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Surgery for Symptomatic Neuroma

Anatomic Distribution and Predictors of Secondary Surgery

Wolvetang, Nicolaas H. A., M.D.; Lans, Jonathan, M.D.; Verhiel, Svenna H. W. L., M.D.; Notermans, Bo J. W., M.D.; Chen, Neal C., M.D.; Eberlin, Kyle R., M.D.

Plastic and Reconstructive Surgery: June 2019 - Volume 143 - Issue 6 - p 1762–1771
doi: 10.1097/PRS.0000000000005664
Reconstructive: Trunk: Original Article
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Background: Neuromas are caused by irregular and disorganized regeneration following nerve injury. Many surgical techniques have been described to address neuroma with varying success. The aim of this study was to evaluate predictive factors for secondary surgery after initial surgical intervention for symptomatic neuroma along with a description of the anatomical distribution of surgically treated symptomatic neuromas.

Methods: Five hundred ninety-eight patients with 641 neuromas that underwent primary surgery for neuroma were identified retrospectively. The diagnosis of neuroma was based on physical examination and patient history in the medical charts. Neuromas were treated by excision, implantation in muscle or bone, excision with direct neurorrhaphy with or without nerve grafting, or other treatments.

Results: The rate of secondary surgery for neuroma was 7.8 percent, and secondary operations were performed at a median of 16.1 months. Excision alone or excision with implantation into bone or muscle had higher rates of secondary surgery compared with excision and direct neurorrhaphy with or without nerve graft. Neuromas were located in the upper extremity (49.61 percent), lower extremity (46.65 percent), and the groin/trunk (3.74 percent).

Conclusions: Symptomatic neuromas are located predominantly in the extremities, and surgery can improve pain, with low secondary surgery rates. Excision with direct neurorrhaphy with or without nerve grafting was associated with lower reoperation rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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Boston, Mass.

From the Department of Orthopaedic Surgery, Hand and Upper Extremity Service, and the Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School.

Received for publication April 16, 2018; accepted December 10, 2018.

Disclosure:Dr. Eberlin is a consultant for AxoGen. The remaining authors have no financial interest to report. No funding was received for this article.

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Kyle R. Eberlin, M.D., Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, 15 Parkman Street, Wang 435, Boston, Mass. 02114, keberlin@mgh.harvard.edu

A neuroma may form as the result of irregular or disorganized neuronal regeneration following nerve injury.1 Following nerve injury, Wallerian degeneration occurs, followed by attempted axonal growth. If this does not occur in an organized manner, a neuroma will result and may be symptomatic.2,3 There are a number of causes, including prior surgery or trauma, but all involve disruption of the perineurium with axonal escape and an inability to regenerate and find terminal nerve endings.1,4,5 Depending on the pathophysiologic mechanism, the neuroma may be a terminal (i.e., “end” or “stump”) neuroma or a neuroma-in-continuity.4,6,7

Not all neuromas are problematic, but a symptomatic neuroma can have a dramatic impact on quality of life.8,9 Symptoms and signs include neuropathic pain in a specific nerve distribution, numbness, paresthesias, cold intolerance, electrical sensations, or a positive Tinel sign.10–14 There is no consensus about the clinical definition of symptomatic neuroma: diagnosis is based predominantly on patient history, physical examination including Tinel sign, and response to diagnostic injection. Prior studies have used symptoms of pain at a specific anatomical location and changes in cutaneous sensibility to identify patients with symptomatic neuroma.4,6,13,15 The reported incidence of painful neuroma in the upper and lower extremities following traumatic injury or surgery is largely unknown but ranges from 4 to 26 percent in prior studies.14,16,17 Neuroma incidence rates in other locations, such as the torso or head and neck, have solely been reported as case reports or case series.18–21

There are various surgical and nonsurgical treatments for symptomatic neuroma.11,22 Surgery most often consists of neuroma excision followed by a technique to address the end of the nerve, including transposition into muscle, bone, or veins; nerve repair with or without grafting; centrocentral coaptation; nerve capping; regenerative peripheral nerve interface; targeted muscle reinnervation; and others.1,7,11,23–39 However, after initial surgical treatment, up to 42 percent of patients may have persistent symptoms and undergo additional intervention.7,15,29,34,40–43

The factors related to secondary surgery for neuroma are not known. It has been suggested that low socioeconomic status, smoking, employment status, duration of pain, and presence of complex regional pain syndrome negatively affect surgical outcomes in treatment of symptomatic neuroma.9,13,29,40,43–45 The aim of this study was to evaluate predictive factors for secondary surgery after initial surgical intervention for symptomatic neuroma. A secondary aim was to describe the distribution of surgically treated symptomatic neuromas throughout the entire body.

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PATIENTS AND METHODS

After institutional review board approval, we retrospectively identified patients (n = 3064) using CPT codes related to surgery for symptomatic neuroma between January 1, 2002, and May 1, 2016, in five urban academic medical centers in the Northeastern United States. (See Appendix, Supplemental Digital Content 1, which shows the CPT codes used to identify patients with surgically treated neuroma, http://links.lww.com/PRS/D491.) Through medical chart review, we included all adult patients who underwent surgery for symptomatic neuroma. We excluded patients who underwent initial surgery for neuroma at a different hospital (n = 32), were not found to have a neuroma intraoperatively (n = 53), those diagnosed with a schwannoma or nerve sheath tumor (n = 38), or those on whom no surgery was performed on a nerve (n = 5). In addition, we excluded head and neck neuromas (n = 141) because the majority of these were of lingual nerves (n = 119), and 90 percent of the nerves at these locations were treated by excision with primary nerve repair, skewing treatment in the presented population. For purposes of analysis, only the first neuroma treated was included. These patients were categorized as having undergone initial surgery for symptomatic neuroma.

We performed a medical chart review to collect data regarding patient, neuroma, and treatment characteristics along with postoperative complications including any subsequent surgery. Secondary surgery for neuroma was defined as additional, unplanned surgery for neuropathic pain of the same nerve as treated during the initial neuroma surgery. If a patient reported pain as a symptom in a presurgical evaluation (for the secondary procedure), this was considered secondary neuroma surgery. Follow-up was defined as the last surgical visit recorded in the medical charts. Time to initial neuroma surgery was defined as the time from the date of initial surgery or the trauma causing neuroma to the date of first neuroma surgery, which was available for 374 patients.

During chart review, description of neuroma or related symptoms was used to identify patients undergoing surgery for neuroma. The most common preoperative symptoms recorded were pain [n = 513 (80 percent)], hyposensitivity [n = 92 (14 percent)], paresthesias [n = 4 (0.6 percent)], weakness [n = 29 (4.5 percent)], or presence of a mass [n = 3 (0.5 percent)] (Fig. 1). Two hundred thirty-two patients had a positive Tinel sign. The preoperative diagnosis was confirmed by operative pathologic evaluation in 362 cases; an additional 201 cases were described as a neuroma by the surgeon intraoperatively (in the absence of pathologic evaluation demonstrating neuroma), and 55 were described as a scarred or injured nerve by the surgeon intraoperatively.

Fig. 1

Fig. 1

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Study Population

We included 598 patients with 641 neuromas and a median age of 43.9 years (interquartile range, 35.1 to 52.6 years) who were followed for a median of 5.1 months (interquartile range, 1.2 to 19.4 months) (Table 1). Patients developed neuromas mostly because of trauma or surgery. A total of 253 patients (40 percent) underwent a preoperative intervention, consisting mainly of diagnostic local anesthetic injection [n = 208 (82 percent)].

Table 1

Table 1

Surgery was performed by 98 surgeons, who were either trained in nerve microsurgery (plastic surgery, orthopedic hand surgery, neurosurgery), or untrained in nerve microsurgery (other surgical specialties). Seventeen surgeons performed more than 14 neuroma operations each, accounting for 73 percent of the operations. Neuromas were treated by excision with nerve implantation in muscle or bone [n = 321 (50 percent)], excision with direct neurorrhaphy with or without nerve grafting [n = 177 (28 percent)], excision only [n = 130 (20 percent)], or other miscellaneous treatments (flap coverage, nerve capping and implantation, or excision and collagen conduit) [n = 13 (2.0 percent)] (Table 2). During the period of this study, no patients were treated by targeted muscle reinnervation or regenerative peripheral nerve interfaces.

Table 2

Table 2

Neuromas were identified in the upper extremity [n = 318 (49.61 percent)], lower extremity [n = 299 (46.65 percent)], and the groin/trunk [n = 24 (3.74 percent)] (Figs. 2 through 5). In the upper extremity, the most common nerves affected were the digital nerves [n = 158 (50 percent)]. In the lower extremity, the interdigital [n = 76 (25 percent)], peroneal [n = 69 (23 percent)], and sural nerves [n = 66 (22 percent)] were similarly affected. The peroneal nerve consisted of the branches of the superficial peroneal nerve [n = 43 (62 percent)], the deep peroneal nerve [n = 12 (17 percent)], and the common peroneal nerve [n = 13 (19 percent)]. In the groin/trunk region, the ilioinguinal nerves [n = 8 (33 percent)] and intercostal nerves [n = 8 (33 percent)] were most commonly affected.

Fig. 2

Fig. 2

Fig. 3

Fig. 3

Fig. 4

Fig. 4

Fig. 5

Fig. 5

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Statistical Analysis

Continuous variables were presented as median and interquartile range or mean and standard deviation depending on normality. Categorical variables were presented as absolute values and percentages.

Surgery type was grouped as (1) excision only, (2) excision and implantation in bone, muscle, or soft tissue; (3) excision with direct neurorrhaphy or nerve graft; or (4) other, including flap coverage, nerve capping and burying or excision, and using a collagen conduit. In addition, the location of the neuroma was grouped into four groups: upper extremity, lower extremity, head and neck, and other (which included groin and trunk). Finally, “other causes of neuroma” included 69 patients with a Morton neuroma. Nerves were grouped by location or by specific nerve. (See Appendix, Supplemental Digital Content 2, which shows the categorization of the nerves with a symptomatic neuroma, http://links.lww.com/PRS/D492.)

To evaluate factors associated with reoperation, we performed a bivariate analysis using the Mann-Whitney U test for nonparametric outcomes and the Fisher’s exact test for categorical variables. To mitigate for confounding, all explanatory variables with a value of p < 0.1 in bivariate analysis were imputed into a multivariable logistic regression modeled using generalized estimating equation. In addition, we included preoperative symptoms (pain versus other) and the type of surgery based on clinical relevance in the statistical model. We used a Cox proportional hazards model to evaluate the predictors that affect the time to secondary neuroma surgery. A value of p < 0.05 was considered statistically significant for all tests. We used STATA 13.0 (StataCorp, College Station, Texas) to execute these analyses.

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RESULTS

Symptomatic neuromas were secondary to traumatic injury in 50 percent and attributable to surgery in 38 percent. The median time from inciting event to primary neuroma surgery was 6.4 months (interquartile range, 1.8 to 14.0 months) for patients with trauma and 13.4 months (interquartile range, 7.8 to 29.0 months) for those where prior surgery was the cause. Thirty-nine patients (5.3 percent) presented with multiple neuromas, mostly located in the upper extremity [n = 26 (55 percent)] and caused by trauma [n = 16 (34 percent)], amputation [n = 10 (21 percent)], previous surgery [n = 19 (40 percent)], or Morton neuroma [n = 2 (4.3 percent)].

Excision alone (OR, 4.9; 95 percent CI, 1.6 to 14.6; p = 0.005) and excision with implantation into bone or muscle (OR, 3.4; 95 percent CI, 1.1 to 10.2; p = 0.027) were independently associated with higher rates of secondary surgery when compared to excision and direct neurorrhaphy with or without nerve graft. When the neuroma was treated by a surgeon who was untrained in microsurgical nerve repair, patients had a lower chance of undergoing a secondary neuroma surgery compared with those treated by a surgeon trained in microsurgical nerve repair (OR, 0.38; 95 percent CI, 0.18 to 0.84; p = 0.016) (Table 3). No predictors that affect the time to secondary neuroma surgery were identified. (See Table, Supplemental Digital Content 3, which shows the Cox proportional hazards model for time to reoperation, http://links.lww.com/PRS/D493.) Minor postoperative complications were noted in 20 patients (3.1 percent), consisting of wound dehiscence, infection, or a hematoma/seroma.

Table 3

Table 3

The rate of secondary surgery for neuroma was 7.8 percent (50 of 641) after a median of 16.1 months (interquartile range, 6.0 to 34.2 months) (Fig. 6). In almost all cases [n = 48 (96 percent)], pain and/or hypersensitivity was the indication for secondary neuroma surgery. The secondary neuroma operations performed were neuroma excision and implantation [n = 31 (62 percent)], neuroma excision [n = 11 (22 percent)], neuroma excision with primary neurorrhaphy with or without graft [n = 5 (10 percent)] or other intervention [n = 3 (6.0 percent)] (Table 4).

Table 4

Table 4

Fig. 6

Fig. 6

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DISCUSSION

We analyzed factors associated with reoperation of symptomatic neuroma. In this study, 641 surgically treated neuromas were identified, 96 percent of which occurred in the extremities. Neuromas were secondary to traumatic injury in 50 percent and surgery in 38 percent, and it was found that initial surgery for neuroma was performed at a median of 9 months after the inciting event.

In this study, neuroma excision and nerve implantation was the most commonly performed technique, followed by excision and neurorrhaphy with or without nerve graft. Reasons for this choice of treatment may include the presence of more neuromas in continuity, or the presence of stump neuromas without an available distal target. The rate of secondary surgery after primary neuroma surgery was 7.8 percent. If a neuroma was treated by excision followed by neurorrhaphy with or without nerve graft, the secondary surgery rates were lower compared to excision alone or excision and implantation.

This study should be considered in light of its strengths and limitations. First, the patients in this study were identified retrospectively using chart review, making the selection dependent on correct coding. Second, the diagnosis of neuroma was based on a combination of patient history and physical examination, and there is no gold standard for diagnosis. In this study, the majority of the patients had histologic confirmation (n = 362) or intraoperative findings corresponding with a neuroma (n = 201). Third, this study did not account for the patients who underwent treatment (1) at a pain clinic or (2) performed by a different surgeon outside our institution. Fourth, newer surgical techniques such as targeted muscle reinnervation and regenerative peripheral nerve interface were not evaluated given the timeframe of this study, although they are increasingly used in the senior author’s (K.R.E.) practice. Lastly, this study did not investigate patient psychosocial factors related to surgery or outcomes.

However, this study may underestimate the surgical failure rate, as secondary surgery is an imperfect proxy for patient outcome. If one neuroma surgery has “failed,” some surgeons may not offer the patient a second operation. It has been reported that patients who have undergone more than three previous operations for neuroma have 66 percent good/excellent pain relief after excision and implantation, compared with 90 percent good/excellent results after initial surgery.29 In patients with persistent pain after initial surgery, central sensitization may have occurred, influencing surgical outcomes when addressing the peripheral impetus.46 Centralization of pain may impact the success of peripheral nerve intervention, although the surgical impact on this phenomenon is not currently well understood.

We also report the anatomical distribution of surgically treated neuromas. Neuromas treated operatively were most common in the upper and lower extremities. In the upper extremities, the digital nerves were predominantly affected as a result of (nonamputation) trauma (65 percent) or amputation (21 percent). In the lower extremity, Morton neuroma (25 percent) was most common, followed by peroneal neuroma (23 percent) and sural neuroma (22 percent); the latter was most often caused by prior surgery (70 percent). A previous study reported that the lower extremity was the most commonly involved anatomical region (54 percent), which is similar to the rate identified in this study.47 It is likely that surgically treated neuromas are most common in the extremities, as they are prone to trauma and often have a thin subcutaneous cover.

Many surgical techniques to treat neuroma have been described. Techniques involving neuroma excision and implantation/burying have historically been the most commonly used, and were the most commonly performed techniques in this study.11,15,29,40,48 In a comparative meta-analysis, Poppler et al. concluded that 77 percent of all patients with neuroma had meaningful improvement of pain regardless of the surgical method used.49 In this study, we identified a lower rate of secondary operation after neuroma excision with nerve reconstruction (direct neurorrhaphy or neurorrhaphy with a nerve graft) compared to other interventions. This is similar to the finding by Pet et al., in which patients treated with traction neurectomy had a relatively high rate of symptomatic recurrence.34 This is also in line with the findings of Guse and Moran, who found that nerve repair had the highest rate of success.50 This study’s finding of lower rates of secondary neuroma surgery in patients undergoing neurorrhaphy with or without nerve graft compared to those undergoing implantation techniques is most likely the result of active treatment of the nerve ending.51 Newer techniques such as targeted muscle reinnervation and use of a regenerative peripheral nerve interface have provided promising results.36,39,52–54 Of the patients treated with primary targeted muscle reinnervation at the time of traumatic amputation, 92 percent were free of pain at follow-up.55

The secondary neuroma surgery rate of 7.8 percent identified in this study is similar to prior studies. Dellon and Mackinnon evaluated 78 neuromas in 60 patients that were treated by resection and implantation into muscle and reported a secondary surgery rate of 6.4 percent.29 Vlot et al. described a secondary surgery rate of 23 percent for digital neuromas and found that avulsion injury and neuroma of the index finger were associated with higher rates of secondary surgery.13 In another study, Decrouy-Duruz et al. evaluated secondary surgery in 231 patients that had neuropathic pain after nerve injury, of which 44 percent were classified as neuroma and were treated with resection and transposition in soft tissue. The remainder were neuroma in continuity or scarred nerves and were treated with neurolysis alone. Their overall reoperation rate was 16 percent; however, because of the different cohort of patients, direct comparison with this study is difficult.47 A retrospective study of 67 patients surgically treated by excision and burying the proximal end of the nerve in the muscle reported a secondary surgery rate of 21 percent.34

The decision for secondary neuroma surgery is complex and based on many factors, including patient symptoms, surgeon experience, and available techniques for reconstruction. Some surgeons are reluctant to offer secondary surgery for neuroma if the first intervention was unsuccessful. In this study, we found that patients undergoing initial neuroma surgery performed by surgeons trained in microsurgery were more likely to undergo secondary surgery. This may be because nerve-trained microsurgeons have more surgical options available for treatment of neuroma compared with nonmicrosurgeons and may be more willing to attempt additional surgical intervention.

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CONCLUSIONS

Patients with symptomatic neuroma may undergo surgical intervention in an attempt to ameliorate symptoms. Surgical treatment of neuroma may improve quality of life for these patients, and most patients will not undergo secondary neuroma surgery. Further investigation into the optimal timing and type of surgical technique is needed to help inform surgical decision-making.

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