Neuroma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [14]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[15] Maria Fernanda Villarreal, M.D. [16]

Synonyms and keywords: Traumatic neuroma; Morton neuroma; Amputation neuroma; Pseudoneuroma; Morton’s metatarsalgia; Plantar interdigital neuroma; Morton's intermetatarsal neuroma; Morton's entrapment; Morton's disease; Morton's neuropathy; Morton's neuralgia; Intermetatarsal neuroma; Intermetatarsal space neuroma; Intermetatarsal nerve entrapment; Interdigital neuroma; Interdigital nerve compression; Interdigital nerve enlargement; Joplin's neuroma; Plantar neuroma; Scar neuroma

Overview

Neuroma (Neuro- is from the Greek for nerve) is defined as a benign tumor of a nerve. However, neuroma commonly refers to any tumor of cells of the nervous system. Neuromas form part of the peripheral nerve sheath tumors and belong to Reactive class of tumors. Neuroma was first described by Thomas Morton in 1876. Neuromas may be classified according to histopathological features into 3 groups: Morton's neuroma, traumatic neuroma, and neoplasic neuromas. The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis. Neuroma is more commonly observed among patients aged between 15 to 50 years old. Neuroma is more commonly observed among middle aged adults. Females are more commonly affected with neuroma than males. The female to male ratio is approximately 5:1. Common risk factors in the development of neuroma include improper footwear and high impact sports (e.g., rock-climbing, ballet dancing). A major complication of neuroma is chronic neuropathic pain. On ultrasound, neuroma is characterized as a well-defined, hypoechoic lesion located in the intermetatarsal space proximal to the metatarsal head. Patients with neuroma usually appear with antalgic posture. Physical examination may be remarkable for tenderness to palpation and dysesthetic pain. Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%. The recurrence rate after surgery is as high as 50%.

Historical Perspective

  • The term neuroma originates from the following two Greek words:
    • neuro- from the Greek word for nerve (νεῦρον)
    • -oma (-ωμα) from the Greek word for swelling
  • In 1876, Neuroma was first described by Thomas Morton

Classification

  • Neuroma may be classified according to histopathological features into following groups:[1][2][3][4]
Classification of neuroma
Types of neuroma Characteristic features Neoplastic nature
Morton neuroma[5][6][7][8][9][10]
  • Symptomatic collapse of the transverse arch by perineural fibrosis around a plantar digital nerve of the foot due to traction and increased pressure/chronic compression on the interdigital nerve
  • Usually located:
    • Third intermetatarsal space (between third and fourth metatarsals) or
    • At the bifurcation of the fourth plantar digital nerve
  • Also known as:
    • Morton’s metatarsalgia
    • Plantar interdigital neuroma
    • Morton's intermetatarsal neuroma
    • Morton's entrapment
    • Morton's disease
    • Morton's neuropathy
    • Morton's neuralgia
    • Intermetatarsal neuroma
    • Intermetatarsal space neuroma
    • Intermetatarsal nerve entrapment
    • Interdigital neuroma
    • Interdigital nerve compression
    • Interdigital nerve enlargement
    • Joplin's neuroma
    • Plantar neuroma
 Non-neoplastic
Traumatic neuroma[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]
  • Arises from nerve injury (often as a result of surgery) leading to interrupted axons termed as neurotmesis
  • Regenerating axons lack an endoneurial tube to follow, resulting in a painful and tender mass of disorganized axons
  • Occurs at the end of injured nerve fibers as a form of unregulated nerve regeneration
  • Subtype of traumatic neuroma, called "Joplin neuroma" (a compression traumatic neuroma)
  • Occurs most commonly near a scar
  • Often very painful
  • Also known as:
    • Amputation neuroma
    • Pseudoneuroma
    • Scar neuroma
Palisaded encapsulated neuroma/solitary circumscribed neuroma
  • Nonpigmented, painless, small, firm nodules
  • Present in proximity to mucocutaneous junctions, usually face
  • Benign but can be mistaken for basal cell carcinoma
  • Surgical removal is the curative treatment
Mucosal neuroma[4][28]
  • Associated with MEN2B (inherited autosomal dominant trait caused by a single mutation in RET proto-oncogene)
  • Grossly present as:
  • Diffusely enlarged lips
  • Tongue nodules
  • Thickened eyelids (diffusely or nodularly), in the first or second decade of life
  • Comprised of markedly enlarged nerve fibers on microscopy
  • No specific treatment
Neoplasic neuroma
  • Solid nodular mass
  • Usually, separate from nerve fibers
 Neoplastic
Acoustic neuroma [29]
  • It's a misnomer
  • It's actually a Vestibular Schwannoma
  • Slow-growing, benign tumor of acoustic nerve
  • Symptoms usually start after the age of 30 and include:
    • Dizziness
    • Persistent headaches
    • Vertigo
    • Loss of balance
    • Tinnitis
    • Numbness
    • Pain/weakness on one side of face
    • Blurred/double vision (temporary)
    • Ataxia
    • Hoarseness of voice
    • Dysphagia
Ganglioneuroma
  • Tumor of sympathetic nerve fibers arising from neural crest cells
Pacinian neuroma[30][31][32][33]
  • Very rare
  • Painful
  • Benign hyperplastic tumor of Pacinian corpuscles (mechanoreceptors responsible for sensitivity to vibration and pressure)
  • Sometimes associated with history of local trauma

Pathophysiology

  • The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis[1]
  • The pathogenesis of traumatic neuroma is characterized by:[34][18][35]
    • Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury
    • Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells
    • Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress)
  • Morton neuroma is characterized by being located in the 3rd web-space, between 3rd and 4th metatarsal heads,[36] or sometimes in the second or fourth interspaces
  • Another subtype of traumatic neuroma is terminal neuroma (also known as "stump neuroma") which can occur after transection of the nerve (e.g. limb amputation)
  • There are no genetic mutations associated with the development of neuroma
  • On gross pathology, characteristic findings of neuroma, include:[37][38]
  • On microscopic histopathological analysis, characteristic findings of neuroma, include:[37][38]
    • Extensive fibrosis around and within the nerve
    • Digital artery
    • Thrombosis
    • Arterial thickening
S-100 Immunostain of Palisaded and Encapsulated Neuroma Source: Ed Uthman at flickr
Histopathology of Palisaded and Encapsulated Neuroma Source: Ed Uthman at flickr
Histopathology of Palisaded and Encapsulated Neuroma [1]
Histopathology of Palisaded and Encapsulated Neuroma [2]

Histopathology of traumatic neuroma

  • Numerous well formed small nerve twigs
  • Limited soft tissue infiltration
  • Contains axons in haphazardly arranged nerves within mature collagenous scar with entrapped smooth muscle
Traumatic neuroma Source: Libre Pathology
Traumatic neuroma [3]
Traumatic neuroma [4]
Traumatic neuroma [5]
Traumatic neuroma [6]

Histopathology of Morton neuroma

  • On gross pathology, morton neuroma resembles traumatic neuroma
  • On histopathology, it is comprised of:
    • Degenerated/demyelinated axons
    • Vascular hyalinization
    • Fibrosis
H&E stain of Morton's neuroma, low magnification [7]
H&E stain of Morton's neuroma, High magnification [8]
H&E stain of Morton's neuroma, Intermediate magnification [9]
H&E stain of Morton's neuroma, Intermediate magnification [10]
H&E stain of Morton's neuroma, High magnification [11]
H&E stain of Morton's neuroma, very high magnification [12]
H&E stain of Morton's neuroma, Intermediate magnification [13]

Common sites of involvement by traumatic neuroma

  • Most common oral locations are:
    • Tongue
    • Near mental foramen of mouth
  • Rarely involves:
    • Head
    • Neck

Causes

Differentiating Neuroma from other Diseases

  • Neuroma must be differentiated from other diseases that cause forefoot pain and numbness such as:[1][38]

Epidemiology and Demographics

  • Neuroma is a uncommon disease[38]

Age

  • Neuroma is more commonly observed among patients aged between 15 to 50 years old[38]
  • Neuroma is more commonly observed among middle aged adults

Gender

  • Females are more commonly affected with neuroma than males
  • The female to male ratio is approximately 5:1[38]

Race

  • There is no racial predilection for neuroma

Risk Factors

  • Common risk factors in the development of neuroma include:[37]
  • Improper footwear/tight shoes
  • High-impact sports (e.g., rock-climbing, ballet dancing)
  • Overpronation

Natural History, Complications and Prognosis

  • The majority of patients with neuroma are symptomatic at the time of diagnosis[1]
  • Early clinical features include neuropathic pain or local tenderness
  • If left untreated, the majority of patients with neuroma may progress to develop difficulty walking and limping
  • A significant complication of neuroma is chronic neuropathic pain
  • Prognosis is generally good, and the survival rate of patients with neuroma is 99%[39][40]

Diagnosis

Symptoms

Physical Examination

  • Patients with neuroma usually appear with antalgic posture[1]
  • Physical examination may be remarkable for:
  • Tenderness to palpation
  • Limitation of range of motion
  • Dysesthetic pain
  • Mulder's sign:
    • Clicking sensation in the involved interspace on palpation with simultaneous squeezing of metatarsal joints

Laboratory Findings

  • There are no specific laboratory findings associated with neuroma[37]

Imaging Findings

MRI

  • On MRI, characteristic findings of neuroma include:[42][43][44][45][46][47][48][49][7][50][51][7]
    • Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound
    • T1: typically low-to-iso signal
    • T2: typically low signal but can sometimes be intermediate in signal
    • T1 C+ (Gd): tends to show intense enhancement
  • On MRI, characteristic findings of traumatic neuroma include:[1]
    • Fusiform swelling of a nerve or a bulbous mass at a nerve end
    • The parent nerve of some small nerve may difficult or impossible to discern
    • T2/STIR:inhomogeneous hyperintensity (may have a hypointense rim)
    • T1 C+ (Gd): variable contrast enhancement
Morton neuroma MRI Source: Radiopedia

Ultrasound

  • Ultrasound can help distinguish neuroma from:[52][53][54]
    • Intermetatarsal bursal swelling or
    • Synovitis in adjacent joints
  • On ultrasound, neuroma is characterized by the following findings:[1][55][56][57][58][59][60][61][62][6][63]
    • Round to ovoid
    • Well-defined, hypoechoic lesion
    • Located in the intermetatarsal space proximal to the metatarsal head
  • On ultrasound, traumatic neuroma is characterized by the following findings:[1]
    • Swollen nerve (mass-like)
    • Hypoechoic
    • Loss of normal fibrillar pattern
    • Usually small, but may be as large as 5 cm

Treatment

Medical Therapy

Conservative therapy for Morton neuroma

  • Morton neuroma should be managed conservatively before proceeding to expensive diagnostic procedures
  • Conservative measures for pain relief include:[64][65][66][67][68][69]
    • Decreasing pressure on the metatarsal heads by using:
      • Metatarsal support
      • Metatarsal bars
      • Metatarsal pads
      • Padded shoe insert (it's important to place inserts properly just proximal to the metatarsal head)
      • Orthotics
      • Specialized orthopedic shoes
      • Broad-toed shoe allowing spread of metatarsal heads
      • Determine proper shoe width while standing with the help of a professional shoe fitting device
    • Strength exercises for intrinsic foot muscles

Non-conservative medical therapy

Surgery

  • Surgery is the mainstay of therapy for neuroma[88][89][90][91][92][93][94][95][96][97][98][99][100][39]
  • Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%
  • The recurrence rate after surgery is as high as 50%

Prevention

  • There are no primary preventive measures available for neuroma[1]
  • Secondary prevention measures include: personal hygiene measures, such as wearing ergonomic shoes

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Neuroma. Radiopedia http://radiopaedia.org/cases/morton-neuroma-2 Accessed on April 21, 2016
  2. ↑ "Neuroma". Dorland's Illustrated Medical Dictionary (32nd ed.). Oxford University Press. 2011. p. 5287. ISBN 978-1-4557-0985-4. Retrieved 25 August 2013.
  3. ↑ Valero J, Gallart J, González D, Deus J, Lahoz M (2015). "Multiple interdigital neuromas: a retrospective study of 279 feet with 462 neuromas". J Foot Ankle Surg. 54 (3): 320–2. doi:10.1053/j.jfas.2014.05.011. PMID 25128316.
  4. ↑ 4.0 4.1 Golan JD, Jacques L (2004). "Nonneoplastic peripheral nerve tumors". Neurosurg Clin N Am. 15 (2): 223–30. doi:10.1016/j.nec.2004.02.001. PMID 15177321.
  5. ↑ Kim JY, Choi JH, Park J, Wang J, Lee I (2007). "An anatomical study of Morton's interdigital neuroma: the relationship between the occurring site and the deep transverse metatarsal ligament (DTML)". Foot Ankle Int. 28 (9): 1007–10. doi:10.3113/FAI.2007.1007. PMID 17880876.
  6. ↑ 6.0 6.1 Read JW, Noakes JB, Kerr D, Crichton KJ, Slater HK, Bonar F (1999). "Morton's metatarsalgia: sonographic findings and correlated histopathology". Foot Ankle Int. 20 (3): 153–61. doi:10.1177/107110079902000303. PMID 10195292.
  7. ↑ 7.0 7.1 7.2 Bencardino J, Rosenberg ZS, Beltran J, Liu X, Marty-Delfaut E (2000). "Morton's neuroma: is it always symptomatic?". AJR Am J Roentgenol. 175 (3): 649–53. doi:10.2214/ajr.175.3.1750649. PMID 10954445.
  8. ↑ Bourke G, Owen J, Machet D (1994). "Histological comparison of the third interdigital nerve in patients with Morton's metatarsalgia and control patients". Aust N Z J Surg. 64 (6): 421–4. PMID 7516653.
  9. ↑ 9.0 9.1 Wu KK (1996). "Morton's interdigital neuroma: a clinical review of its etiology, treatment, and results". J Foot Ankle Surg. 35 (2): 112–9, discussion 187-8. PMID 8722878.
  10. ↑ Post MD (2019). "Mechanical Diagnosis and Therapy and Morton's Neuroma: A Case Report". Physiother Can. 71 (2): 130–133. doi:10.3138/ptc.2018-42. PMC 6484954. PMID 31040508.
  11. ↑ Foltán R, Klíma K, Spacková J, Sedý J (2008). "Mechanism of traumatic neuroma development". Med Hypotheses. 71 (4): 572–6. doi:10.1016/j.mehy.2008.05.010. PMID 18599222.
  12. ↑ Yao C, Zhou X, Zhao B, Sun C, Poonit K, Yan H (2017). "Treatments of traumatic neuropathic pain: a systematic review". Oncotarget. 8 (34): 57670–57679. doi:10.18632/oncotarget.16917. PMC 5593675. PMID 28915703.
  13. ↑ Colella G, Borriello C, Lanza A, Rossiello R, Siniscalchi G (2002). "[Traumatic neuroma of the great auricular nerve. A clinical case]". Minerva Stomatol. 51 (6): 279–83. PMID 12147981.
  14. ↑ Moss CE, Johnston CJ, Whear NM (2000). "Amputation neuroma of the great auricular nerve after operations on the parotid gland". Br J Oral Maxillofac Surg. 38 (5): 537–8. doi:10.1054/bjom.2000.0466. PMID 11010790.
  15. ↑ Hobsley M (1972). "Amputation neuroma of the great auricular nerve after parotidectomy". Br J Surg. 59 (9): 735–6. PMID 4341800.
  16. ↑ Toriumi DM, Sykes J, Wolff A (1987). "Pathologic quiz case 1. Amputation neuroma of the great auricular nerve". Arch Otolaryngol Head Neck Surg. 113 (8): 888–90. PMID 3620156.
  17. ↑ De Roos KP, Neumann HA (1994). "Traumatic neuroma. A rare complication following Muller's phlebectomy". J Dermatol Surg Oncol. 20 (10): 681–2. PMID 7930014.
  18. ↑ 18.0 18.1 Lee EJ, Calcaterra TC, Zuckerbraun L (1998). "Traumatic neuromas of the head and neck". Ear Nose Throat J. 77 (8): 670–4, 676. PMID 9745184.
  19. ↑ Li Q, Gao EL, Yang YL, Hu HY, Hu XQ (2012). "Traumatic neuroma in a patient with breast cancer after mastectomy: a case report and review of the literature". World J Surg Oncol. 10: 35. doi:10.1186/1477-7819-10-35. PMC 3296625. PMID 22330690.
  20. ↑ Chen W, Zhang H, Huang J, Li Y, Zhang Z, Peng Y (2019). "Traumatic neuroma in mastectomy scar: Two case reports and review of the literature". Medicine (Baltimore). 98 (15): e15142. doi:10.1097/MD.0000000000015142. PMID 30985684.
  21. ↑ Baltalarli B, Demirkan N, Yağci B (2004). "Traumatic neuroma: unusual benign lesion occurring in the mastectomy scar". Clin Oncol (R Coll Radiol). 16 (7): 503–4. PMID 15490816.
  22. ↑ Rosso R, Scelsi M, Carnevali L (2000). "Granular cell traumatic neuroma: a lesion occurring in mastectomy scars". Arch Pathol Lab Med. 124 (5): 709–11. doi:10.1043/0003-9985(2000)124<0709:GCTN>2.0.CO;2. PMID 10782152.
  23. ↑ Nomura H, Harimaya K, Orii H, Shiba K, Ueta T, Iwaki T (2002). "Traumatic neuroma of the anterior cervical nerve root with no subjective episode of trauma. Report of four cases". J Neurosurg. 97 (3 Suppl): 393–6. PMID 12408400.
  24. ↑ Arishima H, Takeuchi H, Tsunetoshi K, Kodera T, Kitai R, Kikuta K (2013). "Intraoperative and pathological findings of intramedullary amputation neuroma associated with spinal ependymoma". Brain Tumor Pathol. 30 (3): 196–200. doi:10.1007/s10014-012-0125-x. PMC 3714552. PMID 23187747.
  25. ↑ Ulrich CT, Sommerlad D, Szelenyi A, Seifert V, Marquardt G (2010). "Concurrent schwannoma and intradural neuroma after resection of a cauda equina schwannoma. A case report and first description". Acta Neurochir (Wien). 152 (6): 1061–3, discussion 1063. doi:10.1007/s00701-009-0534-8. PMID 19834641.
  26. ↑ Salas SJ, McFalls JM, Senders ZJ, Kenyon LC, Harrop JS (2013). "Intradural cervical nerve root traumatic neuroma without a history of direct trauma". Clin Neurol Neurosurg. 115 (9): 1879–81. doi:10.1016/j.clineuro.2013.03.018. PMID 23639732.
  27. ↑ Kang J, Yang P, Zang Q, He X (2016). "Traumatic neuroma of the superficial peroneal nerve in a patient: a case report and review of the literature". World J Surg Oncol. 14 (1): 242. doi:10.1186/s12957-016-0990-6. PMC 5018173. PMID 27613606.
  28. ↑ Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M; et al. (1995). "Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B". Science. 267 (5196): 381–3. PMID 7824936.
  29. ↑ Thapa PB, Shahi S, Jha RK, Shrestha D (2019). "Vestibular Schwanomma: An Experience in a Developing World". World J Oncol. 10 (2): 118–122. doi:10.14740/wjon1195. PMC 6497013. PMID 31068992.
  30. ↑ Zanardi F, Cooke RM, Maiorana A, Curti S, Farioli A, Bonfiglioli R; et al. (2011). ""Is this case of a very rare disease work-related?" A review of reported cases of Pacinian neuroma". Scand J Work Environ Health. 37 (3): 253–8. doi:10.5271/sjweh.3132. PMID 21082159.
  31. ↑ Cho HH, Hong JS, Park SY, Park HS, Cho S, Lee JH (2012). "Tender papule rising on the digit: Pacinian neuroma should be considered in differential diagnosis". Int J Med Sci. 9 (1): 83–5. PMC 3245416. PMID 22211094.
  32. ↑ Ide F, Shimoyama T, Kaneko T, Horie N (2006). "Pacinian neuroma in adipose herniation of the buccal mucosa". Int J Oral Maxillofac Surg. 35 (12): 1162–3. doi:10.1016/j.ijom.2006.06.025. PMID 17008055.
  33. ↑ Rhode CM, Jennings WD (1975). "Pacinian corpuscle neuroma of digital nerves". South Med J. 68 (1): 86–9. PMID 1154066.
  34. ↑ Kitcat M, Hunter JE, Malata CM (2009). "Sciatic neuroma presenting forty years after above-knee amputation". Open Orthop J. 3: 125–7. doi:10.2174/1874325000903010125. PMC 2835865. PMID 20224738.
  35. ↑ Hanna SA, Catapano J, Borschel GH (2016). "Painful pediatric traumatic neuroma: surgical management and clinical outcomes". Childs Nerv Syst. 32 (7): 1191–4. doi:10.1007/s00381-016-3109-z. PMID 27179535.
  36. ↑ Perry, Arie (2010). Practical surgical neuropathology : a diagnostic approach. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 978-0443069826.
  37. ↑ 37.0 37.1 37.2 37.3 37.4 Neuroma. Wikipedia. https://en.wikipedia.org/wiki/Neuroma Accessed on April 21, 2016
  38. ↑ 38.0 38.1 38.2 38.3 38.4 38.5 38.6 Wu J, Chiu DT (1999). "Painful neuromas: a review of treatment modalities". Ann Plast Surg. 43 (6): 661–7. PMID 10597831.
  39. ↑ 39.0 39.1 Lee KT, Kim JB, Young KW, Park YU, Kim JS, Jegal H (2011). "Long-term results of neurectomy in the treatment of Morton's neuroma: more than 10 years' follow-up". Foot Ankle Spec. 4 (6): 349–53. doi:10.1177/1938640011428510. PMID 22134434.
  40. ↑ Bauer T, Gaumetou E, Klouche S, Hardy P, Maffulli N (2015). "Metatarsalgia and Morton's Disease: Comparison of Outcomes Between Open Procedure and Neurectomy Versus Percutaneous Metatarsal Osteotomies and Ligament Release With a Minimum of 2 Years of Follow-Up". J Foot Ankle Surg. 54 (3): 373–7. doi:10.1053/j.jfas.2014.08.009. PMID 25481724.
  41. ↑ Locke RK (1993). "Morton's neuroma". J Am Podiatr Med Assoc. 83 (2): 108–9. doi:10.7547/87507315-83-2-108. PMID 8478796.
  42. ↑ AlSharif S, Ferré R, Omeroglu A, El Khoury M, Mesurolle B (2016). "Imaging Features Associated With Posttraumatic Breast Neuromas". AJR Am J Roentgenol. 206 (3): 660–5. doi:10.2214/AJR.14.14035. PMID 26901025.
  43. ↑ Ahlawat S, Belzberg AJ, Montgomery EA, Fayad LM (2016). "MRI features of peripheral traumatic neuromas". Eur Radiol. 26 (4): 1204–12. doi:10.1007/s00330-015-3907-9. PMID 26188658.
  44. ↑ Zanetti M, Ledermann T, Zollinger H, Hodler J (1997). "Efficacy of MR imaging in patients suspected of having Morton's neuroma". AJR Am J Roentgenol. 168 (2): 529–32. doi:10.2214/ajr.168.2.9016241. PMID 9016241.
  45. ↑ Williams JW, Meaney J, Whitehouse GH, Klenerman L, Hussein Z (1997). "MRI in the investigation of Morton's neuroma: which sequences?". Clin Radiol. 52 (1): 46–9. PMID 9022580.
  46. ↑ Unger HR, Mattoso PQ, Drusen MJ, Neumann CH (1992). "Gadopentetate-enhanced magnetic resonance imaging with fat saturation in the evaluation of Morton's neuroma". J Foot Surg. 31 (3): 244–6. PMID 1619223.
  47. ↑ Lee MJ, Kim S, Huh YM, Song HT, Lee SA, Lee JW; et al. (2007). "Morton neuroma: evaluated with ultrasonography and MR imaging". Korean J Radiol. 8 (2): 148–55. doi:10.3348/kjr.2007.8.2.148. PMC 2626779. PMID 17420632.
  48. ↑ Weishaupt D, Treiber K, Kundert HP, Zollinger H, Vienne P, Hodler J; et al. (2003). "Morton neuroma: MR imaging in prone, supine, and upright weight-bearing body positions". Radiology. 226 (3): 849–56. doi:10.1148/radiol.2263011925. PMID 12601213.
  49. ↑ Torres-Claramunt R, Ginés A, Pidemunt G, Puig L, de Zabala S (2012). "MRI and ultrasonography in Morton's neuroma: Diagnostic accuracy and correlation". Indian J Orthop. 46 (3): 321–5. doi:10.4103/0019-5413.96390. PMC 3377144. PMID 22719120.
  50. ↑ Weishaupt D, Treiber K, Jacob HA, Kundert HP, Hodler J, Marincek B; et al. (2002). "MR imaging of the forefoot under weight-bearing conditions: position-related changes of the neurovascular bundles and the metatarsal heads in asymptomatic volunteers". J Magn Reson Imaging. 16 (1): 75–84. doi:10.1002/jmri.10130. PMID 12112506.
  51. ↑ Studler U, Mengiardi B, Bode B, Schöttle PB, Pfirrmann CW, Hodler J; et al. (2008). "Fibrosis and adventitious bursae in plantar fat pad of forefoot: MR imaging findings in asymptomatic volunteers and MR imaging-histologic comparison". Radiology. 246 (3): 863–70. doi:10.1148/radiol.2463070196. PMID 18195378.
  52. ↑ Fazal MA, Khan I, Thomas C (2012). "Ultrasonography and magnetic resonance imaging in the diagnosis of Morton's neuroma". J Am Podiatr Med Assoc. 102 (3): 184–6. PMID 22659760.
  53. ↑ Pastides P, El-Sallakh S, Charalambides C (2012). "Morton's neuroma: A clinical versus radiological diagnosis". Foot Ankle Surg. 18 (1): 22–4. doi:10.1016/j.fas.2011.01.007. PMID 22325999.
  54. ↑ Sharp RJ, Wade CM, Hennessy MS, Saxby TS (2003). "The role of MRI and ultrasound imaging in Morton's neuroma and the effect of size of lesion on symptoms". J Bone Joint Surg Br. 85 (7): 999–1005. PMID 14516035.
  55. ↑ Coraci D, Pazzaglia C, Doneddu PE, Erra C, Paolasso I, Santilli V; et al. (2015). "Post-traumatic neuroma due to closed nerve injury. Is recovery after peripheral nerve trauma related to ultrasonographic neuroma size?". Clin Neurol Neurosurg. 139: 314–8. doi:10.1016/j.clineuro.2015.10.034. PMID 26571458.
  56. ↑ Quinn TJ, Jacobson JA, Craig JG, van Holsbeeck MT (2000). "Sonography of Morton's neuromas". AJR Am J Roentgenol. 174 (6): 1723–8. doi:10.2214/ajr.174.6.1741723. PMID 10845513.
  57. ↑ Pollak RA, Bellacosa RA, Dornbluth NC, Strash WW, Devall JM (1992). "Sonographic analysis of Morton's neuroma". J Foot Surg. 31 (6): 534–7. PMID 1469213.
  58. ↑ Tobajas Asensio E, Tobajas Asensio JA, Boada Apilluelo E, Torres Nuez J (2000). "[Echography evaluation of Morton's neuroma]". An Med Interna. 17 (8): 416–8. PMID 11218988.
  59. ↑ Shapiro PP, Shapiro SL (1995). "Sonographic evaluation of interdigital neuromas". Foot Ankle Int. 16 (10): 604–6. doi:10.1177/107110079501601003. PMID 8574369.
  60. ↑ Sobiesk GA, Wertheimer SJ, Schulz R, Dalfovo M (1997). "Sonographic evaluation of interdigital neuromas". J Foot Ankle Surg. 36 (5): 364–6. PMID 9356915.
  61. ↑ Levine SE, Myerson MS, Shapiro PP, Shapiro SL (1998). "Ultrasonographic diagnosis of recurrence after excision of an interdigital neuroma". Foot Ankle Int. 19 (2): 79–84. doi:10.1177/107110079801900205. PMID 9498579.
  62. ↑ Kankanala G, Jain AS (2007). "The operational characteristics of ultrasonography for the diagnosis of plantar intermetatarsal neuroma". J Foot Ankle Surg. 46 (4): 213–7. doi:10.1053/j.jfas.2007.04.001. PMID 17586431.
  63. ↑ Perini L, Del Borrello M, Cipriano R, Cavallo A, Volpe A (2006). "Dynamic sonography of the forefoot in Morton's syndrome: correlation with magnetic resonance and surgery". Radiol Med. 111 (7): 897–905. doi:10.1007/s11547-006-0088-2. PMID 17021692.
  64. ↑ Kang JH, Chen MD, Chen SC, Hsi WL (2006). "Correlations between subjective treatment responses and plantar pressure parameters of metatarsal pad treatment in metatarsalgia patients: a prospective study". BMC Musculoskelet Disord. 7: 95. doi:10.1186/1471-2474-7-95. PMC 1712337. PMID 17147793.
  65. ↑ Jannink M, van Dijk H, Ijzerman M, Groothuis-Oudshoorn K, Groothoff J, Lankhurst G (2006). "Effectiveness of custom-made orthopaedic shoes in the reduction of foot pain and pressure in patients with degenerative disorders of the foot". Foot Ankle Int. 27 (11): 974–9. doi:10.1177/107110070602701119. PMID 17144963.
  66. ↑ Hsi WL, Kang JH, Lee XX (2005). "Optimum position of metatarsal pad in metatarsalgia for pressure relief". Am J Phys Med Rehabil. 84 (7): 514–20. PMID 15973088.
  67. ↑ Jackson L, Binning J, Potter J (2004). "Plantar pressures in rheumatoid arthritis using prefabricated metatarsal padding". J Am Podiatr Med Assoc. 94 (3): 239–45. PMID 15153584.
  68. ↑ Chang AH, Abu-Faraj ZU, Harris GF, Nery J, Shereff MJ (1994). "Multistep measurement of plantar pressure alterations using metatarsal pads". Foot Ankle Int. 15 (12): 654–60. doi:10.1177/107110079401501205. PMID 7894637.
  69. ↑ Holmes GB, Timmerman L (1990). "A quantitative assessment of the effect of metatarsal pads on plantar pressures". Foot Ankle. 11 (3): 141–5. PMID 2074081.
  70. ↑ Malessy MJA, de Boer R, Muñoz Romero I, Eekhof JLA, van Zwet EW, Kliot M; et al. (2018). "Predictive value of a diagnostic block in focal nerve injury with neuropathic pain when surgery is considered". PLoS One. 13 (9): e0203345. doi:10.1371/journal.pone.0203345. PMC 6135496. PMID 30208078.
  71. ↑ Climent JM, Mondéjar-Gómez F, Rodríguez-Ruiz C, Díaz-Llopis I, Gómez-Gallego D, Martín-Medina P (2013). "Treatment of Morton neuroma with botulinum toxin A: a pilot study". Clin Drug Investig. 33 (7): 497–503. doi:10.1007/s40261-013-0090-0. PMC 3691490. PMID 23740337.
  72. ↑ Thomson CE, Beggs I, Martin DJ, McMillan D, Edwards RT, Russell D; et al. (2013). "Methylprednisolone injections for the treatment of Morton neuroma: a patient-blinded randomized trial". J Bone Joint Surg Am. 95 (9): 790–8, S1. doi:10.2106/JBJS.I.01780. PMID 23636185.
  73. ↑ Schon L (2014). "An injection of corticosteroid plus anesthetic was more effective than anesthetic alone for Morton neuroma". J Bone Joint Surg Am. 96 (4): 334. doi:10.2106/JBJS.9604.ebo028. PMID 24553891.
  74. ↑ Smith RW (2013). "Steroid injection for Morton neuroma - data-based justification". J Bone Joint Surg Am. 95 (9): e64. doi:10.2106/JBJS.M.00172. PMID 23636203.
  75. ↑ Haddad-Zebouni S, Elia D, Aoun N, Okais J, Ghossain M (2006). "[Regression of Morton neuroma after local injection of steroids]". J Radiol. 87 (5): 566–8. PMID 16733414.
  76. ↑ Basadonna PT, Rucco V, Gasparini D, Onorato A (1999). "Plantar fat pad atrophy after corticosteroid injection for an interdigital neuroma: a case report". Am J Phys Med Rehabil. 78 (3): 283–5. PMID 10340428.
  77. ↑ Reddy PD, Zelicof SB, Ruotolo C, Holder J (1995). "Interdigital neuroma. Local cutaneous changes after corticosteroid injection". Clin Orthop Relat Res (317): 185–7. PMID 7671475.
  78. ↑ van Vendeloo SN, Ettema HB (2016). "Skin depigmentation along lymph vessels of the lower leg following local corticosteroid injection for interdigital neuroma". Foot Ankle Surg. 22 (2): 139–41. doi:10.1016/j.fas.2016.01.002. PMID 27301735.
  79. ↑ Park YH, Lee JW, Choi GW, Kim HJ (2018). "Risk factors and the associated cutoff values for failure of corticosteroid injection in treatment of Morton's neuroma". Int Orthop. 42 (2): 323–329. doi:10.1007/s00264-017-3707-8. PMID 29230531.
  80. ↑ Mahadevan D, Salmasi M, Whybra N, Nanda A, Gaba S, Mangwani J (2016). "What factors predict the need for further intervention following corticosteroid injection of Morton's neuroma?". Foot Ankle Surg. 22 (1): 9–11. doi:10.1016/j.fas.2015.03.007. PMID 26869493.
  81. ↑ Mahadevan D, Attwal M, Bhatt R, Bhatia M (2016). "Corticosteroid injection for Morton's neuroma with or without ultrasound guidance: a randomised controlled trial". Bone Joint J. 98-B (4): 498–503. doi:10.1302/0301-620X.98B4.36880. PMID 27037432.
  82. ↑ Yap LP, McNally E (2012). "Patient's assessment of discomfort during ultrasound-guided injection of Morton's neuroma: selecting the optimal approach". J Clin Ultrasound. 40 (6): 330–4. doi:10.1002/jcu.21926. PMID 22585530.
  83. ↑ Hughes RJ, Ali K, Jones H, Kendall S, Connell DA (2007). "Treatment of Morton's neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases". AJR Am J Roentgenol. 188 (6): 1535–9. doi:10.2214/AJR.06.1463. PMID 17515373.
  84. ↑ Rasmussen MR, Kitaoka HB, Patzer GL (1996). "Nonoperative treatment of plantar interdigital neuroma with a single corticosteroid injection". Clin Orthop Relat Res (326): 188–93. doi:10.1097/00003086-199605000-00022. PMID 8620640.
  85. ↑ Markovic M, Crichton K, Read JW, Lam P, Slater HK (2008). "Effectiveness of ultrasound-guided corticosteroid injection in the treatment of Morton's neuroma". Foot Ankle Int. 29 (5): 483–7. doi:10.3113/FAI.2008.0483. PMID 18510900.
  86. ↑ Sofka CM, Adler RS, Ciavarra GA, Pavlov H (2007). "Ultrasound-guided interdigital neuroma injections: short-term clinical outcomes after a single percutaneous injection--preliminary results". HSS J. 3 (1): 44–9. doi:10.1007/s11420-006-9029-9. PMC 2504098. PMID 18751769.
  87. ↑ Hassouna H, Singh D, Taylor H, Johnson S (2007). "Ultrasound guided steroid injection in the treatment of interdigital neuralgia". Acta Orthop Belg. 73 (2): 224–9. PMID 17515235.
  88. ↑ Souza JM, Purnell CA, Cheesborough JE, Kelikian AS, Dumanian GA (2016). "Treatment of Foot and Ankle Neuroma Pain With Processed Nerve Allografts". Foot Ankle Int. 37 (10): 1098–1105. doi:10.1177/1071100716655348. PMC 5363503. PMID 27340257.
  89. ↑ Bibbo C, Rodrigues-Colazzo E, Finzen AG (2018). "Superficial Peroneal Nerve to Deep Peroneal Nerve Transfer With Allograft Conduit for Neuroma in Continuity". J Foot Ankle Surg. 57 (3): 514–517. doi:10.1053/j.jfas.2017.11.022. PMID 29685562.
  90. ↑ Gould JS, Naranje SM, McGwin G, Florence M, Cheppalli S (2013). "Use of collagen conduits in management of painful neuromas of the foot and ankle". Foot Ankle Int. 34 (7): 932–40. doi:10.1177/1071100713478927. PMID 23447512.
  91. ↑ Rungprai C, Cychosz CC, Phruetthiphat O, Femino JE, Amendola A, Phisitkul P (2015). "Simple Neurectomy Versus Neurectomy With Intramuscular Implantation for Interdigital Neuroma: A Comparative Study". Foot Ankle Int. 36 (12): 1412–24. doi:10.1177/1071100715596741. PMID 26297693.
  92. ↑ Williams EH, Williams CG, Rosson GD, Heitmiller RF, Dellon AL (2008). "Neurectomy for treatment of intercostal neuralgia". Ann Thorac Surg. 85 (5): 1766–70. doi:10.1016/j.athoracsur.2007.11.058. PMID 18442581.
  93. ↑ Sood MK, Elliot D (1998). "Treatment of painful neuromas of the hand and wrist by relocation into the pronator quadratus muscle". J Hand Surg Br. 23 (2): 214–9. PMID 9607662.
  94. ↑ Atherton DD, Leong JC, Anand P, Elliot D (2007). "Relocation of painful end neuromas and scarred nerves from the zone II territory of the hand". J Hand Surg Eur Vol. 32 (1): 38–44. doi:10.1016/j.jhsb.2006.10.013. PMID 17126969.
  95. ↑ Hazari A, Elliot D (2004). "Treatment of end-neuromas, neuromas-in-continuity and scarred nerves of the digits by proximal relocation". J Hand Surg Br. 29 (4): 338–50. doi:10.1016/j.jhsb.2004.01.005. PMID 15234497.
  96. ↑ Atherton DD, Fabre J, Anand P, Elliot D (2008). "Relocation of painful neuromas in Zone III of the hand and forearm". J Hand Surg Eur Vol. 33 (2): 155–62. doi:10.1177/1753193408087107. PMID 18443055.
  97. ↑ Mackinnon SE, Dellon AL (1987). "Results of treatment of recurrent dorsoradial wrist neuromas". Ann Plast Surg. 19 (1): 54–61. PMID 3631861.
  98. ↑ Park EH, Kim YS, Lee HJ, Koh YG (2013). "Metatarsal shortening osteotomy for decompression of Morton's neuroma". Foot Ankle Int. 34 (12): 1654–60. doi:10.1177/1071100713499905. PMID 23892930.
  99. ↑ Preston N, Peterson D, Allen J, Kawalec JS, Whitaker J (2018). "Deep Transverse Metatarsal Ligament Transection in Morton's Neuroma Excision: A Cadaveric Study Examining Effects on Metatarsal Alignment". Foot Ankle Spec. 11 (4): 342–346. doi:10.1177/1938640017735888. PMID 29047294.
  100. ↑ Kasparek M, Schneider W (2016). "Transection of the deep metatarsal transverse ligament in Morton's neuroma surgery does not increase risk of splayfoot development". Int Orthop. 40 (5): 953–7. doi:10.1007/s00264-015-2981-6. PMID 26344448.
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