EVALUATION OF SENSORY RECOVERY AFTER RECONSTRUCTION OF DIGITAL NERVES OF THE HAND USING MUSCLE-IN-VEIN CONDUITS IN COMPARISON TO NERVE SUTURE OR NERVE AUTOGRAFTING THEODORA MANOLI, M.D.,* LUKAS SCHULZ, STEPHANE STAHL, M.D., PATRICK JAMINET, M.D., and HANS-EBERHARD SCHALLER, M.D.

Background: Muscle-in-vein conduits are a good alternative solution to nerve autografts for bridging peripheral nerve defects since enough graft material is available and no loss of sensation at the harvesting area is expected. The purpose of this study was to compare regeneration results after digital nerve reconstruction with muscle-in-vein conduits, nerve autografts, or direct suture. Patients and Methods: 46 patients with 53 digital nerve injuries of the hand subjected to direct suture (n 5 22) or reconstruction of 1-6cm long defects with either nerve autografts (n 5 14) or muscle-in-vein conduits (n 5 17) between 2008 and 2012, were examined using the two-point discrimination and Semmes-Weinstein Monofilaments. Results: The follow-up examinations took place 12 to 58 months after surgery. A median reduction of sensibility of 2 Semmes-Weinstein monofilaments compared with intact digits was observed after direct suture (DS) and of 2.5 and 2 Semmes-Weinstein monofilaments after reconstruction with autologous nerve grafts (ANG) and muscle-in-vein conduits (MVC), respectively. No statistically significant differences between all three groups could be found with a significance level set by a P < 0.006 (PDS-ANG 5 0.24, PDS-MVC 5 0.03, PANG-MVC 5 0.52). After harvesting a nerve graft, reduction of sensibility at the donor site occurred in 10 of 14 cases but only in one case after harvesting a muscle-in-vein conduit. Conclusions: Muscle-in-vein conduits may be a good alternative solution to autografts for the reconstruction of digital nerves, since no significant differences could be demonstrated between the C 2014 Wiley Periodicals, Inc. Microsurgery 34:608–615, 2014. two methods. V

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order to achieve the best possible regeneration after reconstruction of peripheral nerve defects, the surgical technique must provide an optimal milieu for the ingrowth of the new axon sprouts after Wallerian degeneration takes place. The new axons grow to their original target guided by the so-called bands of B€ungner, which are endoneural tubes formed by proliferating noninnervated Schwann cells and remaining connective tissue within the basal lamina of the distal nerve stump.1,2 In the case of a sharp transected nerve, direct suture of the proximal and distal stumps can be performed if a tensionless coaptation is possible.3,4 Up to date, autologous nerve autografts are the gold standard for bridging nerve defects in clinical use.4,5 Several disadvantages like the loss of sensory perception at the donor site, the demand of at least two incisions, different diameters of the harvested and the injured nerve and limited graft material led to the development of alternative tubulization techniques. Several synthetic (e.g., silicon, polytetrafluoethylene, polyglycolic acid, or collagen) and biological conduits (e.g., allografts,6 blood vessels, muscles) have been tested in the past.3,4,7,8 In 1993, Brunelli et al. described the Department of Hand, Plastic and Reconstructive Surgery with Burn Center, BG Trauma Center, University of Tuebingen, 72076 Tuebingen, Germany *Correspondence to: Theodora Manoli, M.D., Department of Hand, Plastic and Reconstructive Surgery with Burn Center, BG Trauma Center, University of Tuebingen, Schnarrenbergstr. 95, 72076 Tuebingen, Germany. E-mail: [email protected] Received 21 February 2014; Revision accepted 4 July 2014; Accepted 15 July 2014 Published online 2 August 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/micr.22302 Ó 2014 Wiley Periodicals, Inc.

use of veins filled with fresh skeletal muscle.9 Veins form a barrier against dispersion of outgrowing axons and they inhibit ingrowth of scar tissue into the conduit.7,9 Muscle tissue provides an optimal environment for the ingrowth of regenerating axons into newly formed bands of proliferating Schwann cells along the basal laminae of the muscle fibers. These are biologically similar to the bands of B€ungner formed in regenerating nerve tissue as described above.10–13 Additionally, the interposition of muscle tissue prevents the collapse of the veins and therefore enables bridging of larger defects.9 Regenerating nerves can correctly orientate within muscle-invein conduits due to the accumulation of neurotrophic factors from the distal stump, generating a concentration gradient which enables growing axons to reach their proper target.14–18 Muscle fibers or veins alone achieve good results up for bridging defects of 1–2 cm in length.3,9,19 In combination the distance rises up to 6 cm.20 Several previous studies showed that muscle-invein conduits are reliable for the repair of peripheral nerve defects of both sensory and mixed nerves.5,19,21,22 Brunelli et al. proved histologically that there are higher numbers of regenerating axons in muscle-in-vein conduits in gaps up to 2 cm than in nerve grafts of the same length.9 Geuna et al. showed however no significant differences in the total number, density and size of myelinated fibers between nerve grafts and vein-in-muscle conduits in the sciatic model of the rat. In an additional experiment in the rabbit model, the same group showed that 5.5 cm long nerve defects could be successfully bridged using muscle-in-vein conduits.21

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Table 1. Summary of patients within the tree groups including the distributions of age, of primary or secondary reconstructions, gap length and time point of follow-ups.

Number (male/female) Mean age (range of age) Number of primary reconstructions Number of secondary reconstructions Mean gap length (range) in cm Follow-up in months

Direct suture (DS)

Autologous nerve grafting (ANG)

Muscle-in-vein conduit (MVC)

22 (13/7) 35 (17–63) 22 0 0 12–42

14 (14/0) 32 (11–62) 6 8 (2–23 weeks post trauma) 2.18 (1–6) 13–58

17 (14/3) 38 (15–72) 8 9 (2–15 weeks post trauma) 2.17 (1–6) 14–29

The purpose of this study was the comparison of the outcome after reconstruction of sensory nerves of the hand with muscle-in-vein conduits to the standard methods of autologous nerve grafting or direct nerve suture on a clinical level. PATIENTS AND METHODS

The retrospective study was approved by the ethics committee of the University of Tuebingen (117/ 2012BO2). Patients that underwent either direct suture (DS), autologous nerve grafting (ANG), or reconstruction by a muscle-in-vein conduit (MVC) of one or more sensory digital nerves on the palmar side of the hand between 2008 and 2012 and met the criteria mentioned below were invited to a follow-up examination the earliest 12 months after operation. The age of patients ranged between 11 and 72 years. Thirty-six patients with 43 digital nerve injuries were male and 10 patients with a single digital nerve injury were female. Five patients with six digital nerve injuries were pediatric cases between 11 and 17 years of age. The causes of injuries included sharp transections (nDS 5 17, nANG 5 6, nMVC 5 6), lacerations (nDS 5 1, nANG 5 4, nMVC 5 8) and saw injuries (nDS 5 4, nANG 5 4, nMVC 5 5). All participants had to understand clearly the background of the study and to give their written consent. Parents of patients under 18 years of age provided their informed consent prior to the examination of their children. The level of injury was between the metacarpophalangeal joint and the distal interphalangeal joint. When no direct suture was possible, patients were consecutively treated firstly by ANG between January 2008 and beginning of March 2010 and afterwards by MVC except of three cases, which were treated by ANG in 2012 due to the surgeon’s objective preference of ANG instead of a reconstruction with MVCs. All direct nerve sutures were performed primarily on the day of injury. Nerve reconstruction by means of nerve autografts or muscle-in-vein conduits was either performed primarily or secondary, not later than 6 months after injury. The length of the bridged nerve gap ranged between 1 and 6 cm in both groups ANG and MVC. The distribution of patients within the three groups is depicted in Table 1.

Six patients underwent reconstructions of more than one digital nerve of the same hand; two of them underwent a direct suture of two digital nerves, one of them one direct suture and a reconstruction with a muscle-invein conduit, another one underwent one direct suture and two reconstructions with muscle-in-vein conduits and two patients had two reconstructions with muscle-in-vein conduits. All nerve reconstructions, also from same individuals, were analyzed as distinct cases. Total or subtotal amputations with a combined injury of blood vessels, nerves, tendons, and bones were excluded from the study. Further exclusion criteria were inadequate compliancy for performing the clinical assessment tests of the follow-up examination reliably and pathologies that could have influenced the digital sensibility, i.e., nerve compression syndromes. In total 46 patients with 53 digital nerve injuries were included in the study. Surgical Procedure

All sutures were performed with 10-0 nylon with the aid of an operating microscope. In case of direct nerve suture both nerve stumps were directly approximated and sutured with 2–3 epineural stitches avoiding torsion of both stumps. The medial antebrachial cutaneous nerve was harvested at the palmar side of the ipsilateral proximal forearm for autografting. A muscle-in-vein conduit was prepared as following: A subcutaneous vein, slightly wider than the damaged nerve, was harvested from the palmar side of the forearm. At the same site a fascial incision was performed and a thin muscle strip was excised (Fig. 1a). The muscle was then pulled into the vein along its longitudinal course of fibers using a micro forceps (Figs. 1b–1d). The vein ends of the muscle-invein conduit were then sutured over the nerve stumps including all fascicles. Follow-Up Examination

Static and moving two-point discrimination tests as well as the Semmes-Weinstein monofilament (SWM) test were used to compare the recovered sensibility of the innervated area of the injured nerve to normal sensibility. Normal sensibility was defined as the sensibility assessed at healthy, not previous harmed fingers. If reconstructions Microsurgery DOI 10.1002/micr

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Manoli et al.

Figure 1. Intraoperative photographs depicting the preparation of a muscle-in-vein conduit (scale in mm); (a) Harvest of a subcutaneous vein and a thin muscle slice from the flexor digitorum superficialis muscle at the palmar side of the forearm, (b-c) The muscle slice was pulled through the vein using a micro forceps, (d) Muscle-in-vein conduit with retracted vein ends ready for interposition between the nerve stumps. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

with nerve autografts or muscle-in-vein conduits were performed, the Semmes-Weinstein test was also applied to the graft donor sites at the palmar side of the ipsilateral forearm. Examination of static and moving two-point discrimination was carried out with a two-point discriminator R , North Coast Medical, USA). Testing (Touch-TestV intervals of 1 mm ranging from 1 to 15 mm could be assessed. The patients were asked to close their eyes and the examined finger was slightly held from the dorsal side. Then one or two points were applied to the skin for at least 3 s. Light pressure was added to the weight of the device carefully until blanching of the skin occurred. The test was applied at the fingertip in line of the anatomical course of the examined sensory digital nerve. Three repetitive responses should be accurate for scoring. R SWM were used to assess the Homecraft RolyanV sensibility of the palmar side of the hand. The set consisted of 20 monofilaments whereas each monofilament was labeled with the logarithm to base 10 of the pressure force it produces onto the skin. In order to obtain objective results each monofilament was vertically pressed onto the skin until it slightly bended holding it for 1–2 s. The examination began always with the 2.83 monofilaMicrosurgery DOI 10.1002/micr

ment followed by the next thicker monofilament until the tested person stated a perception with closed eyes. Up to 17 monofilaments (2.83–6.65) had to be used to obtain a positive result. Both healthy and injured digits were examined to calculate a possible reduction of sensibility at the injured sites by means of a level difference. The level difference was calculated by the following way; the 17 monofilaments used were ordered ordinally (1–17 as levels). The level difference between injured and healthy digits was then calculated. All clinical tests were performed by the same assessor (LS) who was independent of the surgical procedure. Statistical Analysis

Analysis of the collected data was carried out with IBM SPSS statistics version 21. The rates of measurable versus not measurable two-point discrimination between all three groups were evaluated using the Fisher’s exact test for count data. The level of significance was initially set by a P-value of 0.05 and after applying the Bonferroni correction for multiple testing (three tests) values less than 0.017 were considered to be significant. The results of two-point discrimination and SWM-test between all three groups were evaluated using the Wilcoxon rank-sum-test to find out whether significant

Muscle-In-Vein Conduits for Nerve Repair

differences between the groups exist. The level of significance was initially set by a P-value of 0.05 and after applying the Bonferroni correction for multiple testing (nine tests) values less than 0.006 were considered to be significant. A Spearman’s rank correlation was additionally applied to the results of two-point discrimination and SWM-test. Finally, age distribution, gap lengths greater than 2 cm and bilateral nerve injuries were assessed according to the SWM-test results for the three groups in this study and a Spearman’s rank correlation was additionally applied to the age and SWMtest. RESULTS

The follow-up examinations took place 12–42 months after direct suture, 13–58 months after nerve autografting and 14–29 months after reconstruction with muscle-invein conduits (Table 1).

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are presented in Figures 2a and 2b. The median static spatial discrimination ability in groups DS, ANG, and MVC was 5.0, 5.5, and 5.0 mm, respectively, which corresponds to a median increase of 2.0, 2.5, and 2.0 mm compared with normal sensibility assessed at the not injured digits, respectively. No statistically significant differences between all three groups could be found (PDS-ANG 5 0.13, PDS-MVC 5 0.60, PANG-MVC 5 0.40). The median moving spatial discrimination ability in groups DS, ANG, and MVC was 3.5, 4.0, and 4.0 mm, respectively, which corresponds to a median increase of 1.5, 2.0, and 2.0 mm compared with normal sensibility, respectively. The MVC-group had, however, an interquartile spread towards better results compared with the ANG-group. No statistically significant differences between all three groups could be found (PDS-ANG 5 0.61, PDS-MVC 5 0.76, PANGMVC 5 0.86).

Two-Point Discrimination

Semmes-Weinstein Monofilament Test (SWMTest)

Since static and moving two-point discrimination function did not recover in all cases, the rate of the measurable two-point discriminations (

Evaluation of sensory recovery after reconstruction of digital nerves of the hand using muscle-in-vein conduits in comparison to nerve suture or nerve autografting.

Muscle-in-vein conduits are a good alternative solution to nerve autografts for bridging peripheral nerve defects since enough graft material is avail...
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