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Inflammatory Reactions to Xenogenic Nerve Wraps

A Report of Three Cases

Zeng, Wenjing MD1; Osterman, Meredith MD2; Stern, Peter J. MD3

doi: 10.2106/JBJS.CC.18.00302
Case Reports
Free
Disclosures

Case: Recurrent carpal tunnel syndrome is a challenging problem. Nerve wraps have been introduced as a barrier to prevent scar traction neuritis for use during revision carpal tunnel surgery. We present 3 cases of inflammatory responses to bovine collagen and porcine subintestinal mucosal nerve wraps in patients undergoing revision carpal tunnel surgery. No patient had evidence of infection, and pathology revealed acute and chronic inflammation. All 3 patients responded favorably following wrap removal.

Conclusions: We recommend caution with the routine use of nerve wraps in the setting of revision carpal tunnel surgery.

1TriHealth Hand Surgery Specialists, Cincinnati, Ohio

2The Philadelphia Hand Center, King of Prussia, Pennsylvania

3Department of Orthopedics, University of Cincinnati College of Medicine, Cincinnati, Ohio

E-mail address for W. Zeng: wenjing_zeng@trihealth.com

Investigation performed at Trihealth Hand Surgery Specialists, Cincinnati, Ohio and University of Cincinnati Department of Orthopedics, Cincinnati, Ohio

Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/A829).

Carpal tunnel decompression is a common procedure with predictable relief of median nerve symptoms. A subset of patients, however, require revision surgery. In a cohort of 97 patients undergoing revision surgery, 43% had persistent carpal tunnel syndrome, showing little or no improvement after carpal tunnel decompression and 20% had recurrent carpal tunnel syndrome, with a period symptom relief followed by recurrence of symptoms1. There are several techniques to prevent scar formation during revision, but no randomized controlled studies compare them. Reports include retrospective case series of vein wrapping, nerve conduits, and various grafts, such as the hypothenar fat graft, palmaris brevis flap, and synovial and fascial flaps2-10. Recently, commercial nerve wraps have also been introduced. NeuraWrap (Integra Lifesciences) is an absorbable xenogenic type I collagen conduit designed for treating injured, compressed, or scarred nerves. It consists of semipermeable bovine collagen and reportedly has the ability to retain nerve growth factors within the inner chamber of the wrap11. Another nerve wrap is Axoguard (AxoGen), an absorbable wrap of porcine small intestinal submucosa that is processed to maintain the tissue's noncollagenous components and extracellular matrix structure. Both materials allow for nerve gliding and act as mechanical barriers to scar tissue12-15.

Each patient was informed that data concerning the case would be submitted for publication, and they provided consent.

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Case Reports

Case 1. A 57-year-old woman presented with a long-standing history of paresthesias in the median nerve distribution. Clinical examination and electrodiagnostic studies were consistent with carpal tunnel syndrome. After 6 months of conservative treatment, she underwent uneventful open carpal tunnel decompression for persistent symptoms. Postoperatively, she experienced no improvement. Five months postoperatively, she underwent a second median nerve exploration. There were no overt signs of compression, no indication of an incomplete previous release, and no evidence of median nerve injury. A limited internal neurolysis was performed under loupe magnification, and the nerve was wrapped with a collagen tube (NeuraWrap; Integra). She reported near complete resolution of symptoms at her first postoperative visit. At 6 weeks of follow-up, she was discharged from care.

She returned 3 months postoperatively with swelling over the incision (Fig. 1). She reported that the volar wrist swelling never subsided following the revision surgery and it increased over time. She reported no numbness, tingling, or pain. On examination, she had focal swelling proximal to her wrist crease with a subcutaneous palpable tubelike structure. There was no Tinel sign over the median nerve and 2-point discrimination was 6 mm in all digits. There was no erythema or fluctuance. Inflammatory values were all within normal limits.

Fig. 1

Fig. 1

Four months following revision, the nerve wrap was removed. There was no sign of infection (Fig. 2). The nerve wrap was extremely adherent to the nerve (Fig. 3). The nerve showed signs of compression at the proximal and distal edges of the wrap with hypertrophy of the nerve at the area of previous neurolysis.

Fig. 2

Fig. 2

Fig. 3

Fig. 3

Routine, acid fast, atypical mycobacterium and fungal cultures were all negative. The pathology revealed fibrous tissue with an acute and chronic inflammatory response to acellular eosinophilic material with minute foci of necrosis (Fig. 4).

Fig. 4

Fig. 4

Ten days postoperatively, she was asymptomatic and her swelling markedly decreased. At 14 months postoperatively, there was no incisional swelling but she did report persistent numbness in the median nerve distribution.

Case 2. A 47-year-old woman presented with numbness and tingling in the median nerve distribution. She underwent open carpal tunnel release, but had persistent symptoms with no improvement postoperatively. Electrodiagnostic studies were unchanged from the preoperative study. Examination demonstrated mild thenar atrophy and 2-point discrimination in the median nerve distribution was 12 to 15 mm. Five months postoperatively, she underwent median nerve exploration. Intraoperatively, there was tenosynovitis surrounding her flexor tendons, but no evidence of infection. Surgical pathology showed benign, mildly hyperplastic noninflammatory synovium. A limited internal neurolysis was performed under loupe magnification, and the median nerve was wrapped with a porcine subintestinal mucosal nerve wrap (Axoguard; Axogen).

Two months following revision, she returned with palpable tenosynovitis at the wrist proximal to the carpal canal (Fig. 5). Her numbness had resolved. She underwent explantation of the nerve wrap. Intraoperatively, there was extensive hypertrophic tenosynovium surrounding the nerve wrap and the flexor tendons, extending distally to the superficial arch. Routine, acid fast, atypical mycobacterium and fungal cultures were all negative. Pathology revealed fibrovascular tissue with fibrinoid necrosis, areas of acute inflammation, focal areas of palisading granulomatous reaction (Fig. 5), as well as areas of chronic inflammation.

Fig. 5

Fig. 5

Five months after nerve wrap explantation, she was asymptomatic.

Case 3. A 54-year-old female presented with left hand numbness and tingling. She had undergone several prior upper extremity surgeries, including cubital tunnel release, open carpal tunnel release, carpal tunnel revision surgery with external neurolysis, pronator release, and wrapping of her median nerve with a bovine collagen nerve wrap (NeuraWrap; Integra). She presented for evaluation 9 years after the prior surgeries with a gradually enlarging volar wrist mass and worsening numbness and tingling throughout her hand.

Examination demonstrated a well-healed incision with a prominence at the wrist in the region of the nerve wrap (Fig. 6). She had mild thenar atrophy. Provocative testing revealed a positive Tinel sign over the median nerve at the wrist. Two-point discrimination was greater than 15 mm in the median nerve distribution, 8 mm on the ulnar aspect of the ring finger, and 6 mm in the small finger.

Fig. 6

Fig. 6

Ultrasound demonstrated stenosis or compression of the median nerve at the level of the nerve wrap, with enlarged cross-sectional area proximally. Electrodiagnostic studies demonstrated decreased motor and sensory latencies of the median nerve at the wrist consistent with carpal tunnel syndrome.

Ten years after her revision carpal tunnel surgery, the median nerve was explored. There was considerable constriction and scarring proximal to the wrist crease, mostly around where the previous nerve wrap had been placed (Fig. 7). The wrap was explanted. Pathology demonstrated granulomatous and inflammatory reaction to fibrin and devitalized collagen and dense fibrosis of the epineurum (Fig. 8).

Fig. 7

Fig. 7

Fig. 8

Fig. 8

Eight months postoperatively, the patient had no recurrent synovitis and was asymptomatic.

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Discussion

Management of post-traumatic scarring around nerves is a challenge faced by all hand surgeons. Multiple procedures have been described for creating a barrier to epineural scarring and include adipofascial or muscle flaps, autologous vein grafts, and, recently, commercially available nerve conduits2,4,16-18. As an alternative, nerve conduits can be used to surround a nerve that has been repaired after a traumatic laceration. Like vein grafts, they are an option for preventing adhesions and scar formation around the injured nerve or one that resides in an unhealthy bed of soft tissue19,20. Two recently introduced neuro-protective barriers are porcine intestinal submucosal wrap (Axoguard) receiving FDA approval in 2003 and the collagen nerve wrap (Neuragen) receiving FDA approval in 200421. More recently, other commercially available nerve wraps have emerged, but are not FDA approved for compressive neuropathy22.

It is unclear, however, what impact placing a nerve wrap has on our patients16. Furthermore, we do not know the biological factors which result in nerve wrap tolerance in most patients and intolerance in others. The vast majority of literature on nerve wraps comprise animal models, though we are not aware of animal studies investigating nerve wraps for compressive neuropathy22. A case series of 5 patients using acellular cadaveric dermis wraps for recurrent cubital tunnel showed promising results without any adverse events23. Soltani et al. reported favorable outcomes in 15 patients without recorded adverse events over 14 months follow-up when utilizing collagen nerve conduits for recurrent compressive neuropathies of both the median and ulnar nerves18. A case series of 12 patients reported favorable outcomes without adverse events over 41 months follow-up in patients undergoing nerve wrapping with porcine subintestinal mucosal wraps in patients with recurrent cubital tunnel syndrome17. Nevertheless, a recent review of the literature by Dy et al. shows that only 3 case series in total have been published on the use of commercially available nerve wraps for compressive neuropathy22. The largest of these series comprised 15 patients.

Only one study documents an adverse event from a nerve tube or wrap. Four patients undergoing explantation of collagen nerve tubes for failed digital nerve repair reported a single case of considerable scar formation and foreign body reaction. Since 2008, 3 complaints of “inflammation” with Neuragen have been reported to the FDA, though details provided are limited24. No complaints have been reported with NeuraWraps. One complaint of considerable swelling, inflammation, and scar formation without evidence of infection has been reported to the FDA with the Axoguard.

We report 3 cases of inflammatory response to the use of nerve wraps for persistent or recurrent carpal tunnel syndrome. In all cases, cultures were negative and pathology demonstrated acute and chronic inflammation. All 3 patients responded favorably following explantation of the wrap. Given the limited data involving complications with these devices, we recommend careful follow-up for adverse reactions with the routine use of nerve wraps in the setting of compressive neuropathy.

Note: We thank Lindsey Lowder, DO, George Mutema, MD, Shiyama Mudali, MD, Ady Kendler, MD, and Amanda Schroeder, MD with their assistance with the preparation of the photomicrographs for this manuscript.

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References

1. Zieske L, Ebersole GC, Davidge K, Fox I, Mackinnon SE. Revision carpal tunnel surgery: a 10-year review of intraoperative findings and outcomes. J Hand Surg Am. 2013;38(8):1530-9.
2. Sotereanos D, Giannakopoulos P, Mitsionis G, Xu J, Herndon J. Vein-graft wrapping for the treatment of recurrent compression of the median nerve. Microsurgery. 1995;16:752-6.
3. Varitimidis S, Riano F, Vardakas D, Sotereanos D. Recurrent compressive neuropathy of the median nerve at the wrist: treatment with autogenous saphenous vein wrapping. J Hand Surg Br. 2000;25:271-5.
4. Rose E. The use of the palmaris brevis flap in recurrent carpal tunnel syndrome. Hand Clin. 1996;12(2):389-95.
5. Fusetti C, Garavaglia G, Mathoulin C, Petri J, Lucchina S. A reliable and simple solution for recalcitrant carpal tunnel syndrome: the hypothenar fat pad flap. Am J Orthop. 2009;38(4):181-6.
6. Chrysopoulo M, Greenberg J, Kleinman W. The hypothenar fat pad transposition flap: a modified surgical technique. Tech Hand Up Extrem Surg. 2006;10(3):150-6.
7. Mahmoud M, El Shafie S, Coppola E, Elfar J. Perforator-based radial forearm fascial flap for management of recurrent carpal tunnel syndrome. J Hand Surg Am. 2013;38(11):2151-8.
8. Craft R, Duncan S, Smith A. Management of recurrent carpal tunnel syndrome with microneurolysis and the hypothenar fat pad flap. Hand 2007;2:85-9.
9. Wulle C. The synovial flap as treatment of the recurrent carpal tunnel syndrome. Hand Clin. 1996;12(2):379-88.
10. Tham S, Ireland D, Riccio M, Morrison W. Reverse radial artery fascial flap: a treatment for the chronically scarred median nerve in recurrent carpal tunnel syndrome. J Hand Surg Am. 1996;21:849-54.
11. Danielsson P, Dahlin L, Povlsen B. Tubulization increases axonal outgrowth of rat sciatic nerve after crush injury. Exp Neurol. 1996;139(2):238-43.
12. NeuraWrap Brochure and Product description. Data on file at Integra LifeSciences Corporation. https://www.integralife.com/file/general/1456850280.pdf. Accessed 2019 Jul 11.
13. Li S, Archibald S, Krarup C, Madison R. Peripheral nerve repair with collagen conduits. Clin Mater. 1992;9(3-4):195-200.
    14. Boeckstyns ME, Sorensen AI, Viñeta JF, Rosén B, Navarro X, Archibald SJ, Valss-Solé J, Moldovan M, Krarup C. Collagen conduit versus microsurgical neurorrhapy: 2-year follow-up of a prospective, blinded clinical and electrophysiological multicenter randomized, controlled trial. J Hand Surg Am. 2013;38(12):2405-11.
    15. AxoGuard Brochure and Product description. Data on file at Axogen Corporation. http://www.axogeninc.com/wp-content/uploads/2019/01/LB-139R06FamilyBrochure-1.pdf. Accessed 2019 Jul 11.
    16. Xu J, Varitimidis SE, Fisher KJ, Tomaino MM, Sotereanos DG. The effect of wrapping scarred nerves with autogenous vein graft to treat recurrent chronic nerve compression. J Hand Surg Am. 2000;25(1):93-103.
    17. Papatheodorou LK, Williams BG, Sotereanos DG. Preliminary results of recurrent cubital tunnel syndrome treated with neurolysis and porcine extracellular matrix nerve wrap. J Hand Surg Am. 2015;40(5):987-92.
    18. Soltani AM, Allan BJ, Best MJ, Mir HS, Panthaki ZJ. Revision decompression and collagen nerve wrap for recurrent and persistent compression neuropathies of the upper extremity. Ann Plast Surg. 2014;72(5):572-8.
    19. Kim P, Hayes A, Ain F, Akelina F, Hays A, Rosenwasser M. Collagen nerve protector in rat sciatic nerve repair: a morphometric and histological analysis. Microsurgery. 2010;30(5):392-6.
    20. Robert S, Strauch B. Nerve conduits: an update on tubular nerve repair and reconstruction. J Hand Surg. 2013;38(6):1252-5.
    21. Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury. 2012;43(5):553-72.
    22. Dy CJ, Aunins B, Brogan DM. Barriers to epineural scarring: role in treatment of traumatic nerve injury and chronic compressive neuropathy. J Hand Surg Am. 2018;43(4):360-7.
    23. Puckett B, Gaston R, Lourie E. A novel technique for the treatment of recurrent cubital tunnel syndrome: ulnar nerve wrapping with a tissue engineered bioscaffold. J Hand Surg Eur. 2011;36:130-4.
    24. Catalog Number PNG620; Event Date 12/9/08. FDA U.S. Food and Drug Administration MAUDE Adverse Event Report.

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