Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Phantom Limb Pain and Painful Neuroma After Dysvascular Lower-Extremity Amputation: A Systematic Review and Meta-Analysis.

BACKGROUND: Phantom limb pain (PLP) and symptomatic neuroma can be debilitating and significantly impact the quality of life of amputees. However, the prevalence of PLP and symptomatic neuromas in patients following dysvascular lower limb amputation (LLA) has not been reliably established. This systematic review and meta-analysis evaluates the prevalence and incidence of phantom limb pain and symptomatic neuroma after dysvascular LLA. METHODS: Four databases (Embase, MEDLINE, Cochrane Central, and Web of Science) were searched on October 5th, 2022. Prospective or retrospective observational cohort studies or cross-sectional studies reporting either the prevalence or incidence of phantom limb pain and/or symptomatic neuroma following dysvascular LLA were identified. Two reviewers independently conducted the screening, data extraction, and the risk of bias assessment according to the PRISMA guidelines. To estimate the prevalence of phantom limb pain, a meta-analysis using a random effects model was performed. RESULTS: Twelve articles were included in the quantitative analysis, including 1924 amputees. A meta-analysis demonstrated that 69% of patients after dysvascular LLA experience phantom limb pain (95% CI 53-86%). The reported pain intensity on a scale from 0-10 in LLA patients ranged between 2.3 ± 1.4 and 5.5 ± .7. A single study reported an incidence of symptomatic neuroma following dysvascular LLA of 5%. CONCLUSIONS: This meta-analysis demonstrates the high prevalence of phantom limb pain after dysvascular LLA. Given the often prolonged and disabling nature of neuropathic pain and the difficulties managing it, more consideration needs to be given to strategies to prevent it at the time of amputation.

Epidemiology, risk factors, diagnosis, and treatment of intra-abdominal traumatic neuromas - a narrative review.

Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.

[Diagnostics and surgical treatment of painful neuromas]. / Diagnostik und chirurgische Therapie schmerzhafter Neurome.

BACKGROUND: Painful neuromas that often develop after peripheral nerve injury require adequate diagnosis and treatment because of the suffering they cause. The scientific basis for the development of painful neuromas has not yet been sufficiently investigated. In addition to conservative procedures, a larger number of surgical techniques are available for treatment of painful neuromas. OBJECTIVE: A review of the basic principles, diagnostic and treatment options for painful neuromas. MATERIAL AND METHODS: Presentation of the scientific basis regarding the development of painful neuromas. Illustration and discussion of the most common diagnostic and treatment procedures. RESULTS: The scientific basis regarding the development of painful neuromas after peripheral nerve injury has not yet been adequately developed. In order to be able to make a correct diagnosis, the use of standardized diagnostic criteria and adequate imaging techniques are recommended. In the sense of a paradigm shift, the use of the formerly neuroma-bearing nerve for reinnervation of target organs is to be preferred over mere burying in adjacent tissue. CONCLUSION: In addition to standardized diagnostics the management of painful neuromas often requires a surgical intervention after all conservative therapeutic measures have been exhausted. As an alternative to restoring the continuity of the injured nerve, targeted reinnervation of electively denervated target organs by the formerly neuroma-bearing nerve is preferable over other techniques.

Left Gluteal Maximus Neuroma Causing Long-Standing Gluteal Pain.

ABSTRACT: Diagnosing buttock pain is a challenge due to complex anatomy and multiple causes. Potential pathologies range from common and benign to rare and life-threatening. Common causes for buttock pain include referred pain from the lumbar spine and sacroiliac joint, hamstring origin tendinopathy, myofascial pain, ischiogluteal bursitis, gluteal pathology, and piriformis syndrome. Rarer causes include malignancy, bone infection, vascular anomalies, and spondyloarthropathies. Other conditions may be present concurrently in the lumbar and gluteal area, which can cloud the clinical picture. Correct diagnosis and early treatment may improve quality of life by providing a targetable reason for their distress, improving pain, and allowing the patient to get back to their activities of daily living. When treating a patient with buttock pain, it is essential to reevaluate the diagnosis when symptoms fail to improve despite appropriate intervention.Here, we discuss a case of a peripheral nerve sheath tumor found in the left gluteus medius muscle of a patient that caused persistent, debilitating buttock pain. After years of treatment for piriformis syndrome and possible spinous causes, the patient was ultimately diagnosed with a peripheral nerve sheath tumor through magnetic resonance imaging with contrast. Peripheral nerve sheath tumors are a diverse group of mostly benign tumors that can occur sporadically or associated with certain disease processes. These tumors usually present with pain, a soft tissue mass, or focal neurological deficits. Upon removal of the tumor, her gluteal pain completely resolved.

Multiple Cutaneous Solitary Circumscribed Neuroma in a Patient with Neurofibromatosis Type 2: An "Incidentaloma" or New Association?

Solitary circumscribed neuroma formerly known as palisaded encapsulated neuroma is a rare, benign neural tumor that usually presents as a painless firm nodule or papule on the face and within oral cavity, although they can occur elsewhere on the body. No association with neurofibromatosis has been reported in the literature. Herein, we report, a previously unreported unique association of neurofibromatosis type 2 (NF-2) with multiple cutaneous solitary circumscribed neuromas in a 24-year-old female. A 24-year-old female with history of NF-2 presented with two slow-growing soft-to-firm papules on the chin and forehead that had been gradually increasing in size over a period of 5 years. The papule on the chin was increasingly tender to palpation. Histologic sections demonstrated a dermal based almost encapsulated, smoothly contoured tumefactive mass composed of spindle cell proliferation with neuroid structures and foci of palisaded growth (resembling schwannoma) and intralesional cleft like spaces. By immunohistochemistry, the lesional cells were strongly and diffusely positive for S-100 and SOX10 with multifocal neurofilament expression while the "capsule" was diffusely reactive for epithelial membrane antigen. The overall features were considered prototypic for solitary circumscribed neuroma. The patient is 18-months post-surgical resection with no evidence of recurrence. In summary, we report for the first time a case of multiple solitary circumscribed neuromas in a patient with known NF2. We highlight pertinent diagnostic clues relevant to surgical pathologist to facilitate recognition (as this tumor is often mistaken for schwannoma or neurofibroma). The clinical behavior is excellent and surgical resection is considered curative.

[Reconstruction of painful neuroma of superficial branch of radial nerve after first dorsal compartment release: presentation of two cases]. / Reconstrucción de neuroma de nervio radial superficial con injerto autólogo de nervio sural: presentación de dos casos.

INTRODUCTION: nerve lesions are potentially catastrophic injuries. They can cause motor loss, severe pain and neuroma formation. The superficial branch of the radial nerve is at risk during first dorsal compartment release, its injury can cause neuroma formation. Autologous nerve reconstruction is the gold standard for treatment of small nerve gaps. CASES PRESENTATION: we present two cases of adult women (F/47 y F/51) with a prior history of first dorsal compartment release in another institution. Both patients developed debilitating neuropathic pain, as well as allodynia in the surgical site. They were diagnosed with superficial radial nerve neuroma. Oral medication and physical therapy was attempted without success. Surgical exploration and autologous nerve reconstruction was performed. Both patients had excellent relief of pain from visual analogue scale (VAS 9-10 to VAS 1-2). Postoperatively, both patients recovered partial sensitivity to pain in the zones distal to the repair. CONCLUSIONS: neuromas are feared complications that occur with unrecognized nerve lesions during surgery, they are difficult to treat and require multidisciplinary management. These two cases demonstrate that autologous nerve reconstruction is an excellent option for recovering function in small gaps of nerve tissue.

INTRODUCCIÓN: las lesiones iatrogénicas de nervio son complicaciones devastadoras de cualquier procedimiento quirúrgico. Ocasionan pérdida motora, dolor y formación de neuromas. En el abordaje para la liberación del primer compartimiento extensor de la muñeca, la rama superficial del nervio radial debe identificarse y protegerse previo a la liberación tendinosa. La lesión de este nervio sensitivo puede ocasionar dolor postoperatorio clínicamente significativo. La reconstrucción nerviosa con nervio autólogo ha demostrado en diversos escenarios buenos resultados para mejorar el dolor y recuperar la conducción nerviosa. PRESENTACIÓN DE LOS CASOS: se presentan dos casos de mujeres adultas (F/47 y F/51) con antecedente de liberación de primer compartimiento dorsal de muñeca en otro centro hospitalario. Desarrollaron posteriormente dolor incapacitante y alodinia en sitio quirúrgico, así como limitación funcional. Fueron evaluadas y diagnosticadas como neuroma de rama superficial del nervio radial. No hubo mejoría con terapia física, por lo que se realizó reconstrucción nerviosa con injerto autólogo de nervio sural. Ambas pacientes tuvieron alivio del dolor de EVA 9-10 hasta EVA 1-2. A los cuatro meses de seguimiento, las dos mujeres recuperaron parcialmente la sensibilidad distal al sitio del neuroma, sin recurrencia del dolor presentado. CONCLUSIONES: los neuromas son complicaciones devastadoras que ocurren con lesiones inadvertidas de nervios motores y sensitivos. La reconstrucción con nervio autólogo es una excelente opción para reconstrucción de pequeños tramos de nervio periférico.

Trigeminal Traumatic Neuroma: a Comprehensive Review of the Literature Based On a Rare Case.

PURPOSE OF REVIEW: Traumatic neuromas in general, and trigeminal traumatic neuromas in particular, are relatively rare entities originating from a damage to a corresponding nerve or its branches. This manuscript is a comprehensive review of the literature on trigeminal traumatic neuromas based on an interesting and challenging case of bilateral intraoral lesions. RECENT FINDINGS: The diagnosis for this patient was bilateral trigeminal traumatic neuromas. It is possible that these patients have a genetic predisposition to the development of these lesions. It is a neuropathic pain condition and may mimic dental and other trigeminal pain entities. Topical treatment with lidocaine gel, utilizing a custom-made neurosensory stent, rendered the patient significant and sustained pain relief. Trigeminal traumatic neuromas present a diagnostic challenge even to a seasoned clinician, due to the complex clinical features that may mimic other entities. Topical medications such as local anesthetics may be a good viable alternative to systemic medications to manage the pain associated with the condition. Early identification of the lesion and the associated pain helps in the succinct management of symptomatic trigeminal traumatic neuromas.

Long-term results of dorsal neuroma/nerve transposition in the surgical management of Morton's neuroma and correlation with intraoperative anatomical variations.

BACKGROUND: Morton's neuroma (MN) is a common cause of forefoot pain. After failure of conservative management, surgical procedures include neurectomy or neuroma preserving procedures; resection of deep transverse intermetatarsal ligament only (DTIML), dorsal neurolysis, dorsal nerve transposition (DNT). OBJECTIVES: This retrospective study evaluates the long-term results of open DNT, and it also reports anatomical variants in the plantar interdigital nerve. MATERIAL AND METHODS: The study included 39 patients (30 females and 9 males) who were treated for MN between 2002 and 2016. RESULTS: The mean pre-operative Giannini score of 13 (0-30) improved to 61 (20-80) (p < .0001), with only 6 patients scoring less than 50 (poor). Using Coughlin's criterion for overall satisfaction, 9 patients (23%) reported excellent, 18 patients (46%) good, 6 patients (15%) fair and 6 patients (15%) reported poor results. In the long term, 25 patients (64%) had no pain, 8 patients (20%) had mild pain, and 6 patients (16%) had severe pain. Ten patients (26%) reported normal sensitivity in their toes, 26 patients (66%) had numbness, and 3 patients (8%) reported dysesthesia in their toes. Twenty-two patients (56%) could wear fashionable shoes, 11 patients (28%) comfortable shoes, and 6 patients (16%) modified shoes. Regarding walking distance, 30 patients (77%) had no limitation, and 9 patients (23%) reported some limitation. Nineteen per cent regretted having surgery. Around 40% (17 out of 43 web spaces) showed anatomical variations in either the nerve or in the web space and we could not identify any specific risk factors in relation to the outcome. CONCLUSION: Dividing the DTIML or dorsal neurolysis should be considered as the primary surgical treatment and, if this fails, neurectomy would be an option. DNT can be considered if one is concerned about stump neuroma, but this may be technically demanding and in some patients it may not be possible. LEVEL OF EVIDENCE: Level IV - Case Control Retrospective study.

Utilization of Techniques for Upper Extremity Amputation Neuroma Treatment and Prevention.

This study aimed to understand the current utilization of surgical approaches for nerve ending management in upper extremity amputation to prevent and treat nerve-related pain. We administered a survey to 190 of 1270 surgeons contacted by email (15% response rate) and analyzed their demographics, practice patterns, and perceptions regarding techniques for nerve ending management in upper extremity amputees. Although many surgical techniques were employed, most surgeons (54%) performed traction neurectomy during amputation and, alternatively, bury nerve into muscle if a neuroma subsequently develops (52%). Surgeons in practice less than 10 years were more likely to perform targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) than surgeons in practice greater than 10 years (p<0.001). TMR and RPNI were performed more frequently for proximal amputations than distal amputations, but there is no consensus regarding the optimal timing to utilize these techniques. Surgeons commonly cited improved prosthetic control, pain, and phantom limb symptoms as reasons for performing TMR and RPNI. Increased physician compensation as a consideration was more commonly cited among TMR non-adopter than adopters (31% vs 14%, p=0.008). There is no consensus regarding techniques for the prevention or treatment of nerve ending pain in upper extremity amputees. TMR and RPNI are being utilized with increasing frequency and both patient and surgeon factors affect implementation in clinical practice.

The Management of Multiple Morton's Neuromas in the Same Foot: A Systematic Review.

The optimal treatment strategy for the presentation of multiple Morton's neuromas in adjacent intermetatarsal spaces of the same foot is yet to be determined. We aimed to summarize and assess the efficacy of current treatment strategies. A systematic review, adhering to PRIMSA guidelines was performed. A computer base search was completed in PubMed, Embase, Cinahl, ISI Web of Science, Scopus and Emcare, for articles reporting the treatment of multiple neuromas in the same foot. The review is registered in the international prospective register of systematic reviews (CRD42020213631). A total of 253 articles were identified, with 7 articles being included in the review. The most common treatment strategy reported was simultaneous neuroma excision using a single incision, while 2 studies each describe simultaneous excision with 2 separate incisions and delayed excision respectively. There is no strong evidence favoring use of delayed excision or multiple incisions. Further high-quality research is required to make more definitive conclusions and future research should investigate other strategies such as non-operative treatment.

A consecutive series of targeted muscle reinnervation (TMR) cases for relief of neuroma and phantom limb pain: UK perspective.

BACKGROUND: Studies have suggested that targeted muscle reinnervation (TMR) can improve symptoms of neuroma pain (NP) and phantom limb pain (PLP) in patients. OBJECTIVES: Our primary objective was to measure changes in NP and PLP levels following TMR surgery at 4-time points (baseline, 3, 6- and 12-months postoperatively). Secondary aims included identification of the character and rate of any surgical complications and patients' satisfaction with TMR. METHODS: A retrospective review of outcomes of 36 patients who underwent TMR surgery to treat intractable NP and/or PLP after major amputation of an upper (UL) or lower limb (LL) at a single centre in London, UK over 7 years. The surgical techniques, complications, and satisfaction with TMR are described. RESULTS: Forty TMR procedures were performed on 36 patients. Thirty patients had complete data for NP and PLP levels at all pre-defined time points. Significant improvements (p<0.01) in both types of pain were observed for both upper and LL amputees. However, there were varying patterns of recovery. For example, UL amputees experienced worsening of PLP in the first few months post-operatively whereas surgical complications were more common in LL cases. Patients were overwhelmingly satisfied with the improvements in their symptoms (90%). CONCLUSIONS: TMR surgery appeared to relieve both NP and PLP although the retrospective nature of this study limits the strength of this conclusion. However, complication rates were high, and it is crucial for surgeons and patients to fully understand the course and outcomes of this novel surgery prior to undertaking treatment.

[Traumatic Neuroma Mimicking Lymph Node Metastasis of Pancreatic Neuroendocrine Neoplasms Developed after Pancreatoduodenectomy-A Case Report].

A traumatic neuroma is a benign tumor consisting of a non-neoplastic growth of injured nerves as a result of trauma or surgery. It is rarely found in an abdominal cavity, but some reports showed that it occurred around the bile duct. We report a case of a 72-year-old man who underwent subtotal stomach-preserving pancreatoduodenectomy for pancreatic neuroendocrine neoplasms 4 years ago. An abdominal contrast-enhanced CT follow-up examination revealed a growing nodule on the dorsal surface of the portal vein. The lesion showed a mild increase in fluorodeoxyglucose uptake in FDG-PET⊘CT. A lymph node metastasis of pancreatic neuroendocrine neoplasms was suspected. Nodule resection was performed for purpose of diagnosis and treatment. The final pathological diagnosis was traumatic neuroma with no evidence of recurrence. Traumatic neuromas developed after pancreatoduodenectomy have not been reported. Postoperative masses around the bile ducts should also be considered traumatic neuromas.

Bilateral intraoral traumatic neuroma: Case report of a diagnostic challenge.

Oral traumatic neuromas (TrNs) are relatively rare lesions and they originate from a damaged nerve. They present a diagnostic challenge, due to the complex clinical features that may mimic odontogenic, musculoskeletal, and other neuropathic pain conditions. We describe an interesting and challenging case of painful bilateral intraoral lesions in a 56-year-old South Indian female patient who presented with clinical features consistent with TrN lesions bilaterally, in relation to different branches of the trigeminal nerve. The patient had undergone numerous aggressive dental treatments and interventions over the past three decades, with little or no pain relief. Topical treatment with lidocaine gel utilizing a custom-made neurosensory stent rendered the patient significant and sustained pain relief.

Incidence, Diagnosis, and Management of Neuromas Following Radiofrequency Ablation Treatment: a Narrative Review.

OBJECTIVE: To determine the epidemiology of neuroma formation as a complication following radiofrequency ablation for chronic pain conditions as well as reviewing the diagnosis and management of neuromas. DESIGN: Evidence-based narrative review and critical appraisal of literature. RESULTS: A comprehensive review of the literature generated one case report describing neuroma formation following lumbar facet medial branch radiofrequency denervation. The rare incidence may be explained by neuroma pathophysiology and peripheral nerve injury produced by radiofrequency ablation, in combination with its asymptomatic nature. Diagnosis of neuromas is predominantly confirmed by clinical history and physical exam with potential for nerve blocks or imaging. Ultrasound has been suggested as a primary imaging modality with magnetic resonance imaging as a secondary option. Neuroma management ranges from conservative therapy to surgery with varying success rates. CONCLUSIONS: Neuroma formation following radiofrequency ablation procedures is exceedingly rare and could be a hypothetical concern in clinical practice. However, the true incidence may be inaccurate given the asymptomatic nature of neuromas.

Practice Patterns and Pain Outcomes for Targeted Muscle Reinnervation: An Informed Approach to Targeted Muscle Reinnervation Use in the Acute Amputation Setting.

BACKGROUND: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) procedures have been shown to improve patient-reported outcomes for the treatment of symptomatic neuromas after amputation; however, the specific indications and comparative outcomes of each are unclear. The primary research questions were what complement of nerves most frequently requires secondary pain intervention after conventional amputation, whether this information can guide the focused application of TMR and RPNI to the primary amputation setting, and how the outcomes compare in both settings. METHODS: We performed a retrospective review of records for patients who had undergone lower-extremity TMR and/or RPNI at our institution. Eighty-seven procedures were performed: 59 for the secondary treatment of symptomatic neuroma pain after amputation and 28 for primary prophylaxis during amputation. We reviewed records for the amputation level, TMR and/or RPNI timing, pain scores, patient-reported resolution of nerve-related symptoms, and complications or revisions. We evaluated the relationship between the amputation level and the frequency with which each transected nerve required neurologic intervention for pain symptoms. RESULTS: The mean pain score decreased after delayed TMR or RPNI procedures from 4.3 points to 1.7 points (p < 0.001), and the mean final pain score (and standard deviation) was 1.0 ± 1.9 points at the time of follow-up for acute procedures. Symptom resolution was achieved in 92% of patients. The sciatic nerve most commonly required intervention for symptomatic neuroma above the knee, and the tibial nerve and common or superficial peroneal nerve were most problematic following transtibial amputation. None of our patients required a revision pain treatment procedure after primary TMR targeting these commonly symptomatic nerves. Failure to address the tibial nerve during a delayed procedure was associated with an increased risk of unsuccessful TMR, resulting in a revision surgical procedure (odds ratio, 26 [95% confidence interval, 1.8 to 368]; p = 0.02). CONCLUSIONS: There is a consistent pattern of symptomatic nerves that require secondary surgical intervention for the management of pain after amputation. TMR and RPNI were translated to the primary amputation setting by using this predictable pattern to devise a surgical strategy that prevents symptomatic neuroma pain. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.