Coverage Policy Manual
Policy #: 2015012
Category: Medicine
Initiated: May 2015
Last Review: May 2023
  Alcohol Injections for Treatment of Peripheral Neuromas

A neuroma is pathology of peripheral nerve that develops as part of a normal reparative process. Neuromas may develop after injury to a nerve or as a result of chronic irritation, pressure, stretch, poor repair of nerve lesions or previous neuromas, laceration, crush injury, or blunt trauma (Rajput, 2012). Neuromas typically appear about 6 to 10 weeks after trauma with most presenting within 1 to 12 months after injury or surgery. They may gradually enlarge over a period of 2 to 3 years and may or may not be painful. Pain from a neuroma may be secondary to traction on the nerve by scar tissue, compression of the sensitive nerve endings by adjacent soft tissues, ischemia of the nervous tissue or ectopic foci of ion channels that elicit neuropathic pain. Patients may describe the pain as a low-intensity dull pain or intense paroxysmal burning pain, often triggered by external stimuli such as touch or temperature. Neuroma formation has been implicated as a contributor of neuropathic pain in residual limb pain, postthoracotomy, postmastectomy, and postherniorrhaphy pain syndromes. They may coexist with phantom pain or can predispose to it.
Morton Neuroma
Morton intermetatarsal neuroma is a common and painful compression neuropathy of the common digital nerve of the foot that may be referred to by other names, including interdigital neuroma, interdigital neuritis, and interdigital or Morton metatarsalgia (Rajput, 2012; Jain, 2013; Clinical Practice Guideline Forefoot Disorders, 2009). It is histologically characterized by perineural fibrosis, endoneurial edema, axonal degeneration and local vascular proliferation. Thus, some investigators do not consider Morton neuroma to be a true neuroma; instead, they consider it to be an entrapment neuropathy that occurs secondary to compression of the common digital nerve under the overlying transverse metatarsal ligament. The incidence and prevalence of Morton neuroma are not clear, but it appears 10-fold more often in women than in men with an average age at presentation of around 50 years (Wu, 1996).
The pain associated with Morton neuroma is usually a throbbing, burning or shooting pain that is localized to the plantar aspect of the foot. It is typically located between the 3rd and 4th metatarsal heads although it may appear in other close-by locations (Rajput, 2012; Jain, 2013). The pain may radiate to the toes and can be associated with paresthesia. The pain can be severe, and the condition may become debilitating to the extent that patients are apprehensive and anxious about walking or touching their foot to the ground. It is aggravated by walking in shoes with a narrow toe box or high heels that cause excessive pronation and excessive forefoot pressure; removal of tight shoes typically relieves the pain.
Although a host of imaging methods may be used to aid diagnosis of Morton neuroma , including plain radiographs, magnetic resonance imaging, and ultrasonography, objective findings are unique to this condition and are primarily used to establish a clinical diagnosis (Rajput, 2012). Thus, a patient’s toes often show splaying or divergence. Patients may describe the feeling of a “lump” on the foot bottom or a feeling of walking on a rolled-up or wrinkled sock. Clinical examination with medial and lateral compression may reproduce the painful symptoms with a palpable “click” on interspace compression (Mulder sign) (Mulder, 1951).
Treatment of Morton Neuroma
Management of patients with a diagnosis of Morton neuroma typically proceeds through a pathway that starts with conservative approaches, such as the use of metatarsal pads in shoes, and orthotic devices that alter supination and pronation of the affected foot.3 These approaches are aimed at reducing pressure and irritation of the affected nerve. They may provide some relief, but do not alter the underlying pathology. There is scant evidence to support the effectiveness or comparative effectiveness of these practices (Jain, 2013; Adams, 2010; Thomson, 2004). In 1 case series, investigators evaluated a 3-stage protocol of “stepped care” through which private practice patients (N=115) advanced from stage I (education plus footwear modifications, and a metatarsal pad) to stage II (steroid injections with local anesthetic or local anesthetic alone), into stage III (surgical resection) if stages I and II did not bring relief within 3 months.8 Overall, 97 of 115 patients (85%) believed that they had improved with the treatment program. However, twenty-four patients (21%) eventually required surgical excision of the nerve and 23 of those (96%) had satisfactory results.
Historically, surgical intervention is considered the definitive therapy. The most common procedure is open excision of the interdigital nerve pathology through a dorsal or plantar approach. A second procedure referred to as nerve decompression with neurolysis or translocation of the affected part of the interdigital nerve has been used to treat Morton neuroma. Although this approach uses smaller incisions and seems to have more rapid recovery than open excision of the neuroma, it is reported to be a more demanding procedure that requires specialist training and equipment and is less common in practice.2 No randomized clinical trials have been reported which compared the effectiveness of different management approaches for Morton neuroma.
A Cochrane systematic review that was originally published in 2004 showed insufficient evidence to assess the effectiveness of surgical and non-surgical interventions for Morton neuroma (Thomson, 2004). A more recent review published in 2013 summarized the results of surgical excision studies that included a total of 250 patients.2 In general, these series were poorly reported and highly heterogeneous, used disparate outcome measures, had short follow-up periods (average, 2-10 years) and could not be directly compared. In the only prospective comparative study of surgical methods, the dorsal approach resulted in earlier weight bearing (mean, 16 days vs 23 days, respectively) and return to work (mean, 22 days vs 37 days, respectively) compared with a plantar approach in 52 total cases at average follow-up of 3 years.9 Painful scars were more common with the plantar approach (n=5) compared with the dorsal approach (n=2), with only 1 patient in each group experiencing a recurrence of symptoms. Other case series of primary neurectomy showed reduction of pain in more than 50% to 100% of patients, with self-reported satisfaction rates from 52% to 86%, at mean follow-up periods that ranged from 24 to 126 months (Jain, 2013). Common complications included paresthesia (51% to 82% reported), scar tenderness or hypersensitivity (6% to 32%), and wound infection (1.4% to 9.7%).
Long-term outcomes of surgical resection have been reported in 2 additional series that involved a total of 159 cases that were refractory to conservative management. One series (N=78) reported mean follow-up of 4.6 years (range, 0.8-8.1 years) (Pace, 2010). With a dorsal approach, a total of 82% of patients with longstanding symptoms (mean duration, 33 months) reported excellent or good results, 10% had a fair result with restriction of activities or pain, while 8% had no improvement at all after surgery. Complications included wound infections in 8 cases that resolved with antibiotics, 5 had persistent hypersensitive scars, and 4 developed local keloid formations. Eight cases (10%) required revision due to neuroma recurrence at a mean of about 2 years after index surgery. The second long-term series (N=81) reported mean follow-up of 15.3 years (range ,10-20 years), the longest available in the literature (Kasparek, 2013).With a mostly dorsal approach (97% of cases), outcomes were reported excellent in 45%, good in in 32% and fair in 15%; 8% reported poor results after surgery and were referred for revision. Paresthesia in the supplying area of the resected nerve was reported in 72% of cases, while normal sensation was reported in 26%. Other surgical complications were not reported in this series.
Ablation Techniques
A third middle approach that has been investigated to treat refractory Morton neuroma involves several minimally invasive procedures aimed at in situ destruction of the pathology, including intralesional alcohol injections (Jain, 2013). Dehydrated ethanol has been shown to inhibit nerve function in vitro, has high affinity for nerve tissue and causes direct damage to nerve cells via dehydration, cell necrosis, and precipitation of protoplasm, leading to neuritis and a pattern of Wallerian degeneration. Technically, ethanol is a sclerosant that cause chemical neurolysis of the nerve pathology, but is considered an ablative procedure for this policy.
This policy will focus on evidence available on the use of alcohol injections, with emphasis on Morton neuroma and the comparative effectiveness of this less-invasive therapy and open surgical resection of the nerve pathology.
Regulatory Status
Alcohol injection for Morton neuroma is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.
The following CPT code would be used to report these procedures:
64632: Destruction by neurolytic agent, plantar common digital nerve

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Alcohol injections for the treatment of Morton neuroma does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, alcohol injections for the treatment of Morton neuroma is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Assessment of efficacy for therapeutic intervention involves a determination of whether the intervention improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures may also be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes but are prone to biases such as non-comparability of treatment groups, placebo effect, and variable natural history of the condition.
Intralesional Alcohol Injections for Morton’s Neuroma
No RCTs or nonrandomized controlled trials were identified. Several case series have been reported on the use of alcohol injections to treat Morton’s neuroma.
The largest study by Hughes and colleagues included 101 consecutive patients (84 women, 17 men, mean age 54 years [range 30-74 years]) who had clinical and ultrasound confirmed diagnosis of Morton’s neuroma with mean symptom duration of 21 months (range 4-48 months) (Hughes, 2007). Prior conservative treatments were not reported. Patients received 4 ultrasound-guided injections of 0.1 mL of 100% ethanol diluted in 0.4 mL bupivacaine (total = 0.5 mL of 20% ethanol) at 14 day intervals. Additional injections were performed at further 14-day intervals if the response was partial or incomplete based on patient-assessed level of pain. The main outcome was pain measured on a visual analog scale (VAS) scored from 0 to 10. A modified Johnson questionnaire score also was used to measure patient
satisfaction with the treatment  (Johnson, 1988). Patients received an average of 4.1 injections (range 3-6), with technical success achieved in all cases. The median (interquartile range) VAS pre-procedural score was 8 (7-8) with a total range of 6-10. This decreased to 0 (0-1) after the injections with a range of 0-10 at average follow-up of 10.5 months (range 7-19 months). Patients reported their outcome as completely satisfied (62%), satisfied with a few reservations (24%), satisfied with major reservations (5%), dissatisfied (3%) and wished they had never had injections (6%). At ultrasound follow-up, the mean decrease in size of 30 lesions compared to pretreatment was 30%, with mean lesion diameter of 10 mm (range 7-15 mm) before and 7 mm (range 5-11 mm) at follow-up. No major complications were reported. Three went on to surgical resection, which was reported as being more technically demanding than typical because of the degree of fibrosis present.
A second series reported on outcomes with intralesional alcohol injections in 75 consecutive patients (66 female, average age 58 years [range 22 to 80 years]) diagnosed with symptomatic Morton’s neuroma (Musson, 2012). A mixture of 0.1 mL of 100% ethanol diluted in 0.4 mL bupivacaine (0.5 mL of 20% ethanol) was injected with real-time ultrasound guidance. A standard course was planned to comprise 4 injections each given 2 weeks apart. Outcomes were patient-reported pain score on a VAS scale (range 0-10), with mean followup of about 14 months (range 6 to 26 months). Technical success of the injections was scored as 100%. The mean VAS pain score prior to treatment was 8.5 (range 4-10) and the mean score after treatment was 4.2 (range 0-10) (p < 0.0001). At follow-up, 32% of patients reported complete symptom resolution, 33% reported partial relief, and 35% reported no relief. Complications of the injections were rare (n = 3) and self-resolving. Seventeen patients (20%) went on to surgery at the time of last follow-up.
A long-term follow-up of outcomes among 45 of the original cohort of Hughes was reported in 2013 (Gurdezi, 2013).  At a mean of 5 years (range 33-73 months), 16 of those 45 (36%) had undergone surgical resection, and 29% (13 of 45) still reported complete resolution of symptoms, compared to 84% in the original study. Satisfaction with treatment was reported by 33%, compared to 62% in the original cohort. These results suggest alcohol injections do not provide a permanent resolution of symptoms for a substantial proportion of patients, although these results are liable to bias due to the retrospective data and selected cases.
Two other case series report short-term outcomes with multiple alcohol injections to treat refractory Morton’s neuroma (Espinosa, 2011; Fanucci, 2004). Therapeutic failure leading to subsequent surgery was reported in 10% of cases (n= 4 of 40) in one study using 34 0.5-1.0 mL injections of 30% ethanol plus carbocaine under ultrasound guidance (Fanucci, 2004). In the second retrospective series, 25 of 32 patients reported no relief of refractory Morton’s neuroma pain with 4 injections (range 3-10) consisting of 1 mL of 20% ethanol with bupivacaine without ultrasound guidance (Espinosa, 2011).  Among those 25, 16 considered surgery, and 9 underwent or scheduled a procedure. The authors of this study state that they no longer use alcohol injections to treat patients with Morton’s neuroma as they believe the procedure is ineffective.
A systematic review that includes the studies cited here plus one by Dockery published in 1999 (Dockery, 1999) compared the need for subsequent surgery following alcohol injections for Morton’s neuroma under ultrasound guidance versus unguided injections (Morgan, 2014). The authors of this review suggest the use of ultrasound guidance for alcohol injections to treat Morton’s neuroma can reduce the need for subsequent surgery compared to unguided treatments.
Summary of Evidence
The body of evidence on alcohol injections is weak, with no controlled studies to compare outcomes with those of surgery in patients who are surgical candidates. Five case series reviewed here document the use of intralesional alcohol injections to treat painful, refractory Morton’s neuroma. The overall results suggest some patients may experience pain relief and express satisfaction with the procedure. However, relief is not universally achieved. Multiple alcohol treatments are required (5 or more); complications include sometimes severe periprocedural pain and allergic reactions; and 20% or more of cases require subsequent surgical extirpation of the neuroma. Some evidence exists that surgery after alcohol
injections in failed cases is more complex and challenging than in untreated patients due to the presence
of fibrosis. This body of evidence is insufficient to form conclusions on the effectiveness of multiple intralesional injections of alcohol as treatment for symptomatic, refractory Morton’s neuroma.
Practice Guidelines and Position Statements
The American College of Foot and Ankle Surgeons released a Clinical Practice Guideline in 2009 on the diagnosis and treatment of forefoot disorders (Mazoch, 2014). The guideline was re-titled in 2012 as a Clinical Consensus Statement. The Clinical Practice Statement reports that 3-7 dilute alcohol injections of 4% alcohol injected at 5-10 day intervals has been associated with an 89% success rate with 82% of patients achieving complete relief of symptoms.
The Association of Extremity Nerve Surgeons issued 2014 Clinical Practice Guidelines (Association of Extremity Nerve Surgeons, 2014) in which they make the following conclusions regarding alcohol injections: “Current methods of denervation treatment include cryoablation and radio frequency ablation, alcohol injections and surgical resection. Aside from surgical resection, all other methods damage tissue in a relatively blind manner without absolute control and may not be a permanent resolution of symptoms. Neuro-destructive procedures may be useful on nerves that are already damaged; however, they should not be used as initial treatment for entrapment neuropathy…The literature regarding alcohol injections is equivocal. There may be some short-term positive effect, but long-term effect is poor for this therapy. Some of the literature recommends using 30% alcohol solution to get effective results. However, there is not enough data to support the use of alcohol. As a general rule, we do not advocate the use of alcohol injections”
2017 Update
A literature search conducted through March 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Intralesional Alcohol Injections for Morton Neuroma
No RCTs or nonrandomized interventional trials were identified. Several case series have been reported on the use of alcohol injections to treat Morton neuroma.
The largest study identified was reported by Pasquali and colleagues, who described a retrospective 2-center case series including 508 patients who received ultrasound-guided alcohol injection from 2001 to 2012 for Morton neuroma (Pasquali, 2015). Eligible patients presented with second or third web space symptoms and had failed 3 months of conservative treatment with insoles and nonsteroidal anti-inflammatory drugs. Patients were injected with a 50% alcohol/mepivacaine solution, with a mean of 3 injections (range 1-4) per neuroma. Pain at the Morton neuroma site was assessed on a visual analog scale (VAS) ranging from 0 to 10, by local adverse reactions at 1 week postprocedure (0=no reaction; 1=minimal swelling, pain, redness; 2=significant swelling, pain redness), and reported patient satisfaction. Pain scores improved from a mean preinjection VAS score of 8.7 to a mean postinjection score of 3.6 at 1 year (change in VAS score, p<0.001). At 1 year postinjection, 74.5% of patients were completely satisfied with the procedure. Fifty (9.3%) feet eventually required operative excision.
Earlier series were identified with smaller numbers of patients. These studies tend to report high rates of patient satisfaction and low complication rates, but provide limited evidence about the effectiveness of alcohol injections compared to alternative treatments or no treatment. Some examples are given below.
For individuals who have Morton neuroma who receive intra-lesional alcohol injection(s), the evidence includes retrospective case series. Relevant outcomes are symptoms, resource utilization, and treatment-related morbidity. The body of evidence is weak, consisting of fewer than 10 case series reporting on treatment response of patients with refractory Morton neuroma. The available series have generally reported that some patients experience pain relief and express satisfaction with the procedure. However, relief is not universally achieved. Some evidence has suggested that surgery after alcohol injections in failed cases is more complex and challenging than in untreated patients due to the presence of fibrosis. There is a lack of controlled trials comparing alcohol injections to alternatives therapies and there are no controlled studies comparing outcomes for alcohol injections to those for surgery in patients who all are surgical candidates. The evidence is insufficient to determine the effects of the technology on health outcomes.
2018 Update
A literature search conducted through April 2018 did not reveal any new information that would prompt a change in the coverage statement.
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2019. No new literature was identified that would prompt a change in the coverage statement.
2020 Update
A literature search was conducted through April 2020.  There was no new information identified that would prompt a change in the coverage statement.  
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2023. No new literature was identified that would prompt a change in the coverage statement.

64632Destruction by neurolytic agent; plantar common digital nerve

References: Pace A, Scammell B, Dhar S.(2010) The outcome of Morton's neurectomy in the treatment of metatarsalgia. Int Orthop. Apr 2010;34(4):511-515. PMID 19484237

Adams WR, 2nd.(2010) Morton's neuroma. Clin Podiatr Med Surg. Oct 2010;27(4):535-545. PMID 20934103

Association of Extremity Nerve Surgeons. 2014 Clinical Practice Guidelines, Edition 1 Accessed March, 2015.

Clinical Practice Guideline Forefoot Disorders Panel, Thomas JL, Blitch ELt, et al.(2009) Diagnosis and treatment of forefoot disorders. Section 3. Morton's intermetatarsal neuroma. J Foot Ankle Surg. Mar-Apr 2009;48(2):251-256. PMID 19232980

Dockery GL.(1999) The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. Nov-Dec 1999;38(6):403-408. PMID 10614611

Espinosa N, Seybold JD, Jankauskas L, et al.(2011) Alcohol sclerosing therapy is not an effective treatment for interdigital neuroma. Foot Ankle Int. Jun 2011;32(6):576-580. PMID 21733418

Fanucci E, Masala S, Fabiano S, et al.(2004) Treatment of intermetatarsal Morton's neuroma with alcohol injection under US guide: 10-month follow-up. Eur Radiol. Mar 2004;14(3):514-518. PMID 14531002

Gurdezi S, White T, Ramesh P.(2013) Alcohol injection for Morton's neuroma: a five-year follow-up. Foot Ankle Int. Aug 2013;34(8):1064-1067. PMID 23669161

Hughes RJ, Ali K, Jones H, et al.(2007) Treatment of Morton's neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. AJR Am J Roentgenol. Jun 2007;188(6):1535- 1539. PMID 17515373

Jain S, Mannan K.(2013) The diagnosis and management of Morton's neuroma: a literature review. Foot Ankle Spec. Aug 2013;6(4):307-317. PMID 23811947

Johnson JE, Johnson KA, Unni KK.(1988) Persistent pain after excision of an interdigital neuroma. Results of reoperation. J Bone Joint Surg Am. Jun 1988;70(5):651-657. PMID 3392057

Kasparek M, Schneider W.(2013) Surgical treatment of Morton's neuroma: clinical results after open excision. Int Orthop. Sep 2013;37(9):1857-1861. PMID 23851648

Mazoch MJ, Cheema GA, Suva LJ, et al.(2014) Effects of Alcohol Injection in Rat Sciatic Nerve as a Model for Morton's Neuroma Treatment. Foot Ankle Int. Aug 5 2014. PMID 25097192

Morgan P, Monaghan W, Richards S.(2014) A systematic review of ultrasound-guided and nonultrasound- guided therapeutic injections to treat Morton's neuroma. J Am Podiatr Med Assoc. Jul 2014;104(4):337-348. PMID 25076076

Mulder JD.(1951) The causative mechanism in morton's metatarsalgia. J Bone Joint Surg Br. Feb 1951;33-B(1):94-95. PMID 14814167

Musson RE, Sawhney JS, Lamb L, et al.(2012) Ultrasound guided alcohol ablation of Morton's neuroma. Foot Ankle Int. Mar 2012;33(3):196-201. PMID 22734280

Nashi M, Venkatachalam AK, Muddu BN.(1997) Surgery of Morton's neuroma: dorsal or plantar approach? J R Coll Surg Edinb. Feb 1997;42(1):36-37. PMID 9046143

Pasquali C, Vulcano E, Novario R, et al.(2015) Ultrasound-guided alcohol injection for Morton's neuroma. Foot Ankle Int. Jan 2015;36(1):55-59. PMID 25367249

Perini L, Perini C, Tagliapietra M, et al.(2016) Percutaneous alcohol injection under sonographic guidance in Morton's neuroma: follow-up in 220 treated lesions. Radiol Med. Jul 2016;121(7):597-604. PMID 26883232

Rajput K, Reddy S, Shankar H.(2012) Painful neuromas. Clin J Pain. Sep 2012;28(7):639-645. PMID 22699131

Thomson CE, Gibson JN, Martin D.(2004) Interventions for the treatment of Morton's neuroma. Foot Ankle Int. Dec 1995;16(12):760-763. PMID 8749346

Wu KK.(1996) Morton's interdigital neuroma: a clinical review of its etiology, treatment, and results. J Foot Ankle Surg. Mar-Apr 1996;35(2):112-119; discussion 187-118. PMID 8722878

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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