Morton’s Neuroma

Stephen J. Miller

Aprajita Nakra

Metatarsalgia or generalized pain in the plantar forefoot area has many causes. A common source of such exasperating discomfort is a peripheral nerve affliction that may involve one or more common digital plantar nerves as they pass through the intermetatarsal spaces.

The first anatomic description of this localized nerve enlargement was clearly illustrated by the Italian anatomist di Civinini in 1835 (1). However, the neuralgic symptoms of this disorder were first accurately described by the English chiropodist, Durlacher, in 1845 (2). He characterized it as attacking “the plantar nerve … between the third and fourth metatarsal bones.”

Ironically, this entity was named after T.G. Morton of Philadelphia, who believed that the pain developed about the fourth metatarsophalangeal articulation because of nerve irritation from its lateral osseous neighbor (3). He should not be confused with T.S.K. Morton, who reported six cases of “Morton’s metatarsalgia” in 1893 (4), or with D.J. Morton, who described the functional anatomic entity, Morton’s syndrome, in 1935 as a cause of metatarsalgia (5).

DEFINITION, ANATOMY, AND INCIDENCE

Morton’s neuroma is a misnomer used to describe this painful pedal neuropathy. The lesion is a benign enlargement of the third common digital branch of the medial plantar nerve located between, and often distal to, the third and fourth metatarsal heads. The region is supplied by a communicating branch from the lateral plantar nerve as well (6, 7, 8, 9) (Fig. 1).

Classically, the nerve passes beneath the deep transverse intermetatarsal ligament on its plantar aspect. The only other structures passing in this immediate area are the third plantar metatarsal artery, with its accompanying vein or veins, and the tendon slip from the third lumbrical muscle that inserts into the extensor hood apparatus on the medial aspect of the fourth toe. This is also the area in which pacinian corpuscles are normally found in the subcutaneous tissues (10). The neurofibrous lesion is separated from the sole by the fat pad, plantar fascia, and connective tissue compartments. The superficial transverse metatarsal ligament is situated superior to the nerve when the region is viewed from the plantar aspect (Fig. 2).

The incidence of Morton’s neuroma in the general population has not yet been determined. Youngswick observed that of 4,000 patients presenting to his clinic with foot complaints, 9.3% were diagnosed with a neuroma (11).

In addition to the third intermetatarsal space, an intermetatarsal neuroma may also occur in other locations, usually within the second intermetatarsal space but rarely in the first or fourth. Out of 113 histologically confirmed neuromas, Bartolomei and Wertheimer found 64% in the third intermetatarsal space, 29% in the second, 6% in the fourth, and 1% in the first (12). Addante et al. evaluated 152 neuroma resections and found that 66% involved the third intermetatarsal space, 18% the second, 4% the fourth, and 2.6% the first (13). Mann and Reynolds found the neuromas evenly distributed between the second and third intermetatarsal spaces (14), whereas Bennett et al. found 68% in the third interspace and 32% in the second (15). Friscia et al. evaluated 366 patients with neuromas and found that 91% of these lesions involved the third intermetatarsal space (16).

The lesions can occur bilaterally as well (0% to 12%) (12,14,17). Less frequently (1% to 4%), neuromas can be found in two intermetatarsal spaces in one foot and rarely in three intermetatarsal spaces in the same foot (12,14,17, 18).

Histologic evidence strongly supports the concept that Morton’s neuroma syndrome is an entrapment neuropathy, resulting from compressive forces, especially against the deep transverse intermetatarsal ligament (19, 20, 21, 22, 23, 24, 25, 26). Incriminating factors include densely packed whorls of collagen, Renaut’s bodies, and thickened endoneural capillaries all formed within the subperineural space of interdigital nerves (25). Also seen are local demyelination and telescoping of myelin in opposite directions on either side of the lesion (26). Confusion has resulted from the many names applied to this lesion, which may be better described as a perineural fibroma (Table 1).

FIG. 1. Anatomy of the plantar nerves and location of classic Morton’s neuroma beneath the deep transverse intermetatarsal ligament. Note the contribution from segments of the medial and lateral plantar nerves.

FIG. 2. Cross section through the forefoot at the level of the metatarsophalangeal joints. The metatarsal artery lies above the neuroma with its accompanying venae comitantes. The lumbrical tendon lies lateral to the neuroma.

TABLE 1. Terminology used to describe Morton’s neuroma

Term	Authors and year
Neuralgic affection … plantar nerve	Durlacher, 1845
A peculiar and painful affection of the fourth metatarsophalangeal joint	Morton, 1876
Luxation podalgia	Dana, 1885
Anterior metatarsalgia	Pollosson, 1889
Metatarsal neuralgia	Bradford, 1891
Morton’s metatarsalgia	Morton, 1893
Morton’s painful affection of the foot	Hoadley, 1893
Morton’s disease	Tubby, 1896
Plantar neuralgia	Jones and Robert, 1897
Morton’s painful disease	Stern, 1904
Morton’s neuralgia	Cush, 1937
Neuritis of the fourth digital nerve	Bettx, 1940
Morton’s toe	McElvenny, 1943
Plantar neuromas	Bickel and Dockerty, 1947
Morton’s toe syndrome	Kite, 1947
Plantar digital neuritis	Nissen, 1948
Lateral plantar neuritis	Hiss, 1949
Metatarsal neuroma	Sandel, 1958
Plantar metatarsal neuritis	Pincus, 1962
Interdigital neuroma	Hauser, 1971
Morton-Durlacher neuralgia	Silverman, 1976
Intermetatarsal neuroma	Goldman, 1979
Thomas Morton disease	Gauthier, 1979
Morton’s neuritis	Milgram, 1980
Plantar interdigital neuroma	Viladot, 1982
Pseudoneuroma	Alexander, Johnson, and Parr, 1987

DIAGNOSIS

Signs and Symptoms

Most symptomatic intermetatarsal neuromas are found in women (12,14,15) and are commonly diagnosed between the fourth and the sixth decades, although these lesions may sometimes be found in teenagers. The patient may be overweight (12). In milder or early cases, the patient may describe a sensation of walking on a wrinkle in the stocking or a lump in the shoe. If the neuroma is large enough, the adjacent toes may be forced to spread apart on weight bearing. Because Morton’s neuroma causes a distinct set of symptoms, the diagnosis can most often be made from the patient’s history (Table 2).

Pain

The pain from this syndrome has been described as sharp, dull, or throbbing, but it classically manifests as a paroxysmal burning sensation “like walking on a hot pebble” or “having a hot poker thrust between the toes.” It is most often localized to the region of the third and fourth plantar metatarsal heads and may radiate distally into adjacent toes, transversely to adjacent metatarsal heads, or proximally up the leg to the knee and, in rare instances, as high as the hip. Bizarre symptoms such as metatarsalgia during orgasm or defecation have been reported, with relief on excision of the neuroma (27).

Even though the patient may describe numbness in the third and fourth toes, a sensory deficit is seldom present. At times, the digits may be hyperesthetic. Patients may describe a cramping sensation in the arch, forefoot, or toes; however, there is no evidence of muscle cramping (28).

The pain is greatly aggravated by walking in shoes and is relieved somewhat by rest, although in acute stages, lancinating or aching pains may occur during periods of inactivity. Sometimes the patient finds irritation even from bed sheets intolerable. A characteristic and virtually pathognomonic indication of a neuroma is the overwhelming desire to remove the shoe, rub the forefoot, and flex the toes. This usually provides dramatic, although transient, relief of pain.

Symptoms are present for a few weeks to several years. However, if the pain is acute, the patient usually seeks help within a few weeks. In many instances, acute pain appears after an incident of trauma which may or may not seem mild. Examples would be stepping on a rock, twisting an ankle, striking the edge of a curb, jamming the foot into the floorboard
in a motor vehicle accident, or simply changing into a new pair of shoes or doing an extraordinary amount of walking. The use of narrow or tight-fitting shoes can both instigate and aggravate symptoms.

TABLE 2. Symptoms of unoperated Morton’s neuroma as reported by patients from two studies

	Study A percentage (n = 65)	Study B percentage (n = 115)
Pain increased with walking	91	—
Relief by rest	89	—
Plantar pain	77	—
Pain in forefoot	—	76
Relief by removing shoe	70	60
Pain radiating to toes	62	—
Burning pain	54	—
Pain between toes	—	43
Numbness into toes or foot	40	23
Aching or sharp pain	40	—
Inability to wear fashionable shoes	—	39
Pain up foot or leg	34	11
Cramping sensation	34	—
Pain at rest	—	19
History of associated injuries	15	—
Pain at night	—	10
Pain in entire foot	—	9
A, From Mann RA, Reynolds JC. Interdigital neuroma: a critical clinical analysis. Foot Ankle 1983;3:238. B, From Bennett GL, Graham CE, Mauldin DM. Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int 1995;16:762.

Palpation

Tenderness and sometimes reproduction of pain can be elicited by squeezing each intermetatarsal space in a dorsoplantar direction at or distal to the metatarsophalangeal joints. On occasion, this maneuver deliver a palpable mass dorsally or plantarly, especially during the application of simultaneous transverse compression of the first and fifth metatarsal heads in the plantar sulcus when the toes are hyperextended. This maneuver also causes the patient a varying amount of pain.

Hyperextending the patient’s toes with one hand and rolling the opposite thumb transversely across the metatarsal hands on the sulcus side may reveal a palpably thickened longitudinal mass (Bratkowski’s sign), which is tender when Morton’s neuroma is present (29).

Mulder’s sign is positive when lateral compression of the forefoot combined with plantar and dorsal pressure produces a silent, palpable, and sometimes painful click in the affected intermetatarsal space as the neuromatous lesion is squeezed plantarly between the adjacent metatarsal heads (30,31). This clicking may also be caused by an adventitial bursa that forms in close association with the neuroma between the metatarsal heads (32).

Local tenderness should be differentiated from arthritic pain by direct palpation of the adjacent metatarsophalangeal joints. Further palpation of the nearby metatarsal shafts helps to rule out a stress fracture.

Differential Diagnosis

Many other disorders have symptoms that may resemble Morton’s neuroma. Some of these are listed in Table 3. Differentiation can usually be made by means of a thorough history and physical examination, although when an element of doubt remains in the face of persistent symptoms, diagnostic testing may be implemented. Even though Morton’s neuroma is a benign lesion, local malignant sarcomas have caused similar presenting symptoms in rare instances (33,34). In addition, other benign neoplasms have been reported to cause “Morton’s metatarsalgia” (35,36).

TABLE 3. Differential diagnosis of Morton’s neuroma

Metatarsal stress fracture

Rheumatoid arthritis

Autoimmune arthritides

Osteochondritis dissecans (Freiberg’s)

Localized vasculitis

Ischemia

Tarsal tunnel syndrome

Nerve root compression syndromes

Peripheral neuritis

Peripheral neuropathy (e.g., diabetic)

Intermetatarsal bursitis

Metatarsophalangeal joint capsulitis

Metatarsophalangeal joint predislocation syndrome

Transfer metatarsalgia

Diagnostic Tests

Radiographs

Weight-bearing radiographs may be taken to help rule out other pathologic conditions and also to evaluate for rotation, enlargement, or juxtaposition of the metatarsal heads that may contribute to the origin of the neuroma (37, 38, 39). Grace et al., in their study of 48 feet with pathologic confirmation of neuroma and 100 asymptomatic patients, found no statistical relationship between radiologic findings or metatarsus proximus and digital divergence (“Sullivan’s sign”) and the physical occurrence of neuromas (40,41). Instead, an increased intermetatarsal angle of the affected interspace was noted in the neuroma-afflicted group. The neuroma itself is not visible on x-ray films or xeroradiography.

Sensory Nerve Conduction Tests

Electrodiagnostic techniques for evaluating Morton’s neuroma are not highly accurate, primarily because of the difficulty in isolating a single interdigital nerve with an electrode (24). However, in one study, the diagnosis was confirmed by electrophysiologic testing of five patients. Positive results were characterized by an abnormal-dip phenomenon, a relatively normal conduction velocity, and normal duration of the sensory compound nerve action potential. These findings are the hallmarks of a neuropathy with a predominant axonal degeneration (42). Therefore, such testing may be reserved for further assessment of patients with metatarsalgia who lack the classic physical signs of Morton’s neuroma (22,43).

Magnetic Resonance Imaging

Cross-sectional magnetic resonance imaging (MRI) through the forefoot has differentiated a Morton’s neuroma mass from the surrounding bone and soft tissues (44). The neuroma appears isointense relative to muscle on T1-weighted images and homogenously or inhomogenously hypointense relative to fat tissue on T2-weighted images. In other words, it is best seen on T1-weighted images as a well-demarcated mass of lower signal intensity (45) (Fig. 3). Studies have shown that T1-weighted axial and coronal images with an axial fast spin-echo T2-weighted sequence detect neuromas more consistently than an enhanced T1-weighted fat-suppressed sequence (46,47). Although the neuroma is often invisible on T2-weighted images, on occasion the presence of fluid-filled bursae will lead to a high signal intensity proximal to the neuroma (48,49).

FIG. 3. Magnetic resonance image of an intermetatarsal neuroma. Coronal T2-weighted image of a neuroma in the third interspace. (Courtesy of George Vito, D.P.M.)

However, MRI has been shown to produce false-negative images, so the accuracy of the scans is not ensured (50). For this reason, as well as for cost considerations, MRI for the diagnosis of Morton’s neuroma may be best considered in patients with recurrent neuroma, atypical symptoms, or coexisting neurologic conditions (51), or it may be used when a neuroma is suspected in an adjacent interspace.

Ultrasonograhy

High-resolution ultrasound appears to be the most promising of the objective imaging techniques for visualizing Morton’s neuroma (52). Studies of ultrasound evaluation compared with surgical and pathologic confirmation have demonstrated a diagnostic accuracy of 95% to 98% (18,53, 54, 55). However, one limitation is that ultrasonography is highly dependent on the operator and the machine. An ultrasonographer with inadequate experience or the use of a low-resolution transducer can produce false-negative test results. The typical sonographic appearance of a neuroma is that of an ovoid, hypoechoic mass oriented parallel to the long axis of the metatarsals, best seen on coronal section through the forefoot (52,55) (Fig. 4). Normal interdigital nerve diameter in that area is about 2 mm. Initial data suggest that the lesion becomes symptomatic when it reaches 5 mm or more in diameter. This test is especially helpful for determining the presence of neuromas in adjacent intermetatarsal spaces preoperatively. It can also be of assistance in diagnosing postsurgical recurrence of intermetatarsal neuroma (56).

FIG. 4. Sonographic image of Morton’s intermetatarsal neuroma. Note the hypoechoic mass oriented parallel to the long axis of the metatarsals. (Courtesy of George Vito, D.P.M.)

Histopathology

On gross examination, a resected specimen of Morton’s neuroma has a shiny, glistening surface that is white to buff yellow. It is generally fusiform and should have two or more easily identifiable digital branches with a distinct bifurcation. Either branch may have a swelling along its course as well. Usually, the nodule can be dissected easily from the surrounding fibroadipose tissue. However, it can be firmly attached to the intermetatarsal bursa or enwrapped in the bursa itself (Fig. 5). In some instances, the bursa may also envelop the lumbrical tendon. The findings of several investigators indicate that the neuroma does not have to be particularly large, nor does it have to be present for a substantial amount of time, to cause pain and for the nerve to undergo significant pathologic changes (38,57,58).

The histopathology is central to the diagnosis and origin of Morton’s neuroma. No histologic examinations of Morton’s neuroma were published until that of Betts in 1940 (59). Since then, there have been many investigations into the histopathology of this lesion (Table 4). Actually, Morton’s neuroma is neither a true neuroma nor a neoplasm. The term neuroma refers only to tumorous nodules that are formed by neural proliferation and dense fibrosis involving both axons and sheath (Schwann’s cells) (60).

The histopathologic investigations of numerous authors support the observations that Morton’s neuroma consists of degenerative alterations of one or more intermetatarsal nerves (Fig. 6). This process is characterized by the following: endoneural and neural edema (early stages); perineural, epineural, and endoneural fibrosis and hypertrophy (late stages); Renaut’s body formation, usually in a subperineural location; hyalinization of the walls of endoneural blood vessels; subintimal and perivascular fibrosis that may lead to occlusion of local blood vessels (resembling a healed vasculitis); mucinous changes endoneurally and perineurally; and demyelination with axonal loss (60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74). Goldman noted perineural epithelial cells lying freely in the endoneurium and assumed that they played a phagocytic role (64) (Fig. 7).

FIG. 5. Gross specimen of resected Morton’s neuroma. Bifurcate digital branches and the fusiform enlargement are clearly visible.

TABLE 4. Histopathology of Morton’s neuroma: a chronology

Authors and year	Material	Findings
Betts, 1940	19 cases	The first to make a histologic examination; found increased fibrous tissue elements
Cottrell, 1940	—	Found progressive thickening of the walls of the endoneural vessels and the perineurium with aging in normal nerves
McElvenny, 1943	12 specimens, 11 patients	Neurofibromas or angioneurofibromas; Renaut’s bodies
Baker and Kuhn, 1944	14 specimens, 11 patients	Resembled amputation neuroma: reactive hyperplasia
King, 1946	5 cases	“Sclerosing neuroma”
Bickel and Dockerty, 1947	18 cases	Interstitial edema and irregular demyelination
Nissen, 1948	27 cases	Local vascular degeneration: an ischemic lesion
Winkler, Felner, and Kimmelstiel, 1948	20 cases	Essentially a degenerative process
Ringertz and Unander-Scharin, 1950	18 specimens, 21 controls	Endoneural edema and demyelination are the characteristic features of Morton’s neuroma
Scotti, 1957	17 cases	“Endarteritis-fibrosis complex’
Viladot and Moragas, 1966	7 cases	Similar degenerative changes; no sign of inflammation or thrombotic injury
Meachin and Abberton, 1971	23 specimens, 19 patients, 23 controls	Nonspecific degenerative reactive changes
Reed and Bliss, 1973	118 cases	“Regressive and productive intermetatarsal elastofibrositis;” elastin tissue proliferation in the fibroadipose tissue surrounding Morton’s neuroma
May, 1976	31 specimens	“Traumatic neuritis” with proliferation of connective tissue elements: neurofibroma
Lassmann, 1976	105 patients	Thickened perineurium, thickened walls of endoneural vessels, endoneural edema and sclerosis, axonal degeneration without wallerian degeneration
Tate and Rusin, 1978	50 specimens	Marked fibrosis and collagenous infiltration; demyelination; axonal degeneration
Goldman, 1979, 1980	133 cases	Demyelination diagnostic of intermetatarsal neuroma; observed distal wallerian degeneration as evidence of axonal degeneration and shift to left in axon diameter population; pathologic process not sparing any components of the peripheral nerve; detailed degenerative activity plus some axon regeneration; Renaut’s bodies
Lassmann, 1979	133 cases	Endoneural vascular fibrosis
Mann and Reynolds, 1983	65 specimens, 11 recurrent neuromas	Similar degenerative changes; classic pathologic findings of neuromas a traumatic neuroma in recurrent lesions
Graham and Graham, 1984	24 neuromas	Venous congestion, entrapment changes, nerve enlargement distal to the transverse metatarsal ligament
Guiloff, Scadding, and Klenerman, 1984	16 patients	Similar degenerative changes: Renaut’s bodies common
Shereff and Grande, 1991	10 specimens	Edema of the endoneurium, fibrosis beneath the perineurium, axonal degeneration and necrosis characteristic of nerve impingement
Bourke, Owen and Machet, 1994	15 patients	“Except for possible demyelination, the so-called typical histologic changes of fibrosis and swelling are similar to that seen as presumed degenerative disease in elderly patients”

FIG. 6. A: Light micrograph. Note the endoneural and perineural fibrosis, the large hyalinzed nodules in the endoneurium, and the dropping out of myelimated fibers (800× magnification). B: Light micrograph. Note the vessels with thickened walls, the hyalinized nodules, and the endoneural fibrosis (2,000× magnification). (Courtesy of Flair Goldman, D.P.M.)

In advanced cases of Morton’s neuroma, Renaut’s bodies (hyaline granules) have been observed in the endoneural tissue (25,61,64). These degenerative structures, first described in 1881 (75), are a nonspecific response to nerve trauma, particularly to compression (76, 77, 78).

FIG. 7. A: Electron micrograph. Note the giant vacuolated endoneural fibroblast (20,000× magnification). B: Electron micrograph. Note the degenerating myelin engulfed by the perineural epithelial cell. Also note multiple micropinocytotic vesicles (25,000× magnification). (Courtesy of Flair Goldman, D.P.M.)

Finally, wallerian degeneration, or fatty degeneration of a nerve fiber caused by loss of nutrition, has been observed in Morton’s neuroma. In addition, evidence of regeneration of axons may in part explain the symptoms associated with the neuroma (24,42,79) (Fig. 8).

Several of the degenerative changes seen histologically in the plantar intermetatarsal nerves are the same in both control specimens and in patients with symptomatic pathologically confirmed Morton’s neuroma. More characteristic
of Morton’s neuroma are demyelination, endoneural edema, and a greater degree of subperineural fibrosis (74,80). Although endoneural edema can be associated with inflammation, only one study observed a leukocytic infiltration into the nerve, and that was only in half of their specimens (n = 10) (73).

FIG. 8. A: Electron micrograph. Note the vesicular degeneration of myelin (18,200× magnification). B: Electron micrograph. Note the cluster of regenerating axons (34,000× magnification). (Courtesy of Flair Goldman, D.P.M.)

In summary, Morton’s neuroma is a progressive, degenerative, and at times regenerative process in which early and late pathologic changes maybe found. Although the intermetatarsal nerves and blood vessels undergo many degenerative changes, endoneural edema, excess fibrosis, and demyelination are diagnostic of the disorder. Therefore, perineural fibroma may be a better term for this lesion. It appears from histopathologic studies that Morton’s neuroma is the result of both crushing and stretching trauma to the interdigital nerves, particularly in the third intermetatarsal space. Goldman was more specific and suggested that the epineurium responds to mechanical compression, whereas the perineurium responds to stretch (64).

ETIOLOGY AND BIOMECHANICS

Many theories have been proposed for the etiology of Morton’s neuroma (Table 5). Histologic findings leave little doubt that the syndrome is indeed a mechanical entrapment neuropathy (23, 24, 25, 26,73). The deep transverse intermetatarsal ligament appears to be the anatomic structure most likely to be responsible for this process.

Less clear is the exact source of these mechanical entrapment forces. A common observation is that most intermetatarsal neuromas occur in the pronated foot (12,38,81,82), where there are not only excessive stretch forces imposed on the interdigital nerves but also compressive and shearing forces from the adjacent hypermobile metatarsal heads (83, 84, 85). The nerve is also subjected to increased trauma by the motion occurring between the medial and lateral columns of the foot, which are divided between the third and fourth metatarsals.

In addition, as the medial and lateral plantar nerves dive plantarly under the arch, a stretch is placed on these nerves during prolonged midstance pronation as the foot is everted, abducted, and dorsiflexed. Tension is increased as these nerves travel around the flexor digitorum brevis sling and are drawn up tightly against the plantar and anterior edge of the unyielding deep transverse intermetatarsal ligament (65). This may help to tether the nerves in both the third and the second intermetatarsal spaces. Further tension and compression on the nerve occurs across this ligament when the toes hyperextend at the metatarsophalangeal joint (23,57,59,61,65,86, 87, 88). Thus, occupations requiring repetitive toe hyperextension can result in the development of an intermetatarsal neuroma, regardless of foot type.

Finally, pointed-toe or narrow shoes can further add compressive forces that favor the production of intermetatarsal neuromas in any foot type (61,65). High-heeled shoes not only throw weight forward onto the ball of the foot and jam the toes into the narrow front of the shoe, but also they force the toes into hyperextension and encourage nerve compression.

Intermetatarsal Bursa

At the level of adjacent metatarsophalangeal joints, an intermetatarsal bursa lies in close proximity to Morton’s neuromas (12,38,58,62,66,67,89, 90, 91, 92, 93, 94, 95). These features have been confirmed on MRI scans (49). Inflammation of these structures creates swelling and compression on the adjacent nerve and may explain some of the acute symptoms associated with neuromas, especially when the patient has a prompt response to corticosteroid injections.

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