| | Reduced Longitudinal Excursion of the Median Nerve in Carpal Tunnel SyndromeAbstract Hough AD, Moore AP, Jones MP. Reduced longitudinal excursion of the median nerve in carpal tunnel syndrome. ObjectiveTo determine if longitudinal excursion of the median nerve is reduced in patients with carpal tunnel syndrome (CTS). DesignCase-control study. SettingUniversity human movement laboratory. ParticipantsNineteen patients with CTS (8 men, 11 women; mean age, 57±15y), and 37 healthy controls (8 men, 29 women; mean age, 48±10y). InterventionsNot applicable. Main Outcome MeasuresLongitudinal excursion of the median nerve, and the ratio of nerve to flexor digitorum superficialis tendon excursion at the carpal tunnel evoked by finger extension. Measurements were taken using a validated Doppler ultrasound technique, and tests were conducted with the elbow positioned in extension and flexion. ResultsMean longitudinal excursion of the median nerve was significantly greater in controls (11.2±2.8mm) than patients (8.3±2.6mm) with the elbow extended (P=.013), but not with the elbow flexed (controls, 12.5±2.5mm; patients, 10.2±3.1mm; P=.089). Mean nerve/tendon excursion ratios were significantly greater in controls (.32±.07) than patients (.23±.06), with the elbow extended (P<.001), and flexed (controls, .36±.06; patients, .28±.10; P=.019). Discriminant analysis identified that 11 (58%) of the 19 patients and 3 (8%) of the 37 controls showed a nerve/tendon excursion ratio of .25 or less when tested with the elbow in extension. ConclusionsReduced longitudinal excursion of the median nerve at the carpal tunnel was identified in a substantial proportion of patients with CTS. Further studies are merited to determine if reduced median nerve excursion at the carpal tunnel is clinically relevant in CTS, and can be influenced by movement-based interventions. CARPAL TUNNEL SYNDROME (CTS) is the most commonly reported peripheral nerve entrapment, with a prevalence rate in a general population estimated at about 3%.1, 2 The pathophysiology is incompletely understood but aspects of mechanical injury within the carpal tunnel are considered most likely.3, 4, 5 Although the mechanical injury is primarily associated with compression of the median nerve as it passes through the carpal tunnel, it has been hypothesized by a number of sources that reduced or restricted longitudinal excursion of the median nerve contributes to the pathophysiologic process.6, 7, 8, 9, 10, 11 Based on this hypothesis, nerve and tendon gliding exercises have been advocated for the conservative and postoperative management of CTS with the putative aim of restoring the normal gliding mechanisms of the nerve and tendons through the carpal tunnel.7, 12 The effectiveness of gliding exercises remain inconclusive,13, 14 and currently only 1 study provides indirect evidence that longitudinal excursion of the median nerve may be reduced in CTS patients.8 Indeed, during the course of the study reported here, Erel et al15 found no significant reduction in the longitudinal excursion of the median nerve in CTS patients compared with asymptomatic controls, when measured by a speckle tracking ultrasound technique proximal to the carpal tunnel. Ultrasound imaging can be used to visualize longitudinal excursion of peripheral nerve trunks in vivo,16 and the movement can be reliably quantified using a Doppler,17 or speckle tracking18 approach. The Doppler technique described in this study was subject to a series of validity studies using string-phantoms and porcine specimens. Using the results of these studies, which are the subject of another article currently in preparation, we estimated that the accuracy of the technique described in this study would be in the region of ±0.7mm (limits of agreement19) when appropriate corrections were made to take account of the effects of intrinsic spectral broadening,20 and out-of-plane (nonlongitudinal) movements.21 The purpose of this study was to use the Doppler technique to determine if there was direct evidence for reduced longitudinal excursion of the median nerve in patients with CTS. Measurements were taken of median nerve and flexor digitorum superficialis (FDS) tendon excursion at the carpal tunnel evoked by active finger extension. The FDS tendon values were used to calculate a nerve/tendon excursion ratio as described by Szabo et al,11 on the basis that this value may control for intersubject anthropometric variations and provide a more sensitive method for detecting reduced nerve excursion. As far as we are aware, this is the first time that longitudinal excursion of the median nerve and the nerve/tendon ratio has been measured directly at the carpal tunnel in vivo. Methods  Experimental Hypothesis Patients with CTS would show reduced longitudinal excursion of the median nerve at the carpal tunnel during finger extension (either absolute or relative to FDS tendon excursion) compared with asymptomatic controls. Study Design and Equipment The study design was a comparative case-control involving 1 group of participants with idiopathic CTS (n=19), and a control group of healthy volunteers (n=37). The sample size calculation was made with reference to data from previous in vivo and cadaveric studies,9, 10, 11, 17, 18, 22 and selected to be sufficient to detect at least a 15% between-group difference with an α level of .05 and a power of 0.8. We used a Sonoace 6000C ultrasound systema with a wide-band linear-array transducer center frequency of 7.5MHz (B-Mode); 5.13MHz (D-Mode) for all image acquisition. An upper-limb support jig was custom designed for the study, consisting of wooden struts attached to the left and right frame-sides of a standard hydraulic plinth, and 1 adjustable upper-limb support that could attach to the left or right struts depending on the limb to be tested. The jig allowed adjustment for forearm length, carrying angle, and positioning of the elbow in flexion or extension (fig 1). Participants We recruited 21 patients with a clinical diagnosis of idiopathic CTS of at least 1 month in duration from local orthopedic clinicians and general practitioners. Thirty-seven asymptomatic volunteers aged 18 years or over were recruited from staff and students at the local university. Prospective volunteers with the following conditions were excluded from participation in either group: (1) history of injury or symptoms attributed to the neck or upper limbs during the previous 6 months, which had required treatment (excluding CTS for the patient group), (2) history of major trauma to the neck or limb to be tested, (3) systemic neuropathy, and (4) pregnancy. Ethics approval was obtained from the local research ethics committee and the university ethics committee. All participants gave written informed consent prior to undertaking the ultrasound test procedure. Prospective patient group volunteers were diagnosed at either an orthopedic or hand clinic consultation (n=18) or by their general practitioner (n=3). Ten of the patient group reported undergoing electrodiagnosis (all reported as positive for CTS). Prior to undergoing the ultrasound test procedure, all patient group volunteers completed a Hand Symptom Diagram (HSD)23 and a Hand Symptom Severity and Functional Status Questionnaire (HSSFSQ).24 The Phalen test25 was conducted on the affected hand (or most severely affected hand in bilateral cases) by the principal researcher. Ultrasound System Settings and Test Procedures We adjusted the ultrasound system settings according to basic tissue Doppler principles26, 27 and previous experience with this specific ultrasound system, including: (1) removing the wall (clutter) filters, (2) setting Doppler power and gain low (20% and 5dB, respectively), and (3) optimizing the scale of the Doppler velocity-time display for low-velocity measurements. General Doppler mode settings were as follows: frequency of 5.13MHz, electronic beam steering on (15°), and sample volume size set to 1mm. The Doppler angle was set to 0° for all tests regardless of beam-to-target angle (correction for actual Doppler angle was made offline later). All the above settings were held constant throughout the ultrasound scanning procedures. The support jig was positioned on the side to be tested, which for patient group participants was the affected side, or the most severely affected side in bilateral cases. The participant lay supine on the plinth with the limb to be tested resting in the support jig such that the glenohumeral joint was at 45° of abduction and the forearm supinated (see fig 1). The elbow was initially positioned in either 90° of flexion or full extension dependent on test sequence (see below). The shoulder girdle was relaxed in a neutral position, and the head supported on a pillow in 0° rotation and side flexion. The length of the forearm component of the jig was adjusted such that the junction of the forearm support and hand plate lay between the proximal and distal wrist creases and held the wrist in 30° of extension. The hand of the participant was strapped to the hand plate using a self-adhesive (Velcro) strap across the metacarpals. The contralateral upper limb was relaxed by the side with the palm down and the participant was asked to maintain this position during all tests. Test Protocols The participant was asked to make a fist, ensuring that the fingers were fully flexed at the metacarpophalangeal and interphalangeal joints and the thumb positioned alongside the index finger. Nerve and tendon excursion was evoked by asking the participant to fully extend the fingers and thumb to the maximum allowed by the hand plate (figs 2A, 2C). The following 4 measurement protocols were conducted in the order shown for the first participant and then reversed for alternate participants to control for any sequencing effects of elbow position: (1) longitudinal excursion of the median nerve (elbow flexed); (2) longitudinal excursion of the flexor digitorum superficialis tendons (elbow flexed); (3) longitudinal excursion of the median nerve (elbow extended); and (4) longitudinal excursion of the flexor digitorum superficialis tendons (elbow extended). Acquisition of Ultrasound Images Longitudinal excursion of the median nerve We placed the transducer longitudinally at the wrist such that a clear image of the median nerve and flexor tendons was acquired in this plane. Duplex Doppler mode was then selected (B/D mode) and the on-screen Doppler sample volume indicator adjusted to lie within the median nerve at approximately the level of the lunate-capitate intercarpal joint. The participant was asked to perform the test movement while the operator ensured that the sample volume was accurately located in the median nerve and a clear Doppler waveform was produced. After any necessary adjustments of the transducer or sample volume location, the test movement was performed and the resultant image containing the Doppler waveform was saved. The test was repeated on a further 2 occasions, so that 3 Doppler waveforms representing nerve excursion were saved (fig 2D). Longitudinal excursion of FDS tendon We repositioned the Doppler sample volume position to lie within the FDS tendons immediately deep to the median nerve. The same image acquisition procedures as described for tests 2 and 4 above were then followed, so that 3 Doppler waveforms representing excursion of the FDS tendons were saved (fig 2B). Transverse displacement of median nerve In addition to the longitudinal excursion measurements, we captured transverse plane displacement of the median nerve produced by the test movement using split-screen B-mode ultrasound (B/B) with the transducer located transversely on the palmar aspect of the wrist joint at the level of the distal wrist crease. Pre- and post-test movement images were frozen on the split-screen display and saved. We included these measurements in order to adjust the Doppler recorded excursion for out-of-plane (nonlongitudinal) movements. Image Management Saved images were transferred to a personal computer into folders according to participant code and test number. When all study data had been collected, the top 30 rows of pixels of each image were removed using the batch crop function of IrfanView,b removing image identification details such as date, time, and participant code. An assistant renamed all participant image folders with randomly assigned code numbers (1 to 58), such that the individual and group identity of each participant image folder was unknown to the principal researcher who subsequently carried out all image measurements. All image measurements were conducted using the ImageJ image analysis and measurement software.c Longitudinal Excursion Measurements The Doppler angle (angle subtended by the center of the Doppler beam and the target nerve or tendon) was determined for each test image by taking the mean of 3 measurements made with the angle calipers. The velocity-time integral (VTI) of the Doppler waveform (representing nerve or tendon excursion) was obtained by setting the lower threshold of ImageJ to 10, isolating the waveform, and using the wand tool to automatically calculate the VTI in pixels (appendix 1). The maximum brightness of the Doppler waveform pixels was also determined for each image using the Min & Max Gray Value measurement option in ImageJ. We included this measurement to allow control for any effects on Doppler recorded excursion of intersubject variability in the strength of the received Doppler signal (due to variations in tissue echogenicity), which we suspected might be present (based on the findings of our validity studies). Transverse Plane Displacement of the Median Nerve We determined the axial location of the median nerve from the B/B-mode ultrasound images using the mean of measurements made from the skin surface to the deep and superficial borders at the central part of the nerve. Axial displacement was calculated as the difference in depth location of the nerve between the split-screen images. Lateral location of the median nerve was determined using the mean of measurements made from the left edge of each image on the split-screen to the lateral and medial borders of the nerve. Lateral displacement was calculated as the difference in lateral location between the split-screen images. The VTI, axial, and lateral displacement in pixels for each image were input into an Excel spreadsheet and converted to millimeters according to the display scale. Adjustment for Intrinsic Spectral Broadening and Transverse Plane Movements The longitudinal excursion values were initially adjusted according to the measured Doppler angle, minus 22° beam-edge correction factor to take account of intrinsic spectral broadening,28, 29 and adjusted for any concurrent transverse plane displacement in accordance with devised geometric formulas (Appendix 2, Appendix 3, Appendix 4). Statistical Analysis Descriptive and inferential statistics were calculated using Exceld and SPSS,e respectively. Results Excluded Data Sets Ultrasound test data on 2 of the 21 patients were excluded from subsequent analysis. One patient was unable to complete the test protocol satisfactorily due to dystonia affecting the wrist and hand, and 1 patient’s data was excluded because the HSD had strongly suggested ulnar nerve entrapment rather than CTS. Transverse Plane Displacement of the Median Nerve Mean axial and lateral displacement of the median nerve was 0.35±0.3mm, and 1.75±1.3mm, respectively. The direction of axial displacement, when it occurred, was from superficial to deep. Lateral displacement was predominantly toward the radial aspect of the limb (n=48). Effect of Elbow Position The mean nerve excursion values were significantly reduced for tests with the elbow positioned in extension compared with flexion (t test, P<.001), although some participants in both groups showed slightly greater nerve movements with the elbow extended (n=12). There was no significant effect of elbow position on FDS tendon movement. Effect of Doppler Signal Strength on Excursion Measurements A significant positive correlation was found between maximum brightness values of the Doppler waveform (produced by variations in Doppler signal strength) and nerve excursion measurements (r range, .48−0.5, P<.001). The association was anticipated from provisional findings in validity studies, and the result confirmed the need to include maximum brightness value of the Doppler waveform as a covariate in subsequent analysis of nerve excursion data. Between-Group Comparison of Nerve and Nerve/Tendon Ratio Excursion The 4 sets of nerve and nerve/tendon ratio excursion data were analyzed individually using univariate analysis of variance, with age, height, BMI, and maximum brightness value of Doppler waveform input as possible covariates.33 The patient group showed significantly reduced excursion for 3 of the 4 measures; median nerve excursion with the elbow extended (P=.013), and both nerve/tendon ratios (elbow flexed, P=.019; elbow extended, P<.001). The patient group also showed a mean reduction in median nerve excursion with the elbow in flexion but this did not reach statistical significance (P=.089). With the exception of maximum brightness of the Doppler waveform (P=.002), none of the covariates (age, height, weight, BMI,) showed a significant effect for any of the test measurements. Discriminant analysis using the nerve/tendon excursion ratio data for the test with the elbow extended placed 11 (58%) of the 19 patients and 3 (8%) of the 37 control subjects in the lower nerve/tendon ratio category with a cutoff point of .25 (table 4). | | |  | Group | Nerve/Tendon Excursion Ratio | Totals | |
|---|
| ≥.25 | <.25 | |
|---|
| Control (n) | 34 | 3 | 37 | | | Patient (n) | 8 | 11 | 19 | | | Control (%) | 91.9 | 8.1 | 100 | | | Patient (%) | 42.1 | 57.9 | 100 | | | | |
Discussion The findings of this study provide the first direct evidence that reduced longitudinal excursion of the median nerve may be present in a substantial proportion of patients with CTS. Although the results are consistent with the indirect measurements reported by Valls-Solé et al,8 they appear to conflict with the results of the ultrasound study by Erel et al.15 Methodologic differences are the most likely explanation for this apparent discrepancy. Erel employed a smaller nerve excursion evoking protocol (metacarpophalangeal flexion), and nerve excursion was measured 5 to 15mm proximal to the carpal tunnel. A particular distinguishing feature of the present study, however, is the inclusion of tendon excursion measurements, and the calculation of the nerve/tendon excursion ratio. Nerve/Tendon Excursion Ratio The magnitude of nerve or tendon excursion evoked by a joint movement is influenced by the distance of the nerve from the axis of the joint.34 Thus for example, during wrist extension flexor tendons traversing the anterior aspect of the wrist are required to accommodate a relatively greater length change the further from the axis of movement they lie, and this biomechanical consideration may partly explain the positive association of CTS with a high wrist index.35, 36 It is hypothesized that flexor tendons traversing the carpal tunnel in subjects with a high wrist index are subject to greater excursion during everyday activity, and are consequently at greater risk of developing tenosynovitis, which may predispose to CTS.36 Equally, it can be argued that greater nerve excursion occurring during everyday activities may predispose to CTS via a direct mechanical effect on the nerve or its specialized gliding tissue.37 In this regard, it is interesting to note that the mean FDS excursion was found to be greater in the patient group than the controls (see table 3), although this difference did not reach statistical significance. If the magnitude of nerve excursion during everyday movements is contributing to CTS then it is possible that mean nerve excursion magnitudes in CTS patients may be above average before the onset of their condition. Therefore, attempts to detect any relative reduction of median nerve excursion in CTS compared with asymptomatic controls could be confounded. It was principally in order to apply some control for this possible anthropometric influence that we included nerve/tendon ratios as an outcome measure of this study. In this respect, it is of particular note that both nerve/tendon ratios were found to show significant between-group differences, but that one of the absolute nerve excursion measures (test with elbow flexed) showed no significant difference. Effect of Proximal Loading of the Median Nerve Tract The mean effect of positioning the elbow in extension was to reduce nerve excursion significantly compared with the same test with the elbow in flexion. On an individual basis, the effect was inconsistent, with some subjects in both patient and control groups showing minimal differences or a small increase in movement with the elbow extended. Previous studies have also identified apparent intersubject variability of effect of proximal loading on subsequent distal excursion,22 which we hypothesize may be related to individual variations in neural extensibility (eg, the relative “slack” in the system). Scrutiny of significance level for between-group differences in nerve excursion and nerve/tendon ratio, however, suggest that proximal loading greatly increases the sensitivity of detecting reduced nerve excursion. Discriminant Analysis Although the discriminant analysis highlighted the fact that a substantially greater number of CTS patients (58%) exhibited “low” nerve/tendon excursion ratios compared with the control group (8%), it also indicates that if reduced nerve excursion does contribute to the pathophysiology of CTS it only does so in some cases. This suggests that studies investigating possible subtypes of CTS (eg, compressive or uniaxial stretch related) may be a useful area of future work. The present study was not designed to identify possible subtypes of CTS, but the finding that a significantly greater number of subjects classified in the “low” nerve/tendon excursion ratio group had their dominant hand tested (affected hand, or most affected hand in bilateral cases) compared with patients classified as “high” nerve/tendon excursion ratio is interesting. Bay et al10 reported that the nerve/tendon excursion ratio was unaffected by simulated carpal tunnel compression in cadaveric specimens, and concluded that if this ratio was indeed reduced in CTS patients that it was more likely to be related to disruption of the specialized gliding tissue surrounding the nerve at this location.37 If one assumes that the dominant hand is likely to be more active during everyday activities then the findings of our study lend support to these conclusions, and may also explain why Tuzuner et al38 found no significant increase in median nerve excursion after endoscopic carpal tunnel decompression. Study Limitations and Implications for Future Research Doppler calculations of velocity and/or excursion require an accurate knowledge of the angle subtended by the Doppler beam and the target tissue.39 Because of the focused nature of the Doppler beam, calculating the Doppler angle with reference to the on-screen indicator only represents the Doppler angle at the center of the beam and does not take account of the maximum and minimum angles present at the beam edges. Therefore, excursion values calculated according to the method described here result in an overestimated value if this factor (intrinsic spectral broadening) is not taken into account.20, 28, 40, 41 Furthermore, the effective edge of the Doppler beam is not a fixed quantity but is influenced by transducer beam geometry, ultrasound system settings (eg, Doppler gain and dynamic range), and the reflective characteristics of the target tissue (as evidenced in this study by the correlation found between maximum brightness on the Doppler waveform and excursion values). The ImageJ threshold level selected during offline measurement of the Doppler waveform as described in this study also influences the excursion calculated. A higher threshold effectively eliminates some of the weaker Doppler signals from the display, thereby indirectly affecting the actual Doppler beam edge. The beam-edge correction factor and ImageJ threshold selected for excursion measurement employed in this study was based on string-phantom, porcine, and in vivo validity studies.21 Although these basic principles would apply for other investigators employing this technique, specific settings will be ultrasound system and setting dependent and would need to be determined by validity studies. Conventional Doppler measurements are based on the assumption that all the movement of interest is occurring in 1 direction (eg, longitudinally) and no out-of-plane movements are concurrently occurring (eg, lateral or axial). Any concurrent out-of-plane movement will affect the accuracy of the longitudinal excursion calculated. It was known from previous studies that lateral and axial movements of the median nerve were likely to occur during the selected test protocol42, 43 and therefore formulas based on geometric principles were devised to take account of concurrent out-of-plane movements as illustrated in Appendix 3, Appendix 4. Although we believe the out-of-plane movement corrections applied in this study to be sound theoretically, they are based on the assumption that the movements occur in a continuous linear manner and their experimental accuracy remains to be determined. The validity of the nerve and tendon excursion values reported in this study can be ascertained to some degree with reference to previous studies. The mean nerve and tendon excursion values calculated in this study are approximately 15% to 20% higher than reported in cadaveric and invasive in vivo studies.9, 11, 44 We believe that the most likely explanation for this is because some wrist extension was occurring during the test movement due to incomplete fixation of the hand by the self-adhesive strap, and this would have led to higher evoked excursion.44 The mean nerve/tendon excursion ratios recorded for the control group in this study were consistent with those found previously in cadaveric studies.10, 11 All ultrasound test protocols and image measurements were conducted by a single operator who was the principal researcher on the project. The researcher was blinded to group membership during the offline measurement of the saved images, but the possibility that experimenter bias was present during image acquisition (which was not blinded) cannot be completely ruled out although every effort was made to acquire Doppler waveforms in a consistent and unbiased manner. Despite these limitations, the results of the study suggest that exploration of a causative role of reduced median nerve excursion in CTS, and the influence of mechanical interventions such as gliding exercises on nerve excursion, is warranted. Nerve excursion measurements in addition to conventional outcome measures would be key components of such study, as would diagnostic profiling of the patients, including electrodiagnosis, compression-based tests (eg, Phalen), and tests with stretch-based components (eg, tethered median nerve stress test45, 46 or upper-limb neurodynamic tests47, 48). The profiling element could help identify CTS subtype characteristics that could lead to optimized case-by-case management of this condition. Conclusions This study has found that the mean ratio of median nerve and FDS tendon excursion at the wrist, evoked by finger movement, was significantly less in patients with CTS compared with asymptomatic controls. The results of this study indicate that reduced longitudinal excursion of the median nerve is present in a substantial proportion of CTS patients. The possibility that reduced excursion of the median nerve contributes to the pathophysiology in some cases, possibly a subtype, of CTS cannot be excluded, and this hypothesis merits further investigation. Suppliers Appendix 1. Measurement of the VTI (A) Doppler waveform from a test image. (B) Using ImageJ, the lower display threshold has been set at 10 (upper at maximum), waveform has been isolated by cutting the baseline, and the area automatically measured using the wand tool. Appendix 2. Beam-edge correction method θ′ is the Doppler angle taken from the center of the beam to the target (T). The effective minimum Doppler angle is θL and the beam-edge correction factor is η (determined as 22° for the system and measurement set-up described in this study). Appendix 3. Calculating the effect of lateral movement of the target occurring concurrently with longitudinal movement The target is assumed to move longitudinally in the direction A (T to Ta). If this movement is accompanied by lateral movement in the direction B, the actual vector of movement is given by C (T to Tc). Because the Doppler measurement method calculates the distance C, the true longitudinal movement (A) is given by √(C2−B2). This correction assumes that concurrent lateral movement occurs in a consistent linear manner throughout the acquisition of the Doppler waveform. Appendix 4. 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