Chapter | 28 |

Carpal tunnel syndromeLuca Padua, Costanza Pazzaglia, Ana Isabel-de-la-Llave-Rincon

CHAPTER CONTENTS

Introduction 361

Anatomy 361

Patho-biomechanism of carpaltunnel syndrome 362

Sensitization mechanisms in carpaltunnel syndrome 362

Diagnosis of carpal tunnel syndrome 363

Clinical examination 363

Questionnaires 364

Electrodiagnostic evaluation 364

Ultrasound assessment 364

Prognosis 365

Prognosis of untreated carpaltunnel syndrome 365

Therapy 365

Carpal tunnel syndrome and pregnancy 366

Conclusion 366

INTRODUCTION

Carpal tunnel syndrome (CTS) is characterized by a com-pression of the median nerve in the carpal tunnel. It is acommon pathology affecting an estimated 10% of thepopulation according to the American Academy of Neu-rology (AAN 1993a,b, Olney 2001). It is considered themost common nerve compression disorder of the arm,with reported prevalence rates of 3.8% (95% CI, 3.1–4.6%) for women and 2.7% (95% CI, 2.1–3.4%) formen (Atroshi et al 1999). Bland et al (2003) found an

annual incidence of 139.4 cases per 100,000 femalesand 67.2 cases per 100,000 males, with a female:maleratio of 2.1. Bongers et al (2007) have recently reportedan incidence rate of CTS of 1.8/1000 (95% CI, 1.7–2.0).In females the incidence was 2.8 (95% CI, 2.6–3.1) andin males 0.9 (95% CI, 0.8–1.0) showing a female:maleratio of 3:1 (Bongers et al 2007). Further, this studyshowed that in 2001 the incidence of CTS was calculatedto be 1.5 times higher than in 1987 (this difference disap-peared after subdividing patients by age and sex) (Bongerset al 2007). It has been estimated that in the USA aroundone million people require care for CTS, around 200,000surgical interventions are needed and that the social costsare in the millions of dollars range (Tanaka et al 1995).

Analysis of the literature raises the difficulty of accu-rately estimating the incidence and prevalence of CTSdue to the fact that it is a very common pathology and,as we discuss below, can be associated with manual work.This last controversial association means that incidenceand prevalence of CTS are often calculated in a specificwork-population. Moreover, another confounding factorcould be the method used to diagnose CTS, as Atroshiet al (1999) reported. In Atroshi et al’s (1999) study, thecombination of clinical and neurophysiological evalua-tions contributed to diagnosing CTS in 1 in 5 symptom-atic subjects in the general population.

ANATOMY

In the carpal tunnel the median nerve is surrounded bybones on three sides with the transverse carpal ligament onthe top. The nerve lies within the nine flexor tendons of thehand, and supplies function, feeling and movement to firstdigit of the hand and one-half of the ring finger (Fig 28.1).

361© 2011 Elsevier Ltd.

DOI: 10.1016/B978-0-7020-3528-9.00028-5

The median branches for finger and wrist flexors origi-nate in the forearm, while motor branches, that controlthe thumb flexor and adductor muscles, and sensorybranches, that provide over half the hand with the senseof touch, usually originate at the end of the tunnel.

Compression of the nerve can be due to a decrease inthe size of the canal, an increase of the size of tendons,or both. For further information, readers are referred toHeidelberg (1989).

PATHO-BIOMECHANISM OF CARPALTUNNEL SYNDROME

In most case CTS is idiopathic (Sternbach 1999) butsometimes it is associated with trauma, pregnancy, hypo-thyroidism, multiple myeloma, amyloidosis, rheumatoidarthritis, or acromegaly (Stevens et al 1992). As discussedabove, in this pathology the changes occurring in the car-pal tunnel are responsible for the median compression.For example:

• Rheumatoid arthritis causes inflammation of theflexor tendons determining median nervecompression.

• Pregnancy and hypothyroidism cause fluid retention intissues, which swells the tenosynovium (we discuss therole of pregnancy in more detail later in this chapter).

• Acromegaly causes the compression of the nervebecause of the abnormal growth of bones around thehand and wrist.

• Tumours (usually benign), such as a ganglion or alipoma, can protrude into the carpal tunnel, reducingthe amount of space. This is exceedingly rare (< 1%).Carpal tunnel tumours can mimic CTS (Padua et al2006) and in these cases the use of ultrasoundevaluation has been crucial. This topic will bediscussed below (Granata et al 2008).

• Obesity also increases the risk of CTS; a BMI > 29(obese individuals) increases the risk by 2.5 compared

to a BMI < 20 (slender individuals) (Werner et al1994).

• Double crush syndrome is a speculative and debatedtheory which postulates that when there iscompression or irritation of nerve branchescontributing to the median nerve in the neck oranywhere above the wrist, this increases the liability ofthe nerve to compression in the wrist. Pierre-Jerome &Bekkelund (2005) reported that patients with CTSexperienced a higher incidence of narrowing of thecervical foramen when compared to controls. Theseauthors hypothesized that the compromised neuralforamen could potentially lead to nerve compressionand possibly a double crush syndrome in patientswith CTS. However, there is little evidence that thissyndrome really exists in CTS (Wilbourn & Gilliatt1997, Russell 2008).

• There is a great number of traumas can cause CTS(Colles’ fracture, dislocation of one of the carpalbones of the wrist, haematoma forming inside thewrist, etc.).

• The role of manual activities and CTS is still a matterof debate. A number of authors found that there isstrong relation between hand positions and increasedpressure on the carpal tunnel (Keir et al 1998, Luchettiet al 1998) and strongly supports the hypothesis thatforceful use of the hands, repetitive use of the hands,and hand-arm vibration may cause or contribute toCTS. But other studies do not support the relationshipbetween manual activity and CTS (Chiang et al 1993,Moore & Garg 1994). Despite researchers’ efforts, thedebate is still far from concluded.

Readers are referred to other texts for a greater under-standing of these mechanisms (Werner 2006, Van Rijnet al 2009).

SENSITIZATION MECHANISMSIN CARPAL TUNNEL SYNDROME

Although the aetiology of CTS is not completely under-stood, there is some evidence involving the whole noci-ceptive system. Previous studies have investigated thefunction of nociceptive thermo-receptive fibres in CTSpatients. Different studies found elevated thermal painthresholds in the fingers and the palm within the affectedhand in patients (Arendt-Nielsen et al 1991, Westerman &Delaney 1991, Goadsby & Burke 1994). Lang et al (1995)suggested that pain intensity in CTS depends on altera-tions of peripheral and central nervous function.

More recent studies reported that 45%ofCTS patients alsoreported spreading proximal symptoms, which might berelated to central nervous system mechanisms (Zanneteet al 2006, 2007). Chow et al (2005) found that neck painwas present in 14% of patients with CTS. Tucker et al

Transversecarpal ligament

Flexor tendons

Flexor tendons

Tenosynovium

Median nerveCarpal bones

Fig 28.1 Anatomy of the carpal tunnel.

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(2007) found bilateral generalized increase in vibrationthresholds in patients with CTS which suggests a generalizeddisturbance of somato-sensory functions rather than theexistence of an isolated peripheral neuropathy. In fact, twoimage studies have shown cortical remapping in the primarysomato-sensory cortex (S1) in patients with CTS supportinga possible role of central mechanisms in CTS (Tecchio et al2002, Napadow et al 2006).

Additionally, recent clinical studies also support the pres-ence of peripheral and central sensitization mechanisms inpatients with moderate CTS. Fernandez-de-las-Penas et al(2009a) found bilateral widespread decrease in pressure painthresholds in patients with unilateral CTS (clinically andneurophysiological) when compared to healthy controls.This study reported bilateral lower pressure pain thresholds(PPT) over themedian, radial andulnar nerve, the carpal tun-nel, the C5–C6 zygapophyseal joint and the tibialis anteriormuscle. A significant decrease inPPToverC5–C6 zygapophy-seal joint may represent the existence of segmental sensitiza-tion of the nociceptive system in CTS, whereas a bilateraldecrease in PPT over the tibialis anterior muscle indicatemulti-segmental sensory sensitization or sensitization of thecentral nervous system in patients with CTS (Fernandez-de-las-Penas et al 2009a). De-la-Llave Rincon et al (2009)reported that patients with unilateral CTS also show a bilater-ally thermal hyperalgesia (lower heat pain thresholds andreduced cold pain threshold), but not hypoaesthesia (normalthermal detection threshold) as compared to healthy sub-jects. Again, bilateral changes in patients with unilateral diag-nosis (clinical and neurophysiological) of CTS reflect centralsensitization mechanisms. These clinical findings are sup-ported by animal studies where peripheral neural pathologyin one local area can cause widespread effects, includingeffects in apparently uninvolved limbs (Koltzenburg et al1999, Kleinschnitz et al 2005).

A recent study investigating impairments in fine motorcontrol and ability skills also showed bilateral deficits infine motor control ability and pinch grip force in unilat-eral CTS (Fernandez-de-las-Penas et al 2009b). Theauthors of this study hypothesized that bilateral motorcontrol impairment and pinch grip force deficit can reflecta reorganization of the motor control strategy of the cen-tral nervous system as a consequence of the pain in CTS,which was supported by Tamburin et al (2008).

Finally, these studies also showed that bilateral sensoryand motor deficits were associated to the intensity andduration of pain symptoms, supporting a role of theperipheral drive to initiate and maintain central wide-spread sensitization (De-la-Llave-Rincon et al 2009,Fernandez-de-las-Penas et al 2009a,b). Gracely et al(1992) proposed a model of neuropathic pain in whichongoing nociceptive afferent input from a peripheralnociceptive focus dynamically maintains altered centralprocessing. In such instances, it can be suggested the pain-ful condition, that is the ischaemia of the nervi nervorum(Watkins & Maier 2004) (the nerves innervating the

connective tissue layers of the nerve itself) sensitized bythe compression of the median nerve in the carpal tunnel(Hall & Elvey 1999), may as such act as a trigger forgradual sensitization of nociceptive pathways in CTSpatients. New studies should investigate the role of thesesensitization mechanisms in the evolution of CTS.

DIAGNOSIS OF CARPAL TUNNELSYNDROME

Clinical examination

The gold standard for the diagnosis of CTS is consideredthe clinical picture, according to the AAN (1993a,b)diagnostic criteria: paraesthesia, pain, swelling, weaknessor clumsiness of the hand provoked or worsened by sleep,sustained hand or arm position, repetitive action of thehand or wrist that is mitigated by changing posture orby shaking of the hand, sensory deficits in the medianinnervated region of the hand and motor deficit orhypotrophy of the median innervated thenar muscles.Wainner et al (2005) developed a clinical predictionrule for the diagnosis of CTS. The rule identified consistedof 1 question (shaking hands for symptom relief), wrist-ratio index > 0.67, symptom severity scale score > 1.9,reduced median sensory field of digit 1, and age > 45years (LR ¼ 18.3).

Recent studies have evidenced the relationship betweenthe distribution of sensory symptoms and the severity ofCTS, according to the neurophysiological classification.Patients with lower severity of pathology complain of sen-sory symptoms with a glove distribution, while patientswith higher severity of pathology complain of sensory symp-toms with the ‘classical’ median distribution (Caliandro et al2006).

The patient history is extremely important for the differ-ential diagnosis, especially as CTS can be secondary toendocrinal and metabolic pathologies; therapy for the pri-mary pathology can remit the CTS. For clinical examina-tion, in addition it is possible to use a historic andobjective scale (Hi-Ob) of CTS that includes two measures(Giannini et al 2002). The first has clinical history andobjective sub-scores: (1) nocturnal paraesthesia only;(2) nocturnal and diurnal paraesthesia; (3) sensory deficit;(4) hypotrophy or motor deficit of the median innervatedthenar muscles; (5) plegia of median thenar eminencemuscles. The second evaluates, by patient-orientedmeasurement, the presence or absence of pain with aforced-choice answer (‘yes’ or ‘no’). Therefore, the Hi-Obscore is composed of a number (Hi-Ob) with or withoutthe pain variable (Giannini et al 2002).

The physical examination includes the Phalen test(Fig 28.2), performed by a prolonged (1-minute) passiveforced flexion of the wrist; the Tinel test that consists

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of a percussion of the median nerve trophism of the the-nar eminence; motor function of the median innervatedmuscles; and sensory function (cotton wool is used as astandard material for skin stimulation).

Questionnaires

As doctors want to help patients, the assessment ofpatients’ perspective is also useful in the comprehensiveevaluation of CTS. The most common used questionnaireis the Boston Carpal Tunnel Questionnaire (BCTQ)(Levine et al 1993). The BCTQ evaluates two domains ofCTS: ‘symptoms’ (SYMPT ¼ patient-oriented symptom)assessed on an 11-step scale; and ‘functional status’(FUNCT ¼ patient-oriented function) assessed on a 8-stepscale. Each item includes five possible responses, and thescore for each section (SYMPT or FUNCT) is calculatedas the mean of the responses to the individual items.The use of this questionnaire in several multi-centricstudies on CTS showed interesting results; while functionhas a linear significant correlation when assessed both byphysicians and patients, symptoms do not have a clearlinear correlation (Padua et al 2002). Patients with mild-to-moderate CTS seemed to function well, although severesymptoms may be reported by the patient. However,when nerve impairment becomes severe, the patient’shand function is extremely impaired although symptomsmay be milder. The data show that the patient’s point ofview is reliable (Padua et al 2002).

Electrodiagnostic evaluation

Electrodiagnostic evaluation is very important to definethe impairment of the median nerve. It is now acceptedthat, in order to increase the sensitivity of conventionalnerve conduction studies (sensory digit-wrist and motorwrist-thenar), segmentary and/or comparative tests shouldbe used (see below) as stated in AAN and AAEM recom-mendations (AAN 1993a,b). When the standard tests yieldnormal results (‘standard negative’ hands), the followingstudies increase the electrodiagnostic sensitivity:

1. Segmental motor or sensory conduction tests in palm-wrist segment.

2. Comparative studies (median-ulnar or median radial)3. Segmental/comparative studies (as disto-proximal ratio)

A study conducted on CTS patients showed that the sensi-tivity of standard tests can reach 83.5%, comparative/seg-mental tests can disclose abnormal findings in a further11.4% of cases, providing CTS electro-diagnosis in about7 of 10 ‘standard negative’ cases. The overall sensitivityof protocol thus reaches 94.9% (Padua et al 1999). Theseverity of neurophysiologic CTS impairment can beassessed and scored according to a published neurophy-siologic classification (Padua et al 1997a,b).

ULTRASOUND ASSESSMENT

Thanks to the advances in technology (refinement of high-frequency broadband linear-array transducers, and sensitivecolour and power Doppler technology), the low cost, thewide availability, and the ease of use, ultrasound (US) hasrecently been applied to the study of tendons and nerves.

In tendon and nerve imaging, US can assess a greatnumber of pathologies such as dislocations, degenerativechanges, extrinsic or intrinsic focal compression. More-over US can support clinical and electrophysiological test-ing and in most cases, a focused US examination can beperformed more rapidly and efficiently than MR imaging(Martinoli et al 2002).

From a technical point of view, although tendons andnerves share similar characteristics (dimensions, tubularconformation, and striated appearance) US can easily differ-entiate them. Tendons have a fibrillar pattern of parallelhyperechoic lines in the longitudinal plane because of colla-gen bundles and endotendineum septa with a hyperechoicround to ovoid image containing bright dots (Fornage &Rifkin 1988, Martinoli et al 1993); nerves have a fascicularpattern due to hypoechoic parallel linear, the neuronalfascicles, separated by hyperechoic bands (the interfascicularepineurium) (Graif et al 1991, Silvestri et al 1995).On trans-verse scans, nerves assume a honeycomb-like appearancewith hypoechoic dots surrounded by a hyperechoicbackground (Fig 28.3).

Ultrasound has been mainly tested in the evaluation ofCTS because of the complementary perspective it provides(Beekman & Visser 2003, Hobson-Webb & Padua 2009,Karadag et al 2010, Smith et al 2009). CTS can be assessedby using the following measures: cross-sectional area(CSA), swelling ratio, retinacular bowing, retinacularthickness, flattening ratio. Several studies have shown thatthe most useful diagnostic criterion is the CSA, which isthe area of median nerve calculated at the wrist, both byusing the ellipse formula or by manual tracing; the bestcut off value is CSA of � 9.875 mm2 at the pisiform level(Wang et al 2008).

Fig 28.2 The Phalen test.

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Moreover, more sensitive tests have been developed inorder to obtain the best sensitivity and specificity. Forexample, the wrist-to-forearm ratio (WFR) of mediannerve area can be considered more sensitive than measureof median nerve area at the wrist alone (Hobson-Webbet al 2008). The sensitivity of the combination of USand neurophysiology is higher than that of neurophysiol-ogy or US alone. US is hence a useful complementarytool for CTS assessment, with a positive correlationbetween US findings and conventional measures of CTSseverity (clinical, neurophysiological and patient-oriented)(Padua et al 2008).

In conclusion, there is increasing evidence that US is auseful complement in a neurophysiology laboratory, itgreatly increases the diagnostic power and therapeuticwork-up of patients with mononeuropathies (Padua et al2007) and the morphological evaluation of nerves helpsin avoiding severe misdiagnoses (e.g. a median nervetumour that may mimic CTS), especially in cases with atyp-ical neurophysiological findings (Padua & Martinoli 2008).

PROGNOSIS

Prognosis of untreated carpal tunnelsyndrome

The knowledge of evolution of untreated CTS is veryimportant in order to administer the best therapeuticapproach. Only a few studies have evaluated this topic(Padua et al 1998, 2001, Resende et al 2003, Ortiz-Corredor et al 2008) and all authors agreed that many

patients improved spontaneously. When the evolution isanalyzed according to the initial picture, it is observedthat CTS hands with initial low severity tend to get worsewhile CTS hands with initial high severe impairment tendto improve (this is observed in all CTS measurements,either patient-oriented or neurophysiologic).

Moreover, the factor that is most predictive of untreatedCTS evolution is the duration of symptoms. In particular, along duration of symptoms is a negative prognostic factoraccording to all patient-oriented measurements. Converselya long duration of symptoms is not significantly associatedwith a bad neurophysiological or clinical examination out-come. With regard to the positive prognostic value of handstress at the baseline, note that this value is probably due tothe interruption of the stress. In this sense it is interestingto note that in the entrapment syndrome the ‘natural his-tory’ can be influenced by the physicians with an explana-tion of the patho-physiology of CTS. If doctors, whilegiving the patients the diagnosis, also provide practicalinformation about the hand positions to be avoided, theycan alter the natural course of the pathology.

Therapy

With regard to the conservative options of CTS therapy areview by Piazzini et al (2007), including 33 randomizedcontrolled trials, showed that there is a strong evidence(level 1) on efficacy of local and oral steroids; moderateevidence (level 2) that vitamin B6 is ineffective andthat splints are effective, and limited or conflicting evi-dence that NSAIDs, diuretics, yoga, laser and ultrasoundare effective whereas exercise therapy and botulinum

A B

C D

Fig 28.3 The median nerve at the wrist (in the carpal tunnel): note the change in shape and position among the nerve and thetendons in relation to the different wrist angle A¼ neutral position, B¼ 45� wrist flexion, C¼ 90� wrist flexion and D¼ maximalwrist extension.

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toxin B injection are ineffective. A recent systematic reviewfocused on neural mobilization interventions for themanagement of CTS included six studies and found weakto strong effects of neural gliding exercises with benefitsseen across different outcome measures (Medina McKeon& Yancosek 2008). Nevertheless, these authors proposedthat the benefit of neural gliding may be best identifiedwithin a specific subpopulation of CTS patients. It is pos-sible that neural gliding may be more effective in a popu-lation with less advanced CTS. A clinical prediction ruleidentifying CTS patients who will benefit from neuralmobilization interventions is urgently needed.

Regarding the surgical approach, a Cochrane review of2003 concluded that surgical treatment relieves symptomssignificantly better than splinting but further research isneeded to discover whether this conclusion applies topeople with mild symptoms and whether surgical treat-ment is better than steroid injection (Verdugo et al 2003).

Analyzing the factors that influence the surgical resultsin different populations, a number of studies have beenperformed, e.g. the results of surgical decompression weresimilar in men and women (Mondelli et al 2004a). Onthe other hand elderly patients showed less improvementwith respect to younger patients, presumably due togreater preoperative damage and less repair capacity ofthe compressed nerve, but this aspect was not a contrain-dication for surgical release in elderly patients (Mondelliet al 2004b). Also the presence of comorbidity has beeninvestigated, e.g. patients with diabetes have the sameprobability of positive surgical outcome as patients withidiopathic CTS (Mondelli et al 2004a).

In the same trend, the analysis of cost-effectiveness ofnon-surgical versus surgical treatment showed that sur-gery, rather than non-surgical care, should be consideredas the initial form of treatment when patients are diag-nosed with CTS (confirmed by nerve conduction studies),as this provides symptom resolution with a favourablecost analysis (Pomerance et al 2009).

CARPAL TUNNEL SYNDROME ANDPREGNANCY

Because CTS is frequent during pregnancy (PRCTS) it canbe considered a distinct entity. Studies have shown thatPRCTS does not disappear after delivery (it may improvebut on the contrary it may remain and the prolongedcompression may result in median nerve defect) so CTSsymptoms must be accurately assessed in pregnantwomen, and when present they must be monitored eitherclinically or neuro-physiologically (the role of ultrasoundin PRCTS is not well known and must be assessed as itcould be a non-invasive monitoring tool).

In cases of early appearance (before the last trimester)the median compression must be well assessed as it may

result in acute or disabling CTS and improvement is lessfrequent. In case of severe CTS with early onset the surgicaldecompression during pregnancy may prevent nerve dam-age and a negative psychological influence after delivery.

Appearance of CTS symptoms in the last trimester is themore usual condition and has a higher probability ofimprovement after delivery; but around half of womenmay complain of CTS symptoms for a long time post par-tum, so clinical and neurophysiological monitoring issuggested. Note that despite improvement of symptoms,the distal sensory conduction velocity of the median nerveimproved but remained delayed in 84% of women longafter delivery (Mondelli et al 2007).

Apart from acute CTS, which may be an emergency(with the need for rapid surgical decompression), the firstline in approaching PRCTS should be conservative ther-apy. But in absence of improvement and the presence ofsevere neurophysiological CTS (disappearance of sensoryor motor responses) or disabling symptoms, surgicaldecompression before delivery must be considered inorder to prevent not only nerve damage but also deterio-ration of quality of life due to difficulty and anxiety inhandling the baby.

CONCLUSION

Although CTS has been defined as “complex issues with a‘simple’ condition” (Olney 2001), and this is confirmedby the high number of publications concerning all aspectsof CTS, in recent years efforts have been conducted toimprove knowledge of this condition. Tools importedfrom other fields, such as ultrasound, have been commonlyaccepted in improving the diagnostic sensibility, althoughthe gold standard remains the clinical picture. The naturalhistory of the pathology shows that some untreated CTSpatients can improve, but this is probably due to the doctorexplaining to the patient how to avoid wrong hand posturesand thus reducing the stresses on the hand. Conservativetherapies have been used andwere demonstrated to be effec-tive, but surgical decompression, also used in elderly or dia-betic patients, remains the definite cure and is efficient fromthe cost effectiveness point of view.

The opinion of the authors concerning surgical decom-pression, based on clinical experience and on unpub-lished data on the natural history of CTS, is that surgeryis suggested in severe cases (either neuro-physiologicallyor clinically) with duration of symptoms longer than 1year and in patients over 50 years old. A brief period ofconservative therapy can be tried in cases of acute CTS,but any case in which we suspect an acute CTS that isnot secondary to a particularly stressing event – a very rarebut very severe condition – urgent decompression must beconsidered together with a comprehensive assessment of apossible primary subclinical cause.

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