J Orthop Sci (2010) 15:113 DOI 10.

1007/s00776-009-1416-x

Review article Current concepts of carpal tunnel syndrome: pathophysiology, treatment, and evaluation
SHIGEHARU UCHIYAMA1, TOSHIROU ITSUBO1, KOICHI NAKAMURA1, HIROYUKI KATO1, TAKASHI YASUTOMI2, and TOSHIMITSU MOMOSE3
1 2 3

Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan Department of Orthopaedic Surgery, Shiokawa Hospital, Hokuto, Yamanashi, Japan Department of Orthopaedic Surgery, Japanese Red Cross Suwa Hospital, Suwa, Nagano, Japan

Abstract The current concepts of carpal tunnel syndrome (CTS) with respect to its pathophysiology, treatment, and evaluation are discussed. With regard to the pathophysiology of idiopathic CTS, biomechanical studies to determine the kinematics of the exor tendon, and the median nerve inside the carpal tunnel may provide valuable insights. Different degrees of excursion between the exor tendons and the median nerve could cause strain and microdamage to the synovial tissue; this has been microscopically observed. A biomechanical approach for elucidating the events that trigger the development of CTS seems interesting; however, there are limitations to its applications. Endoscopic carpal tunnel release (ECTR) is a useful technique for achieving median nerve decompression. However, it is not considered superior to conventional open carpal tunnel release in terms of fast recovery of hand function. Unless the effect of inserting a cannula into the diseased carpal tunnel on the median nerve function is quantitatively elucidated, ECTR will not be regarded as a standard procedure for relieving the median nerve from chronic compression. The treatment of CTS should be evaluated on the basis of patient-oriented questionnaires as well as conventional instruments because these questionnaires have been validated and found to be highly responsive to the treatment. It should be noted that nerve conduction studies exclusively evaluate the function of the median nerve, whereas patient-oriented questionnaires take into account not only the symptoms of CTS but other accompanying pathologies as well, such as exor tenosynovitis. In Japan, the number of CTS patients is expected to rise; this may be attributed to a general increase in the life-span of the Japanese and increase in the number of diabetic patients. Thus, more efforts should be directed toward elucidating the pathophysiology of so-called idiopathic CTS, so that new treatment strategies can be established for CTS of different pathologies.

Introduction Carpal tunnel syndrome (CTS), the most common form of entrapment neuropathy, is estimated to occur in 3.8% of the general population.1 On the basis of clinical examinations and nerve conduction studies (NCSs), it has been approximated that one in every ve subjects who complain of symptoms such as pain, numbness, and a tingling sensation in the hands could have CTS.1 Although this syndrome is widely recognized, its etiology remains largely unclear. Furthermore, idiopathic CTS is the most common diagnosis in patients with these symptoms. Recent magnetic resonance imaging (MRI), histological, and biomechanical studies have strongly suggested that the development of idiopathic CTS is closely related to abnormalities of the synovial tissue within the carpal tunnel.210 Despite this equivocal nature of CTS etiology, simple decompression of the median nerve by division of the transverse carpal ligament (TCL) is the treatment of choice and is considered to yield excellent results in 75% of the patients.11 However, this implies that the remaining 25% of the patients may not experience satisfactory relief from the symptoms a notable percentage considering the increasing number of CTS patients.12 This increase in the number of CTS cases is probably attributable to the general increase in the life-span of people and the increased number of diabetic patients. Because of the high prevalence of CTS, many hand surgeons have placed emphasis on clinical research for this condition, and numerous relevant reports are published every year. In this review of CTS, we discuss the pathophysiology of CTS and the currently employed approaches for its diagnosis, evaluation, and treatment.

Offprint requests to: S. Uchiyama Received: June 6, 2009 / Accepted: September 22, 2009

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

Pathophysiology Idiopathic CTS Traditionally, idiopathic CTS has been believed to be caused by an incompatibility between the size of the median nerve and the contents of the carpal tunnel,13 which leads to increased pressure within the carpal tunnel14 and disturbance in the blood ow to the median nerve. Compression of the nerve inside the carpal tunnel may induce venous congestion and subsequent edema; and prolonged epineurial edema causes broblast invasion into the affected tissue and subsequent formation of constricting scar tissue around the median nerve.13 The nerve proximal to the compression site becomes enlarged because of an increase in the amount of endoneurial connective tissue,15 edema in the epineurium and endoneurial space, or obstruction of axoplasmic ow.13 Mechanical factors Biomechanical studies to determine the characteristics of the kinematics of the exor tendons and the median nerve inside the carpal tunnel can provide valuable insights into the pathomechanics of idiopathic CTS. This is because the exor tendon and median nerve lie in close proximity, and each can signicantly affect the others kinematics and mechanical properties. The carpal tunnel is dorsally and radioulnarly surrounded by the carpal bones and volarly surrounded by the TCL, through which run eight nger exor tendons, the exor pollicis longus tendon, the synovium, and the median nerve. The tendons transmit force generated by the forearm muscles to the digital phalanxes. These tendons pass through a exor pulley system that includes the TCL and digital pulleys, where synovial uid keeps friction between the tendon and pulleys low through both boundary and uid lm lubrication.16 The frictional coefcient of the tendonpulley interface is calculated to be approximately 0.04, which is greater than that between the cartilages in a diarthrodial joint.17 In vivo measurements have revealed the tendon excursion to be 2450 mm during active exion and extension of the wrist and ngers.18 The excursion of the median nerve has also been measured: it has been found to range from 3 to 12 mm in preserved cadavers,19 from 9 to 14 mm in fresh frozen cadavers,20 and from 11.0 to 28.8 mm during wrist and elbow movement in vivo.21,22 In addition, the exor tendons and median nerve move independently as well as concurrently in all anatomical directions (proximal-distal, radial-ulnar, and volar-dorsal directions).23 Different degrees of excursion between the exor tendons and the median nerve could result in strain and microdamage to the synovial tissue10 as well as the median nerve.24

Furthermore, shear modulus of the subsynovial connective tissue in CTS patients is found to be signicantly higher than that in control subjects.9 This nding may be consistent with the fact that brosis of the synovial tissue within the carpal tunnel is often observed in CTS patients. In one study, the tendon force was measured in vivo using a buckle-type transducer positioned over the carpal tunnel during pinching activities involving the thumb and digits; the maximum force recorded was 12.0 kgf, with a mean applied pinch force of 3.5 kgf.25 During active exion of the digits, the exor digitorum profundus and exor pollicis longus tendons bear forces of 6.4 and 4.2 kgf, respectively.25 Similar measurements were conducted in more recent studies, and similar values were reported.26,27 Because these values were measured after division of the TCL, the tendon force proximal to the TCL may have been even greater than that due to friction between the tendon and the TCL, which has been estimated to be around 0.1 N when an external force of 2 N is applied.28 Furthermore, it is known that the exor tendons move upward from the oor of the carpal tunnel during active nger movement.2931 This movement of the exor tendons generates a compression (or reaction) force between the tendons and the TCL. On the basis of a theoretical model, it has been estimated that almost the same amount of force of the exor tendon can be applied to the TCL during nger movement.32 Those ndings support the possibility of wear and degeneration of the tendon and the surrounding synovium during everyday activities, which are believed to play an important role in the development of idiopathic CTS; however, it remains unclear as to how much force or friction and how many cycles are needed to cause degeneration of the synovial tissue and exor tendons and to affect the median nerve. Damage of the synovial tissue can be caused by factors such as the applied force and the duration and rate of loading, which are closely related to physical activity. Kursa et al. found that during high-precision, isometric pinch maneuvers with the ngers in a static condition the tendon forces are independent of the loading rate.26 This nding may facilitate the development of preventive strategies against tendinopathy of the exor tendons and subsequent CTS. Morphological changes in synovial tissue In many studies, microscopic histological examinations have been performed to examine alterations in the synovial tissue, including subsynovial connective tissue, around the exor tendons. Only 10% of the synovial specimens resected from patients with idiopathic CTS exhibited inammatory changes, but most exhibited edema or brosis.33,34 Moreover, detailed histological

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examinations of synovial tissue obtained from CTS patients revealed an increase in broblast density, collagen ber size, and vascular proliferation35 and a decrease in the elastin content around the synovial vessels; these ndings were indicative of chronic degeneration. Electron microscopic analyses of synovial tissue specimens obtained from patients with idiopathic CTS revealed deformed collagen brils with a spiral appearance, distinct from those in people without CTS; however, the process that leads to the altered morphology of the collagen brils remains to be claried.7 Biochemical changes in synovial tissue Mechanical stress applied to the synovial tissue inside the carpal tunnel can also cause biochemical alterations to the tissue. The expression of dermatan, keratan, and chondroitin sulfate in the synovium was compared between CTS patients and controls. Immunostaining revealed greater keratan reactivity in the tissues of CTS patients. This suggests that altered proteoglycan ratios may reduce the ability of the synovium to bear the compression forces, thus increasing the force incident on the median nerve inside the carpal canal.36 In addition, repetitive exposure of the tendons to compression or tensile strength can increase the proteoglycan content in the tendon matrix, thus causing metaplasia or hypertrophy of the tendon, which can in turn increase the pressure within the carpal tunnel.37,38 In an attempt to elucidate the role of tenascin-C, which is often involved in tissue remodeling and vascular stenosis, in the pathogenesis of CTS, Tsujii et al. found that mechanical strain on the exor tenosynovium regulates the production of tenascin-C by the synovial lining and connective tissue.8 On the basis of these biomechanical and histological ndings, it has been speculated that insult to the synovium and the exor tendons due to aging or repetitive and forceful movement of the wrist and ngers could lead to degeneration of the synovium and the tendons, leading to enlargement of the carpal tunnel from the inner side. Thus, the volume of the carpal tunnel contents increases, leading to median nerve compression and, eventually, idiopathic carpal tunnel syndrome. Secondary CTS Many other conditions apart from idiopathic CTS can increase the pressure within the carpal tunnel and cause median nerve compression inside the tunnel; these conditions include abnormalities of the exor tendons, synovium, or the structure inside the median nerve and space-occupying lesions. In patients with symptoms of CTS, the underlying pathology should always be scruti-

nized. Specic diseases that affect the synovium and can cause secondary CTS include diabetes, rheumatoid arthritis, sarcoidosis, purulent tenosynovitis, tuberculosis, systemic lupus erythematosus, hypo- or hyperthyroidism, gout, and amyloidosis. Diabetes The number of diabetic patients in Japan has been increasing. According to an annual report released by the Japanese Ministry of Health and Welfare, almost 21,200,000 people, or one-fth of the Japanese adult population, are suspected to have diabetes.39 More attention should be paid to the possibility of CTS in diabetic patients because of its peculiar etiology and varied responses to treatment. The prevalence of CTS in diabetic patients is extremely high: It is estimated to occur in 14% patients without diabetic polyneuropathies and in up to 30% of those with diabetic polyneuropathies.40 The incidence of carpal tunnel release (CTR) surgery among patients with type 2 diabetes is estimated to be 414 times that in the general population.41 The degree to which median nerve function can be recovered after CTR is less among diabetic patients than among nondiabetic persons.42 The less favorable outcome of CTR in diabetic patients may be attributed to the loss of normal regenerative ability in the peripheral nerve because of microangiopathy, macrophage dysfunction, abnormalities in the retrograde cell body reaction, Schwann cell dysfunction, or decreased expression of neurotrophic factors and their receptors.43,44 Recently, Nishimura et al. demonstrated the role of tenascin-C, an extracellular matrix glycoprotein, in diabetic entrapment neuropathy using a rat model.45 They reported that tenascin-C-expressing myobroblasts may constrict axons by inducing collagen contraction in the endoneurium. They also found that distal latency of the tibial nerve was more prolonged in diabetic rats than in nondiabetic rats, and that the blood glucose levels positively correlated with distal latency. It is undoubtedly mandatory that the blood glucose levels of patients be well controlled after surgery to ensure better recovery of nerve function. In CTS patients with diabetes, surgery should be indicated after due consideration to not only the severity of the symptoms but also the regenerative ability of the median nerve. Amyloid deposition Amyloidosis causes CTS because of amyloid deposition not only within the peripheral nerve but also in the synovium of the exor tendons in the carpal tunnel. 2Microglobulin amyloid causes median nerve palsy in the carpal tunnel of patients undergoing long-term hemodialysis. For example, 50% of the patients who have undergone hemodialysis for 2025 years undergo

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

surgery for CTS. CTS is found to be signicantly associated with destructive spondyloarthropathy, which is a serious complication of long-term hemodialysis; it is also caused by deposition of 2-microglobulin amyloid along the spine.46 CTS can also appear as an initial symptom in transthyretin (TTR) amyloidosis. In previous studies, 10%20% of all synovial biopsy specimens obtained from patients who underwent CTR exhibited amyloid deposition, and 59% of all the specimens with amyloid deposits tested positive for TTR amyloid.47.48 However, it could not be determined whether such TTR amyloid deposition was sufcient to cause CTS. In cases where amyloid deposits are identied in the tenosynovium during CTR, systemic amyloidosis rarely develops during long-term follow-up,49 although some patients denitely need special care to prevent systemic amyloidosis.50,51 The term idiopathic CTS may not be appropriate if amyloidosis is identied as the cause of the condition. Because TTR deposition on the synovium is more common in older patients, the possibility of such deposition being the primary cause of CTS cannot be ruled out. In such cases, further studies are needed to clarify whether any of the clinical, electrophysiological, or imaging ndings correspond to those of idiopathic CTS. Pregnancy Pregnancy and labor may lead to the development of peripheral nerve disorder, including CTS, facial nerve palsy, lumbosacral radiculopathy, meralgia paresthetica, and femoral neuropathy, among which CTS is the most frequently observed. CTS may be caused by edema associated with uid retention in the synovium, which exerts pressure on the median nerve. Other lower extremity neuropathies may be more frequently caused by mechanical compression associated with increased abdominal girth.52 A recent long-term follow-up study on pregnant women with CTS (up to 3 years after delivery) has reported evident alleviation of the symptoms, but about 50% of the women involved complained of some symptoms 3 years after delivery.53 These results suggest that uid retention may be responsible for the development of CTS but cannot always explain the postdelivery symptoms of CTS. Such patients may be diagnosed with idiopathic CTS at a later stage. Space-occupying lesion and others An increase in the carpal tunnel pressure due to spaceoccupying lesions such as those associated with wrist fracture and/or dislocation, lunatomalacia, ganglions, lipoma, or synovial cysts can also cause CTS. Although brolipomatous hamartoma of the median nerve is rare, it should also be considered as a possible primary lesion of the median nerve. This condition is characterized by epineurial expansion due to the brofatty tissue that

surrounds and separates the nerve fascicles. Crosssectional MRI of the affected area reveals alternating lesions of high and low signal intensity.54 Trigger digit and CTS Idiopathic CTS often accompanies tendon and synovial abnormalities at other sites. Trigger digit accompanies idiopathic CTS55 in approximately 20% of patients.5658 If the primary lesion in idiopathic CTS is a synovial abnormality, as described above, it may lead to exor tendon entrapment at the A1 pulley owing to enlargement of the tendon and its synovium. A recent prospective study has revealed a high prevalence of CTS in patients with trigger digit, wherein 91 of 211 patients with trigger digit (43%) had CTS.55 Trigger digit occasionally develops after CTR with division of the TCL.5658 This may be because of an alteration in the tendon mechanics, wherein the exor tendon shifts volarly and increases the friction between the A1 pulley and the tendon.56,57 Although this hypothesis is probably accurate, further studies are required to prove it. Double crush hypothesis Carpal tunnel syndrome is often accompanied by a more proximal neuropathy such as cervical radiculopathy. In such a case, suboptimal results can be obtained even after successfully decompressing the median nerve at the wrist. Upton and McComas proposed a concept of double crush wherein one-site compression of the peripheral nerve renders the more distal nerve susceptible to compression caused by impaired axoplasmic ow.59 Since then, conicting results for the concomitant occurrence of this neuropathy have been obtained. This hypothesis has been supported by experimental studies in animals.6062 Nemoto et al. conducted experiments that showed the vulnerability of the canine sciatic nerve in the double-crush situation. They concluded that proximal compression of the peripheral nerve possible decreased its ability to withstand further compression in the more distal part.60 On the other hand, clinical data have not convincingly supported this hypothesis. Although imaging studies can reveal the coexistence of cervical neuropathy and CTS,63 neurophysiological data do not support this hypothesis. Kwon et al. failed to show a signicant correlation not only between median sensory parameters and C6 and C7 radiculopathies but also between median motor responses and C8 radiculopathy.64 Shibuya et al. concluded that dual entrapment lesions did not increase the vulnerability of the peripheral nerve to compression; rather, the vulnerability was proportional to the severity of each lesion. It is difcult to prove clinically that CTS occurs because of the suscep-

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

tibility of the median nerve to compression due to preexisting cervical radiculopathy.65

These examinations certainly add some diagnostic value to the evaluation of CTS, but it should be kept in mind that they are not exclusive for a CTS diagnosis.

Diagnosis Symptoms and physical ndings Carpal tunnel syndrome is diagnosed on the basis of the patients present history and clinical ndings. Bilateral CTS is considerably common, but the symptoms may not occur simultaneously in both hands. Symptoms involving the contralateral side become more evident with time.66 During the early stage of the disease, patients may complain of numbness in the digits, nocturnal symptoms, or numbness experienced when holding a phone or newspaper. These symptoms may be due to transient ischemia of the median nerve. As the disease advances, the carpal tunnel volume decreases because edema subsides, possibly leading to brosis of the median nerve. Patients may experience some relief from pain but may develop sensory loss or experience awkwardness during thumb movements. During physical examination, two-point discrimination or the Semmes-Weinstein monolament test reveals sensory disturbance over the median nerve distribution area. Thenar muscle atrophy occurs during the advanced stage of the disease. The results of Phalens test and Tinel sign should be carefully assessed. The sensitivity of Phalens test for diagnosing CTS is 67%83%, and the specicity is 40%98%; the sensitivity of the Tinel sign is 48%73%, and specicity is 30%94%.6769 The variations in these values indicate inconsistencies in the scheme of examination and interpretation of the results. Based on a review of the published data regarding the accuracy of these traditional tests, some researchers have questioned their diagnostic value.70 Other provocation tests include the carpal tunnel compression test and hand elevation test. The carpal tunnel compression test has a sensitivity of 75% and a specicity of 93%; but when the test is performed with wrist exion, its sensitivity and specicity increase to 86% and 95%, respectively.71 The hand elevation test is conducted by asking the patient to raise the affected hand and hold it in that position for 1 min. The test is considered positive if the patient experiences tingling and numbness in the median nerve distribution area. The sensitivity and specicity of this test are 76%88% and 98%99%, respectively.72 When the patient maintains his or her hand in the raised position, there is a reduction in the blood supply to the already compromised nerve because of lowering of the local blood pressure. Furthermore, venous congestion just distal to the compression site of the median nerve may render the nerve ischemic. Neurophysiological test In most cases where the complaints and ndings are typical, the diagnosis of CTS is relatively easy. However, this is not always the case. CTS is often accompanied by other entrapment neuropathies or tenosynovitis of the exor tendons. The patient may complain of pain or a snapping phenomenon rather than numbness. When entrapment neuropathy involves some other site (e.g., in the case of cubital tunnel syndrome), the patient may complain of awkwardness during nger and thumb motion as well as numbness in the thumb and all ngers. Moreover, the presence of a cervical lesion may further complicate the symptoms. In such cases, CTS cannot be conrmed merely by physical examination; objective examinations are necessary. NCSs are the most common tests used to assess the function of the median nerve, which crosses the wrist. These studies usually comprise measuring motor distal latency, compound muscle action potential, sensory nerve conduction velocity (SCV), and sensory nerve action potential. The American Academy of Orthopaedic Surgeons recommends that NCSs be performed according to the protocol and guidelines issued by the American Academy of Neurology/American Association of Neuromuscular and Electrodiagnostic Medicine/American Academy of Physical Medicine and Rehabilitation (AAN/AANEM/ AAPMR). The motor distal latency and SCV reect the function of large myelinated bers such as the A- and A- bers. Because some symptoms of CTS, such as pain, are related to the small unmyelinated (C) bers, efforts have been made to evaluate the function of these bers by measuring the current perception threshold (CPT),73,74 sympathetic skin response,75 and vibratory threshold.76 CPT measurement with the neurometer has proven to be a reliable quantitative sensory test. Nishimura et al. found that the A- bers are the rst to be compromised in CTS, followed by the other smaller bers such as the A- and C bers.73 Vasomotor function, quantied by measuring skin vasoconstriction with laser Doppler velocimetry, is found to be compromised in patients with CTS compared to that of controls.77 However, these tests have not been widely used for the diagnosis of CTS thus far because they do not offer greater sensitivity or specicity for an accurate diagnosis.78 For CPT measurements to become routine procedures of diagnostic value, a device that enables easy and reliable data collection is necessary.

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

Role of MRI Although the tests described above are useful for evaluating median nerve function, they cannot reveal the cause of nerve compression or elongation. Imaging studies, including MRI and ultrasonography, can be useful for this purpose. Recent MRI studies on CTS patients have provided valuable insights into the pathophysiology of idiopathic CTS. Enlargement of the cross-sectional area (CSA) of the median nerve at the proximal end of the carpal tunnel, increased signal intensity over the median nerve, and palmar bowing of the TCL are characteristic ndings of idiopathic CTS.79 These ndings vary depending on the stage of the disease: Proximal enlargement of the CSA and increased signal intensity of the median nerve are more pronounced during the advanced stage of the disease.5,80 High-signal intensity over the median nerve on T2weighted MRI scans indicates accumulation of the axonal transportation, myelin sheath degeneration, or edema.81 Palmar bowing of the TCL may indicate enlargement of the structures within the carpal tunnel, such as the exor tendons or synovial tissue. In addition, sagittal images are useful to show the site accurately and determine the severity of nerve compression.82 Although idiopathic CTS is associated with characteristic MRI ndings, no parameter that can be used to dene CTS clearly has yet been identied. MRI offers the highest diagnostic sensitivity for idiopathic CTS rst through the overall assessment of the images (96%), which largely depends on the assessors skill, followed by increased signal intensity over the median nerve (91%); however, its specicity is low (33%38%).83 Jarvik et al. demonstrated that in patients with idiopathic CTS the MRI ndings can be used to predict the surgical outcome, independent of NCSs. The length of the abnormal nerve signal on T2-weighted MRI and the medianulnar sensory latency difference were identied as the best predictors of surgical outcome. Furthermore, patients preferred MRI over NCSs.84 Because MRI is expensive, its routine use for patients with typical symptoms of CTS may not currently be practical. Instead, it can be used to determine the point of nerve entrapment after failure of CTR, for differential diagnosis in the case of ambiguous symptoms, and to conrm the presence of space-occupying lesions. However, the current diagnostic procedures can be rened by the application of new technologies, for example, by in vivo three-dimensional visualization of the median nerve using tractography on a magnet and microstructural diffusion parameters.85 Role of ultrasonography Recently, the possibility of using ultrasonography for diagnosis has been receiving increasing attention

because it is a simple, easy-to-perform, noninvasive procedure for delineating the conformation of the median nerve. Usually, the CSA of the median nerve is measured at the level of its entry into or exit from the carpal tunnel or at the forearm level.8691 CTS is diagnosed on the basis of an increase in the CSA at the entry level or a discrepancy between the CSA at the entry level and the distal forearm level. The diagnostic accuracy of this method can be high,8691 although the reported cutoff values vary because of differences in the gold standards or devices used for diagnosis, the severity of the disease, or other factors. Data obtained for Japanese populations have demonstrated that the diagnostic sensitivity and specicity were 67% and 97%, respectively, when the mean carpal nerve area (average of the areas measured at the distal edge of the TCL, the hook of the hamate, and the wrist crease) was used as the diagnostic criterion. Furthermore, when this criterion was combined with the results of NCSs, the sensitivity and specicity were 84% and 94% respectively.90 Ultrasonographic diagnosis can be universally employed when a standardized protocol is used because the measurements thus obtained are found to be reproducible, regardless of whether the examination is performed by an experienced technician or an inexperienced one after a short learning period.92 Magnetic resonance imaging and ultrasonography can also be used to determine whether endoscopic carpal tunnel release (ECTR) is indicated. This is because they can depict possible space-occupying lesions or anatomical abnormalities that can cause damage to the median nerve during introduction of the cannula assembly.

Treatment Conservative treatment Because the pathophysiology of idiopathic CTS remains unclear, denitive treatment strategies have not yet been established. Treatment may be selected considering the stage of the disease, the severity of the symptoms, or the patients preference. The various available options for conservative treatment include splinting, local injection of corticosteroids, or oral treatment with other medications such as corticosteroids, vitamin B6, vitamin B1293 or nonsteroidal anti-inammatory drugs (NSAIDs). As the condition improves or remains stable in a signicant number of patients without any treatment over 2 years of follow-up,94,95 it is difcult to determine the effect of conservative treatment in relieving the symptoms of CTS. Splinting, local injection of corticosteroids into the carpal tunnel, and oral corticosteroid treatment have proven effective in some cases.96

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Through a search of the Cochrane database, Marshall et al. found that local corticosteroid injection alleviates the symptoms of CTS, but this effect lasts only for 1 month after the injection.97 They also found that compared to oral corticosteroid treatment local corticosteroid injection alleviates the symptoms to a signicantly greater extent for up to 3 months. Furthermore, the concomitant use of two local corticosteroids does not enhance the clinical benets.97 Although corticosteroid treatment is effective in reducing inammation and edema, it limits tenocyte function by reducing collagen and proteoglycan synthesis, thus reducing the mechanical strength of the tendon and ultimately leading to further degeneration.98101 The effects of corticosteroids or local anesthetic agents on the nerve bers or cells and the synovial tissue should also be considered.102 Further research is required to clarify the appropriate injection method and the optimum preparation, dose, and volume of corticosteroid.103

the cannula, although the latter point is not well dened. Results of ECTR Once the possibility of iatrogenic injury to the median nerve is recognized and successful attempts have been made to reduce complications, ECTR, by either the one-portal or two-portal technique, can yield results comparable with those of OCTR in terms of good symptom resolution, better physical ndings and NCSs results, and low rates of serious complications.111118 Pajardi et al. reported the results obtained for 12 702 patients who were treated by ECTR by a one-portal system (MicroAire, Charlottesville, VA, USA). They found that in 88% of the patients the symptoms were completely resolved within 210 days of the procedure; however, six patients developed major complications because of iatrogenic nerve injuries.111 In another study involving 3206 wrists of 2247 patients who were treated with Chow and Hantess two-portal technique, the symptoms were completely or largely resolved in 93% of the patients, and recurrence rate was 0.6%.113 Hankins et al. reviewed the cases of 14 722 patients who underwent ECTR by Browns two-portal technique119 for decompression of the median nerve, and they encountered only one case of iatrogenic nerve injury.116 How do surgeons who prefer to use ECTR detect space-occupying lesions before surgery or identify difcult cases where conversion to OCTR may be warranted? Ultrasonography or MRI may be useful for this purpose. However, none of the above-mentioned reports have provided practical answers to this question. Comparison with OCTR Although ECTR is useful for achieving median nerve decompression, its effectiveness in comparison with the minimally invasive OCTR for restoring function of the affected hand early after treatment is debated. The grip strength temporarily decreases after ECTR because of pain over the wound area, which is the case after any CTR procedure. Although it is difcult to compare directly ECTR and techniques involving limited palmar incision because of the ambiguity in the denition of resuming daily activities, the average time required to resume daily activities or work after ECTR may not be less. A recent study by Jugovac et al. reported a median time of 5 days to resume daily activities or 10 days to resume work.120 In another study by Yung et al., all patients regained function in the affected hands and had no difculties with activities of daily living (ADLs) within 4 weeks after CTR with a 1.5-cm palmar incision.121 Acharya and Auchincloss reported that the time required to resume all evaluated ADLs after OCTR was 13 days.122

Surgery: open carpal tunnel release When conservative treatment fails, surgery is indicated. Currently, surgery is known to be more effective than splinting104 and perhaps all the other conservative treatment measures.105 CTR with TCL division is accepted as the most reliable procedure for relieving symptoms. The TCL can be divided by numerous methods, including conventional open carpal tunnel release (OCTR), mini-OCTR, and ECTR. OCTR is universally accepted by both hand surgeons and general surgeons,106 and high success rates can be expected with this procedure, although some wound-related symptoms may persist for 2 years of follow-up.107 This surgery is indicated for CTS with any type of pathology.

Surgery: ECTR The one-portal and two-portal techniques of ECTR have gained popularity since their introduction two decades ago.108,109 Okutsu et al. have proved with a continuous infusion technique that complete decompression of the median nerve can be brought about by their one-portal endoscopic technique.110 Visualizing the dorsal aspect of the TCL through an arthroscope initially seemed a highly innovative, attractive approach. However, ECTR can result in iatrogenic injuries such as transection of the median nerve, exor tendons, or even the ulnar nerve, mostly because of technical errors. Such injuries can usually be avoided by adhering to the recommended procedure: (1) the TCL should not be cut if soft tissue is obstructing the view; and (2) the procedure should immediately be revised to OCTR if the surgeon experiences some difculty when introducing

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

According to Yung et al., pillar pain, dened as tenderness over the thenar or hypothenar regions, was noted in 27% patients at 3 months after CTR with limited palmar incision.121 Ruch et al. found that tenderness over the wound was minimal or absent in 92% patients between 4 and 10 weeks of follow-up.123 With ECTR, the TCL is divided, and the subcutaneous fatty tissue and palmar fascia are left intact. In another study, although the sensory nerve function over the palm could be preserved, some tenderness over the scar or around the TCL edges persisted in 40% of the patients at 6 months after the surgery.124 Quantitative methods for evaluating scar tenderness should be employed to compare the results obtained with all the above procedures. A common feature of all the available CTR procedures is that the TCL is divided either endoscopically or openly. The postoperative courses follow similar patterns: decompression of the median nerve is denitely achieved, but grip strength temporarily decreases after the surgery, and pain over and around the wound persists for awhile. These results suggest that so long as the TCL is divided to save the median nerve, immediate postoperative pain over and around the wound, accompanied by a decrease in grip strength, cannot be avoided. Inherent weakness of ECTR Even if endoscopic surgeons insist that ECTR is a reliable, effective, safe procedure, most orthopedic surgeons nd it difcult to accept this viewpoint because of the inherent limitation of ECTR namely, that the surgeon has to insert the cannula (diameter 5.5 mm in Chows technique) into the diseased carpal tunnel. As mentioned earlier, in idiopathic CTS, the pressure in the carpal tunnel is greater than usual, and the possibility of its increasing further during the procedure is concerning. Insertion of the cannula into the carpal tunnel can cause compression or elongation the median nerve, especially if the nerve is already adhering to the TCL or synovial tissues. The pressure that the median nerve has to sustain during insertion of the cannula into the carpal tunnel has never been quantitatively measured. There have been reports of iatrogenic damage to the median nerve, even if the procedure is followed accurately.125 The maximum pressure that can be tolerated without injury to the median nerve is unknown because there is no way to investigate this point. Unless the effect of cannula insertion on the median nerve function can be quantitatively elucidated, ECTR will not come to be regarded as a standard procedure for rescuing the median nerve from chronic compression. This is evident in the fact that only 25% hand surgeons in Japan prefer ECTR over OCTR.126 This percentage would be even lower if the sample were expanded to include a larger group of orthopedic surgeons who regularly treat CTS.

As ECTR undoubtedly has limitations and has not been proven to offer considerable advantages over OCTR,115,127 the former should not be attempted without a thorough understanding of the anatomy of the target site, the technical pitfalls, and the possibility of iatrogenic nerve injury. Furthermore, it should be noted that even experts who perform ECTR do not know the threshold pressure that can cause iatrogenic injury to the median nerve during introduction of the cannula into the diseased carpal tunnel. If the indications for ECTR could be clearly dened, this procedure could emerge as one of the standard techniques for median nerve decompression.

Patient-oriented questionnaires for CTS Recently, the pre- and postoperative status of CTS patients has been evaluated using not only physical examinations but also patient-oriented questionnaires. The latter type of evaluation is crucial because patient satisfaction should always be measured as an indicator of treatment outcomes. Patient-oriented questionnaires that are currently available for Japanese CTS patients are the 36-item short-form health survey (SF-36); the disabilities of the arm, shoulder, and hand (DASH) questionnaire; the QuickDASH; and the carpal tunnel syndrome instrument (CTSI, or Boston questionnaire). The Japanese versions of these questionnaires were developed through cross-cultural adaptation,128130 and they are self-administered rather than scored as per the physicians assessment.131 Responsiveness examined by calculating the standard response mean (mean change/standard deviation) and effect size (mean change/standard deviation of the baseline value) to the CTSI-symptom severity (CTSISS) and the CTSI-functional status (CTSI-FS) was found to be good at 3 months after CTR surgery. The reported values of effect size and standard response mean were 1.01.9 and 0.621.30, respectively, where a score of >0.8 is considered to imply high responsiveness, one of approximately 0.5 moderate responsiveness, and one of <0.2 low responsiveness. These values were higher than those obtained with the DASH (0.461.13) or the SF-36 (0.391.0).130,132134 The scores on the DASH and CTSI-FS are affected more by functional changes, whereas those on the CTSI-SS are affected by paresthesia, pain, or both, which may rapidly be alleviated postoperatively. Although the DASH and SF-36 are less sensitive to treatment for CTS, they may be useful for evaluating the relative impact of CTS on the upper extremities or the whole body. Although the responsiveness to both patient-oriented questionnaires on CTS and parameters assessed in NCSs is good, there have been conicting reports on the

S. Uchiyama et al.: Current concepts of carpal tunnel syndrome

correlation between these parameters. Chan et al. reported that there is no signicant relationship between electrodiagnostic ndings and the functional status of patients or the severity of the symptoms.135 Schrijver et al. found modest correlations between neurophysiological and clinical outcome measures and between the changes in these two categories of outcome measures at 12 months after surgery.136 Longstaff et al. found no relation between the symptoms and severity of electrophysiological abnormalities.137 Dhong et al. found that the NCS results correlated more signicantly with the score on the symptom severity scale than with that on the functional scale.138 Mondelli et al. found no correlation between the CTSI score and the NCS results obtained before surgery or between the degrees of improvement in these two parameters.139 Dudley-Porras et al. found no relation between the CTSI score and NCS results before surgery but a signicant relationship between clinical improvement and an improvement in the SCV after surgery.140 Although some of these authors have conicting views, none disputes the need for NCSs in evaluating CTS patients.141 Nerve conduction studies exclusively serve to depict the median nerve function in CTS patients. Moreover, as mentioned in the context of CTS pathophysiology, changes in the exor tendon synovium are not only closely related to the development of idiopathic CTS; they also trigger digit or tenosynovial hypertrophy, all of which can restrict ADLs. In other words, the DASH or CTSI scores can also be affected by impairments due to pain from tendon abnormalities. Furthermore, while NCSs can be used to evaluate each hand independently, patient-oriented questionnaires are designed to cover the affected side as well as the contralateral side, which is often also involved in CTS.

effect of inserting a cannula into the diseased carpal tunnel on the median nerve function is elucidated quantitatively, ECTR will not be regarded as a standard procedure for relieving the median nerve from chronic compression. The treatment of CTS should be evaluated on the basis of patient-oriented questionnaires as well as conventional instruments because these questionnaires have been validated and found to be highly responsive to the treatment. In Japan, the number of CTS patients is expected to rise, which may be attributed to a general increase in the life-span of the Japanese and increase in the number of diabetic patients. Thus, more efforts should be directed toward elucidating the pathophysiology of socalled idiopathic CTS, so new treatment strategies can be established for CTS of different pathologies.
Acknowledgment. We thank P.C. Amadio, MD (Consultatnt, Department of Orthopedic Surgery Professor of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic) for critically reviewing the article.

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Conclusion The current concepts of CTS with respect to its pathophysiology, treatment, and evaluation have been discussed. In particular, the role of ECTR in current surgical procedures was studied. On the basis of biomechanical and histological ndings, it has been speculated that insult to the synovium and the exor tendons due to aging or repetitive and forceful movement of the wrist and ngers could lead to degeneration of the synovium and the tendons, in turn leading to enlargement of the carpal tunnel from the inner side. Thus, the volume of the carpal tunnel contents increases, leading to median nerve compression and eventually the idiopathic carpal tunnel syndrome. ECTR is a useful technique for achieving median nerve decompression. However, it is not considered to be superior to OCTR in terms of fast recovery of hand function. Unless the

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