Human amniotic membrane as adjunct to nerve and tendon repair in the lower extremity Lauren Kishman DPM1, Eric Lew DPM1, Mark Hardy DPM FACFAS2

1Residents, Podiatric Medicine and Surgery, Kaiser Permanente / Cleveland Clinic 2Staff, Department of Foot and Ankle Surgery, HealthSpan Physicians Group, Cleveland Ohio

Statement of Purpose Cases

Analysis and Discussion

Literature Review

Post-operative scar tissue and adhesion development is inherent to foot and ankle surgery. This complication is particularly problematic following the release of nerve entrapments and flexor tendon repairs. The development of adhesions following these procedures is common and the resulting complications significant with recurrent pain, limited motion and/or neuritis resulting. The ability to limit scar and adhesion formation following these challenging procedures would have significant positive impact on patient satisfaction and post-operative outcomes.

The development of post-operative scar tissue and adhesions is inherent to foot and ankle surgery. Two areas in which this complication is particularly challenging are in the release of nerve entrapments and flexor tendon repairs. The goal of nerve release surgery, such as tarsal tunnel release, is to decompress the affected nerve. Post-operative scar formation re-establishes that unwanted incarceration leading to impedance of vascularity and limitation of nerve gliding thus precipitating the return of symptomatology1. Due to the commonality of this issue in tarsal tunnel release, the use of barrier techniques have been advocated to insulate the posterior tibial nerve from recurrent compression1. Modalities for insulation have included silicone ensheathment 2,3, radial forearm free flap4, and more recently autogenous saphenous vein graft wrapping5-8. Success rates have been mediocre at best in these modalities with satisfaction rates averaging 65% with vein wrapping5-8. Unobstructed tendon gliding is key to tendon function with limitation resulting in recurrent pain, decreased motion and resulting functional impairment. The use of numerous mechanical barrier products as well as biochemical products have been advocated to decrease tendon adhesion yet the literature is mixed with no consensus as to the optimal medium to reduce scar formation9.

Paramount in the development of adhesions and scar tissue is inflammation. A direct correlation can be made between the amount of inflammation at a wound site and the scarring and adhesion that develops10. Human amniotic membrane (HAM) is composed of a single epithelial layer, a thick basement membrane, and an avascular stroma11. HAM has been shown to modulate wounds toward fetal healing with anti-inflammation, anti-scarring, anti-microbial and anti-angiogenesis9, 11. Its use in ophthalmic surgery has been well established where is has shown to decrease inflammation as well as have regenerative capabilities11,12. Recent literature has sought to broaden the usage of amniotic membrane with studies showing successful use in prevention of pelvic and abdominal adhesions as well as in treatment of burns, ulcerations and trauma. Specific to our discussion is the use of amniotic membrane to decrease inflammation, adhesions and scar formation in peri-neural and peri-tendinous tissue. Studies in animal models have shown significantly less perineural adhesions and fibrosis in nerves wrapped in human amniotic membrane following neurorrhapy in comparison to control13,14. No studies to date have been performed on human subjects. In regards to tendon repair, histological analyses of animal tendon models have shown a significant decrease in adhesions when augmented with amniotic membrane15,16. A concurrent decreased cellularity of the inflammatory response and greater organization of fibroblasts and collagen fibers leading to improved modulus of strength has been cited16

The following are case reports of posterior tibial nerve release and peroneal tendon repair augmented with cryopreserved human amniotic membrane (Amnoix Medical, Marietta, GA).

Case 1

65 year old African American male presented with 1 year history of neuropathic pain to right lower extremity. Denied injury to the area. The patient had nerve conduction velocity(NCV) tests performed at outside facility, which were consistent with tarsal tunnel syndrome. He was prescribed Gabapentin with improvement of pain. Past medical history benign and non-contributory. Physical examination revealed intact neurovascular status. Negative tinel’s sign upon percussion of posterior tibial nerve right lower extremity. Minimal pain was elicited to palpation tarsal tunnel. Ankle and pedal exam otherwise unremarkable. Radiographs were negative for any boney abnormalities. Review of NCV study revealed prolonged sensory and distal latency to the abductor hallucis and abductor digiti quinti muscles consistent with tarsal tunnel syndrome of the right lower extremity.

Operative technique The patient was placed in the supine position where he underwent general anesthesia. No tourniquet was utilized. 0.25% marcaine with epinephrine was infiltrated along the proposed skin incision line. Skin incision was made overlying the tarsal tunnel. The flexor retinaculum was incised. Blunt dissection was carried down to the level of the posterior tibial artery, which was identified and retracted for protection. A moderate amount of varicosities were noted and these were ligated and cauterized as appropriate. The tibial nerve was identified 4 cm proximal to the medial malleolus and was freed along its entire course. The nerve was followed until it split into its terminal branches and dove underneath the abductor hallucis and quadratus plantae muscles. The nerve was then wrapped with cryopreserved human amniotic membrane secured with Vicryl suture tacks (Figure 1a,b). The flexor retinaculum was not reapproximated. Subcutaneous and skin closer were performed in the routine manner and patient was placed in a posterior splint. Post-operative course consisted of non-weightbearing in posterior splint for 1 week at which time patient was transitioned to apropulsive gait in fracture boot. Patient was allowed full weight bearing following suture removal at 2 weeks post-operatively.

The patient healed without complication and is currently 7 months post-op without recurrence of neuropathic symptomatology.

Figure 1a,b. Wrapping of the posterior tibial nerve with cryopreserved human amniotic membrane.

Case 2

The patient was a 59 year old African American female who presented with complaint of pain to the outside of the right ankle x 1 month duration. Patient described pain as constant and dull in nature with insidious onset. Denied any history of trauma. Previous treatments had consisted of low dye tapping, anti-inflammatory medications and immobilization in fracture boot with no significant improvement in symptomatology. Past medical history was significant for obesity and PVD; otherwise non-contributory. Upon physical examination, pain was noted to palpation of peroneal tendon course from posterior to lateral malleolus as well as at insertion into 5th metatarsal base. Pain was also noted with maximal inversion. Manual muscle testing revealed pain with eversion though strength was maintained. Pedal and ankle joint range of motion was noted to be full. Increase in medial longitudinal arch height noted. Physical examination was otherwise unremarkable. Radiographic evaluation was positive for findings consistent with high arched foot type but otherwise unremarkable. MRI analysis revealed a high grade intrasubstance tear of the peroneus brevis tendon, without complete tendon tear or tendinous retraction as well as a low grade intrasubstance tear of the peroneus longus tendon (Figure 2a,b).

Operative technique Patient was placed on the operating room table in the supine position where she underwent general anesthetic. A midcalf tourniquet was utilized for hemostasis. A curvilinear skin incision was made along the course of the peroneal tendons at the lateral aspect right ankle. The peroneal tendon sheath was located. Hypertrophic synovium and effusion was noted along the course of the tendon sheath. Upon further inspection of the peroneus brevis tendon, significant fibrosis encompassing approximately 80% of the tendon with near complete attenuation was noted at its turn near the lateral malleolus. The longus tendon was noted to be mildly hypertrophic but of normal texture and contour. The midsubstance of the brevis tendon was unsalvageable and thus excised in total. Excised tendon was sent for pathology. The proximal and distal aspects of the brevis tendon were anastomosed with the peroneus longus tendon utilizing a fish scale technique and fiberwire in buried knot running fashion. A low lying muscle belly was noted and this was also excised. The anastomosed peroneal tendons were then wrapped with cryopreserved human amniotic membrane secured with vicryl (Figure 3). The superficial peroneal retinaculum was repaired and tendons noted to move freely without subluxation. Deep, subcutaneous and skin closures were performed in routine fashion. A posterior splint was applied. Pathology report of excised peroneal brevis tendon was significant for fibrocollagenous tendinous tissue with myxoid degeneration. Post-operative course consisted of 2 weeks non-weightbearing in posterior splint. Patient

Figure 2a,b. MRI analysis revealing a high grade intrasubstance tear of the peroneus brevis tendon, without complete tendon tear or tendinous retraction as well as a low grade intrasubstance tear of the peroneus longus tendon

was then allowed apropulsive weightbearing in fracture boot for 4 weeks. The patient was allowed full weightbearing in boot or brace at 6 weeks post-op. Physical therapy was instituted at 6 weeks post-op. Patient healed uneventfully and is currently 5 months post op. She has finished physical therapy and is currently painfree without signs/symptoms of adhesions.

Human amniotic membrane has been proven to have anti-inflammatory, anti-scar, and anti-angiogenic affects with support in the ophthalmic literature11,12. Existing research in animal models has shown significant decrease in scar and adhesion formation in both nerve and tendon repair in comparison to control 13-16. To date, there have been no published studies on the effectiveness of HAM augmentation on nerve or tendon repair in a human model. The cases presented here characterize our results in our initial experience with this product. Similar results have been demonstrated in a case report by Jay on the use of amniotic membrane augmented for repair of posterior tibial and Achilles tendon repair9. Given these initial findings, cryopreserved amniotic membrane shows great promise in the prevention of adhesions and scar formation often associated with post-operative nerve release and tendon repair. Future randomized controlled studies into the use of human amniotic membrane on human subjects need to be undertaken to determine the actual benefit of this product.

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Figure 3. Peroneus brevis tendon ensheathed in human amniotic membrane following repair.