Sensitivity, Specificity, and Variability of Nerve Conduction Velocity Measurements in Carpal Tunnel Syndrome

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1 12 Sensitivity, Specificity, and Variability of Nerve Conduction Velocity Measurements in Carpal Tunnel Syndrome Henry L. Lew, MD, PhD, Elaine S. Date, MD, Steven S. Pan, MD, Peter Wu, MD, Paul F. Ware, MD, Wade S. Kingery, MD ABSTRACT. Lew HL, Date ES, Pan SS, Wu P, Ware PF, Kingery WS. Sensitivity, specificity, and variability of nerve conduction velocity measurements in carpal tunnel syndrome. Arch Phys Med Rehabil 2005;86:12-6. Objective: To explore the diagnostic values of 8 commonly used electrodiagnostic techniques for measuring median nerve conduction velocity (NCV) in carpal tunnel syndrome (CTS). Design: Sensitivity and specificity analyses. Setting: A hospital-based electrodiagnostic laboratory. Participants: Forty-four normal hands and 136 symptomatic hands. Interventions: Not applicable. Main Outcome Measures: (1) Long-segment studies: antidromic wrist-to-digit sensory NCV without subtraction, (2) short-segment studies: transcarpal palm-to-wrist mixed NCV without subtraction, and (3) 2 segment studies: antidromic transcarpal sensory NCV with subtraction (differential calculation from wrist-to-digit and palm-to-digit segments). Both onset and peak latency values were obtained for calculating the NCV. Sensitivity, specificity, and coefficient of variance were calculated for each NCV study. Results: The short-segment, onset latency based transcarpal mixed NCV yielded the highest sensitivity (75%). Conclusions: Results from measurement of a single, shortnerve segment tended to be superior to results obtained by either long-segment studies or differential subtraction between 2 segments of the same nerve in the electrodiagnosis of CTS. Explanations for our results are offered from both electrophysiologic and statistical perspectives. Key Words: Carpal tunnel syndrome; Eletrodiagnosis; Rehabilitation; Sensitivity and specificity by American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation From the Physical Medicine and Rehabilitation Service, VA Palo Alto Health Care System, Palo Alto, CA (Lew, Date, Pan, Ware, Kingery); Division of PM&R, Stanford University School of Medicine, Stanford, CA (Lew, Date, Pan, Kingery); and Palo Alto Medical Foundation, Palo Alto, CA (Wu). No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors(s) or upon any organization with which the author(s) is/are associated. Reprint requests to Henry L. Lew, MD, PhD, PM&R Service 117, VAPAHCS, 3801 Miranda Ave, Palo Alto, CA 94304, henrylew@stanford.edu /05/ $30.00/0 doi: /j.apmr MANY ELECTRODIAGNOSTIC TECHNIQUES have been developed to assist in the diagnosis of carpal tunnel syndrome (CTS), the most common nerve entrapment syndrome. 1,2 However, there is no consensus as to which technique is the most sensitive or specific The discrepancies between previous studies have been attributed to lack of consistency regarding (1) the techniques used (sensory vs motor, antidromic vs orthodromic), (2) use of parameters (peak latency vs onset latency), (3) inclusion and exclusion criteria, and (4) statistical analysis. Moreover, previous data have rarely been discussed from the perspective of coefficient of variance (CV). In 1991, the American Academy of Electrodiagnostic Medicine s (AAEM) Quality Assurance Committee performed an exhaustive critical analysis of the CTS electrodiagnostic literature 12 and concluded that (1) median sensory nerve conduction studies (NCSs) are more sensitive than median motor NCSs and (2) short-segment median sensory or mixed NCSs (wrist-to-palm) are more sensitive than long-segment sensory (wrist-to-digit) or mixed NCSs. By using standardized measurement techniques and statistical analysis, we sought to analyze the sensitivity, specificity, and CV of 8 commonly used electrodiagnostic techniques in the diagnosis of CTS. The techniques were (1) long-segment: antidromic digital (wrist-todigits) sensory nerve conduction velocity (NCV), (2) shortsegment: transcarpal (palm-to-wrist) mixed NCV, and (3) 2 segments: antidromic transcarpal sensory NCV (derived from the difference between wrist-to-digit and palm-to-digit segments of the same nerve branch). METHODS The local institution s human subjects subcommittee approved the experimental protocol and informed consent was obtained for all testing. References Group and Control Group Subjects with no symptoms or signs of median mononeuropathy were recruited from among healthy volunteers. The exclusion criteria were (1) numbness, tingling, or pain in the hands or digits; (2) history of median, radial, or ulnar mononeuropathy; (3) other peripheral neuropathy; and (4) diabetes. Forty-four healthy subjects (24 men, 20 women; mean age, y; range, 25 80y) were recruited. Results of studies from only the right hands were included to minimize inherent biologic variability. 13 To establish the normative database, we randomly selected 20 of the 44 healthy subjects as our reference group, and the remaining 24 subjects were assigned as the control group for later comparison with the CTS group (136 symptomatic hands). CTS Group Patients referred to our electrodiagnostic laboratories with suspected CTS were recruited for this study. The clinical diagnosis of CTS was based on the presence of numbness, tingling, or pain in a median nerve distribution that had occurred at least 3 times a week for at least 3 months. Patients with either a history of CTS release surgery, absent median sensory nerve action potential (SNAP), diminished ulnar SNAP amplitude ( 12 V), or prolonged ulnar sensory distal latency ( 3.7ms) 14 were excluded. One hundred seventy hands were screened and 34 were eliminated, based on the exclusion criteria, leaving 136 hands for final analysis. The excluded subjects were older than the recruited subjects (mean age, y vs y, P.05),

2 TRANSCARPAL NERVE CONDUCTION, Lew 13 Fig 1. Eight commonly used electrodiagnostic tests for CTS. Abbreviations: D1, digit 1 ; D2, digit 2; D3, digit 3; D4, digit 4; NA, not available; P, palm; SNCV, sensory nerve conduction velocity; W, wrist. and the excluded subjects were predominantly male (81.2% vs 47.8%, P.001). By using the normative values derived from our reference group, we compared CTS and control groups to determine the sensitivity and specificity of various electrodiagnostic techniques. Electrodiagnostic Studies Limb temperature (recorded over distal wrist crease) was maintained at or above 32 C. We used a standard electrodiagnostic instrument a with bandwidth setting of 20Hz to 3kHz, gain of 20 V/division, and sweep speed of 1ms/division. The 8 electrodiagnostic techniques are described in the following sections. Long-segment studies (antidromic wrist-to-digit sensory NCV without subtraction). Figure 1 illustrates our standardized electrode placements for stimulation and recording. The median nerve was stimulated at the wrist. For digits 2, 3, and 4 (D2, D3, D4), the active recording ring electrode was placed 14cm distal to the stimulation site. For digit 1 (D1), the active recording ring electrode was placed 10cm distal to stimulation sites, measured in a straight line with the thumb extended, and on the palmar plane of the hand. 3 The active ring recording electrode was always separated from the reference electrode by 3cm, and the just supramaximal response was used for determination of latency. Both onset latency and peak latency were recorded. Short-segment studies (transcarpal palm-to-wrist mixed NCV without subtraction). The median nerve was stimulated in the mid-palm (between the second and third metacarpals), and waveforms were recorded at the wrist (8cm proximal to the

3 14 TRANSCARPAL NERVE CONDUCTION, Lew Table 1: Reference Values, Means, Sensitivities, and Specificities of 8 Electrodiagnostic Tests Reference Group Control Group CTS Group Lower Limit CV Mean Mean Sensitivity Specificity Long segment: wrist-to-digit sensory NCV (antidromic wrist-to-digit without subtraction) 1 OL D PL D OL D PL D OL D PL D OL D PL D (avg 39.5) 96 Short segment: transcarpal mixed NCV (palm-to-wrist without subtraction) 5 OL PL (avg 56) 96 Two segments: transcarpal sensory NCV (antidromic wrist-to-digit and palm-to-digit difference) 6 OL D PL D OL D PL D OL D PL D (avg 40.5) 88 Abbreviations: avg, average; OL, onset latency based, PL, peak latency based. stimulation site) with bar electrodes. Both peak and onset latencies were measured. Two segment studies (antidromic transcarpal sensory NCV with subtraction). The median nerve was stimulated at the wrist and at the palm. The distance between stimulation sites (wrist, palm) was 8cm. The active recording ring electrodes were placed at D2, D3, and D4. Again, both onset latency and peak latency were recorded. Statistical Analysis Data from 20 reference subjects were used to develop the normative means and standard deviations (SDs) for the previously mentioned techniques. There were 8 tests but 16 parameters because both onset and peak latency data were collected. NCV values were calculated by dividing the distance traveled over the corresponding latency. Then, the 24 control subjects were compared with the CTS patients to derive sensitivity and specificity values. We used the Wilcoxon nonparametric signed-rank test to compare the CVs in each pair of reference values. Statistical analysis was performed by using SAS, versions 8.1. b RESULTS Table 1 summarizes the mean NCV values in the reference, control, and CTS groups. The lower limits of reference values were derived by subtracting 2 SDs from the means (left half of table 1). The CV for each reference value was derived from the SD divided by the mean. For ease of visualization, NCV values based on onset latency and peak latency are listed in sequence. In the long-segment wrist-to-digit NCV without subtraction, the calculated wrist-to-digit NCV values based on onset latency were all faster than those derived from peak latency because onset latency was always shorter. The CV of each reference value reflects the standardized variability of each parameter: larger CV suggests greater variability of the measured value. Among the long-segment and 2-segment nerve conduction parameters, the CVs based on onset latency were all larger than those estimated from peak latency (signed-rank test, P.05; table 1, middle column). This trend was not observed in the short-segment studies. Because the SNAP amplitudes obtained with recording electrodes over the median nerve at the wrist were consistently larger, it was relatively easy to specify the onset latencies in short-segment studies. The sensitivity and specificity values are listed in the last 2 columns on the right side of table 1. Among the 8 tests (16 parameters), test 5 (onset latency based NCV) yielded the highest sensitivity (75%). The sensitivities of other tests were relatively low (between 33% 46%). All tests had very high specificities, ranging from 83% to 100%. A post hoc analysis was added to compare median and ulnar sensory peak latencies from digits 4 and 5. The analysis of latency difference between D4 and D5 showed a mean value of.07.22ms (upper limit.51ms) in the reference group, as shown in table 2. By using the previously mentioned reference values, very low sensitivity (25%) and very high specificity (100%) were derived. In this scenario, in which the mean centers on zero, it is not appropriate to use CV to evaluate data variability. DISCUSSION In this study, we attempted to explore the diagnostic values of 8 commonly used electrodiagnostic techniques for CTS by comparing their sensitivity, specificity, and CV. Our results showed that the short-segment, onset latency based transcarpal mixed NCSs had the highest sensitivity (75%). Although our normative values were similar to data reported by other authors, 3,4,15-20 the sensitivity values in our study were relatively low. Perhaps the inclusion and exclusion criteria caused this decline in sensitivity. Because we excluded patients with

4 TRANSCARPAL NERVE CONDUCTION, Lew 15 Table 2: Reference Values, Means, Sensitivity, and Specificity of Latency Comparison Between D4 (median) and D5 (ulnar) Reference Group Control Group CTS Patients Upper Limit Sensitivity Specificity either unobtainable SNAP or history of CTS release surgery, our chosen patient population could be shifted toward milder cases of CTS. Although we purposefully divided the healthy subjects into a reference group and a control group to decrease the possibility of falsely enhancing the specificity, the resultant specificities were still high (83% 100%). It may suggest that our healthy subjects were genuinely free from CTS. Atroshi et al 21 estimated an overall positive rate of 18% (ie, 82% specificity) by electrophysiologic tests in an age- and gender-stratified asymptomatic sample that was randomly selected from the general population. The specificity values in our study are higher than those reported in several population-based studies, perhaps because only healthy adults were included in the control group. Therefore, the generalizability of our results is limited because the control group did not precisely represent the general population. Short-segment (palm-to-wrist, 8cm) NCSs theoretically have better diagnostic sensitivity than long-segment (wrist-to-digit, 14cm) studies because the effect of the focal pathology on NCV may be diluted in long-segment studies. This phenomenon was reflected in the sensitivity section of our results, which is also consistent with the AAEM report. 12 Although shortsegment (palm-to-wrist) NCSs showed a similar transcarpal concept with the 2-segment NCSs (derived from the difference between wrist-to-digit and palm-to-digit results), the latter had low sensitivity values (average, 40.5%), whereas the former yielded a higher sensitivity (average, 56%). It implies that direct measurement from a single nerve segment may be superior to indirect differential calculation from 2 related nerve segments. From the perspective of data variability, the variance increases as a result of doubling the measurement error. Not surprisingly, we found that all the 2-segment transcarpal NCV (derived from 2 sets of latency and distance measurements) had larger CVs. Because larger CVs also correspond with wider ranges of normal limits in the reference values, the sensitivities of these tests would therefore be lower. We have yet to explain why the onset latency based transcarpal mixed NCV showed much higher sensitivity than its peak latency counterpart (75% vs 37%). A possibility may come from a pathophysiologic standpoint: in the earlier phases of CTS, the fast conducting, larger myelinated fibers may be affected to a larger degree. If this is true, it will have a more pronounced effect on the onset-phase of the SNAP waveform morphology. In the 2002 summary statement of AAEM, the American Academy of Neurology, and the American Academy of Physical Medicine and Rehabilitation, 24 and a previous study on combined sensory index, 1 the validity and reliability of comparing electrophysiologic measures have been established. Our present study focused on the sensitivity, specificity, and variability of single nerve parameters derived from median NCS. We acknowledge that these values are influenced by biologic determinants such as the subjects age, concurrent disease, gender, body mass index, or other anthropometric factors. 22 Theoretically, it would be best to calculate median-ulnar peak latency difference from a single finger such as D4. Nevertheless, we did a retrospective analysis of the median-ulnar peak latency difference by comparing median and ulnar latency values obtained from D4 and D5, respectively. The result was a very low sensitivity (25%) and very high specificity (100%). Because the latency differences were obtained from 2 separate measurements (wrist-to-digit 4, wrist-to-digit 5), the measurement error naturally increased 2-fold. The increased variability widened the range of the normal limits in the reference values and contributed partially to the low sensitivity. Another likely explanation for the low sensitivity lies with the inclusion and exclusion criteria. Because we excluded patients with unobtainable SNAP and previous CTS release surgery, the CTS group was probably milder in disease severity than one would expect in a typical CTS population. This was reflected by the small difference between the mean latency comparison values in CTS group and the upper limit derived from reference group (.53ms vs.51ms). CONCLUSIONS Our study showed that among the 8 median NCV tests, the short-segment, onset latency based transcarpal NCV was most sensitive in diagnosing CTS. 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