Original Article
227
Prospective Clinical Study on Digital Nerve Repair with Collagen Nerve Conduits and Review of Literature
1 Department of Plastic Surgery and Hand Surgery, Klinikum rechts der
Isar, Technische Universität München, Munich, Germany 2 Department of Plastic Surgery, Agaplesion Diakonieklinikum Hamburg, Klinik für Plastische Chirurgie, Hamburg, Germany 3 Plastic, Hand and Reconstructive Surgery, Burn Unit, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
Felix Paprottka, MD1
Address for correspondence Joern Andreas Lohmeyer, MD, PhD, Department of Plastic Surgery, Agaplesion Diakonieklinikum Hamburg, Hohe Weide 17, 20259 Hamburg, Germany (e-mail: [email protected]).
J Reconstr Microsurg 2014;30:227–234.
Abstract
Keywords
► digital nerve reconstruction ► nerve conduit ► collagen I conduit ► nerve injury ► hand
Little data are available concerning conduit repair of digital nerve lesions. We are presenting a prospective two-center cohort study on digital nerve reconstruction with collagen nerve conduits. The data are put into the context of a comprehensive review of existing literature. Over a period of 3 years, all consecutive digital nerve lesions that could not be repaired by tensionless coaptation with a gap length of less than 26 mm were reconstructed with nerve conduits made from bovine collagen I. Sensibility was assessed 1 week, 3, 6, and 12 months postoperatively by static and moving 2-pointdiscrimination (2PD) and monofilament testing. Forty-nine digital nerve lesions in 40 patients met the inclusion criteria. The mean nerve gap was 12.3 2.3 mm (span 5–25 mm). Forty nerve reconstructions could be included in the 12-month follow-up. Three cases, assessed 12 months postoperatively, showed excellent sensibility (static 2PD < 6 mm). Seventeen achieved good (2PD 6–10 mm), 5 fair (2PD 11–15 mm), 6 poor (2PD > 15 mm, but protective sensibility), and 9 achieved no sensibility. Monofilament test results were significantly better if gap length was shorter than 12 mm. Our results confirm tubulization as one possible technique in nerve reconstruction for gap lengths of 5 to 25 mm.
Nerve injuries are common in trauma surgery and appear more frequently if the upper extremity is affected.1 Nerves are affected in approximately 10% of all hand injuries that require surgical treatment.2 The consequences may be numbness and an impairment of motor function. After repair, an intensive period of rehabilitation is required. Sick leave and sometimes the need for a change in profession and partial or even permanent total disability may have severe socioeconomic consequences for the patient and society.3,4 If the
upper extremity is affected, the most frequently injured nerves are the proper and common digital nerves, followed by the median and ulnar nerves.2,5 Complete transection of a peripheral nerve requires reconstruction of the continuity between the proximal and distal nerve stump. The gold standard for nerve injuries that cannot be overcome by direct tensionless coaptation is the nerve autograft. Primary repair by end-to-end coaptation can be performed in approximately 82% of the cases.6 Thus, usually 18% require nerve
received July 26, 2013 accepted after revision September 7, 2013 published online December 12, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1358788. ISSN 0743-684X.
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Joern Andreas Lohmeyer, MD, PhD1,2 Yasmin Kern, MD1 Daniel Schmauss, MD1 Felix Stang, MD3 Frank Siemers, MD, PhD3 Peter Mailaender, MD, PhD3 Hans-Guenther Machens, MD, PhD1
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Fig. 1 Collagen I nerve conduit (NeuraGen, Integra) in a wet state (internal diameter 2 mm).
reconstruction by means of grafting or tubulization. In some cases, end-to-side neurorrhaphy can be an alternative.7 Digital nerve lesions are ideal for clinical outcome studies since results are easy to compare, but only a few studies provide comparable data for nerve reconstruction with artificial hollow conduits. We are presenting the final outcome of a prospective two-center study on digital nerve reconstruction with collagen nerve conduits in the context of a comprehensive summary of the pertinent published outcome studies.
Methods Over a period of 3 years, all consecutive digital nerve lesions with a gap length of equal to or less than 26 mm were reconstructed with NeuraGen nerve conduits (►Fig. 1), made from bovine collagen I (Integra Lifesciences, Plainsboro, NJ). A maximum conduit length of 30 mm and a minimum overlap of 2 mm on each side limited gap length to 26 mm. Subsequent to informed consent, no patient refused to participate in the study. Cases were excluded from the study if reconstruction was performed later than 12 months following injury, or if severe wound contamination was evident. Further defined exclusion criteria were the diagnosis of polyneuropathy, pre-existing damage to the injured nerve (e.g., trauma or chronic compression disease), injury at
different levels of the nerve, acute local infection, lack of soft-tissue coverage and life expectancy < 1 year due to malignancy or other systemic diseases. The study has been approved by the local ethical review board and is registered at Current Controlled Trials (ISRCTN18539256). We restricted the indication for tubulization to common and proper palmar digital nerves. NeuraGen conduits are available in a maximum length of 30 mm. The semipermeable tubes are made from bovine tendon and are available in different diameters ranging from 1.5 to 7 mm. In our study, all patients received conduits with an internal diameter of 2 or 3 mm. In a moist state, wall thickness is quite precisely 0.5 mm. Conduits are soft, pliable and completely degraded within 36 months after insertion in monkeys.8 All patients were operated on by microsurgically trained plastic surgeons. A clinical example is shown in ►Fig. 2A, B. The operating microscope was used in all operations. The repair of concomitant injuries to the hand, as well as exposure of the severed nerve ends, was performed under tourniquet control. This had to be released (followed by meticulous hemostasis) prior to insertion of the nerve ends into the conduit to prevent bleeding into the lumen since the formation of a blood clot inside the tube might be detrimental to nerve regeneration. After proper debridement, proximal and distal nerve endings were inserted into the conduit with an overlap of approximately 3 mm. To evacuate the conduit from potentially remaining blood clots, the lumen was rinsed with normal saline after each suture, which was usually performed with one 9–0 nylon suture in a horizontal mattress fashion through the conduit and epineurium at both sides. We decided to administer a single-shot of 1.5 g cefuroxime intravenously to prevent infection. Immobilization of the adjacent joints was assured for 14 days. In the case of concomitant tendon repair early mobilization was performed. Sensibility was assessed using static and moving twopoint discrimination (2PD) and monofilament testing in the first postoperative week and after 3, 6, and 12 months. For 2PD tests, we used the Mackinnon-Dellon Disk-Criminator (Mackinnon-Dellon Partnership, Baltimore, MD). Modified guidelines of the American Society for Surgery of the Hand (ASSH) were used to stratify the 2PD measurements (excellent, < 6 mm; good, 6–10 mm; fair, 11–15 mm; poor, > 15 mm).9 Furthermore, 2PD of the uninjured contralateral
Fig. 2 (A, B) A 66-year-old male patient presenting an acute laceration of the radial proper digital nerve of the index. Primary conduit repair of the 10 mm gap with an overlap of 3 mm at distal and proximal stump. Journal of Reconstructive Microsurgery
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229
finger was assessed and the difference of injured and uninjured nerve was calculated to form a Δ2PD to avoid bias by inter-individual differences in normal sensibility. Monofilaments with calibrated pressure of 0.07, 0.4, 2, 4, and 10 g were used (Touch-Test Sensory Evaluator, North Coast Medical Inc., Morgan Hill, CA). For the lowest reported monofilament, inconsistent or consistent (100%) detection of monofilament touch was reported. Sensibility testing was performed without digital nerve block for the intact nerve.
Exact Wilcoxon–Mann–Whitney Rank Sum Test was used to look for significant correlation between possible influencing factors and outcome scores. Fisher’s exact test was used to compare our results with the results found in the literature.
Results
Fig. 4 Δ2PD (difference of the static 2-point discrimination of injured and uninjured contralateral digit) at the three follow-up visits (pr. sens., protective sensibility; mo, months). Results are classified in Δ2PD 3 mm, 4–6 mm, 7–12 mm, > 12 mm with and without protective sensibility.
Two study centers were included for evaluation. Together, 55 nerve reconstructions with NeuraGen conduits were recorded in 45 patients. Five patients (6 nerve repairs) had to be excluded, three due to delay of nerve reconstruction > 365 days after injury. Two patients were recorded as collagen conduit repairs but were not further assessed. Of the remaining patients 88% were available for follow-up at 3 months, 92% at 6 months, and 82% at 12 months. The male to female ratio was 45:4 (92% male). The mean age at operation time was 37.9 years (17–75 years, median 31 years). The dominant hand was affected in 35% of the cases. The index finger was affected most often (47%), followed by the thumb (24%), middle and ring finger (12% each). The little finger was injured in two cases (4%). The mean nerve gap length after debridement measured 12.3 mm (5–25 mm, median 12 mm). The mean conduit length was 18.4 mm (7–30 mm, median 18 mm). The mean distance of the proximal coaptation to the fingertip was
75 mm (40–135 mm, median 70 mm). Cut injuries were reported in 63%, crush or tension injuries in 37%. The ratio of acute versus delayed repair was 76 to 24%. The mean delay was 95 days (19–264 days). No patient suffered from alcoholism, diabetes, neuropathy, or collagenous diseases; 39% were active smokers. The return of sensibility at the different time-points measured with static 2PD and Semmes-Weinstein monofilament testing is depicted in ►Figs. 3–5. We saw significantly better results in the monofilament test in cases of sharp versus crush injuries (p < 0.05) and when the nondominant hand was involved (p < 0.05). Monofilament test results were significantly better if gap length was shorter than 12 mm (p < 0.05). We did not observe a significant influence of patient’s age, sex, smoking habits, study center, and primary versus secondary reconstruction (►Table 1).
Fig. 3 Return of sensibility according to the modified guidelines of the American Society for Surgery of the Hand. Continuous progress is seen until the last examination at 12 months. No further significant reduction of the rate of complete failure of regeneration without protective sensibility after 6 months.
Fig. 5 Monofilament test results at the three follow-up visits. “ þ ” indicates that the specific stimulus is always recognized. “o” indicates that the stimuli are infrequently recognized. “-” indicates no recognition. Journal of Reconstructive Microsurgery
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Statistics
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Table 1 Correlation between possible influencing factors and monofilament testing outcome
Gap length < 12 mm Cut injury Smoker Primary reconstruction Dominant hand affected
Lowest reported monofilament
p
Yes
2g
0.038
No
4g
Yes
2g
No
4g
Yes
2 g inconsistent
No
2g
Yes
2g
No
2 g inconsistent
Yes
4g
No
2g
0.035 0.259 0.729 0.027
Notes: The median force of the lowest reported monofilaments is shown. For the lowest reported monofilament, inconsistent or consistent (100%) detection of monofilament touch was reported.
Discussion The tension-free nerve coaptation is the method of choice for reconstruction after complete nerve transection. Retraction of the nerve endings, tissue loss due to trauma or necessary debridement can lead to extended nerve gaps that require alternative surgery. Today, the gold standard is the autologous nerve graft, but graft harvesting usually causes some degree of donor site morbidity and the amount of nerves suitable for transplantation is limited.10,11 Artificial nerve conduits have become a possible alternative to nerve grafting, the biggest advantage being that they obviate the need for a nerve donor site. Only few clinical studies exist that deal with the use of biodegradable artificial hollow nerve conduits for digital nerve repair.12 In 1990, Mackinnon and Dellon were the first to report on 15 digital nerve lesions being reconstructed with hollow polyglactin (PGA) conduits.13 Casanas et al stated sensibility improvement in every case after 17 digital nerve repairs with PGA-conduits,14 but results were not further specified. We found one further published meeting abstract presenting data on 19 digital nerve repairs with PGA-conduits.15 At a mean 17 months postoperatively, return of 2PD was documented in 74% of reconstructions. However, as a meeting abstract, it remains unclear to which extent methods and results of that study were peer-reviewed. In 2000, Weber et al compared 46 PGA-conduit repairs with 56 direct coaptations (partly under tension) or nerve grafts in a prospective randomized study. No significant difference was seen in outcome between the two groups as a whole.16 However, three conduit removals and six fingers that were amputated later were not accounted for evaluation, and the percentage of follow-up at only 3, 6, and 9 months was higher in the control group. Laroas et al published their results on 28 PGA-conduit repairs in 2003.17 The authors report that with sensory reJournal of Reconstructive Microsurgery
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education the success rate can be increased to 100%. This looks like an unreasonable conclusion, with only one failure in the medium-sized defect group. Furthermore, it remains unclear how many results were included with a follow-up of less than 12 months. Range of follow-up was 6 to 74 months. However, results were excellent with 93% regaining a 2PD of 3 to 15 mm. In contrast, Wangensteen and Kalliainen found postoperative improvement in only 35% of cases after nerve reconstruction with collagen I conduits. However, the study does not provide specific information about the outcome in digital nerve repair. Instead results are summarized for all treated nerves. 2PD measurements were only performed in 21% of repairs and patients in need of surgical revision were more likely to be examined. Average follow-up with 2PD measurements was 371 days; it is not mentioned how many patients were examined in less than 12 months following surgery. 18 Taras et al presented more favorable results with the same conduit in 2011.19 In all 21 nerve reconstructions moving 2PD of at least 8 mm was found 12 to 59 months after tubulization. Six patients did not regain measurable static 2PD. For 2PD measurements the two pins were applied transversely to the long axis of the finger. Thus, values were only measured up to 8 mm and everything above that was rated as poor. Most other studies also rate the static 2PD range of 9 to 15 mm as good. In the same study in four cases moving 2PD was worse than static 2PD, which seems rather unlikely. Thus, there are some limitations in comparing the results with other studies. The most recent study about digital nerve reconstruction with collagen I conduits was published by Haug et al in 2013.20 The authors present their results of 42 NeuraGen conduit reconstructions with a follow-up of 12 months. The failure rate, according to a static 2PD > 15mm, was as high as 60%. However, the authors rated the functional outcome as good in the majority of cases using a new sum score comprising seven different clinical tests. Usual perception would probably have led to a different conclusion. In 2005, Bertleff et al compared 21 poly-(DL-lactide-εcaprolactone) conduit repairs to 13 direct coaptations and stated overall good sensory recovery without significant differences between groups.21 On average, gap length was 6 to 8 mm. Results were not categorized. Other reports complained about the rigidity of the material, which might be especially troublesome at the joint levels.22,23 Thomsen et al presented the only data on 10 digital nerve reconstructions with porcine collagen I þ III conduits (Revolnerv, Orthomed, St. Jeannet, France).24 All six cases with a gap length of 5 to 20 mm and a follow-up of at least 12 months showed static 2PD of 4 to 15 mm. Clinical studies on digital nerve repair with conduits often present different scoring systems that render direct comparison difficult. Two grading systems with several modifications are mainly used. First, the Medical Research Council (MRC) classification, was promoted and standardized as a grading scale for motor and sensory outcome.25 Both, static and moving 2PD are used for classification. The alternate guideline of the ASSH uses a more subtle distinction in the 2PD
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230
Polyglycolic acid
Polyglycolic acid
Polyglycolic acid
Polyglycolic acid
Bovine collagen I
Bovine collagen I
Polyglycolic acid
Porcine collagen I þ III
poly(DL-lactideε-caprolactone)
Bovine collagen I
Bovine collagen I
Bovine collagen I
Mackinnon and Dellon (1990)
Weber et al (2000) a
Laroas et al (2003)b
Battiston et al (2005)
Bushnell et al (2008)
Lohmeyer et al 2009
Pafilas et al (2009) c
Thomsen et al (2010)
Chiriac et al (2012)
Taras et al (2011)d
Haug et al (2013)e
Present study (19 d–8.7 mo)
24%
(1 case 4 y, others < 1 y)
27%
(1–19 d)
Not specified
(delay not specified)
4%
(3–11 mo; mean, 5.5 mo)
100%
Not specified
(1 week–37 mo)
64%
Not specified
(1–16 mo)
61%
(delay not specified)
67%
(8%: 4–20 d, 10%: > 20 d)
18%
(delay not specified)
100%
2° reconstructions (delay)
(FU 12 mo)
40
(FU 12 mo)
42
(FU 12–59 mo)
21
(FU 14–36 mo)
8
(FU 12–17mo)
6
(FU mean, 17 mo)
19
(FU 12 mo)
(mean, 38 y)
17–75
(mean, 47 y)
11–83y
(mean, 44 y)
23–72
(mean, 45 y)
26–61 y
(mean, 33 y)
19–49 y
not specified
(mean, 38 y)
12–66 y
(mean, 39 y)
(FU 12–22 mo) 12
18–50 y
(mean, 40.3 y)
15–67 y
(mean, 44 y)
15–73
(mean, 36 y)
17–65y
(mean, 31 y)
Not specified.
Patient’s age
9
(FU 12–74 mo)
18
(FU 6–74 mo)
28
(FU 3–12 mo)
46
(FU 11–32 mo)
15
FU digital nerves. n (range)
(mean, 12.3 mm)
5–25 mm
(mean, 12 mm)
5–26 mm
(mean, 12 mm)
5–17 mm
(mean, 13.1 mm)
5–25 mm
(mean, 11.7 mm)
5–20 mm
(mean, 22 mm)
15–35 mm
(mean, 12.7 mm)
6–18 mm,
conduit 20 mm
not specified,
(mean, 20 mm)
10–40 mm
(mean, 21 mm)
10–40 mm
(mean, 7 mm)
5–30 mm
(mean, 17 mm)
5–30 mm
Gap length
8%
3
7%
3
43%
9
0%
0
17%
1
25%
3
44%
4
15
15%
6
40%
17
29%
11–15
No ps
0%
23%
9
19%
8
0
50%
4
0%
0
26%
5
17%
2
0%
0
32%
6
7%
2
26%
12
13%
2
ASSH classification, n, s2PD/mm
20%
8
67%
14
13%
1
17%
1
47%
9
33%
4
44%
4
11%
2
39%
11
43%
20
33%
5
6 (S4)
28%
43%
17
40%
17
6
13%
1
83%
5
26%
5
42%
5
56%
5
58%
11
54%
15
30%
14
53%
8
7–15 (S3þ)
38%
15
60%
25
5%
1
75%
6
0%
0
26%
5
25%
3
0%
0
32%
6
7%
2
26%
12
13%
2
> 15 (S3-S0)
MRCC, n, s2PD/mm:
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Abbreviations: ASSH, American Society for Surgery of the Hand; FU, follow-up; mo, months; MRCC, Medical Research Council classification; ps, protective sensibility; s2PD, static 2-point discrimination; y, years; 2°, secondary. Note: Whenever possible, results from FU < 12 months were excluded. a Weber (2000): For patients who did not return for the complete 12-month period (7 patients), the results of their last visit, whether at 3, 6, or 9 months were used. b Unclear in how many patients FU was < 12 months. c Published meeting abstract. d s2PD was not measured above 8 mm, m2PD measurements sometimes lead to a higher MRCC Score. e Additional data from personal communication.
Conduit-material
Authors
Table 2 Overview of digital nerve repair studies on artificial conduits providing data, which meet the ASSH or MRC classification
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measurements into five classes (normal, < 6 mm; fair, 6– 10 mm; poor, 11–15 mm; protective and anesthetic).26 Studies that provided data which fit the ASSH or MRC classification are summarized in ►Table 2.12,13,15–17,19,20,22,24,27,28 Both classifications are helpful tools in providing a standardized base needed for comparison. Including the presented data, nine studies could be found for comparison. However, some studies do rely on other classifications or do not specify the results in a comparable state.14,21,29 Due to short or unclear follow-up intervals the studies by Weber et al16 and Laroas et al17 were excluded from calculating the overall rate of poor outcome (S0–S3). In the remaining cumulative 150 nerve repairs, 68% showed static 2PD 15 mm (►Table 1). Six studies specified the presence of protective sensibility. In those studies, 23 of 114 conduit repairs (20%) resulted in no return of protective sensibility. In reverse, 80% recovered some degree of sensibility after digital nerve repair with artificial degradable conduits. This study confirms that the technique of tubulization with collagen nerve conduits can support good or excellent regeneration in approximately 51% of cases. However, regeneration failed completely in 23%. This poses the question why regeneration is excellent in some cases but absent in others, even though circumstances seem to be comparable. Histological workup in revision surgery showed neuromatous tissue within the collagen I conduit without inflammatory cells or granulomas.18 In our own experience, histological sections revealed chronic inflammatory response with perivascular leukocyte accumulation in all three explanted conduits in one patient. Indication for conduit removal and nerve grafting was set after complete absence of regenerative signs 6 months postoperatively. In four other conduit removals, mild foreign body reaction was seen only in one patient 6 months after implantation. We did not observe a significant influence with regard to patient’s age, sex, smoking habits, study center, and primary or secondary reconstruction. Significant better sensibility was seen after reconstruction of sharp versus crush injuries and if the nondominant hand was afflicted. Sharp injuries are known to correlate with better recovery, as well as the young age of the patient.16,30 Furthermore, we observed a significantly better return of sensibility if gap length was shorter than 12 mm. Weber et al also demonstrated worsening 2PD with increasing gap length. In their study PGA-conduit removal was necessary in 3 of 62 cases.16 Rinker and Liau confirmed a tendency to better results with gaps < 10 mm versus 10 mm. Worse results were reported in patients with a worker’s compensation claim, and in smokers. Two implant extrusions were seen in 36 PGA-conduit repairs.31 Implant extrusions have not yet been reported for collagen I conduits. Besides the nerve autograft, alternative techniques to the use of artificial conduits in nerve reconstruction are autologous veins with or without intraluminal muscle-slices, acellular nerve allografts and the end-to-side neurorrhaphy. Direct comparison of PGA-conduits to autologous vein grafts showed no significant differences in outcome after digital nerve repair in 68 cases in a prospective randomized study.31 Journal of Reconstructive Microsurgery
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Autologous vein grafts have shown comparable results to direct nerve repair or nerve grafting of digital nerve lesions in several small clinical trials.32,33 Some authors suggest filling the lumen with autologous muscle to prevent collapse. Results are reported equivalent to the autologous nerve graft.34 However, there is no conclusive evidence that results are superior to empty veins, and although donor site morbidity is minimal, operation time and trauma is further extended due to muscle harvesting. Despite the multiple studies describing the utilization of growth-promoting factors inside the lumens of nerve conduits, they have not been introduced in clinical practice. Tissue-engineered conduits enriched with neurotrophic factors will probably be an important developmental field from a future perspective.35 Processed nerve allografts are now commercially available as Avance (AxoGen Inc., Alachua, FL). In a recent evaluation of 35 sensory allograft nerve repairs in the upper extremities, return of sensibility was found to be significant in 89% of digital nerve repairs.36 This study outcome is very promising, but acquiring consent for allogeneic transplantation might be an issue for some patients. Further evaluation of this technique is required to estimate its role in peripheral nerve reconstruction.
Conclusion Today, peripheral nerve defects can be overcome by implementing different techniques without establishing the definite superiority of any one method. Specific advantages and drawbacks have to be taken into account when choosing the desired option. Collagen conduits for digital nerve repair are able to support peripheral nerve regeneration. They are associated with a complete failure rate with no protective sensibility for 12 months after surgery in approximately 20% and achieve some degree of 2PD in approximately 68% of cases. The shorter the nerve gap, the better the expected outcome for reconstruction.16 The maximum gap length to be bridged by conduit repair should not exceed 30 mm. Better results are seen if the defect is shorter than 12 mm.
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21 Bertleff MJ, Meek MF, Nicolai JP. A prospective clinical evaluation of
which primary repair can be achieved by end-to-end approximation: review of 2,181 nerve lesions. Microsurgery 1993;14(4): 244–246 Beris A, Lykissas M, Korompilias A, Mitsionis G. End-to-side nerve repair in peripheral nerve injury. J Neurotrauma 2007;24(5): 909–916 Archibald SJ, Krarup C, Shefner J, Li ST, Madison RD. A collagenbased nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates. J Comp Neurol 1991;306(4):685–696 Dellon AL, Kallman CH. Evaluation of functional sensation in the hand. J Hand Surg Am 1983;8(6):865–870 Stang F, Stollwerck P, Prommersberger KJ, van Schoonhoven J. Posterior interosseus nerve vs. medial cutaneous nerve of the forearm: differences in digital nerve reconstruction. Arch Orthop Trauma Surg 2013;133(6):875–880 Paprottka FJ, Wolf P, Harder Y, et al. Sensory recovery outcome after digital nerve repair in relation to different reconstructive techniques: meta-analysis and systematic review. Plast Surg Int 2013;2013:704589 Lohmeyer JA, Siemers F, Machens HG, Mailänder P. The clinical use of artificial nerve conduits for digital nerve repair: a prospective cohort study and literature review. J Reconstr Microsurg 2009; 25(1):55–61 Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg 1990; 85(3):419–424 Casanas J, Serra J, Orduna M, Garcia-Portabella M, Mir X. Repair of digital sensory nerves of the hand using polyglycolic acid conduits. J Hand Surg Br 2000;25(Suppl I):44 Pafilas DN, Vekris M, Gartzonikas D, Korompilias AV, Beris A. Digital nerve reconstruction in the hand using biodegradable polyglycolic acid conduits. J Bone Joint Surg 2009;91 (Suppl I):97 Weber RA, Breidenbach WC, Brown RE, Jabaley ME, Mass DP. A randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans. Plast Reconstr Surg 2000; 106(5):1036–1045, discussion 1046–1048 Laroas G, Battiston B, Sard A, Ferrero M, Dellon AL. Digital nerve reconstruction with the bioabsorbable neurotube. Clin Exp Plast Surg 2003;35:125–128 Wangensteen KJ, Kalliainen LK. Collagen tube conduits in peripheral nerve repair: a retrospective analysis. Hand (NY) 2010;5(3): 273–277 Taras JS, Jacoby SM, Lincoski CJ. Reconstruction of digital nerves with collagen conduits. J Hand Surg Am 2011;36(9):1441–1446 Haug A, Bartels A, Kotas J, Kunesch E. Sensory recovery 1. year after bridging digital nerve defects with collagen tubes. J Hand Surg Am 2013;38(1):90–97
biodegradable neurolac nerve guides for sensory nerve repair in the hand. J Hand Surg Am 2005;30(3):513–518 Chiriac S, Facca S, Diaconu M, Gouzou S, Liverneaux P. Experience of using the bioresorbable copolyester poly(DL-lactide-ε-caprolactone) nerve conduit guide Neurolac™ for nerve repair in peripheral nerve defects: report on a series of 28 lesions. J Hand Surg Eur Vol 2012;37(4):342–349 Meek MF. More than just sunshine with implantation of resorbable (p(DLLA-epsilon-CL)) biomaterials. Biomed Mater Eng 2007;17(5): 329–334 Thomsen L, Bellemere P, Loubersac T, Gaisne E, Poirier P, Chaise F. Treatment by collagen conduit of painful post-traumatic neuromas of the sensitive digital nerve: a retrospective study of 10 cases. Chir Main 2010;29(4):255–262 Mackinnon SE, Dellon AL. Surgery of the Peripheral Nerve. New York: Thieme; 1988 American Society for Surgery of the Hand. The Hand, Examination and Diagnosis. 3rd ed. New York: Churchill Livingstone; 1990 Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery 2005;25(4):258–267 Bushnell BD, McWilliams AD, Whitener GB, Messer TM. Early clinical experience with collagen nerve tubes in digital nerve repair. J Hand Surg Am 2008;33(7):1081–1087 Taras JS, Nanavati V, Steelman P. Nerve conduits. J Hand Ther 2005; 18(2):191–197 Lohmeyer JA, Hülsemann W, Mann M, Schmauss D, Machens HG, Habenicht R. [Return of sensibility after digital nerve reconstruction in children: How does age affect outcome?] Handchir Mikrochir Plast Chir 2013;45(5):265–270 Rinker B, Liau JY. A prospective randomized study comparing woven polyglycolic acid and autogenous vein conduits for reconstruction of digital nerve gaps. J Hand Surg Am 2011;36(5):775–781 Chiu DT, Strauch B. A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. Plast Reconstr Surg 1990;86(5):928–934 Walton RL, Brown RE, Matory WE Jr, Borah GL, Dolph JL. Autogenous vein graft repair of digital nerve defects in the finger: a retrospective clinical study. Plast Reconstr Surg 1989;84(6): 944–949, discussion 950–952 Battiston B, Tos P, Cushway TR, Geuna S. Nerve repair by means of vein filled with muscle grafts I. Clinical results. Microsurgery 2000;20(1):32–36 Konofaos P, Ver Halen JP. Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg 2013;29(3):149–164 Cho MS, Rinker BD, Weber RV, et al. Functional outcome following nerve repair in the upper extremity using processed nerve allograft. J Hand Surg Am 2012;37(11):2340–2349
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Collagen Nerve Conduits
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227
Prospective Clinical Study on Digital Nerve Repair with Collagen Nerve Conduits and Review of Literature
1 Department of Plastic Surgery and Hand Surgery, Klinikum rechts der
Isar, Technische Universität München, Munich, Germany 2 Department of Plastic Surgery, Agaplesion Diakonieklinikum Hamburg, Klinik für Plastische Chirurgie, Hamburg, Germany 3 Plastic, Hand and Reconstructive Surgery, Burn Unit, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
Felix Paprottka, MD1
Address for correspondence Joern Andreas Lohmeyer, MD, PhD, Department of Plastic Surgery, Agaplesion Diakonieklinikum Hamburg, Hohe Weide 17, 20259 Hamburg, Germany (e-mail: [email protected]).
J Reconstr Microsurg 2014;30:227–234.
Abstract
Keywords
► digital nerve reconstruction ► nerve conduit ► collagen I conduit ► nerve injury ► hand
Little data are available concerning conduit repair of digital nerve lesions. We are presenting a prospective two-center cohort study on digital nerve reconstruction with collagen nerve conduits. The data are put into the context of a comprehensive review of existing literature. Over a period of 3 years, all consecutive digital nerve lesions that could not be repaired by tensionless coaptation with a gap length of less than 26 mm were reconstructed with nerve conduits made from bovine collagen I. Sensibility was assessed 1 week, 3, 6, and 12 months postoperatively by static and moving 2-pointdiscrimination (2PD) and monofilament testing. Forty-nine digital nerve lesions in 40 patients met the inclusion criteria. The mean nerve gap was 12.3 2.3 mm (span 5–25 mm). Forty nerve reconstructions could be included in the 12-month follow-up. Three cases, assessed 12 months postoperatively, showed excellent sensibility (static 2PD < 6 mm). Seventeen achieved good (2PD 6–10 mm), 5 fair (2PD 11–15 mm), 6 poor (2PD > 15 mm, but protective sensibility), and 9 achieved no sensibility. Monofilament test results were significantly better if gap length was shorter than 12 mm. Our results confirm tubulization as one possible technique in nerve reconstruction for gap lengths of 5 to 25 mm.
Nerve injuries are common in trauma surgery and appear more frequently if the upper extremity is affected.1 Nerves are affected in approximately 10% of all hand injuries that require surgical treatment.2 The consequences may be numbness and an impairment of motor function. After repair, an intensive period of rehabilitation is required. Sick leave and sometimes the need for a change in profession and partial or even permanent total disability may have severe socioeconomic consequences for the patient and society.3,4 If the
upper extremity is affected, the most frequently injured nerves are the proper and common digital nerves, followed by the median and ulnar nerves.2,5 Complete transection of a peripheral nerve requires reconstruction of the continuity between the proximal and distal nerve stump. The gold standard for nerve injuries that cannot be overcome by direct tensionless coaptation is the nerve autograft. Primary repair by end-to-end coaptation can be performed in approximately 82% of the cases.6 Thus, usually 18% require nerve
received July 26, 2013 accepted after revision September 7, 2013 published online December 12, 2013
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1358788. ISSN 0743-684X.
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Joern Andreas Lohmeyer, MD, PhD1,2 Yasmin Kern, MD1 Daniel Schmauss, MD1 Felix Stang, MD3 Frank Siemers, MD, PhD3 Peter Mailaender, MD, PhD3 Hans-Guenther Machens, MD, PhD1
Collagen Nerve Conduits
Lohmeyer et al.
Fig. 1 Collagen I nerve conduit (NeuraGen, Integra) in a wet state (internal diameter 2 mm).
reconstruction by means of grafting or tubulization. In some cases, end-to-side neurorrhaphy can be an alternative.7 Digital nerve lesions are ideal for clinical outcome studies since results are easy to compare, but only a few studies provide comparable data for nerve reconstruction with artificial hollow conduits. We are presenting the final outcome of a prospective two-center study on digital nerve reconstruction with collagen nerve conduits in the context of a comprehensive summary of the pertinent published outcome studies.
Methods Over a period of 3 years, all consecutive digital nerve lesions with a gap length of equal to or less than 26 mm were reconstructed with NeuraGen nerve conduits (►Fig. 1), made from bovine collagen I (Integra Lifesciences, Plainsboro, NJ). A maximum conduit length of 30 mm and a minimum overlap of 2 mm on each side limited gap length to 26 mm. Subsequent to informed consent, no patient refused to participate in the study. Cases were excluded from the study if reconstruction was performed later than 12 months following injury, or if severe wound contamination was evident. Further defined exclusion criteria were the diagnosis of polyneuropathy, pre-existing damage to the injured nerve (e.g., trauma or chronic compression disease), injury at
different levels of the nerve, acute local infection, lack of soft-tissue coverage and life expectancy < 1 year due to malignancy or other systemic diseases. The study has been approved by the local ethical review board and is registered at Current Controlled Trials (ISRCTN18539256). We restricted the indication for tubulization to common and proper palmar digital nerves. NeuraGen conduits are available in a maximum length of 30 mm. The semipermeable tubes are made from bovine tendon and are available in different diameters ranging from 1.5 to 7 mm. In our study, all patients received conduits with an internal diameter of 2 or 3 mm. In a moist state, wall thickness is quite precisely 0.5 mm. Conduits are soft, pliable and completely degraded within 36 months after insertion in monkeys.8 All patients were operated on by microsurgically trained plastic surgeons. A clinical example is shown in ►Fig. 2A, B. The operating microscope was used in all operations. The repair of concomitant injuries to the hand, as well as exposure of the severed nerve ends, was performed under tourniquet control. This had to be released (followed by meticulous hemostasis) prior to insertion of the nerve ends into the conduit to prevent bleeding into the lumen since the formation of a blood clot inside the tube might be detrimental to nerve regeneration. After proper debridement, proximal and distal nerve endings were inserted into the conduit with an overlap of approximately 3 mm. To evacuate the conduit from potentially remaining blood clots, the lumen was rinsed with normal saline after each suture, which was usually performed with one 9–0 nylon suture in a horizontal mattress fashion through the conduit and epineurium at both sides. We decided to administer a single-shot of 1.5 g cefuroxime intravenously to prevent infection. Immobilization of the adjacent joints was assured for 14 days. In the case of concomitant tendon repair early mobilization was performed. Sensibility was assessed using static and moving twopoint discrimination (2PD) and monofilament testing in the first postoperative week and after 3, 6, and 12 months. For 2PD tests, we used the Mackinnon-Dellon Disk-Criminator (Mackinnon-Dellon Partnership, Baltimore, MD). Modified guidelines of the American Society for Surgery of the Hand (ASSH) were used to stratify the 2PD measurements (excellent, < 6 mm; good, 6–10 mm; fair, 11–15 mm; poor, > 15 mm).9 Furthermore, 2PD of the uninjured contralateral
Fig. 2 (A, B) A 66-year-old male patient presenting an acute laceration of the radial proper digital nerve of the index. Primary conduit repair of the 10 mm gap with an overlap of 3 mm at distal and proximal stump. Journal of Reconstructive Microsurgery
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229
finger was assessed and the difference of injured and uninjured nerve was calculated to form a Δ2PD to avoid bias by inter-individual differences in normal sensibility. Monofilaments with calibrated pressure of 0.07, 0.4, 2, 4, and 10 g were used (Touch-Test Sensory Evaluator, North Coast Medical Inc., Morgan Hill, CA). For the lowest reported monofilament, inconsistent or consistent (100%) detection of monofilament touch was reported. Sensibility testing was performed without digital nerve block for the intact nerve.
Exact Wilcoxon–Mann–Whitney Rank Sum Test was used to look for significant correlation between possible influencing factors and outcome scores. Fisher’s exact test was used to compare our results with the results found in the literature.
Results
Fig. 4 Δ2PD (difference of the static 2-point discrimination of injured and uninjured contralateral digit) at the three follow-up visits (pr. sens., protective sensibility; mo, months). Results are classified in Δ2PD 3 mm, 4–6 mm, 7–12 mm, > 12 mm with and without protective sensibility.
Two study centers were included for evaluation. Together, 55 nerve reconstructions with NeuraGen conduits were recorded in 45 patients. Five patients (6 nerve repairs) had to be excluded, three due to delay of nerve reconstruction > 365 days after injury. Two patients were recorded as collagen conduit repairs but were not further assessed. Of the remaining patients 88% were available for follow-up at 3 months, 92% at 6 months, and 82% at 12 months. The male to female ratio was 45:4 (92% male). The mean age at operation time was 37.9 years (17–75 years, median 31 years). The dominant hand was affected in 35% of the cases. The index finger was affected most often (47%), followed by the thumb (24%), middle and ring finger (12% each). The little finger was injured in two cases (4%). The mean nerve gap length after debridement measured 12.3 mm (5–25 mm, median 12 mm). The mean conduit length was 18.4 mm (7–30 mm, median 18 mm). The mean distance of the proximal coaptation to the fingertip was
75 mm (40–135 mm, median 70 mm). Cut injuries were reported in 63%, crush or tension injuries in 37%. The ratio of acute versus delayed repair was 76 to 24%. The mean delay was 95 days (19–264 days). No patient suffered from alcoholism, diabetes, neuropathy, or collagenous diseases; 39% were active smokers. The return of sensibility at the different time-points measured with static 2PD and Semmes-Weinstein monofilament testing is depicted in ►Figs. 3–5. We saw significantly better results in the monofilament test in cases of sharp versus crush injuries (p < 0.05) and when the nondominant hand was involved (p < 0.05). Monofilament test results were significantly better if gap length was shorter than 12 mm (p < 0.05). We did not observe a significant influence of patient’s age, sex, smoking habits, study center, and primary versus secondary reconstruction (►Table 1).
Fig. 3 Return of sensibility according to the modified guidelines of the American Society for Surgery of the Hand. Continuous progress is seen until the last examination at 12 months. No further significant reduction of the rate of complete failure of regeneration without protective sensibility after 6 months.
Fig. 5 Monofilament test results at the three follow-up visits. “ þ ” indicates that the specific stimulus is always recognized. “o” indicates that the stimuli are infrequently recognized. “-” indicates no recognition. Journal of Reconstructive Microsurgery
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Statistics
Collagen Nerve Conduits
Lohmeyer et al.
Table 1 Correlation between possible influencing factors and monofilament testing outcome
Gap length < 12 mm Cut injury Smoker Primary reconstruction Dominant hand affected
Lowest reported monofilament
p
Yes
2g
0.038
No
4g
Yes
2g
No
4g
Yes
2 g inconsistent
No
2g
Yes
2g
No
2 g inconsistent
Yes
4g
No
2g
0.035 0.259 0.729 0.027
Notes: The median force of the lowest reported monofilaments is shown. For the lowest reported monofilament, inconsistent or consistent (100%) detection of monofilament touch was reported.
Discussion The tension-free nerve coaptation is the method of choice for reconstruction after complete nerve transection. Retraction of the nerve endings, tissue loss due to trauma or necessary debridement can lead to extended nerve gaps that require alternative surgery. Today, the gold standard is the autologous nerve graft, but graft harvesting usually causes some degree of donor site morbidity and the amount of nerves suitable for transplantation is limited.10,11 Artificial nerve conduits have become a possible alternative to nerve grafting, the biggest advantage being that they obviate the need for a nerve donor site. Only few clinical studies exist that deal with the use of biodegradable artificial hollow nerve conduits for digital nerve repair.12 In 1990, Mackinnon and Dellon were the first to report on 15 digital nerve lesions being reconstructed with hollow polyglactin (PGA) conduits.13 Casanas et al stated sensibility improvement in every case after 17 digital nerve repairs with PGA-conduits,14 but results were not further specified. We found one further published meeting abstract presenting data on 19 digital nerve repairs with PGA-conduits.15 At a mean 17 months postoperatively, return of 2PD was documented in 74% of reconstructions. However, as a meeting abstract, it remains unclear to which extent methods and results of that study were peer-reviewed. In 2000, Weber et al compared 46 PGA-conduit repairs with 56 direct coaptations (partly under tension) or nerve grafts in a prospective randomized study. No significant difference was seen in outcome between the two groups as a whole.16 However, three conduit removals and six fingers that were amputated later were not accounted for evaluation, and the percentage of follow-up at only 3, 6, and 9 months was higher in the control group. Laroas et al published their results on 28 PGA-conduit repairs in 2003.17 The authors report that with sensory reJournal of Reconstructive Microsurgery
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education the success rate can be increased to 100%. This looks like an unreasonable conclusion, with only one failure in the medium-sized defect group. Furthermore, it remains unclear how many results were included with a follow-up of less than 12 months. Range of follow-up was 6 to 74 months. However, results were excellent with 93% regaining a 2PD of 3 to 15 mm. In contrast, Wangensteen and Kalliainen found postoperative improvement in only 35% of cases after nerve reconstruction with collagen I conduits. However, the study does not provide specific information about the outcome in digital nerve repair. Instead results are summarized for all treated nerves. 2PD measurements were only performed in 21% of repairs and patients in need of surgical revision were more likely to be examined. Average follow-up with 2PD measurements was 371 days; it is not mentioned how many patients were examined in less than 12 months following surgery. 18 Taras et al presented more favorable results with the same conduit in 2011.19 In all 21 nerve reconstructions moving 2PD of at least 8 mm was found 12 to 59 months after tubulization. Six patients did not regain measurable static 2PD. For 2PD measurements the two pins were applied transversely to the long axis of the finger. Thus, values were only measured up to 8 mm and everything above that was rated as poor. Most other studies also rate the static 2PD range of 9 to 15 mm as good. In the same study in four cases moving 2PD was worse than static 2PD, which seems rather unlikely. Thus, there are some limitations in comparing the results with other studies. The most recent study about digital nerve reconstruction with collagen I conduits was published by Haug et al in 2013.20 The authors present their results of 42 NeuraGen conduit reconstructions with a follow-up of 12 months. The failure rate, according to a static 2PD > 15mm, was as high as 60%. However, the authors rated the functional outcome as good in the majority of cases using a new sum score comprising seven different clinical tests. Usual perception would probably have led to a different conclusion. In 2005, Bertleff et al compared 21 poly-(DL-lactide-εcaprolactone) conduit repairs to 13 direct coaptations and stated overall good sensory recovery without significant differences between groups.21 On average, gap length was 6 to 8 mm. Results were not categorized. Other reports complained about the rigidity of the material, which might be especially troublesome at the joint levels.22,23 Thomsen et al presented the only data on 10 digital nerve reconstructions with porcine collagen I þ III conduits (Revolnerv, Orthomed, St. Jeannet, France).24 All six cases with a gap length of 5 to 20 mm and a follow-up of at least 12 months showed static 2PD of 4 to 15 mm. Clinical studies on digital nerve repair with conduits often present different scoring systems that render direct comparison difficult. Two grading systems with several modifications are mainly used. First, the Medical Research Council (MRC) classification, was promoted and standardized as a grading scale for motor and sensory outcome.25 Both, static and moving 2PD are used for classification. The alternate guideline of the ASSH uses a more subtle distinction in the 2PD
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230
Polyglycolic acid
Polyglycolic acid
Polyglycolic acid
Polyglycolic acid
Bovine collagen I
Bovine collagen I
Polyglycolic acid
Porcine collagen I þ III
poly(DL-lactideε-caprolactone)
Bovine collagen I
Bovine collagen I
Bovine collagen I
Mackinnon and Dellon (1990)
Weber et al (2000) a
Laroas et al (2003)b
Battiston et al (2005)
Bushnell et al (2008)
Lohmeyer et al 2009
Pafilas et al (2009) c
Thomsen et al (2010)
Chiriac et al (2012)
Taras et al (2011)d
Haug et al (2013)e
Present study (19 d–8.7 mo)
24%
(1 case 4 y, others < 1 y)
27%
(1–19 d)
Not specified
(delay not specified)
4%
(3–11 mo; mean, 5.5 mo)
100%
Not specified
(1 week–37 mo)
64%
Not specified
(1–16 mo)
61%
(delay not specified)
67%
(8%: 4–20 d, 10%: > 20 d)
18%
(delay not specified)
100%
2° reconstructions (delay)
(FU 12 mo)
40
(FU 12 mo)
42
(FU 12–59 mo)
21
(FU 14–36 mo)
8
(FU 12–17mo)
6
(FU mean, 17 mo)
19
(FU 12 mo)
(mean, 38 y)
17–75
(mean, 47 y)
11–83y
(mean, 44 y)
23–72
(mean, 45 y)
26–61 y
(mean, 33 y)
19–49 y
not specified
(mean, 38 y)
12–66 y
(mean, 39 y)
(FU 12–22 mo) 12
18–50 y
(mean, 40.3 y)
15–67 y
(mean, 44 y)
15–73
(mean, 36 y)
17–65y
(mean, 31 y)
Not specified.
Patient’s age
9
(FU 12–74 mo)
18
(FU 6–74 mo)
28
(FU 3–12 mo)
46
(FU 11–32 mo)
15
FU digital nerves. n (range)
(mean, 12.3 mm)
5–25 mm
(mean, 12 mm)
5–26 mm
(mean, 12 mm)
5–17 mm
(mean, 13.1 mm)
5–25 mm
(mean, 11.7 mm)
5–20 mm
(mean, 22 mm)
15–35 mm
(mean, 12.7 mm)
6–18 mm,
conduit 20 mm
not specified,
(mean, 20 mm)
10–40 mm
(mean, 21 mm)
10–40 mm
(mean, 7 mm)
5–30 mm
(mean, 17 mm)
5–30 mm
Gap length
8%
3
7%
3
43%
9
0%
0
17%
1
25%
3
44%
4
15
15%
6
40%
17
29%
11–15
No ps
0%
23%
9
19%
8
0
50%
4
0%
0
26%
5
17%
2
0%
0
32%
6
7%
2
26%
12
13%
2
ASSH classification, n, s2PD/mm
20%
8
67%
14
13%
1
17%
1
47%
9
33%
4
44%
4
11%
2
39%
11
43%
20
33%
5
6 (S4)
28%
43%
17
40%
17
6
13%
1
83%
5
26%
5
42%
5
56%
5
58%
11
54%
15
30%
14
53%
8
7–15 (S3þ)
38%
15
60%
25
5%
1
75%
6
0%
0
26%
5
25%
3
0%
0
32%
6
7%
2
26%
12
13%
2
> 15 (S3-S0)
MRCC, n, s2PD/mm:
Journal of Reconstructive Microsurgery
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Abbreviations: ASSH, American Society for Surgery of the Hand; FU, follow-up; mo, months; MRCC, Medical Research Council classification; ps, protective sensibility; s2PD, static 2-point discrimination; y, years; 2°, secondary. Note: Whenever possible, results from FU < 12 months were excluded. a Weber (2000): For patients who did not return for the complete 12-month period (7 patients), the results of their last visit, whether at 3, 6, or 9 months were used. b Unclear in how many patients FU was < 12 months. c Published meeting abstract. d s2PD was not measured above 8 mm, m2PD measurements sometimes lead to a higher MRCC Score. e Additional data from personal communication.
Conduit-material
Authors
Table 2 Overview of digital nerve repair studies on artificial conduits providing data, which meet the ASSH or MRC classification
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measurements into five classes (normal, < 6 mm; fair, 6– 10 mm; poor, 11–15 mm; protective and anesthetic).26 Studies that provided data which fit the ASSH or MRC classification are summarized in ►Table 2.12,13,15–17,19,20,22,24,27,28 Both classifications are helpful tools in providing a standardized base needed for comparison. Including the presented data, nine studies could be found for comparison. However, some studies do rely on other classifications or do not specify the results in a comparable state.14,21,29 Due to short or unclear follow-up intervals the studies by Weber et al16 and Laroas et al17 were excluded from calculating the overall rate of poor outcome (S0–S3). In the remaining cumulative 150 nerve repairs, 68% showed static 2PD 15 mm (►Table 1). Six studies specified the presence of protective sensibility. In those studies, 23 of 114 conduit repairs (20%) resulted in no return of protective sensibility. In reverse, 80% recovered some degree of sensibility after digital nerve repair with artificial degradable conduits. This study confirms that the technique of tubulization with collagen nerve conduits can support good or excellent regeneration in approximately 51% of cases. However, regeneration failed completely in 23%. This poses the question why regeneration is excellent in some cases but absent in others, even though circumstances seem to be comparable. Histological workup in revision surgery showed neuromatous tissue within the collagen I conduit without inflammatory cells or granulomas.18 In our own experience, histological sections revealed chronic inflammatory response with perivascular leukocyte accumulation in all three explanted conduits in one patient. Indication for conduit removal and nerve grafting was set after complete absence of regenerative signs 6 months postoperatively. In four other conduit removals, mild foreign body reaction was seen only in one patient 6 months after implantation. We did not observe a significant influence with regard to patient’s age, sex, smoking habits, study center, and primary or secondary reconstruction. Significant better sensibility was seen after reconstruction of sharp versus crush injuries and if the nondominant hand was afflicted. Sharp injuries are known to correlate with better recovery, as well as the young age of the patient.16,30 Furthermore, we observed a significantly better return of sensibility if gap length was shorter than 12 mm. Weber et al also demonstrated worsening 2PD with increasing gap length. In their study PGA-conduit removal was necessary in 3 of 62 cases.16 Rinker and Liau confirmed a tendency to better results with gaps < 10 mm versus 10 mm. Worse results were reported in patients with a worker’s compensation claim, and in smokers. Two implant extrusions were seen in 36 PGA-conduit repairs.31 Implant extrusions have not yet been reported for collagen I conduits. Besides the nerve autograft, alternative techniques to the use of artificial conduits in nerve reconstruction are autologous veins with or without intraluminal muscle-slices, acellular nerve allografts and the end-to-side neurorrhaphy. Direct comparison of PGA-conduits to autologous vein grafts showed no significant differences in outcome after digital nerve repair in 68 cases in a prospective randomized study.31 Journal of Reconstructive Microsurgery
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Autologous vein grafts have shown comparable results to direct nerve repair or nerve grafting of digital nerve lesions in several small clinical trials.32,33 Some authors suggest filling the lumen with autologous muscle to prevent collapse. Results are reported equivalent to the autologous nerve graft.34 However, there is no conclusive evidence that results are superior to empty veins, and although donor site morbidity is minimal, operation time and trauma is further extended due to muscle harvesting. Despite the multiple studies describing the utilization of growth-promoting factors inside the lumens of nerve conduits, they have not been introduced in clinical practice. Tissue-engineered conduits enriched with neurotrophic factors will probably be an important developmental field from a future perspective.35 Processed nerve allografts are now commercially available as Avance (AxoGen Inc., Alachua, FL). In a recent evaluation of 35 sensory allograft nerve repairs in the upper extremities, return of sensibility was found to be significant in 89% of digital nerve repairs.36 This study outcome is very promising, but acquiring consent for allogeneic transplantation might be an issue for some patients. Further evaluation of this technique is required to estimate its role in peripheral nerve reconstruction.
Conclusion Today, peripheral nerve defects can be overcome by implementing different techniques without establishing the definite superiority of any one method. Specific advantages and drawbacks have to be taken into account when choosing the desired option. Collagen conduits for digital nerve repair are able to support peripheral nerve regeneration. They are associated with a complete failure rate with no protective sensibility for 12 months after surgery in approximately 20% and achieve some degree of 2PD in approximately 68% of cases. The shorter the nerve gap, the better the expected outcome for reconstruction.16 The maximum gap length to be bridged by conduit repair should not exceed 30 mm. Better results are seen if the defect is shorter than 12 mm.
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Collagen Nerve Conduits
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