Ultrasound-Guided Hyaluronic Acid Injection for the Management of Morton’s Neuroma

Methods

This retrospective study was approved by the institutional review board of the Kangwon National University Hospital. Among the 83 patients, 8 were males and 75 were females. The average age was 48 (range, 25-62; Table 1). We included patients whose symptoms lasted more than 2 months with Morton’s neuroma in their third intermetatarsal space with definite Mulder’s click. Those who had symptoms of less than 2-month duration, previous steroid injection, negative Mulder’s click, diabetes mellitus, coexisting arthropathy such as rheumatoid arthritis or severe forefoot deformities such as forefoot cavus or hallux valgus on plain radiographs were excluded.

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Table 1.

Demographic Data.

Total included patients	83
Men	8
Women	75
Age in years (range)	48 (25~62)

All patients received custom made insoles with metatarsal pads previously. Ultrasound-guided hyaluronic acid injections were performed on all patients weekly for 3 weeks. Pain during walking using visual analogue scale (VAS) and AOFAS Forefoot Scale were prospectively evaluated at 5 time points: preinjection and 2, 4, 6, and 12 months postinjection. Prior to injections, we confirmed the locations of the nerves with ultrasound (Figure 1). With patients in a supine position, the probe was applied transversely at the plantar side of the metatarsal heads. The needle was inserted from the dorsal aspect of the foot toward the enlarged nerve (Figure 2). 1 milliliters of HA (Sodium hyaluronic acid, 10 mg/ml; NEOHYAL; Arpgen Pharmaceutical, Inc, Seongnam, Gyunggi, Republic of Korea) was injected around the neuroma.

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Figure 1.

Patient’s coronal ultrasound images. Neuroma located in third intermetatarsal space.

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Figure 2.

Patient in supine position. The probe was applied transversely at the plantar sides of the metatarsal heads. The needle was inserted from the dorsal aspect of the foot toward the enlarged nerve.

Results

Significant improvement in VAS and AOFAS Forefoot Scale was seen at 2 months after hyaluronic acid injections (P < .05). VAS was improved from 73.1 initially to 24.6 at 2 months, 22.2 at 4 months, 22.7 at 6 months, and 23.0 at 12 months (Figure 3). The AOFAS Forefoot Scale was also improved from 32.2 initially to 83.4 at 2 months, 85.2 at 4 months, 86.0 at 6 months, and 86.5 at 12 months (Figure 4). Overall satisfaction revealed that 84% were satisfied or very satisfied while 16% were neutral (Figure 5). None of the patients were dissatisfied. There were 14 patients with concomitant numbness of involved toes at the initial visit. None of the patients showed any improvement from sensory loss after the injections. A total of 3 (3.6%) patients complained of severe pain for 1 or 2 days; 2 (2.4%) patients complained of discomfort due to hematoma formation due to the injection itself; both pain and hematoma occurred after a single HA injection out of 3 injections, and all resolved spontaneously. Otherwise, no definite complication occurred.

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Figure 3.

After injection, VAS was significantly decreased, and continued until 12 months.

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Figure 4.

After injection, AOFAS Forefoot Scale was improved, and continued until 12 months.

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Figure 5.

After injection, overall satisfaction revealed that 84% were satisfied or very satisfied, while 16% were neutral. The graph shows overall satisfaction according to satisfaction grade.

Discussions

The exact causes of Morton’s neuroma are still unknown. It is assumed that foot irritation, nerve damage, nerve compression, and foot deformity may cause Morton’s neuroma. It affects mostly women aged between 40 and 50 and frequently occurs between the third and the fourth metatarsal bones. This may be related to the use of shoes with high heels or with a constricting toe box.^6,19 Clinical diagnosis of Morton’s neuroma may be confirmed by demonstration of a Mulder’s click. Ultrasonography and MRI can also be useful for diagnosis.

There are various treatment options for Morton’s neuroma. There are many conservative treatments available. Patients can be instructed to use footwear that does not enclose the forefoot and to take antiinflammatory medications. In addition, corticosteroid injection and/or nerve blocks with local anesthetic are often used. Injections with alcohol ⁵ or botulinum toxin ³ are suggested by some authors. Operative treatment, such as neurectomy, release of the intermetatarsal ligament, or metatarsal osteotomies may be indicated if conservative modalities fail.

Hyaluronic acid is nonsulphated, linear glycosaminoglycan. It is actively secreted by the tendon sheath and in joints is an important component of the synovial fluid. ⁷ It is a major component of the extracellular membrane and has been proven to be safe and tolerable. Its positive effects on tendon injury and osteoarthritis have been studied widely. HA is effective in the treatment of osteoarthritis in knee joints, and its use has been approved by the Food and Drug Administration. ¹⁶ In many experimental studies, which were performed after operative procedures for tendon injuries or in the treatment of chronic tendinopathies using different hyaluronic acid compounds, positive results such as reduced formation of scar and granulation tissue after tendon repair, less adhesions and gliding resistance and improved tissue healing were observed. After flexor tendon surgery, a greater total range of active motion and function of fingers, with an earlier return to work and daily activities, were observed. ¹ Similarly, in patients suffering from elbow, ¹⁶ patella, ¹³ and shoulder^{2,4,11,12,14,17} tendon disorders, pain was reduced, and function was improved. The positive effect of hyaluronic acid can be attributed to the antiinflammatory activity, enhanced cell proliferation, and collagen deposition, besides the lubricating action on the sliding surface.^6,10

In addition, there are several studies about positive roles of hyaluronic acid for regeneration and reduced scar formation of peripheral nerves. Wang et al asserted that during the fibrin matrix phase of nerve regeneration, hyaluronic acid organizes the extracellular matrix into a hydrated open lattice, thereby facilitating migration of the regenerating axons. ²⁰ According to his research, hyaluronic acid increased nerve conduction velocity and myelinated axon counts much more than the normal saline group after hyaluronic acid was injected at injured sciatic nerves. Ozgenel showed from his study significant reduction in perineural scar thickness after hyaluronic acid injection at injured sciatic nerve. ¹⁵ Therefore, it seemed reasonable for us to believe that hyaluronic acid may have positive roles on Morton’s neuroma as well. Histologically, there is endoneural and perineural fibrosis in Morton’s neuroma. Hyaluronic acid may lessen adhesion and inflammatory change around Morton’s neuroma.

In general, conservative treatments of Morton’s neuroma mostly focus on local steroid injections. However, long-term favorable results are questionable. Complications after steroid injections such as fat necrosis and loss of skin pigmentation are problematic. It can be difficult to perform neurectomy in patients with previous steroid injections due to soft tissue breakdown such as fat atrophy. As stated above, operative treatment should only be considered after failure of conservative treatment. Neurectomy may result in a painful stump neuroma, numbness, or dysesthetic pain. Kasparek and Schneider reported that numbness was assessed in 72 % (72 feet), a normal sensibility in 26 % (26 feet) and dysesthesia in 1 % after excision of neuromas. ⁹ In addition, interdigital neurectomy may result in digital vessel injury at 39% according to Su et al. ¹⁸

VAS and AOFAS scores were used to evaluate the effects of HA injection. VAS was thought to be useful in comparing neuropathic pain caused by Morton’s neuroma, and AOFAS scores were useful in reflecting patients’ quality of life, despite its restrictions in predicting the clinical course of Morton’s neuroma, due to multiple factors included in the score: pain, function, and alignment. The results of this study showed that hyaluronic acid can be effective and beneficial for 1 year. Effectiveness at 2 months follow up was very clear. Both VAS and AOFAS Forefoot Scale were improved. Most of the patients were satisfied with the outcome. Hyaluronic acid did not influence the initial numbness associated with the neuromas. It is possible that hyaluronic acid lessened inflammation, scar formation and adhesion around the neuromas. However, it is not clear from this study if hyaluronic acid aided in nerve regeneration, as no patient noted any improvement in initial numbness after the injections. Hyaluronic acid proved to be safe to use from this study. Temporary discomfort for 1 or 2 days such as pain and hematoma occurred in a few cases. There were no long term complications at least for 12 months after hyaluronic acid injections.

This study had a number of limitations. First, this study was a retrospective review. Second, it was not a comparative study so it could not be compared with results from a control group. Third, the initial treatment varied among patients. Their diverse initial treatments including stretching, physiotherapy and oral medications might have influenced the clinical course after the injections. Fourth, the study only had follow up for 12 months. However, this was the first attempt to use HA for the management of Morton’s neuroma, and it will be helpful for studies in the future.

Conclusion

In the present study, ultrasound-guided hyaluronic injection was effective for pain relief and functional improvement in patients with Morton’s neuroma for at least 12 months. However, numbness associated with Morton’s neuroma should be addressed more cautiously since it may persist without much improvement.