized the need for methods that minimize biases due to research design, sampling protocols, and reference standards. Correspondence and reprint requests to Joy C. MacDermid, PhD, Room 429, IAHS, School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada; e-mail: . doi:10.1197/j.jht.2004.02.015

ABSTRACT: The purposes of this systematic review were to examine the properties of clinical tests usd in the diagnosis of carpal tunnel syndrome (CTS) and to provide estimates of their sensitivity and specificity. A literature search was conducted using two databases—PubMed and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)—from 1986 to June 2003, and hand-searching reference lists of retrieved articles. Two reviewers evaluated the papers for quality using an evaluation tool developed by one of the authors. Estimates of sensitivity and specificity were determined by averaging values across studies weighted by sample size. Although 60 studies were reviewed in detail, many were of poor quality (mean quality score was 6.6 of 12, with only 15 of 60 obtaining a score of 8 or greater). The most frequently studied test was Phalen’s, with an overall estimate of 68% sensitivity and 73% specificity. Next was Tinel’s, with estimates of 50% and 77%, and then carpal compression, with estimates of 64% and 83% for sensitivity and specificity, respectively. Two-point discrimination and testing of atrophy or strength of the abductor pollicis brevis proved to be specific but not very sensitive. The estimates determined in this review should help therapists choose clinical tests with the appropriate balance of sensitivity and specificity required for diagnosing carpal tunnel syndrome in their specific clinical environments. J HAND THER. 2004;17:309–319.

Conflicting results on the sensitivity and specificity of clinical tests used in diagnosis of CTS have been reported in a previous narrative review.4 With the increased emphasis on evidence-based practice, narrative reviews have been less favored, because it is thought that there is a greater opportunity for authors to introduce biases in the way that they select and/or interpret published studies. Thus, a more recent review5 reported on a systematic evaluation of 21 studies that investigated the accuracy of clinical tests using electrodiagnosis as the gold standard. This review noted significant flaws in the available literature using 17 review criteria developed for the study. These criteria included evaluation of some of the elements of research design (sampling, procedures, follow-up, and data analysis) emphasized by Sackett,3 whereas others were notably lacking (i.e., the importance of an appropriate control group). Nevertheless, this paper was an important step in analyzing available literature with the objective of making evidence-based recommendations for selection of appropriate clinical tests to assist in diagnosis of CTS. Unfortunately, high variability and poor research design limited the ability to perform metaanalyses or make conclusive recommendations. The April–June 2004 309

TABLE 1. Description of Diagnostic Tests for Carpal Tunnel Syndrome—Subjective/History Element

Description of Positive Result

Symptom/hand diagram38

Patient completes a diagram of where symptoms are located; patterns are characterized as classic, probable, possible or unlikely Classic: Tingling, numbness, or decreased sensation with or without pain in at least two of digits 1, 2, or 3; palm and dorsum of the hand excluded: wrist pain or radiation proximal to the wrist allowed Probable: Same as for classic, except palmar symptoms allowed unless confined solely to ulnar aspect Possible: Tingling, numbness, decreased sensation, and/or pain in at least one of digits 1, 2, or 3 Unlikely: No symptoms in digits 1, 2, or 3 Patients report waking at night and flicking (shaking) their hands to relieve symptoms

Flick sign39

authors suggested that there was support for the use of wrist flexion and carpal compression tests, but that two-point discrimination had low sensitivity in diagnosis of CTS. The purpose of this review was to identify and synthesize evidence that might lead to more definitive recommendations on selection of specific clinical tests for the diagnosis of CTS. The review was to be broader and include more recent studies than previous papers. The secondary purpose was to use available data on sensitivity and specificity to provide more stable estimates of diagnostic accuracy.

METHODS Literature Search A literature search was conducted using two databases—PubMed and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)— and hand-searching reference lists of retrieved articles. The search terms and resultant hits were as follows: A. PubMed (limitations—English only, abstract and human) from 1986 to June 2003 1. (carpal tunnel syndrome) AND (diagnosis) NOT (electrodiagnosis) AND (sensitivity and specificity [MESH]) OR sensitivity (WORD) OR (diagnosis [SH] OR diagnostic use [SH] OR specificity [WORD])—975 hits 2. (carpal tunnel syndrome AND clinical diagnosis) AND (sensitivity and specificity [MESH]) OR sensitivity (WORD) OR (diagnosis [SH] OR diagnostic use [SH] OR specificity [WORD])—667 hits B. CINAHL (carpal tunnel syndrome) AND (diagnosis)—475 hits 310

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A total of 1,015 abstracts were reviewed by the first author to identify studies that addressed the diagnostic accuracy of clinical tests. The major reasons for rejection at abstract review were: 1. The paper did not address diagnosis 2. The paper did not contain primary data 3. The paper did not include clinical diagnostic tests (e.g., may have addressed electrodiagnosis, some instances of imaging, but no tests that could be performed routinely by a hand therapist). Seventy-five references remained after the abstract review. The full articles were reviewed by the two authors as described subsequently.

Quality Criteria A quality assessment instrument was designed by the first author to evaluate the rigor of diagnostic accuracy studies. These criteria were based on principles of evidence-based practice and appraisal of diagnostic tests outlined by Sackett.3 Essential components include a blinded evaluation, a gold standard reference as applied to all patients in the study, and selection of appropriate patients and control subjects. The assessment instrument comprised the first 12 items of Appendix A. While attempting to synthesize the retrieved information, it became apparent that the scale did not address an important element. Because assessors require a level of skill to perform physical examination techniques such as provocative tests or sensory evaluation, it was felt that this contribution should be addressed when evaluating studies. Training, skill, and experience might affect the internal validity of an individual study, but almost certainly will affect the generalizability. We noted that this aspect of methodology was poorly described in most of the published studies. Because it was inappropriate to change the critical appraisal instrument during the course of the review, the training and skill of the evaluator(s) were not rated in the studies reviewed. However, it is recommended that two additional questions be added to the assessment instrument (items 13 and 14 in Appendix A).

Rating Process Two raters independently read and rated the identified studies using the rating scale as described previously in this article. On completion of the first 15 studies, the authors met and reviewed the item scores of these papers. Disagreements were resolved by consensus. The authors then reviewed the evaluation criteria and agreed on the interpretation of controversial situations. A lack of agreement was observed on less than 5% of the item scores for the first set of evaluations. The majority of the

TABLE 2. Description of Diagnostic Tests for Carpal Tunnel Syndrome—Provocative Tests Test

Positive Result

Rationale

Method

Phalen’s40–43 Wrist flexion text

Flexion increases pressure in carpal tunnel; median nerve is compromised by high pressures in carpal tunnel, which are exacerbated by extreme wrist flexion

Patient places elbows on table, forearm vertical, wrist falls into gravityassisted flexion for up to one minute; the fingers are left in an extended position

Paresthesia develops or increases in median nerve distribution

Wrist extension Reverse Phalen’s

Wrist extension increases pressure in carpal tunnel as above

Patient actively extends wrist and fingers for two minutes

Paresthesia develops or increases in median nerve distribution

Carpal compression Durkan’s

Direct pressure on median nerve further compromises impaired nerve

Tinel’s

Regenerating nerve fibers are susceptible to mechanical deformation

Examiner compresses median nerve by pressing over proximal edge of carpal ligament (proximal wrist crease) with thumbs Examiner taps along the median nerve at the carpal tunnel

Paresthesia develops or increases in median nerve distribution Tingling or electric shocks felt along median nerve

Tourniquet Gilliat

Increase in vascular pressure in compromised nerve will cause symptoms

Examiner uses a blood pressure cuff on the patient’s arm to the level of their systolic blood pressure

Tethered median nerve stress46,47

Produces maximum excursion of the median nerve and thus accelerates localized neuroschemia; in chronic CTS, adherence of the median nerve to the flexor tendons, the presence of pseudoneuroma, and the close proximity of the flexor tendons to the volar forearm Lumbricals can move into the carpal tunnel during finger flexion; thought that this might increase compression Not clearly specified but further vascular compromise might underlie test

Examiner hyperextends index finger by pressing on distal end (supinated)

Paresthesia develops or increases in median nerve distribution within 60 seconds. Produces proximal forearm radiation in chronic carpal tunnel

Lumbrical provocation

Hand elevation

Patient is asked to make a fist for one minute

Reproduce or worsen symptoms

Pateint elevates both arms with elbows and shoulders in relaxed position; position is held for up to two minutes

Symptoms of paresthesia are reproduced

Variations

Precautions

1. Examiner passively flexes wrist in full flexion (elbow extended) 2. Patient places wrist dorsums together forcing both wrists into flexion 3. Time for symptoms to emerge can be recorded 4. Add-ons in combined tests include making fist or carpal compression Patient places palms together forcing both wrists into extension; one minute time limit

False-negatives may result in patients with limited wrist flexion or when profound numbness exists as positional effects may not be perceived

False-negatives may result in patients with limited wrist extension or when profound numbness exists as positional effects may not be perceived

Pressure cuff or algometer used to apply pressure; location of pressure at exit of canal also reported; has been combined with wrist flexion Tapping with Queen’s square reflex hammer may increase sensitivity; tapping may be just at proximal edge of ligament or may transverse median nerve from distal to proximal edge of carpal tunnel

A Tinel’s test is thought to test regenerating nerve fibers, therefore may not be present in mild disease44,45

Not positive in acute CTS (ie, less than three weeks’ duration)

Requires independent testing; validity compromised by possibility that other nerve is compressed (eg, thoracic outlet syndrome)

CTS = carpal tunnel syndrome.

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TABLE 3. Description of Diagnostic Tests for Carpal Tunnel Syndrome—Sensory/Motor Tests Test

Method

Positive Result

Variations

Precautions

Touch threshold—SemmesWeinstein Monofilaments (SWMF) or Weinstein Enhanced Sensory Test (WEST)

A five piece SWMF/ WEST set is used; filaments are applied (to just bend) on digit pulps; 2.83 usually applied three times

Variation in application techniques (rate, number, contact time) and decision rules30; variations in test protocols are common

Bilateral symptoms and ulnar neuropathy complicate comparative site; skin calluses, increased threshold with aging; five piece kit may be preferable for diagnosis, 20-piece kit may be preferable for outcome evaluation

Vibration threshold measured with tuning forks

Tuning fork (256 cps) is hit and the prong applied tangentially to fingertip pulp D1– D3 of affected side and comparative site

Vibration threshold measured with vibrometer

Vibration stimulus is applied to digital pulp

Decision rules can vary; a threshold greater than 2.83 is abnormal in digits D1–D3; usually D2 or D3 assessed; comparison with D5 may improve specificity by eliminating thresholds greater than 2.83 because of calloused skin or aged related decline Patient signals whether feeling is different compared with normal site (D5) or alternate side (can be increased or decreased) Thresholds greater than norms

Current perception threshold

Patient touched by equipment that stimulates sensory nerves by delivering current at different frequencies

Two-point discrimination

Patient has to distinguish between touch of prongs (either one or two); prongs should be applied until skin just blanches Thenar muscles are innervated by median nerve; compromise of motor fibers results in impairment of these muscles Thenar muscles are innervated by median nerve; compromise of these fibers leads to atrophy

Thenar weakness

Thenar atrophy

Patient signals when stimulus is perceived, thresholds and frequency ratios are compared with established norms; computer software performs these analyses >5 mm on pulps is considered abnormal

Oxford grading of abductor pollicis brevis indicates less than grade 5

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Models vary with respect to frequencies of vibration and contact area48–50 Different models vary mainly on software

Expensive

Disk-Criminator is well-suited; other devices are on the market

Paper clips are sometimes used but are unable to provide required flat, even stimulus

Devices which could measure actual force are more sensitive but not widely available; customized test units developed by some

Quantitative test methods deficient

Expensive

Visual inspection of abductor pollicis brevis reveals loss of muscle bulk

disagreements related to scoring items when there was an inadequate description within the text of the article. A minority of disagreements was due to failure of one of the raters to find specific information while reviewing the article. All disagreements were easily resolved when the authors consulted the text 312

Variation in application techniques (rate, number, duration, end of tuning fork) and decision rules

of the article together. For the remaining articles, the authors independently read and rated the quality using the same instrument. The articles and review ratings were exchanged and the authors determined their agreement on the score for any items in which disagreements were noted.

Methods for Synthesis of Retrieved Information Establishing an objective method for synthesis of the retrieved information proved to be problematic. Cutoff scores were not established for the instrument, and they were not considered appropriate because the relative importance of items varies within and across studies. Nevertheless, studies that scored poorly, particularly on the first items on the scale (marked with an asterisk) addressing blinding, reference standards, and sampling, must be considered to be of poorer quality. The difficulty in synthesizing information across different diagnostic accuracy studies when dealing with CTS relates to a number of issues, the most serious of which is difficulty in defining a gold standard diagnosis for CTS. The lack of a single test that meets this gold standard results in difficulties in defining cases and controls. Another issue is differences in the study samples. For example, diagnostic tests would be expected to perform quite differently when cases are drawn from community-based samples versus clinically based samples. It was apparent in many of the studies that there was a general lack of awareness of appropriate methodologies for designing and interpreting diagnostic test studies. Nevertheless, the authors felt it was important to identify a strategy to synthesize some of the available information, providing more stable estimates of diagnostic accuracy. The authors discussed these issues and decided to classify each test into one of three categories. They agreed that results from individual studies were likely to be very unreliable because the methodologies were of poor quality. Therefore, if a clinical test was only evaluated in a single study of low to medium power, it was classified as ‘‘unable to make recommendations.’’ Tests in which sensitivity and specificity were both less than 50% were considered to have relatively little value in any clinical circumstance and therefore were classified as ‘‘not useful in diagnosis of CTS.’’ The remaining tests, in which either sensitivity or specificity was greater than 50%, were classified as ‘‘potentially useful in diagnosis of CTS.’’ The authors agreed that subjects could be considered to have a diagnosis of CTS if they presented with symptoms consistent with CTS and if that diagnosis was substantiated by any of the following: electrodiagnosis, positive response to splinting/injection/ surgery, or a clinical diagnosis by an experienced clinician. It was felt that the best estimate of sensitivity was the average across such studies, in which sensitivity was weighted by the study sample size. Estimation of specificity was more problematic, because different types of comparison/control groups were used. Studies that include normal asymptomatic controls might produce falsely high

specificity because persons without symptoms would be expected to have ‘‘negative’’ results for most diagnostic tests. In addition, asymptomatic individuals would not present to a clinician for diagnosis, that is, they do not present a diagnostic dilemma. When the comparison group comprises patients with symptoms of CTS but a negative electrodiagnosis, specificity may be underestimated, because it is highly probable that some of those patients actually do have CTS. Therefore, the authors agreed to calculate specificity estimates for all studies together and for studies with these different types of comparison groups (see Table 5). The estimates were averages of the specificity values reported in the studies, weighted by the study sample size.

RESULTS Of the 75 papers reviewed, four were rejected because they did not specifically address diagnostic accuracy. These studies typically looked at differences in a clinical criterion in patients versus cases, but did not specify cutoff criteria or use specific criteria to classify patients. Eleven studies6–16 were not included in data synthesis because they only addressed tests that were classified as ‘‘unable to make recommendations.’’ Tests were classified in this category if there were limited source data. The tests included: specific elements of the history (when methods varied between studies), sensory evaluations performed by the Automated Tactile Tester (ATT),17 the Wisconsin Functional Sensory and Psychomotor Battery,6,7 the seven-minute stress test,11 combined wrist and finger (fist) flexion,18 subjective feeling of swelling,19 Levine’s questionnaire when used for diagnosis,20 the relief maneuver,21 square wrist,22 moving two-point discrimination, and diagnostic scales recently developed by Graham15 and Kamath.16 The remaining 60 papers contained tests that were classified as ‘‘potentially useful in diagnosis of CTS.’’ The quality of the reviewed papers varied widely with scores ranging from 1 to 12 of 12 (Table 4). A file of the ratings of individual studies is available on request from the authors. It should be noted that the majority of studies failed to report on the diagnosis of the subjects without CTS and on the reliability of the diagnostic tests. Few studies indicated whether the testers were blinded to the gold standard results, and less than half described noncases that would represent a spectrum of patients who would normally present for differential diagnosis. Only 15 studies20,22–35 had quality scores of 8 or greater out of 12. Table 5 contains summaries of the numerical syntheses performed on the diagnostic tests. The largest synthesis was performed for Phalen’s test with over 3000 cases and 1600 controls, providing an overall estimate of 68% sensitivity and 73% April–June 2004 313

TABLE 4. Summary of Quality Evaluation of Studies Examining Diagnostic Tests for Carpal Tunnel Syndrome Criterion Number and Topic 1. 2. 3. 4. 5. 6.

No. of Studies That Met Criterion

Blind comparison Gold standard Applied to all Severity cases Noncases differential diagnosis Noncases spectrum

14 48 46 28 27 6

Criterion Number and Topic 7. 8. 9. 10. 11. 12.

No. of Studies That Met Criterion

Sample size Test description Test interpretation Reliability 2 3 2 tables Statistics

43 49 46 8 44 41

Notes: Total number of studies evaluated = 60. Fifteen of 60 studies had quality scores $8/12. Mean quality score = 6.7/12. See Appendix A for more detailed description of each criterion.

specificity. The second largest pool of data was on Tinel’s test and suggests that it is less sensitive and somewhat more specific. Tests with less than 50% sensitivity included the flick test, the tethered median nerve test, the fist (lumbrical provocation) test, static two-point discrimination, and abductor pollicis brevis weakness/atrophy. Although the latter two tests are positive in a small percentage of patients with CTS, specificity is very high. Thus, when these abnormalities are found, they provide strong support for a CTS diagnosis.

The results confirmed the expectation that specificity would be higher in studies using normal controls than in studies with symptomatic controls. The largest number of such studies was averaged for Phalen’s test, in which specificity was 86% and 65% in these two respective situations.

DISCUSSION Clinical diagnosis of CTS is an important issue given the high prevalence of CTS, the potential

TABLE 5. Average Sensitivity and Specificity of Carpal Tunnel Syndrome Diagnostic Tests across Studies Weighted by Sample Size

Test Phalen’s Tinel’s

References 18–22,25,26,31,32,35,51–71

Specificity— Symptoms Specificity and Negative Specificity— Number Average All Asymptomatic Electrodiagnostic Number of Average of Test Controls Cases Sensitivity Controls Studies 3218 2640

68 50

1637 1614

73 77

86 84

65 65

1985

64

1082

83

88

64

640 190 5036 306 254

57 80 47 59 48

360 238 3854 316 92

78 92 62 61 76

86 90

55

68

51 26

293 159

75 48

226 175

72 81

90 92

60 71

381 107

24 29

212 88

95 80

92

98 80

107 46

12 80

88 63

94 61

811

72

567

62

26,31,58,78,82,83

343

55

170

81

24,48,78,79,84–87

377

50

590

73

18,19,22,26,31,32,35, 52–56,58,60,62–75

Carpal compression (CC) Wrist extension CC + wrist flexion Flick Gilliat Tethered median nerve Hand diagram Fist (lumbrical provocation) Static two-point Abductor pollicus brevis (APB) strength APB atrophy Current perception threshold Semmes-Weinstein monofilament Vibration with tuning fork Vibrometry

22,25,26,28,51–53,58, 60,62,63,68,70–72,74,76 18,26,31,53,68,72,75 18,62,77 23,32,34,72 54,55,58,72,74 29,31,46,69

20,32,38,65,67,70 27,74

17,36,54,58,78,79 25,72

25,72 80,81

17,30,31,33,36,54,

94

86

70

85

67

57,58,70,78,79

Overall sensitivity and specificity were determined by calculating a weighted average over all studies (weighted by sample size). Mean ‘‘specificity—asymptomatic controls’’ was calculated from studies that used healthy controls. Mean ‘‘specificity—symptoms and negative electrodiagnostic test’’ was calculated from subjects who had carpal tunnel syndrome-like symptoms but negative electrodiagnostic findings. Excluded from analyses are tests classified as ‘‘unable to make recommendations’’ (see text for list of tests).

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resulting disability, and the predictable response to treatment.40 In fact, of the conditions seen by hand therapists, there is no other single condition for which so many different clinical diagnostic tests have been described. The large number of articles retrieved and evaluated in this review reflects this emphasis on diagnostic tests for CTS, and exceeds the 21 papers reported on in a previous systematic review.5 MassyWestropp et al.5 excluded studies that did not compare clinical tests against electrodiagnosis as the gold standard, whereas the present review included studies in which the gold standard was successful treatment and/or electrodiagnosis. The previous review excluded studies that calculated sensitivity and specificity from a combination of tests. In our review, we critically appraised such articles, but were unable to use the data for statistical compilation. Finally, some of the variation between systematic reviews must be due to variation in methods of searching the literature. Because Massy Westropp et al.5 did not describe their search terms, the extent of these differences cannot be evaluated. Several common flaws were noted in the studies. Some of these arose because there is no agreement on a gold standard diagnosis for CTS. Several studies used normal controls, frequently without performing electrodiagnostic tests on them. The assumption was that a lack of symptoms was sufficient to establish the lack of the target diagnosis. However, it is known that abnormal electrodiagnostic results can occur in the absence of symptoms. More importantly, clinical diagnostic tests serve to differentiate patients with similar symptoms but with different disorders. Therefore, it is important that this diagnostic dilemma be replicated in studies evaluating diagnostic tests. Investigators who fail to do so are likely to report elevated specificity values, which cannot be generalized to the clinical situation. On the other hand, there are research designs that can result in a control group that includes some persons with CTS. A number of studies, particularly those done in conjunction with an electrodiagnostic laboratory, included control subjects with typical CTS symptoms and negative electrodiagnostic results. Most clinicians, particularly hand therapists, would consider these patients to have CTS and a falsely negative electrodiagnosis. Inclusion of these patients as control subjects is likely to provide a low estimation of clinical test performance. An appropriate control group for CTS diagnostic test studies should include persons who have similar pathology in different areas (eg, compression in the cubital tunnel or at Guyon’s canal) or different pathologies in the same area (tendinitis, arthritis, trigger fingers, and so on). Furthermore, appropriate diagnostic tests/examinations should be conducted to establish that these diagnoses were in fact the

cause of the patient’s symptoms. In general, sampling procedures were not designed to develop this type of control group, nor were precise descriptions of the control group included in many of the studies presented in this review. In many of the reviewed studies, the investigators failed to document the reliability of the diagnostic tests or to adequately describe how they were performed and/or interpreted. In fact, a number of common tests are performed in a variety of different ways. The clinical test evaluated in a diagnostic study should be described in sufficient detail so that others can replicate it. Ideally, the description would include instrument(s), test protocol, calibration procedures, and training/experience of the examiners. As stated previously, the importance of the training/ experience of the examiners became apparent during the course of the review and led to modification of the appraisal instrument. In some test procedures such as sensory evaluation, we would anticipate that clinical training and experience have a substantial impact on the interpretation of test results and observations. However, in most studies, there was no description of the testers or their qualifications. With other clinical tests, even inexperienced evaluators may be able to correctly perform and interpret them. Documentation of the experience required to obtain valid results is important, particularly when deciding which tests may be used in different situations.

Assessment Recommendations Given the variety of diagnostic tests for CTS, the large number of studies evaluating their properties, and the widely disparate results from these studies, it was difficult to make firm conclusions on the value of specific tests. Thus, we were faced with the same difficulty in synthesizing available studies as noted in a previous systematic review.5 However, we felt that it was important to go beyond generic or subjective recommendations, which could easily be accomplished in a narrative review. Therefore, we classified tests into three groups: ‘‘unable to make recommendations,’’ ‘‘not useful,’’ and ‘‘potentially useful’’ in the diagnosis of CTS. We also used a simplistic ‘‘meta-analysis’’ strategy in which we combined estimated sensitivity and specificity reported for individual tests across studies weighted by sample size. We quantified the impact of the control group on obtained specificity by combining specificity across tests according to three methods. Not surprisingly, the results demonstrated that specificity is high when normal control subjects are used and less favorable when persons with symptoms consistent with CTS are included in the control group. Although our meta-analysis strategy may be simplistic, we felt it was valuable to provide more April–June 2004 315

stable estimates, particularly on test sensitivity. For example, it is difficult to make decisions based on the numerous studies evaluating Phalen’s test given that sensitivity ranges from 10% to 91%.4 The sensitivity of 68% achieved over 3000 cases provides relatively strong evidence that this test is useful, although falsenegatives can be anticipated. Although others5 have suggested that two-point discrimination is specific, but not sensitive, we were able to confirm these characteristics. Across six studies and over 500 patients (see Table 5) specificity was 95%, whereas sensitivity was only 24%. For some clinical tests, variations in study results may be due to differences in how tests are performed. Vibration is a good example. Experimental evidence has suggested that vibration sensibility is affected early in compression, and this finding has served as the physiological foundation for its use as a diagnostic test. However, we noted extreme variations in how this test was performed. Different frequencies and different ends of the tuning fork were used to provide the stimulus. Variation across studies using vibrometers was even more extreme. Although one might expect vibrometers to be more accurate than tuning forks, the data do not support this. Given the wide variation in devices, modes of application, frequencies, and methods for defining abnormality, it is difficult, at this time, to determine the value of vibration in diagnosing CTS. A number of authors33,36 have questioned the accuracy of Semmes-Weinstein Monofilament test (SWMF) in the diagnoses of CTS. Our meta-analysis strategy included data from over 1300 patients and suggests that monofilament testing does provide useful information, although specificity is lower than sensitivity. Due to the wide variation between studies and the important role of the examiner in conducting tests, future definitive studies must include detailed descriptions of test methodologies and testers. Provocative and sensorimotor tests are not used in isolation, but rather within a clinical reasoning framework. Most commonly, these tests are used to confirm or refute the suspicion of CTS based on a given patient’s history/symptom presentation. Typically, patients would initially be treated with night splints after a clinical diagnosis of CTS. Response to this intervention would form an additional component of subsequent diagnostic evaluations before consideration for surgery. The accuracy of diagnostic tests for CTS is not as critical as it is for a diagnostic test in which a false-negative might end in death (e.g., differentiation between benign and malignant tumor) and/or a false-positive might result in unnecessary high-risk interventions such as surgery, radiation, or chemotherapy. However, tests for CTS must still be able to make a significant contribution to clinical decision making. This review established that a number of provocative and sensori316

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motor tests meet the level of accuracy required. Higher sensitivity is needed for screening (low prevalence) and higher specificity is appropriate when prevalence is high or when considering surgery. Hand therapists can select the tests appropriate for their clinical situation using the sensitivity and specificity of specific tests determined by our systematic review and simplistic meta-analysis.

Limitations of This Review The primary limitation of this review was introduced by the inherent difficulties in establishing a gold standard diagnosis for CTS. This difficulty, combined with methodologic flaws, made interpretation difficult. Although we established a process to use the results of multiple studies to provide more stable estimates of sensitivity and specificity, there is no guarantee that these choices increased the validity of our results. It is possible that we did not identify all relevant studies. However, the number of studies in this review was large and exceeded the total covered in a previous systematic review.5 We, therefore, feel it is unlikely that we missed important evidence. Although systematic reviews have been purported to decrease bias, more detailed evaluation of this process has demonstrated that results can vary between different systematic reviews according to the search strategies and critical appraisal instrument used.37 Thus, we should not consider the findings of this review to be conclusive concerning the value of clinical tests in the diagnosis of CTS. Furthermore, a systematic review requires that issues be addressed using specific and documented methods. Clinical commentaries within this context are not valued. Therefore, discussions on why certain tests may be better in specific situations or relevant in different stages of CTS are beyond the scope of this review. Also, studies that would support clinical commentaries are unlikely to be retrieved using a search strategy designed to identify diagnostic test studies. The authors recommend that clinicians augment information from systematic reviews with information from other types of studies, including narrative reviews, to achieve a broader understanding of clinical tests used in the diagnosis of CTS.

Recommendations for Future Studies Despite the high quantity of studies available, additional studies are required to make clearer recommendations regarding diagnostic tests for CTS. These studies should adhere to the methodologic principles outlined in the quality assessment tool (Appendix A). In particular, it is essential to carefully select appropriate patients who present a diagnostic dilemma. All patients should undergo

a blinded assessment to establish their true diagnosis. In the case of CTS, symptoms consistent with CTS and verified either by electrodiagnosis or response to surgery or injection should be considered sufficient to establish that the patient does have CTS. Normal electrodiagnostic studies and a verified alternative diagnosis should be considered criteria for the control group. These alternate diagnoses should include compressive neuropathies affecting the ulnar nerve or the median nerve proximal to the carpal tunnel, and alternate pathologies (bone/ muscle/tendon disorders) affecting the hand. Examiners should be blinded to the reference standard diagnosis when assessing patients within the context of the study. In addition, detailed descriptions of the test methods and examiner training/expertise should be provided. If reliability data are available, they should be presented and referenced. Otherwise, reliability should be evaluated within the context of the study. Sufficient sample size and appropriate statistics are obviously necessary and, at a minimum, should include sensitivity and specificity. If a sufficient number of investigators adhere to these principles, a future systematic review may be able to perform a meta-analysis across only those studies that demonstrate high quality and provide a more valid estimate of sensitivity and specificity of diagnostic tests. There is a need to establish the use of specific clinical diagnostic tests as performed by hand therapists. This is most clearly evident in published studies evaluating the accuracy of SWMF. Wide support exists within the hand therapy community for using SWMF to assess sensation, and yet there is considerable controversy in the literature on the validity of SWMF in the diagnosis of CTS.33,36 Although a number of studies have found acceptable levels of sensitivity for SWMF, specificity has been repeatedly questioned. Clinical judgment may aid in the identification of reasons, other than CTS, for abnormal thresholds. However, studies that define concrete decision rules do not provide for these exceptions. Studies that compare concrete decision rules with more complex decision-making, as performed by hand therapists, should be conducted to determine the role of professional judgment and expertise in interpretation of these tests. Without such studies, hand therapists will have difficulty justifying diagnoses based on these tests. Finally, a number of tests identified in the systematic review were classified as ‘‘unable to make recommendations’’ because there was insufficient evidence to either support or refute their use. These tests warrant further study. CTS is a clinical syndrome defined by history and supported by a clinical examination that may include specific clinical tests designed to classify patients

either as having CTS or not. This systematic review identified a number of clinical tests that can be used by hand therapists to assist in making this diagnosis.

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APPENDIX A Criteria for Evaluating Quality of Studies on Diagnostic Tests Criteria 1.* 2.* 3.* 4. 5.* 6. 7. 8. 9. 10. 11. 12. 13. 14.

Y

N

Was there an independent, blind comparison with a reference standard test? Was the selected reference standard/true diagnosis a gold standard or reasonable alternative? Was the reference standard applied to all patients? Did the actual cases include an appropriate spectrum of severity? Were the ‘‘noncases’’ patients who might reasonably present for differential diagnosis? Did the ‘‘noncases’’ include an appropriate spectrum of patients with alternate diagnoses? Did the study have an adequate sample size? Was the description of the test maneuver described in sufficient detail to permit replication? Were exact criteria for interpreting the test results provided? Was the reliability of the test procedures documented? Were the number of positive and negative results reported for both cases and noncases? Were appropriate statistics (sensitivity, specificity, likelihood ratios) presented? Were the skills/expertise of the tester (clinical test) described? Did the tester have the appropriate skills/expertise to reliably perform the tests?

The validity and/or applicability of the study results could be questioned if there is a significant problem with any of these criteria, although the items with an asterisk (*) are particularly important. The clinician must make the final decision based on a preponderance of the information. This form and the detailed criteria for the evaluation of each item were designed by MacDermid based on principles of evidence-based practice described by Sackett.3 Note that criteria 13 and 14 were not used in this review, but were suggested as additions to the evaluation tool after the study was completed.

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