Ultrasound in Med. & Biol., Vol. -, No. -, pp. 1–6, 2015 Copyright Ó 2015 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/$ - see front matter
http://dx.doi.org/10.1016/j.ultrasmedbio.2015.05.013
d
Original Contribution DIAGNOSIS OF SEVERE CARPAL TUNNEL SYNDROME USING NERVE CONDUCTION STUDY AND ULTRASONOGRAPHY KAZUHIRO FUJIMOTO,* TSUKASA KANCHIKU,* KENJI KIDO,y YASUAKI IMAJO,* MASAHIRO FUNABA,* and TOSHIHIKO TAGUCHI* * Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; and y Department of Orthopaedic Surgery, Ehime Rosai Hospital, Niihama, Ehime, Japan (Received 16 December 2014; revised 14 May 2015; in final form 16 May 2015)
Abstract—This study investigated the correlation between nerve conduction study and ultrasonographic findings for assessment of the usefulness of ultrasonography in determining carpal tunnel syndrome severity. Hands of adults with carpal tunnel syndrome were assessed using ultrasound and nerve conduction studies and grouped according to median nerve cross-sectional area (CSA). There were significant differences (p , 0.01) in mean median nerve CSA between controls, patients with median sensory nerve conduction velocity #40 m/s and patients with absent sensory nerve action potential and between controls, patients with median nerve distal motor latency $4.5 ms and patients with absent compound muscle action potentials of the abductor pollicis brevis. This is the first report to define median nerve CSA cutoff values (18 mm2) for determining carpal tunnel syndrome severity in patients with absent compound muscle action potentials of the abductor pollicis brevis. Median nerve CSA values below the cutoff values should prompt clinicians to consider other disorders, such as cervical compressive myelopathy. (E-mail: [email protected]) Ó 2015 World Federation for Ultrasound in Medicine & Biology. Key Words: Carpal tunnel syndrome, Nerve conduction study, Ultrasonography, Median nerve, Cross-sectional area.
INTRODUCTION
quantitatively evaluate CTS severity using NCS. Some authors report that ulnar nerve distal motor latency (DML) and distal sensory latency can be significantly longer in patients with CTS than in controls (Chen and Tsai 2014; Kiylioglu et al. 2011; Yemisci et al. 2011). In cases of combined CTS and ulnar tunnel syndrome, CTS diagnosis using the 2 L-INT test may also be difficult. Measuring median nerve DML after palmar stimulation is very useful in diagnosing severe CTS (Kanatani et al. 2012). However, as the severity of the chronic nerve compression injury increases over time, axonal damage ensues and leads to the absence of DML, as well as the absence of sensory nerve conduction velocity (SCV), in later stages. In addition, in severe CTS, palmar stimulation may trigger adductor pollicis CMAPs or flexor pollicis brevis CMAPs by stimulating the deep branch of the ulnar nerve; therefore, palmar stimulation is inappropriate for routine testing. Ultrasonography (US) has recently been found to be useful for CTS diagnosis. This method enables accurate measurement of the median nerve cross-sectional area (CSA) in all patients with CTS, which reportedly ranges
Carpal tunnel syndrome (CTS) is the most common form of entrapment neuropathy. Diagnosis is currently based on the characteristic clinical symptoms of CTS and supported by nerve conduction study (NCS) findings. Some researchers, for example, Bland (2000), Padua et al. (1997) and Stevens (1997), have reported electrophysiologic classification systems for CTS; these classification systems typically grade the relative absence of sensory nerve action potentials (SNAPs) or compound muscle action potentials (CMAPs). CTS severity is difficult to quantify in the absence of SNAPs or abductor pollicis brevis (APB)-CMAPs. In these cases, clinicians perform a second lumbrical–interosseous latency comparison (2 L-INT) test (Kaul and Pagel 2002; Nobuta et al. 2005; Sheean et al. 1995). However, in the absence of 2 L-CMAPs (Inukai et al. 2013; Ozben et al. 2012), it is very difficult to
Address correspondence to: Kazuhiro Fujimoto, 1-1-1 Minami Kogushi, Ube City, Yamaguchi 755-8505, Japan. E-mail: kafuji@ yamaguchi-u.ac.jp 1
2
Ultrasound in Medicine and Biology
from 13 to 15 mm2 (Kaymak et al. 2008; Kim et al. 2013; Kotevoglu and Saglam 2005; Sarrıa et al. 2000). The aim of the present study was to investigate the correlation between NCS and US findings for assessing the usefulness of US in determining CTS severity. METHODS We selected patients with CTS who were diagnosed on the basis of characteristic clinical symptoms and NCS findings (group P). We then chose a group of age-matched controls (group C). Details on these groups are provided in Table 1. Patients with history of diabetes mellitus, extracorporeal dialysis, other peripheral nerve disorders and cervical spine operations were excluded. Fifty-three adults diagnosed as having CTS (81 hands) and 67 volunteers (67 unaffected hands) were studied. Among the patients diagnosed with CTS, there were16 men and 65 women, aged 34–86 y (mean 5 65 y). Of the 81 affected hands, 51 underwent CTS surgery. The other 30 were treated by splinting or local corticosteroid injections. All study participants provided informed consent, and the study design was approved by an ethics review board of Ehime Rosai Hospital. Criteria of clinical features Clinical examination consisted of rating each subject according to the following criteria: (i) history of nocturnal paresthesia and hand pain; (ii) sensory disturbance in the median nerve distribution area in the hand; (iii) weakness or atrophy of thenar muscles innervated by the median nerve; (iv) Tinel sign at the carpal tunnel; and (v) positive Phalen test, in which the wrist is flexed for 1 min, and the patient is asked to report whether their usual symptoms occur. Electrophysiologic investigation During the testing, an infrared lamp was used to maintain each subject’s hand surface temperature at .32 C. One neurologist performed the NCSs on all patients using the Nicolet Viking IV NCS system (Nicolet, Madison, WI, USA). All patients underwent the following examinations: (i) median SCV, lengths from index finger to wrist of 100– 140 mm; (ii) median DML, length from wrist to APB of Table 1. Patients with carpal tunnel syndrome (group P) and age-matched controls (group C) Sex Group Hands P C
81 67
Age (y) 65 (34–86) 62 (40–82)
Treatment
Male Female Operation Conservative 16 9
65 58
51 -
30 -
Volume -, Number -, 2015
70 mm; (iii) 2 L-INT test, lengths from wrist to 2L or INT of 100 mm. We classified CTS severity using the following NCS measurements: Group S1 comprised hands with median SCVs #40 m/s; group S2, hands with absent SNAPs; group D1, hands with median DMLs $4.5 ms; and group D2, hands with absent APB-CMAPs. The 2L-INT test was performed on all patients. We further grouped patients with absent SNAPs, APB-CMAPs and 2L-CMAPs into group L. Ultrasound examination Ultrasound examination of the median nerve at the wrist was performed on the same day as the NCS by an orthopedist who was blinded to the NCS results and had 3 y of experience with musculoskeletal US examinations. The US examination was performed using a 4.8- to 11MHz linear-array transducer (Aplio 300, Toshiba Medical Systems, Tochigi, Japan). All wrists were examined in the neural position with palm up and finger semiextended. Transverse images that measured the median nerve CSA at the carpal tunnel inlet at the level of scaphoid-pisiform were recorded (Fig. 1). The median nerve CSA was measured using the direct tracing method. Statistical analysis Correlations between median nerve CSA and SCV within groups C and S1, as well as between median nerve CSA and DML within groups C and D1, were assessed using the Pearson (r) correlation coefficient. One-way analysis of variance was used to assess correlations between patients in groups C, S1 and S2; between patients in groups C, D1 and D2; and between patients in groups C, L and all other patients. The cutoff values of median nerve CSA used to differentiate between groups C and P, groups S1 and S2, groups D1 and D2 and Group L and all other patients were determined by calculating the receiver operating characteristic curve. The optimal cutoff values of median nerve CSA were defined as the values that allow discrimination between groups with the highest sensitivity and specificity. All p values , 0.05 were regarded as indicating statistical significance. RESULTS As outlined in Table 2, 42 hands were diagnosed with CTS in group S1, 39 in group S2, 68 in group D1 and 13 in group D2. The percentages of patients who received surgical treatment were 43% in group S1, 85% in group S2, 57% in group D1 and 92% in group D2. Median nerve CSAs (mean 6 standard deviation) determined with US were 9.3 6 1.8 mm2 for group C; 15.0 6 2.5 mm2 for group P; 13.6 6 2.0 mm2 for group S1; 16.6 6 1.9 mm2 for group S2; 14.4 6 2.0 mm2 for
Nerve conduction study of severe carpal tunnel syndrome d K. FUJIMOTO et al.
3
Fig. 1. Ultrasonographic images of (1) normal and (2) pathologic median nerve cross-sectional area. A 5 measurement A; P 5 pisiform bone; S 5 scaphoid bone.
group D1; and 18.4 6 1.6 mm2 for group D2. We observed significant differences in mean median nerve CSA between groups C, S1 and S2 (R2 5 0.64, p , 0.01) (Fig. 2) as well as between groups C, D1 and D2 (R2 5 0.61, p , 0.01) (Fig. 3). In addition, median nerve CSA significantly correlated with SCV (p , 0.01) (Fig. 4) and DML (p , 0.01) (Fig. 5). In determining the median nerve CSA cutoff values for differentiating between groups C and P, between
groups S1 and S2 and between groups D1 and D2, the areas under the receiver operating characteristic curve for the median nerve CSA (Az) were 0.970, 0.868 and 0.940, respectively. US measurement of CSA had high
Table 2. Electrophysiologic classification* Group P
S1
S2
D1 D2
42 0 42
26 13 39
68 13 81
* Group S1 5 hands with median sensory nerve conduction velocity #40 m/s; group S2 5 hands with absent sensory nerve action potential; group D1 5 hands with median distal motor latency $4.5 ms; group D2 5 hands with absent abductor pollicis brevis compound muscle action potentials.
Fig. 2. Mean median nerve cross-sectional area (CSA) in groups C, S1 and S2.
4
Ultrasound in Medicine and Biology
Fig. 3. Mean median nerve cross-sectional area (CSA) in groups C, D1 and D2.
sensitivity and specificity in diagnosing CTS severity. The most clinically effective US cutoff values for median nerve CSA were 13 mm2 (sensitivity 5 86%, specificity 5 97%) between groups C and P, 15 mm2 (sensitivity 5 90%, specificity 5 71%) between groups S1 and S2 and 18 mm2 (sensitivity 5 85%, specificity 5 94%) between groups D1 and D2. In 4 hands in 4 patients, there was a complete absence of 2L-CMAPs in this study. In group L, the mean CSA was 20.0 6 1.2 mm2 which significantly differed from the CSAs for group C, group L and other patients (p , 0.01). The most clinically effective median nerve cutoff value between group L and all other patients was 19 mm2 (sensitivity 5 100%, specificity 5 89%), with an Az of 0.994. DISCUSSION At present, CTS diagnosis is generally based on characteristic clinical symptoms supported by NCS findings. Characteristic clinical symptoms include history of
Fig. 4. Correlation between median nerve cross-sectional area (CSA) and sensory nerve conduction velocity (SCV). Circles 5 group S1; squares 5 group C.
Volume -, Number -, 2015
Fig. 5. Correlation between median nerve cross-sectional area (CSA) and distal motor latency (DML). Circles 5 group D1; squares 5 group C.
nocturnal paresthesia and hand pain, sensory disturbance in the median nerve distribution area in the hand, weakness or atrophy of thenar muscles innervated by the of median nerve, Tinel sign at the carpal tunnel and positive Phalen test. Graham (2008) reported that CTS-6, a validated clinical diagnostic aid used to estimate the probability of CTS on the basis of the presence or absence of six clinical findings recorded as part of the history or noted on physical examination. A nerve conduction study is required for quantitatively evaluating the severity of the functional nerve disorder in CTS. Some earlier reports also described an electrophysiologic classification approach to classification of CTS functional severity. For example, the classification of Padua et al. (1997) uses a six-point scale: 1 5 no CTS (normal NCS and no electrophysiologic evidence of CTS); 2 5 minimal (abnormal comparative tests); 3 5 mild (delayed median SCV but normal median DML); 4 5 moderate (delayed median SCV and prolonged median DML); 5 5 severe (absence of median SNAPs and prolonged median DML); and 6 5 extremely severe (absence of median SNAPs and APB-CMAPs). It is difficult to quantitatively evaluate severe or extreme stages of CTS. Ultrasound has been widely accepted as also useful for CTS diagnosis (Cartwright et al. 2012; Roll et al. 2011; Tai et al. 2012), particularly for determining median nerve CSA (Kaymak et al. 2008; Kim et al. 2013; Kotevoglu and Saglam 2005; Sarrıa et al. 2000). Nakamichi and Tachibana (2000) reported that median nerve enlargement was due to compressive lesions. They suggested the following US median nerve CSA cutoff values for diagnosing CTS: 14 mm2 at the carpal tunnel inlet, 11 mm2 at the center of the hook of the hamate and 13 mm2 at the carpal tunnel outlet. In the present study, we used US to measure median nerve CSA at these three points, and values in all patients were largest at the
Nerve conduction study of severe carpal tunnel syndrome d K. FUJIMOTO et al.
carpal tunnel inlet. Therefore, we used median nerve CSA at the carpal tunnel inlet to set cutoff values for determining CTS diagnostic severity. Researchers have reported that for patients who were evaluated as being in the ‘‘normal’’ stage of CTS using the Padua classification system, but who had findings of false-positive NCS records, the clinicians were able to correctly diagnose CTS using US to determine median nerve CSA (Mhoon et al. 2012; Koyuncuoglu et al. 2005; Rahmani et al. 2011). They confirmed that using the median nerve CSA value contributed to a higher rate of accurate CTS diagnoses. Researchers have also reported statistically significant correlations between median nerve CSA and severity of electrophysiologic abnormalities in patients categorized in the mild or moderate Padua stages of CTS (Altinok et al. 2004; Domanasiewicz et al. 2009; Mondelli et al. 2008; Nakamichi and Tachibana 2002). Some studies have reported a typical correlation between median nerve CSA and normal, mild or moderate levels of electrophysiologic abnormality in patients with CTS. A few reports have described a correlation between median nerve CSA and severe levels of electrophysiologic abnormality in persons with CTS (Azami et al. 2014; Karada g et al. 2010; Kasius et al. 2012). The present study sought to investigate the correlation between NCS and US findings and to assess the usefulness of median nerve CSA in cases of severe CTS, such as those with absence of SNAPs and CMAPs. We found that median nerve CSA significantly correlated with SCV. The mean median nerve CSA value in hands with absent SNAPs was 16.6 mm2. This value is comparable to those of previous studies (17.4 mm2 [Azami et al. 2014], 17.7 mm2 [Kasius et al. 2012], 16.3 mm2 [Rahmani et al. 2011]). The median nerve CSA cutoff value that discriminated between the values in groups S1 and S2 was 15 mm2. Ooi et al. (2014) reported a similar cutoff value of 14 mm2 between the moderate and severe stages of Padua’s classification system. We similarly found that median nerve CSA significantly correlated with motor nerve conduction velocity. In the absence of APB-CMAPs, the mean median nerve CSA value calculated in the present study was 18.4 mm2. The median nerve CSA cutoff value that discriminated between groups D1 and D2 was 18 mm2. To the best of our knowledge, this is the first report describing a cutoff value for median nerve CSA in the absence of APB-CMAPs. In addition, four patients in the present study had absent APB-CMAPs and 2L-CMAPs. Generally, 2L-CMAPs are relatively preserved in persons with CTS (Kaul and Pagel 2002; Nobuta et al. 2005; Sheean et al. 1995). However, Inukai et al. (2013) reported absent APB-CMAPs and 2L-CMAPs in 8 of 17 hands in patients
5
with severe CTS. Absence of 2L-CMAPs may be more common in CTS than previously thought. The mean median nerve CSA in group L was 20.0 6 1.2 mm2; we observed a significant difference in mean median nerve CSA values between group C, group L and other patients. We found that the most clinically effective US mean median nerve CSA cutoff value was 19 mm2. This finding will be very valuable in diagnosing severe CTS, which is difficult to evaluate quantitatively using NCS alone. We conclude that median nerve CSA is a very useful measurement for quantitatively evaluating severe CTS in the absence of SNAPs and CMAPs. In comparison with NCS, US measurement of median nerve CSA is simple and non-invasive, and high-resolution US is less susceptible to inter-laboratory differences (Webb and Padua 2009). The wrist-to-forearm ratio of median nerve CSA has been reported previously (Klauser et al. 2009). This method is very useful as it is not as heavily influenced by individual variance as the one-point measurement of median nerve CSA. However, we evaluated the onepoint median nerve CSA value at the wrist because it was less susceptible to inter-laboratory differences than was the wrist-to-forearm ratio (Webb and Padua 2009). For median nerve CSA values ,15 mm2 in the absence of SNAPs, we suggest that clinicians should consider the likely cause to be a lesion distal to the dorsal nerve root ganglion rather than CTS. These conditions may occur in cervical radiculopathy (in particular, radiculopathy of C6 or C7), brachial plexopathy, demyelinating disease, compression neuropathy proximal to the wrist, ischemic monomelic neuropathy, polyneuropathy (including diabetic mellitus and mononeuropathy multiplex) and infections (Lyme disease, tabes dorsalis, leprosy). If cases in which the median nerve CSA is ,18 mm2 in the absence of APB-CMAPs, and in cases involving absence of APB-CMAPs and 2L-CMAPs when the median nerve CSA is ,19 mm2, we suggest that the likely cause is a disorder proximal to the wrist, for example, brain lesion, cervical disc disease, spondylosis, stenosis, radiculopathy, spinal cord injury, brachial plexopathy, demyelinating disease, compression neuropathy proximal to the wrist, ischemic monomelic neuropathy, polyneuropathy (including diabetic mellitus and mononeuropathy multiplex) and infections (Lyme disease, tabes dorsalis, leprosy). This study had some limitations: The numbers of patients in the groups were small (particularly in group L), a single operator measured CSA, the US probe used was mainly vascular, and we did not evaluate surgical outcome because some patients could not be followed long term. Nevertheless, the study findings indicate that the use of NCS together with US is a very useful strategy for diagnosis of severe CTS.
6
Ultrasound in Medicine and Biology
CONCLUSIONS Median nerve CSA is a useful diagnostic measurement in diagnosing severe CTS, particularly when SNAPs or CMAPs are absent. In the absence of SNAPs, the cutoff value for median nerve CSA was 15 mm2. In the absence of APB-CMAPs, the cutoff value for median nerve CSA was 18 mm2. When median nerve CSA in severe CTS is ,15 mm2 in the absence of SNAPs or ,18 mm2 in the absence of APB-CMAPs, we suggest that clinicians investigate the presence of other disorders, such as radiculopathy, polyneuropathy and medial nerve disorders proximal to the wrist. REFERENCES Altinok T, Baysal O, Karakas HM, Sigirci A, Alkan A, Kayhan A, Yologlu S. Ultrasonographic assessment of mild and moderate idiopathic carpal tunnel syndrome. Clin Radiol 2004;59:916–925. Azami A, Maleki N, Anari H, Iranparvar Alamdari M, Kalantarhormozi M, Tavosi Z. The diagnostic value of ultrasound compared with nerve conduction velocity in carpal tunnel syndrome. Int J Rheum Dis 2014;17:612–620. Bland JD. A neurophysiological grading scale for carpal tunnel syndrome. Muscle Nerve 2000;23:1280–1283. Cartwright MS, Hobson-Webb LD, Boon AJ, Alter KE, Hunt CH, Flores VH, Werner RA, Shook SJ, Thomas TD, Primack SJ, Walker FO. Evidence-based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012; 46:287–293. Chen SH, Tsai TM. Ulnar tunnel syndrome. J Hand Surg Am 2014;39: 571–579. Domanasiewicz A, Koszewicz M, Jabtecki J. Comparison of the diagnostic values of ultrasonography and neurography in carpal tunnel syndrome. Neurol Neurochir Pol 2009;43:433–438. Graham B. The value added by electrodiagnostic testing in the diagnosis of carpal tunnel syndrome. J Bone Joint Surg Am 2008;90: 2587–2593. Inukai T, Uchida K, Kubota C, Takamura T, Nakajima H, Baba H. Second lumbrical–interossei nerve test predicts clinical severity and surgical outcome of carpal tunnel syndrome. J Clin Neurosci 2013;20: 1224–1227. Kanatani T, Fujioka H, Kurosaka M, Sumi M, Yamasaki K. Usefulness of distal motor latency measurement after palmar stimulation in advanced carpal tunnel syndrome. J Clin Neurophysiol 2012;29: 260–262. Karada g YS, Karada g O, Cic¸ekli E, Ozt€urk S, Kiraz S, Ozbakir S, Filippucci E, Grassi W. Severity of carpal tunnel syndrome assessed with high frequency ultrasonography. Rheumatol Int 2010;30: 761–765. Kasius KM, Claes F, Verhagen WI, Meulstee J. Ultrasonography in severe carpal tunnel syndrome. Muscle Nerve 2012;45:334–337. Kaul MP, Pagel KJ. Value of the lumbrical–interosseous technique in carpal tunnel syndrome. Am J Phys Med Rehabil 2002;81:691–695. Kaymak B, Ozc¸akar L, Cetin A, Candan Cetin M, Akinci A, Hasc¸elik Z. A comparison of the benefits of sonography and electrophysiologic measurements as predictors of symptom severity and functional status in patients with carpal tunnel syndrome. Arch Phys Med Rehabil 2008;89:743–748. Kim HS, Joo SH, Cho HK, Kim YW. Comparison of proximal and distal cross-sectional areas of the median nerve, carpal tunnel, and nerve/ tunnel index in subjects with carpal tunnel syndrome. Arch Phys Med Rehabil 2013;94:2151–2156.
Volume -, Number -, 2015 Kiylioglu N, Akyildiz UO, Ozkul A, Akyol A. Carpal tunnel syndrome and ulnar neuropathy at the wrist: Comorbid disease or not? J Clin Neurophysiol 2011;28:520–523. Klauser AS, Halpern EJ, De Zordo T, Feuchtner GM, Arora R, Gruber J, Martinoli C, L€oscher WN. Carpal tunnel syndrome assessment with US: Value of additional cross-sectional area measurements of the median nerve in patients versus healthy volunteers. Radiology 2009;250:171–177. Kotevoglu N, Saglam SG. Ultrasound imaging in the diagnosis of carpal tunnel syndrome and its relevance to clinical evaluation. Joint Bone Spine 2005;72:142–145. Koyuncuoglu HR, Kutluhan S, Yesildag A, Oyar O, Guler K, Ozden A. The value of ultrasonographic measurement in carpal tunnel syndrome in patients with negative electrodiagnostic tests. Eur J Radiol 2005;56:365–369. Mhoon JT, Juel VC, Hobson-Webb LD. Median nerve ultrasound as a screening tool in carpal tunnel syndrome: Correlation of cross sectional area measures with electrodiagnostic abnormality. Muscle Nerve 2012;46:871–878. Mondelli M, Filippou G, Gallo A, Frediani B. Diagnostic utility of ultrasonography versus nerve conduction studies in mild carpal tunnel syndrome. Arthritis Rheum 2008;59:357–366. Nakamichi K, Tachibana S. Enlarged median nerve in idiopathic carpal tunnel syndrome. Muscle Nerve 2000;23:1713–1718. Nakamichi K, Tachibana S. Ultrasonographic measurement of median nerve cross-sectional area in idiopathic carpal tunnel syndrome: Diagnostic accuracy. Muscle Nerve 2002;26:798–803. Nobuta S, Sato K, Komatsu T, Miyasaka Y, Hatori M. Clinical results in severe carpal tunnel syndrome and motor nerve conduction studies. J Orthop Sci 2005;10:22–26. Ooi CC, Wong SK, Tan AB, Chin AY, Abu Bakar R, Goh SY, Mohan PC, Yap RT, Png MA. Diagnostic criteria of carpal tunnel syndrome using high-resolution ultrasonography: Correlation with nerve conduction studies. Skeletal Radiol 2014;43:1387–1394. Ozben S, Acar H, Gunaydin S, Genc F, Ozer F, Ozben H. The second lumbrical–interosseous latency comparison in carpal tunnel syndrome. J Clin Neurophysiol 2012;29:263–267. Padua L, LoMonaco M, Gregori B, Valente EM, Padua R, Tonali P. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands. Acta Neurol Scand 1997; 96:211–217. Rahmani M, Ghasemi Esfe AR, Vaziri-Bozorg SM, Mazloumi M, Khalilzadeh O, Kahnouji H. The ultrasonographic correlates of carpal tunnel syndrome in patients with normal electrodiagnostic tests. Radiol Med 2011;116:489–496. Roll SC, Smith JC, Evans KD, Evans DE. Diagnostic accuracy of ultrasonography vs. electromyography in carpal tunnel syndrome: A systematic review of literature. Ultrasound Med Biol 2011;37: 1539–1553. Sarrıa L, Cabada T, Cozcolluela R, Martınez-Berganza T, Garcıa S. Carpal tunnel syndrome: Usefulness of sonography. Eur Radiol 2000; 10:1920–1925. Sheean GL, Houser MK, Murray MF. Lumbrical–interosseous latency comparison in the diagnosis of carpal tunnel syndrome. Electroencephalogr Clin Neurophysiol 1995;97:285–289. Stevens JC. AAEM Minimonograph #26: The electrodiagnosis of carpal tunnel syndrome. American Association of Electrodiagnostic Medicine. Muscle Nerve 1997;20:1477–1486. Tai TW, Wu CY, Su FC, Chern TC, Jou IM. Ultrasonography for diagnosing carpal tunnel syndrome: A meta-analysis of diagnostic test accuracy. Ultrasound Med Biol 2012;38:1121–1128. Webb LDH, Padua L. Median nerve ultrasonography in carpal tunnel syndrome: Findings from two laboratories. Muscle Nerve 2009; 40:94–97. Yemisci OU, Yalbuzdag SA, Cosar SN, Oztop P, Karatas M. Ulnar nerve conduction abnormalities in carpal tunnel syndrome. Muscle Nerve 2011;44:352–357.
http://dx.doi.org/10.1016/j.ultrasmedbio.2015.05.013
d
Original Contribution DIAGNOSIS OF SEVERE CARPAL TUNNEL SYNDROME USING NERVE CONDUCTION STUDY AND ULTRASONOGRAPHY KAZUHIRO FUJIMOTO,* TSUKASA KANCHIKU,* KENJI KIDO,y YASUAKI IMAJO,* MASAHIRO FUNABA,* and TOSHIHIKO TAGUCHI* * Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; and y Department of Orthopaedic Surgery, Ehime Rosai Hospital, Niihama, Ehime, Japan (Received 16 December 2014; revised 14 May 2015; in final form 16 May 2015)
Abstract—This study investigated the correlation between nerve conduction study and ultrasonographic findings for assessment of the usefulness of ultrasonography in determining carpal tunnel syndrome severity. Hands of adults with carpal tunnel syndrome were assessed using ultrasound and nerve conduction studies and grouped according to median nerve cross-sectional area (CSA). There were significant differences (p , 0.01) in mean median nerve CSA between controls, patients with median sensory nerve conduction velocity #40 m/s and patients with absent sensory nerve action potential and between controls, patients with median nerve distal motor latency $4.5 ms and patients with absent compound muscle action potentials of the abductor pollicis brevis. This is the first report to define median nerve CSA cutoff values (18 mm2) for determining carpal tunnel syndrome severity in patients with absent compound muscle action potentials of the abductor pollicis brevis. Median nerve CSA values below the cutoff values should prompt clinicians to consider other disorders, such as cervical compressive myelopathy. (E-mail: [email protected]) Ó 2015 World Federation for Ultrasound in Medicine & Biology. Key Words: Carpal tunnel syndrome, Nerve conduction study, Ultrasonography, Median nerve, Cross-sectional area.
INTRODUCTION
quantitatively evaluate CTS severity using NCS. Some authors report that ulnar nerve distal motor latency (DML) and distal sensory latency can be significantly longer in patients with CTS than in controls (Chen and Tsai 2014; Kiylioglu et al. 2011; Yemisci et al. 2011). In cases of combined CTS and ulnar tunnel syndrome, CTS diagnosis using the 2 L-INT test may also be difficult. Measuring median nerve DML after palmar stimulation is very useful in diagnosing severe CTS (Kanatani et al. 2012). However, as the severity of the chronic nerve compression injury increases over time, axonal damage ensues and leads to the absence of DML, as well as the absence of sensory nerve conduction velocity (SCV), in later stages. In addition, in severe CTS, palmar stimulation may trigger adductor pollicis CMAPs or flexor pollicis brevis CMAPs by stimulating the deep branch of the ulnar nerve; therefore, palmar stimulation is inappropriate for routine testing. Ultrasonography (US) has recently been found to be useful for CTS diagnosis. This method enables accurate measurement of the median nerve cross-sectional area (CSA) in all patients with CTS, which reportedly ranges
Carpal tunnel syndrome (CTS) is the most common form of entrapment neuropathy. Diagnosis is currently based on the characteristic clinical symptoms of CTS and supported by nerve conduction study (NCS) findings. Some researchers, for example, Bland (2000), Padua et al. (1997) and Stevens (1997), have reported electrophysiologic classification systems for CTS; these classification systems typically grade the relative absence of sensory nerve action potentials (SNAPs) or compound muscle action potentials (CMAPs). CTS severity is difficult to quantify in the absence of SNAPs or abductor pollicis brevis (APB)-CMAPs. In these cases, clinicians perform a second lumbrical–interosseous latency comparison (2 L-INT) test (Kaul and Pagel 2002; Nobuta et al. 2005; Sheean et al. 1995). However, in the absence of 2 L-CMAPs (Inukai et al. 2013; Ozben et al. 2012), it is very difficult to
Address correspondence to: Kazuhiro Fujimoto, 1-1-1 Minami Kogushi, Ube City, Yamaguchi 755-8505, Japan. E-mail: kafuji@ yamaguchi-u.ac.jp 1
2
Ultrasound in Medicine and Biology
from 13 to 15 mm2 (Kaymak et al. 2008; Kim et al. 2013; Kotevoglu and Saglam 2005; Sarrıa et al. 2000). The aim of the present study was to investigate the correlation between NCS and US findings for assessing the usefulness of US in determining CTS severity. METHODS We selected patients with CTS who were diagnosed on the basis of characteristic clinical symptoms and NCS findings (group P). We then chose a group of age-matched controls (group C). Details on these groups are provided in Table 1. Patients with history of diabetes mellitus, extracorporeal dialysis, other peripheral nerve disorders and cervical spine operations were excluded. Fifty-three adults diagnosed as having CTS (81 hands) and 67 volunteers (67 unaffected hands) were studied. Among the patients diagnosed with CTS, there were16 men and 65 women, aged 34–86 y (mean 5 65 y). Of the 81 affected hands, 51 underwent CTS surgery. The other 30 were treated by splinting or local corticosteroid injections. All study participants provided informed consent, and the study design was approved by an ethics review board of Ehime Rosai Hospital. Criteria of clinical features Clinical examination consisted of rating each subject according to the following criteria: (i) history of nocturnal paresthesia and hand pain; (ii) sensory disturbance in the median nerve distribution area in the hand; (iii) weakness or atrophy of thenar muscles innervated by the median nerve; (iv) Tinel sign at the carpal tunnel; and (v) positive Phalen test, in which the wrist is flexed for 1 min, and the patient is asked to report whether their usual symptoms occur. Electrophysiologic investigation During the testing, an infrared lamp was used to maintain each subject’s hand surface temperature at .32 C. One neurologist performed the NCSs on all patients using the Nicolet Viking IV NCS system (Nicolet, Madison, WI, USA). All patients underwent the following examinations: (i) median SCV, lengths from index finger to wrist of 100– 140 mm; (ii) median DML, length from wrist to APB of Table 1. Patients with carpal tunnel syndrome (group P) and age-matched controls (group C) Sex Group Hands P C
81 67
Age (y) 65 (34–86) 62 (40–82)
Treatment
Male Female Operation Conservative 16 9
65 58
51 -
30 -
Volume -, Number -, 2015
70 mm; (iii) 2 L-INT test, lengths from wrist to 2L or INT of 100 mm. We classified CTS severity using the following NCS measurements: Group S1 comprised hands with median SCVs #40 m/s; group S2, hands with absent SNAPs; group D1, hands with median DMLs $4.5 ms; and group D2, hands with absent APB-CMAPs. The 2L-INT test was performed on all patients. We further grouped patients with absent SNAPs, APB-CMAPs and 2L-CMAPs into group L. Ultrasound examination Ultrasound examination of the median nerve at the wrist was performed on the same day as the NCS by an orthopedist who was blinded to the NCS results and had 3 y of experience with musculoskeletal US examinations. The US examination was performed using a 4.8- to 11MHz linear-array transducer (Aplio 300, Toshiba Medical Systems, Tochigi, Japan). All wrists were examined in the neural position with palm up and finger semiextended. Transverse images that measured the median nerve CSA at the carpal tunnel inlet at the level of scaphoid-pisiform were recorded (Fig. 1). The median nerve CSA was measured using the direct tracing method. Statistical analysis Correlations between median nerve CSA and SCV within groups C and S1, as well as between median nerve CSA and DML within groups C and D1, were assessed using the Pearson (r) correlation coefficient. One-way analysis of variance was used to assess correlations between patients in groups C, S1 and S2; between patients in groups C, D1 and D2; and between patients in groups C, L and all other patients. The cutoff values of median nerve CSA used to differentiate between groups C and P, groups S1 and S2, groups D1 and D2 and Group L and all other patients were determined by calculating the receiver operating characteristic curve. The optimal cutoff values of median nerve CSA were defined as the values that allow discrimination between groups with the highest sensitivity and specificity. All p values , 0.05 were regarded as indicating statistical significance. RESULTS As outlined in Table 2, 42 hands were diagnosed with CTS in group S1, 39 in group S2, 68 in group D1 and 13 in group D2. The percentages of patients who received surgical treatment were 43% in group S1, 85% in group S2, 57% in group D1 and 92% in group D2. Median nerve CSAs (mean 6 standard deviation) determined with US were 9.3 6 1.8 mm2 for group C; 15.0 6 2.5 mm2 for group P; 13.6 6 2.0 mm2 for group S1; 16.6 6 1.9 mm2 for group S2; 14.4 6 2.0 mm2 for
Nerve conduction study of severe carpal tunnel syndrome d K. FUJIMOTO et al.
3
Fig. 1. Ultrasonographic images of (1) normal and (2) pathologic median nerve cross-sectional area. A 5 measurement A; P 5 pisiform bone; S 5 scaphoid bone.
group D1; and 18.4 6 1.6 mm2 for group D2. We observed significant differences in mean median nerve CSA between groups C, S1 and S2 (R2 5 0.64, p , 0.01) (Fig. 2) as well as between groups C, D1 and D2 (R2 5 0.61, p , 0.01) (Fig. 3). In addition, median nerve CSA significantly correlated with SCV (p , 0.01) (Fig. 4) and DML (p , 0.01) (Fig. 5). In determining the median nerve CSA cutoff values for differentiating between groups C and P, between
groups S1 and S2 and between groups D1 and D2, the areas under the receiver operating characteristic curve for the median nerve CSA (Az) were 0.970, 0.868 and 0.940, respectively. US measurement of CSA had high
Table 2. Electrophysiologic classification* Group P
S1
S2
D1 D2
42 0 42
26 13 39
68 13 81
* Group S1 5 hands with median sensory nerve conduction velocity #40 m/s; group S2 5 hands with absent sensory nerve action potential; group D1 5 hands with median distal motor latency $4.5 ms; group D2 5 hands with absent abductor pollicis brevis compound muscle action potentials.
Fig. 2. Mean median nerve cross-sectional area (CSA) in groups C, S1 and S2.
4
Ultrasound in Medicine and Biology
Fig. 3. Mean median nerve cross-sectional area (CSA) in groups C, D1 and D2.
sensitivity and specificity in diagnosing CTS severity. The most clinically effective US cutoff values for median nerve CSA were 13 mm2 (sensitivity 5 86%, specificity 5 97%) between groups C and P, 15 mm2 (sensitivity 5 90%, specificity 5 71%) between groups S1 and S2 and 18 mm2 (sensitivity 5 85%, specificity 5 94%) between groups D1 and D2. In 4 hands in 4 patients, there was a complete absence of 2L-CMAPs in this study. In group L, the mean CSA was 20.0 6 1.2 mm2 which significantly differed from the CSAs for group C, group L and other patients (p , 0.01). The most clinically effective median nerve cutoff value between group L and all other patients was 19 mm2 (sensitivity 5 100%, specificity 5 89%), with an Az of 0.994. DISCUSSION At present, CTS diagnosis is generally based on characteristic clinical symptoms supported by NCS findings. Characteristic clinical symptoms include history of
Fig. 4. Correlation between median nerve cross-sectional area (CSA) and sensory nerve conduction velocity (SCV). Circles 5 group S1; squares 5 group C.
Volume -, Number -, 2015
Fig. 5. Correlation between median nerve cross-sectional area (CSA) and distal motor latency (DML). Circles 5 group D1; squares 5 group C.
nocturnal paresthesia and hand pain, sensory disturbance in the median nerve distribution area in the hand, weakness or atrophy of thenar muscles innervated by the of median nerve, Tinel sign at the carpal tunnel and positive Phalen test. Graham (2008) reported that CTS-6, a validated clinical diagnostic aid used to estimate the probability of CTS on the basis of the presence or absence of six clinical findings recorded as part of the history or noted on physical examination. A nerve conduction study is required for quantitatively evaluating the severity of the functional nerve disorder in CTS. Some earlier reports also described an electrophysiologic classification approach to classification of CTS functional severity. For example, the classification of Padua et al. (1997) uses a six-point scale: 1 5 no CTS (normal NCS and no electrophysiologic evidence of CTS); 2 5 minimal (abnormal comparative tests); 3 5 mild (delayed median SCV but normal median DML); 4 5 moderate (delayed median SCV and prolonged median DML); 5 5 severe (absence of median SNAPs and prolonged median DML); and 6 5 extremely severe (absence of median SNAPs and APB-CMAPs). It is difficult to quantitatively evaluate severe or extreme stages of CTS. Ultrasound has been widely accepted as also useful for CTS diagnosis (Cartwright et al. 2012; Roll et al. 2011; Tai et al. 2012), particularly for determining median nerve CSA (Kaymak et al. 2008; Kim et al. 2013; Kotevoglu and Saglam 2005; Sarrıa et al. 2000). Nakamichi and Tachibana (2000) reported that median nerve enlargement was due to compressive lesions. They suggested the following US median nerve CSA cutoff values for diagnosing CTS: 14 mm2 at the carpal tunnel inlet, 11 mm2 at the center of the hook of the hamate and 13 mm2 at the carpal tunnel outlet. In the present study, we used US to measure median nerve CSA at these three points, and values in all patients were largest at the
Nerve conduction study of severe carpal tunnel syndrome d K. FUJIMOTO et al.
carpal tunnel inlet. Therefore, we used median nerve CSA at the carpal tunnel inlet to set cutoff values for determining CTS diagnostic severity. Researchers have reported that for patients who were evaluated as being in the ‘‘normal’’ stage of CTS using the Padua classification system, but who had findings of false-positive NCS records, the clinicians were able to correctly diagnose CTS using US to determine median nerve CSA (Mhoon et al. 2012; Koyuncuoglu et al. 2005; Rahmani et al. 2011). They confirmed that using the median nerve CSA value contributed to a higher rate of accurate CTS diagnoses. Researchers have also reported statistically significant correlations between median nerve CSA and severity of electrophysiologic abnormalities in patients categorized in the mild or moderate Padua stages of CTS (Altinok et al. 2004; Domanasiewicz et al. 2009; Mondelli et al. 2008; Nakamichi and Tachibana 2002). Some studies have reported a typical correlation between median nerve CSA and normal, mild or moderate levels of electrophysiologic abnormality in patients with CTS. A few reports have described a correlation between median nerve CSA and severe levels of electrophysiologic abnormality in persons with CTS (Azami et al. 2014; Karada g et al. 2010; Kasius et al. 2012). The present study sought to investigate the correlation between NCS and US findings and to assess the usefulness of median nerve CSA in cases of severe CTS, such as those with absence of SNAPs and CMAPs. We found that median nerve CSA significantly correlated with SCV. The mean median nerve CSA value in hands with absent SNAPs was 16.6 mm2. This value is comparable to those of previous studies (17.4 mm2 [Azami et al. 2014], 17.7 mm2 [Kasius et al. 2012], 16.3 mm2 [Rahmani et al. 2011]). The median nerve CSA cutoff value that discriminated between the values in groups S1 and S2 was 15 mm2. Ooi et al. (2014) reported a similar cutoff value of 14 mm2 between the moderate and severe stages of Padua’s classification system. We similarly found that median nerve CSA significantly correlated with motor nerve conduction velocity. In the absence of APB-CMAPs, the mean median nerve CSA value calculated in the present study was 18.4 mm2. The median nerve CSA cutoff value that discriminated between groups D1 and D2 was 18 mm2. To the best of our knowledge, this is the first report describing a cutoff value for median nerve CSA in the absence of APB-CMAPs. In addition, four patients in the present study had absent APB-CMAPs and 2L-CMAPs. Generally, 2L-CMAPs are relatively preserved in persons with CTS (Kaul and Pagel 2002; Nobuta et al. 2005; Sheean et al. 1995). However, Inukai et al. (2013) reported absent APB-CMAPs and 2L-CMAPs in 8 of 17 hands in patients
5
with severe CTS. Absence of 2L-CMAPs may be more common in CTS than previously thought. The mean median nerve CSA in group L was 20.0 6 1.2 mm2; we observed a significant difference in mean median nerve CSA values between group C, group L and other patients. We found that the most clinically effective US mean median nerve CSA cutoff value was 19 mm2. This finding will be very valuable in diagnosing severe CTS, which is difficult to evaluate quantitatively using NCS alone. We conclude that median nerve CSA is a very useful measurement for quantitatively evaluating severe CTS in the absence of SNAPs and CMAPs. In comparison with NCS, US measurement of median nerve CSA is simple and non-invasive, and high-resolution US is less susceptible to inter-laboratory differences (Webb and Padua 2009). The wrist-to-forearm ratio of median nerve CSA has been reported previously (Klauser et al. 2009). This method is very useful as it is not as heavily influenced by individual variance as the one-point measurement of median nerve CSA. However, we evaluated the onepoint median nerve CSA value at the wrist because it was less susceptible to inter-laboratory differences than was the wrist-to-forearm ratio (Webb and Padua 2009). For median nerve CSA values ,15 mm2 in the absence of SNAPs, we suggest that clinicians should consider the likely cause to be a lesion distal to the dorsal nerve root ganglion rather than CTS. These conditions may occur in cervical radiculopathy (in particular, radiculopathy of C6 or C7), brachial plexopathy, demyelinating disease, compression neuropathy proximal to the wrist, ischemic monomelic neuropathy, polyneuropathy (including diabetic mellitus and mononeuropathy multiplex) and infections (Lyme disease, tabes dorsalis, leprosy). If cases in which the median nerve CSA is ,18 mm2 in the absence of APB-CMAPs, and in cases involving absence of APB-CMAPs and 2L-CMAPs when the median nerve CSA is ,19 mm2, we suggest that the likely cause is a disorder proximal to the wrist, for example, brain lesion, cervical disc disease, spondylosis, stenosis, radiculopathy, spinal cord injury, brachial plexopathy, demyelinating disease, compression neuropathy proximal to the wrist, ischemic monomelic neuropathy, polyneuropathy (including diabetic mellitus and mononeuropathy multiplex) and infections (Lyme disease, tabes dorsalis, leprosy). This study had some limitations: The numbers of patients in the groups were small (particularly in group L), a single operator measured CSA, the US probe used was mainly vascular, and we did not evaluate surgical outcome because some patients could not be followed long term. Nevertheless, the study findings indicate that the use of NCS together with US is a very useful strategy for diagnosis of severe CTS.
6
Ultrasound in Medicine and Biology
CONCLUSIONS Median nerve CSA is a useful diagnostic measurement in diagnosing severe CTS, particularly when SNAPs or CMAPs are absent. In the absence of SNAPs, the cutoff value for median nerve CSA was 15 mm2. In the absence of APB-CMAPs, the cutoff value for median nerve CSA was 18 mm2. When median nerve CSA in severe CTS is ,15 mm2 in the absence of SNAPs or ,18 mm2 in the absence of APB-CMAPs, we suggest that clinicians investigate the presence of other disorders, such as radiculopathy, polyneuropathy and medial nerve disorders proximal to the wrist. REFERENCES Altinok T, Baysal O, Karakas HM, Sigirci A, Alkan A, Kayhan A, Yologlu S. Ultrasonographic assessment of mild and moderate idiopathic carpal tunnel syndrome. Clin Radiol 2004;59:916–925. Azami A, Maleki N, Anari H, Iranparvar Alamdari M, Kalantarhormozi M, Tavosi Z. The diagnostic value of ultrasound compared with nerve conduction velocity in carpal tunnel syndrome. Int J Rheum Dis 2014;17:612–620. Bland JD. A neurophysiological grading scale for carpal tunnel syndrome. Muscle Nerve 2000;23:1280–1283. Cartwright MS, Hobson-Webb LD, Boon AJ, Alter KE, Hunt CH, Flores VH, Werner RA, Shook SJ, Thomas TD, Primack SJ, Walker FO. Evidence-based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012; 46:287–293. Chen SH, Tsai TM. Ulnar tunnel syndrome. J Hand Surg Am 2014;39: 571–579. Domanasiewicz A, Koszewicz M, Jabtecki J. Comparison of the diagnostic values of ultrasonography and neurography in carpal tunnel syndrome. Neurol Neurochir Pol 2009;43:433–438. Graham B. The value added by electrodiagnostic testing in the diagnosis of carpal tunnel syndrome. J Bone Joint Surg Am 2008;90: 2587–2593. Inukai T, Uchida K, Kubota C, Takamura T, Nakajima H, Baba H. Second lumbrical–interossei nerve test predicts clinical severity and surgical outcome of carpal tunnel syndrome. J Clin Neurosci 2013;20: 1224–1227. Kanatani T, Fujioka H, Kurosaka M, Sumi M, Yamasaki K. Usefulness of distal motor latency measurement after palmar stimulation in advanced carpal tunnel syndrome. J Clin Neurophysiol 2012;29: 260–262. Karada g YS, Karada g O, Cic¸ekli E, Ozt€urk S, Kiraz S, Ozbakir S, Filippucci E, Grassi W. Severity of carpal tunnel syndrome assessed with high frequency ultrasonography. Rheumatol Int 2010;30: 761–765. Kasius KM, Claes F, Verhagen WI, Meulstee J. Ultrasonography in severe carpal tunnel syndrome. Muscle Nerve 2012;45:334–337. Kaul MP, Pagel KJ. Value of the lumbrical–interosseous technique in carpal tunnel syndrome. Am J Phys Med Rehabil 2002;81:691–695. Kaymak B, Ozc¸akar L, Cetin A, Candan Cetin M, Akinci A, Hasc¸elik Z. A comparison of the benefits of sonography and electrophysiologic measurements as predictors of symptom severity and functional status in patients with carpal tunnel syndrome. Arch Phys Med Rehabil 2008;89:743–748. Kim HS, Joo SH, Cho HK, Kim YW. Comparison of proximal and distal cross-sectional areas of the median nerve, carpal tunnel, and nerve/ tunnel index in subjects with carpal tunnel syndrome. Arch Phys Med Rehabil 2013;94:2151–2156.
Volume -, Number -, 2015 Kiylioglu N, Akyildiz UO, Ozkul A, Akyol A. Carpal tunnel syndrome and ulnar neuropathy at the wrist: Comorbid disease or not? J Clin Neurophysiol 2011;28:520–523. Klauser AS, Halpern EJ, De Zordo T, Feuchtner GM, Arora R, Gruber J, Martinoli C, L€oscher WN. Carpal tunnel syndrome assessment with US: Value of additional cross-sectional area measurements of the median nerve in patients versus healthy volunteers. Radiology 2009;250:171–177. Kotevoglu N, Saglam SG. Ultrasound imaging in the diagnosis of carpal tunnel syndrome and its relevance to clinical evaluation. Joint Bone Spine 2005;72:142–145. Koyuncuoglu HR, Kutluhan S, Yesildag A, Oyar O, Guler K, Ozden A. The value of ultrasonographic measurement in carpal tunnel syndrome in patients with negative electrodiagnostic tests. Eur J Radiol 2005;56:365–369. Mhoon JT, Juel VC, Hobson-Webb LD. Median nerve ultrasound as a screening tool in carpal tunnel syndrome: Correlation of cross sectional area measures with electrodiagnostic abnormality. Muscle Nerve 2012;46:871–878. Mondelli M, Filippou G, Gallo A, Frediani B. Diagnostic utility of ultrasonography versus nerve conduction studies in mild carpal tunnel syndrome. Arthritis Rheum 2008;59:357–366. Nakamichi K, Tachibana S. Enlarged median nerve in idiopathic carpal tunnel syndrome. Muscle Nerve 2000;23:1713–1718. Nakamichi K, Tachibana S. Ultrasonographic measurement of median nerve cross-sectional area in idiopathic carpal tunnel syndrome: Diagnostic accuracy. Muscle Nerve 2002;26:798–803. Nobuta S, Sato K, Komatsu T, Miyasaka Y, Hatori M. Clinical results in severe carpal tunnel syndrome and motor nerve conduction studies. J Orthop Sci 2005;10:22–26. Ooi CC, Wong SK, Tan AB, Chin AY, Abu Bakar R, Goh SY, Mohan PC, Yap RT, Png MA. Diagnostic criteria of carpal tunnel syndrome using high-resolution ultrasonography: Correlation with nerve conduction studies. Skeletal Radiol 2014;43:1387–1394. Ozben S, Acar H, Gunaydin S, Genc F, Ozer F, Ozben H. The second lumbrical–interosseous latency comparison in carpal tunnel syndrome. J Clin Neurophysiol 2012;29:263–267. Padua L, LoMonaco M, Gregori B, Valente EM, Padua R, Tonali P. Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands. Acta Neurol Scand 1997; 96:211–217. Rahmani M, Ghasemi Esfe AR, Vaziri-Bozorg SM, Mazloumi M, Khalilzadeh O, Kahnouji H. The ultrasonographic correlates of carpal tunnel syndrome in patients with normal electrodiagnostic tests. Radiol Med 2011;116:489–496. Roll SC, Smith JC, Evans KD, Evans DE. Diagnostic accuracy of ultrasonography vs. electromyography in carpal tunnel syndrome: A systematic review of literature. Ultrasound Med Biol 2011;37: 1539–1553. Sarrıa L, Cabada T, Cozcolluela R, Martınez-Berganza T, Garcıa S. Carpal tunnel syndrome: Usefulness of sonography. Eur Radiol 2000; 10:1920–1925. Sheean GL, Houser MK, Murray MF. Lumbrical–interosseous latency comparison in the diagnosis of carpal tunnel syndrome. Electroencephalogr Clin Neurophysiol 1995;97:285–289. Stevens JC. AAEM Minimonograph #26: The electrodiagnosis of carpal tunnel syndrome. American Association of Electrodiagnostic Medicine. Muscle Nerve 1997;20:1477–1486. Tai TW, Wu CY, Su FC, Chern TC, Jou IM. Ultrasonography for diagnosing carpal tunnel syndrome: A meta-analysis of diagnostic test accuracy. Ultrasound Med Biol 2012;38:1121–1128. Webb LDH, Padua L. Median nerve ultrasonography in carpal tunnel syndrome: Findings from two laboratories. Muscle Nerve 2009; 40:94–97. Yemisci OU, Yalbuzdag SA, Cosar SN, Oztop P, Karatas M. Ulnar nerve conduction abnormalities in carpal tunnel syndrome. Muscle Nerve 2011;44:352–357.
