Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues. For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs. A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls. Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.

Raasveld FV ，Liu WC ，Mayrhofer-Schmid M ，Wainger BJ ，Valerio IL ，Renthal W ，Eberlin KR ... -  《-》

Revision Surgery for Recurrent Morton Neuroma with Use of a Collagen Conduit.

Painful neuromas of the foot and ankle frequently pose a treatment dilemma because of persistent pain or recurrence after resection. Primary surgical treatment of painful neuromas includes simple excision with retraction of the residual nerve ending to a less vulnerable location1-4. The use of a collagen conduit for recurrent neuromas is advantageous, particularly in areas with minimal soft-tissue coverage options, and is a technique that has shown 85% patient satisfaction regarding surgical outcomes7. Additionally, the use of a collagen conduit limits the need for deep soft-tissue dissection and reduces the morbidity typically associated with nerve burial. Specific steps include appropriate physical examination, preoperative planning, and supine patient positioning. The patient is placed supine with a lower-extremity bolster under the ipsilateral extremity in order to allow improved visualization of the plantar surface of the foot. A nonsterile tourniquet is placed on the thigh. The incision site is marked out, and a longitudinal plantar incision is made until proximal healthy nerve is identified-typically approximately 1 to 2 cm, but the incision can be extended up to 6 cm. The incision is made between the metatarsals, with blunt dissection carried down to the neuroma. The neuroma is sharply excised distally through healthy nerve, and a whip stitch is placed to facilitate the collagen conduit placement. The collagen conduit is passed dorsally into the intermetatarsal space and secured to the dorsal fascia of the foot. The wound is closed with 3-0 nylon horizontal mattress sutures. Postoperatively, a soft dressing is applied to the operative extremity, and patients are advised to be non-weight-bearing for two weeks. At two weeks, patients begin partial weight-bearing with use of a boot, and physical therapy is initiated. No antibiotics are necessary, and 300 mg of gabapentin is prescribed and tapered off by the six-week follow-up visit. Follow-ups are conducted at 2, 6, 12, 24, and fifty-two weeks. It is necessary to monitor for signs and symptoms of infection, surgical complications, and neuroma recurrence during follow-up appointments. Simple excision of the neuroma with proximal burial into muscle or bone is a common surgical technique. However, inadequate resection of the nerve or poor surgical technique can lead to recurrent neuromas. For neuromas not responding to simple excision, other techniques have been utilized, including cauterization, chemical agents, nerve capping, and muscle or bone burial5,6. The results of these techniques have varied, and none has gained clinical superiority over the other6. A study analyzing the use of collagen conduits for painful neuromas of the foot and ankle has shown this technique to be a safe and successful alternative to the previously discussed methods of resection7. That study by Gould et al. found that 85% of patients had a substantial reduction in pain, with mean visual analog scale (VAS) pain scores reducing from 8 to 10 preoperatively to 0 to 4 postoperatively7. Moreover, alternative biological conduits, such as the greater saphenous vein, have proven to be costly in time and resources, as this structure is often utilized in cardiovascular bypass surgery and its harvest conveys a risk of iatrogenic nerve injury to the patient7.Numerous studies focusing on excision of recurrent Morton neuromas via a plantar approach have found variable success rates. Of the patients surveyed in those studies, 75% reported substantial pain improvement. However, <50% of these queried patients reported complete pain relief8,9. Studies analyzing the dorsal approach for revision Morton neuroma excision found similar success rates. Approximately 78% of patients reported good or excellent postoperative outcomes, and significant improvements were observed in patient postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores for pain interference, intensity, and global physical health10,11. One study comparing outcomes following plantar versus dorsal approaches for recurrent Morton neuroma found no significant difference in postoperative patient outcomes. That study suggested that surgeons utilize the approach with which they are most comfortable12. Gould et al. reported an 85% success rate with collagen conduit, which was similar to if not slightly improved compared with the other prior studies. The utilization of a collagen conduit technique thus offers comparable patient outcomes for patients with difficult neuromas7. Recurrent neuroma resection with the use of a collagen conduit has proven to provide satisfactory patient outcomes regarding pain and neuritis symptoms7. The goal of any neuroma resection is to greatly diminish or entirely eliminate nerve pain. Based on the available evidence, there has been no proven clinical superiority of any particular technique over the others6. However, in the present example case, the location of the patient's neuroma in this video makes it 85% likely that the patient will report satisfactory outcomes and 50% likely that the patient will be entirely symptom-free7. At two weeks postoperatively, the patient reported well controlled pain, absence of burning or tingling sensation, full range of movement in the foot, and intact sensation throughout all major nerve distributions, including the saphenous; superficial peroneal nerve; deep peroneal nerve; and sural, medial, and lateral plantar nerves. However, sensation is absent distal to the site of a neuroma resection. Careful preoperative planting is of utmost importance.Ruling out other potential pathologies is necessary to ensure proper outcomes.Meticulous dissection should be carried out, with delicate handling of the proximal nerve ending.Excision of the nerve should be done sharply through the healthy portion of the nerve.Appropriate sizing of the nerve conduit (with a commercially available industry sizer) should be performed.The nerve conduit should be passed dorsally and secured to the dorsal fascia without any tension. MRI = magnetic resonance imagingUS = ultrasoundVAS = visual analog scale.

Scheinberg M ，Underwood M ，Sankey M ，Sanchez T ，Shah A ... -  《-》

Painful neuromas: a potential role for a structural transmembrane protein, ankyrin G.

Kretschmer T ，Nguyen DH ，Beuerman RW ，Happel LT ，England JD ，Tiel RL ，Kline DG ... -  《-》

Surgery for lower extremity symptomatic neuroma: Long-term outcomes.

Traumatic neuroma caused by injuries or surgery can result in neuropathic pain, functional impairment, and psychological distress, which has an impact on quality of life. The aim of this study was to identify the factors related to successful treatment of symptomatic lower extremity symptomatic neuromas using patient-reported outcome measures (PROMs). Thirty-two patients with 48 symptomatic neuromas completed the PROMIS mobility, PROMIS pain interference (PI), Numeric Rating Scale (NRS) for pain (0-10) for both pre- and post-operative pain, and the PROMIS depression at a mean of 8.9±4.5 years following neuroma surgery. Neuromas were located around the foot and ankle (n=18, 38%), leg (n=14, 29%), around the knee (n=13, 27%), and in the thigh (n=3, 6.3%). Surgical treatment included neuroma excision and implantation (n=29, 60%) followed by neuroma excision alone or excision with placement in the subcutaneous tissue (n=12, 25%). We performed multivariable analysis to identify the factors influencing the PROMs. Patients reported significant reduction in mean NRS pain after surgery (7.3 vs 4.9, p=0.0013). Higher PROMIS depression scores were independently associated with inferior PROMIS mobility scores (β=-0.38, p=0.001), higher PROMIS PI scores (β=0.68, p<0.001), and higher NRS pain scores (β=0.1, p=0.001). Additionally, smoking was independently associated with higher NRS pain scores (β=1.59, p=0.049) CONCLUSION: Surgical treatment of symptomatic neuromas of the lower extremity provides a long-term improvement in 59% of patients, but 19% of patients still reported severe persistent pain despite surgical treatment. Smoking and negative mood have negative effects on patient-reported outcomes after neuroma surgery.

Anantavorasakul N ，Lans J ，Macken AA ，Sood RF ，Chen NC ，Eberlin KR ... -  《-》

Evaluation of MRI features of neuromas in oncological amputees, and the relation to pain.

The impact of time on neuroma growth and morphology on pain intensity is unknown. This study aims to assess magnetic resonance imaging (MRI) differences between symptomatic and non-symptomatic neuromas in oncological amputees, and whether time influences MRI-detected neuroma dimensions and their association with pain. Oncological patients who underwent traditional extremity amputation were included. Post-amputation MRIs were assessed before decision for neuroma surgery. Chart review was performed for residual limb pain (numeric rating scale, 0-10) and the presence of neuropathic symptoms. Neuromas were classified as symptomatic or non-symptomatic, with neuroma size expressed as radiological neuroma-to-nerve-ratio (NNR). Among 78 neuromas in 60 patients, the median NNR was 2.0, and 56 neuromas (71.8%) were symptomatic with a median pain score of 3.5. NNR showed no association with symptomatology or pain intensity but correlated with a longer time-to-neuroma-excision interval and a smaller nerve caliber. Symptomatic neuromas were associated with lower extremity amputation, T2 heterogeneity, and the presence of heterotopic ossification. Lower extremity amputation, T2 heterogeneity, perineural edema, and presence of heterotopic ossification were associated with more painful neuromas. MRI features associated with symptomatic neuromas and pain intensity were identified. Awareness of the potential clinical significance of these imaging features may help in the interpretation of MRI exams and may aid clinicians in patient selection for neuroma surgery in oncological amputees.

van Vliet E ，Raasveld FV ，Liu WC ，Valerio IL ，Eberlin KR ，Newman ET ，Jarraya M ，Simeone FJ ，Husseini JS ... -  《-》