Neuroma
Synonyms and keywords: Traumatic neuroma; Morton neuroma; Amputation neuroma; Pseudoneuroma; Mortons 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; Terminal neuroma; Stump 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 ()
-oma (-) from the Greek word for swelling
- neuro- from the Greek word for nerve ()
- -oma (-) 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:

# Pathophysiology
- The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis
- The pathogenesis of traumatic neuroma is characterized by:
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)
- 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's neuroma is characterized by being located in the 3rd web-space, between 3rd and 4th metatarsal heads, 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, includes: 
Adherent fibrofatty tissue
Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule)
</=2cm in size
- Adherent fibrofatty tissue
- Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule)
- </=2cm in size
- On microscopic histopathological analysis, characteristic findings of neuroma, include:
Extensive fibrosis around and within the nerve
Digital artery
Thrombosis
Arterial thickening
- Extensive fibrosis around and within the nerve
- Digital artery
- Thrombosis
- Arterial thickening

## 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

## Common sites of involvement by traumatic neuroma
- Most common oral locations are:
Tongue
Near mental foramen of mouth
- Tongue
- Near mental foramen of mouth
- Rarely involves:
Head
Neck
- Head
- Neck

# Causes
- Common causes of neuroma include:
Indirect nerve trauma
Especially during a surgery
Cone biopsy (rare complication)
55% of hysterectomy patients have microneuromas, associated with childbirth
Traction injury
Chronic repetitive stress
- Indirect nerve trauma
Especially during a surgery
Cone biopsy (rare complication)
55% of hysterectomy patients have microneuromas, associated with childbirth
Traction injury
Chronic repetitive stress
- Especially during a surgery
- Cone biopsy (rare complication)
- 55% of hysterectomy patients have microneuromas, associated with childbirth
- Traction injury
- Chronic repetitive stress
- Morton's neuroma is associated with:
Wearing tight shoes and high heels
Overpronation
Abnormal positioning of toes
Flat feet
Forefoot problems such as:
Bunions
Hammer toes
High foot arches
- Wearing tight shoes and high heels
- Overpronation
- Abnormal positioning of toes
- Flat feet
- Forefoot problems such as:
Bunions
Hammer toes
- Bunions
- Hammer toes
- High foot arches

# Epidemiology and Demographics
- Neuroma is an uncommon disease

## Age
- Neuroma is more commonly observed among patients aged between 15 to 50 years old
- 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

## Race
- There is no racial predilection for neuroma

# Risk Factors
- Common risk factors in the development of neuroma include:
Improper footwear/tight shoes
High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing)
Overpronation
- Improper footwear/tight shoes
- High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing)
- Overpronation

# Natural History, Complications and Prognosis
- The majority of patients with neuroma are symptomatic at the time of diagnosis
- 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%

# Diagnosis

## Symptoms
- Neuroma  is usually asymptomatic
- Symptoms of neuroma may include:
Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel:
Shooting
Burning
Stabbing
Raw
Gnawing
Sickening sensations
Numbness
Paresthesia over the injured area
Dysesthesia (painful hypersensitivity to normal light tactile stimuli)
Functional impairment
Psychological distress (severely decreasing the quality of life)
- Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel:
Shooting
Burning
Stabbing
Raw
Gnawing
Sickening sensations
- Shooting
- Burning
- Stabbing
- Raw
- Gnawing
- Sickening sensations
- Numbness
- Paresthesia over the injured area
- Dysesthesia (painful hypersensitivity to normal light tactile stimuli)
- Functional impairment
- Psychological distress (severely decreasing the quality of life)

## Physical Examination
- Patients with neuroma usually appear with antalgic posture
- Physical examination may be remarkable for:
Tenderness to palpation
Limitation of range of motion
Dysesthetic pain
Mulder's sign:
Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb
- Tenderness to palpation
- Limitation of range of motion
- Dysesthetic pain
- Mulder's sign:
Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb
- Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb

## Laboratory Findings
- There are no specific laboratory findings associated with neuroma

## Imaging Findings

### MRI
- On MRI, characteristic findings of neuroma include:
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
- 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:
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
- 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

### Ultrasound
- Ultrasound can help distinguish neuroma from:
Intermetatarsal bursal swelling or
Synovitis in adjacent joints
- Intermetatarsal bursal swelling or
- Synovitis in adjacent joints
- On ultrasound, neuroma is characterized by the following findings:
Round to ovoid
Well-defined, hypoechoic lesion
Located in the intermetatarsal space proximal to the metatarsal head
- 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:
Swollen nerve (mass-like)
Hypoechoic
Loss of normal fibrillar pattern
Usually small, but may be as large as 5 cm
- 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's neuroma
- Morton's neuroma should be managed conservatively before proceeding to expensive diagnostic procedures
- Conservative measures for pain relief include:
Decreasing pressure on the metatarsal heads by using:
Metatarsal support
Metatarsal bars
Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as:
Metatarsal pads
Toe crest pads
Tapping the toe area
Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot
Specialized orthopedic shoes
Comfortable shoes (with the help of a professional shoe fitting device) having:
Wider toe box allowing spread of metatarsal heads
Low heels
Good arch support
Physical therapy
Ice massage
Strength exercises for intrinsic foot muscles
Resting
- Decreasing pressure on the metatarsal heads by using:
Metatarsal support
Metatarsal bars
Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as:
Metatarsal pads
Toe crest pads
Tapping the toe area
Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot
Specialized orthopedic shoes
Comfortable shoes (with the help of a professional shoe fitting device) having:
Wider toe box allowing spread of metatarsal heads
Low heels
Good arch support
- Metatarsal support
- Metatarsal bars
- Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as:
Metatarsal pads
Toe crest pads
- Metatarsal pads
- Toe crest pads
- Tapping the toe area
- Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot
- Specialized orthopedic shoes
- Comfortable shoes (with the help of a professional shoe fitting device) having:
Wider toe box allowing spread of metatarsal heads
Low heels
Good arch support
- Wider toe box allowing spread of metatarsal heads
- Low heels
- Good arch support
- Physical therapy
- Ice massage
- Strength exercises for intrinsic foot muscles
- Resting

### Non-conservative medical therapy
- When conservative measures fail, following medical therapy is used for non-surgical treatment of neuroma:
Tricyclic antidepressants
Anticonvulsants (more effective)
Serotonin-norepinephrine reuptake inhibitors
Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness:
Steroid
Local anaesthetic
Anti-inflammatory drugs (orally or injected into the toe area), such as:
Ibuprofen (Advil, Motrin)
Naproxen (Aleve, Naprosyn)
Painkillers (not recommended for long-term treatment)
- Tricyclic antidepressants
- Anticonvulsants (more effective)
- Serotonin-norepinephrine reuptake inhibitors
- Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness:
Steroid
Local anaesthetic
- Steroid
- Local anaesthetic
- Anti-inflammatory drugs (orally or injected into the toe area), such as:
Ibuprofen (Advil, Motrin)
Naproxen (Aleve, Naprosyn)
- Ibuprofen (Advil, Motrin)
- Naproxen (Aleve, Naprosyn)
- Painkillers (not recommended for long-term treatment)

## Surgery
- Surgical excision is the treatment of choice for neuroma
- Surgical excision is associated with a relatively favorable success rate of approximately 80%
- Recurrence rate after surgery is as high as 50%

## Prevention
- There are no primary preventive measures available for neuroma
- Secondary prevention measures include: personal hygiene measures, such as wearing ergonomic shoes

# Differential Diagnosis
- Neuroma must be differentiated from other diseases that cause forefoot pain and numbness such as:
Stress fracture (neck of the metatarsal)
Rheumatoid arthritis
Hammer toe
Neurofibroma
- Stress fracture (neck of the metatarsal)
- Rheumatoid arthritis
- Hammer toe
- Neurofibroma