Management of Carpal Tunnel Syndrome
Endorsed by: ASSH, ASPS, ACR, ACS, ASA
Observation
Strong evidence supports Thenar atrophy is strongly associated with ruling-in carpal tunnel syndrome, but poorly associated with ruling-out carpal tunnel syndrome.
Strong Evidence Strong Evidence
There were two high quality (Claes, 2013; Naranjo, 2007) and two moderate quality studies (Gomes, 2006; Makanji, 2014) with strong evidence that the presence of thenar atrophy can rule in the diagnosis of CTS.  Pooling the results into a meta-analysis demonstrated a strong association with electrodiagnostic studies (EDS) that used the criteria for the diagnosis of CTS established by the American Association of Electrodiagnostic Medicine (AANEM). The individual studies, as well as the meta-analysis, showed that the absence of thenar atrophy did not rule out the diagnosis of CTS.  The meta-analysis did not include two moderate quality studies (De Krom, 1990 or Gerr, 1998) because of variations in the electrodiagnostic test methods and also because of the availability of higher quality evidence examining the utility of thenar atrophy. The study by Claes was somewhat limited by its exclusion of the patients with severe thenar atrophy.  The studies also did not clearly differentiate loss of thenar muscle bulk on a neurogenic basis versus disuse atrophy, for example in cases of trapeziometacarpal joint osteoarthritis.
 
Physical Signs
Strong evidence supports not using the Phalen Test, Tinel Sign, Flick Sign, or Upper limb neurodynamic/nerve tension test (ULNT) criterion A/B as independent physical examination maneuvers to diagnose carpal tunnel syndrome, because alone, each has a poor or weak association with ruling-in or ruling-out carpal tunnel syndrome.
Strong Evidence Strong Evidence
Evidence from five high quality studies (Gok, 2008; Naranjo, 2007; Vanti, 2011; Vanti, 2012; Wainner, 2005) and one moderate quality study (Tan, 2012) supports not using the Phalen Test, Tinel Sign, Flick Sign, or ULNT criterion A/B as independent physical examination maneuvers to rule in or rule out the diagnosis of carpal tunnel syndrome.  Each of these studies showed poor agreement with electrodiagnostic tests as the reference standard.  The EDS criteria in some instances used the AANEM criteria and in others general EDS methods. A meta-analysis of the performance of the Tinel sign and Phalen test also demonstrated poor agreement to this reference standard. 
 
Maneuvers
Moderate evidence supports not using the following as independent physical examination maneuvers to diagnose carpal tunnel syndrome, because alone, each has a poor or weak association with ruling-in or ruling-out carpal tunnel syndrome: • Carpal Compression test • Reverse Phalen Test • Thenar Weakness or Thumb Abduction Weakness or Abductor Pollicis Brevis Manual Muscle Testing • 2-point discrimination • Semmes-Weinstein Monofilament Test • CTS-Relief Maneuver (CTS-RM) • Pin Prick Sensory Deficit; thumb or index or middle finger • ULNT Criterion C • Tethered median nerve stress test • Vibration perception – tuning fork • Scratch collapse test • Luthy sign • Pinwheel
Moderate Evidence Moderate Evidence
Several moderate and high quality studies provided a moderate level of evidence to suggest that the various tests listed above were not found to have been used as individual tests to rule in or rule out the diagnosis of CTS.  CTS-RM had a moderate association to the reference standard when ruling-in CTS according to one high quality study (Gok, 2008) however the generalizability of these results is unclear because the study sample only contained female subjects. Meta-analysis could not be performed on any of these studies due to inconsistent reporting or lack of sufficient evidence. The reference standard for comparison was the use of either electrodiagnostic studies (EDS) following AANEM criteria or other general EDS methods.  There is conflicting evidence of whether or not combining tests helps to rule in or rule out the diagnosis of CTS, as the test combinations were not validated or weighted to ensure reliability, accuracy, and/or clinical relevance; any valid scales are evaluated in the diagnostic scales recommendation.
History Interview Topics
Moderate evidence supports not using the following as independent history interview topics to diagnose carpal tunnel syndrome, because alone, each has a poor or weak association with ruling-in or ruling-out carpal tunnel syndrome: • Sex/gender • Ethnicity • Bilateral symptoms • Diabetes mellitus • Worsening symptoms at night • Duration of symptoms • Patient localization of symptoms • Hand dominance • Symptomatic limb • Age • BMI
Moderate Evidence Moderate Evidence
Two high quality studies (Claes, 2013; Katz, 1990) and several moderate quality studies investigated the relationship between history interview topics and CTS as compared to a reference standard which was the use of either EDS following AANEM criteria or general EDS methods. When examined individually, each of the factors listed above had a poor or weak association with EDS based on the likelihood ratio. Sex/gender data pooled in a meta-analysis, also showed a poor association with electrodiagnostic testing.
 
Patient Reported Numbness and Pain
Limited evidence supports that patients who do not report frequent numbness or pain might not have carpal tunnel syndrome.
Limited Evidence Limited Evidence

One moderate quality study (MacDermid, 1997) found a strong or moderate association between CTS and patient reporting of frequent numbness or frequent pain. 
 

Hand-Held Nerve Conduction Study (NCS)
Limited evidence supports that a hand-held nerve conduction study (NCS) device might be used for the diagnosis of carpal tunnel syndrome.
Limited Evidence Limited Evidence
There was one moderate quality study (Tan, 2012) evaluating the use of a hand-held NCS device for the diagnosis of CTS. This study showed that a handheld NCS device can rule in or rule out the diagnosis of CTS, in patients with typical symptoms of CTS, using EDS following AANEM criteria as the reference standard. The hand-held NCS device closely parallels the severity of disease compared with the neurological assessment as well. 
MRI
Moderate evidence supports not routinely using MRI for the diagnosis of carpal tunnel syndrome.
Moderate Evidence Moderate Evidence
There was one high quality study (Jarvik, 2002) evaluating MRI for the diagnosis of CTS. Findings on MRI had a weak or poor association as a rule out test for CTS as compared to a classic or probable hand pain diagram and nerve conduction study. Only severe fascicular swelling, severe flexor tenosynovitis, or severe increased muscle signal had a strong association with CTS, suggesting that MRI would be insensitive in identifying the diagnosis of CTS in the majority of patients in whom these findings would be unlikely to be present.
Diagnostic Ultrasound
Limited evidence supports not routinely using ultrasound for the diagnosis of carpal tunnel syndrome.
Limited Evidence Limited Evidence
There were five high quality (Naranjo, 2007; Moran, 2009; Ziswiler, 2005; Wong, 2004; Claes, 2013) and seven moderate quality studies (Abdel Ghaffar, 2012; Dejaco, 2013; Fowler, 2014; Hashemi, 2009; Moghtaderi, 2012; Nakamichi, 2002; Pastare, 2009) evaluating ultrasound for the diagnosis of CTS compared with EDS as the reference standard. These studies showed conflicting results regarding the utility of ultrasound (US) as either a rule in or rule out test in the diagnosis of CTS. In general, there was variation between the studies for the cut-off value for making the diagnosis or for exclusion of CTS. The ideal location for measuring the cross-sectional area (CSA) of the median nerve for indicating the diagnosis of CTS also varied between studies.  There is a general agreement that a CSA greater than 12-13 mm is strongly correlated with EDS.  As a rule out study for CTS, there is a strong correlation with CSA below 8 mm. One moderate quality (Abdel Ghaffar, 2012) and one low quality study (Mallouhi, 2006) suggest that a US measurement of nerve hypervascularity may have a strong association as a rule out study for CTS. 
Diagnostic Scales
Moderate evidence supports that diagnostic questionnaires and/or electrodiagnostic studies could be used to aid the diagnosis of carpal tunnel syndrome.
Moderate Evidence Moderate Evidence
The evaluation of diagnostic tools, either scales based on clinically acquired information from the history and physical examination, or electrodiagnostic tests, requires a clear consensus on a reference standard against which the performance of these diagnostic tests can be compared. This type of consensus still does not exist with respect to carpal tunnel syndrome. It is recognized that electrodiagnostic testing has long been considered to represent a reference standard but this assumption is untenable because these tests clearly have false positive and negative results. Beyond this there simply is no consensus supporting any single diagnostic tool as a reference standard. Where clinical diagnostic scales are taken as the reference standard, electrodiagnostic tests may demonstrate poor sensitivity and specificity. The same is true of clinical diagnostic scales when electrodiagnostic tests are taken as the reference standard. Agreement between electrodiagnostic tests and clinical diagnostic tests, regardless of which is taken as the reference standard, is also complicated by the binary nature of the comparison. Electrodiagnostic data is, by and large, continuous in nature and so establishing a hard cutoff point to compare to clinical diagnostic scales seems potentially arbitrary. At least one of the clinical diagnostic scales, the CTS-6, attempts to address this by defining the diagnosis in probabilistic terms as a continuous variable. Given this set of circumstances the Workgroup sought to evaluate the role of clinical diagnostic tests and electrodiagnostic testing in the evaluation of CTS in the context in which they are used, in other words, in clinical settings where a patient presents with complaints that might be attributable to this condition.
 
There were two clinical diagnostic tests studied in high quality investigations, the Katz Hand Diagram and the CTS-6. The Boston Carpal Tunnel Scale, a status instrument most frequently used to measure outcomes of treatment for CTS was also evaluated in two high quality studies.
 
In comparison to electrodiagnostic testing Katz et al demonstrated high sensitivity (0.96) and good negative predictive value (0.91) for the “classic”, “probable” or “possible” designations however, positive predictive value and specificity were low. This indicates that, using electrodiagnostic testing as a reference standard, the Katz Hand Diagram used in this way had more value as a “rule out test”. Sensitivity decreased and specificity increased if comparison to electrodiagnostic tests was made only using “classic” or “probable” results. Sensitivity decreased further and specificity was commensurately increased when only “classic” results were compared to electrodiagnostic testing. Defined using only “classic” or “classic” or “probable” results the Katz Hand Diagram was considered weak or poor as either a “rule in” or “rule out” test. Vanti made similar observations using AANEM electrodiagnostic definitions for CTS in demonstrating that the “classic” or “probable” results functioned as a strong “rule out” test.
 
Graham took a different approach to evaluating the respective roles of electrodiagnostic testing and the CTS-6, an instrument that expresses the probability of CTS. The pre-test probability of CTS was established using the CTS-6 and then the post-test probability after electrodiagnostic testing was estimated using likelihood ratios established with two electrodiagnostic standards for CTS, one lax (with higher sensitivity and lower specificity) and one stringent (with lower sensitivity and higher specificity). This study showed that the changes in probability after electrodiagnostic testing, using either electrodiagnostic definition, were small and probably below a clinically relevant standard. This suggests that the most appropriate setting for electrodiagnostic testing is where there is uncertainty about the clinical diagnosis.
 
There were two high quality studies evaluating the Boston Carpal Tunnel Syndrome Questionnaire (Wainner, Naranjo). Both of these studies used electrodiagnostic tests as the reference standard. The results were consistent in both studies in showing that this instrument functioned as either a weak or poor “rule in” or “rule out” test. This may have been due to the fact that the scale was actually developed as a status instrument rather than as a diagnostic scale.
Increased Risk of CTS (Strong Evidence)
Strong evidence supports that BMI and high hand/wrist repetition rate are associated with the increased risk of developing carpal tunnel syndrome (CTS).
Strong Evidence Strong Evidence
BMI evaluated as a continuous variable was shown to be associated with development of CTS in four high quality (Armstrong, 2008; Bonfiglioli, 2013; Evanoff, 2014; Garg, 2012) and three moderate quality studies (Burt, 2011; Hlebs, 2014; Nordstrom, 1997). Only one moderate quality study (Goodson, 2014) found an insignificant result for the relationship between BMI and CTS. When evaluated as a categorical variable, five moderate quality studies (Becker, 2002; Burt, 2011; Burt, 2013; Coggon, 2013; Geoghegan, 2004) found a correlation between increasing BMI and development of CTS, while one high quality study (Hakim, 2002) and two moderate quality (Mondelli, 2006; Violante, 2007) studies found no significance.
 
High hand/wrist repetition rate at work was significantly associated to an increased risk of CTS by two high quality (Armstrong, 2008; Evanoff, 2014) and four moderate quality studies (Chiang, 1990; Coggon, 2013; Goodson, 2014; Silverstein, 1987).  In all studies, the hand/wrist repetition involved moderate to high hand forces.  One of the high quality studies (Armstrong, 2008) showed an insignificant association in two of the categories of repetition, but still showed a significant increase between the high and low quartile categories.
Increased Risk of CTS (Moderate Evidence)
Moderate evidence supports that the following factors are associated with the increased risk of developing carpal tunnel syndrome (CTS): • Peri-menopausal • Wrist Ratio/Index • Rheumatoid Arthritis • Psychosocial factors • Distal upper extremity tendinopathies • Gardening • ACGIH Hand Activity Level at or above threshold • Assembly line work • Computer work • Vibration • Tendonitis • Workplace forceful grip/exertion
Moderate Evidence Moderate Evidence
Peri-menopausal status was shown in one high quality study (Hakim, 2002) to be associated with an increased risk of CTS development, but no association was found between CTS and post-menopausal status.
 
Wrist ratio/index (ratio of wrist depth to width >0.7mm) was significantly associated with an increased risk of CTS in one high (Armstrong, 2008) and six moderate quality studies (Boz, 2004; Gordon, 1988; Hlebs, 2014; Moghtaderi, 2005; Sabry, 2009; Shariff-Mollayousefi, 2008). 
 
Rheumatoid arthritis was associated with an increased risk of CTS in one high quality (Garg, 2012) and one moderate quality study (Burt, 2011).  One moderate quality study (Geoghegan, 2004) showed an association between osteoarthritis and CTS.
 
Mood (“felt down, blue or depressed always/never, compared to seldom”) was associated with increased risk of CTS in one high quality study (Garg, 2012). One moderate quality study (Coggon, 2013) showed an association with increased risk based on self-rated mental health.
 
Hand, wrist or elbow tendinopathies (musculoskeletal conditions) were associated with increased risk of CTS in one high quality (Garg, 2012) and two moderate quality studies (Aktas, 2008; Nordstrom, 1997).
 
Gardening was associated with an increased risk of developing CTS in one high quality study (Garg, 2012).
 
The American Conference of Governmental Industrial Hygienists (ACGIH) hand activity level (HAL) is a standardized method for evaluating jobs that involves expert observation, direct measurement or video analysis to assess both pinch/grip force and hand/wrist repetition rate. There was one high quality (Bonfiglioli, 2013) and three moderate quality (Burt, 2011; Burt, 2013; Violante, 2007) studies, showing significant associations to increased risk of CTS when the ACGIH HAL was at or above the threshold limit.  In addition, there was one high quality study (Garg, 2012) that showed an association with CTS by hazard ratio but this finding was limited by a wide confidence interval that included a value of 1.0 (HR: 2.01, CI: 0.8-5.0).
 
Assembly line work was associated with increased risk for the development of CTS in one high quality (Armstrong, 2008) and two low quality studies (Bonfiglioli, 2006; Lecler, 1998).
 
Computer work was significantly associated with increased risk of CTS by three moderate quality studies (Ali, 2006; Coggon, 2013; Eletheriou, 2012).  One study found an increased association with an average of greater than eight hours of computer use per day and more than four years of computer work (Ali, 2006).  Another study found an association between an increased risk of CTS and working on a keyboard or mouse for more than four hours per day (Coggon, 2013).  The third study found an association with a very high number of keystrokes typed per year and a higher risk of CTS (Eleftheriou, 2012). There was one moderate quality study (Ali, 2006) evaluating internet use for leisure, which also found a significant result for increasing risk of CTS.
 
The use of vibrating hand-held tools was associated with an increased risk of CTS in one high quality (Armstrong, 2008) and three moderate quality studies (Coggon, 2013; Dale, 2014; Nordstrom, 1997).
 
Tendonitis in the shoulder, hand, finger, or wrist was shown to increase risk of CTS by one high quality (Armstrong, 2008) and one low quality study (Werner, 2005).
 
Workplace forceful grip/exertion was found to be significantly associated with increased risk of CTS by one high quality (Armstrong, 2008) and four moderate quality studies (Burt, 2011; Burt, 2013; Dale, 2014; Evanoff, 2012).
Increased Risk of CTS (Limited Evidence)
Limited evidence supports that the following factors are associated with the increased risk of developing carpal tunnel syndrome (CTS): • Dialysis • Fibromyalgia • Varicosis • Distal radius fracture
Limited Evidence Limited Evidence
Comorbidities including dialysis, fibromyalgia, and varicosis each had one moderate quality study (Shin, 2008; Fahmi, 2013; De Krom, 1990) showing that each has a significantly increased risk of CTS.
 
Wrist fracture showed an increased risk of CTS in two moderate quality studies (Geoghegan, 2004; Dyer, 2008). One moderate quality study (Morgenstern, 1991) showed an insignificant relationship, but that study included only female participants and therefore the findings may not be generalizable. 
Decreased Risk of CTS
Moderate evidence supports that physical activity/exercise is associated with a decreased risk of developing carpal tunnel syndrome (CTS).
Moderate Evidence Moderate Evidence
Vigorous exercise was associated with reduced risk of CTS in one moderate quality study (Goodson, 2014).  In the same study, increased risk of CTS was associated with wrist straining exercise (e.g., weight lifting, mountain biking, racquet sports), but that risk was reduced if there was also vigorous exercise.  Another moderate quality study (Eleftheriou, 2012) found an association between regular physical activity (e.g., basketball, football, tennis, jogging, and swimming) and reduced risk of CTS.
Factors Showing No Associated Risk of CTS (Moderate Evidence)
Moderate evidence supports that the use of oral contraception and female hormone replacement therapy (HRT) are not associated with increased or decreased risk of developing carpal tunnel syndrome (CTS).
Moderate Evidence Moderate Evidence
Oral contraception use among females was shown to have no significant relationship to the development of CTS in three moderate quality studies (Geoghehan, 2004; Mondelli, 2006; Morgenstern, 1991). Oral HRT use among females was shown to have no significant relationship to the development of CTS in one high quality and one moderate quality study (Hakim, 2002; Geoghehan, 2004). 
Factors Showing No Associated Risk of CTS (Limited Evidence)
Limited evidence supports that race/ethnicity and female education level are not associated with increased or decreased risk of developing carpal tunnel syndrome (CTS).
Limited Evidence Limited Evidence
Education level among females showed no significant relationship to the development of CTS in one moderate quality (Bonfiglioli, 2007) and two low quality studies (Kaplan, 2008; Wright, 2014). Race/ethnicity showed no significant relationship to the development of CTS in one moderate quality study (Nathan, 2002).
Factors Showing Conflicting Risk of CTS
Limited evidence supports that the following factors have conflicting results regarding the development of carpal tunnel syndrome (CTS): • Diabetes • Age • Gender/Sex • Genetics • Comorbid drug use • Smoking • Wrist bending • Workplace
Limited Evidence Limited Evidence
Diabetes showed a conflicting relationship to CTS development.  One high quality study (Armstrong, 2008) did not demonstrate a significant association with CTS. The odds ratio was elevated but there was a wide confidence interval that included a value of 1.0 (OR 2.45, CI: 0.92-6.53).  Three moderate quality studies (Becker, 2002; Geoghegan, 2004; Plastino, 2011) found significant associations between diabetes and an increased risk of CTS and one (Coggon, 2013) did not find an association.
 
Age showed a conflicting relationship to CTS development. Two high quality studies (Armstrong, 2008; Bonfiglioli, 2013) showed increased risk in older workers on a continuous scale. Two other high quality studies (Evanoff, 2014; Garg, 2012) measuring age on a continuous scale showed insignificant results but with slightly increased risk ratios and narrow confidence limits. Two moderate quality studies (Morgenstern, 1991; Shin, 2008) also found a significantly increased risk of CTS when measuring age continuously and one moderate quality study (Silverstein, 1987) found an insignificant relationship. When measured categorically, one high quality study (Hakim, 2002) showed an increasing association at age >46 and one moderate quality study (Violante, 2007) found an increasing association among all categories.  Two moderate quality studies (Eleftheriou, 2012; Mondelli, 2006) did not find a significant association between categories of age and CTS development.
 
Female gender/sex was associated with increased risk of CTS in one high quality (Bonfiglioli, 2013) and three moderate quality studies (Burt, 2011; Eleftheriou, 2012; Violante, 2007), while two high quality (Armstrong, 2008; Evanoff, 2014) and two moderate quality studies (Shin, 2008; Silverstein, 1987) showed no significant association.
 
Family history/genetics was associated with increased risk of CTS in one high quality (Hakim, 2002) and two moderate quality studies (Bonfiglioli, 2007; Burt 2011), while two moderate quality studies (Nordstrom, 1997; Violante, 2007) showed no significant correlation. The studies used varying diagnostic methods, and two of the studies evaluated female populations, which may have contributed to the conflicting results.
 
Comorbid drug use showed a conflicting relationship to CTS development. One high quality study (Hakim, 2002) found no association with thyroxine replacement. One moderate quality study (Geoghegan, 2004) reported an increasing risk of CTS with insulin, sulphonyl, or thyroxine.  Two moderate quality studies reported no association to CTS when using diuretics (Morgenstern, 1991) or metformin (Geoghegan, 2004).
 
Smoking had a conflicting relationship to CTS development. Two moderate quality studies (Eleftheriou, 2012; Violante, 2007) found an association of increasing risk, one moderate quality study (Coggon, 2013) found an inverse association, and one moderate quality study (Geoghegan, 2004) found no association.
 
Wrist bending had a conflicting relationship to CTS development. One high (Armstrong, 2008) and one moderate quality study (De Krom, 1990) showed an increased risk while two moderate quality studies (Dale, 2014; Evanoff, 2012) displayed an insignificant association. One moderate quality study (Nordstrom, 1997) showed an insignificant result with a short duration of wrist bending and an increased risk of CTS with more frequent wrist bending.
 
Many recent high and moderate quality studies were identified and provide new insights into workplace factors associated with CTS.  However, the studies did not consider the relative contributions of personal and work-related factors on CTS, so it is difficult to calculate risk attributable to different risk factors from the data. Some occupational factors and workplace exposures were evaluated by single studies with weak designs or relatively weak exposure assessment methods.  The findings from those studies, therefore, did not contribute to the conclusions. Workplace categories include: clerical/office work, industrial, construction, farming, hospital, professional, technical, managerial, sales, skilled trades (agriculture, fabrication, machining, transporter techs, electricians, plumbers, construction), and other jobs. 
Immobilization
Strong evidence supports that the use of immobilization (brace/splint/orthosis) should improve patient reported outcomes.
Strong Evidence Strong Evidence
There are two high quality studies (Hall 2013 and Manente 2001) that directly compare the use of brace/splint to no use of brace/splint to treat carpal tunnel syndrome.  Hall 2013 compared 8 weeks of full-time splinting versus no splinting. The authors showed statistically significant improvement in pain and function (Boston Questionnaire for assessment of carpal tunnel symptom functional status scale, Boston Questionnaire for assessment of carpal tunnel symptom severity, AS, phalens, grip strength, Purdue Pegboard Test score, Semmes Weinstein monofilaments).  The authors describe statistically significant differences when comparing percent change in these factors from pre to post treatment.  There were some baseline/pretreatment differences between the groups, such that it calls into question whether these factors were actually statistically different after treatment.  Manente 2001 compared four weeks of night bracing to no intervention.  The treated group showed a reduction in the Boston Carpal Tunnel Questionnaire symptomatic score (from 2.75 to 1.54 at 4 weeks; p<0.001) and functional score (from 1.89 to 1.48 at 4 weeks; p<0.001). Subjects’ Global Impression of Change Questionnaire documented improvement in the braced group at 4 weeks (p=0.006). Subjects’ Global Impression of Change Questionnaire documented improvement in the braced group at 4 weeks (p=0.006).
 
Steroid Injections
Strong evidence supports that the use of steroid (methylprednisolone) injection should improve patient reported outcomes.
Strong Evidence Strong Evidence
There is one high quality study (Atroshi 2013) that directly compares the use of steroid injection to placebo to treat carpal tunnel syndrome.  In a prospective, randomized, double-blinded, placebo controlled study, the efficacies of 40mg methylprednisolone and 80mg methylprednisolone were compared to placebo injection at various time lines (10 weeks and 1 year). At 10 weeks, there was greater improvement in the CTS symptom severity score in the group receiving injections of 40mg or 80mg methylprednisolone (p<0.003) versus placebo injections; but there was no difference amongst the groups at 1 year.  However, patients receiving 80mg methylprednisolone injection were less likely to go on to need surgery than placebo injection (p=0.04). A small p-value (p<.05) indicates that this difference was not observed due to chance, subsequently favoring the alternative hypothesis of methylprednisolone injection improving patient outcomes.
 
Several high quality studies (Dammers 2006[1-3], Wong 2001, and Wong 2005) compare various doses of injected or routes of administration of methylprednisolone to treat carpal tunnel syndrome.  In a double blinded, randomized study, Dammers 2006 compare the efficacy of 20, 40, and 60mg methylprednisolone injections to treat carpal tunnel syndrome. There was no significant difference in treatment response at 1 year. In a randomized double blind controlled trial, Wong 2005 compare a the effects of a single 80mg methylprednisolone injection with saline injection at 8 weeks versus two 80mg methylprednisolone injections 8 weeks apart. There was no significant difference between groups respect to Global Symptom Score, electrophysiological study, or functional outcomes (p=0.26). In a prospective randomized double-blind study, Wong 2001 compared 25mg methylprednisolone orally for 10 days and placebo injection to 15mg methylprednisolone injection with oral placebo. The steroid injection provided significant improvement based on Global Symptom Score at 12 weeks.
 
Magnet Therapy
Strong evidence supports not using magnet therapy for the treatment of carpal tunnel syndrome.
Strong Evidence Strong Evidence

Several high quality studies (Colbert 2010, Weintraub 2008) evaluated the use of magnets in treating carpal tunnel syndrome.  In a prospective randomized double-blinded controlled trial, Weintraub 2008 evaluated the efficacy of a magnet (simultaneous static and time-varying dynamic magnetic field stimulation 4 hours/day for two months).  No significant measures of improvement were noted.  In a randomized, double-blind controlled trial, Colbert 2010 evaluated the efficacy of magnet (wore nightly for 6 weeks a neodymium magnet of 15 or 45mTesla) versus placebo magnet on the treatment of carpal tunnel syndrome.  No significant measures of improvement were noted.

Oral Treatments
Moderate evidence supports no benefit of oral treatments (diuretic, gabapentin, astaxanthin capsules, NSAIDs, or pyridoxine) compared to placebo.
Moderate Evidence Moderate Evidence
Two high quality studies (Chang 1998 and Hui 2011) compare various oral regimens to treat carpal tunnel syndrome. In a prospective randomized double-blind study placebo controlled study, Chang 1993 compare various 4 week oral medication regimens (diuretic [trichlormethiazide 2mg daily] versus NSAID [tenoxicam-SR 20mg daily] versus steroid [2 weeks of prednisolone 20mg daily followed by 2 weeks of 10mg daily]) to placebo. No significant changes from baseline were noted in the placebo, diuretic, or NSAID arms. However, the steroid arm improved significantly at 4 weeks, based on GSS Questionnaire. A review of the data provided indicates that at 4 weeks, the steroid arm had statistically significant improvement over the NSAID and diuretic arms based on GSS Questionnaire. Hui 2011 failed to show any significance when comparing oral Gabapentin to placebo.
 
Oral Steroids
Moderate evidence supports that oral steroids could improve patient reported outcomes as compared to placebo.
Moderate Evidence Moderate Evidence
Two high quality studies (Chang 1998 and Hui 2011) compare various oral regimens to treat carpal tunnel syndrome. In a prospective randomized double-blind study placebo controlled study, Chang 1993 compare various 4 week oral medication regimens (diuretic [trichlormethiazide 2mg daily] versus NSAID [tenoxicam-SR 20mg daily] versus steroid [2 weeks of prednisolone 20mg daily followed by 2 weeks of 10mg daily]) to placebo. No significant changes from baseline were noted in the placebo, diuretic, or NSAID arms. However, the steroid arm improved significantly at 4 weeks, based on GSS Questionnaire. A review of the data provided indicates that at 4 weeks, the steroid arm had statistically significant improvement over the NSAID and diuretic arms based on GSS Questionnaire. Hui 2011 failed to show any significance when comparing oral Gabapentin to placebo.
 
Ketoprofen Phonophoresis
Moderate evidence supports that ketoprofen phonophoresis could provide reduction in pain compared to placebo.
Moderate Evidence Moderate Evidence
In a randomized controlled trial, Soyupek 2012 compared phonophoresis with corticosteroid versus phonophoresis with nonsteroidal anti-inflammatory drug use.  Phonophoresis with corticosteroid showed statistically significant improved in VAS score.  In a prospective, randomized, double-blinded controlled trial, Yildiz 2011 compared the efficacy of 2 weeks of treatment with placebo ultrasound, ultrasound, or ketoprofen phonophoresis.   The group that underwent ketoprofen phonophoresis for two weeks demonstrated significant improvement in VAS score over the sham ultrasound and the ultrasound group at two weeks and eight weeks.  
 
Therapeutic Ultrasound
Limited evidence supports that therapeutic ultrasound might be effective compared to placebo.
Limited Evidence Limited Evidence
One high quality study (Ebenbichler 1998) evaluated the use of ultrasound in treating carpal tunnel syndrome.  In a randomized controlled trial, Ebenbichler 1998 evaluated the efficacy of ultrasound (20 sessions of 15 minute interventions of 1MHz, 1.0 W/cm, pulse mode 1:4 at 5 sessions/week for 2 weeks followed by 2 sessions/week) versus placebo ultrasound on the treatment of carpal tunnel syndrome.  Multiple measures showed significant improvement in the ultrasound group: grip strength, motor distal latency (p<0.001), and pinch strength.
 
Laser Therapy
Limited evidence supports that laser therapy might be effective compared to placebo.
Limited Evidence Limited Evidence
Several high quality studies (Chang 2008, Evcik 2007, Fusakul 2014) evaluated the use of laser therapy in treating carpal tunnel syndrome.  In a randomized, controlled trial, Chang 2008 evaluated the efficacy of a laser (830nm diode with 10Hz, 50% duty cycle, 60 mW, 9.7J/cm) versus placebo laser on the treatment of carpal tunnel syndrome.  The treatment was rendered for 10 minutes daily for 5 days a week for two weeks.  After 4 weeks, the laser treatment provided significantly improved grip strengths, digital prehension, and lateral prehension (p<0.05).  In a randomized controlled trial, Evcik 2007 evaluated the efficacy of laser (7J/2min) versus placebo laser.  The treatment was rendered five times per week for two weeks.  After four weeks, significant improvement in grip strength and pinch strength was noted (p<0.001); there was also significant improvement in sensory nerve velocity, sensory distal latency, and motor distal latency (p<0.001).  In a randomized double-blinded controlled trial, Fusakul 2014 evaluated the efficacy of laser (gallium-aluminum-arsenide at a dose of 18J/session) versus placebo laser.  Grip strength and pinch strength was significantly improved.  At 12 weeks follow up, distal motor latency was significantly improved (p<0.05).
 
Surgical Release Location
Strong evidence supports that surgical release of the transverse carpal ligament should relieve symptoms and improve function.
Strong Evidence Strong Evidence
There were 17 high quality (Atroshi 2006, Castillo 2014, Cellocco 2005, Cellocco 2009, Cresswell 2008, Gerritsen 2002, Hamed 2009, Hui 2005, Ismatullah 2013, Jarvik 2009, Larsen  2013, Malhotra 2007, Saw 2003, Sennwald 1995, Suppaphol 2012, Trumble 2002, and Zyluk 2006) and 10 moderate quality (Andreu 2013, Aslani 2012, Capa-Grasa 2014, Dumontier 1995, Elsharif 2014, Faraj 2012, Ly-Pen 2012, Tarallo 2014, Tian 2007, and Ucar 2012) studies demonstrating that release of the transverse carpal ligament is an effective treatment for patients with CTS.
 
Surgical Release Procedure
Limited evidence supports that if surgery is chosen, a practitioner might consider using endoscopic carpal tunnel release based on possible short term benefits.
Limited Evidence Limited Evidence
Eleven high quality (Atroshi 2006, Atroshi 2009, Ejiri 2012, Kang 2013, Larsen  2013, MacDermid 2003, Malhotra 2007, Saw 2003, Sennwald 1995, Trumble 2002, and Wong 2003) and 6 moderate quality (Agee 1992, Aslani 2012,  Dumontier 1995, Ferdinand 2002, Jacobsen 1996, and Tian 2007) studies evaluated whether endoscopic carpal tunnel release provided any benefit over open or “mini-open” release at early follow up (3 months to one year). Three high quality studies (Atroshi 2009, Saw 2003 and Trumble 2002) favored endoscopic release for symptom relief in the first 3-6 months after surgery and one study (Saw 2003) demonstrated an earlier return to work. One high quality (Atroshi 2009) and one moderate quality study (Tian 2007) examined long term outcomes for endoscopic release versus open release and did not find any advantage of one method over the other. Studies comparing “mini-open” to standard release were inconclusive.
 
Surgical Procedures Versus Nonoperative Treatments
Strong evidence supports that surgical treatment of carpal tunnel syndrome should have a greater treatment benefit at 6 and 12 months as compared to splinting, NSAIDs/therapy, and a single steroid injection.
Strong Evidence Strong Evidence
Four high quality (Gerritsen 2002, Hui 2005, Ismatullah 2013, and Jarvik 2009) and 3 moderate quality (Andreu 2013, Ly 2005, and Ly-Pen 2012) studies compared the effectiveness of surgical treatment to non-operative treatment for the relief of CTS symptoms. All three studies showed that surgery was superior for the relief of daytime and nocturnal paresthesias and return of grip strength.  Of these, one high quality (Gerritson 2002) and one moderate quality study (Andreu 2013) examined the long term outcomes for surgery versus conservative treatment and found better results with surgery 
 
Adjunctive Techniques
Moderate evidence supports that there is no benefit to routine inclusion of the following adjunctive techniques: epineurotomy, neurolysis, flexor tenosynovectomy, and lengthening/reconstruction of the flexor retinaculum (transverse carpal ligament).
Moderate Evidence Moderate Evidence
Epineurotomy: There are two high quality studies (Leinberry 1997and Crnkovic 2012) and one moderate quality study (Blair 1996) that evaluated carpal tunnel release alone versus the addition of epineurotomy of the median nerve. The Leinberry (1997) evaluated patients at 11.8 months after surgery. There was no significant difference found in clinical evaluation (Boston Questionnaire, APB strength, Phalen’s, Tinel’s, or two-point discrimination) or in symptom recurrence. Crnkovic (2012) studied nerve volume measured by MRI as an index of nerve recovery. Patients were evaluated at 3 and 6 months after surgery and no significant differences was noted at either time point. There were also no differences found for the symptoms of pain between the groups. Blair (1996) found no differences in post-operative two-point discrimination, pain, or ability to complete activities of daily living at a minimum of two years following surgery. There were also no differences electrodiagnostic parameters.
 
Neurolysis: There was one high quality study (Mackinnon 1991) and one moderate quality study (Lowry 1988) which evaluated the addition of neurolysis of the median nerve to a standard carpal tunnel release. The Mackinnon study focused on internal neurolysis and found no differences in thenar atrophy, muscle strength, pressure threshold, vibration threshold and static two-point discrimination at 12 months after surgery. No difference was noted in pinch or grip strength. The Lowry study evaluated the NCS findings at 3 months after surgery and did not find a difference in nerve conduction velocity or distal motor and sensory latency. Neither study found a difference in symptom relief or recurrence.
 
Flexor Tenosynovectomy: There was one high quality study (Shum 2002) evaluating flexor tenosynovectomy as an adjunct to carpal tunnel release. There was no difference in surgical site infection, scar sensitivity, wrist motion, finger motion, or Boston Carpal Tunnel Questionnaire at 12 months following surgery.
 
Flexor Retinaculum Reconstruction/Lengthening: There was one high quality study (Dias 2004) that evaluated flexor retinaculum lengthening/reconstruction. Six months following surgery there were no differences in grip strength, Jebsen Taylor score, Phalen test, pinch strength, Boston Carpal Tunnel Questionnaire score or symptom recurrence. 
 
Bilateral Versus Staged Carpal Tunnel Release
Limited evidence supports that simultaneous bilateral or staged endoscopic carpal tunnel release might be performed based on patient and surgeon preference. No evidence meeting the inclusion criteria was found addressing bilateral simultaneous open carpal tunnel release.
Limited Evidence Limited Evidence
There were two low strength studies (Fehringer 2002, Nesbitt 2006) which looked at simultaneous and staged endoscopic carpal tunnel releases. There were no studies that met our inclusion criteria which evaluated open release. The results of these studies were conflicting. For example, grip strength in short term follow-up was better in the staged group, but return to work was faster in the simultaneous group. Patient-specific factors, such as quality of life, non-employment work, care-giving, family and community responsibilities were not addressed. Both studies were limited in that there was no randomization of treatment protocols. Patients selected simultaneous or staged procedures, and both groups were satisfied with their choices.  At 6 month follow up, there was no difference between the two groups.
 
Because no studies comparing simultaneous versus staged procedures for open release were considered, there are no data to support concurrent or sequential bilateral open carpal tunnel releases. This does not constitute a mandate that bilateral simultaneous carpal tunnel releases should be performed endoscopically. 
 
Implications of two versus one surgical experience such as two anesthetics, total analgesic consumption, costs of two OR and perioperative nursing unit visits were not addressed.
 
Local Versus Intravenous (IV) Regional Anesthesia
Limited evidence supports the use of local anesthesia rather than intravenous regional anesthesia (Bier block) because it might offer longer pain relief after carpal tunnel release; no evidence meeting our inclusion criteria was found comparing general anesthesia to either regional or local anesthesia for carpal tunnel surgery.
Limited Evidence Limited Evidence
There were two moderate quality studies comparing local anesthesia to intravenous regional anesthesia. Nabhan (2011) studied 43 patients randomized to receive either local anesthesia or intravenous regional anesthesia using prilocaine. Three patients in the intravenous regional anesthesia group and one patient in the local anesthesia group required supplementation with additional local infiltration at the surgery site. The tourniquet was inflated longer in the intravenous regional anesthesia group but the operating time was the same in both groups. There were no other differences between the groups.
 
Sorensen et al (2013) randomized 38 patients to have endoscopic carpal tunnel release under either local anesthesia with ropivicaine or intravenous regional anesthesia with mepivicaine. The group treated with local anesthesia had less pain at the end of the procedure as well as two hours after surgery was completed although pain during the procedure was equal in the two groups.
 
Buffered Versus Plain Lidocaine
Moderate evidence supports the use of buffered lidocaine rather than plain lidocaine for local anesthesia because it could result in less injection pain.
Moderate Evidence Moderate Evidence
There were two high quality studies evaluating the use of buffered lidocaine for local anesthesia. Vossinakis et al (2004) studied 21 patients undergoing sequential, bilateral carpal tunnel release under local anesthesia. In each case one hand was anesthetized with lidocaine buffered with sodium bicarbonate and the other hand with plain lidocaine. Following infiltration the patients reported pain on a 100 mm visual analog scale. Those receiving the buffered solution reported less pain and the difference between the groups was statistically significant.
 
Watts et al (2004) randomized 64 patients to have a carpal tunnel release under local anesthesia using either plain lidocaine or lidocaine buffered with sodium bicarbonate. One minute after infiltration, and before application of a tourniquet, pain was measured on a 100 mm visual analog scale. Although patients who received buffered lidocaine reported less pain, the difference from those receiving the plain lidocaine was not statistically significant.
 
Aspirin Use
Limited evidence supports that the patient might continue the use of aspirin perioperatively; no evidence meeting our inclusion criteria addressed other anticoagulants.
Limited Evidence Limited Evidence
One low quality study (Brunetti 2013) met our inclusion criteria. This study examined only aspirin use that was either continued or stopped five days before surgery and resumed three days postoperatively. Compared with controls that were not on aspirin, there were no differences in either hematoma formation or other general complications.  There is no evidence meeting our criteria on any other anticoagulant therapies.
 
Preoperative Antibiotics
Limited evidence supports that there is no benefit for routine use of prophylactic antibiotics prior to carpal tunnel release because there is no demonstrated reduction in postoperative surgical site infection.
Limited Evidence Limited Evidence
There were two low quality studies (Harness, Tosti) which evaluated the use of prophylactic antibiotics in carpal tunnel release. Neither study showed a statistically significant difference between the groups receiving prophylactic antibiotics and those not receiving antibiotics. There is insufficient evidence to support the routine use of prophylactic antibiotics to prevent surgical site infections in carpal tunnel release. 
 
Supervised Versus Home Therapy
Moderate evidence supports no additional benefit to routine supervised therapy over home programs in the immediate postoperative period. No evidence meeting the inclusion criteria was found comparing the potential benefit of exercise versus no exercise after surgery.
Moderate Evidence Moderate Evidence

Routine post-operative therapy after carpal tunnel release was examined in 6 high and moderate quality studies. From these, two moderate quality studies (Hochberg 2001 and Jerosch-Herold 2012) addressed interventions not relevant to current core practices of postoperative rehabilitation. Two high quality studies (Fagan 2004, Pomerance 2007) and two moderate quality studies (Alves 2011, and Provinciali 2000) addressed the need for supervised therapy in addition to a home program in the early postoperative period, the early use of laser, or the role of sensory reeducation in the later stages of recovery.

One moderate quality study (Alves 2011) evaluated the use of laser administered to the carpal tunnel in 10 daily consecutive sessions at a 3J dosage and found no difference in pain/symptom reoccurrence in comparison to placebo.
 
One high quality study (Pomerance 2007) and one moderate quality study (Provinciali 2000) compared in-clinic or therapist supervised exercise programs in addition to a home program to a home program alone. The studies were somewhat limited by an incomplete description of who delivered home programs, exercise/education content and dosage, and treatment progression. Pomerance (2007) compared a two week program directed by a therapist combined with a home program alone and found no additional benefit in terms of grip or pinch strength in comparison to the home program alone. Provinciali (2000) compared one hour sessions over 10 consecutive days of in-clinic physiotherapy comprising a multimodal program with a home program that was progressed in terms of strength/endurance. No benefit was found in outcome when measured by a CTS-specific patient reported instrument. 

Postoperative Immobilization
Strong evidence supports no benefit to routine postoperative immobilization after carpal tunnel release.
Strong Evidence Strong Evidence
There were two high quality studies (Bury et al, Finsen et al) and four moderate quality studies (Cebesay et al, Cook et al, Huemer et al, Martins et al) that evaluated post-operative splinting in comparison to no splinting.  These studies did not identify any clear benefit to immediate post-operative splinting. 
 
One high quality study (Bury et al) showed no short or long-term difference in regards to grip strength, pinch strength, and range of motion between patients splinted for 2 weeks post-operatively and patients who had no splinting.  A second high quality study (Finsen et al) also showed no difference in grip strength and pinch at 1.4 and 5.9 months between the splinted and unsplinted groups.
 
A moderate strength study (Cook et al) did show a statistically significant improvement in grip and pinch strength at 2 weeks and 4 weeks in patients who were not splinted and allowed to begin early range of motion exercises compared with patients splinted for 2 weeks.   A treatment effect of allowing early range of motion exercises may have contributed to the increase in the improvement in motion in the short term. At three months after surgery, there was no difference between the splinted and unsplinted groups in regards to grip and pinch strength.
 
One moderate strength study (Martins, RS) did show a short-term benefit to post-operative splinting in regards to 2-point discrimination at 2 weeks in patients that were splinted, but this effect was not present at the 3 month follow-up.
 
One high quality study (Ritting et al) showed no difference in wound complications between patients who removed a bulky, post-operative dressing at 48-72 hours and patients who kept their dressing on for 2 weeks.  At two weeks follow-up, the group who removed their dressing early had better grip and 3-point pinch strength, however, there was no difference in 3-point pinch strength between the groups at week follow up six and 12 weeks after surgery.  Of note, the patients randomized to early dressing removal had better grip strength pre-operatively, compared to the group randomized to maintaining the dressing for 2 weeks, which may have accounted for the differences observed.  

ACKNOWLEDGEMENTS
Guideline Work Group:
Brent Graham, MD, MSc, FRCSC, Chair
Allan E. Peljovich, MD, MPH, Vice-Chair
Robert Afra, MD
Mickey S. Cho, MD
Rob Gray, MD
John Stephenson, MD
Andrew Gurman, MD 
Joy MacDermid, PhD
Gary Mlady, MD
Atul T. Patel, MD
David Rempel, MD, MPH
Tamara D. Rozental, MD
Mohammad Kian Salajegheh, MD 

Additional Contributing Members:
Julie Adams, MD
Jay Mark Evans, MD
John Lubahn, MD
Wilson Zachary Ray, MD
Robert Spinner, MD
Grant Thomson, MD, MSc

Guidelines Oversight Chair:
Michael Warren Keith, MD

Clinical Practice Guidelines Section Leader:
Kevin Shea, MD

AAOS Council on Research and Quality Chair:
Kevin John Bozic, MD, MBA


AAOS Staff:
William Shaffer, MD, AAOS Medical Director
Deborah Cummins, PhD, Director, Research & Scientific Affairs
Jayson Murray, MA, Manager, Evidence-Based Medicine Unit
Mukarram Mohiuddin, MPH, Lead Research Evidence-Based Medicine Research Analyst
Kyle Mullen, MPH, Evidence-Based Medicine Research Analyst
Peter Shores, MPH, Evidence-Based Medicine Statistician
Kaitlyn Sevarino, MBA, Evidence-Based Quality and Value Coordinator
Yasseline Martinez, Administrative Coordinator
Erica Linskey, Administrative Assistant 

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