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Clinical Course and Prognostic Factors in Conservatively Managed Carpal Tunnel Syndrome: A Systematic Review

Open AccessPublished:October 03, 2015DOI:https://doi.org/10.1016/j.apmr.2015.09.013

      Abstract

      Objective

      To summarize the available evidence regarding the course of symptoms and prognostic factors in patients with diagnosed carpal tunnel syndrome (CTS) who are treated conservatively.

      Data Sources

      Computerized databases, reference checking, and experts in the field were used to identify studies for inclusion in the review.

      Study Selection

      Multiple reviewers were used to identify studies which included adults (aged ≥18y) diagnosed with CTS in either a clinical setting or population setting. The study must have observed the course of CTS over at least a 6-week period in patients receiving no treatment or usual care that included conservative (nonsurgical) treatments. The design was of a longitudinal cohort study with either prospective or retrospective data collection. There were no language restrictions, and none of the research identified was only reported in abstract form.

      Data Extraction

      Methodological bias was assessed using the Quality in Prognosis Studies tool. A high risk of bias (predominantly relating to study attrition, confounding, and/or statistical analysis and reporting) was judged to be present in 8 studies. Designs showed wide variability with respect to characteristics of the included population, definition of CTS, assessment of prognostic factors, types of interventions provided, and types of outcome measures applied. This prevented pooled estimates from being produced.

      Data Synthesis

      A negative outcome at 3 years' follow-up of conservatively treated participants ranged from 23% to 89%. Four included studies observed the rate of surgical intervention after initial conservative management and found this to be 57% to 66%. Evidence regarding factors predicting the negative outcome of no treatment or conservative treatment was graded, taking into account the number of studies evaluating the factor, the methodological quality of these studies, and the consistency of the available evidence. There was 100% agreement in at least 3 cohorts with a medium or high risk of bias that symptom duration, a positive Phalen's test, and thenar wasting were associated with a negative outcome of conservative management; however, not all results were statistically significant, and hence the overall judgment remained inconclusive.

      Conclusions

      Results of this review should be treated with caution because of the heterogeneity of studies and the risks of bias identified. However, the course of CTS appears variable, and poor prognosis may be predicted by a longer symptom duration, a positive Phalen's test, and thenar wasting.

      Keywords

      List of abbreviations:

      CTS (carpal tunnel syndrome), QUIPS (Quality in Prognosis Studies)
      Carpal tunnel syndrome (CTS) is a chronic focal compressive neuropathy caused by the entrapment of the median nerve at the level of the carpal tunnel.
      • Alfonso C.
      • Jann S.
      • Massa R.
      • Torreggiani A.
      Diagnosis, treatment and follow-up of the carpal tunnel syndrome: a review.
      CTS is the most common of the entrapment neuropathies, accounting for 90% of presentations,
      • Aroori S.
      • Spence R.A.
      Carpal tunnel syndrome.
      and is characterized by numbness, tingling, hand and arm pain, and muscle dysfunction.
      • Ibrahim I.
      • Khan W.S.
      • Goddard N.
      • Smitham P.
      Carpal tunnel syndrome: a review of the recent literature.
      Between 55% and 65% of CTS cases present bilaterally,
      • Bland J.D.
      • Rudolfer S.M.
      Clinical surveillance of carpal tunnel syndrome in two areas of the United Kingdom, 1991–2001.
      and the condition can be associated with hypothyroidism, diabetes, and rheumatoid arthritis, among others. CTS may present in late pregnancy but is usually transient.
      Studies in different countries have reported varying results with respect to the incidence of CTS.
      • Atroshi I.
      • Englund M.
      • Turkiewicz A.
      • Tägil M.
      • Petersson I.F.
      Incidence of physician-diagnosed carpal tunnel syndrome in the general population.
      A survey of the Skåne Health Care Register in Sweden by Atroshi et al
      • Atroshi I.
      • Englund M.
      • Turkiewicz A.
      • Tägil M.
      • Petersson I.F.
      Incidence of physician-diagnosed carpal tunnel syndrome in the general population.
      was age adjusted to the 2000 U.S. standard population to allow comparison with the results of a U.S.-based survey of the Rochester Epidemiology Project.
      • Gelfman R.
      • Melton III, L.J.
      • Yawn B.P.
      • Wollan P.C.
      • Amadio P.C.
      • Stevens J.C.
      Long-term trends in carpal tunnel syndrome.
      The estimated incidence of CTS in Sweden was reported as 324 per 100,000 in women compared with 542 per 100,000 in the United States, and in men, 166 per 100,000 in Sweden compared with 303 in the United States.
      • Atroshi I.
      • Englund M.
      • Turkiewicz A.
      • Tägil M.
      • Petersson I.F.
      Incidence of physician-diagnosed carpal tunnel syndrome in the general population.
      • Gelfman R.
      • Melton III, L.J.
      • Yawn B.P.
      • Wollan P.C.
      • Amadio P.C.
      • Stevens J.C.
      Long-term trends in carpal tunnel syndrome.
      The explanation for variation between countries is unknown; however, suggested possibilities include differences in health care–seeking behavior and variation in etiologic factors including occupation, diabetes, and inflammatory joint disease.
      • Atroshi I.
      • Englund M.
      • Turkiewicz A.
      • Tägil M.
      • Petersson I.F.
      Incidence of physician-diagnosed carpal tunnel syndrome in the general population.
      The treatment of CTS is often categorized as either surgical or conservative (nonsurgical). Surgical treatment is generally recommended for those with severe CTS (ie, evidence of denervation of the median nerve), while conservative treatments are recommended for the initial management of those who have intermittent or mild symptoms or in whom surgery is contraindicated.
      • Page M.J.
      • Massy-Westropp N.
      • O'Connor D.
      • Pitt V.
      Splinting for carpal tunnel syndrome.
      The U.S. standardized annual incidence of carpal tunnel release surgery per 100,000 persons was 166 in Sweden compared with 171 in the United States and, among men, 58 in Sweden compared with 96 in the United States.
      • Atroshi I.
      • Englund M.
      • Turkiewicz A.
      • Tägil M.
      • Petersson I.F.
      Incidence of physician-diagnosed carpal tunnel syndrome in the general population.
      • Gelfman R.
      • Melton III, L.J.
      • Yawn B.P.
      • Wollan P.C.
      • Amadio P.C.
      • Stevens J.C.
      Long-term trends in carpal tunnel syndrome.
      Examples of conservative treatment include oral steroids, steroid injections, physical therapy, electrotherapy, night splinting, and workplace alterations.
      • Huisstede B.M.
      • Hoogvliet P.
      • Randsdorp M.S.
      • Glerum S.
      • van Middelkoop M.
      • Koes B.W.
      Carpal tunnel syndrome. Part I: effectiveness of nonsurgical treatments—a systematic review.
      In United Kingdom primary care, steroid injections and night splinting form the mainstay of conservative treatment options, as indicated by national care pathways (eg, National Institute for Health and Care Excellence Clinical Knowledge Summaries).

      National Institute for Health and Care Excellence. Carpal tunnel syndrome. 2012. Available at: http://cks.nice.org.uk/carpal-tunnel-syndrome#!scenariorecommendation:1. Accessed April 10, 2014.

      NHS: Institute for Innovation and Improvement. Carpal Tunnel Syndrome (CTS) - The Map of Medicine. 2012. Available at: http://app.mapofmedicine.com/mom/127/page.html?department-id=8&specialty-id=1037&pathway-id=3411&page-id=8741&history=clear. Accessed October 25, 2012.

      Guidelines for the management of CTS by the American Association of Orthopaedic Surgeons

      American Academy of Orthopaedic Surgeons. AAOS guideline on the treatment of carpal tunnel syndrome: 2011 report for the “re-issue” of the original guideline 2011. Available at: http://www.aaos.org/Research/guidelines/CTS_Treatment_REIssue.pdf. Accessed November 28, 2012.

      conclude that patients with more severe and prolonged CTS may not benefit from extended conservative treatment. However, the authors were unable to recommend in which patients conservative treatments were unlikely to be effective.

      American Academy of Orthopaedic Surgeons. AAOS guideline on the treatment of carpal tunnel syndrome: 2011 report for the “re-issue” of the original guideline 2011. Available at: http://www.aaos.org/Research/guidelines/CTS_Treatment_REIssue.pdf. Accessed November 28, 2012.

      Cochrane systematic reviews of conservative treatments for CTS
      • O'Connor D.
      • Marshall S.C.
      • Massy-Westropp N.
      • Pitt V.
      Non-surgical treatment (other than steroid injection) for carpal tunnel syndrome.
      have included the assessment of local corticosteroid injections
      • Marshall S.
      • Tardif G.
      • Ashworth N.
      Local corticosteroid injection for carpal tunnel syndrome.
      and splinting.
      • Page M.J.
      • Massy-Westropp N.
      • O'Connor D.
      • Pitt V.
      Splinting for carpal tunnel syndrome.
      With respect to splinting, the authors conclude that there is limited evidence that night splinting is more effective than no treatment in the short-term. They do, however, suggest that more research is needed on the long-term effects of this intervention.
      • Page M.J.
      • Massy-Westropp N.
      • O'Connor D.
      • Pitt V.
      Splinting for carpal tunnel syndrome.
      With regard to steroid injections, it was concluded that robust evidence demonstrates clinical improvement up to 1 month compared with placebo, but relief beyond this period has not yet been shown.
      • Marshall S.
      • Tardif G.
      • Ashworth N.
      Local corticosteroid injection for carpal tunnel syndrome.
      With ongoing clinical uncertainty regarding the most effective management strategy for CTS, there is a clear need for a greater understanding of the likely long-term course of CTS symptoms (overall prognosis) of the condition and patient factors that may be associated with outcome (prognostic factors).
      Outcomes and predictors of surgical outcome have been well reported in the literature. However, few studies and no systematic reviews have been performed to summarize the evidence for prognosis and prognostic factors in conservatively managed disease—that is, that which can be delivered in a primary care environment. An estimate of average prognosis is required by public health policymakers in order for the population burden of a condition to be assessed. Understanding the future outcomes of patients with a particular condition in relation to current practice and even in the absence of clinical care (the natural history) is crucial because it allows the potential impact of interventions to be more fully assessed.
      • Hemingway H.
      • Croft P.
      • Perel P.
      • et al.
      Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.
      Such information is not only important when considering the potential benefits of interventions, but also in order to inform patients, clinicians, and policymakers of the potential harms, variations (such as underuse, overuse, misuse), and potential impact on health care efficiencies.
      • Hemingway H.
      • Croft P.
      • Perel P.
      • et al.
      Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.
      This systematic review and narrative synthesis initially focuses on summarizing the prognosis research regarding the general course of CTS. The “start point” of this review will be the point of diagnosis of CTS that is being treated conservatively or with no clinical treatment. The “endpoint” will vary depending on the primary study. This synthesis therefore seeks to describe the course of CTS being managed either with no intervention or with conservative approaches.
      The second part of this systematic review aims to identify predictors of long-term outcome (prognostic factors) in CTS. A prognostic factor is “any measure that, among people with a given health condition (start point), is associated with a subsequent clinical outcome (endpoint).”
      • Riley R.D.
      • Hayden J.A.
      • Steyerberg E.W.
      • et al.
      Prognosis research strategy (PROGRESS) 2: prognostic factor research.
      (p1) Prognostic factor research thus seeks to identify the predictive value of such factors.
      Research of prognostic factors aims to identify features that could potentially contribute to the development of prognostic models or represent predictors of differential treatment response, which may further contribute to a stratified care approach to a condition. Prognostic factors may also represent modifiable targets for interventions and could hence lead to the development of new management strategies through an improved understanding of disease mechanisms.
      • Riley R.D.
      • Hayden J.A.
      • Steyerberg E.W.
      • et al.
      Prognosis research strategy (PROGRESS) 2: prognostic factor research.

      Methods

      Identification and selection of literature

      Details of the protocol for this systematic review were registered on PROSPERO (CRD42013006608) and can be accessed at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013006608#.VYk_RflVhBc. Eligible publications had to report the course of CTS symptoms (persistence/recovery or severity of pain or other symptoms) and/or the association between a potential prognostic factor and outcome, as well as meeting the following eligibility criteria: (1) The study included adults (aged ≥18y) diagnosed with CTS in either a clinical setting or population setting. Studies in pregnant women and in populations such as specific occupational groups were excluded. (2) The study observed the course of CTS over at least a 6-week period in patients receiving no treatment or usual care that included conservative (nonsurgical) treatments. Studies reporting risk factors for onset of CTS as opposed to predictors of outcome were excluded, as were studies investigating predictors of the effectiveness of a specific treatment (which would ideally require a review of randomized controlled trials and is planned for the future). (3) The design was of a longitudinal cohort study with either prospective or retrospective data collection. (4) There were no language restrictions, and none of the research identified was only reported in abstract form.
      A systematic computerized search of the literature was conducted in MEDLINE, Embase, AMED, HMIC, PsycINFO, CINAHL, Cochrane, SCI-EXPANDED, and CPCI-S from their inception until December 2013. The MEDLINE search strategy can be found in supplemental appendix S1 (available online only at http://www.archives-pmr.org/). References of all included full-text articles were hand-searched, and the first 15 pages of Google Scholar results for “carpal tunnel syndrome” and “prognosis” were screened as a further check for relevant hits. Experts were contacted to identify any further studies or publications in the gray literature that had not been identified in the search. The titles were screened by 1 reviewer (C.B.) and abstracts were screened by 2 reviewers (C.B., L.C.), and full articles of potentially eligible studies were retrieved. Such articles were screened by the 2 reviewers independently for eligibility and included in the review if they met the prespecified criteria.

      Quality assessment

      All selected studies were assessed independently for quality by 2 reviewers (C.B. and L.C.) using the Quality in Prognosis Studies (QUIPS) tool.
      • Hayden J.A.
      • van der Windt D.A.
      • Cartwright J.L.
      • Cote P.
      • Bombardier C.
      Assessing bias in studies of prognostic factors.
      The QUIPS tool assesses bias in the following 6 domains: (1) study participation; (2) study attrition; (3) prognostic factor measurement; (4) outcome measurement; (5) study confounding; and (6) statistical analysis and reporting. Judgments of low, moderate, or high risk of bias were made for each applicable domain using descriptors recommended by Hayden et al.
      • Hayden J.A.
      • van der Windt D.A.
      • Cartwright J.L.
      • Cote P.
      • Bombardier C.
      Assessing bias in studies of prognostic factors.
      Summated scores for overall study quality are not generally recommended; however, assessment of the overall risk of bias is suggested to be useful when synthesizing existing evidence.
      • Hayden J.A.
      • van der Windt D.A.
      • Cartwright J.L.
      • Cote P.
      • Bombardier C.
      Assessing bias in studies of prognostic factors.
      With the use of suggestions from Hayden,
      • Hayden J.A.
      • van der Windt D.A.
      • Cartwright J.L.
      • Cote P.
      • Bombardier C.
      Assessing bias in studies of prognostic factors.
      studies were judged to be of low overall risk of bias if all or most of the domains were judged as low risk, and studies in which all or most of the domains were judged as high risk were considered to be of high overall risk of bias. Studies with a moderate risk of bias were those with all or most of the domains being judged as moderate risk. Differences between reviewers were discussed, and a decision was made by agreement. Agreement between reviewers (C.B., L.C.) regarding the judgment of overall risk of bias was presented as a percentage of agreement.

      Data extraction

      Data were extracted by 1 reviewer (C.B.) and checked by another reviewer (L.C.). Data extraction included details of the study setting, population demographics, diagnostic criteria of CTS used, management approaches used, prognostic factors (type of factors and how measured), outcome measures (definition and instrument used), sample size, rate of attrition, and length of follow-up. With regard to clinical course, the percentage of patients with a negative outcome after conservative treatment or no treatment was recorded. All reported prognostic factors were listed and measures of association with their significance levels recorded.

      Analysis

      Results regarding the course of symptoms in patients with untreated and conservatively treated CTS were summarized narratively. Pooling of results was not possible because of heterogeneity with regard to study setting, case definition, follow-up periods, and measures of outcome. We summarized findings for the reported prognostic factors by taking into account the number of studies evaluating the factor, the risk of bias of these studies, and the consistency of the available evidence (as defined as significant association with the same direction). A level of evidence was defined for each factor, based on Sackett
      • Sackett D.L.
      • Straus S.E.
      • Richardson W.S.
      Evidence-based medicine. How to practice and teach EMB.
      and Ariens
      • Ariens G.A.
      • van Mechelen W.
      • Bongers P.M.
      • Bouter L.M.
      • van der Wal G.
      Physical risk factors for neck pain.
      and colleagues, and adapted for use with the QUIPS tool (table 1).
      Table 1Levels of evidence for prognostic factors
      • Sackett D.L.
      • Straus S.E.
      • Richardson W.S.
      Evidence-based medicine. How to practice and teach EMB.
      • Ariens G.A.
      • van Mechelen W.
      • Bongers P.M.
      • Bouter L.M.
      • van der Wal G.
      Physical risk factors for neck pain.
      Level of EvidenceDefinition
      StrongConsistent findings (≥75%) in at least 2 cohorts with a low risk of bias
      ModerateConsistent findings (≥75%) in 1 cohort with a low risk of bias and at least 1 cohort with a moderate/high risk of bias
      WeakFindings of 1 cohort with a low risk of bias or consistent findings (≥75%) in at least 3 cohorts with a moderate/high risk of bias
      InconclusiveInconsistent findings irrespective of study quality, or less than 3 cohorts with a moderate/high risk of bias
      No evidenceNo data presented

      Results

      Selection of studies

      Figure 1 presents a flow chart of study selection. A total of 15,572 citations were identified (6987 MEDLINE, 6445 Embase, 197 AMED, 19 HMIC, 92 PsycINFO, 707 CINAHL, 755 Cochrane, 370 SCI-EXPANDED and CPCI-S). After the removal of duplicates and a screen of the titles, 146 abstracts were screened and 42 full-text publications retrieved for further eligibility screening. Twenty-six articles were excluded for the following reasons: 1 foreign language duplicate was found; 3 studies reported conditions not specific to CTS (ie, wrist pain or unspecified entrapment neuropathies); 6 studies reported outcomes in a specific population; 4 studies reported the etiology of CTS only; 6 studies reported on outcomes of specific treatments; and 6 studies used a design other than that described in the selection criteria. Sixteen articles (reporting on 16 cohorts) met all eligibility criteria and were included in the review.

      Study characteristics

      Table 2 summarizes the characteristics of the studies including the QUIPS score, study design and setting, study population, interventions used in the study, the primary outcome measure including the definition of a negative outcome, and the duration of follow-up. The table also presents the percentage of the cohort experiencing a negative outcome (eg, surgery) of conservative or no management.
      Table 2Summary of study characteristics and results regarding the course of symptoms of prognostic cohort studies in CTS
      Author, Year, LocationRisk of Bias (QUIPS Score)Study PopulationInterventions Provided to Entire CohortPrimary Outcome Measure/Duration of Follow-UpMeasure of Negative Outcome of Conservative ManagementProportion of Patients Treated Conservatively Experiencing Negative Outcome
      Treated Populations: Prospective Cohort Studies
       Boyd et al,
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      2005, Canada
      HighSetting: tertiary hand and upper limb center

      CTS diagnosis: clinical findings and electrophysiological abnormality

      68% female

      Mean age: 49.3y

      N=25 patients (47 wrists)

      Dropout: 17%
      Splint: all wrists

      Surgery: 27 (57%) wrists
      No surgery vs surgery by 6mo

      12wk, with an option to continue follow-up >6mo
      Progression to surgery57% of wrists
       Duckworth et al,
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      2013, Scotland
      ModerateSetting: hand clinic

      CTS diagnosis: clinical findings and electrophysiological abnormality

      67% female

      Mean age ± SD: males 57±14y; females 54±14y

      N=275 patients

      Dropout: 28%
      Splint: all patients

      Injection: 150 (55%) (of whom 38 had surgery)

      Surgery: 122 (44%) patients

      No further treatment: 3 (1%) patients
      QuickDASH score

      1y
      Progression to surgery58% of patients
       Goodwill,
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      1965, England
      HighSetting: electromyography laboratory

      CTS diagnosis: paresthesia and pain with electrophysiological abnormality

      93% female

      Age bands:

      30–39y: n=7 patients

      40–49y: n=19

      50–59y: n=39

      60–69y: n=18

      ≥70y: n=13

      N=96 patients (155 wrists)

      Dropout: 0%
      Splint: 98 (63%) wrists

      Injection: 58 (37%) wrists

      Surgery: 55 (35%) wrists
      Judgment made at follow-up: cured, temporary relief, or no relief

      1–3y (average 14mo)
      Evidence of symptomsAfter steroid injection: 88% of patients

      After splinting: 89% of patients

      After surgery: 5% of patients
       Kaplan et al,
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      1990, United States
      HighSetting: hand clinic

      CTS diagnosis: presence of pain or paresthesia and clinical findings (thenar atrophy, altered sensation, or Phalen's sign) 75% female

      Mean age: 55y

      N=229 patients (331 wrists)

      Dropout: 12%
      Splint: “most patients”

      Nonsteroidal anti-inflammatory drugs: 149 (65.2%) patients

      Oral steroid: 61 (26.8%) patients

      Steroid injection: 38 (16.4%) patients
      Success of therapy as defined by absence of symptoms for >6mo

      Minimum of 6mo or until had surgical release (average 15.4mo)
      Evidence of symptoms after 6mo

      Progression to surgery
      82% of wrists

      66% of wrists
       Katz et al,
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      1998, United States
      ModerateSetting: surgical clinics

      CTS diagnosis: paresthesia involving at least 2 digits (thumb or index, middle or ring fingers) and symptom duration of at least 1mo

      74% female

      Surgical cohort: >55y mean age ± SD, 68.0±9.1y; <55y compensation nonrecipient mean age ± SD 42.0±7.3y; compensation recipient mean age ± SD, 39.0±8.1y.

      Nonsurgical cohort >55y mean age ± SD, 64.0±7.0y; compensation nonrecipient mean age ± SD, 41.0±8.9y; compensation recipient mean age ± SD, 37.0±8.8y

      N=297 patients

      Dropout: 31%
      Nonsurgical cohort: 34 patients received surgery at <3mo and were not included in analyses.

      By 30mo:

      Splint: 76 (94%) patients

      Injection: 36 (44%) patients

      Physical or occupational therapy: all
      Change in status in symptom severity, functional limitations, and health status were recorded over time. Associations were measured for patients crossing between nonsurgical and surgical cohorts after >3mo.

      Follow-up took place at 6, 18, and 30mo
      Would not be happy to live the rest of their lives with symptoms60% of patients
       Kiylioglu et al,
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      2009, Turkey
      ModerateSetting: electromyography laboratory

      CTS diagnosis: clinical findings, supported by electrophysiological abnormality

      90% female

      Diabetic rehabilitation group mean age ± SD, 59.3±7.4y; diabetic untreated group mean age ± SD, 54.6±11.1y; idiopathic rehabilitation group mean age ± SD, 47.8±9.9y; idiopathic surgery group mean age ± SD, 49.2±9.8y

      N=42 patients (80 wrists)

      Dropout: 0 (assumed)
      Treatment methods not controlled or standardized

      “Rehabilitation”: patients treated with splints, paraffin treatments, and/or oral nonsteroidal anti-inflammatories
      Symptom severity score and functional status (Boston questionnaire translated into Turkish)

      Patients were followed up in the early follow-up period (3–5mo) and late follow-up period (6–12mo).
      Percentage improvement in symptom severity scale

      Percentage improvement in function severity scale
      Rehabilitation 82%

      Surgery 77%

      Untreated 25%



      Rehabilitation 73%

      Surgery 85%

      Untreated 17%
      Treated Populations: Retrospective Cohort Studies
       Kouyoumdjian et al,
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      2003, Brazil
      HighSetting: electromyography laboratory

      CTS diagnosis: symptoms including hand paresthesia, numbness, and pain mainly at night.

      95.8% female

      Surgical cure group mean age 46y (range, 24–70); unchanged/worse group 44y (range, 39–58y); nonsurgical cure group mean age 61y (range, 48–79y); worse group mean age 50y (range, 30–83y)

      N=165 patients (222 wrists)

      Dropout: 69%
      Surgery: 147 (66%) wrists

      Nonsurgical (splint, local injection, medication, and others): 75 (34%) wrists
      General patient satisfaction: complete relief; improved “much better”; improved “little”; unchanged; worsened

      Poorly recorded. Between 5 and 10y (mean, 5.9y after surgery)
      Symptoms unchanged or worse23.7% of wrists
       Lian et al,
      • Lian B.T.
      • Urkude R.
      • Verma K.K.
      Clinical profile, electrodiagnosis and outcome in patients with carpal tunnel syndrome: a Singapore perspective.
      2006, Singapore
      HighSetting: electromyography laboratory

      CTS diagnosis: clinical history and examination, confirmed using American Association of Electrodiagnostic Medicine criteria and additional testing if this was normal

      81.3% female

      Mean age: 53.6y

      N=115

      Dropout: 14%
      Conservative management: 88 (77%) patients

      Surgery: 27 (23%) patients
      Clinician review of medical records and decision made as to category: resolved; improved; same; worse

      Follow-up took place at 3 and 6mo (limited data available)
      Symptoms unchanged or worse68.5% of patients
       Miranda et al,
      • Miranda B.H.
      • Asaad K.
      • Cerovac S.
      Carpal tunnel syndrome study: local corticosteroids, conversion to surgery and NHS implications.
      2013, United Kingdom
      HighSetting: plastic surgery clinic

      CTS diagnosis: based on clinical symptoms

      Sex not reported

      Mean age ± SD: 56±3y

      N=134

      Dropout 10%
      Injection: 66 (49%) patients

      Surgery: 68 (51%) patients
      Symptom relief and/or surgery

      22.5±0.5mo
      Progression to surgery62% of patients
       Muhlau et al,
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      1984, Germany
      ModerateSetting: electromyography laboratory

      CTS diagnosis: distal motor latency was >4.7ms

      Sex and age not reported

      N=157 (214 wrists)

      Dropout: 38%
      Conservative management: 72 (48%) wrists

      Surgery: 112 (52%) wrists
      An overall categorization was made at follow-up: cured; clear improvement; slight improvement; unchanged findings; further deterioration. These were then dichotomized so that groups 1 and 2 = cured, and 3, 4, and 5 = not cured.

      Follow-up was at least 2y and defined as when the patient had reached a “steady state.”
      No evidence of cure68% of patients
      Treated Populations: Retrospective Follow-Up Study of a Population-Based Case Series
       DeStefano et al,
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      1997, United States
      ModerateSetting: patients identified from the Marshfield Epidemiologic Study Area

      CTS diagnosis: ICD-9-CM code 354.0 and evidence of a clinical and/or electrophysiological abnormality in the records.

      62% female

      Mean age: 62y

      N=425

      Dropout: 0%
      Analgesia: 143 (34%) patients

      Nonsteroidal anti-inflammatories: 132 (31%) patients

      Injection: 6 (1%) patients

      Splint: 295 (69%) patients

      Surgery: 198 (47%) patients
      No surgery vs surgery and resolution of symptoms

      Median follow- up 1979–1983: 12.0y (5th and 95th percentiles: 10.0 and 14.8y, respectively). 1984–1988: 7.3y (5.0–9.8y)
      Evidence of symptoms1mo: 75% of patients

      2y: 40%

      8y: 22%
      Treated Populations: Secondary Analysis of Katz et al,
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      1998
       Katz et al,
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      1998, United States
      ModerateSetting: surgical clinics

      CTS diagnosis: paresthesia involving at least 2 digits (thumb or index, middle or ring fingers) and symptom duration of at least 1mo

      72% female

      Mean age ± SD: 43±11y

      N=253 patients

      Dropout: 20%
      Surgery: 179 (71%) patientsOut of work at 18mo

      Questionnaires were completed at 6, 18, and 30mo.
      Work absence at 18mo due to CTS23% of patients
      Untreated Populations: Prospective Cohort Studies
       Ortiz-Corredor et al,
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      2008, Columbia
      HighSetting: electromyography laboratory

      CTS diagnosis: as per Rempel et al,
      • Rempel D.
      • Evanoff B.
      • Amadio P.C.
      • et al.
      Consensus criteria for the classification of carpal tunnel syndrome in epidemiologic studies.
      1998

      81.1% female

      Mean age ± SD: 48.8±10.2y

      N=132 patients

      Not possible to determine dropout
      The course of untreated CTS was observed.The Historic and Objective Scale was used as the clinical classification. The electrophysiological classification was according to Padua et al,
      • Padua L.
      • Lo Monaco M.
      • Padua R.
      • Gregori B.
      • Tonali P.
      Neurophysiological classification of carpal tunnel syndrome: assessment of 600 symptomatic hands.
      1997 (mild; moderate A; moderate B; severe; extreme)

      24.2±4.2mo
      Deterioration in the Historic and Objective Scale23.4% of patients
       Padua et al,
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      1998, Italy
      ModerateSetting: electromyography laboratory

      CTS diagnosis: based on neurophysiological evaluation graded: negative, minimal, mild, moderate, severe, and extreme (Padua et al
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      )

      78.8% female

      Mean age ± SD: 48.8±10.2y

      N=80

      Dropout: 84%
      The course of untreated CTS was observed.Patient-reported global improvement scale: stable, worse, improved

      Neurophysiological classification: negative, minimal, mild, moderate, severe, extreme

      11.6mo (range, 5–23)
      Clinical outcome: unchanged

      Clinical outcome: worse
      Neurophysiological classification

      Negative 50%

      Minimal 38%

      Mild 15%

      Moderate 27.5%

      Severe 0%

      Extreme 50%

      Negative 50%

      Minimal 31%

      Mild 58%

      Moderate 45%

      Severe 20%

      Extreme 0%
       Padua et al,
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      2001, Italy
      ModerateSetting: electromyography laboratory

      CTS diagnosis: based on clinical diagnostic criteria proposed by the American Academy of Neurology and the American Association of Electrodiagnostic Medicine

      82% female

      Mean age ± SD: 52.0±13.4y

      N=202 (267 wrists) with a further 62 (87 wrists) reevaluated by telephone

      Dropout: 34%
      The course of untreated CTS was observed.Electrophysiological changes, patient-reported changes, and clinical changes were used to describe if patients had improved, remained stationary, or worsened.

      10–15mo
      Neurophysiologic class



      Symptoms

      Function

      Historic and Objective Scale

      Pain
      Stationary 57%

      Worsening 16%

      Stationary 45%

      Worsening 21%

      Stationary 61%

      Worsening 16%

      Stationary 46%

      Worsening 32%

      Stationary 62%

      Worsening 12%
      Untreated Populations: Retrospective Cohort Studies
       Resende et al,
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      2003, Brazil
      HighSetting: electromyography laboratory

      CTS diagnosis: clinical findings, supported by electrophysiological abnormality

      N=12

      Dropout not possible to determine
      The course of untreated CTS was observed.Clinical and electrophysiological changes were observed.

      4–9y
      Conduction studiesMarked improvement 25% (of which 100% had improvement in symptoms)

      Slight improvement 15% (of which 33% had worsening of clinical symptoms)

      No significant change 50% (of which 50% had worsening of clinical symptoms)

      Worsening 10% (of which 50% had worsening of clinical symptoms)
      NOTE. Compensation recipient and nonrecipient indicates that the patient received compensation or did not receive compensation, respectively, following litigation proceedings.
      Abbreviations: ICD-9-CM, International Classification of Diseases9th RevisionClinical Modifications; QuickDASH, shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire.
      One study
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      was a retrospective follow-up study of cases identified in the Marshfield Epidemiologic Study Area, a population-based cohort. All other studies were based in secondary or tertiary care, of which 6 were in surgical clinics and 8 in electromyography laboratories. No studies were based in primary care. The case definitions used to identify CTS differed: 6 studies used clinical features only, while the remaining 10 studies required accompanying electrophysiological abnormalities. The combination of clinical characteristics used and the electrophysiological criteria also varied between studies. The interventions used in the studies included wrist splinting (7 studies), nonsteroidal anti-inflammatory drugs (3 studies), other analgesia (2 studies), oral steroids (3 studies), local steroid injections (6 studies), and paraffin treatment (1 study). Three studies provided conservative management without specifying which mode exactly. In 4 studies,
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      the course of (clinically) untreated CTS was observed. In some studies, parts of the cohort were treated surgically. Their specific outcomes were not included in this review. A range of outcome measures were used: 3 studies used a surgical episode as a proxy for a negative outcome; 1 study used the shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) score; 5 used measures of global improvement; 2 used a change in symptom and function severity scores; 1 used the Historic and Objective Scale
      • Giannini F.
      Quantitative assessment of historical and objective findings: a new clinical severity scale of CTS.
      ; 1 used work absence; 2 observed electrophysiological changes; and 1 used absence of clinical contact as an indicator of recovery. The follow-up periods ranged from 12 weeks to 10 years.

      Methodological quality

      The results of the quality assessment are presented in table 3. In 4 studies that investigated the course of CTS symptoms only, the prognostic factor domain was not assessed. The percentage agreement between the authors (C.B., L.C.) with regard to judgment of the overall risk of bias was 75%, and 100% after discussion. Further adjudication was therefore not required.
      Table 3Results of methodological assessment of prognostic cohort studies on CTS
      Author, YearStudy ParticipationStudy AttritionPrognostic Factor MeasurementOutcome MeasurementStudy ConfoundingStatistical Analysis and ReportingOverall Risk of Bias
      Studies Including an Analysis of Prognostic Factors
       Boyd et al,
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      2005
      HighHighModerateModerateModerateHighHigh
       DeStefano et al,
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      1997
      LowModerateModerateModerateModerateModerateModerate
       Duckworth et al,
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      2013
      ModerateHighModerateModerateHighLowModerate
       Goodwill,
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      1965
      HighHighHighHighHighHighHigh
       Kaplan et al,
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      1990
      HighHighHighHighHighHighHigh
       Katz et al,
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      1998
      LowModerateModerateModerateLowHighModerate
       Katz et al,
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      1998
      LowHighModerateLowHighLowModerate
       Kiylioglu et al,
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      2009
      ModerateHighModerateModerateModerateHighModerate
       Kouyoumdjian et al,
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      2003
      ModerateHighModerateModerateHighHighHigh
       Muhlau et al,
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      1984
      ModerateHighLowModerateModerateLowModerate
       Padua et al,
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      2001
      LowModerateLowModerateModerateModerateModerate
      Studies Observing the Course of CTS Only (With No Analysis of Prognostic Factors)
       Lian et al,
      • Lian B.T.
      • Urkude R.
      • Verma K.K.
      Clinical profile, electrodiagnosis and outcome in patients with carpal tunnel syndrome: a Singapore perspective.
      2006
      HighHighNAHighHighHighHigh
       Miranda et al,
      • Miranda B.H.
      • Asaad K.
      • Cerovac S.
      Carpal tunnel syndrome study: local corticosteroids, conversion to surgery and NHS implications.
      2013
      HighHighNAHighHighHighHigh
       Ortiz-Corredor et al,
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      2008
      ModerateModerateNALowHighHighHigh
       Padua et al,
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      1998
      HighHighNALowHighLowModerate
       Resende et al,
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      2003
      HighHighNAHighHighModerateHigh
      Abbreviation: NA, not applicable.
      Eight studies were judged to have a moderate risk of bias and 8 to have a high risk of bias. The domains that carried a particularly high risk of bias across all studies were study attrition (12 studies), study confounding (10 studies), and statistical analysis and reporting (9 studies). Study attrition tended to be at high risk of bias because the response rates in several studies were low (see table 3), attempts to collect information on participants who dropped out were often lacking, reasons for loss to follow-up were rarely provided, and differences between those lost to follow-up and those actively followed up were not frequently compared. Study confounding was also a frequent finding largely because not all potential confounders were appropriately accounted for, and hence the observed associations of the potential prognostic factors with outcome were likely to be at least partly explained by other (unmeasured) factors. This was particularly true in studies using retrospectively collected data. Statistical analysis and reporting was commonly identified as being of high risk of bias because presentation of the data was frequently insufficient, and in some studies selective reporting of results was evident.

      Course of CTS

      For each included study, table 2 describes results regarding the course of CTS in conservatively treated or untreated patients by describing the proportion of patients who experience a negative outcome, the definition of which varied between studies (ie, persisting or worsening symptoms, progression to surgery, or work absence because of CTS). Table 4 further summarizes results regarding the course of CTS in terms of the percentage of patients reporting a negative outcome for different follow-up time points.
      Table 4Course of CTS in conservatively treated or untreated patients
      No. of StudiesSample Size Range% of Cases Reporting Deterioration Within:
      3mo6mo12mo3y15y
      Untreated cases
       4
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      12–344NANA32–5823.450
      Studies observing cases receiving surgery as a consequence of conservative management failure (% of patients receiving surgery NOT outcome of surgery)
       4
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      • Miranda B.H.
      • Asaad K.
      • Cerovac S.
      Carpal tunnel syndrome study: local corticosteroids, conversion to surgery and NHS implications.
      47–331NA575862–66NA
      Studies of conservatively managed patients reporting other definitions of negative outcome
       9
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      • Lian B.T.
      • Urkude R.
      • Verma K.K.
      Clinical profile, electrodiagnosis and outcome in patients with carpal tunnel syndrome: a Singapore perspective.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      80–42568.5–7582% improvement of up to 82%
      Percent change provided in positive direction.26
      23–8922–23.7
      NOTE. The percentages shown are not cumulative, since it cannot be assumsed that patients reporting a change in symptoms at 6 months would not have reported something different at an earlier or later date if the study had provided them with such opportunity.
      Abbreviation: NA, not applicable.
      Percent change provided in positive direction.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      Four studies examined the course of untreated CTS.
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      Ortiz-Corredor et al
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      observed that of 132 patients with untreated CTS over a 2-year period, 23.5% showed a deterioration in the Historic and Objective Scale score, but most cases did not show an electrophysiological deterioration (89 remained the same, 33 recovered, and 10 deteriorated). Only 1 patient had both an electrophysiological and clinical deterioration. Padua et al
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      reported whether the clinical outcome was unchanged or worse in groups of patients with different electrophysiological classifications. They found the clinical outcome was worse in 50% of patients with negative electrophysiology, 27.5% with moderate studies, and 50% with extreme studies. Padua et al
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      further observed the electrophysiological, symptomatic, functional, Historic and Objective Scale, and pain changes in patients with CTS. They reported that 16%, 21%, 16%, 32%, and 12% of patients in each of these outcome areas worsened, while 27%, 34%, 23%, 23%, and 26% of patients improved. Resende et al
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      presented the change in electrophysiological measures and accompanying change in symptoms over a 4- to 9-year period and found that 25% of patients had a marked improvement in electrophysiological outcome (100% of whom had improvement in terms of symptoms); 15% showed slight improvement (of whom 33% had worsening of symptoms); 50% showed no significant change (of whom 50% had worsening in terms of symptoms); and 10% had a worsening of electrophysiological measurements (of whom 50% had a worsening of clinical symptoms).
      In summary, 32% to 58% of participants receiving no treatment were reported to have a negative outcome at 12 months' follow-up in 2 studies,
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      both of which were of moderate risk of bias. The 2 further studies reporting at 3 and 10 years were at high risk of bias and reported a negative outcome in 23.4%
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      and 50%
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      of participants.
      In the 9 cohorts receiving conservative treatment, 68.5% to 75% of patients were reported to have a negative outcome within 3 months' follow-up
      • Lian B.T.
      • Urkude R.
      • Verma K.K.
      Clinical profile, electrodiagnosis and outcome in patients with carpal tunnel syndrome: a Singapore perspective.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      ; 82% within 6 months
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      ; 23% to 89% within 3 years
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      ; and 22% to 24% within 10 years.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      A wide variation in findings was noted according to risk of bias, with studies of a moderate risk of bias appearing to show lower percentages of patients with a negative outcome (eg, 23%–68% at 3y
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      ), compared with studies of high risk of bias (82% at 6mo
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      and 89% at 3y
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      ). Four studies
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      • Miranda B.H.
      • Asaad K.
      • Cerovac S.
      Carpal tunnel syndrome study: local corticosteroids, conversion to surgery and NHS implications.
      used a surgical episode as a marker of negative outcome of conservative management. A range of 57% to 66% of patients were observed to receive surgery after conservative management over a period of 1 to 3 years.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      • Miranda B.H.
      • Asaad K.
      • Cerovac S.
      Carpal tunnel syndrome study: local corticosteroids, conversion to surgery and NHS implications.
      In summary, the reported course of conservatively managed CTS is highly variable, but symptoms do improve over time.

      Prognostic factors predicting negative outcome of CTS

      Eleven of the studies presented data on the association between potential prognostic factors and a negative outcome of conservatively managed CTS. Table 5 presents potential prognostic factors observed in the studies and reported associations. Not all studies presented estimates of associations with confidence intervals. Some presented P values only; some simply reported a finding as nonsignificant. Therefore, the number of studies investigating each association, the number of studies of moderate or high risk of bias (none were of low risk), and the number showing an association (direction and significance) are summarized.
      Table 5Prognostic factors and strength of association for an unfavorable outcome of CTS in patients who are conservatively treated or untreated
      Prognostic FactorDirection of Association and SignificanceRisk of Bias (No. of Studies)No. and % of Studies Demonstrating Predictive Association With a Negative Outcome (Statistically Significant)Level of Evidence
      Demographic characteristics
       Female sex+
      Statistically significant.
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.


      +
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.


      0
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.


      0
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      Moderate (5)

      High (1)
      2/6: 33%

      (1/6: 17%)
      Inconclusive
       Increasing age (group not otherwise specified or >50y)+
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      Moderate (7)3/10: 30%

      (3/10: 30%)
      Inconclusive
      0
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      Statistically significant.
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      +
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.


      Statistically significant.
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.


      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      High (3)
       Obesity+
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.


      Statistically significant.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      Moderate (2)1/2: 50%

      (0/2: 0%)
      Inconclusive
       Litigation+
      Statistically significant.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      Moderate (3)1/3: 33%

      (1/3: 33%)
      Inconclusive
      0
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
       Deprivation quintile
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)0/1: 0%Inconclusive
       Vibration tool use
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)0/1: 0%Inconclusive
       Occupation status+
      Statistically significant.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      Moderate (1)(1/1: 100%)Inconclusive
       Smoking+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
      Comorbidity
       Diabetes+
      Statistically significant.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      Moderate (1)(1/1: 100%)Inconclusive
       Diabetes or hypothyroid+
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       Pregnancy or injury-associated CTS
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)0/1: 0%Inconclusive
       Arthritis+
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       Previous fracture or sprain0
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      High (1)0/1: 0%Inconclusive
       Stenosing flexor tenosynovitis+
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      High (1)(1/1: 100%)Inconclusive
       Mental health status+
      Statistically significant.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.
      Moderate (1)(1/1: 100%)Inconclusive
      Disease characteristics
       Tinel's sign positive+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       Phalen's sign positive+
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      Moderate (2)

      High (1)
      3/3: 100%

      (2/3: 67%)
      Inconclusive
      +
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      +
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
       Thenar wasting+
      Statistically significant.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      Moderate (2)

      High (1)
      3/3: 100%

      (2/3: 67%)
      Inconclusive
      +
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      +
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
       Paresthesia+
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      High (1)(1/1: 100%)Inconclusive
       Abnormal 2-point discrimination0
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.


      +
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      Moderate (1)

      High (1)
      1/2: 50%

      (1/2: 50%)
      Inconclusive
       Semmes-Weinstein monofilament testing0
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.
      Moderate0/1: 0%Inconclusive
       Electrophysiological severity+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.


      0
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.


      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      Moderate (3)

      High (2)
      2/5: 40%

      (0/5: 0%)
      Inconclusive
      +
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
       Symptom severity
      Statistically significant.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      Moderate (2)

      High (1)
      1/3: 33%

      (1/3: 33%)
      Inconclusive
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      +
      Statistically significant.
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
       Functional severity+
      Statistically significant.
      • Katz J.N.
      • Lew R.A.
      • Bessette L.
      • et al.
      Prevalence and predictors of long-term work disability due to carpal tunnel syndrome.


      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.


      0
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      Moderate (3)

      High (1)
      1/4: 25%

      (1/4: 25%)
      Inconclusive
       CTS category of severity
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      +
      Statistically significant.
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)(1/1: 100%)Inconclusive
       Sensory SF-MPQ+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       Affective SF-MPQ+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       SF-360
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      High (1)0/1: 0%Inconclusive
       DASH0
      • Boyd K.U.
      • Gan B.S.
      • Ross D.C.
      • Richards R.S.
      • Roth J.H.
      • MacDermid J.C.
      Outcomes in carpal tunnel syndrome: symptom severity, conservative management and progression to surgery.
      High (1)0/1: 0%Inconclusive
       Hi-Ob
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      Moderate (1)0/1: 0%Inconclusive
       Visual analog scale+
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (1)1/1: 100%

      (0/1: 0%)
      Inconclusive
       Laterality: left only
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)0/1: 0%Inconclusive
       Laterality: right only
      Statistically significant.
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)0/1: 0%Inconclusive
       Laterality: left > right
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)0/1: 0%Inconclusive
       Laterality: right > left
      • DeStefano F.
      • Nordstrom D.L.
      • Vierkant R.A.
      Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
      Moderate (1)0/1: 0%Inconclusive
       Bilateral+
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      Moderate (2)

      High (1)
      2/3: 67%

      (1/3: 33%)
      Inconclusive
      +
      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.


      0
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
       Grip strength0
      • Katz J.N.
      • Keller R.B.
      • Simmons B.P.
      • et al.
      Maine carpal tunnel study: outcomes of operative and nonoperative therapy for carpal tunnel syndrome in a community-based cohort.


      • Duckworth A.D.
      • Jenkins P.J.
      • Roddam P.
      • Watts A.C.
      • Ring D.
      • McEachan J.E.
      Pain and carpal tunnel syndrome.
      Moderate (2)0/2: 0%Inconclusive
       Hand stress
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      Moderate (1)0/1: 0%Inconclusive
       Increasing symptom duration+
      Statistically significant.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Muhlau G.
      • Both R.
      • Kunath H.
      Carpal tunnel syndrome—course and prognosis.
      Moderate (3)

      High (2)
      5/5: 100%

      (3/5: 60%)
      Inconclusive
      +
      • Kiylioglu N.
      • Bicerol B.
      • Ozkul A.
      • Akyol A.
      Natural course and treatment efficacy: one-year observation in diabetic and idiopathic carpal tunnel syndrome.
      +
      Statistically significant.
      • Kaplan S.J.
      • Glickel S.Z.
      • Eaton R.G.
      Predictive factors in the non-surgical treatment of carpal tunnel syndrome.
      +
      • Kouyoumdjian J.A.
      • Morita M.P.
      • Molina A.F.
      • et al.
      Long-term outcomes of symptomatic electrodiagnosed carpal tunnel syndrome.
      NOTE. 0, not significant and direction not provided; +, predictive of a negative outcome; −, not predictive of a negative outcome.
      Abbreviations: DASH, Disabilities of the Arm, Shoulder and Hand questionnaire; Hi-Ob, Historical and Objective Scale; SF-36, Medical Outcomes Study 36-Item Short-Form Health Survey; SF-MPQ, Short-Form McGill Pain Questionnaire.
      Statistically significant.
      In total, 39 potential prognostic factors were identified from the studies. All of these were found to have inconclusive levels of evidence of an association with a negative outcome. This was due to inconsistencies in study findings, nonsignificant results, low numbers of studies investigating each factor, and the moderate to high risk of bias of the studies included.

      Discussion

      This study is the first systematic review of the prognosis of conservatively managed CTS. A substantial amount of heterogeneity exists in terms of study setting, case definition, follow-up periods, and measures of outcome between the included studies, which prevented a meta-analysis from being conducted. A best-evidence synthesis was therefore presented.

      Course of CTS

      Four studies
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      observed the course of untreated CTS, which is helpful when considering the need for or impact of treatment. These studies suggest that a proportion (28%–62%)
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      • Padua L.
      • Padua R.
      • Aprile I.
      • Pasqualetti P.
      • Tonali P.
      Multiperspective follow-up of untreated carpal tunnel syndrome: a multicenter study.
      • Ortiz-Corredor F.
      • Enriquez F.
      • DiazRuiz J.
      • Calambas N.
      Natural evolution of carpal tunnel syndrome in untreated patients.
      • Resende L.A.
      • Tahara A.
      • Fonseca R.G.
      • Sardenberg T.
      The natural history of carpal tunnel syndrome: a study of 20 hands evaluated 4 to 9 years after initial diagnosis.
      of patients will recover or not deteriorate further in the absence of treatment, and hence a certain period of “watchful waiting” (not clearly defined by the available evidence) may be considered clinically when discussing treatment options with patients. When considering potential mechanisms for recovery (not including mechanisms of treatment) Padua
      • Padua L.
      • Padua R.
      • Lo Monaco M.
      • et al.
      Natural history of carpal tunnel syndrome according to the neurophysiological classification.
      suggests that certain undefined CTS cases are self-limiting because of a process of neural adaption, whereby the functional relationship between the nerve and the carpal tunnel adapts over time.
      Because of outcomes being measured at discrete time points by each study, it was not possible to provide a cumulative percentage of patients recovering in each period and thus provide clearer information about what is happening to patients with CTS over time. Table 4 does, however, show that a proportion of patients can be observed to have deteriorated from baseline at any point between 3 months and 10 years, suggesting that the course of CTS is likely to be highly variable. It is possible that the studies with longer follow-up periods are representative of patients who improve and relapse over time, but since none of the studies were designed to observe the longitudinal course of CTS (ie, at a week-to-week or month-to-month level), such a symptom course could not be illustrated by this review.
      With regard to symptom relapse, only 1 study
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      specifically addressed this issue. Goodwill
      • Goodwill C.J.
      The carpal tunnel syndrome. Long-term follow-up showing relation of latency measurements to response to treatment.
      reported that 85% of patients initially responding to conservative treatment approaches relapsed within 1 to 4 years. The possibility of future relapse therefore puts into question the observations of all studies conducted over a shorter time frame. A further consideration is that a recurrence of symptoms after a conservative treatment that then responds to a further episode of conservative management (if deemed clinically appropriate) may not necessarily represent treatment failure. However, longitudinal data that may describe this phenomenon were not available, again emphasizing the importance of long-term studies with repeated assessment of symptoms in patients with CTS.
      The observed between-study variability may be partially explained by substantial differences in study setting, study design, case definitions, interventions (the effectiveness of which cannot be compared between studies), and outcomes used, but possibly also by differences in patient or disease factors (potential prognostic factors) between studies.

      Prognostic factors predicting negative outcome of conservatively managed CTS

      Because of inconsistencies between study findings and the lack of studies with a low risk of bias, it was not possible to identify conclusive evidence for any of the factors reported by individual studies to predict a negative outcome of conservative management. There was, however, 100% agreement in at least 3 or more cohorts with a medium or high risk of bias that symptom duration, a positive Phalen's test, and thenar wasting were associated with a negative outcome of conservative management. However, not all results were statistically significant, and hence the overall judgment remained inconclusive.
      Because of a lack of robustness in design and conduct of most of the included studies, the overall body of evidence identified was felt to be of moderate and high risk of bias. This limited whether the synthesized evidence could be considered as conclusive, and as such, evidence regarding the prognosis of untreated and conservatively treated CTS remains weak. To improve future research, key recommendations would include identifying patients with CTS at baseline using a robust case definition of the condition. Patients should be followed up for a prolonged period (>3y), preferably at a number of time points using a clinically meaningful, valid, and reliable outcome measure. This would allow a longitudinal picture of CTS to be mapped. Attempts could be made to reduce attrition or better describe the risk of attrition bias by collecting information from nonresponders and to provide a description and reason for any loss to follow-up. Ideally, all potential prognostic factors should be included and measured at baseline using valid and reliable measures.
      • Hayden J.A.
      • van der Windt D.A.
      • Cartwright J.L.
      • Cote P.
      • Bombardier C.
      Assessing bias in studies of prognostic factors.
      To capture the start point of the condition and its earliest management, it would be beneficial to set such a study in primary care, where it is likely most patients present initially with their symptoms and commence treatment.

      Study limitations

      We searched electronic databases considered to be important and relevant to the topic. Titles were screened by 1 person because of the significant number; therefore human error may have led to some titles being missed. Studies not included in databases and not identified through reference checking, Google Scholar, and expert advice may have been overlooked, such as unpublished cohort studies. Because the review did not find strong evidence for any of the prognostic factors, it is unlikely that further unpublished material would have strongly influenced our conclusions. The review focused on studies observing the course of symptoms in patients being treated conservatively for CTS but excluded cohorts being allocated specific treatments. Predictors of differential treatment response (moderators) are best identified by randomized trials, and therefore a further systematic review of these studies is planned.
      Results of studies presenting only descriptive results and P values were included in the review without any risk estimates. All evidence found could therefore be included, but there is a possibility that the lack of statistical significance was due to small sample sizes and hence represent a lack of evidence for some of the prognostic factors rather than a genuine absence of association. Future prognosis research in the area of CTS should therefore ensure that estimates of associations with outcome are adequately reported and that the study population is of adequate sample size to investigate the hypothesized associations with outcome.
      The unit of analysis differed between studies; that is, some analyzed outcomes at the patient level (not necessarily taking into account the laterality of the condition), while others analyzed outcomes at the wrist level (ie, patients with bilateral symptoms may be included as 2 cases, not taking dependence of outcomes within individuals into account). Issues relating to the statistical analysis of bilateral CTS have been discussed at length for clinical trials by Page et al.
      • Page M.J.
      • O'Connor D.A.
      • Pitt V.
      • Massy-Westropp N.
      Reporting of allocation method and statistical analyses that deal with bilaterally affected wrists in clinical trials for carpal tunnel syndrome.
      A unit-of-analysis error, which may give rise to overly narrow confidence intervals and small P values, may occur when data are analyzed on the basis of the number of wrists without adjustment for nonindependence.
      • Page M.J.
      • O'Connor D.A.
      • Pitt V.
      • Massy-Westropp N.
      Reporting of allocation method and statistical analyses that deal with bilaterally affected wrists in clinical trials for carpal tunnel syndrome.
      Such an error may also occur in prognosis research, including the reviewed studies, and be a further source of bias. Future prognostic studies should, where possible, take into consideration this risk of bias in their design and analysis plan.

      Implications for clinical practice

      Patients presenting with CTS can be informed of the possibility of recovery with no treatment or conservative treatment (ie, that they will not require surgery); however, factors that help to predict their likelihood of falling into this group have not been robustly determined. Increasing symptom duration, a positive Phalen's test, and thenar atrophy are likely to be prognostic factors of poor outcome of conservatively managed CTS but need confirmation in further well-designed prognostic studies. The review did not identify electrophysiological severity as a significant predictor of a negative outcome of conservative management. This may have implications for services that ration surgery to patients with more severe results and suggests that other factors should be taken into consideration alongside laboratory investigations.

      Conclusions

      In this review, we found useful descriptions of both the course of untreated CTS and that of conservatively managed CTS. Although none of the studies were of low risk of bias, studies of moderate and high risk of bias showed a widely ranging course of symptoms, with 23% to 89% of participants reporting a negative outcome at 3 years' follow-up. We found no consistent evidence to support factors that predict future outcome and that help to explain the wide variability in the course of symptoms.
      There is likely to be an optimum time by which conservative management should be deemed to have failed and surgical intervention considered in order to prevent long-term harm, although this point has not been clearly determined, nor is it clearly possible to predict which patients may be included in this group.

      Supplemental Appendix S1 Medline Search Strategy

      • 1.
        median neuropathy/ or exp carpal tunnel syndrome/
      • 2.
        “carpal tunnel syndrome”.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept, rare disease supplementary concept, unique identifier]
      • 3.
        Nerve Compression Syndromes/
      • 4.
        entrapment neuropath*.ti,ab.
      • 5.
        exp Median Nerve/
      • 6.
        nerve entrapment*.ti,ab.
      • 7.
        Hand/ and Pain/
      • 8.
        Pain/ and Wrist/
      • 9.
        (carpal$ adj3 tunnel$).mp.
      • 10.
        1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9
      • 11.
        exp Prognosis/
      • 12.
        exp Disease Progression/
      • 13.
        prognos*.mp.
      • 14.
        predict*.mp.
      • 15.
        factor*.mp.
      • 16.
        risk*.mp.
      • 17.
        model*.mp.
      • 18.
        evolution.mp.
      • 19.
        history.mp.
      • 20.
        indicator*.mp.
      • 21.
        course.mp.
      • 22.
        rule*.mp.
      • 23.
        transition*.mp.
      • 24.
        determinant*.mp.
      • 25.
        pattern*.mp.
      • 26.
        subgroup*.mp.
      • 27.
        sub-group*.mp.
      • 28.
        screen*.mp.
      • 29.
        long-term.mp.
      • 30.
        progress*.mp.
      • 31.
        modif*.mp.
      • 32.
        mediat*.mp.
      • 33.
        or/11-32
      • 34.
        exp Epidemiologic Studies/
      • 35.
        cohort*.mp.
      • 36.
        follow-up.mp.
      • 37.
        follow-up.mp.
      • 38.
        (“case control” or “case controlled”).mp.
      • 39.
        retrospective*.mp.
      • 40.
        prospective*.mp.
      • 41.
        ((patient* or medical) adj3 (record* or review* or histor*)).mp.
      • 42.
        longitudinal*.mp.
      • 43.
        inception.mp.
      • 44.
        observation*.mp.
      • 45.
        time series.mp.
      • 46.
        outcome*.mp.
      • 47.
        or/34-46
      • 48.
        33 and 47
      • 49.
        10 and 48

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