Introduction

Development of neuromas has rarely been described in veterinary literature, most frequently as a result of tail docking in dogs (amputation neuromas),¹ but also following accidental or iatrogenic injury.² Neuromas represent nonneoplastic disorganized nerve tissue that develops during neural fiber regeneration following peripheral nerve injury without guidance.^3,4 Although most neuromas remain asymptomatic, clinical manifestation can be multimodal, such as pain, dysesthesia, and sensory or motor nerve dysfunction.^2–6 Clinical signs of traumatic neuromas usually develop later after nerve injury, and early-onset pain has only been described in a human case report.^4,7,8

This case report describes the microsurgical treatment of a neuroma, which manifested in severe pain 10 days after iatrogenic tibial nerve injury in a dog. This case demonstrates early and painful neuroma formation after nerve injury, and the microsurgical management, which has not yet received much attention in veterinary medicine.

Case Report

A 12 yr old, 21 kg, castrated male beagle was referred for surgical resection of a grade 2 soft-tissue sarcoma on the medial aspect of the right calcaneus without metastatic disease. A reverse saphenous conduit flap was planned to allow tension-free closure. However, during surgical preparation of the flap, the tibial nerve was inadvertently partially transected (about 70% of the nerve diameter) where it emerges from deep to superficial in the mid tibia. The surgeon reattached the nerve with two simple interrupted sutures using USP 5-0 absorbable, monofilament suture material. The dog recovered uneventfully without neurological deficits and was discharged the following day. However, 10 days after surgery, the patient presented with an acute non–weight-bearing lameness on the operated leg. On clinical examination, the patient showed discomfort and severe pain in the area of the injured nerve. No nerve deficits were elicited on neurological examination.

For further diagnostics, a low-field magnetic resonance imaging (MRI) examination^a of the painful area was conducted under general anesthesia. At the level of the nerve injury, an irregular tubular enlargement of the tibial nerve was visible, measuring 16 mm in length and 2.5 mm in diameter (Figure 1). The lesion appeared hyperintense to the muscular tissue in T1- and isointense in T2-weighted images. Mild and generalized enhancement was apparent on postcontrast images. These findings were suspicious for a neuroma formation.

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Conservative treatment with oral analgesics was administered over a course of 11 days (gabapentin^b, 10 mg/kg q 8 hr orally; meloxicam^c, 0.1 mg/kg q 24 hr orally). An alleviation of the symptoms did not occur. Given the refractory severe pain symptoms, the owners were advised to perform microsurgical resection of the neuromatous area and microsurgical reconstruction of the nerve.

General anesthesia was induced using methadone^d (0.2 mg/kg IV), midazolam^e (0.1 mg/kg IV), and propofol^f and maintained with 1.5% isoflurane in oxygen. Perioperative medication included carprofen^g (4 mg/kg IV), cefazolin^h (22 mg/kg IV), and a constant rate infusion of fentanylⁱ (10 μg/kg/hr IV). The skin was aseptically prepared for surgery, and the dog was positioned in dorsal recumbency with the affected hindlimb suspended for draping. A medial approach to the right distal tibia was performed to identify the tibial nerve. The neuroma was found as a 1.5 cm long, fusiform, tumorous swelling of the tibial nerve in the distal third of the tibia (Figure 2A). Before manipulation of the nerve, local anesthesia was induced with a lidocaine-hydrochloride^j (20 mg/mL) splash block. A microsurgical resection of the neuroma was performed, including all disrupted fascicles and surrounding scar tissue, while sparing the intact fascicles (Figure 2A,B). The defect was spanned using a 1.5 cm cutaneous saphenous nerve graft, which was harvested from the initial flap donor site at the proximal tibia (Figure 2B). The cut end of the donor nerve was buried in soft tissue. Epineural suture technique was performed by three epineural sutures proximally and two distally using nonabsorbable monofilament suture USP 8-0^k (Figure 2C). The wound was closed in a routine fashion. Postoperatively, the dog received methadone (0.2 mg/kg IV). A light full-limb bandage was placed, maintained, and changed regularly for 3 wk.

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The excised neuroma was formalin fixated for 24 hr, paraffin embedded, and cut using a microtome to 10 nm. Staining was conducted according to the standard techniques for hematoxylin and eosin staining^l. Imaging was performed using a Nikon DS-Ri2 microscope camera^m at 10-fold magnification. The examination confirmed typical features of a traumatic neuroma showing disorganized axons embedded in collagenous tissue.

The dog showed pain relief and weight-bearing the day after surgery with normal motor nerve function and sensation. The patient was discharged with carprofen (4 mg/kg q 24 hr orally) for 10 days. Exercise restriction to leash walks was recommended over the course of 1 mo.

Examinations after 2 days and 2 and 4 wk revealed continuous improvement. The patient made a full recovery and was lameness free by the last follow-up 6 mo after surgery. The owners and the referring veterinarian reported good cosmetic outcome and no apparent lameness or neurological deficits.

Discussion

In the presented case, iatrogenic tibial nerve injury led to a neuroma formation that resulted in extreme pain and discomfort for the patient. Any form of nerve injury that disrupts the axons, for example, nerve transection during limb amputations, can result in painful neuromas.⁴ The reason for the low number of diagnosed cases in veterinary practice may be that most neuromas remain asymptomatic. According to human studies, 1%–30% of amputations will result in painful neuromas.^4,9,10 However, surgeons should be aware of this condition if animals develop severe pain following surgery.

In the current patient, clinical symptoms were observed 10 days after the initial nerve injury. Interestingly, this is contrary to previous reports of traumatic neuromas that describe a late onset of clinical signs 6–10 wk (range, 1–12 mo) after nerve injury.^4,8 Only one previous human study reported early onset of neuromatous pain after saphenous nerve transection 1 wk following total knee arthroplasty, similar to our case.⁷ From a histopathological point of view, axonal regrowth from the proximal injured nerve end begins within 2–7 days after nerve injury, and distinct histopathological appearance of a neuroma is visible 28 days after surgery.^5,11 In comparison, histopathological diagnosis of neuroma formation was possible at 21 days after initial nerve injury in this case. A potential explanation for this would be that the absorbable suture material may have increased the inflammatory response and accelerated the process of histopathological and clinical manifestation in our patient.

Regardless of whether there is a history of nerve injury, a thorough medical history and physical examination should be performed if a painful neuroma is suspected. The tibial nerve, as a mixed function peripheral nerve containing both motor and sensory fibers, supplies muscles extending the hock and flexing the digits and provides cutaneous sensory innervation to the plantar surface of the foot and the caudal surface of the limb.⁶ Animals with severe tibial nerve injury may therefore clinically present with a dropped hock joint during weight-bearing and gastrocnemius muscle atrophy.⁶ In the current case, the dog showed neuralgic pain at a trigger point as the predominant symptom, while still retaining normal sensory and motor nerve function. This may be attributed to the rather distal lesion site with primarily sensory, rather than motor nerve fibers.⁴

In human medicine, neuroma diagnosis is most often purely based on the clinical examination. Alternatively, local nerve blocks, electrodiagnostic testing, MRI, or ultrasound can be used to confirm the diagnosis and localize the neuroma.^2,4,12 Interestingly, it is reported that patients who show instant pain relief following a local nerve block will respond to microsurgical neuroma resection, whereas patients who do not respond are poor surgical candidates.⁴ Although this was not performed in the current patient, we would suggest this diagnostic and therapeutic procedure as a first step.

MRI helped to confirm the suspicion of a neuroma and to plan surgery. Whereas normal peripheral nerves appear isointense compared to muscular tissue on T1- and T2-weighted MRIs, lesioned nerves and neuromas are reported to show a T2-hyperintensity and contrast enhancement.¹³ However, the most indicative sequences in the current case were T1 pre- and postcontrast images (Figure 1). The observed T1-hyperintensity could be attributed to a high proportion of adipose tissue in the nerve sheath, and additional fat-suppressed sequences (e.g., T2 short tau inversion recovery) may have been useful for further characterization. The primary MRI features of neuromas remain their size, bulbous shape, loss of fascicular pattern, and continuity with the parent nerve.¹²

Management of a neuroma depends on the severity of injury, clinical symptoms, time of recognition, relevance of the affected nerve function, and the availability of a surgeon trained in microsurgery.^4,14 In human medicine, microsurgical treatment is recommended if symptomatic neuromas are resistant to analgesics.^3,4,15,16 Therefore, we opted for early microsurgical resection of the neuroma. A variety of surgical methods are described in literature for human medicine.^4,14–16 Regardless of which treatment is chosen, it must focus on diminishing pain, restoring function, minimizing scar formation, and preventing recurrence of neuroma.^4,14 In veterinary medicine, microsurgical techniques are infrequently used and require specialized training to perform.⁶ If the distal nerve stump is available for reconnection or the nerve is in anatomic continuity, microsurgical neuroma excision and primary nerve coaptation should be favored.^4,16–18

In the presented case, nerve injury resulted in formation of an in-continuity neuroma. An in-continuity neuroma arises from a partial nerve injury, in which nerve continuity is still preserved.⁴ Management of neuromas in a nerve that is still in continuity is challenging. The neuroma has to be resected in a sliced fashion using a microsurgical technique. All dysfunctional or disrupted fascicles and the surrounding scar tissue need to be removed while the intact nerve fascicles should be preserved.^4,18,19 The meticulous microsurgical realignment and the amount of tension are key concerns during nerve repair.¹⁸ If tension-free primary nerve repair is not feasible, nerve grafting is recommended.^2,20 In our patient, we harvested a graft of the right cutaneous saphenous nerve to span the defect after neuroma excision. The cutaneous saphenous nerve has a purely sensory function, is readily accessible subcutaneously, and is constant in position, thus highly suitable as a peripheral nerve graft.^2,21 The harvested nerve graft undergoes Wallerian degeneration but aids as a mechanical guidance for the ingrowing axons.²⁰ For nerve grafting, traditional epineural suture technique was used in the patient (Figure 2C). The most important points to consider are to obtain continuity with a minimum of tension and sutures (4–8 single interrupted sutures) while using fine, nonabsorbable suture material (USP 8-0 or 9-0) to reduce inflammatory reaction, which could lead to recurrent neuroma formation.^19,20 Two previous veterinary studies reported grouped fascicular repair in autologous saphenous nerve grafting with good outcome.^2,21 Little comparative literature about different nerve repair techniques is available in human or veterinary medicine. However, although other techniques of nerve repair (grouped fascicular, fascicular) may allow more accurate fascicular alignment, they do not provide benefits over the epineural suture technique, due to more extensive dissection and suture material needed.^19,20,22

Nerves require structural alignment to an end organ. Without this, the nerve will have axonal growth without a target and will once more form a neuroma. Thus, neuroma resection without a target is not recommended. Human studies have reported that restoration of the continuity decreases recurrence rates of painful neuromas and yields improved outcome compared to simple neuroma excision, which resulted in recurrence rates of up to 65%.^9,16 A previous animal study reported undesirably poor functional outcomes without reconstruction of a sciatic neurotmesis in comparison to the use of an artificial nerve graft or autograft.¹⁷ In this case, nerve continuity was restored using an autograft rather than excising the neuroma alone to reduce the risk of recurrence. However, further research is needed before definitive recommendations can be made for the treatment of neuromas in veterinary patients. Concerning the prevention of neuroma formation, microsurgical nerve repair or grafting should be performed soon after nerve injury to provide best possible conditions for regeneration.^3,4,14 If the distal nerve ending is not available (in limb amputations) or reconnection is undesired in noncritical sensory nerves, transposition into muscle tissue or bone marrow is strongly recommended to prevent neuroma formation^4,14,15.

Conclusion

Clinical signs of painful neuromas can occur early after nerve injury. Microsurgical neuroma resection and epineural nerve repair resulted in instant pain relief while preserving nerve function in this patient. Currently, there are only a few places where veterinary surgeons can acquire microsurgical training. In our case, the neuroma formation happened after iatrogenic nerve injury. Microsurgical skills need to be increasingly acquired by veterinary surgeons to allow repair of nerve injuries and prevent neuroma formation. To the best of our knowledge, this is the first report describing early-onset pain and successful microsurgical treatment of a posttraumatic neuroma of the tibial nerve in veterinary medicine.

We would like to acknowledge Sonja Wolf for performing the histopathology. Further we wish to express sincere gratitude to Francesca Del Chicca for the magnetic resonance imaging report and her outstanding support in the interpretation of results.