CME Objectives: After completion of this article, the reader should be able to A) report the increased incidence of carpal tunnel syndrome in patients with diabetes, B) understand the ultrasonographic findings of carpal tunnel syndrome in diabetic patients with and without peripheral neuropathy, and C) describe the relationship between ultrasonographic and electrophysiologic findings in diabetic patients with carpal tunnel syndrome and in diabetic patients with carpal tunnel syndrome and peripheral neuropathy. Level: Advanced Accreditation: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)i. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Carpal Tunnel Syndrome
CME ARTICLE
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2014 SERIES
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NUMBER 6
Sonography of the Median Nerve in Carpal Tunnel Syndrome with Diabetic Neuropathy ABSTRACT Kim L-N, Kwon H-K, Moon H-I, Pyun S-B, Lee H-J: Sonography of the median nerve in carpal tunnel syndrome with diabetic neuropathy. Am J Phys Med Rehabil 2014;93:897Y907.
Authors:
Objective: The aim of this study was to determine the criteria for ultrasonographic
Li-Na Kim, MD Hee-Kyu Kwon, MD, PhD Hyun-Im Moon, MD Sung-Bum Pyun, MD, PhD Hang-Jae Lee, MD
measurement of the cross-sectional area (CSA) of the median nerve and differential diagnosis of patients with carpal tunnel syndrome (CTS) with or without diabetic polyneuropathy (DPN).
Affiliations: From the Department of Physical Medicine & Rehabilitation, Sahmyook Medical Center, Seoul, Republic of Korea (L-NK); Department of Physical Medicine & Rehabilitation, College of Medicine, Korea University, Seoul, Republic of Korea (H-KK, H-IM, S-BP); and Department of Physical Medicine & Rehabilitation, College of Medicine, Bundang CHA Medical Center, Sungnam City, Gyeonggi Province, Republic of Korea (H-JL).
Correspondence: All correspondence and requests for reprints should be addressed to: Hee-Kyu Kwon, MD, PhD, Department of Physical Medicine & Rehabilitation, College of Medicine, Korea University, 73, Inchon-ro, Seongbuk-gu, Seoul 136-705, Republic of Korea.
Design: One hundred eighty-seven patients were divided into five groups: healthy controls, CTS, diabetes with CTS but without DPN, DPN only, and both DPN and CTS. The CSAs of the median nerve were measured at four levels, and cutoff values to diagnose CTS with DPN were obtained.
Results: All the CSAs were larger in the DPN group compared with those in the control group. The CSAs of the median nerve at the wrist revealed no significant differences among the groups with CTS; however, these groups demonstrated larger CSAs at the wrist and a higher wrist/forearm ratio compared with the DPN only group. The cutoff value for the CSA at the wrist that yielded the highest sensitivity and specificity was 11.6 mm.
Conclusions: The CSA of the median nerve at the wrist and the wrist/forearm ratio could be useful for diagnosing the comorbidity of CTS with DPN. Key Words: Carpal Tunnel Syndrome, Diabetic Polyneuropathy, Ultrasonography, Median Nerve
Disclosures: Supported by Korea University Grant. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. 0894-9115/14/9310-0897 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000084
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T
he incidence of diabetes is steadily increasing, and it is estimated that 35%Y45% of diabetic patients have diabetic symmetric polyneuropathy.1 Patients with diabetic neuropathy show characteristic symptoms, and the condition is usually confirmed on the basis of a nerve conduction study (NCS).1 Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, results from compression of the median nerve as it passes through the carpal tunnel. CTS is usually diagnosed on the basis of clinical symptoms and confirmed with an NCS.2 Patients with DPN are known to show a higher incidence of CTS.3 In one study, the prevalence of clinical CTS was 2% in the reference population, 14% in diabetic patients without DPN, and 30% in those with DPN.4 Kim et al.5 reported that 6.8% of diabetic patients had asymptomatic electrophysiologic CTS and postulated that asymptomatic CTS is related to the vulnerability of the peripheral nerve at entrapment sites, rather than early DPN. Because symptoms of DPN may mimic those of CTS, confirming a clinical diagnosis of CTS in patients with DPN is difficult. Although NCSs are highly specific for the diagnosis of DPN and CTS, it can be difficult to differentiate the conditions in certain patients, especially in those with advanced DPN. Because CTS and DPN may produce similar abnormalities with respect to median nerve conduction, using diagnostic criteria based on a standard NCS may lead to false-positive or false-negative results.6,7
In recent years, the accuracy of highresolution diagnostic ultrasound (US) equipment has greatly improved, facilitating visualization of the minute details of the peripheral nerves.8,9 As a result, the number of studies on sonography for the diagnosis of entrapment neuropathies, including CTS, has been increasing, and a few reports on sonographic measurement of the peripheral nerves of patients with DPN are also available.1,2,10Y12 Buchberger et al.13 first described the sonographic features of CTS, which include the median nerve flattening ratio, cross-sectional area (CSA) of the median nerve at the carpal tunnel, and increased bowing of the flexor retinaculum. Wang et al.14 reported that the most consistent sonographic finding for CTS was a significant increase in the CSA at the level of the pisiform bone, which was equivalent to that of the carpal tunnel inlet. In the American Association of Neuromuscular and Electrodiagnostic Medicine guidelines for the US diagnosis of CTS, measurement of median nerve CSA at the wrist has been established as an accurate method and may be used as a diagnostic test for CTS.15 A recent study regarding US evaluation of the median nerve in diabetic patients reported that the CSA of the median nerve in the carpal tunnel of patients with DPN was greater than that in healthy individuals or patients without DPN.12 However, there has been no report comparing the US features of DPN and CTS. This study attempted to obtain criteria to diagnose the comorbidity of CTS with DPN by comparing the
FIGURE 1 Patient selection.
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TABLE 1 Patient characteristics
No. hands Age, yrs Men/women Duration of diabetes mellitus, yrs HbA1c, % BMI
Group 1
Group 2
Group 3
Group 4
Group 5
30 57.8 (7.8) 12/17 NA NA 22.9 (4.4)
63 57.7 (12.8) 0/63 NA NA 25.6 (4.4)
35 59.5 (14.0) 22/7 11.5 (9.0) 9.7 (3.0) 23.7 (5.4)
29 63.6 (12.3) 4/31 10.1 (7.4) 8.5 (1.9) 25.9 (3.4)
30 65.8 (10.4) 10/20 15.4 (11.9) 8.7 (2.3) 24.5 (4.3)
Values are mean (standard deviation). Group 1, healthy controls; group 2, patients with CTS only; group 3, patients with CTS and diabetes mellitus but without DPN; group 4, patients with DPN only; group 5, patients with CTS and DPN. BMI, body mass index; HbA1c, glycated hemoglobin; NA, not applicable.
US CSAs of median nerves in patients with CTS, DPN, and CTS with DPN.
study, and informed consent was provided by all participants.
METHODS
Electrophysiologic Evaluation
Participants
The electrophysiologic evaluation was performed using a Dantec Counterpoint Mk2 (Dantec, Copenhagen, Denmark) in all patients. The temperature of each hand was maintained at or greater than 32-C. For the diagnosis of diabetic polyneuropathy (DPN), motor and sensory conduction studies were carried out in unilateral upper and lower extremities. Motor conduction studies were performed in the median, ulnar, peroneal, and tibial nerves, and F waves were recorded for each nerve. Sensory nerve action potentials (SNAPs) were obtained from the median, ulnar, and sural nerves. H-reflex studies were also performed. Needle electromyography was carried out in three muscles in each extremity to reduce the patients’ discomfort. The muscles that were selected covered different myotomes and different peripheral innervations and were also proximally and distally located in order, thereby ruling out the possibility of a radiculopathy or an entrapment neuropathy other than CTS (e.g., biceps brachii, pronator teres, and first dorsal interossei). Diabetic neuropathy was diagnosed using criteria modified from the suggestions of the Diabetes Control and Complications Trial.16,17 For the diagnosis of CTS, the median compound muscle action potential (CMAP) was recorded over the abductor pollicis brevis muscle with median nerve stimulation 8 cm proximal to the active recording electrode. The onset latency and baseline-topeak amplitude were measured. The median SNAP was recorded antidromically with the bar electrode over the third digit, and median nerve stimulation was performed at two points, one 7 cm proximal to the recording electrode in the palm and the other 14 cm proximally at the wrist. CTS was diagnosed if
From June 2011 to January 2012, at Korea University Hospital, a prospective study was conducted in 30 healthy controls and 108 patients with symptoms of CTS, including numbness and tingling sensations in the lateral four fingers with or without thumb weakness, and 124 patients with type 2 diabetes mellitus who were referred for the evaluation of DPN with symptoms of numbness and tingling sensations in the hands and the feet. Patients with other causes of peripheral polyneuropathy, such as long-term alcohol intake or chronic kidney disease, were excluded. All subjects underwent an electrophysiologic study. Of the 108 patients with symptoms of CTS, 23 had normal findings, 22 were diagnosed with cervical radiculopathy, and 63 showed findings consistent with CTS. Of the 124 patients with type 2 diabetes mellitus, 30 had normal findings, 35 had findings consistent with CTS but without features of DPN, 29 were diagnosed with DPN, and 30 were diagnosed with both CTS and DPN. This prospective patients diagnosed with CTS, 35 diabetic patients with electrophysiologic evidence of CTS without DPN, 29 diabetic patients with DPN, and 30 diabetic patients with CTS and DPN (Fig. 1). All patients underwent a sonographic examination on the same day, after an electrophysiologic evaluation. On the basis of the electrophysiologic findings, a total of 187 patients were classified into five groups as follows: group 1, healthy controls; group 2, patients with CTS only; group 3, diabetic patients with CTS but without DPN; group 4, patients with DPN only; and group 5, patients with CTS and DPN. Detailed demographic data for the patients are shown in Table 1. Review board approval was obtained for this www.ajpmr.com
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FIGURE 2 US transverse scanning was performed at four different levels. The CSA of the median nerve was measured at the mid flexor retinaculum (A), distal wrist crease (B), 5 cm proximal to this level (C), and at the proximal third of the forearm (D). The ratio of B/C was also calculated.
the results of the NCS fulfilled three of the following criteria18,19: (1) median SNAP peak latency was greater than 3.7 milliseconds; (2) SNAP peak latency of the proximal 7-cm segment was greater than the peak latency of the distal 7-cm segment; (3) SNAP amplitude was less than 20 KV, including a conduction block with an SNAP amplitude drop of greater than 50% with respect to the wrist stimulation, as compared with that of the palm stimulation; (4) median CMAP distal latency was greater than 4.2 milliseconds; and (5) CMAP amplitude was less than 4.5 mV. CTS was diagnosed in patients with diabetic neuropathy if they met the following criteria: (1) the ratio of the distal motor latency of the median to the ulnar nerve was greater than 1.5; (2) the ratio of the distal sensory latency of the median to the ulnar nerve was greater than 1.2; (3) the amplitude ratio of the median SNAP to the ulnar SNAP was less than 0.6; and (4) the wrist-to-palm latency difference was greater than the palm-to-digit latency difference in the median sensory nerve.17 If the results of the NCS fulfilled two of the
four abovementioned criteria, the patients were diagnosed with diabetic neuropathy and CTS.
Ultrasonography US was performed using an HD15 Ultrasound Imaging System (Philips, Bothell, WA). The examiner was blinded to the results of the electrodiagnosis. The transducer was always kept perpendicular to the median nerve to avert anisotropy. No additional force other than the weight of the probe was applied, and the wrist was kept in a neutral position to avoid causing any artificial nerve deformity. The volar wrist crease and the pisiform bone were used as initial external reference points and landmarks during scanning. The median nerve was imaged in the axial plane at four points: the mid flexor retinaculum (level A), the proximal flexor retinaculum (distal wrist crease, level B), 5 cm proximal to the distal wrist crease (level C), and the proximal one-third of the forearm (level D) (Fig. 2). CSA measurements were performed at the inner border of the thin hyperechoic
TABLE 2 Median nerve CSA as detected with US (square millimeter) Group 1 Level Level Level Level Ratio
A B C D B/C
7.56 (1.48) 7.58 (1.25) 6.23 (0.89) 6.47 (0.77) 1.22 (0.18)
Group 2
Group 3 b
12.89 (5.21) 13.46 (6.12)b 7.16 (2.09) 7.06 (1.73) 1.82 (0.51)b
12.04 (3.49) 12.27 (3.24) 7.32 (1.98) 7.16 (1.93) 1.71 (0.37)
Group 4
Group 5 a
8.87 (3.02) 9.01 (3.01)a 7.10 (1.84)a 7.39 (1.62)a 1.27 (0.29)
11.77 (2.63)d 12.51 (2.96)d 8.41 (1.98)c,d 8.35 (1.74)c,d 1.55 (0.47)c,d
Values are mean (standard deviation). Group 1, healthy controls; group 2, patients with CTS only; group 3, patients with CTS and diabetes mellitus but without DPN; group 4, patients with DPN only; group 5, patients with CTS and DPN. a Group 1 vs. group 4 differences in CSA at A, B, C, and D were significant at P G 0.05. b Group 2 vs. group 4 differences in CSA at A, B, and ratio B/C were significant at P G 0.05. c Group 2 vs. group 5 differences in CSA at C, D, and ratio B/C were significant at P G 0.05. d Group 4 vs. group 5 differences in CSA at A, B, C, D, and ratio B/C were significant at P G 0.05.
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TABLE 3 Cutoff values for median nerve CSA for the diagnosis of CTS in patients with DPN Cutoff Value, mm2
Sensitivity
Specificity
Area Under the ROC Curve
10.5 11.6 1.28
70.0 73.3 73.3
76.2 90.5 71.4
0.775 0.863 0.735
Level A Level B Ratio B/C
ROC, receiver operating characteristic.
epineurial rim with a continuous tracing technique. The CSA ratio of the wrist to the forearm (B/C; wrist to forearm ratio [WFR]) was calculated.
Statistics The Statistical Package for the Social Sciences (version 12; Statistical Package for the Social Sciences Inc, Chicago, IL) and MedCalc (version 12.5) software packages were used for statistical analysis. Only one hand from each patient was used for analysis. The CSAs were compared among the groups using the Student’s t test. Because the CSAs of the median nerve were significantly different between groups 4 and 5, the cutoff values of those CSAs and WFR for the diagnosis of CTS with DPN were obtained by evaluating a receiver operating characteristic curve with the MedCalc program. The analyses also evaluated the correlations among CSA of the median nerve and the electrophysiologic parameters in groups 2, 3, and 5 that were diagnosed with CTS, regardless of the DPN status, using Pearson correlation coefficient.
(P 9 0.05). In comparisons between groups 2 and 5, there were no significant differences in the CSAs of the median nerve at levels A and B, but the corresponding values at levels C and D in group 2 were larger than those in group 5 (P G 0.05); the WFR was larger in group 2. The CSAs of the median nerve at all levels and the WFR were larger in group 5 than in group 4 (P G 0.05) (Table 2). In the assessments for comorbidities, the cutoff values for CSAs to differentiate DPN from CTS with DPN were 10.5 mm2 and 11.6 mm2 at levels A and B, respectively, and the WRF was 1.28. The sensitivities and specificities of these values are shown in Table 3. The cutoff values for CSA at level B showed the highest sensitivity and specificity. The electrophysiologic parameters in groups 2, 3, and 5, which had CTS, regardless of DPN status, revealed significant correlations of CSAs at levels A and B with the distal latency of the median CMAPs and the distal onset, peak latencies, and amplitudes of median SNAPs; further, the CSAs at levels B and C were weakly correlated with the forearm median motor conduction velocities (Table 4).
RESULTS The composition of the groups is listed in Figure 1. The sonographic and NCS results for the patients are shown in Table 2. The CSAs of the median nerve showed significant differences at all levels in comparisons between group 1 and group 4 (P G 0.05). In comparisons between group 2 and group 4, there were significant differences in the CSAs of the median nerve at levels A and B and in the WFR (P G 0.05). There were no significant differences between Groups 2 and 3 at any level
DISCUSSION In this study, the CSAs of the median nerve were larger in the patients with DPN compared with those of the healthy controls at every level. From a pathophysiologic perspective, the nerve swelling that accompanies the early phases of compression neuropathy has been partly correlated with intraneural edema.20 Because the increase in water content that accompanies nerve swelling seems to be correlated with a cascade of events that ultimately
TABLE 4 Pearson correlation coefficients between median NCS parameters and CSA
Level Level Level Level a b
SNAP Distal Latency (Onset)
SNAP Distal Latency (Peak)
SNAP Amplitude
CMAP Distal Latency
Forearm Motor Conduction Velocity
0.430b 0.520b 0.239b 0.199b
0.412b 0.516b 0.232b 0.214b
j0.169a j0.294b j0.205b j0.229b
0.430b 0.464b 0.279b 0.178b
j0.173a j0.228b j0.207b j0.077
A B C D
P G 0.05. P G 0.01.
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lead to axon loss,21 it is conceivable that the nerve CSA is positively correlated with the severity of the neurophysiologic findings.10 Pastare et al.2 reported the occurrence of increasing sonographic abnormalities as the neurophysiologic severity of the CTS increased. One of the putative mechanisms in the pathogenesis of diabetic neuropathy is increased polyol pathway activity leading to the accumulation of sorbitol and fructose.22Y24 Suzuki et al.25 reported that sorbitol itself, as well as a secondary accumulation of sodium caused by an increase in sorbitol, might be a major contributing factor for the increase in intracellular hydration in a hydrogen nuclear magnetic resonance study. There have been only a few reports regarding the sonographic findings in DPN. Watanabe et al.1 found increased CSAs and hypoechoic areas in the peripheral nerves of diabetic patients. In their study, the CSAs were negatively correlated with motor nerve conduction velocity and latency. Recently, Liu et al.26 reported an optimal CSA cutoff value for the sural nerve to diagnose diabetic cutaneous neuropathy using a 22-MHz US, suggesting its value in the evaluation of diabetic cutaneous nerve neuropathy. When Watanabe et al.12 compared the median nerve CSAs in the carpal tunnels of diabetic patients with DPN and patients without DPN, they found greater CSAs in patients with DPN. Although they excluded patients with symptoms of CTS, it was possible that patients with subclinical CTS were included in their study. Therefore, the results of their study might not have solely represented the sonographic features of DPN. In this study, all patients were electrophysiologically diagnosed, and sonographic measurements of median nerve CSAs were compared among healthy controls, patients with CTS only, diabetic patients with CTS but without DPN, patients with DPN only, and patients with CTS and DPN. Because patients with generalized forms of peripheral polyneuropathy might have diffuse enlargement along the entire lengths of the affected nerves, the CSAs of the median nerve at four different levels were measured to accurately characterize and differentiate DPN, CTS, and CTS with DPN. In one other study comparing median nerve CSAs among patients with CTS, diabetic patients with CTS, and diabetic patients with CTS and DPN, the nerve CSAs of the diabetic patients with CTS were found to be significantly higher. However, in comparison with CSA in diabetic patients with CTS, CSAs were significantly reduced at the wrist and in the carpal tunnel of diabetic patients with CTS and
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DPN.27 The authors explained that this peculiar finding might be partially related to the loss of the neuronal regenerative capacity in advanced DPN. In the present study, the CSAs of the median nerve were larger in the patients with DPN compared with those of the healthy controls at every level. Because there was no significant difference in the body mass indices among the groups, the results might not be affected by body mass index. In contrast, these findings indicated that the median nerve CSAs revealed diffuse swelling in the patients with DPN, which seems to be compatible with the pathophysiology of DPN. The CSAs of the median nerves at levels A and B were larger in the patients with CTS compared with those in the patients with DPN but did not show a difference among the patients with CTS only, the diabetic patients with CTS but without DPN, and the patients with CTS and DPN. The results demonstrated that the patients with CTS had larger CSAs, regardless of the presence of coexisting DPN, especially at levels A and B. This could be explained by the fact that the degree of edema was greater in the CTS patients than in the DPN patients at the entrapment site, the carpal tunnel. This was also supported by the finding that the WFR was greater in the patients with CTS only, as compared with that in the patients with both CTS and DPN. Moreover, the results that the patients with CTS and DPN demonstrated a smaller increase in WFR than the CTS only group, as well as larger CSAs at every level compared with those with DPN, could be explained by median nerve swelling at the entrapment site and possible retrograde degeneration. On the basis of the study results, the authors propose cutoff values for CSAs at levels A and B that could be used to diagnose coexisting CTS and DPN, which were 10.5 mm2 and 11.6 mm2, respectively. In comparison with the values used for the diagnosis of CTS in nondiabetic patients, 8.6 mm2 and 9.2 mm2, which were also obtained from the participants in this study, the abovementioned cutoff values are larger. The sensitivities and specificities of the cutoff CSA values for the diagnosis of coexisting CTS and DPN were 70.0% and 76.2%, respectively, at level A, and 73.3% and 90.0%, respectively, at level B; thus, the values were higher at level B. Regarding the evaluation of the correlation between the CSAs of the median nerve and the electrophysiologic parameters in groups 2, 3, and 5, which had CTS, significant correlations were found of CSAs at the mid flexor retinaculum and the wrist and the latency of median CMAPs and the latencies and amplitudes of the median SNAPs, and the CSAs at the wrist and forearm levels revealed a weak
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correlation to the forearm median motor conduction velocities. The limitations of this study included a small sample size in each group, a lack of correlation with the US and clinical findings, and a female predominance in the study population. This study demonstrated that the patients with DPN had diffuse nerve swelling, but the patients with CTS had swelling of the median nerve at the entrapment site (levels A and B), regardless of coexisting DPN. In addition, the CTS patients with DPN demonstrated larger CSAs not only at the entrapment site but also at levels proximal to the entrapment site as well as an increase in the WFR. The cutoff values for CSAs at level B and the increase in the WRF could facilitate US differential diagnosis for patients with DPN and patients with both CTS and DPN. REFERENCES 1. Watanabe T, Ito H, Sekine A, et al: Sonographic evaluation of the peripheral nerve in diabetic patients: The relationship between nerve conduction studies, echo intensity, and cross-sectional area. J Ultrasound Med 2010;29:697Y708 2. Pastare D, Therimadasamy AK, Lee E, et al: Sonography versus nerve conduction studies in patients referred with a clinical diagnosis of carpal tunnel syndrome. J Clin Ultrasound 2009;37:389Y93 3. Perkins BA, Olaleye D, Bril V: Carpal tunnel syndrome in patients with diabetic polyneuropathy. Diabetes Care 2002;25:565Y9 4. Wilbourn AJ: Diabetic entrapment and compression neuropathies, in TP DP (ed): Diabetic Neuropathy. Philadelphia, PA, Saunders, 1999, pp 481Y508
ratio in carpal tunnel syndrome. Clin Neurophysiol 2008;119:1353Y7 12. Watanabe T, Ito H, Morita A, et al: Sonographic evaluation of the median nerve in diabetic patients: Comparison with nerve conduction studies. J Ultrasound Med 2009;28:727Y34 13. Buchberger W, Judmaier W, Birbamer G, et al: Carpal tunnel syndrome: Diagnosis with high-resolution sonography. AJR Am J Roentgenol 1992;159:793Y8 14. Wang LY, Leong CP, Huang YC, et al: Best diagnostic criterion in high-resolution ultrasonography for carpal tunnel syndrome. Chang Gung Med J 2008; 31:469Y76 15. Cartwright MS, Hobson-Webb LD, Boon AJ, et al: Evidence-based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012;46:287Y93 16. Dyck PJ, Thomas PK: Diabetic Neuropathy, ed 2. Philadelphia, PA, WB Saunders, 1999 17. Kwon HK, Kim LN, Park YK, et al: Frequency of carpal tunnel syndrome according to the severity of diabetic neuropathy. J Korean Acad Rehabil Med 2005;29:272Y5 18. Lee HJ, Kwon KH: Electrodiagnostic classification of severity of carpal tunnel syndrome. J Korean Assoc EMG Electrodiagn Med 2004;6:1Y3 19. Kwon HK, Hwang M, Yoon DW: Frequency and severity of carpal tunnel syndrome according to level of cervical radiculopathy: Double crush syndrome? Clin Neurophysiol 2006;117:1256Y9 20. Sugimoto H, Miyaji N, Ohsawa T: Carpal tunnel syndrome: Evaluation of median nerve circulation with dynamic contrast-enhanced MR imaging. Radiology 1994;190:459Y66 21. Powell HC, Myers RR: Pathology of experimental nerve compression. Lab Invest 1986;55:91Y100
5. Kim WK, Kwon SH, Lee SH, et al: Asymptomatic electrophysiologic carpal tunnel syndrome in diabetics: Entrapment or polyneuropathy. Yonsei Med J 2000; 41:123Y7
22. Yasuda H, Terada M, Maeda K, et al: Diabetic neuropathy and nerve regeneration. Prog Neurobiol 2003; 69:229Y85
6. Hansson S: Segmental median nerve conduction measurements discriminate carpal tunnel syndrome from diabetic polyneuropathy. Muscle Nerve 1995;18:445Y53
23. Gabby KH, Merola LO, Field RA: Sorbitol pathway: Presence in nerve and cord with substrate accumulation in diabetes. Science 1966;151:209Y10
7. Gazioglu S, Boz C, Cakmak VA: Electrodiagnosis of carpal tunnel syndrome in patients with diabetic polyneuropathy. Clin Neurophysiol 2011;122:1463Y9
24. Gabby KH, O’Sullivan JB: The sorbitol pathway: Enzyme location and content in normal and diabetic nerve and cord. Diabetes 1968;17:239Y43
8. Buchberger W, Schon G, Strasser K, et al: Highresolution ultrasonography of the carpal tunnel. J Ultrasound Med 1991;10:531Y7
25. Suzuki E, Yasuda K, Miyazaki S, et al: 1H-NMR analysis of nerve edema in the streptozotocin-induced diabetic rat. J Lab Clin Med 1994;124:627Y37
9. Wiesler ER, Chloros GD, Cartwright MS, et al: The use of diagnostic ultrasound in carpal tunnel syndrome. J Hand Surg Am 2006;31:726Y32
26. Liu F, Zhu J, Wei M, et al: Preliminary evaluation of the sural nerve using 22-MHz ultrasound: A new approach for evaluation of diabetic cutaneous neuropathy. PLoS One 2012;7:e32730
10. Padua L, Pazzaglia C, Caliandro P, et al: Carpal tunnel syndrome: Ultrasound, neurophysiology, clinical and patient-oriented assessment. Clin Neurophysiol 2008; 119:2064Y9 11. Hobson-Webb LD, Massey JM, Juel VC, et al: The ultrasonographic wrist-to-forearm median nerve area www.ajpmr.com
27. Chen SF, Huang CR, Tsai NW, et al: Ultrasonographic assessment of carpal tunnel syndrome of mild and moderate severity in diabetic patients by using an 8-point measurement of median nerve cross-sectional areas. BMC Med Imaging 2012;12:15
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CME Self-Assessment Exam Questions CME Article 2014 Series Number 6: Kim et al. 1. In this study which is true when comparing ultrasonographic findings in patients with diabetic neuropathy to in the control group: A. The cross sectional areas of median nerve are larger at all levels studied. B. The wrist to forearm cross sectional ratio is increased. C. The cross sectional areas of median nerve is increased at the wrist only. D. The wrist to forearm cross sectional ratio is decreased. 2. In this study which of the following was seen on ultrasound in patients with carpal tunnel syndrome: A. The cross sectional area of median nerve is significantly decreased at the wrist. B. The cross sectional areas of the median nerve are significanctly increased at all levels studied C. The cross sectional area of median nerve is significanctly increased at the wrist. D. None of the above
4. Which of the following is true A. The incidence of carpal tunnel syndrome is greater in patients with diabetes than in the general population B. The incidence of carpal tunnel syndrome in diabetic patients with peripheral neuropathy is greater than in the general population C. The incidence of carpal tunnel syndrome in diabetic patients with peripheral neuropathy is greater than in diabetic patients without peripheral neuropathy D. All of the above 5. In this study ultrasonographic findings at the wrist correlated with which electrophysiologic parameters: A. Distal latency of the median CMAP B. SNAP peak latency C. SNAP amplitude D. All of the above
3. When compared to controls patients with diabetic neuropathy and carpal tunnel syndrome displayed which of the following ultrasonographic findings A. Increased cross sectional areas of median nerve at the wrist B. Increased cross sectional area of the median nerve in the forearm C. Increased cross sectional wrist to forearm ratio D. All of the above (Continued on next page)
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Carpal Tunnel Syndrome
CME ARTICLE
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2014 SERIES
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NUMBER 6
Sonography of the Median Nerve in Carpal Tunnel Syndrome with Diabetic Neuropathy ABSTRACT Kim L-N, Kwon H-K, Moon H-I, Pyun S-B, Lee H-J: Sonography of the median nerve in carpal tunnel syndrome with diabetic neuropathy. Am J Phys Med Rehabil 2014;93:897Y907.
Authors:
Objective: The aim of this study was to determine the criteria for ultrasonographic
Li-Na Kim, MD Hee-Kyu Kwon, MD, PhD Hyun-Im Moon, MD Sung-Bum Pyun, MD, PhD Hang-Jae Lee, MD
measurement of the cross-sectional area (CSA) of the median nerve and differential diagnosis of patients with carpal tunnel syndrome (CTS) with or without diabetic polyneuropathy (DPN).
Affiliations: From the Department of Physical Medicine & Rehabilitation, Sahmyook Medical Center, Seoul, Republic of Korea (L-NK); Department of Physical Medicine & Rehabilitation, College of Medicine, Korea University, Seoul, Republic of Korea (H-KK, H-IM, S-BP); and Department of Physical Medicine & Rehabilitation, College of Medicine, Bundang CHA Medical Center, Sungnam City, Gyeonggi Province, Republic of Korea (H-JL).
Correspondence: All correspondence and requests for reprints should be addressed to: Hee-Kyu Kwon, MD, PhD, Department of Physical Medicine & Rehabilitation, College of Medicine, Korea University, 73, Inchon-ro, Seongbuk-gu, Seoul 136-705, Republic of Korea.
Design: One hundred eighty-seven patients were divided into five groups: healthy controls, CTS, diabetes with CTS but without DPN, DPN only, and both DPN and CTS. The CSAs of the median nerve were measured at four levels, and cutoff values to diagnose CTS with DPN were obtained.
Results: All the CSAs were larger in the DPN group compared with those in the control group. The CSAs of the median nerve at the wrist revealed no significant differences among the groups with CTS; however, these groups demonstrated larger CSAs at the wrist and a higher wrist/forearm ratio compared with the DPN only group. The cutoff value for the CSA at the wrist that yielded the highest sensitivity and specificity was 11.6 mm.
Conclusions: The CSA of the median nerve at the wrist and the wrist/forearm ratio could be useful for diagnosing the comorbidity of CTS with DPN. Key Words: Carpal Tunnel Syndrome, Diabetic Polyneuropathy, Ultrasonography, Median Nerve
Disclosures: Supported by Korea University Grant. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. 0894-9115/14/9310-0897 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000084
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T
he incidence of diabetes is steadily increasing, and it is estimated that 35%Y45% of diabetic patients have diabetic symmetric polyneuropathy.1 Patients with diabetic neuropathy show characteristic symptoms, and the condition is usually confirmed on the basis of a nerve conduction study (NCS).1 Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, results from compression of the median nerve as it passes through the carpal tunnel. CTS is usually diagnosed on the basis of clinical symptoms and confirmed with an NCS.2 Patients with DPN are known to show a higher incidence of CTS.3 In one study, the prevalence of clinical CTS was 2% in the reference population, 14% in diabetic patients without DPN, and 30% in those with DPN.4 Kim et al.5 reported that 6.8% of diabetic patients had asymptomatic electrophysiologic CTS and postulated that asymptomatic CTS is related to the vulnerability of the peripheral nerve at entrapment sites, rather than early DPN. Because symptoms of DPN may mimic those of CTS, confirming a clinical diagnosis of CTS in patients with DPN is difficult. Although NCSs are highly specific for the diagnosis of DPN and CTS, it can be difficult to differentiate the conditions in certain patients, especially in those with advanced DPN. Because CTS and DPN may produce similar abnormalities with respect to median nerve conduction, using diagnostic criteria based on a standard NCS may lead to false-positive or false-negative results.6,7
In recent years, the accuracy of highresolution diagnostic ultrasound (US) equipment has greatly improved, facilitating visualization of the minute details of the peripheral nerves.8,9 As a result, the number of studies on sonography for the diagnosis of entrapment neuropathies, including CTS, has been increasing, and a few reports on sonographic measurement of the peripheral nerves of patients with DPN are also available.1,2,10Y12 Buchberger et al.13 first described the sonographic features of CTS, which include the median nerve flattening ratio, cross-sectional area (CSA) of the median nerve at the carpal tunnel, and increased bowing of the flexor retinaculum. Wang et al.14 reported that the most consistent sonographic finding for CTS was a significant increase in the CSA at the level of the pisiform bone, which was equivalent to that of the carpal tunnel inlet. In the American Association of Neuromuscular and Electrodiagnostic Medicine guidelines for the US diagnosis of CTS, measurement of median nerve CSA at the wrist has been established as an accurate method and may be used as a diagnostic test for CTS.15 A recent study regarding US evaluation of the median nerve in diabetic patients reported that the CSA of the median nerve in the carpal tunnel of patients with DPN was greater than that in healthy individuals or patients without DPN.12 However, there has been no report comparing the US features of DPN and CTS. This study attempted to obtain criteria to diagnose the comorbidity of CTS with DPN by comparing the
FIGURE 1 Patient selection.
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TABLE 1 Patient characteristics
No. hands Age, yrs Men/women Duration of diabetes mellitus, yrs HbA1c, % BMI
Group 1
Group 2
Group 3
Group 4
Group 5
30 57.8 (7.8) 12/17 NA NA 22.9 (4.4)
63 57.7 (12.8) 0/63 NA NA 25.6 (4.4)
35 59.5 (14.0) 22/7 11.5 (9.0) 9.7 (3.0) 23.7 (5.4)
29 63.6 (12.3) 4/31 10.1 (7.4) 8.5 (1.9) 25.9 (3.4)
30 65.8 (10.4) 10/20 15.4 (11.9) 8.7 (2.3) 24.5 (4.3)
Values are mean (standard deviation). Group 1, healthy controls; group 2, patients with CTS only; group 3, patients with CTS and diabetes mellitus but without DPN; group 4, patients with DPN only; group 5, patients with CTS and DPN. BMI, body mass index; HbA1c, glycated hemoglobin; NA, not applicable.
US CSAs of median nerves in patients with CTS, DPN, and CTS with DPN.
study, and informed consent was provided by all participants.
METHODS
Electrophysiologic Evaluation
Participants
The electrophysiologic evaluation was performed using a Dantec Counterpoint Mk2 (Dantec, Copenhagen, Denmark) in all patients. The temperature of each hand was maintained at or greater than 32-C. For the diagnosis of diabetic polyneuropathy (DPN), motor and sensory conduction studies were carried out in unilateral upper and lower extremities. Motor conduction studies were performed in the median, ulnar, peroneal, and tibial nerves, and F waves were recorded for each nerve. Sensory nerve action potentials (SNAPs) were obtained from the median, ulnar, and sural nerves. H-reflex studies were also performed. Needle electromyography was carried out in three muscles in each extremity to reduce the patients’ discomfort. The muscles that were selected covered different myotomes and different peripheral innervations and were also proximally and distally located in order, thereby ruling out the possibility of a radiculopathy or an entrapment neuropathy other than CTS (e.g., biceps brachii, pronator teres, and first dorsal interossei). Diabetic neuropathy was diagnosed using criteria modified from the suggestions of the Diabetes Control and Complications Trial.16,17 For the diagnosis of CTS, the median compound muscle action potential (CMAP) was recorded over the abductor pollicis brevis muscle with median nerve stimulation 8 cm proximal to the active recording electrode. The onset latency and baseline-topeak amplitude were measured. The median SNAP was recorded antidromically with the bar electrode over the third digit, and median nerve stimulation was performed at two points, one 7 cm proximal to the recording electrode in the palm and the other 14 cm proximally at the wrist. CTS was diagnosed if
From June 2011 to January 2012, at Korea University Hospital, a prospective study was conducted in 30 healthy controls and 108 patients with symptoms of CTS, including numbness and tingling sensations in the lateral four fingers with or without thumb weakness, and 124 patients with type 2 diabetes mellitus who were referred for the evaluation of DPN with symptoms of numbness and tingling sensations in the hands and the feet. Patients with other causes of peripheral polyneuropathy, such as long-term alcohol intake or chronic kidney disease, were excluded. All subjects underwent an electrophysiologic study. Of the 108 patients with symptoms of CTS, 23 had normal findings, 22 were diagnosed with cervical radiculopathy, and 63 showed findings consistent with CTS. Of the 124 patients with type 2 diabetes mellitus, 30 had normal findings, 35 had findings consistent with CTS but without features of DPN, 29 were diagnosed with DPN, and 30 were diagnosed with both CTS and DPN. This prospective patients diagnosed with CTS, 35 diabetic patients with electrophysiologic evidence of CTS without DPN, 29 diabetic patients with DPN, and 30 diabetic patients with CTS and DPN (Fig. 1). All patients underwent a sonographic examination on the same day, after an electrophysiologic evaluation. On the basis of the electrophysiologic findings, a total of 187 patients were classified into five groups as follows: group 1, healthy controls; group 2, patients with CTS only; group 3, diabetic patients with CTS but without DPN; group 4, patients with DPN only; and group 5, patients with CTS and DPN. Detailed demographic data for the patients are shown in Table 1. Review board approval was obtained for this www.ajpmr.com
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FIGURE 2 US transverse scanning was performed at four different levels. The CSA of the median nerve was measured at the mid flexor retinaculum (A), distal wrist crease (B), 5 cm proximal to this level (C), and at the proximal third of the forearm (D). The ratio of B/C was also calculated.
the results of the NCS fulfilled three of the following criteria18,19: (1) median SNAP peak latency was greater than 3.7 milliseconds; (2) SNAP peak latency of the proximal 7-cm segment was greater than the peak latency of the distal 7-cm segment; (3) SNAP amplitude was less than 20 KV, including a conduction block with an SNAP amplitude drop of greater than 50% with respect to the wrist stimulation, as compared with that of the palm stimulation; (4) median CMAP distal latency was greater than 4.2 milliseconds; and (5) CMAP amplitude was less than 4.5 mV. CTS was diagnosed in patients with diabetic neuropathy if they met the following criteria: (1) the ratio of the distal motor latency of the median to the ulnar nerve was greater than 1.5; (2) the ratio of the distal sensory latency of the median to the ulnar nerve was greater than 1.2; (3) the amplitude ratio of the median SNAP to the ulnar SNAP was less than 0.6; and (4) the wrist-to-palm latency difference was greater than the palm-to-digit latency difference in the median sensory nerve.17 If the results of the NCS fulfilled two of the
four abovementioned criteria, the patients were diagnosed with diabetic neuropathy and CTS.
Ultrasonography US was performed using an HD15 Ultrasound Imaging System (Philips, Bothell, WA). The examiner was blinded to the results of the electrodiagnosis. The transducer was always kept perpendicular to the median nerve to avert anisotropy. No additional force other than the weight of the probe was applied, and the wrist was kept in a neutral position to avoid causing any artificial nerve deformity. The volar wrist crease and the pisiform bone were used as initial external reference points and landmarks during scanning. The median nerve was imaged in the axial plane at four points: the mid flexor retinaculum (level A), the proximal flexor retinaculum (distal wrist crease, level B), 5 cm proximal to the distal wrist crease (level C), and the proximal one-third of the forearm (level D) (Fig. 2). CSA measurements were performed at the inner border of the thin hyperechoic
TABLE 2 Median nerve CSA as detected with US (square millimeter) Group 1 Level Level Level Level Ratio
A B C D B/C
7.56 (1.48) 7.58 (1.25) 6.23 (0.89) 6.47 (0.77) 1.22 (0.18)
Group 2
Group 3 b
12.89 (5.21) 13.46 (6.12)b 7.16 (2.09) 7.06 (1.73) 1.82 (0.51)b
12.04 (3.49) 12.27 (3.24) 7.32 (1.98) 7.16 (1.93) 1.71 (0.37)
Group 4
Group 5 a
8.87 (3.02) 9.01 (3.01)a 7.10 (1.84)a 7.39 (1.62)a 1.27 (0.29)
11.77 (2.63)d 12.51 (2.96)d 8.41 (1.98)c,d 8.35 (1.74)c,d 1.55 (0.47)c,d
Values are mean (standard deviation). Group 1, healthy controls; group 2, patients with CTS only; group 3, patients with CTS and diabetes mellitus but without DPN; group 4, patients with DPN only; group 5, patients with CTS and DPN. a Group 1 vs. group 4 differences in CSA at A, B, C, and D were significant at P G 0.05. b Group 2 vs. group 4 differences in CSA at A, B, and ratio B/C were significant at P G 0.05. c Group 2 vs. group 5 differences in CSA at C, D, and ratio B/C were significant at P G 0.05. d Group 4 vs. group 5 differences in CSA at A, B, C, D, and ratio B/C were significant at P G 0.05.
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TABLE 3 Cutoff values for median nerve CSA for the diagnosis of CTS in patients with DPN Cutoff Value, mm2
Sensitivity
Specificity
Area Under the ROC Curve
10.5 11.6 1.28
70.0 73.3 73.3
76.2 90.5 71.4
0.775 0.863 0.735
Level A Level B Ratio B/C
ROC, receiver operating characteristic.
epineurial rim with a continuous tracing technique. The CSA ratio of the wrist to the forearm (B/C; wrist to forearm ratio [WFR]) was calculated.
Statistics The Statistical Package for the Social Sciences (version 12; Statistical Package for the Social Sciences Inc, Chicago, IL) and MedCalc (version 12.5) software packages were used for statistical analysis. Only one hand from each patient was used for analysis. The CSAs were compared among the groups using the Student’s t test. Because the CSAs of the median nerve were significantly different between groups 4 and 5, the cutoff values of those CSAs and WFR for the diagnosis of CTS with DPN were obtained by evaluating a receiver operating characteristic curve with the MedCalc program. The analyses also evaluated the correlations among CSA of the median nerve and the electrophysiologic parameters in groups 2, 3, and 5 that were diagnosed with CTS, regardless of the DPN status, using Pearson correlation coefficient.
(P 9 0.05). In comparisons between groups 2 and 5, there were no significant differences in the CSAs of the median nerve at levels A and B, but the corresponding values at levels C and D in group 2 were larger than those in group 5 (P G 0.05); the WFR was larger in group 2. The CSAs of the median nerve at all levels and the WFR were larger in group 5 than in group 4 (P G 0.05) (Table 2). In the assessments for comorbidities, the cutoff values for CSAs to differentiate DPN from CTS with DPN were 10.5 mm2 and 11.6 mm2 at levels A and B, respectively, and the WRF was 1.28. The sensitivities and specificities of these values are shown in Table 3. The cutoff values for CSA at level B showed the highest sensitivity and specificity. The electrophysiologic parameters in groups 2, 3, and 5, which had CTS, regardless of DPN status, revealed significant correlations of CSAs at levels A and B with the distal latency of the median CMAPs and the distal onset, peak latencies, and amplitudes of median SNAPs; further, the CSAs at levels B and C were weakly correlated with the forearm median motor conduction velocities (Table 4).
RESULTS The composition of the groups is listed in Figure 1. The sonographic and NCS results for the patients are shown in Table 2. The CSAs of the median nerve showed significant differences at all levels in comparisons between group 1 and group 4 (P G 0.05). In comparisons between group 2 and group 4, there were significant differences in the CSAs of the median nerve at levels A and B and in the WFR (P G 0.05). There were no significant differences between Groups 2 and 3 at any level
DISCUSSION In this study, the CSAs of the median nerve were larger in the patients with DPN compared with those of the healthy controls at every level. From a pathophysiologic perspective, the nerve swelling that accompanies the early phases of compression neuropathy has been partly correlated with intraneural edema.20 Because the increase in water content that accompanies nerve swelling seems to be correlated with a cascade of events that ultimately
TABLE 4 Pearson correlation coefficients between median NCS parameters and CSA
Level Level Level Level a b
SNAP Distal Latency (Onset)
SNAP Distal Latency (Peak)
SNAP Amplitude
CMAP Distal Latency
Forearm Motor Conduction Velocity
0.430b 0.520b 0.239b 0.199b
0.412b 0.516b 0.232b 0.214b
j0.169a j0.294b j0.205b j0.229b
0.430b 0.464b 0.279b 0.178b
j0.173a j0.228b j0.207b j0.077
A B C D
P G 0.05. P G 0.01.
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lead to axon loss,21 it is conceivable that the nerve CSA is positively correlated with the severity of the neurophysiologic findings.10 Pastare et al.2 reported the occurrence of increasing sonographic abnormalities as the neurophysiologic severity of the CTS increased. One of the putative mechanisms in the pathogenesis of diabetic neuropathy is increased polyol pathway activity leading to the accumulation of sorbitol and fructose.22Y24 Suzuki et al.25 reported that sorbitol itself, as well as a secondary accumulation of sodium caused by an increase in sorbitol, might be a major contributing factor for the increase in intracellular hydration in a hydrogen nuclear magnetic resonance study. There have been only a few reports regarding the sonographic findings in DPN. Watanabe et al.1 found increased CSAs and hypoechoic areas in the peripheral nerves of diabetic patients. In their study, the CSAs were negatively correlated with motor nerve conduction velocity and latency. Recently, Liu et al.26 reported an optimal CSA cutoff value for the sural nerve to diagnose diabetic cutaneous neuropathy using a 22-MHz US, suggesting its value in the evaluation of diabetic cutaneous nerve neuropathy. When Watanabe et al.12 compared the median nerve CSAs in the carpal tunnels of diabetic patients with DPN and patients without DPN, they found greater CSAs in patients with DPN. Although they excluded patients with symptoms of CTS, it was possible that patients with subclinical CTS were included in their study. Therefore, the results of their study might not have solely represented the sonographic features of DPN. In this study, all patients were electrophysiologically diagnosed, and sonographic measurements of median nerve CSAs were compared among healthy controls, patients with CTS only, diabetic patients with CTS but without DPN, patients with DPN only, and patients with CTS and DPN. Because patients with generalized forms of peripheral polyneuropathy might have diffuse enlargement along the entire lengths of the affected nerves, the CSAs of the median nerve at four different levels were measured to accurately characterize and differentiate DPN, CTS, and CTS with DPN. In one other study comparing median nerve CSAs among patients with CTS, diabetic patients with CTS, and diabetic patients with CTS and DPN, the nerve CSAs of the diabetic patients with CTS were found to be significantly higher. However, in comparison with CSA in diabetic patients with CTS, CSAs were significantly reduced at the wrist and in the carpal tunnel of diabetic patients with CTS and
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DPN.27 The authors explained that this peculiar finding might be partially related to the loss of the neuronal regenerative capacity in advanced DPN. In the present study, the CSAs of the median nerve were larger in the patients with DPN compared with those of the healthy controls at every level. Because there was no significant difference in the body mass indices among the groups, the results might not be affected by body mass index. In contrast, these findings indicated that the median nerve CSAs revealed diffuse swelling in the patients with DPN, which seems to be compatible with the pathophysiology of DPN. The CSAs of the median nerves at levels A and B were larger in the patients with CTS compared with those in the patients with DPN but did not show a difference among the patients with CTS only, the diabetic patients with CTS but without DPN, and the patients with CTS and DPN. The results demonstrated that the patients with CTS had larger CSAs, regardless of the presence of coexisting DPN, especially at levels A and B. This could be explained by the fact that the degree of edema was greater in the CTS patients than in the DPN patients at the entrapment site, the carpal tunnel. This was also supported by the finding that the WFR was greater in the patients with CTS only, as compared with that in the patients with both CTS and DPN. Moreover, the results that the patients with CTS and DPN demonstrated a smaller increase in WFR than the CTS only group, as well as larger CSAs at every level compared with those with DPN, could be explained by median nerve swelling at the entrapment site and possible retrograde degeneration. On the basis of the study results, the authors propose cutoff values for CSAs at levels A and B that could be used to diagnose coexisting CTS and DPN, which were 10.5 mm2 and 11.6 mm2, respectively. In comparison with the values used for the diagnosis of CTS in nondiabetic patients, 8.6 mm2 and 9.2 mm2, which were also obtained from the participants in this study, the abovementioned cutoff values are larger. The sensitivities and specificities of the cutoff CSA values for the diagnosis of coexisting CTS and DPN were 70.0% and 76.2%, respectively, at level A, and 73.3% and 90.0%, respectively, at level B; thus, the values were higher at level B. Regarding the evaluation of the correlation between the CSAs of the median nerve and the electrophysiologic parameters in groups 2, 3, and 5, which had CTS, significant correlations were found of CSAs at the mid flexor retinaculum and the wrist and the latency of median CMAPs and the latencies and amplitudes of the median SNAPs, and the CSAs at the wrist and forearm levels revealed a weak
Am. J. Phys. Med. Rehabil. & Vol. 93, No. 10, October 2014
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correlation to the forearm median motor conduction velocities. The limitations of this study included a small sample size in each group, a lack of correlation with the US and clinical findings, and a female predominance in the study population. This study demonstrated that the patients with DPN had diffuse nerve swelling, but the patients with CTS had swelling of the median nerve at the entrapment site (levels A and B), regardless of coexisting DPN. In addition, the CTS patients with DPN demonstrated larger CSAs not only at the entrapment site but also at levels proximal to the entrapment site as well as an increase in the WFR. The cutoff values for CSAs at level B and the increase in the WRF could facilitate US differential diagnosis for patients with DPN and patients with both CTS and DPN. REFERENCES 1. Watanabe T, Ito H, Sekine A, et al: Sonographic evaluation of the peripheral nerve in diabetic patients: The relationship between nerve conduction studies, echo intensity, and cross-sectional area. J Ultrasound Med 2010;29:697Y708 2. Pastare D, Therimadasamy AK, Lee E, et al: Sonography versus nerve conduction studies in patients referred with a clinical diagnosis of carpal tunnel syndrome. J Clin Ultrasound 2009;37:389Y93 3. Perkins BA, Olaleye D, Bril V: Carpal tunnel syndrome in patients with diabetic polyneuropathy. Diabetes Care 2002;25:565Y9 4. Wilbourn AJ: Diabetic entrapment and compression neuropathies, in TP DP (ed): Diabetic Neuropathy. Philadelphia, PA, Saunders, 1999, pp 481Y508
ratio in carpal tunnel syndrome. Clin Neurophysiol 2008;119:1353Y7 12. Watanabe T, Ito H, Morita A, et al: Sonographic evaluation of the median nerve in diabetic patients: Comparison with nerve conduction studies. J Ultrasound Med 2009;28:727Y34 13. Buchberger W, Judmaier W, Birbamer G, et al: Carpal tunnel syndrome: Diagnosis with high-resolution sonography. AJR Am J Roentgenol 1992;159:793Y8 14. Wang LY, Leong CP, Huang YC, et al: Best diagnostic criterion in high-resolution ultrasonography for carpal tunnel syndrome. Chang Gung Med J 2008; 31:469Y76 15. Cartwright MS, Hobson-Webb LD, Boon AJ, et al: Evidence-based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome. Muscle Nerve 2012;46:287Y93 16. Dyck PJ, Thomas PK: Diabetic Neuropathy, ed 2. Philadelphia, PA, WB Saunders, 1999 17. Kwon HK, Kim LN, Park YK, et al: Frequency of carpal tunnel syndrome according to the severity of diabetic neuropathy. J Korean Acad Rehabil Med 2005;29:272Y5 18. Lee HJ, Kwon KH: Electrodiagnostic classification of severity of carpal tunnel syndrome. J Korean Assoc EMG Electrodiagn Med 2004;6:1Y3 19. Kwon HK, Hwang M, Yoon DW: Frequency and severity of carpal tunnel syndrome according to level of cervical radiculopathy: Double crush syndrome? Clin Neurophysiol 2006;117:1256Y9 20. Sugimoto H, Miyaji N, Ohsawa T: Carpal tunnel syndrome: Evaluation of median nerve circulation with dynamic contrast-enhanced MR imaging. Radiology 1994;190:459Y66 21. Powell HC, Myers RR: Pathology of experimental nerve compression. Lab Invest 1986;55:91Y100
5. Kim WK, Kwon SH, Lee SH, et al: Asymptomatic electrophysiologic carpal tunnel syndrome in diabetics: Entrapment or polyneuropathy. Yonsei Med J 2000; 41:123Y7
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6. Hansson S: Segmental median nerve conduction measurements discriminate carpal tunnel syndrome from diabetic polyneuropathy. Muscle Nerve 1995;18:445Y53
23. Gabby KH, Merola LO, Field RA: Sorbitol pathway: Presence in nerve and cord with substrate accumulation in diabetes. Science 1966;151:209Y10
7. Gazioglu S, Boz C, Cakmak VA: Electrodiagnosis of carpal tunnel syndrome in patients with diabetic polyneuropathy. Clin Neurophysiol 2011;122:1463Y9
24. Gabby KH, O’Sullivan JB: The sorbitol pathway: Enzyme location and content in normal and diabetic nerve and cord. Diabetes 1968;17:239Y43
8. Buchberger W, Schon G, Strasser K, et al: Highresolution ultrasonography of the carpal tunnel. J Ultrasound Med 1991;10:531Y7
25. Suzuki E, Yasuda K, Miyazaki S, et al: 1H-NMR analysis of nerve edema in the streptozotocin-induced diabetic rat. J Lab Clin Med 1994;124:627Y37
9. Wiesler ER, Chloros GD, Cartwright MS, et al: The use of diagnostic ultrasound in carpal tunnel syndrome. J Hand Surg Am 2006;31:726Y32
26. Liu F, Zhu J, Wei M, et al: Preliminary evaluation of the sural nerve using 22-MHz ultrasound: A new approach for evaluation of diabetic cutaneous neuropathy. PLoS One 2012;7:e32730
10. Padua L, Pazzaglia C, Caliandro P, et al: Carpal tunnel syndrome: Ultrasound, neurophysiology, clinical and patient-oriented assessment. Clin Neurophysiol 2008; 119:2064Y9 11. Hobson-Webb LD, Massey JM, Juel VC, et al: The ultrasonographic wrist-to-forearm median nerve area www.ajpmr.com
27. Chen SF, Huang CR, Tsai NW, et al: Ultrasonographic assessment of carpal tunnel syndrome of mild and moderate severity in diabetic patients by using an 8-point measurement of median nerve cross-sectional areas. BMC Med Imaging 2012;12:15
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CME SELF-ASSESSMENT EXAM
INSTRUCTIONS TO OBTAIN CATEGORY 1 CME CREDITS:
AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
1. Read the Designated CME Articles in this issue.
Vol. 93, No. 10 & October 2014
2. Read the following CME Self- Assessment Exam Questions. 3. Photocopy and complete the CME Self-Assessment Exam Answering Sheet and CME Evaluation. 4. Send the completed Answering Sheet and Evaluation to: CME Department, AAP National Office, 7250 Parkway Drive, Suite 130, Hanover, MD 21076.
T
his is an adult learning experience and there is no requirement for obtaining a certain score. The objective is to have each participant learn from the total experience of studying the article, taking the exam, and being able to immediately receive feedback with the correct answers. For complete information, please see BInstructions for Obtaining Continuing Medical Education Credit[ at the front of this issue. Every question must be completed on the exam answering sheet to be eligible for CME credit. Leaving any item unanswered will make void the participant’s response. This CME activity must be completed and postmarked by December 31, 2015. The documentation received will be compiled throughout the calendar year, and once a year in January, participants will receive a certificate indicating CME credits earned for the prior year of work. This CME activity was planned and produced in accordance with the ACCME Essentials.
CME Self-Assessment Exam Questions CME Article 2014 Series Number 6: Kim et al. 1. In this study which is true when comparing ultrasonographic findings in patients with diabetic neuropathy to in the control group: A. The cross sectional areas of median nerve are larger at all levels studied. B. The wrist to forearm cross sectional ratio is increased. C. The cross sectional areas of median nerve is increased at the wrist only. D. The wrist to forearm cross sectional ratio is decreased. 2. In this study which of the following was seen on ultrasound in patients with carpal tunnel syndrome: A. The cross sectional area of median nerve is significantly decreased at the wrist. B. The cross sectional areas of the median nerve are significanctly increased at all levels studied C. The cross sectional area of median nerve is significanctly increased at the wrist. D. None of the above
4. Which of the following is true A. The incidence of carpal tunnel syndrome is greater in patients with diabetes than in the general population B. The incidence of carpal tunnel syndrome in diabetic patients with peripheral neuropathy is greater than in the general population C. The incidence of carpal tunnel syndrome in diabetic patients with peripheral neuropathy is greater than in diabetic patients without peripheral neuropathy D. All of the above 5. In this study ultrasonographic findings at the wrist correlated with which electrophysiologic parameters: A. Distal latency of the median CMAP B. SNAP peak latency C. SNAP amplitude D. All of the above
3. When compared to controls patients with diabetic neuropathy and carpal tunnel syndrome displayed which of the following ultrasonographic findings A. Increased cross sectional areas of median nerve at the wrist B. Increased cross sectional area of the median nerve in the forearm C. Increased cross sectional wrist to forearm ratio D. All of the above (Continued on next page)
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CME Self-Assessment Exam
Am. J. Phys. Med. Rehabil. & Vol. 93, No. 10, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
STANDARDIZED CME SELF-ASSESSMENT EXAM ANSWERING SHEET
The answers to any essay questions must be typed or computer printed on a separate piece of paper and attached to this page. After finishing this exam: 1. Check your answers with the correct answers on page 924. 2. Photocopy and complete the CME Evaluation and Certification on the next page and mail to CME Department, AAP National Office, 7250 Parkway Drive, Suite 130, Hanover, MD 21076. 3. This educational activity must be completed and postmarked by December 31, 2015. AAP Members may complete and submit this CME Answering Sheet and the following Standardized CME Activity Evaluation page and Certification page online through the membersonly section of the AAP web page at www.physiatry.org.
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AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
Please photocopy this form and complete the information required for each CME Activity. Journal Issue Month and Year Volume Number CME Article Number CME Article Author’s Name
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C
D
3.
A
B
C
D
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A
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C
D
5.
A
B
C
D
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American Journal of Physical Medicine & Rehabilitation - Standardized CME Activity Evaluation Please photocopy this form and complete the information required for each CME Activity. Journal Issue Month and Year CME Article Number
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These new skills will improve my work performance and professional competencies in the following areas: (Check all that apply):
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906
CME Self-Assessment Exam
Am. J. Phys. Med. Rehabil. & Vol. 93, No. 10, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
CME ACTIVITY CERTIFICATION Please photocopy this form and complete the information required for each CME Activity. Journal Issue Month and Year CME Article Number
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I, certify that I have met the criteria for CME credit by studying the designated materials, by responding to the self-assessment questions, by reviewing those parts of the article dealing with any question(s) answered incorrectly, and by referring to the supplemental materials listed in the references. This educational activity is designated for 11⁄2 category 1 CME credits. (maximum of 11⁄2 credits)
Indicate total credits claimed:
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If you are not an AAP member or a Journal subscriber, have you enclosed payment of $15 with your exam? 䡺 Yes 䡺 No Payment Options: 䡺 Check (Payable to AAP)
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