Should You Perform Sclerosing Injections For Neuromas?

Yes. Advocating for a multi-step approach, the authors share research evidence and practice experience in favor of including sclerosing injections in one’s treatment pathway for Morton’s neuroma.

By Patrick DeHeer, DPM, FACFAS, FASPS and Joseph Altepeter, DPM

Italian anatomist Filippo Civinini first recognized the pathological process of an intermetatarsal neuroma in the literature in 1835,¹ and American surgeon Thomas Morton later eponymously described this condition in 1876.² The management of intermetatarsal neuroma has undergone much evolution since local blood-letting was the standard of care.² We contend that one thing remains true since its debut in the timeline of this evolution: sclerosing injection therapy is a more than viable rung in the treatment ladder for intermetatarsal neuromas.

What The Literature Reveals About Sclerosing Injections

Roughly half of patients presenting with an intermetatarsal neuroma may have improvement of symptoms with shoe gear modification alone, obviating treatment progression to more invasive management.³ For patients with residual symptoms, however, the next step in the majority of treatment protocols is administration of corticosteroid injection.^3,4 Physicians widely use corticosteroid injections, which certainly have diagnostic value, with variable therapeutic benefit as well.⁵ But, is injectable corticosteroid the end all be all of non-surgical management of an intermetatarsal neuroma?

The results of a 2017 randomized controlled trial from Lizano-Diez and colleagues⁵ suggest not. The authors randomized 41 patients with a clinical and magnetic resonance imaging (MRI) diagnosis of Morton’s neuroma to receive three rounds of either anesthetic alone or a corticosteroid plus a local anesthetic, administered at two week intervals. They evaluated American Orthopaedic Foot and Ankle Society (AOFAS) scores and visual analog scales (VAS) after each of the three injections, as well as three and six months after the initial injection. The only significant difference between the groups was at the second visit, when VAS was significantly lower in the corticosteroid group, and AOFAS scores were significantly lower in the anesthetic group. Otherwise, there was no difference in outcome between the two groups, most importantly in the longer term.⁵ The authors concluded that “the injection of a corticosteroid plus a local anesthetic was not superior to a local anesthetic alone in terms of pain and function improvement in patients with Morton’s neuroma.”⁵

It is well-established that the histological findings of an interdigital neuroma preclude it from being classified as a true neoplasm, as it is likely degenerative in nature.^6,7 Histologic changes that one often sees in excised nerves include the presence of Renaut bodies; perineural, epineural, and/or endoneural fibrosis; degenerative vascular changes; and axonal demyelination, among others.^6,7 When present, a minimally invasive therapy targeting these changes such as sclerosing injections, would be of great potential benefit.

One study fueling the argument against the use of sclerosing injections is that in 2014 by Mazoch and team.⁸ This was an animal study including 22 rats, with essentially a single 0.5 ml application of either 0.5% marcaine as a control, or 4%, 20% or 30% ethanol solution with 0.5% marcaine administered under direct visualization into or around a total of 44 disease-free sciatic nerves.⁸ All rats were sacrificed at ten days, subsequently performing histologic examination of the nerves. The authors concluded that there was “no histologic evidence of necrosis or inflammation to the nerve or surrounding tissue,” and “no observable histological change in apoptosis, or cell number, in response to the alcohol injection.”⁸

Correlating these findings with the studies indicating positive clinical response to sclerosing injections,^9-14 it seems reassuring that these injections (regardless of location and concentration) are not damaging healthy nerve or surrounding tissues. This extrapolation contradicts concerns drawn from a 1983 article that concluded glycerol causes myelin disintegration and axonolysis.¹⁵ Additionally, it would have been more ideal for Mazoch and team to assess histological changes in the rat nerves after multiple injections to more closely mimic clinical application observed in human medicine, as a single sclerosing injection in a human patient with an intermetatarsal neuroma would constitute gross undertreatment.

On the other hand, a recently published study from DeHeer and colleagues¹⁶ compares histological findings of 19 surgically excised neuromas; eight treated with sclerosing injections and 11 treated with non-sclerosing injections prior to surgical excision. Each of the neuromas underwent evaluation by the same pathologist, assessing for perineural fibrosis, intraneural fibrosis, endarterial thickening and inflammation. The authors did find a visible difference between the sclerosing and non-sclerosing therapy groups.¹⁶ The nerves treated with sclerosing therapy consistently demonstrated mild or no perineural fibrosis and intraneural fibrosis.

Conversely, the non-sclerosing group consistently demonstrated moderate-to-severe perineural (P=.292) and intraneural fibrosis (P=.008).¹⁶ These findings are not consistent with the aforementioned Mazoch and team study,8 owing possibly to the diseased (or disease-free) state of the included specimen, poor extrapolation from animal model to human pathology or incongruous sclerosing injection protocol. Despite a small population evaluated in this study, the authors concluded that the difference in fibrosis between the two groups was primarily attributable to the effect of sclerosing therapy.¹⁶

There are some articles that question the medium-to-long term efficacy of sclerosing injections. One such study, published in 2013 by Gurdezi and coworkers,¹⁷ falsely inspired a 2014 AOFAS Choosing Wisely recommendation on the management of intermetatarsal neuroma, suggesting avoidance of alcohol injections.¹⁸ The study followed up with 45 patients at an average 61 months after successful treatment with alcohol sclerosing injections. These patients were previously the subjects of a 2007 study by Hughes and colleagues.¹¹ In the original article, 100 patients with intermetatarsal neuroma received 20% ethyl alcohol sclerosing injection therapy, with 84 percent complete resolution of pain, with another 10 percent having partial resolution of pain.¹¹

In the follow-up article,¹⁷ a reported 29 percent of the patients remained completely pain free, with 40 percent having mild or moderate symptoms, and 16 percent having undergone surgical excision by five years post-therapy (16 percent being much lower than the 47 percent requiring surgical excision after single corticosteroid injection therapy in an article from Rasmussen and team¹⁹).

What the authors of this follow-up study fail to discuss is how the loss of over half of the patients from the original study may have impacted the results.¹⁷ It is not unreasonable to consider that many of those who did not follow up for the subsequent study may have indeed remained symptom-free. Also, while the authors describe various non-surgical methods for treating neuromas, they do not specify what maintenance therapies patients had after the original study.¹⁷ This is an important consideration given that biomechanical issues are a likely etiology of neuroma formation.

A study by Lorenzen and colleagues¹³ highlights the importance of maintenance therapy, specifically with the use of orthopedic inserts to control functional and mechanical disorders. The authors retrospectively evaluated 104 consecutive cases including 92 patients with Morton’s neuroma treated with alcohol injection. Group A consisted of 51 cases with Morton’s neuroma alone, while group B consisted of 53 cases with Morton’s neuroma associated with mechanical metatarsalgia.¹³ In 89 percent of cases, patients were either completely satisfied or had minor reservations. At a mean two years follow-up a total of six cases of symptom recurrence, five of which occurred in group B, with four patients not using their prescribed orthopedic inserts. The authors concluded that symptom recurrence is often associated with mechanical metatarsalgia and the targeted treatment of this “plays an important role in the prevention of recurrence of pathology.”¹³

In Conclusion

Physicians treating intermetatarsal neuromas should take a multi-step approach, and we believe this should include the use of alcohol sclerosing injections. Initial modification of shoe gear and pathology-specific orthoses is certainly important. An injection of the provider’s preferred corticosteroid-anesthetic combination can aid in diagnosis with potential for therapeutic effect. Then for persistent symptomatology, alcohol sclerosing injections can target the underlying histological changes seen in intermetatarsal neuromas. Following this series of injections, maintenance therapy with mindfulness of shoe gear and orthoses when indicated are indicated to prevent recurrence of symptoms.

Dr. DeHeer is the Residency Director of the St. Vincent Hospital Podiatry Program in Indianapolis. He is a Fellow of the American College of Foot and Ankle Surgeons, the American Society of Podiatric Surgeons, the American College of Foot and Ankle Pediatrics and the Royal College of Physicians and Surgeons of Glasgow. He is a Diplomate of the American Board of Foot and Ankle Surgery.

Dr. Altepeter is a third-year resident with the St. Vincent Hospital Podiatric Residency Program in Indianapolis.

No. Citing his personal experience, along with pitfalls in the literature, this author feels that more comparative studies are necessary, along with examination of and training in alternative options for patients with intermetatarsal neuromas.

By Peter Bregman, DPM, FACFAS, FAENS

Over the past 20 years or so, I’ve observed many fellow podiatrists claim that sclerosing alcohol injections are very effective and obviate the need for any type of surgery. Early on in my career, I tried the injections for my patients with what I would call very mixed results. Most would get some temporary relief but almost no one was cured. I therefore abandoned the procedure and have not performed any since then.

At some point I researched sclerosing alcohol injections and applications in other parts of the body. Through this research, especially from interventional radiology studies, I believe that the percentage of alcohol needed to effectively “kill” the nerve target was 20% at minimum, or even higher.

In an article by Gary Dockery, DPM in 1999 he describes using 4% solution of dehydrated alcohol in the treatment of 100 patients in a prospective study.¹ He showed very good results. However, the study was very limited in that it was not a level I or II study. After my own literature review, and discovering that a 4% concentration of alcohol was nowhere near the amount needed to achieve a chemical neurolysis or to kill the nerve, I hypothesized that the anesthesia itself was responsible for the therapeutic effect.

So, in my opinion, if we really want to know what is the active agent that produces the therapeutic effect, then a new study is in order.This study would ideally use and compare: saline alone; a 4% alcohol solution; a 20% alcohol solution; plain local anesthesia; and local/anesthesia with 4mg/ml of dexamethasone phosphate.

The mechanism providing temporary relief of nerve pain with alcohol sclerosing injections is likely related to the effects on the sodium and potassium channels. It is possible, however, that the 4% dehydrated alcohol may alter or change the chemistry of the solution by changing pH or some other mechanism that allows for its therapeutic effect. There are other articles published that used 4% alcohol sclerosing solution to treat neuromas, but again they did not use placebo or just the anesthesia without the alcohol as a control.^2,3

In an article by Hughes and colleagues in 2007,⁴ they did a prospective study using 20% alcohol solution and had about an 84 percent success rate as defined by subjective statements made by the patients treated. However, there were several pitfalls of the study. It was not a level I or II study and it did not compare any placebo or anesthesia alone. They chose the 20% solution after researching the literature on the necessary minimum concentration to effectively achieve chemical neurolysis or destruction of the nerve tissue.⁴

This is why I believe that the current protocol by many doctors of using 4% is negligible and has no real benefit at least from a destructive viewpoint. So, if that is the case, I would challenge any person using this 4% cocktail to omit the alcohol entirely or replace it with vitamin B, ketorolac or dexamethasone phosphate. I think the results, based on my experience, would be very similar. The mean follow up was less than one year⁴ as well in the aforementioned study, which I do not think is enough time to determine “success.” I feel at least two to three years would provide a more valuable set of data.

The other challenge is that not all neuromas are created equal. I’ve observed that some look relatively normal when visualized intraoperatively, yet still cause symptoms and some look classically bulbous from the fibrosis present and the repetitive injury of the tethering effect of the deep transverse metatarsal ligament. This means that it is very difficult to compare apples to apples or one neuroma to another.

Not only is there such a wide variety of thoughts on the proper concentration of alcohol solution one could use for treatment of Morton’s neuroma, there is also the technique involved to consider. It is thought that using ultrasound-guided injection is a must for accurate and proper delivery of the sclerosing agent into the nerve sheath or just above.⁴ This is mostly from literature from interventional radiologists, so there certainly may be some bias to this concept, but it makes sense to be as accurate as possible. If this is the case, then we know that many doctors do not use ultrasound, thus changing the outcome, perhaps.

I reviewed a 2016 blog by Richard Blake in Podiatry Today where he himself states that it takes at least 20% concentration of alcohol to deliver the chemical neurolysis, yet he advocates and performs injections of 6% without any explanation as to why.⁵ He does, however say that, “You definitely do not want to damage other structures in your attempt to desensitize the nerve.”

So, while I think there is nothing dangerous about using a 4% solution to perform these injections, and they may in fact be helpful in the temporary relief of symptoms through other mechanisms rather than true chemical neurolysis, I cannot advocate spending the money on the alcohol or the seven to 10 treatments.¹ I would advocate treating symptomatically with local anesthetic and some other additive medication which potentially may be more effective.

However, if one wants to truly attempt to destroy the tissue on a permanent basis then I would recommend using 20 to 30% alcohol under a very stringent protocol so as to avoid creating more damage then you started with.

Lastly, I think from a practice management aspect some physicians may advocate treatment using these injections as a revenue generator. Despite this possibility, it is of the utmost importance for treatment decisions to stem from evidence-based techniques and protocols, not from income potential.

Final Thoughts

I would be remiss given the subject matter of this article not to mention that the whole purpose of the treatment in question is to avoid neurectomy. Unless one sees the damage done and suffering of patients for whom neurectomy has failed on a regular basis, I do not think one can fully understand the risk of performing this relatively simple but potentially devasting procedure.

As an advocate of decompression surgery for neuromas, I am puzzled by the lack of adoption of this procedure which has a very high success rate when performed open and done properly.⁶ I feel that surgeons who “dabble” in decompression and then have too many failures incorrectly conclude that it does not have a high success rate. Without proper training you cannot achieve the best results. We must create awareness and teach this concept at the very basic level of training. If decompression has zero risk of a stump neuroma and a neurectomy has a much higher risk level for this complication, why would one want to risk that?

It is for these reasons above that I do not advocate for alcohol sclerosing injections for neuromas in the context of the commonly-used protocols in the field. 

Dr. Bregman is a Diplomate of the American Board of Foot and Ankle Surgery, a Fellow of the American College of Foot and Ankle Surgeons and a Fellow and Past President of the Association of Extremity Nerve Surgeons. He is in practice in Las Vegas, Nev.

Point References

1. Civinini F. Su d’un nervoso gangliare rigonfiamento alla pianta del piede. Men Chir Arcispedale di Pistoia. 1835.

2. Morton TG. A peculiar and painful affection of the fourth metatarso-phalangeal articulation. Am J Med Sci. 1876;71:37.

3. Bennett GL, Graham CE, Mauldin DM. Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int. 1995;16(12):760-793.

4. Jain S, Mannan K. The diagnosis and management of morton’s neuroma: a literature review. Foot Ankle Spec. 2013;6(4):307-317.

5. Lizano-Diez X, Ginés-Cespedosa A, Alentorn- Geli E, et al. Corticosteroid injection for the treatment of morton’s neuroma: a prospective, double-blinded, randomized, placebo-controlled trial. Foot Ankle Int. 2017;38(9):944–951.

6. Piña‐Oviedo S, Del Valle L, Baquera-Heredia J, Ortiz-Hidalgo C. Immunohistochemical characterization of Renaut bodies in superficial digital nerves: further evidence supporting their perineural cell origin. J Peripher Nerv Syst. 2009;14(1):22-26.

7. Kay D, Bennett G. Morton’s neuroma. Foot Ankle Clin. 2003;8:49-59.

8. Mazoch MJ, Cheema GA, Suva LJ, Thomas RL. Effects of alcohol injection in rat sciatic nerve. Foot Ankle Int. 2014:35(11):1187-1191.

9. Dockery GL. The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. 1999;38(6):403-408.

10. Hughes RJ, Ali K, Jones H, Kendall S, Connell DA. Treatment of morton’s neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. AJR. 2007;188(6):1535– 1539.

11. Hyer CF, Mehl LR, Block AJ, et al. Treatment of recalcitrant intermetatarsal neuroma with 4% sclerosing alcohol injection: a pilot study. J Foot Ankle Surg. 2018;57:870-875.

12. Lorenzen P, Rettore C. Mechanical metatarsalgia as a risk factor for relapse of Morton’s neuroma after ultrasound-guided alcohol injection. J Foot Ankle Surg. 2018;57:870-875.

13. Musson RE, Sawhney JS, Lamb L, et al. Ultrasound-guided alcohol injection for Morton’s neuroma. Foot Ankle Int. 2012;33(3):196-201.

14. Pasquali C, Vulcano E, Novario R, et al. Ultrasound-guided alcohol injection for Morton’s neuroma. Foot Ankle Int. 2015;36(1):55-59.

15. Rengachary SS, Watanabe IS, Singer P, Bopp WJ. Effect of glycerol on peripheral nerve: an experimental study. Neurosurgery. 1983;13(6):681–688.

16. DeHeer PA, Bains RS, Grebenyuk FR, Patel S, Nguyen T. Effects of 4% ethanol sclerosing injection on morton’s neuroma: a histologic study. J Am Podiatr Med Assoc. 2020;110(5). doi: 10.7547/17-094.

17. Gurdezi S, White T, Ramesh P. Alcohol injection for morton’s neuroma: a five-year follow-up. Foot Ankle Int. 2013;34(8):1064–1067.

18. AOFAS Board of Directors. American Orthopedic Foot & Ankle Society: five things physicians and patients should question. Choosing wisely: an initiative of the ABIM foundation. Available at: https://www.choosingwisely.org/societies/ american-orthopaedic-foot-ankle-society/ . Published September 17, 2014. Accessed April 6, 2021.

14. Rasmussen MR, Kitaoka HB, Patzer GL. Nonoperative treatment of plantar interdigital neuroma with a single corticosteroid injection. Clin Orthop Relat Res. 1996;326:188-193.

Counterpoint References

1. Dockery GL. Treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. 1999;38(6):403-408.

2. Hyer CF, Mehl LR, Block AJ, Vancourt RB. Treatment of intermetatarsal neuroma with 4% sclerosing alcohol. J Foot Ankle Surg. 2005;44(4):287-291.

3. Mozena J, Clifford J. Efficacy of chemical neurolysis for treatment of interdigital nerve compression of the foot. J Am Podiatr Med Assoc. 2007;97(3):203-206.

4. Hughes, RJ, Ali K, Jones H, Kendall S, Connel DA. Treatment of Morton’s neuroma with alcohol injections under sonographic guidance: Follow up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.

5. Blake R. What are the best injections for Morton’s neuroma? Podiatry Today. Available at: https://www.podiatrytoday.com/blogged/what-are-best-injections-morton%E2%80%99s-neuroma . Published July 1, 2016. Accessed April 7, 2021.

6. Barrett SL, Walsh AS. Endoscopic decompression of intermetatarsal nerve entrapment: a retrospective study. J Am Podiatr Med Assoc. 2006;96(1):19-23.