arpal Tunnel Syndrome. Part I: Effectiveness of Nonsurgicalreatments–A Systematic Review
ionka M. Huisstede, PhD, Peter Hoogvliet, MD, PhD, Manon S. Randsdorp, MD, Suzanne Glerum, MD,
arienke van Middelkoop, PhD, Bart W. Koes, PhD
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ABSTRACT. Huisstede BM, Hoogvliet P, Randsdorp MS,lerum S, van Middelkoop M, Koes BW. Carpal tunnel syn-rome. Part I: effectiveness of nonsurgical treatments–a sys-ematic review. Arch Phys Med Rehabil 2010;91:981-1004.
Objective: To review literature systematically concerningffectiveness of nonsurgical interventions for treating carpalunnel syndrome (CTS).
Data Sources: The Cochrane Library, PubMed, EMBASE,INAHL, and PEDro were searched for relevant systematic
eviews and randomized controlled trials (RCTs).Study Selection: Two reviewers independently applied the
nclusion criteria to select potential studies.Data Extraction: Two reviewers independently extracted
he data and assessed the methodologic quality.Data Synthesis: A best-evidence synthesis was performed
o summarize the results of the included studies. Two reviewsnd 20 RCTs were included. Strong and moderate evidenceas found for the effectiveness of oral steroids, steroid injec-
ions, ultrasound, electromagnetic field therapy, nocturnalplinting, and the use of ergonomic keyboards compared withstandard keyboard, and traditional cupping versus heat pads
n the short term. Also, moderate evidence was found forltrasound in the midterm. With the exception of oral andteroid injections, no long-term results were reported for any ofhese treatments. No evidence was found for the effectivenessf oral steroids in long term. Moreover, although higher dosesf steroid injections seem to be more effective in the midterm,he benefits of steroids injections were not maintained in theong term. For all other nonsurgical interventions studied, onlyimited or no evidence was found.
Conclusions: The reviewed evidence supports that a numberf nonsurgical interventions benefit CTS in the short term, buthere is sparse evidence on the midterm and long-term effec-iveness of these interventions. Therefore, future studies shouldoncentrate not only on short-term but also on midterm andong-term results.
From Department of General Practice (Huisstede, Randsdorp, Glerum,an Middelkoop, Koes) and Department of Rehabilitation Medicine (Huisstede,oogvliet, Randsdorp), Erasmus Medical Center, Rotterdam, The Netherlands.No commercial party having a direct financial interest in the results of the research
upporting this article has or will confer a benefit on the authors or on any organi-ation with which the authors are associated.
Reprint requests to Bionka M. Huisstede, PhD, Erasmus Medical Center—niversity Medical Center Rotterdam, Dept of Rehabilitation Medicine, Room-016, PO Box 2040, 3000 CA Rotterdam, The Netherlands, e-mail:
ARPAL TUNNEL SYNDROME, 1 of the 6 peripheralnerve entrapments located in the upper extremity,1 is
aused by compression of the median nerve as it passes throughhe carpal tunnel.
Twenty-nine percent of those with chronic complaints of thepper extremity reported complaints in the wrist/hand area.2
he prevalence of possible or probable CTS in the generalopulation depends on nuances of the definition used, but it isited as being 5.3% in women and 2.1% in men.3 Among thoseith work-related upper-extremity disorders, work-relatedTS is one of the most disabling and costly, representing aajor cause of lost work days and workers’ compensation costs
n the United States (U.S. Department of Health and Humanervices, 1996). In the United States, 400,000 operations to
reat CTS are performed each year, costing a total of $2illion.4
Characteristic complaints of CTS are pain, paresthesia, andumbness in the fingers and hand (in the area innervated by theedian nerve), often exacerbated at night.5 The exact patho-
hysiology of how the pressure in the carpal tunnel increasesver time is unclear,6 although it is known that the occurrencef CTS is associated with an average hand force requirement ofreater than 4kg, repetitiveness at work (cycle time �10s, or50% of cycle time performing the same movements), and a
aily 8-hour energy-equivalent frequency-weighted accelera-ion of 3.9m/s2.7
Many interventions, both nonsurgical and surgical, haveeen suggested to treat CTS. No therapy for CTS is universallyccepted,8 although monodisciplinary as well as multidisci-linary clinical guidelines have been developed.9,10
Nonsurgical treatment options vary from rest or activityodification to splinting, or the use of oral medication such as
onsteroidal anti-inflammatory drugs or oral steroids.11 In de-ompression surgery, open as well as endoscopic techniquesave been used. The most frequently reported treatments areplinting (56.3%) and nonsteroidal anti-inflammatory agents50.8%).12 Two Cochrane reviews have been written concern-ng nonsurgical treatment options to treat CTS. One of theseeviews13 concerned the effectiveness of all types of nonsur-ical treatments other than steroid injections. This reviewhowed short-term benefit from treatment with ultrasound,plinting, oral steroids, yoga, and carpal bone mobilization. Noignificant results were found in favor of other nonsurgical
List of Abbreviations
CI confidence intervalCTS carpal tunnel syndromeDASH Disability of the Arm, Shoulder and HandMD mean differenceRCT randomized controlled trialRR relative riskVAS visual analog scale
982 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
A
reatments. The second review14 reported on the effectivenessf local corticosteroid injections. Corticosteroid injectionsere more effective than placebo after 1 month and also more
ffective than oral corticosteroids after 3 months. No signifi-ant clinical benefit was found for corticosteroid injectionsompared with other treatments or in favor of multiple injec-ions compared with 1 injection.
Since the publication of these Cochrane reviews, severalCTs have been published, and we wondered whether theonclusions made in the Cochrane reviews would remainhe same or would need modification. To optimize further theuality of care for patients with CTS given by clinicians and byedical and paramedical staff working in primary care, an
verview of the current state of the art regarding evidence-ased information is needed that can support developing andpdating evidence-based protocols and guidelines for interven-ions. Therefore, we systematically reviewed scientific litera-ure to provide an up-to-date overview of the evidence for theffectiveness of interventions to treat CTS. This article, part I,oncentrates on nonsurgical interventions to treat CTS.
METHODS
earch StrategyA search of relevant systematic reviews on CTS was per-
ormed in the Cochrane Library. In addition, relevant reviewsnd RCTs in PubMed, EMBASE, CINAHL, and PEDro wereearched (1) for interventions included in the systematic re-iews from the date of the search strategy of the review up toanuary 2010 (ie, recent RCTs), and (2) from the beginning ofhe database to January 2010 (ie, additional RCTs).
Key words related to the disorder such as “carpal tunnelyndrome,” “median nerve entrapment,” and “interventions”ere included in the literature search. The complete search
trategy is described in appendix 1.
nclusion CriteriaSystematic reviews and/or RCTs were considered eligible
or inclusion if they fulfilled all of the following criteria: (1) thetudy included patients with CTS, (2) CTS was not caused byn acute trauma or any systemic disease (such as osteoarthritis,heumatoid arthritis, diabetes mellitus, or other connectiveissue disease) as described in the definition of complaints ofhe arm, neck, and/or shoulder (CANS), (3) an intervention forreating the disorder was evaluated, and (4) results on pain,unction or recovery were reported. There were no languageestrictions.
If a subset of the total number of patients included in a studyet our inclusion criteria, the study was included only if the
utcomes of the subset were assessed and reported indepen-ently.Studies on the effectiveness of analgesics given presurgery,
uring surgery, or directly postsurgery and in which the effectf these analgesics on pain as a result of the surgery wastudied are excluded from this review.
lied the inclusion criteria to select potential relevant studiesrom the title and abstracts of the references retrieved by theiterature search. A consensus method was used to solve anyisagreements concerning inclusion of studies, and a thirdeviewer (B.W.K.) was consulted if disagreement persisted.
RCTs published after the search data mentioned in the
Cochrane) review and RCTs investigating interventions not
rch Phys Med Rehabil Vol 91, July 2010
ummarized in a (Cochrane) review were included in theresent study.
ategorization of the Relevant LiteratureRelevant publications are categorized under 3 headers: Sys-
ematic reviews, Recent RCTs, and Additional RCTs. Theeader “Systematic reviews” describes all Cochrane andochrane-based systematic reviews. The header “RecentCTs” contains all RCTs published from the final date of the
earch strategy that the systematic review covered. Finally, theeader “Additional RCTs” describes all RCTs concerning in-erventions that have not yet been described in a systematiceview.
ata ExtractionTwo researchers (M.S.R./S.G., B.M.H.) independently ex-
racted the data. Information was collected on the study pop-lation, interventions used, outcome measures, and outcome. Aonsensus procedure was used to solve any disagreement be-ween the researchers.
The follow-up period was categorized into the short term0–3mo), the midterm (4–6mo), and the long term (�6mo).
ethodologic Quality AssessmentTo identify potential risks of bias of the included RCTs, 2
eviewers (M.S.R., B.M.H.) independently assessed the meth-dologic quality of each RCT. The 12 quality criteria (table 1)nd operationalization of these criteria (appendix 2) weredapted from Furlan et al.15 Each item was scored as “yes,”no,” or “don’t know.” High quality was defined as a score of0% or more (ie, a “yes” score on 50% or more of the criteria)n the methodologic quality assessment. A consensus proce-ure was used to solve any disagreement between the review-rs.
ata SynthesisIf quantitative analysis of the studies was not possible be-
ause of diverse outcome measures and other clinical hetero-eneity, a meta-analysis was not performed. In that case, weummarized the results using a rating system consisting of 5evels of scientific evidence, taking into account the method-logic quality and the outcome of the original studies (best-vidence synthesis).16 All RCTs together—that is, the numberf RCTs found in the reviews plus the number of recent RCTsr the number of additional RCTs—determined the availableumber of RCTs for a certain intervention. The article wasncluded in the best-evidence synthesis only if a comparisonas made between the groups (treatment vs placebo, treatments control, or treatment vs another treatment) and the level ofignificance was reported. The results of the study were labeledsignificant” if 1 of the 3 outcome measures had significantesults.
The level of evidence was ranked and divided into theollowing levels:
1. Strong evidence for effectiveness: consistent (�75% ofthe trials report consistent findings); positive (signifi-cant) findings within multiple higher-quality RCTs
2. Moderate evidence for effectiveness: consistent positive(significant) findings within multiple lower-qualityRCTs and/or 1 high-quality RCT
3. Limited evidence for effectiveness: positive (significant)findings within 1 low-quality RCT
4. Conflicting evidence for effectiveness: provided by con-flicting (significant) findings in the RCTs (�75% of the
trials report consistent findings)
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983EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
5. No evidence found for effectiveness of the inventions:RCTs available, but no (significant) differences betweenintervention and control groups were reported
6. No systematic review or RCT found
RESULTS
haracteristics of the Included StudiesThe initial literature search resulted in the identification of 4
ystematic reviews from the Cochrane Library and 47 reviews7 from PubMed, 29 from EMBASE, 11 from CINAHL). Wedentified another 750 RCTs (241 from PubMed, 276 fromMBASE, 177 from CINAHL, 56 from PEDro). Finally, afterelection based on the content of the titles, abstracts, and fullext of the references, 2 Cochrane reviews and 26 recent RCTs25 from PubMed 1 from PEDro, none from EMBASE orINAHL) met our inclusion criteria. No additional RCTs were
ound. Four RCTs (2 from PubMed,17 2 from EMBASE18,19)ere initially included based on the content of their abstract.ecause the full texts were not available in national and inter-ational medical libraries, we contacted the authors by e-mail;owever, no full-text articles were received, so these articlesould not be included in the present review. The data extractionf the included studies is presented in appendix 3 (systematiceviews) and appendix 4 (recent RCTs).
ethodologic Quality of the Included StudiesThe results of the methodologic quality assessment of the 20
ncluded recent and additional RCTs are presented in table 2.he Cochrane review of O’Connor et al13 (which reported ononsurgical treatment other than steroid injections) used theethodologic quality criteria of the Cochrane Reviewers Hand-
ook 4.0.20 Eight quality items were described, and RCTs wereefined as high-quality (A), moderate-quality (B), or low-uality (C). Moderate RCTs had a score of 50% or more on theuality criteria. Therefore, we decided that A and B studycores would be defined as high-quality RCTs (table 3). Theethodologic quality criteria of Jadad et al21 were used in theochrane review of Marshall et al14 reporting on corticosteroid
njections. Five quality items were described, and they definedoor-quality and good-quality studies (table 4).A total of 53 RCTs are included in our systematic review. Of
hese, 29 RCTs (55%) were of high quality, and 8% of the
Table 1: Methodologic Qualit
Item
1. Was the method of randomization adequate?2. Was the treatment allocation concealed?
Was knowledge of the allocated interventions adequately pr3. Was the patient blinded to the intervention?4. Was the care provider blinded to the intervention?5. Was the outcome assessor blinded to the intervention?Were incomplete outcome data adequately addressed?6. Was the dropout rate described and acceptable?7. Were all randomized participants analyzed in the group to8. Are reports of the study free of suggestion of selective ouOther sources of potential bias:9. Were the groups similar at baseline regarding the most im10. Were co-interventions avoided or similar?11. Was the compliance acceptable in all groups?12. Was the timing of the outcome assessment similar in all
tudies scored 40% to 50% of the total score. (
ffectiveness of InterventionsStrong and moderate evidence for the effectiveness of non-
urgical interventions for the treatment of CTS is presented inable 5. A complete overview of levels of evidence for theffectiveness of all the identified nonsurgical interventions isresented in table 6.
. Nonsurgical Treatment (other than steroid injections)The Cochrane review of O’Connor13 (search up to February
001, PubMed; up to March 2002, EMBASE; up to December001, CINAHL and PEDro) included 21 trials (n�923) study-ng the effectiveness of all types of nonsurgical treatmentsother than steroid injections) for CTS. The trials presentedndings in 12 treatment areas: splinting, ultrasound, ergonomiceyboards, oral medication, vitamins, exercise, yoga, mobili-ation, magnet therapy, chiropractic care, laser, and acupunc-ure. Furthermore, we found 18 recent RCTs (n�963) on theffectiveness of splinting, ultrasound, laser, oral medication,anual therapy, magnetic field stimulation, acupuncture, mas-
age therapy, heat wrap therapy, cupping therapy, botulinum Boxin, iontophoresis, and exercise. No additional RCTs wereound.
.1. SplintingIn the systematic review of O’Connor,13 3 RCTs22-24 on
plinting were included. Furthermore, 7 recent RCTs25-31 onplinting were found.
ifferent Positions for a Wrist Splint ComparedSystematic review. One low-quality RCT22 (n�90) in the
ochrane review of O’Connor13 compared the short-term ef-ects of a wrist splint in neutral position with a wrist splinted in0° extension. After 2 weeks of treatment, significant overallnd nocturnal improvement (RR�2.43, 95% CI, 1.12–5.28;nd RR�2.14, 95% CI, .99–4.65, respectively) was found inavor of the splint in neutral position.
We concluded that there is limited evidence that the use ofwrist splint in neutral position is more effective than an
xtended wrist position of 20° in patients with CTS in the shorterm (2 weeks).
octurnal Hand Brace Versus No TreatmentSystematic review. O’Connor13 found 1 low-quality RCT23
teria: Sources of Risk of Bias
Judgment
Yes / No / UnsureYes / No / Unsure
ed during the study?Yes / No / UnsureYes / No / UnsureYes / No / Unsure
Yes / No / Unsureh they were allocated? Yes / No / Unsuree reporting? Yes / No / Unsure
ant prognostic indicators? Yes / No / UnsureYes / No / UnsureYes / No / Unsure
ps? Yes / No / Unsure
y Cri
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n�80) that compared a nocturnal hand brace with no treatment.
Arch Phys Med Rehabil Vol 91, July 2010
Table 2: Methodologic Quality Scores of the Included RCTs
Abbreviations: �, Yes; �, No; ?, unsure; ITT, intention to treat; NA, not applicable (in an intervention such as surgery, compliance is not an issue).
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ignificant results were found in favor of a nocturnal hand braceompared with no treatment on symptom improvementWMD��1.07; 95% CI, �1.29 to �.85), hand functionWMD��.55; 95% CI, �.82 to �.28), and overall improvementRR�4.00; 95% CI, 2.34–6.84) at 4 weeks of follow-up.
Recent RCTs. In the low-quality RCT of Premoselli etl,29 (n�50) the positive results found in the review of’Connor13 were confirmed at 3 and 6 months of follow-up:
ignificantly better results in favor of a nocturnal neutral wristplint were found on symptoms (mean differences � SD,plint, 1.07�.39, vs control, �.02�.24, P�.001; and splint,.22�.39, vs control, .17�.29, P�.001, respectively) and
Table 3: Methodologic Quality Scores o
Reference Randomization?Allocation
Concealment?BlindingPatients?
BlindingCaregiver?
BlindingOutcom
Assessor
Ebenbichleret al35 � � � � �
Hui et al44 � � � � �
Spooneret al46 � � � � �
Carteret al54 � � � � �
Changet al42 � � � � �
Herskovitzet al43 � � � � �
Rempelet al52 � � � � �
Aigneret al56 � � � � �
Ozkulet al63 � ? � � �
Oztaset al36 � ? � � �
Pal et al45 � ? � � �
Daviset al51 � � � � �
Manenteet al23 � � � � �
Burkeet al22 � ? � � �
Garfinkelet al34 � � � � �
Koyuncuet al37 � ? � � �
Stranskyet al47 � ? � � �
Tal-AkabiandRushton49 � � � � �
Akalinet al32 � ? � � �
Tittiranondaet al53 � ? � � �
Walkeret al24 � ? � � �
OTE. Definition of O’Connor et al:13 A, high quality: all criteria met; Briteria not met.bbreviations: �, Yes; �, No; ?, unsure; �, partly met.
unction (mean differences � SD, splint, .53�.22, vs control, s
.15�.43, P�.0001; and splint, .75�.28, vs control, .04�.30,�.0004, respectively).It was concluded that there is moderate evidence in the short
erm and limited evidence in the midterm that a nocturnal handrace is more effective than no therapy in the treatment ofatients with CTS.
ull-time use of a Wrist Splint Versus Night-Only UseSystematic review. In the low-quality RCT of Walker et
l24 (n�24) included in the review of O’Connor13 that com-ared the full-time use of a wrist splint with night-only use, no
Cochrane Review of O’Connor et al13
Nolectionias?
NoPerformance
Bias?
NoAttrition
Bias?
QualityScore
According toO’Connor
et al13Score
MaximumStudyScore
OurDefinition ofHigh or Low
Quality ofStudy
� � � A 8 8 High� � � A 8 8 High
� � � A 8 8 High
� � � B 8 7 High
� � � B 8 7 High
� � � B 8 7 High
� � � B 8 6 High
� � � B 8 5 High
� � � B 8 5 High
� � � B 8 3 High� � � B 8 4 High
� � � C 8 5 Low
� � � C 8 4 Low
� � � C 8 3 Low
� � � C 8 3 Low
� � � C 8 3 Low
� � � C 8 3 Low
� � � C 8 3 Low
� � � C 8 2 Low
� � � C 8 2 Low
� � � C 8 2 Low
derate quality: 1 or more criteria partly met; C, low quality: 1 or more
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ignificant differences were found on symptom improvement
Arch Phys Med Rehabil Vol 91, July 2010
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986 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
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WMD��.21; 95% CI, �.83 to .41) or hand functionWMD��.21; 95% CI, �.87 to .45) at 6 weeks of follow-up.
In conclusion, there is no evidence for the effectiveness of aull-time use of a wrist splint compared with night-only use inatients with CTS in the short term.
Table 5: Strong and Moderate Evidence for Effectivenessof Nonsurgical Interventions for CTS
Nonsurgical Interventions to TreatCTS
Strong or ModerateEvidence Found
Physiotherapy ✓abc
Oral ✓de
Injection ✓fghij
Other nonsurgical interventions ✓klmno
Strong or moderate evidence found.
hort-term:Moderate evidence: ultrasound* vs placebo at 7wk of follow-up.Moderate evidence: ultrasound* vs laser.Strong evidence: oral steroids* vs placebo at 2wk of follow-up.Moderate evidence: oral steroids* vs placebo at 4wk of follow-up.Strong evidence: corticosteroid injections* vs placebo.Moderate evidence: local* vs systemic steroids injection.Moderate evidence: local corticosteroid injection* vs oral steroids.Moderate evidence: insulin injections as additive to steroids
injections in patients with noninsulin-dependent diabetesmellitus.
Moderate evidence: nocturnal hand brace* vs no therapy.Moderate evidence: wrist splinting vs prednisone.*Moderate evidence: ergonomic keyboard* vs standard keyboard.Moderate evidence: dynamic magnetic field therapy* vs placebo
therapy.Moderate evidence: cupping therapy vs head† pads.
idterm:Moderate evidence: ultrasound*� vs placebo.Moderate evidence: 60mg methylprednisone* vs 20 or 40mg
methylprednisone in the midterm.
ong-term:
f*in favor of
rch Phys Med Rehabil Vol 91, July 2010
rist Splint Versus Hand BraceRecent RCTs. One recent high-quality RCT (n�120)31
ompared a wrist splint with a hand brace. Both groups worehe orthotic devices for 3 months at night. No significantifferences between the groups were found on the symptomeverity score, on the function severity score of the Bostonarpal Tunnel Questionnaire, and on pain from baseline to 3onths of follow-up and to 9 months of follow-up.Therefore, there is no evidence for the effectiveness of a
ight hand brace compared with night splinting of the wrist forhe treatment of CTS in the short term.
endon and Nerve Gliding Exercises as Additive toplintingSystematic review. One low-quality trial32 (n�36) found
o significant differences on symptom improvement, handunction, grip strength, and pinch strength for nerve and tendonliding exercises as additive to a neutral wrist splint at 3onths of follow-up.Recent RCTs. The low-quality study of Baysal et al25
n�56) reported on ultrasound, splinting, and nerve and tendonliding exercises. Patients were divided into 3 treatmentroups. Group 1 was treated with a splint and nerve and tendonliding exercises, group 2 with a splint and ultrasound treat-ent, and group 3 with a splint, nerve and tendon gliding
xercises, and ultrasound treatment. No results between theroups were presented. However, within the 3 treatmentroups, significant differences were found on pain (VAS), griptrength, pinch strength, the symptom severity scale, and theunction status scale at 8 weeks of follow-up.
One recent high-quality RCT26 (n�51) studied 2 types ofplints (a neutral wrist and metacarpophalangeal splint, group; and a wrist cock-up splint, group 2) with and without tendonnd nerve gliding exercises (groups 3 and 4, respectively).ignificant results within the groups (no P value given) onymptoms (group 1, 38%, vs group 2, 17%; groups 3 and 4, noercentages given) at 8 weeks of follow-up and pinch strengthno further data given) within the groups were found at 4 weeks
corticosteroid injectionShort-term:–Single vs 2 local
corticosteroid injections(15mg methylprednisone)
Short-term:Midterm:Long-term:–Novel approach vs classic
approach of injectionShort-term:–Proximal approach vs
distal approach ofinjection
Long-term:–Corticosteroid injection*
vs iontophoresisShort-term:–Corticosteroid injection vs
phonophoresisMidterm:–Corticosteroid injection vs
EMLA creamShort-term:
Injections other than
steroid
–Botulinum B toxin vsplacebo
Midterm:
Insulin as additive to
steroid injection
–In noninsulin-dependentdiabetes mellitus: steroidinjections followed byNPH injection* vs steroidinjections followed byplacebo injections
Short-term:
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NE
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Splinting
–Splinting in neutral position* vs splinting in extended wristposition of 20°
Short term (2wk):–Nocturnal hand brace* vs no therapyShort-term:Midterm:–Full-time use wrist splint vs night-only splintShort-term:–Night wrist splint vs night hand braceShort-term:–6wk day-and-night splint followed by 4wk night-splint and
4wk nerve gliding exercises* vs same treatment withoutnerve gliding exercises
Short-term:–Active neurodynamic exercises* as additive to night splint
during heavy activities plus tendon gliding exercisesMidterm:–Neutral wrist plus MCP splint (NW) vs wrist cock-up splint
(WCP) vs NW plus tendon and nerve gliding exercises (E)vs WCP plus E
Short-term:–Splint plus nerve and tendon gliding exercises (NTE) vs
splint plus ultrasound vs splint plus NTE plus ultrasoundShort-term:–Wrist splint vs oral prednisone*Short-term:–Low-level laser as additive to splintingShort-term:–Yoga vs wrist splintingShort-term:
Chiropractic treatment
–Chiropractic treatment vs medical treatmentMidterm:
Ergonomic keyboards
–Ergonomic keyboard* vsstandard keyboardShort-term:–Apple keyboard* vs standard keyboardMidterm:–Microsoft keyboard* vs standard keyboardMidterm:–Other ergonomic keyboards vs regular keyboardMidterm:
Magnet therapy
–Magnet therapy vs placeboShort-term:
Magnetic field therapy
–Dynamic magnet field therapy vs placeboShort-term:
Acupuncture
–Laser acupuncture vs placeboShort-term:–Acupuncture vs oral steroidsShort-term:
Heat wrap therapy
–Heat wrap therapy* vs oral placeboShort-term (3d):
Cupping therapy
–Cupping therapy* vs heat padsShort-term (7d):
Iontophoresis
–Dexamethasone iontophoresis vs PlaceboMidterm:Long-term:
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bbreviations: �, limited evidence found; ��, moderate evidence found; ���, strong evidence found; d, days; EMLA, Eutectic mixture of Local Anesthetic; MCP, metacarpo-halangeal; mo, month; NE, no evidence found for effectiveness of the treatment: RCTs available, but no differences between intervention and control groups were found; NPH,
988 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
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The low-quality RCT of Pinar et al28 (n�35) compared 2roups of patients with CTS: a day-and-night splint and aonsurgical training program (nerve and gliding exercises)ere applied for 6 weeks to both groups. Subsequently, a night
plint only was used in both groups, and nerve and glidingxercises were continued in the experimental group for theemaining 4 weeks. Significant progress was detected on griptrength between the experimental group and the control groupmean � SD, 4.2�4.1 vs 1.3�1.5, respectively) at 10 weeks ofollow-up in favor of the experimental group. Furthermore,etween-group analyses showed no significant differences onain and pinch strength.The low-quality study of Heebner and Roddey27 (n�60)
nvestigated active neurodynamic exercises as additive to stan-ard care (consisting of splinting at night during heavy activ-ties plus tendon gliding exercises). No significant differencesn the DASH Questionnaire, symptom severity score, andeurodynamic irritability of the median nerve were found at 6onths of follow-up. Significant differences were found on the
unction severity scale in favor of standard care with activeeurodynamic exercises at 6 months of follow-up (standardare with active neurodynamic exercises, 2.2 [mean], com-ared with standard care, 2.9; P�.016).In conclusion, there is limited evidence that 6 weeks of
ay-and-night splinting with a nonsurgical training programollowed by 4 weeks of night splint with nerve gliding exer-ises is more effective than the same treatment without nerveliding exercises in the short term, and that active neurody-amic exercises as additive to standard care (ie, night splinturing heavy activities plus tendon gliding exercises) is moreffective (limited evidence) than standard care alone in theidterm. There is no evidence for the effectiveness of a neutralrist and metacarpophalangeal splint compared with a wrist
ock-up splint with and without tendon and nerve glidingxercises. Furthermore, there is no evidence for the effective-ess of treatment with a splint plus nerve and tendon glidingxercises compared with treatment with a splint plus ultrasoundr compared with treatment with a splint plus tendon glidingxercises plus ultrasound in the short term.
plinting Versus Oral PrednisoneRecent RCTs. One recent high-quality RCT33 (n�71)
ompared splinting of the wrist in neutral position for 4 weeksith oral prednisolone 20mg/d for 2 weeks followed by0mg/d for 2 weeks. Significant differences were reported onhe function status score in favor of oral steroids compared withplinting (mean � SD, splint, .16�.17, vs oral steroids,26�.21; P�.03), but no significant differences were found onhe symptom severity scale at 3 months of follow-up.
In conclusion, there is moderate evidence that oral steroidsre more effective than splinting of the wrist to treat CTS in thehort term.
plinting Versus Splinting Plus Low-Level Laser TherapyRecent RCTs. One recent high-quality RCT30 compared a
ull-time hand splint in neutral position for 3 months withplinting plus 10 sessions of low-level laser therapy. Onlyignificant within-group results were reported on the symptomeverity score of the Boston Carpal Tunnel Questionnaire andor grip strength within the splinting group. No significantifferences between the groups were found on the Bostonarpal Tunnel Questionnaire (function capacity and symptom
everity scores). At 3 months of follow-up, no comparison
etween the groups for grip strength was made. s
rch Phys Med Rehabil Vol 91, July 2010
Therefore, there is no evidence for the effectiveness ofplinting compared with splinting plus low-level laser therapyn the short term.
plinting Versus YogaSystematic review. One low-quality RCT (n�51)34 in the
eview of O’Connor13 compared yoga with wrist splinting andound no significant differences on pain at 8 weeks ofollow-up.
In conclusion, there is no evidence for the effectiveness ofoga compared with wrist splinting to treat CTS in the shorterm.
.2 Ultrasoundltrasound Versus PlaceboSystematic review. An analysis of pooled data from 2
rials35,36 (n�63) of ultrasound treatments compared with pla-ebo of O’Connor13 showed no significant effects on pain,ymptoms, or function at 2 weeks of follow-up. However, 1igh-quality trial35 showed significant symptom improvementfter 7 weeks in patients treated with ultrasoundWMD��.99; 95% CI, �1.77 to �.21), which was main-ained at 6 months of follow-up (WMD��1.86; 95% CI,
2.67 to �1.05).Thus, there is no evidence for the effectiveness of ultrasound
ompared to placebo at 2 weeks of follow-up, but there isoderate evidence that ultrasound is more effective than pla-
ebo in the treatment of patients with CTS at 7 weeks ofollow-up and in the midterm.
ltrasound: Comparison of IntensitiesSystematic review. One high-quality RCT36 (n�30) in-
luded in the review of O’Connor13 compared 2 intensities ofltrasound (1.5W/cm2 and 0.8W/cm2) but found no significantifferences regarding pain and symptom improvement betweenhese intensities after 2 weeks.
Therefore, we conclude there is no evidence for the effec-iveness of an ultrasound intensity of 1.5W/cm2 compared with.8W/cm2 in the short term.
ltrasound: Different Frequencies ComparedSystematic review. At 4 weeks of follow-up in another
ow-quality RCT37 (n�21) included in the review of’Connor,13 2 different frequencies (1 and 3MHz) were com-ared, but no significant differences were found on pain andunction. It was concluded that there is no evidence for theffectiveness of 1 or 3MHz frequency of ultrasound in patientsith CTS in the short term.
ltrasound Versus Laser TherapyRecent RCTs. In a high-quality RCT38 (n�90), ultra-
ound was compared with laser therapy. Ultrasound ap-eared to be significantly more effective than laser therapyn pain (MD between groups, �4.4; 95% CI, �4.9 to �3.1;�.001) and function (hand grip strength: MD betweenroups, 12.1; 95% CI, 5.7–27.6; P�.001) at 4 weeks ofollow-up.
Therefore, there is moderate evidence that ultrasound isore effective than laser therapy in the treatment of patientsith CTS in the short term.
.3 Laser TherapyRecent RCTs. Three recent RCTs on laser therapy were
ound. In the high-quality RCT of Irvine et al39 (n�15), no
ignificant differences were found between low-level laser
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herapy and placebo on a symptom severity scale and on handerformance score at 9 weeks of follow-up.In the high-quality study of Evcik et al40 (n�81), no signif-
cant differences were found between the low-level laser ther-py and placebo treatment on hand grip strength, pinch grip,ain, and functional capacity at 12 weeks of follow-up.The high-quality study of Shooshtari et al41 (n�80) com-
ared low-level laser therapy to placebo. No comparisons be-ween the 2 groups were made. Significant differences wereound on pain and hand grip within the low-level laser therapyroup (mean � SD, from 7.8�.42 before treatment to.98�.12 at 3 weeks of follow-up, P�.001; and from9.81�5.06kg before treatment to 22.86�5.13kg at 3 weeks ofollow-up, P�.001, respectively). Within the placebo group,ignificant differences were found for pain (mean � SD, from.01�.36 before treatment to 7.62�0.4 at 3 weeks of follow-p; P�.001), but no significant differences were found forand grip.In conclusion, there is no evidence for the effectiveness of
aser therapy compared with placebo as an intervention to treatTS in the short term.
.4 Oral Medications and VitaminsSystematic review. Six RCTs42-47 (n�243) in the Co-
hrane review of O’Connor13 reported on oral medication oritamins. Three high-quality RCTs compared oral steroids withlacebo. 42-44 Pooling of the data of these 3 trials demonstratedignificant changes in favor of oral steroids on symptom im-rovement (WMD��7.23; 95% CI, �10.31 to �4.14) at 2eeks of follow-up. One RCT42 found significant differencesn symptom improvement at 4 weeks of follow-upWMD��10.8; 95% CI, �15.26 to �6.34).
Two other high-quality RCTs compared nonsteroidal anti-nflammatory drugs42 and diuretics45 with placebo. No signif-cant benefit on symptom improvement was reported for non-teroidal anti-inflammatory drugs or diuretics versus placebo at
weeks of follow-up. One high-quality study46 and 1 low-uality study 47 found no significant differences between vita-in B6 and placebo on overall symptoms at 10 to 12 weeks of
ollow-up.Recent RCTs. The long-term effects of the study of Chang
t al42 included in the Cochrane review of O’Connor13 wereeported by the high-quality RCT of Chang et al48 (n�109).hang48 compared oral prednisolone given for 4 weeks (20mgaily for 2 weeks followed by 10mg daily for 2 weeks) withral prednisolone given for 2 weeks (20mg daily for 2 weeksnd placebo for 2 weeks). No significant differences on overallmprovement were found at 12 months of follow-up.
In conclusion, there is strong evidence after 2 weeks andoderate evidence after 4 weeks that oral steroids are more
ffective than placebo. There is no evidence for the effective-ess of 20mg daily of prednisolone for 2 weeks followed by0mg daily of the same drug for 2 weeks versus 20mg pred-isolone daily for 2 weeks followed by placebo in the longerm. Furthermore, there is no evidence for the effectiveness ofnti-inflammatory drugs or diuretica in the short term. In ad-ition, there is no evidence for the effectiveness of vitamin B6o treat CTS in the short term.
.5 Other Nonsurgical Treatments
obilization and Manual TherapySystematic review. The low-quality RCT of Tal-Akabi and
ushton49 (n�21) on carpal bone mobilization demonstrated aignificant benefit on symptoms compared with no treatment
WMD��1.43; 95% CI, �2.19 to �.67) at 3 weeks of follow- b
p. Further, no significant results were found on any outcomeegarding pain, function, or improvement comparing neurody-amic with carpal bone mobilization after 3 weeks of follow-p. No significant results were found on any outcome regardingunction by comparing neurodynamic with carpal bone mobi-ization in the short term.
Recent RCTs. The high-quality study of Bialosky et al97
eported on a neurodynamic technique intended to providenatomic stress across the median nerve and combined thisntervention with splinting for 3 weeks. This intervention wasompared with sham therapy. Both groups were also treatedith a splint for 3 weeks. After 3 weeks of treatment, no
ignificant differences between the groups were found on pain,he DASH Questionnaire, or grip strength.
The high-quality study of Burke et al50 (n�22) compared 2anual therapy interventions: the Graston instrument–assisted
oft tissue mobilization plus home exercises with manual softissue mobilization by a clinician plus home exercises. Im-roved results were found within groups, but there were noignificant differences between the 2 groups on pain, range ofotion (flexion and extension), grip strength, and the Bostonarpal Tunnel Questionnaire (functional status scale and the
ymptom severity scale) at 6 months of follow-up.Therefore, there is limited evidence that carpal bone mobi-
ization is more effective than no treatment in the short term.o evidence was found for the effectiveness of neurodynamicersus carpal bone mobilization in the short term, for theffectiveness of a neurodynamic technique plus splinting com-ared with a sham therapy plus splinting group in the shorterm, or for the effectiveness of Graston instrument–assistedoft tissue mobilization plus home exercises compared withoft tissue mobilization plus home exercises to treat CTS in theidterm.
hiropractic TreatmentSystematic review. No significant differences on hand
unction between chiropractic treatment (ie, manual thrusts,yofascial massage and loading, ultrasound, and nocturnalrist splint) and medical treatment (ie, ibuprofen and wrist
plint) were found in a low-quality trial of Davis et al51 (n�91)t 13 weeks of follow-up.
Therefore, there is no evidence for the effectiveness ofhiropractic therapy compared with medical treatment for CTSn the midterm.
rgonomic KeyboardsSystematic review. Two RCTs52,53 included in the review
f O’Connor13 studied ergonomic keyboards compared withontrol. The high-quality study of Rempel et al52 (n�18)ompared an ergonomic keyboard with a standard keyboardnd found significant changes on pain and hand function inavor of the ergonomic keyboard (WMD��2.40, 95% CI,
4.45 to �0.35; WMD��2.20, 95% CI, �12.08 to 7.68,espectively) at 3 months of follow-up. The low-quality studyf Tittiranonda et al53 (n�80) found no significant differencesn pain among 3 ergonomic keyboards (ie, comfort keyboardystem, Apple adjusTable keyboard, and Microsoft naturaleyboard) and a regular keyboard at 6 months of follow-up. Atmonths of follow-up, significant changes on hand functionere found in favor of the Apple keyboard and the Microsofteyboard compared with a regular keyboard (WMD�.93, 95%I, .26–1.60; WMD�1.92, 95% CI, .84–3.00, respectively),ut no significant differences were found on hand function inhe ergonomic keyboard group.
Thus, there is moderate evidence that an ergonomic key-
oard is more effective than a standard keyboard in the short
Arch Phys Med Rehabil Vol 91, July 2010
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990 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
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erm. In the midterm, there is limited evidence that an Appleeyboard and a Microsoft keyboard are more effective than aegular keyboard, but no evidence for the effectiveness of otherrgonomic keyboards compared with a regular keyboard.
agnet TherapySystematic review. One high-quality RCT (n�30)54 com-
ared magnet therapy with placebo and found no significantenefit on pain between these groups at 2 weeks of follow-up.Therefore, we found no evidence for the effectiveness ofagnet therapy.
agnetic Field TherapyRecent RCTs. Significant differences were found in a
igh-quality study of Weintraub and Cole55 (n�36) on theeuropathy Pain Scale (total composite; reduction: treatmentroup, 42%, compared with controls, 24%; P�.04) betweenimultaneous and time-varying dynamic magnetic field stimu-ation on the wrist and sham therapy from baseline to 2 monthsf follow-up. In contrast, no significant differences were foundn pain and Patients Clinical Global Impression of Change atmonths of follow-up.Therefore, we found moderate evidence for the effectiveness
f dynamic magnetic field therapy in the short term to treatatients with CTS.
cupunctureSystematic review. A high-quality RCT (n�26)56 demon-
trated no significant differences between laser acupuncturend placebo on night pain at 3 weeks of follow-up.
Recent RCTs. The high-quality study of Yang et al57 com-ared 4 weeks of acupuncture (8 sessions) with oral steroidsfirst 2 weeks, 20mg prednisolone daily, followed by 2 weeksf 10mg prednisolone daily). Both interventions resulted inetter but no significant differences on the Global Symptomcore at 4 weeks of follow-up (mean percent change � SDrom baseline to 4 weeks, acupuncture group, �70�24.6, vsteroid group, �64.7�27.6).
It was concluded that there is no evidence for the effective-ess of laser acupuncture for the treatment of CTS in the shorterm, or for the effectiveness of acupuncture compared withral steroid drugs to treat CTS in the short term.
assage TherapyRecent RCTs. The low-quality study RCT of Moraska et
l58 (n�27) compared a targeted massage protocol (focused onhe affected upper extremity and addressing areas of constric-ion, ischemia, and nerve entrapment) with a general massagerotocol (relaxing massage to reduce tension of the back, neck,nd upper extremities) for 6 weeks. Significant effects wereound on grip strength at 10 weeks of follow-up in favor of theargeted massage group (targeted massage group, mean from5.1kg to 29.5kg; 95% CI, 27.7–31.3kg; vs the general mas-age group, mean from 25.1kg to 26.3kg; P�.04). No signif-cant differences were found on pinch strength (at 6wk), symp-om severity score (at 10wk), function status scale (at 6wk),nd the Grooved Pegboard Test (at 6wk). The low-qualitytudy of Field et al59 (n�16) also examined massage therapy asreatment for CTS, but they compared a 15-minute massagence a week for a 4-week period plus self-massage daily withcontrol group without treatment. Significant differences were
ound in favor of the massage group on CTS (ie, loss oftrength, tingling, numbness, burning, or pain to the affectedegion; massage group, from 3.00 at the first day to 2.22 at the
ast day compared with controls, from 3.00 at the first day to w
rch Phys Med Rehabil Vol 91, July 2010
.00 at the last day; P�.05), pain (massage group, from 4.11 ataseline to 2.59 at 4 weeks of follow-up compared with con-rols, from 6.17 at baseline to 4.83 at 4 weeks of follow-up;�.05), and grip strength (massage group, from 6.61 at base-
ine to 7.8 at 4 weeks of follow-up compared with controls,rom 5.58 at baseline to 6.25 at 4 weeks of follow-up; P�.05)fter 3 treatment sessions at 4 weeks of follow-up.
Therefore, there is limited evidence that a targeted massagerotocol is more effective than a general massage protocol, andhat massage therapy for 15 minutes once a week with self-assage daily is more effective than no treatment in the short
erm.
eat Wrap TherapyRecent RCTs. One recent low-quality RCT60 (n�22) stud-
ed low-level heat wrap therapy (104°F; 40°C) for 3 days (withtotal of 26 time points) compared with oral placebo with a
ollow-up of 2 days. Significant differences in favor of low-evel heat wrap therapy were found on pain at 20 of the 26 timeoints (P�.05), joint stiffness reduction at 19 of the 26 timeoints (P�.05), grip strength (mean � SD, heat wrap,.1�1.6kg, vs oral placebo, 0.8�1.4kg; P�.012) and symptomeverity scale (mean � SD, heat wrap, .97�.16, vs oral pla-ebo, .14�.14; P�.001). After 3 days, significant differencesn favor of heat wrap therapy were found on function statuscale, but not at 5 days of follow-up (mean � SD, heat wrap,65�.16, vs oral placebo, .00�.16, P�.006, and heat wrap,57�.22, vs oral placebo, .12�.20, P�.07, respectively).
There is limited evidence that heat wrap therapy is moreffective than oral placebo in the short term (3 days ofollow-up).
upping TherapyRecent RCTs. The high-quality study of Michalsen et al61
ompared traditional cupping therapy with heat pads (controlroup). At day 7, significant differences were found on pain at restMD��22.9; 95% CI, �35.3 to �10.5), the Levine CTS scoresymptom severity, mean difference, �22.9, 95% CI, �35.3 to10.5; functional status, MD �0.6, 95% CI, �0.8 to �0.3), and
he DASH score (MD��11.1; 95% CI, �17.1 to �5.1).Therefore, we concluded that cupping therapy is more
ffective (moderate evidence) than heat pads at 7 days ofollow-up.
njections Other Than SteroidsRecent RCTs. An injection with botulinum B toxin into
ach of the 3 hypothenar muscles was compared with placebon the low-quality study of Breuer et al62 (n�20). The studyeported no significant differences on Clinical Global Impres-ion of Severity at 13 weeks of follow-up.
Thus, there is no evidence for the effectiveness of botulinumtoxin compared with ibuprofen and wrist splint to treat
atients with CTS in the midterm.
nsulin as Additive to a Steroid InjectionSystematic review. The high-quality study of Ozkul et al63
nvestigated insulin as additive to steroid injection (methyl-rednisolone 20mg in 1mL) for 7 weeks in patients withoninsulin-dependent diabetes mellitus and found significantifferences on the Global Symptom scale in favor of steroidnjection plus insulin injections at 8 weeks of follow-up (noxact data and P value given).
In conclusion, there is moderate evidence that in patients
991EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
lus insulin injections are more effective than steroid injectionslone for the treatment of CTS in the short term.
onthophoresisRecent RCTs. One recent RCT of high quality64 found no
ignificant differences on the Levine Questionnaire betweenexamethasone iontophoresis and a control group (iontophore-is with distilled water) at 3 and 6 months of follow-up.
We concluded there is no evidence for the effectiveness ofexamethasone iontophoresis compared with a placebo con-rolled group in midterm and long term.
. Corticosteroid injectionsMarshall14 conducted a Cochrane review (search up toay 2006) on local corticosteroid injection versus placebo
njection or other nonsurgical interventions in improvinglinical outcome and also to determine how long symptomelief lasted. Twelve RCTs were included (n�671) in thiseview. Furthermore, 3 recent RCTs were found.
orticosteroid Injections Versus PlaceboSystematic review. One high-quality study65 (n�60) in-
luded in the review of Marshall14 demonstrated significantlinical improvement in favor of local corticosteroid (40mgethylprednisolone) compared with placebo injection
RR�3.83; 95% CI, 1.82–8.05) 1 month after treatment.Another high-quality study66 (n�81) compared 1.5mg beta-ethasone with placebo and found significant clinical improve-ent in favor of corticosteroid injections 2 weeks after treat-ent (RR�2.04; 95% CI, 1.26–3.31). Pooling of the data of
he 2 RCTs demonstrated significant clinical improvement inavor of corticosteroid injection in the short term (RR�2.58;5% CI, 1.72–3.87).In conclusion, we found strong evidence that a corticosteroid
njection is more effective than placebo in the treatment ofatients with CTS in the short term.
ocal Versus Systemic Corticosteroid InjectionSystematic review. One high-quality trial67 (n�37)
howed a better rate of improvement with a local corticosteroidnjection (betamethasone 1.5mg) than with a systemic cortico-teroid injection (betamethasone 1.5mg) (RR�3.17; 95% CI,.02–9.87) at 1 month of follow-up.Therefore, there is moderate evidence that local corticoste-
oid injections are more effective than systemic corticosteroidnjections to treat CTS in the short term.
orticosteroid Injection Versus Oral SteroidSystematic review. One high-quality trial68 (n�60) in-
luded in the Cochrane review14 found no significant differ-nces on symptom improvement on the Global Symptom Scoret 2 weeks of follow-up and significant differences on symptommprovement on the Global Symptom Score in favor of corti-osteroid injections (15mg methylprednisolone) compared withral steroids (25mg methylprednisolone) at 8 weeks and 12eeks of follow-up (WMD��7.16, 95% CI, �11.46 to2.86; and WMD��7.10, 95% CI, �11.68 to �2.52,
espectively).Recent RCTs. The long-term effects of the study of Wong
t al68 were reported by the high-quality study of Hui et al.69 Ofhe 80 randomized participants, 35 did not require surgicalreatment in 80 weeks of follow-up; no significant differencesetween these groups were found on the Global Symptom
core at 80 weeks of follow-up (steroid injection, 69.5% im- l
rovement compared with baseline, vs oral prednisolone,1.9% improvement compared with baseline; P�.05).Thus, there is moderate evidence that corticosteroid injec-
ions are more effective than oral steroids in the short term.urthermore, there is no evidence for the effectiveness oforticosteroid injections compared with oral steroids in thereatment of patients with CTS in the long term.
orticosteroid Injection Versus Anti-inflammatoryedication Plus SplintingSystematic review. In one high-quality trial70 (n�23) in-
luded in the Cochrane review of Marshall,14 there was noignificant improvement in symptoms between the injectionroup (40mg methylprednisolone) and the anti-inflammatoryedication (120mg acemetacin) plus splinting group at 2 and 8eeks after treatment. Also, on pain (VAS), no significant
mprovement was found at 2 and 8 weeks of follow-up.We concluded that there is no evidence for the effectiveness of
orticosteroid injection compared with anti-inflammatory medica-ion plus splinting as intervention for CTS in the short term.
orticosteroid Injection Versus Helium-Neon LaserreatmentSystematic review. In the low-quality study of Lucantoni et
l71 (n�40), at 20 days of follow-up, significant differencesere found in favor of corticosteroid injections with 20mgethylprednisolone compared with helium-neon laser on
ymptom improvement (RR�1.89; 95% CI, 1.12–3.17). How-ver, significant effects were no longer reported at 6 months ofollow-up.
Therefore, there is limited evidence that corticosteroid in-ections are more effective than helium-neon laser in the shorterm, but no evidence was found for the effectiveness in theidterm.
ifferent Doses of Local Corticosteroid InjectionsSystematic review. The low-quality study of O’Gradaigh
nd Merry72 (n�64) found no significant differences on clin-cal symptoms between the 25-mg hydrocortisone local injec-ion group and the 100-mg hydrocortisone group at 6 weeks ofollow-up.
Recent RCTs. One high-quality RCT73 (n�172) reportingn corticosteroid injections to treat CTS was found. At 1 yearf follow-up, better but nonsignificant differences in treatmentesponse were found for an injection with 60mg methylpred-isone compared with injections with 20mg or 40mg of theame medication. At 6 months of follow-up, significantly betteresults were found in favor of the 60-mg doses compared withhe other 2 doses (60-mg group, 73% [32/44] vs 40-mg group,3% [23/43]) and 40mg (60-mg group, 73% [32/44] vs 20-mgroup, 56% [25/45]) of the same medication.In conclusion, there is no evidence for the effectiveness of
5-mg hydrocortisone local injections compared with 100-mgydrocortisone injections in the short term. There is moderatevidence that 60mg methylprednisone is more effective than 20r 40mg methylprednisone in the midterm, but no evidence forhe effectiveness of 60mg methylprednisone compared with 20r 40mg methylprednisone to treat CTS in the long term.
hort-Versus Long-Acting Corticosteroid InjectionSystematic review. The low-quality study of O’Gradaigh
nd Merry72 (n�39) also examined the effectiveness of short-cting local corticosteroid (100mg hydrocortisone) versus
ong-acting corticosteroid (20mg triamcinolone). No signifi-
Arch Phys Med Rehabil Vol 91, July 2010
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992 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
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ant effects were found on clinical symptoms at 6 weeks ofollow-up.
Thus, there is no evidence for the effectiveness of short-cting compared with long-acting corticosteroid injection in thereatment of patients with CTS in the short term.
ingle Versus 2 Local Corticosteroid InjectionsSystematic review. One high-quality RCT74 (n�40) found
o significant differences on the Global Symptom Score be-ween a single and 2 local corticosteroid injections (15mgethylprednisolone) 8, 24, and 40 weeks after injection.We concluded there is no evidence for the effectiveness of a
ingle compared with 2 local corticosteroid injections with5mg methylprednisolone in the treatment of patients withTS in the short term, midterm, and long term.
ifferent Approaches of Corticosteroid Injection into thearpal TunnelSystematic review. One low-quality RCT75 (n�57) of the 2
CTs included in the review of Marshall14 compared an injection3mg betamethasone disodium phosphate and 3mg betamethasonecetate suspension mixed with 0.5cc lidocaine HCl 2% solution)elivered 4cm proximal to the wrist flexor crease to an injectionore distal at the anterior wrist flexion crease. No significant
ifferences were found on the clinical Neurologic Symptom Scoret 11 months of follow-up. The low-quality study of Habib et al76
n�42) examined a novel approach of local corticosteroid injec-ions compared with the classic approach. In the novel approach,atients were injected with 12mg methylprednisolone acetate us-ng a 1-mL insulin syringe with a 29-gauge � 1/2-in � 3-cmeedle mixed with .15mL lidocaine 2%. The needle was totallynserted (35° directing the needle toward the carpal tunnel) whileolding the hand in a midextended position. No significant differ-nces were found between the 2 approaches on overall improve-ent at 12 weeks of follow-up.Therefore, there is no evidence for the effectiveness of a
ovel approach compared with the classic approach in the shorterm, or for a proximal compared with a distal approach oforticosteroid injection to treat CTS in the long term.
orticosteroid Injection Versus Iontoforese orhonophorese of SteroidsSystematic review. Two RCTs77,78 studied the efficacy of
ocal steroid injection compared with iontophoresis or phono-horesis. The low-quality study of Gökoglu et al78 (n�30)ompared an injection with 40mg methylprednisone with ion-ophoresis of dexamethasone (0.4%) and found significantlyetter results in favor of the corticosteroid injection on painWMD��1.70; 95% CI, �2.38 to �1.02) and no significantffect on the functional status scale and the symptom severitycale at 8 weeks of follow-up. The low-quality study of Aygult al77 (n�21) found no significant differences between thenjection group (1mL dexamethasone) and the phonophoresisroup (dexamethasone 0.4%) on the symptom severity scalend the functional status scale at 4 months of follow-up.
Thus, there is limited evidence that a corticosteroid injections more effective than iontophoresis in the short term, and novidence for the effectiveness of corticosteroid injection com-ared with phonophoresis in the midterm.
orticosteroid Injection Versus EMLA-crèmeRecent RCTs. The low-quality study of Moghtaderi et al79
ompared treatment with a steroid injection with 40mg meth-lprednisolone with the daily use of eutectic mixture of local
nesthetic (EMLA) cream and found significant differences on m
rch Phys Med Rehabil Vol 91, July 2010
ain at 4 weeks of follow-up within both groups (mean � SD,MLA, from 5.8�.98 at baseline to 2.1�1.2 at 4 weeks of
ollow-up, P�.001; injection, from 5.7�1.0 at baseline to.6�1.4 at 4 weeks of follow-up, P�.001). No comparisonetween the 2 groups was made.We concluded that there is no evidence for the effectiveness of
steroid injection compared with EMLA cream in the short term.
DISCUSSIONThe aim of this systematic review was to present an overview
f the current state of the art regarding the effectiveness of non-urgical interventions for management of CTS. In comparisonith the conclusions of the Cochrane reviews of O’Connor13 andarshall,14 we found similar results for most interventions in-
luded in these reviews. However, we also found benefit forlectromagnetic field therapy, ergonomic keyboards, cuppingherapy compared with heat pads in the short term, and ultrasoundn the midterm. Furthermore, our findings showed midterm—buto long-term—benefit of steroid injections.
Strong and moderate evidence for effectiveness was found fororticosteroids (oral or injected), and a corticosteroid injectioneems to be the most effective. In the midterm, moderate evidenceas found for a higher dose of injected methylprednisone (60mg)
ompared with a lower dose (20 or 40mg). However, the includedtudies that presented long-term results of steroids compared withther interventions found that the positive results for the effec-iveness of steroids were not maintained in the long term. Similaresults were found in patients with other upper-extremity tendi-opathies, such as the trigger finger80 and lateral epicondylitis.81 Iteems that corticosteroid injections do not resolve the cause ofTS but merely suppress its symptoms. The mechanism behind
his effect of corticosteroids in CTS remains unclear, but annti-inflammatory or a neovascular component may play a role. Inontrast, the finding that the effects of low and high doses do notiffer significantly in the long term raises the question whether theffect is in fact a result of their pharmacologic properties. Alter-ative explanations are possible. However, caution is needed withhe use of corticosteroid injections because postinjection recur-ence can increase, as reported in patients with lateral epicondy-itis.82,83 Moreover, some authors suggest that potential harmelated to corticosteroid injections includes osteonecrosis and ten-on rupture.84 In the review of Nichols,84 17 animal studies werencluded. Ten of these studies provide evidence that corticosteroidnjections cause musculoskeletal structural or functional damage.
ore studies are needed to elucidate the mechanism and effect oforticosteroids in the longer term.
Ultrasound used as an intervention to treat CTS showed someromising results. Moderate evidence was found for the effective-ess of ultrasound in the short term and midterm. Further, weound moderate evidence that ultrasound is more effective thanaser therapy in the short term. Ultrasound has a long history ofse in physiotherapy practice.85 It is assumed to increase temper-ture in deep tissue by increasing blood flow, tissue metabolism,nd nerve function.86-88 Nerve generation can indeed be influ-nced by temperature.89 Further, in patients with peripheral neu-opathy, a reversible conduction block as a result of acute ultra-ound may occur.90 According to Watson,85 the clinical outcomef ultrasound appears to be dose-dependent. The studies we in-luded that reported on the effectiveness of different intensities36
r frequencies37 of ultrasound found no evidence for this state-ent; however, they only studied results at 2 and 4 weeks,
espectively. More RCTs are needed to establish the efficacy andafety of ultrasound in the short term, midterm, and long term inatients with CTS.
Moderate evidence was found for the effectiveness of dynamic
agnetic field therapy in the short term. This conclusion was
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993EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
ade on the basis of 1 small (n�36) high-quality study. Althougho significant differences were found on pain measured on a VAS,ignificantly better results were found on the Neuropathy Paincale, with a pain reduction of 42% in the treatment groupompared with 24% in the control group. More research is neededo confirm these findings and explore the effect of this treatment inhe midterm and long term.
Splinting is a commonly used nonsurgical intervention to treatTS.10,91 We found moderate evidence for the effectiveness of these of a nocturnal hand brace compared with no treatment in thehort term. Further, we found that night splinting is as effective ashole-day splinting. This may suggest that a patient can wear a
plint only at night to achieve a similar improvement in outcome.owever, the RCTs we found studied splinting in the short term
nd midterm only. No long-term results for the effectiveness ofplinting were found.
Further, moderate evidence was found for the effectivenessf an ergonomic keyboard compared with a standard keyboardn the short term. Typing is an activity involving repetition,ibration, and sustained posture. It is known that these move-ents may contribute to symptoms of work-related upper ex-
remity disorders in general92 and to CTS in particular.7 Ourndings contribute to this statement for patients with CTS.
tudy LimitationsSome limitations of this review and its conclusions should
e addressed. First, we refrained from statistical pooling of theesults of the individual trials. This was done because of theerceived heterogeneity of the studies. A single-point estimate ofhe effect of the interventions included for CTS would probablyot do justice to the differences among the trials regarding patientharacteristics, interventions, and outcome measures. The use of aest-evidence synthesis is a next-best solution and a transparentethod that is commonly applied in the field of musculoskeletal
isorders when statistical pooling is not feasible or clinicallyiable.16
Second, only 55% of the included RCTs were of high quality.herefore, more high-quality RCTs are needed to obtain evidence-ased results with a low risk of bias. We used the list of Furlan15
hat was constructed by the Cochrane Back Review Group. Thisist was constructed to assess interventions in the field of neck andack disorders but can also be used in and appears very suitable tother fields.93,94 Furlan15 indicated that studies with serious flaws
R placebos [mh] OR placebo* [tw] OR random* [tw] OR research
ated as having a high risk of bias. Therefore, these studies arendicated as low-quality studies in our review. Although selecting
border between high and low quality is arbitrary, there is em-irical evidence from a methodologic study conducted with datarom the Cochrane Collaboration Back Review Group that ahreshold of fewer than 50% of the criteria is associated withias.95
Third, the included Cochrane reviews of O’Connor13 and Mar-hall14 used different methodologic quality criteria compared withur criteria based on Furlan et al.96 Because of the high credibilitynd validity of Cochrane reviews, we decided to apply the meth-dologic quality criteria and definitions of high-quality and low-uality studies used in a Cochrane review. However, the qualityriteria of the 2 Cochrane reviews included fewer items than our2 quality criteria. This could contribute to bias in outcome ofvidence and conclusions. Further, O’Connor13 used an A (ie,igh quality: all criteria met), a B (ie, moderate quality: 1 or moreriteria partly met) and a C (ie, low quality: 1 or more criteria notet) as methodologic quality scores. For our review, we decided
o rank A and B as high-quality and C as low-quality studies.owever, we also looked at the number of items that were scoredositive. Based on our definition and use of high quality (ie, 50%r more of the items were scored positive), we found a discrep-ncy in 3 of the studies: Oztas et al36 scored 3 out of 8 items butt was ranked as B (ie, of high quality). Out of 8 items, Davis51 and
anente et al23 scored 5 and 4 items positively, respectively, butoth were ranked as C (ie, of low quality). This could introduceotential bias. However, even if we had changed the rankings ofhese 3 studies, our additional analysis shows that our studyonclusions would not have changed.
CONCLUSIONSIn conclusion, strong and moderate evidence was found for the
ffectiveness of interventions to treat CTS with oral steroids,teroid injections, ultrasound, electromagnetic field therapy, noc-urnal splinting, ergonomic keyboards compared with a standardeyboard, and cupping therapy compared with heat pads in thehort term. Also, moderate evidence was found for ultrasound inhe midterm. With the exception oral or injected steroids, noong-term results were reported for any of these treatments. More-ver, although a higher dose of steroid injections seems to be moreffective in the midterm, the benefits of steroids injections were
r those in which fewer than 6 of the criteria are met should be not maintained in the long term.
APPENDIX 1: SEARCH STRINGS
ubMedTS“Carpal tunnel syndrome”[mh] OR (“median nerve”[mh] AND (compress* OR entrapment)) OR “carpal tunnel” OR ((median*
ND (nervus OR nerve)) AND (compress* OR entrapment))Therapy(randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND controlled[Title/Abstract] AND trial[Title/
bstract]))Systematic Reviews((meta-analysis [pt] OR meta-analysis [tw] OR metanalysis [tw]) OR ((review [pt] OR guideline [pt] OR consensus [ti] OR
uideline* [ti] OR literature [ti] OR overview [ti] OR review [ti]) AND ((Cochrane [tw] OR Medline [tw] OR CINAHL [tw] ORNational [tw] AND Library [tw])) OR (handsearch* [tw] OR search* [tw] OR searching [tw]) AND (hand [tw] OR manual [tw]R electronic [tw] OR bibliography* [tw] OR database* OR (Cochrane [tw] OR Medline [tw] OR CINAHL [tw] OR (National
tw] AND Library [tw]))))) OR ((synthesis [ti] OR overview [ti] OR review [ti] OR survey [ti]) AND (systematic [ti] OR criticalti] OR methodologic [ti] OR quantitative [ti] OR qualitative [ti] OR literature [ti] OR evidence [ti] OR evidence-based [ti])))UTNOT (case* [ti] OR report [ti] OR editorial [pt] OR comment [pt] OR letter [pt])RCTs(randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation
mh] OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR “clinical trial”tw] OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR “latin square” [tw]
design [mh:noexp] OR comparative study [mh] OR evaluation
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994 EFFECTIVENESS OF NONSURGICAL TREATMENTS FOR CARPAL TUNNEL SYNDROME, Huisstede
A
tudies [mh] OR follow-up studies [mh] OR prospective studies [mh] OR cross-over studies [mh] OR control* [tw] ORrospective* [tw] OR volunteer* [tw]) NOT (animal [mh] NOT human [mh])Limits ActivatedHumans, English, French, German, Dutch
MBASETS“carpal tunnel syndrome”/ OR (“median nerve”/ AND “nerve compression”/) OR (“median nerve”/ AND (compress* OR
ntrapment)):ti,ab OR “carpal tunnel” OR ((median* AND (nervus OR nerve)) AND (compress* OR entrapment))Therapy“randomized controlled trial”:it OR (randomized:ti,ab AND controlled:ti,ab AND trial:ti,ab)Systematic Reviews(“review”/exp AND (medline:ti,ab OR medlars:ti,ab OR embase:ti,ab OR pubmed:ti,ab) OR scisearch:ti,ab OR psychlit:ti,ab OR
syclit:ti,ab OR psycinfo:ti,ab OR pyschinfo:ti,ab OR cinahl:ti,ab OR “hand search”:ti,ab OR “manual search”:ti,ab OR “electricatabase”:ti,ab OR “bibliographic database”:ti,ab OR “pooled analysis”:ti,ab OR “pooled analyses”:ti,ab OR pooling:ti,ab OReto:ti,ab OR dersimonian:ti,ab OR “fixed effect”:ti,ab OR “mantel haenszel”:ti,ab OR “retracted article”:ti,ab) OR (“metanalysis”/exp OR “meta analysis” OR “meta-analysis” OR “meta-analyses”:ti,ab OR “meta analyses”:ti,ab OR “systematiceview”:ti,ab OR “systematic overview”:ti,ab OR “quantitative review”:ti,ab OR “quantitative overview”:ti,ab OR “methodologiceview”:ti,ab OR “methodologic overview”:ti,ab OR “integrative research review”:ti,ab OR “research integration”:ti,ab ORquantitative synthesis”:ti,ab)RCTs
(“controlled clinical trial”/exp OR “randomized controlled trial”:ti OR “controlled clinical trial”:it OR “randomization”/ ORdouble blind procedure”/ OR “single blind procedure”/ OR “crossover procedure”/ OR “clinical trial”:it OR ((“clinical trial” ORsingl* OR doubl* OR tripl*)) AND (mask* OR blind*)) OR (“Latin square design”/ OR “latin square” OR “latin-square”) ORplacebo”/ OR placebo* OR “random sample”/ OR “comparative study”:it OR “evaluation study”:it OR evaluation/exp OR “followp”/exp OR “prospective study”/ OR control* OR prospective* OR volunteer*) NOT (animals/exp NOT humans/exp)LimitsctivatedHumans, English, French, German, Dutch
INAHLTS(MH “Carpal tunnel syndrome”) or ((MH “median nerve”) and (compress* or entrapment)) or “carpal tunnel” or ((median* and
erv*) and (compress* or entrapment))Reviews(MH “Systematic Review”)Clinical Trials(MH “Clinical Trials�”)
EDroCarpal tunnel syndrome
APPENDIX 2: OPERATIONALIZATION CRITERIA METHODOLOGIC QUALITYCriteria for a judgment of “yes” for the sources of risk of bias1. Was the method of randomization adequate?A random (unpredictable) assignment sequence. Examples of adequate methods are coin toss (for studies with 2 groups), rolling
dice (for studies with 2 or more groups), drawing of balls of different colors, drawing of ballots with the study group labels fromdark bag, computer-generated random sequence, preordered sealed envelopes, sequentially-ordered vials, telephone call to a
entral office, and preordered list of treatment assignments.Examples of inadequate methods are alternation, birth date, social insurance/security number, date in which they are invited to
articipate in the study, and hospital registration number.2. Was the treatment allocation concealed?Assignment generated by an independent person not responsible for determining the eligibility of the patients. This person has
o information about the persons included in the trial and has no influence on the assignment sequence or on the decision aboutligibility of the patient.
Was knowledge of the allocated interventions adequately prevented during the study?3. Was the patient blinded to the intervention?This item should be scored “yes” if the index and control groups are indistinguishable for the patients or if the success of blinding
as tested among the patients and it was successful.4. Was the care provider blinded to the intervention?This item should be scored “yes” if the index and control groups are indistinguishable for the care providers or if the success
f blinding was tested among the care providers and it was successful.5. Was the outcome assessor blinded to the intervention?Adequacy of blinding should be assessed for the primary outcomes. This item should be scored “yes” if the success of blinding
as tested among the outcome assessors and it was successful or:
● For patient-reported outcomes in which the patient is the outcome assessor (eg, pain, disability): the blinding procedure isadequate for outcome assessors if participant blinding is scored “yes.”
● For outcome criteria assessed during scheduled visit and that supposes a contact between participants and outcome assessors(eg, clinical examination): the blinding procedure is adequate if patients are blinded and the treatment or adverse effects of
the treatment cannot be noticed during clinical examination.
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● For outcome criteria that do not suppose a contact with participants (eg, radiography, magnetic resonance imaging): theblinding procedure is adequate if the treatment or adverse effects of the treatment cannot be noticed when assessing the mainoutcome.
● For outcome criteria that are clinical or therapeutic events that will be determined by the interaction between patients and careproviders (eg, co-interventions, hospitalization length, treatment failure), in which the care provider is the outcome assessor:the blinding procedure is adequate for outcome assessors if item “E” is scored “yes.”
● For outcome criteria that are assessed from data of the medical forms: the blinding procedure is adequate if the treatment oradverse effects of the treatment cannot be noticed on the extracted data.
Were incomplete outcome data adequately addressed?6. Was the dropout rate described and acceptable?The number of participants who were included in the study but did not complete the observation period or were not included
n the analysis must be described and reasons given. If the percentage of withdrawals and dropouts does not exceed 20% forhort-term follow-up and 30% for long-term follow-up and does not lead to substantial bias, a “yes” is scored. (N.B. theseercentages are arbitrary, not supported by literature).7. Were all randomized participants analyzed in the group to which they were allocated?All randomized patients are reported/analyzed in the group they were allocated to by randomization for the most importantoments of effect measurement (minus missing values) irrespective of noncompliance and co-interventions.8. Are reports of the study free of suggestion of selective outcome reporting?In order to receive a “yes,” the review author determines whether all the results from all prespecified outcomes have been
dequately reported in the published report of the trial. This information is either obtained by comparing the protocol and the report,r in the absence of the protocol, assessing that the published report includes enough information to make this judgment.Other sources of potential bias9. Were the groups similar at baseline regarding the most important prognostic indicators?In order to receive a “yes,” groups have to be similar at baseline regarding demographic factors, duration and severity of
omplaints, percentage of patients with neurological symptoms, and value of main outcome measures.10. Were co-interventions avoided or similar?This item should be scored “yes” if there were no co-interventions or they were similar between the index and control groups.11. Was the compliance acceptable in all groups?The reviewer determines whether the compliance with the interventions is acceptable, based on the reported intensity, duration,
umber, and frequency of sessions for both the index intervention and control interventions. For example, physiotherapy treatments usually administered over several sessions; therefore, it is necessary to assess how many sessions each patient attended. Foringle-session interventions (for example, surgery), this item is irrelevant.
12. Was the timing of the outcome assessment similar in all groups?Timing of outcome assessment should be identical for all intervention groups and for all important outcome assessments.
2wk RR�2.43 (95% ci, 1.12 to 5.28)In favor of splint in neutral positionSymptom relief at night2wk RR�2.14 (95% ci, .99 to 4.65)In favor of splint in neutral position
Nocturnal brace No treatment Symptom improvement 2wk WMD��1.03 (95% CI, �1.31 to �.75)In favor of nocturnal brace4wk wmd��1.07 (95% CI, �1.29 to �.85)In favor of nocturnal brace
Hand function 2wk WMD��.52 (95% CI, �.79 to �.25)In favor of nocturnal brace4wk WMD��.55 (95% CI, �.82 to �.28)In favor of nocturnal brace
Overall improvement 4wk RR�4.00 (95% CI, 2.34 to 6.84)In favor of nocturnal brace
Full-time splint Nighttime splint Symptom improvement WMD��.21 (95% ci, �.83 to .41)Hand function WMD��.21 (95% CI, �.87 to .45)
Nerve/tendon gliding Splint only Symptom improvement 3mo WMD��3.68 (95% CI, �8.56 to 1.20)Exercises and splint Hand function 3mo WMD��1.00 (95% CI, �4.72 to 2.72)
Grip strength 3mo WMD�5.06 (95% CI, �5.51 to 15.63)Pinch strength 3mo WMD�5.27 (95% CI, �.94 to 11.48)
Neurodynamic Control group Improved pain RR�15.00 (95% CI, 1.02 to 220.92)Mobilization hand function RR�9.00 (95% CI, .59 to 137.65)
Wrist flexion WMD�7.28 (95% CI, �3.33 to 17.89)Wrist extension WMD�6.00 (95% CI, �4.56 to 16.56)
symptom improvement WMD��.57 (95% CI, �1.73 to .59)
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Yoga Splint Pain (VAS) 8wk WMD��1.40 (95% CI, �2.73 to �.07)Grip strength 8wk WMD��3.10 (95% CI, �44.57 to 38.37)
UltrasoundPulsed ultrasound
therapyx Symptom improvement 2wk WMD��.11 (95% CI, �.67 to .45)
7wk WMD��.99 (95% CI, �1.77 to �.21)In favor of ultrasound6mo WMD��1.86 (95% CI, �2.67 to �1.05)In favor of ultrasound
Pain (VAS) 6mo WMD��1.10 (95% CI, �2.92 to .72)Grip strength 6mo WMD�4.16 (95% CI, �.88 to 9.20)Pinch strength 6mo WMD�.74 (95% CI, �.17 to 1.65)Self-reported
improvement6mo RR�1.91 (95% CI, 1.13 to 3.23)
Continuous ultrasoundtherapy of 2different intensities,1.5W and 0.8W
x Pain (VAS)Symptom improvement
WMD��.70 (95% CI, �2.28 to .88)WMD��.30 (95% CI, �.90 to .30)
Ultrasound therapy1MHz
Ultrasound therapy3MHz
Improved pain RR�.63 (95% CI, .26 to 1.52)
Oral medication orvitamins
Diuretics(trichlormethiazideor bendrofluazide
x Symptom improvement 4wk WMD�.80 (95% CI, �3.67 to 5.27)6mo RR�.98 (95% CI, .68 to 1.42)
NSAIDs (tenoxicam) x Symptom improvement 2wk WMD�3.10 (95% CI, �1.96 to 8.16)4wk WMD�3.20 (95% CI, �2.33 to 8.73)
Oral steroids(prednisone orprednisolone)
x Symptom improvement 2wk WMD��7.23 (95% CI, �10.31 to �4.14)In favor of oral steroids4wk WMD��10.8 (95% CI, �15.26 to �6.34)In favor of oral steroids8wk WMD��6.46 (95% CI, �11.93 to �.99)
Not estimableRR�.80 (95% CI, .41 to 1.56)WMD�.85 (95% CI, �10.83 to 12.53)WMD��.86 (95% CI, �9.26 to 7.54)WMD�.86 (95% CI, �.32 to 2.04)RR�3.27 (95% CI, .15 to 72.23)
Ergonomic keyboardsErgonomic keyboards Standard keyboard Pain (VAS) 12wk WMD��2.40 (95% CI, �4.45 to �.35)
In favor of ergonomic keyboardHand function 12wk WMD��2.20 (95% CI, �12.08 to 7.68)
In favor of ergonomic keyboard
Comfort keyboardsystem
Regular keyboard Pain (VAS)Hand function
6mo WMD�.97 (95% CI, �.64 to 2.58)6mo WMD�.57 (95% CI, �.15 to 1.29)
Apple adjustablekeyboard
Regular keyboard Pain (VAS)Hand function
6mo WMD�.70 (95% CI, �.97 to 2.37)6mo WMD�.93 (95% CI, .26 to 1.60)In favor of apple keyboard
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15mgmethylprednisolone2 times injection4cm proximal to thewrist flexor crease(3mgbetamethasonedisodiumphosphate, 3 mgbetamethasoneacetate suspension,0.5 cc lidocaine HCl2% solution)
15mgmethylprednisolone1 time distalinjection at theanterior wrist flexioncrease (3mgbetamethasonedisodiumphosphate, 3mgbetamethasoneacetate suspension,0.5cc lidocaine HCl2% solution)
Global Symptom ScoreSymptom ScoreClinical Neurologic
8wk MD��3.80 (95% CI, �9.27 to 1.67)24wk MD��2.90 (95% CI, �9.20 to 3.40)40wk MD�1.50 (95% CI, �4.76 to 7.76)11mo WMD�2.17 (95% CI, �1.07 to 5.41)
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Pain (VAS)Functional status scaleSymptom SeverityScale
8wk WMD��1.70 (95% CI, �2.38 to �1.02)8wk WMD��.28 (95% CI, �.95 to .39)8wk WMD��.29 (95% CI, �.63 to .05)
1mL dexamethasone 3MHz and intensity of1.0W/cm2 and 0.1%dexamethasone
Symptom severity scaleFunctional status scale
4mo WMD��.40 (95% CI, �.93 to .13)4mo WMD��.17 (95% CI, �.53 to .19)
bbreviations: x, studies in which the intervention group was compared to a placebo group; NSAIDs, nonsteroidal anti-inflammatory drugs; NPH, Neutral Protamine Hagedorn.
et al29nocturnal neutral wristsplint for 6mo (n�25)
Mo treatment(n�25)
Levine’s Questionnaire:symptoms(6mo)
P�.001 3mo differences:mean � SD, splint,* 1.07�.39, vs control, �.02�.24
P�.001 6mo differences:splint,* 1.22�.39, vs control, .17�.29
Functions P�.0001 3mo differences:(6mo) mean � SD, splint,* .53�.22, vs control, �.15�.43
P�.0004 6mo differences:splint,* .75�.28, vs control, .04�.30
De Angeliset al31
Wrist splint “CAMP TIELLE”at night for 3mo (n�61)
Hand brace“MANU” at nightfor 3mo (n�59)
Pain (VAS)(9mo)
P�.647
Comparison between groups: differences frombaselineto 3mo follow-up: mean (95% CI), .10(�7.10 to 11.36)
P�.380 to 9mo follow-up: 3.10 (�6.42 to 16.67)Boston Carpal TunnelQuestionnaireSymptom severityscore (9mo)
P�.556 Comparison between groups: differences frombaselineto 3mo follow-up: mean (95% CI), �.06 (�.34 to.18)
P�.778 to 9mo follow-up: .07 (�.28 to .36)Function severity score(9mo)
P�.471 Comparison between groups: differences frombaselineto 3mo follow-up: mean (95% CI), .19 (�.16 to .34)
P�.656 to 9mo follow-up: .17 (�.22 to .35)Brininger
et al26Group 1: neutral wrist andMCP splint (n�13)group 2: wrist cock-upsplint (n�14)All groups had a treatmentperiof of 4k
Group 3: idem plustendon and nervegroup 1 plus tendonand nerve glidingexercises (n�13)group 4: idemgroup 2 plus tendonand nerve glidingexercises (n�11)
Symptoms (8wk)Pinch strength (4wk)
Significant, no Pvalue given NotsignificantNo P valuegivenSignificant, no Pvalue given
No occasional symptoms: group 1: 38% vs group2: 17%†
group 3 and group 4†
all groups†
Pinaret al28
Nerve gliding exercises for10wk plus splint 10 weeks(n�19 hands)
Nerve glidingexercises for 6wkplus splint 10wk(n�16 hands)
Pain value (VAS)(10wk)
P�.05 Mean � SD, 6.9�1.4 to 1.0�1.6 in experimentalgroup vs 6.9�1.5 to 1.6�1.8 in control group
Grip strength (kg)(10wk)
P�.05 in favor ofexperimentalgroup
Mean � SD, 17.8�6.1 to 22.0�6.8 in experimentalgroup* vs 20.4�4.7 to 21.7�4.3 in control group
Pinch strength (kg)(10wk)
P�.05 Mean � SD, 4.1�1.7 to 5.4�1.8 in experimentalgroup vs 4.3�1.3 to 4.9�1.1 in control group
HeebnerandRoddey27
Standard care plus activeneurodynamic exercises(3–5 times/d; group 1)(n�30)
Standard care (ie,splinting at nightand at heavyactivities, tendongliding exercises3–5 times/d; group2; n�30)
DASH Questionnaire(6mo)
P�.164 No exact data given
The Brigham andWomen’s HospitalCarpal Tunnel SpecificQuestionnaire:Symptom severityscore (6mo)
P�.080 No exact data given
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P�.05 Changes after 12wk: mean � SD, laser, 22.8�6.9,vs placebo, 19.6�7.3
Pinch grip (kg) (12wk) P�.05 Changes after 12wk: laser, 5.7�1.6, vs placebo:4.8�1.5
Functional capacity(12wk)
Not significant No exact data given
Shooshtariet al41
Low-power laser therapy atanterior side of wrist andpalm for 15 sessions (5times/wk; n�40)
Control group: flashlaser (n�40)
Pain (VAS) (3wk) P�.001
P�.001
Low-power laser: mean � SD, from 7.8�.42 beforetreatment to 4.98�.12 after treatment(†)Control: from 8.01�.36 before treatment
to 7.62�0.4 after treatment(†)Hand grip (kg) (3wk) P�.001 Low-power laser: mean � SD, from 19.81�5.06
before treatment to 22.86�5.13 after treatment(†)P�.801 Control: from 21.46�6.23 before treatment to
21.52�6.05 after treatment(†)Oral medication and
vitamins
Changet al48
Prednisolone 20mg for 2 wkand 10mg for 2 wk (n�53)
Prednisolone 20mgfor 2wk and placebo
Overall improvement(12mo)
Not significant 49% improvement in 4-wk group vs 35.7%improvement in 2-wk group at 12mo follow-up
Other nonsurgical
treatments
Bialoskyet al97
NDT intended to provideanatomical stress acrossthe median nerve 6sessions in 3wk plussplinting (n�20)
Sham therapy(minimizedanatomical stressacross the mediannerve) 6 sessions in3wk plus splinting(n�20)
Clinical pain (VAS)
DASH Questionnaire(3wk)
P�.73
P�.99
NDT group: mean � SD, from 51.3�28.8 atbaseline to 34.7�27.5 at 3wk follow-up vs shamgroup: from 45.0�28.5 at baseline to 37.9�29.5 at3wk follow-upNDT group: from 36�15.5 at baseline to 30.6�19.4at 3wk follow-up vs sham group: from 41.3�19.0 atbaseline to 35.9�17.9 at 3wk follow-up
Grip strength P�.56 Mean grip strength: 22�9.6 at baseline to24.9�10.0 at 3wk follow-up, no exact data given onthe 2 groups
Burkeet al50
Graston Technique protocol(GISTM), 2 treatments/wkfor 4 wk followed by 1treatment a week for 2 wkand home exercises (n�12)
Manual STM 2treatments a weekfor 4 weeksfollowing 1treatment a weekfor 2 weeks andhome exercises(n�10)
Pain (VAS) (3mo afterthe last treatmentsession)Range of motion (°)(3mo after the lasttreatment session)
GISTM: mean � SD (95% CI), from61.5�26.56 (46.5–76.5) at baseline to9.2�11.04 (3.0–15.4) vs STM: from 60.5�17.9 (49.4–71.6) at baseline to 33.7� 28.84 (15.8–51.6) at 3mo†
Wrist extensionGISTM: mean � SD (95% CI), from38.1�9.98 (32.5–43.7) at baseline to 43.9�.70 (37.8–50.0) at 3mo vs STM: from 36.4�13.23 (28.2–44.6)at baseline to 45.8� 10.57 (39.2–52.4) at 3mo†
Wrist flexionGISTM: mean � SD (95% CI), from44.8�8.91 (39.3–49.8) at baseline to49.9�8.44 (45.1–54.7) vs STM: from47.5�8.05 (42.5–52.5) at baseline to 49.3�
12.2 (41.8–56.8) at 3mo†
Grip strength (3moafter the last treatmentsession)
GISTM: mean � SD (95% CI), from20.2�8.79 (15.2–25.2) at baseline to25.4�7.67 (21.1–29.7) vs STM: from23.5�6.78 (19.3–27.7) at baseline to 24.9�
6.32 (21.0–28.8) at 3mo†
Levine CTSQuestionnaireFunctional scale (3moafter the last treatmentsession)
GISTM: mean � SD (95% CI), from 2.1�.93 (1.6–2.6) at baseline to 1.6�.72 (1.2–2.0) at 3mo vs STM:from 2.4�.85 (1.9–2.9) at baseline to 1.7�.68 (1.3–2.1) at 3mo†
Symptom severityscale (3mo after thelast treatment session)
GISTM: mean � SD (95% CI), from 3.0�.73 (2.6–3.4) at baseline to 1.8�.61 (1.5–2.1) at 3mo vs STM:from 2.7�.64 (2.3–3.1) at baseline to 2.2�.59 (1.8–2.6) at 3mo†
WeintraubandCole55
Dynamic magnetic fieldstimulation to the wrist 4h/d for 2mo (n�17)
Sham therapy(n�19)
Pain (VAS) (2mo) Not significantNo P valuegiven
Treatment group: mean � SD, from 6.82�2.08 atbaseline to 4.15�2.13 at 2mo vs sham therapy:from 5.17�1.54 at baseline to 3.78�2.27 at 2mo
TM protocol twice-weekly30-min sessions for 6wk(n�14)
GM twice-weekly30-min sessions for6wk (n�13)
Grip strength (10wk) P�.04 TM group*: mean (95% CI), from 25.1 at baselineto 29.5kg (27.7–31.3 kg) at 12wk follow-up vs GMgroup: from 25.1kg (mean) to 26.3kg at 12wkfollow-up
Pinch strength (6wk) P�.11 TM group: mean (95% CI), from 6.6kg at baselineto 8.3kg (7.7–8.9) at 6wk follow-up vs GM group:from 6.6kg at baseline to 7.2kg (6.6–7.8) at 6wkfollow-up
P�.80 TM group: mean (95% CI), from 2.3 at baseline to1.8 (1.6–2.0) at 10wk follow-up vs GM group: from2.3 at baseline to 1.9 (1.7–2.1) at 10wk follow-up
Function status scale(10wk)
P�.34 Only the following data are given: TM group: mean� SD, 1.6�0.2 after 4wk follow-up. GM group:1.7�0.2 after 6wk follow-up
Grooved Pegboard Test(10wk)
P�.41 TM group: mean � SD, from 104 at baseline to98�4.8 after 6wk follow-up vs GM group: from 104at baseline to 95�5.2 after 6wk follow-up
Michlovitzet al60
Heat wrap with heat to104°F (40°C) for 8 hoursdaily (this temperaturemaintained continuouslybecause of exposure to air)for 3d (n�10)
Oral placebo for 3d4 times daily, 2tablets (n�12)
Pain relief (5d) P�.001 Heat wrap*: mean � SD, 2.18�.34 vs oral placebo:0.95�.25 at day 1 to 3/hour 0 to 8 daily (thistemperature maintained
P�.05 Heat wrap* vs oral placebo at 20 of 26 time pointsJoint stiffnessreduction (5d)
P�.004 Heat wrap*: mean � SD, 21.8�5.5 vs oral placebo:4.9�3.1 at day 1 to 3/hour 0 to 8
P�.05 Heat wrap* vs oral placebo at 19 of 26 time pointsGrip strength (5d) P�.012 Heat wrap*: mean � SD, 6.1�1.6kg vs oral
placebo: 0.8�1.4kg at 5d follow-upPatient-rated wristevaluation
P�.013 Heat wrap*: mean � SD, 27.3�5.9 vs oral placebo:7.9� 5.39 at 5d follow-up
Levine CTSQuestionnaireSymptom severityscale
P�.001 Heat wrap*: mean � SD, .97�.16 vs oral placebo:.14�.14 at 5d follow-up
Function status scale P�.006 Heat wrap: mean � SD, .65�.16 vs oral placebo:.00�.16 at 3d follow-up
P�.07 Heat wrap: .57�.22 vs oral placebo: .12�.20 at day5
Michalsenet al61
Cupping therapy (n�26) Heating pad (controlGroup; n�26)
Pain at rest (7d) Significant Cupping* vs heating pad: differences at day 7:MD��22.9 (95% CI, �35.3 to �10.5)
Levine CTSQuestionnaireSymptom severity (7d)
Significant Cupping* vs heating pad: differences at day 7:MD��0.6 (95% CI, �0.9 to �0.2)
Functional status Significant Cupping* vs heating pad: differences at day 7:MD��0.6 (95% CI, �0.8 to �0.3)
DASH score Significant Cupping* vs heating pad: differences at day 7:MD��11.1 (95% CI, �17.1 to �5.1)
Breueret al62
Injection with botulinumtoxin B into each of the 3hypothenar muscles groups(n�11)1.2500U botulinum B (n�9)2.5000U botulinum B (n�1)3.7500U botulinum B (n�1)
(n�9) West Haven-YaleMultidimensional PainInventory (13wk)
Not significantNo P valuegiven
No exact data given
Amirjaniet al64
Iontophoresis with 0.4%dexamethasone sodiumphosphate with distilledwater (treatment group;n�9)
Hui et al69 local injection of 15mgmethylprednisolone into thecarpal tunnel with oralplacebo for 10d (n�30)
Local injection withnormal saline withoral prednisolone25mg daily for 10d(n�30)
Global symptom score(80wk)
P�.07 Steroid injection: mean � SD, 25.0�6.41 at aselineto 13.57�7.47 at 2wk follow-up vs oralprednisolone: 25.73�8.31 at baseline to 17.77�
9.98 at 2wk follow-up.
P�.004 Steroid injection: mean � SD, 14.30�8.42 at 12 wk†
Long-term results from thestudy of Wong et al68
P�.05 Steroid injection: 69.5% improvement comparedwith baseline vs oral prednisolone: 51.9%improvement compared with baseline after 7 mo inparticipants who did not require surgery (n�19 andn�16, respectively)
Dammerset al73
3 doses ofmethylprednisonecompared: 20mg vs 40mgvs 60mg (n�45, n�43,n�44, respectively)
Free of symptoms (1y) P�.05 6mo: 60mg group* 73% (32/44) vs 40mg group53% (23/43)
Treatment responsesymptoms (1y)
P�.05P�.4711
60mg group* 73% (32/44) vs 20mg group 56% (25/45) 1y: 20mg group 47% vs 40mg group 41% vs60mg group 52%
Moghtaderiet al79
One injection of 40mgMethylprednisolone acetateat the wrist (n�35)
Daily application ofEMLA cream on thevolar aspect of thewrist
Pain (VAS) (30d) P�.001P�.001
EMLA: mean � SD, from 5.8�.98 at baseline to2.1�1.2 at 4wk follow-up vs Injection: mean � SD,from 5.7�1.0 at baseline to 1.6�1.4 at 4wk follow-up†
In favor of.No comparison between the groups was made.
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