Cryogenic neuroablation is a safe, minimally invasive option that is less painful than alcohol injections and may facilitate a reduced risk of stump neuromas, according to this author. By Lawrence Fallat, DPM Morton’s neuroma (perineural fibroma) is a common painful forefoot disorder that can present treatment challenges to all podiatric physicians. The common digital nerves, usually in the second and third intermetatarsal spaces, become enlarged in the area of the deep transverse metatarsal ligament and subsequently cause pain in the ball of the foot with cramping, pain and numbness of the toes. Histological findings of the nerve include endoneural edema with perineural, epineural and endoneural fibrosis. Endarterial thickening occurs along with axonal loss and demyelination. These findings are consistent with a degenerative process and it is generally accepted that this occurs as a result of nerve entrapment. Conservative treatment consists of shoe modification, orthotics, NSAIDs and steroid injections. Neurolytic agents such as phenol and, more commonly, diluted 4% alcohol have been advocated.1 When conservative treatment fails, surgical intervention may be indicated. Excision of the neuroma is the most common surgical procedure performed but significant failure rates have been reported.2,3 Poor results can occur from incomplete excision or the formation of a stump neuroma that can be more troublesome than the original pain. With this in mind, one should consider the possible use of cryogenic neuroablation, which describes the destruction of axons to prevent them from carrying painful impulses. This technique involves applying extremely cold temperatures between –50ºC and –70ºC to the nerve. This results in degeneration of the intracellular elements, axons and myelin sheath with Wallerian degeneration.4 These changes are consistent with a second-degree nerve lesion. The epineurium and perineurium remain intact, and this prevents the formation of stump neuromas as the nerve regenerates. The preservation of these structures differentiates cryosurgery from surgical excision and neurolytic agents. Comparing Alcohol Injections To Cryosurgery I have used 4% alcohol injections for many years but with mixed results. Some patients do respond favorably to this treatment but many continue to have neuroma pain. In my experience, many patients have severe pain associated with the alcohol injections and approximately 50 percent of patients do not complete the series of injections because of pain associated with these injections. We recently had two patients who were treated in the emergency room later in the day because of burning pain at the injection site. I am also concerned about the effect of the alcohol on the peripheral nerves. Presumably the alcohol destroys the axon and its myelin sheath but it cannot be tissue specific and must also destroy the endoneurium, perineurium and epineurium. If the destruction of the nerve is complete, there will be a neurotomesis that will invariably form a stump neuroma as the axons regenerate. In this sense, the nerve destruction may carry the same risks as neuroma excision. It’s also important to keep in mind that the long-term results of alcohol injections have not been reported. With cryosurgery, the destruction of the axons is almost completely painless. I used to perform the procedure using only 1/2 cc of local anesthetic for the skin where I made the incision. I did not use any anesthetic to block the nerve. When I applied the ice ball to the neuroma, the patients experienced only a mild burning sensation that resolved after one to two minutes. There was only minimal postoperative discomfort that was controlled with NSAIDs. More significantly, cryogenic neuroablation does not destroy the epineurium or perineurium, the basic architecture of the nerve. As a result, stump neuromas do not form as the nerve regenerates. Having performed this procedure for approximately 200 patients over the last three years, I have found that very few patients have had a recurrence of their neuroma pain. If the pain returns a year or two later, I simply repeat the procedure. Axons regenerate at the rate of 1 to 3 mm per day. The prevailing thinking is that the ice ball destroys a 1-cm portion of the nerve. Therefore, the axon regeneration should be complete within several weeks. It appears the long lasting relief is due to the reduction of neural edema and fibrosis of the neuroma. Researchers have also reported similar long-term relief using cryosurgery to treat painful trigeminal nerve pathology.5,6 Pertinent Pointers On The Cryosurgery Technique In regard to the specific technique, I first palpate the area of the greatest neuroma pain on the plantar surface of the foot and mark it with a surgical pen. Then I inject the local anesthetic, injecting 3 cc of 1% plain lidocaine into the intermetatarsal space and injecting an additional 1 cc of lidocaine with epinephrine just below the skin dorsally for homeostasis. One should prep the surgical site with betadine and make a 3-mm incision dorsally with a number 65 beaver blade. Use a trocar or angiocatheter to separate the tissue as you advance to the area of pain that you have marked. You will see the deep transverse metatarsal ligament, which you may section if you prefer. Proceed to insert the 2-mm cryoneedle into the area of the neuroma and administer a three-minute freeze cycle. This is followed by a 30-second defrost and another three-minute freeze cycle. Irrigate the wound with 2 cc of 0.5% plain Marcaine and 0.25 cc of steroid. How Should You Handle Postoperative Care? No sutures are required but you should apply a mildly compressive dressing. Give the patient a NSAID to reduce postoperative discomfort. If the patient has only undergone the percutaneous cryosurgery procedure performed, have him or her reduce activity for the next two to three days and apply ice to the surgical site when resting. These patients can remove the dressing the next morning, shower and use a Band-Aid with a topical antibiotic. The incision usually heals in about three days. The destruction of the axons is immediate with cryosurgery so the patients should only feel mild discomfort, which usually resolves in about one week. The patients are usually able to wear normal shoes and be reasonably active during this period. However, if the deep transverse ligament has been released, the surgical site is more uncomfortable and may take two to three weeks to heal. Reviewing Results, Potential Limitations And Contraindications Of Cryosurgery The majority of patients obtain complete relief or significant improvement following cryosurgery. All of my patients who have had cryogenic neuroablation have maintained full motor function with no greater loss of sensation than they had prior to the procedure. The results from this procedure are not considered permanent but, in my experience, some of my patients have reached the three-year mark with no recurrence of neuroma pain. When no relief occurs, it is usually because of dense scar tissue related to a previous excision of the neuroma.7 Performing a percutaneous adhesiotomy or inserting the cryoneedle through the plantar aspect of the foot can overcome this obstacle. Another limitation of this procedure appears to be the size of the neuroma and excessive fibrosis from previous neurectomy. If the neuroma is 3 cm diameter or greater, the 1 cm ice ball may not be able to penetrate the entire mass. In my experience, patients with very large neuromas and excessive scar tissue have also failed all previous treatment including alcohol injections. There is a very low incidence of complications associated with cryosurgery. Infections are rare as is abscess formation at the incision site. However, since cryosurgery involves very cold temperatures, one should avoid performing this procedure for patients who have peripheral vascular disease and conditions such as Raynaud’s phenomena. Final Notes Cryogenic neuroablation is a very safe, minimally invasive procedure that one can perform in the office and achieve very good relief of Morton’s neuroma pain. The postoperative recovery period with this procedure is short as patients only need to reduce activity for two to three days. Unlike alcohol injections, the procedure is not painful and patient acceptance is excellent. Dr. Fallat is a Clinical Assistant Professor within the Department of Family Medicine at the Wayne State University School of Medicine in Detroit. He is the Director of Podiatric Surgical Residency for the Oakwood Healthcare System in Dearborn, Mich. Dr. Fallat is board-certified by the American Board of Podiatric Surgery and is a Fellow of the American College of Foot and Ankle Surgeons. References 1. Dockery GL, Nilsson RZ. Intralesional injections. Clin Podiatr Med Surg 1986; 3:473-485. 2. Gudas CJ, Mattana GM. Retrospective analysis of intermetatarsal Neuroma excision with preservation of the transverse metatarsal ligament. J Foot Surg. 1986; 25:259-463. 3. Bradley MD, Miller WA, Evans JP. Plantar Neuroma: analysis of results following surgical excision in 145 patients. South Med J 1976; 69:853-845. 4. Davies E, Pounder D, Mansour S, Jeffery, I.T.A. Cryosurgery for chronic injuries of the cutaneous nerves in the upper limb. JBJS Vol. 82-B No.3. April 2000; p 413-415. 5. Barnard D, Lloyd J, Evans J. Cryoanalgesia in the management of chronic facial pain. J. Maxillofac Surg. 1981;9: 101-102. 6. Zakrzgwska JM, Nally FF. The role of cryotherapy (cryoanalgesia) in the management of paroxysmal neuralgia: A six year experience. Br J Oral Maxfac Surg. 1988; 26:18-25. 7. Caporusso EF, Fallat LM, Savoy-Moore R, Cryogenic Neuroablation for the Treatment of Lower Extremity Neuromas. J. Foot Ankle Surg. 41;286-290, 2002. Reviewing the literature and sharing pearls from his own experience, the author says sclerosing injections can be effective for treating intermetatarsal neuromas. By Charles F. Peebles, DPM My choice of sclerosing injections for treating neuromas comes down to one question: “What would I do if my neuroma didn’t respond to other conservative options?” Well, I wouldn’t treat my patients any differently than I would treat myself. Sclerosing injections with dehydrated alcohol are being used with increasing frequency in treating intermetatarsal neuromas and recurrent or “stump” neuromas. One can use this modality without significant risk to the patient and it does not compromise tissues in the event that surgical intervention is required. Numerous podiatric physicians have added this technique to their treatment algorithm for this condition with significant success. When conservative therapy fails, one may consider alternative methods, including various injections, neural destructions and surgical interventions (see “Where Does Injection Therapy Fall In The Treatment Algorithm?” below). However, using 4% alcohol sclerosing injections has shown significant promise as a conservative intervention for intermetatarsal or recurrent neuromas prior to surgical release or excision. Where Does Injection Therapy Fall In The Treatment Algorithm? One must consider conservative modalities and surgical options when treating intermetatarsal neuromas. When it comes to conservative management, you want to address mechanical etiologies through the use of padding, strapping and orthotic fabrication. Doing so helps to eliminate the pathologic forces that induce neuroma formation. Shoe selection and modification are essential in decreasing the tension on the nerve structures. One may also employ physical therapy modalities in order to decrease inflammation in the region and relieve neural tension from more proximal etiologies. If these modalities fail, one may pursue injection therapy. Injections with corticosteroids, vitamin B12 and ethyl alcohol have been employed with varying success in treating intermetatarsal neuromas.1-7 Surgical intervention consists of excising the involved nerve via neurectomy or releasing the deep intermetatarsal ligament. The success rates of these treatment options vary from 76 to 97 percent with most ranging closer to the former.5-10 Common complications may include infection, hematoma/seroma formation and recurrent or stump neuromas. When it comes to recurrent neuromas, treatment considerations include much more involved surgical intervention with success rates lower than those for primary neuromas. Conservative options include massage and desensitization modalities in combination with local steroid infiltration. Surgical management attempts to prevent nerve regrowth and eliminate symptoms. Neurectomy, epineuroplasty and nerve implantation have all been attempted with varying success in treating recurrent neuromas. Given the potential for complications with any surgical intervention, it is important to exhaust all conservative options prior to surgery. Taking A Closer Look At The Effectiveness Of Sclerosing Injections Injections of absolute ethyl alcohol (dehydrated sterile alcohol) affect nerves through damage at the cellular level. The cellular effect involves dehydration, necrosis and precipitation of protoplasm. Dehydrated alcohol is soluble in local anesthetic. When it is introduced near nerve tissue, it causes neuritis and chemical neurolysis via Wallerian nerve degeneration.11 While the injected solution has a high affinity for nerve tissue and the desired effect on these tissues, the low concentration reportedly does not have any systemic effect as 90 to 98 percent of ethyl alcohol is oxidized by the body.12 In a 1999 study, the author showed 89 percent improvement with complete relief in 82 of 100 patients who were treated with the sclerosing injections. According to the study, follow-up ranged from six months to two years.5 Patients received a minimum of three injections and no more than seven injections. In regard to the 11 patients who failed injection therapy, the author didn’t identify any soft tissue complications and subsequently proceeded to surgical removal of the neuroma. The author did identify atrophy of the nerve tissue in the patients who failed conservative therapy and a series of sclerosing injections.5 I used these same techniques to treat intermetatarsal and recurrent neuromas, and presented my results in April 2001.7 I treated 29 neuromas (18 primary and 11 recurrent) with sclerosing injections that were given, on average, seven days apart. Marking the site of maximum tenderness prior to injection, I performed all the injections proximal to the entrapped or damaged nerve. Patients received a minimum of three injections and not more than seven injections. I discontinued the therapy if there were complete resolution of symptoms or no relief after three injections. We scheduled follow-up visits one month after the final injection and six months after the final injection in order to determine the success of therapy. (Some patients returned for other podiatric-related complaints up to three years after sclerosing therapy.) We defined success on patients’ subjective assessment that they had obtained greater than 90 percent relief. In the primary treatment group, 78 percent of neuromas (14 of 18) were treated successfully with sclerosing therapy. In the recurrent neuroma group, 82 percent of neuromas (nine of 11) were treated successfully.7 There was one side effect, which was local irritation of the plantar foot distal to the injection site but it resolved after one day. Patients who did not have successful therapy had the option of surgical intervention and we saw no injection-related complications intraoperatively or postoperatively. Clinical Exam Keys To Identifying Intermetatarsal Neuromas Before embarking on any treatment plan, one must correctly diagnose intermetatarsal neuromas as forefoot pain can be caused by a variety of conditions. When patients have an intermetatarsal neuroma, the typical presenting complaint includes pain or tingling in the ball of the foot with ambulation and occasional radiation to the digits. These symptoms are most common in the third interspace, followed by the second interspace, and infrequently in the first or fourth interspace. Patients tend to relate an increase in symptoms when they wear dress shoes, especially high heels. They will often have relief of these symptoms when they cease wearing the dress shoes or when they wear more supportive shoes. Patients may describe the pain as burning, tingling, shooting or they may say it feels like a bruised region in the forefoot. Also be aware that similar symptoms may return after the removal of a previously treated neuroma or following trauma to a nerve. While the key finding from the clinical exam is pain in the interspace at the level of the deep transverse intermetatarsal ligament, be aware that you will sometimes see edema in this region. Also keep in mind that these patients will usually have no pain directly plantar to the metatarsal heads. In order to reproduce the patient’s symptoms, one should dorsiflex the digits and palpate the deep intermetatarsal ligament. Dorsal-plantar palpation of the interspace with compression of the medial and lateral aspects of the foot often allows palpation of an inflamed nerve. This palpable “click” is commonly called Mulder’s sign.13 One may also pursue diagnostic testing to either confirm your clinical diagnosis or rule out a variety of differential diagnoses.14 How To Perform Alcohol Sclerosing Injections If initial conservative therapy in the form of orthotics, shoe modifications and/or physical therapy modalities has failed, one should consider sclerosing injections with dehydrated alcohol. Prior to initiating this therapy, inform patients that you will be giving them three serial injections and will evaluate success based on their clinical response. Let them know that they may receive up to seven injections. Caution them that pain is often associated with the initial injection due to the induced damage to the nerve but this typically resolves with subsequent injections. In order to prepare the injection solution, one would mix 48 ml of 0.5% bupivicaine HCl with epinephrine with 2 ml of dehydrated alcohol. This produces a 50 ml solution of 4% sclerosing solution, which is good for three months. Initially, one should mark the point of maximum tenderness at the region of the neuroma “bulb.” Proceed to introduce the 1.25-inch, 27-gauge needle dorsally and manipulate it until the patient experiences pain and radiation to one or both toes. At this point, you should proceed to inject 0.5 cc of 4% sclerosing solution into the intermetatarsal nerve. One would subsequently perform injections every five to 10 days. In my experience, it averages out to every seven days. If you appreciate skin or soft tissue atrophy plantarly, discontinue the injections. One should follow up with the patients one month after the final injection to determine short-term success and give them instructions to follow up if they have persisting symptoms. Encourage functional support throughout the injection and post-injection process. If sclerosing injections fail to provide relief, one should proceed to discuss surgical intervention with the patient in order to alleviate his or her symptoms. Final Notes In my experience, I have found that using sclerosing injections with dehydrated alcohol is an excellent alternative to surgical excision or release in treating both primary and recurrent neuromas. Dr. Peebles is a Fellow of the American College of Foot and Ankle Surgeons, and is on the faculty of the Podiatry Institute. References 1. Bennett GL, Graham CE, Mauldin DM: Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int. 16:760-763, 1995. 2. Greenfield J, Rea J, Illfeld FW: Morton’s interdigital neuroma: indications for treatment by local injection versus surgery. Clin Orthop 185: 142-144, 1984. 3. Steinberg MD: The use of vitamin B-12 in Morton’s neuralgia. J Am Podiatry Assoc 45: 41-42, 1955. 4. Dockery GL, Nilson RZ: Intralesional injections. Clin Pod Med Surg 3: 473-485, 1986. 5. Dockery GL: The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg 38(6): 403-408, 1999. 6. Peebles CF: Sclerosing injections in the treatment of intermetatarsal neuromas. In Mahan KT, Miller SJ, Ruch JA, Yu GV, Vickers NS, eds. Update 2001: The Proceedings of the Annual Meeting of the Podiatry Institute Tucker, GA: The Podiatry Institute, Inc: 2001: 34-36. 7. Peebles CF: The use of sclerosing injections in the treatment of neuromas. In Mahan KT, Miller SJ, Ruch JA, Yu GV, Vickers NS, eds. Update 2003: The Proceedings of the Annual Meeting of the Podiatry Institute Tucker, GA: The Podiatry Institute, Inc: 2003: 122-124. 8. Downey MS: Recurrent interdigital neuroma: current considerations and treatment approaches. In Vickers NS, Miller SJ, Mahan KT, Yu GV, Camasta CA, Ruch JA, eds. Reconstructive Surgery of the Foot and Leg – Update ’96 Tucker, GA: The Podiatry Institute, Inc: 1996: 186-192. 9. Banks AS, Vito GR, Giorgini TL: Recurrent intermetatarsal neuroma: a follow-up study. JAPMA 86(7): 299-306, 1996. 10. Intermetatarsal neuroma: Preferred Practice Guideline from American College of Foot Ankle Surgeons. 1996. 11. Rengachry SS, Watanabe IS, Singer P, Bopp WJ: Effect of glycerol on peripheral nerve: an experimental study. Neurosurgery 13:681-688, 1983. 12. Package Insert. Dehydrated Alcohol Injections, USP. American Regent Laboratories, Inc., Subsidiary of Luitpold Pharmaceuticals, Shirley, NY 11967. 13. Mulder JD: The causative mechanism in Morton’s metatarsalgia. J Bone Joint Surg 33B:94-95, 1951. 14. Wu KK: Morton’s interdigital neuroma: a clinical review of its etiology, treatment and results. J Foot Ankle Surg 35:112-119, 1996. Editor’s Note: For a related article, see “Is Injection Therapy The Best Solution For Foot Neuromas?” in the January 2002 issue or check out the archives at www.podiatrytoday.com .