The role of fasciae in Civinini–Morton's syndrome

Abstract

This study evaluates the pathogenetic role of the perineural connective tissue and foot fasciae in Civinini–Morton's neuroma. Eleven feet (seven male, four female; mean age: 70.9 years) were dissected to analyse the anatomy of inter-metatarsal space, particularly the dorsal and plantar fasciae and metatarsal transverse ligament (DMTL). The macrosections were prepared for microscopic analysis. Ten Civinini–Morton neuromas obtained from surgery were also analysed. Magnetic resonance images (MRIs) from 40 patients and 29 controls were compared. Dissections showed that the width of the inter-metatarsal space is established by two fibrous structures: the dorsal foot fascia and the DMTL, which, together, connect the metatarsal bones and resist their splaying. Interosseous muscles spread out into the dorsal fascia of the foot, defining its basal tension. The common digital plantar nerve (CDPN) is encased in concentric layers of fibrous and loose connective tissue, continuous with the vascular sheath and deep foot fascia. Outside this sheath, fibroelastic septa, from DMTL to plantar fascia, and little fat lobules are present, further protecting the nerve against compressive stress. The MRI study revealed high inter-individual variability in the forefoot structures, although only the thickness of the dorsal fascia represented a statistically significant difference between cases and controls. It was hypothesized that alterations in foot support and altered biomechanics act on the interosseous muscles, increasing the stiffness of the dorsal fascia, particularly at the points where these muscles are inserted. Chronic rigidity of this fascia increases the stiffness of the inter-metatarsal space, leading to entrapment of the CDPN.

Introduction

Civinini–Morton's metatarsalgia is characterized by swelling of the common digital plantar nerve (CDPN), known as ‘neuroma' (Adams, 2010). Although the term usually means a swelling or tumor of nerve tissue, Civinini–Morton's metatarsalgia is not a true neuroma (Larson et al. 2005). Many possible causes are described: repeated microtrauma to the foot (Wu, 2000; Ayub et al. 2005; Decherchi, 2007; Ǻkermark et al. 2008; Pardal-Fernandez & Rodriguez-Vazquez, 2011; Rajput et al. 2012); local ischemia leading to nerve scarring (Nissen, 1948); bursitis (Bossley & Cairney, 1980); entrapment neuropathy (Jones & Tubby, 1898; Mulder, 1951; Graham & Graham, 1984; Viladot, 1992; Perini et al. 2006); increased tension in the foot fasciae (Stecco, 2014). Because the pathogenesis of this condition is doubtful (Hassouna & Singh, 2005), there is no ‘gold standard' for treatment either (Thomson et al. 2004). The classical treatment is neurectomy (Adams, 2010), but some authors (Gauthier, 1979; Dellon, 1992; Diebold et al. 1996; Barrett, 2011; Bauer et al. 2015) have suggested neurolysis as an alternative, supporting the concept that Civinini–Morton's disease is an entrapment syndrome (Gauthier, 1979). The cause of compression is in fact not clear, and for this reason some surgeons cut only the deep metatarsal transverse ligament (DMTL; Barrett, 2011), others suggest metatarsal osteotomy as well (De Prado, 2003).

The aim of this study is to evaluate all these forefoot structures, in both cadavers and living patients, to understand the cause of nerve entrapment and whether inter-individual variations can be identified in the morphology and contents of the inter-metatarsal channel.

Materials and methods

Macroscopic study

Dissections (approved by the local ethics committee) were conducted on 11 foot specimens (seven male, four female; mean age: 70.9 years) obtained from the ‘Body Donation Program' at the Institute of Anatomy, University of Padova (Porzionato et al. 2012). The second and third inter-metatarsal spaces of five unembalmed feet were dissected via a longitudinal cutaneous incision along the mid-line from the ankle to the proximal phalanges. Initially, only the skin was cut and raised medially and laterally to allow examination of the subcutaneous tissue, which was then carefully removed to expose the dorsal foot fascia. With toes II and III splayed, the dorsal foot fascia was cut at the level of the second inter-metatarsal space. The DMTL was then exposed and dissected, to reveal the CDPN and its bifurcation. The same technique was also used to dissect the third inter-metatarsal space. The sole of the foot was dissected via a longitudinal plantar incision from the heel to the base of the toes.

Microscopic and immunohistochemical study

From the remaining six embalmed feet, specimens of the region between rays II and IV were obtained from the mid-shaft of the metatarsal bones to the mid-half of the proximal phalanges. From each of these specimens, after decalcification in Kristensen's solution for 20 days, two coronal sections 1 cm thick were obtained for histological studies: the proximal section was chosen at the level of the metatarsal heads; and the distal one at the base of the proximal phalanges. Specimens were mounted on cardboard to avoid deformations and artifacts, fixed in 10% formalin solution, and embedded in paraffin. Sections 10 μm thick were cut and stained with hematoxylin and eosin, van Gieson for elastic fibers, Azan–Mallory for collagen fibers, and Alcian blue for hyaluronan. Four immunohistochemical stains were also applied: anti-S100 to identify nerve structures; hyaluronan-binding protein as a hyaluronan marker; and anti-collagen antibodies II and III (rabbit antibodies; Abcam) to ascertain the presence of collagen types II and III. The optimal dilution of the antibodies had been evaluated in the datasheet in a series of previous studies (Stecco et al. 2007) and various tests in the authors' laboratory. Lastly, collagen III antibody was used at a dilution of 1 : 100 and collagen II antibody at 1 : 200, after proteinase K digestion. Sections were incubated in a DAKO Autostainer System. All preparations were observed under a DM4500-B light microscope (Leica Microsystems, Wetzlar, Germany) and recorded in full color mode (24-bit) with a digital camera (DFC 480; Leica Microsystems).

Surgical samples

The study was approved by the local ethics committee. Informed consent was obtained from each participant. Between February 2013 and 2014, a total of 10 patients (10 female; average age 49.2 years) underwent resection of the inter-digital nerve because of symptomatic Morton neuroma. The resected neuromas were fixed in 10% formalin solution and embedded in paraffin. The same stains of the macrosections were used for all these specimens.

Radiological study

The analysis (approved by the regional ethics committee) was conducted on 40 magnetic resonance images (MRIs) of the forefoot of patients with clinical and radiological diagnosis of Civinini–Morton's syndrome (35 females, five males; mean age 58 years), and on 29 MRIs of patients with other foot and ankle pathologies (22 females and seven males; mean age 42 years). Images were randomly and anonymously selected from the archives of the radiology center of Euganea Medica (Padova). Each MRI was obtained on a 1T MR system (Philips Panorama; Philips Medical Systems, Best, the Netherlands), images being acquired with a standard protocol, including T1, T2, proton density sequence with long TR and short TR, and short tau inversion recovery. The analysis was conducted on T2 sequence characterized by the following parameters: axial plane, TR 1750, TE 100, FOV 130 × 130, matrix 220 × 174 thickness 4 mm, anisotropic voxels 4 × 0.59 × 0.74 mm, spatial resolution 0.59 × 0.74 mm. Analysis was carried out on an Aquarius Workstation (version 3.6.2.3; TeraRecon, San Mateo, CA, USA). Sections corresponding to the region of metatarsal heads and the metatarsophalangeal joints of toes II, III and IV were selected. The following measurements at the level of inter-metatarsal spaces II and III were recorded:

1. mean thickness of DMTL;

2. mean thickness of plantar fascia;

3. mean thickness of vertical fibrous septa of inter-metatarsal spaces;

4. mean thickness of dorsal fascia;

area of the inter-metatarsal channel, bounded dorsally by the DMTL, plantarly by the plantar fascia, and laterally by the flexor tendons and their sheaths.

The ligament and the fascia were identified by their anatomical location and as hypointense structures comprised between two layers of adipose tissue. For each of these parameters, six measures were taken and mean values were calculated. Analyses were independently conducted by two authors (IF and VM), who were blinded to subject identification. Mean values and standard deviations of all measurements were calculated.

Statistical analyses

To reveal differences between cases and controls in these parameters, statistical analysis included Student's t-test. A value of P < 0.05 was considered statistically significant. Statistical calculations were carried out with prism 3.0.3 software (GraphPad Software, San Diego, CA, USA).

Results

Macroscopic anatomy: dissection of dorsal region

The dorsal foot fascia, thin although highly resistant, covers the extensor tendons and inter-metatarsal spaces, which are filled with adipose tissue. The dorsal fascia on the remaining part of the forefoot is a thin membrane, through which underlying structures can be seen, but it condenses distally into a thick dorsal lamina, directed transversely, connecting the adjacent metatarsophalangeal joints. The dorsal fascia ends just after the base of the proximal phalanx; it holds the toe rays in close contact, limiting any splaying. It also is reinforced by the tendinous expansions of the interosseous tendons, establishing connections with them. Deep in the dorsal fascia is the fascia of the extensor digitorum brevis, which covers the extensor digitorum brevis muscle and tendons. At the level of the metatarsal heads, this layer fuses with the dorsal foot fascia.

The interosseous dorsal fascia is the deepest layer, covering the osseous layer and fusing with the capsules of the metatarsophalangeal joints. The dorsal and plantar interosseous muscles arise from the metatarsal shafts to reach the proximal phalanges. These muscles also establish a connection with the dorsal fascia, by sending tendinous expansions to it. The interosseous muscles cover the plantar metatarsal arteries, coming from the plantar arterial arch and then dividing into the two digital plantar branches. The inter-metatarsophalangeal bursa could not be seen in any specimen. Plantar to these is the plantar interosseous fascia, running under the metatarsal bones and inter-metatarsal spaces; distally, it is strengthened by the DMTL, which connects the metatarsal heads. The DMTL is composed of three or four fibrous bands, intertwined to form a reticular structure.

Briefly, the dorsal aspect of the forefoot shows two transverse structures that define the distance between adjacent metatarsal rays: the dorsal fascia and the DMTL. Both help to avoid excessive splaying of the toes: the section of the dorsal fascia provides a considerable increase in the inter-digital distance; after dissection of the DMTL, this space widens further (Fig.1).

Fig 1.

Macroscopic anatomy of the inter-metatarsal channel. (A) Schematic view of the region between the II and the IV metatarsal bone, from which anatomical specimens were taken. (B) Dorsal fascia of the foot (arrow) overlying the CDPN (asterisk). (C) After cutting the dorsal fascia, it is possible to obtain a good widening of the inter-metatarsal space and to visualize DMTL (arrow). The asterisk indicates CDPN's bifurcation. (D) CDPN (asterisk) is clearly visible after section of DMTL. Also note the further widening of the inter-metatarsal space.

Macroscopic anatomy: dissection of plantar region

The thick plantar skin adheres firmly to subcutaneous tissue rich in adipose lobules, which are separated by vertical connective septa arising from the dermis. The plantar fascia lies deeper, branching distally into five digital expansions that diverge toward the toes. At the root of the toes, they are linked by the superficial transverse metatarsal ligament. Septa deriving from the digital slips of the plantar fascia pass dorsally and define the digital and inter-digital arches: the former holds the flexor tendons and the latter the neurovascular bundles. At the level of the metatarsophalangeal joints, the CDPN is only separated from the DMTL by a thin layer of loose connective tissue. Distal to the DMTL, the CDPN bifurcates into proper digital branches, which diverge to continue on the sides of the toes.

Microscopic anatomy

The interosseous area between the metatarsophalangeal joints dorsal to the DMTL is roughly rectangular in shape, with its long axis directed dorso-plantarly. The dorsal foot fascia appears as a thin fibrous structure on the back of the metatarsal bones. Its mean thickness in the specimens was 1.12 mm (Table1). The dorsal foot fascia is composed of up to three layer of fibrous connective tissue, separated by loose connective tissue. The dorsal foot fascia covers the extensor tendons and bridges the interosseous area, continuing on the back of the adjacent metatarsal bone. Its deep aspect gives origin to vertical slips that deepen in the inter-metarsal space, connecting with the interosseous muscles. This fascial system contains no elastic fibers, but it does have a moderate quantity of hyaluronic acid. Also the joint capsule receives tendinous expansions from the interosseous muscles (Fig.2). Between two interosseous muscles, a thin space filled by loose connective tissue and whose boundaries are shown by the deep fascia covering the interosseous muscles can be appreciated. A true bursa with a well-defined synovial membrane could not be seen in any of the specimens. In the plantar region of each metatarsophalangeal joint the plantar plates could be recognized. They are fibrocartilaginous structures in continuity with the joint capsule and with the DMTL. The connection between the DMTL and the plantar plates forms a stiff structure that divides the inter-metatarsal region transversely: dorsally there are bones and interosseous muscles; and plantarly the inter-metatarsal channel for the neurovascular bundle. In the plantar plates, immunohistochemical staining for collagen II (a marker of cartilaginous tissue) revealed much of this fiber, which gradually decreases along the DMTL, marking the transition from the cartilage of the plantar plate to the fibrous ligaments (Fig.3). Due to the continuity between plantar plate and DMTL, cartilaginous metaplasia of the ligament was observed, making the transverse connection even stiffer. Hyaluronic acid, very rich in the plantar plate, diminishes toward the DMTL, where it is absent. The DMTL contains no collagen III (Fig.4).

Table 1.

Thickness of dorsal fascia and DMTL as evaluated in the histological samples (mm)

Specimens	Dorsal fascia in the space II	Dorsal fascia in the space III	DMTL thickness in the space II	DMTL thickness in the space III
1	1.03	1.32	0.95	0.85
2	1.14	1.1	1	1.15
3	0.74	0.89	0.91	0.84
4	1.15	1.01	0.97	1.23
5	0.94	0.91	0.94	1.01
6	1.14	1.35	1.22	1.58
Mean value	1.02	1.09	0.99	1.11
SD	0.16	0.20	0.11	0.28

DMTL, deep metatarsal transverse ligament.

Fig 2.

Coronal view of the inter-metatarsal space and its relationship with CDPN. (A) Macroscopic anatomy. (B) Scheme of inter-metatarsal arrangement. (C) Microscopic anatomy.

Fig 3.

DMTL and plantar plate. (A) Immunohistochemical staining for collagen II, showing the gradual transition from the cartilaginous plantar plate to the fibrous DMTL. (B) Alcian blue staining: hyaluronic acid, abundant in the plantar plate, is absent in DMTL.

Fig 4.

(A) immunohistochemical staining for collagen III in the plantar region. (B) Immunoistochemical staining showing the presence of collagen III in the neural sheath.

Near the plantar plates, the flexor tendons run in their common sheath, which is continuous with the plantar plate and devoid of elastic fibers. The sheath is strengthened on its sides by connective tissue septa, directed to the plantar fascia. Some of these are vertical; others turn obliquely to reach the next inter-metatarsal space (Fig.5).

Fig 5.

Microscopic anatomy of the inter-metatarsal channel. CDPN runs just plantar to DMTL. Under the nerve, a fat pad bounded by fibro-elastic septa is visible. (A) Azan Mallory staining. (B) Van Gieson staining.

In the region of the metatarsal heads, the plantar fascia divides into four longitudinal fascicles, plantar to the flexor tendons. They are connected by transverse fibers, thus forming a scalloped structure, with thicker fibers at the level of the vertical septa and thinner ones in the inter-metatarsal space. The plantar fascia does not contain any elastic fibers. Superficial to the plantar fascia is a layer of adipose tissue, made up of small lobules bounded by connective tissue septa, which connect the plantar fascia to the dermis.

The inter-metatarsal channel defined by these structures can be divided into a dorsal part, near the DMTL, on the same layer as the flexor tendons, and a plantar part, in the layer of vertical septa. The first part contains the lumbrical tendon laterally and the neurovascular bundle medially. At this level, the CDPN has a protective sheath composed of concentric fibrous layers separated by loose connective tissue (Fig.6). The nerve with its sheath has a mean area of 1.11 mmq.

Fig 6.

Neural sheath of CDPN. (A) Hematoxylin-eosin staining showing connective tissue sheath. (B) S100 staining highlights the myelin sheath, surrounded by the connective sheath.

This sheath is divided into the following portions:

1. endoneurium, which covers individual nerve fibers, outside their myelin sheaths;

2. perineurium, wrapping the main nerve bundles;

3. epineurium, ensheathing the whole nerve.

The neural connective sheath has no elastic fibers. Hyaluronic acid is scarce. Outside this structure is another system, the paraneurium, composed of two or three layers, thinner and more loosely packed, separated by loose connective tissue, with elastic fibers and adipocytes. This structure is in continuity with the vascular sheaths of the digital arteries. The plantar half of the inter-metatarsal channel shows vertical septa, rich in elastic fibers varying in size, from the plantar fascia to the paraneurium. There is always a thick Y-shaped septum, running in the middle of the space from the plantar fascia: this septum, before reaching the neurovascular bundle, bifurcates into two transverse branches directed toward the flexor sheaths and connected to the paraneurium; a vessel and a nerve are contained within the thickness of this septum. Thinner septa arise from these main septa, forming a mesh of collagen and elastic fibers, binding small adipose lobules, with a mean area of 1.51 mmq. The whole neurovascular bundle in the inter-metatarsal space crosses a fat pad, organized into small lobules. The fat pads of the adjacent inter-metatarsal spaces are separated by fibrous septa connecting the flexor sheaths to the plantar fascia.

The microscopic anatomy of neuroma tissue shows in all the specimens an evident alteration of the neural connective sheaths, due to the widespread presence of an amorphous, eosinophilic substance, enveloping a few small cells (Fig.7). As this material accumulates, it displaces nerve fascicles and alters sheath morphology, preventing a clear view of the organization of the fibers into epineural, perineural and endoneural layers. The nerve fascicles are covered in thick perineural sheaths, made up of an increasing number of concentric fibrous laminae, closely adherent to one another. Particularly noticeable is the lack of loose connective tissue and adipocytes, among both perineural layers and nerve fascicles. The branches of the plantar metatarsal artery show greatly thickened walls, with slit-like lumens, which appeared to be completely closed. Arterial branches are also surrounded by thickened fibers, continuous with the connective tissue around the nerve.

Fig 7.

Microscopic anatomy of the Morton neuroma. (A) Azan Mallory stain, note the fibrosis of the connective sheaths enveloping the nerve. (B) S100 immunohistochemical stain highlights the myelin sheath. Note the displacing of the nerve fiber bundles. (C) Hematoxylin-eosin stain. Note the sclerosis of the little vessels. (D) Van Gieson stain for the elastic fibers (stained in black). Note the absence of elastic fibers in this sample.

Imaging

In patients, the neuroma was found just distal to the DMTL. The smallest lesions, ovoid in section, appeared dorsal, at the level of the bones. As they increased in size, the lesions tended to expand toward the plantar region and become dumbbell-shaped. Measurements made on MRIs of both controls and patients with Civinini–Morton's syndrome yielded the following results (Table2). Statistical analysis of these data showed the following.

Table 2.

Mean values of measurements on MRIs in healthy subjects and patients with Civinini–Morton's syndrome

	Mean values for space II (± standard deviation)		Mean values for space III (± standard deviation)		Mean values for II and III space (± SD)
	Cases	Controls	Cases	Controls	Cases	Controls
DMTL thickness (mm)	0.99 (± 0.4)	0.92 (± 0.31)	0.95 (± 0.41)	0.89 (± 0.3)	0.87 (± 0.31)	0.91 (± 0.31)
Plantar fascia thickness (mm)	0.86 (± 0.095)	0.85 (± 0.13)	0.86 (± 0.096)	0.95 (± 0.41)	0.86 (± 0.095)	0.89 (± 0.3)
Vertical septa thickness (mm)	0.84 (± 0.26)	0.82 (± 0.13)	0.79 (± 0.11)	0.85 (± 0.15)	0.82 (± 0.2)	0.83 (± 0.14)
Dorsal fascia thickness (mm)	0.8 (± 0.12)	0.84 (± 0.14)	0.85 (± 0.14)	0.86 (± 0.16)	0.8 (± 0.11)	0.87 (± 0.13)
Inter-metatarsal area (mm2)	48.99 (± 14.97)	53.85 (± 15.57)	52.84 (± 15.12)	56.65 (± 14.66)	50.91 (± 15.07)	55.25 (± 15.06)

DMTL, deep metatarsal transverse ligament.

• DMTL thickness did not differ significantly between patients and controls, either in overall results (P = 0.53) or in space II (P = 0.45) or space III (P = 0.54);

• Plantar fascia thickness did not significantly differ (P = 0.26; in space II, P = 0.85; in space III, P = 0.19) between cases and controls. Vertical septa showed no statistically significant differences in thickness (P = 0.57 in space II; P = 0.64 in space III; P = 0.058 between cases and controls);

• The dorsal fascia was significantly thinner in patients (P = 0.079 in space II; P = 0.031 in space III; P = 0.038 between cases and controls).

• The inter-metatarsal area showed no statistically significant differences (P = 0.097 in space II; P = 0.19 in space III; P = 0.29 between cases and controls; Fig.8).

Fig 8.

Inter-metatarsal area: inter-individual variation of shape and size. MRI study.

Inter-observer variability ranged from 5 to 10%.

Discussion

Both ultrasound (US) and MRI are used in evaluating patients with metatarsalgia and diagnosing Morton's neuroma (Lee et al. 2007; Lee, 2009). US is less expensive and time consuming than MRI, and allows a real-time localization and visualization of pain (ultrasonographic Tinel sign; Chipman et al. 2009), but is also user dependent. On the other hand, MRI provided static and non-operator-dependent images being able to visualize the surrounding soft tissues (Zanetti & Weishaupt, 2005). A recent meta-analysis showed that sensibility of US is equal to that of MRI for identification of Morton's neuroma (Bignotti et al. 2015). With reference to the plantar fascia, several studies have assessed plantar fascia thickness using US or MRI. It has generally been accepted that a thickness of 4 mm with associated inflammatory changes would be consistent with plantar fasciitis (Ozdemir et al. 2005; Karabay et al. 2007; Pascual Huerta & Alarcon Garcıa, 2007). In the present study, the thicknesses of the DMTL, plantar fascia, vertical fibrous septa of inter-metatarsal spaces and dorsal fascia were evaluated. Even if measuring structures with a thickness of 1 mm is quite unlikely with a 1T, the current data should be considered as relative values. In fact, they were used to make a comparison between patients and controls, and not to indicate a reference value suggesting a pathology. Moreover, the ligament and the fascia are easy to recognize, because of their high-contrast resolution due to their hypointense signal, bounded by adipose tissue. This study highlighted high inter-individual variability in the forefoot structures analysed, although this was not related to increased risk of Civinini–Morton's metatarsalgia. The only value that showed a statistically significant difference between cases and controls was the thickness of the dorsal fascia. Dissections clearly demonstrated how this fascia, together with the DMTL, is responsible for defining the distance between adjacent toe rays and avoiding excessive splaying of the toes. More than simple boundaries of the inter-metatarsal region, they are key elements for Civinini–Morton's syndrome: excessive stiffness of these structures can result in inter-metatarsal channel narrowing, with the risk of nerve entrapment. The dorsal fascia section indeed greatly increases the inter-digital space; after division of the DMTL, this space widens further. This entire system, besides, is dissected both during operations applying the dorsal approach for neurectomy (Singh et al. 2005) and neurolysis (Rosson & Dellon, 2005; Barrett, 2011), in order to give a proper view of the CDPN.

The observed connection between the dorsal fascia and the interosseous muscles can be regarded as an anatomical basis of the dorsal fascia tensioning: a prolonged contraction of these muscles can chronically stretch the dorsal fascia, making it stiffer and dehydrated. This can explain the fascial thinning observed in patients.

Comparisons between patients and controls show no differences in DMTL thickness, which revealed moderate inter-individual variations in both groups. Nor did the plantar fascia and its septa vary significantly between groups. The inter-metatarsal area showed marked variations in both size and shape, and in both cases and controls, although significant differences were not found between groups.

The inter-metatarsophalangeal bursa could not be seen during dissection. It is a thin, ‘functional' structure, which normally has a virtual lumen. Whenever it is distended by fluid, such as inflammatory fluid or contrast dye, it gains volume and can be well visualized. Also, Bossley & Cairney (1980) in their classic work about inter-metatarsophalangeal bursa affirm that before dissection they injected heated, dyed gelatin into the bursa ‘because the bursa is normally thin-walled and sometimes communicates with the joint'. Only during microscopic examination can a thin space between the adjacent interosseous muscles be appreciated, whose boundaries are shown by the deep fascia covering the interosseous muscles.

The channel for the neurovascular bundle is bounded dorsally by DMTL and plantarly by a fat pad. The latter is organized into small lobules, bounded by a thick mesh of collagen and elastic fibers. This arrangement, similar to a sponge, is highly different from that of the subcutaneous adipose tissue of the rest of the body. Indeed, instead of a metabolic function, it plays a mechanical role, absorbing the compressive shock typical of walking, so that its role is similar to that of the heel fat pad (Fig.5).

The neural connective sheath is made up of concentric layers of fibrous connective tissue, separated by loose connective tissue, thus forming a telescopic arrangement that cushions the nerve, allowing it to move independently of the surrounding tissue. During foot movements, the layers of the sheath slide one over another, protecting the nerve from traction by surrounding structures. The paraneurium, outside this sliding system, is composed of loosely packed fibrous layers separated by adipose tissue: this adds a cushioning effect to the sliding system, which reduces compressive stress. The paraneurium represent the interface between the nerve sheath and the inter-metatarsal channel: being connected to the DMTL and, via vertical septa, to the plantar fascia, it is stretched by them, guaranteeing an opening space around the nerve. Excess traction by surrounding structures provides a mechanical stimulus to the sheath, which could react with the proliferation of fibroblasts. The reactive fibrosis observed in Morton's neuroma specimens and described in the literature (Ringertz & Unander-Scharin, 1950; Lassmann et al. 1976; Giakoumis et al. 2013) can be regarded as a consequence of nerve entrapment. The excess fibrous content of these laminae, no more intertwined with loose connective layers, changes the sheath into a stiff channel that, instead of protecting the nerve, still worsens its entrapment; besides, the accumulation of collagen compresses the small vessels that run within the sheath, thus causing nerve ischemia, that in turn worsens fibrosis. It is essential to treat the patients at the beginning of this vicious cycle, when alterations are still reversible, in order to restore normal sheath's anatomy.

Some authors suggest adding distal metatarsal osteotomy to neurolysis (De Prado, 2003; Bauer et al. 2015), assuming that one component of Morton's metatarsalgia derives from plantar hyperpressure. The current anatomical specimens showed no significant morphological alterations of the metatarsal bones; in any case, they may easily be splayed after dissection of the DMTL and dorsal foot fascia. These findings suggest that nerve compression in Civinini–Morton's syndrome is primarily due to connective tissue (Barrett, 2006), while the metatarsal bones may contribute to further nerve entrapment once a neuroma has developed, or if there are associated bony deformities of the forefoot. In cases that have not yet developed metatarsal alterations, after neurolysis the bones play no further role in compressing the nerve: in these patients, metatarsal osteotomy may be avoided, thus allowing earlier recovery by averting the edema and swelling caused by osteotomy (Bauer et al. 2015). Pre-operative evaluation of the forefoot is thus important: apart from allowing a search for fascial thinning, it can also rule out the bone deformities often associated with Civinini–Morton's syndrome (Kasparek & Schneider, 2013).

Conclusions

This study highlights for the first time the possible role of an alteration of the dorsal fascia of the foot in CDPN compression and thus provides an explanation for the treatment of this disease by neurolysis, other than manual therapies aimed at decreasing myofascial tension of the metatarsal region. It was also hypothesized that altered foot support and biomechanics may act on the interosseous muscles and increase the stiffness of the dorsal fascia, particularly at the point where these muscles are inserted. Chronic rigidity of this fascia causes increased stiffness of the inter-metatarsal space (Fig.9). Neuroma may be considered as the final manifestation. Future implications of this research will be to study patients who have no neuroma but who report symptoms suggestive of Morton's metatarsalgia: in these patients, the dorsal fascia should be examined by MRI or US to ascertain whether it is already altered. This may be a predictive sign of foot alteration leading to neuroma if not treated properly.

Fig 9.

Possible role of dorsal fascia of foot in CDPN compression.

Author contributions

Carla Stecco: dissections and histology, data interpretation. Ilaria Fantoni: dissection and imaging study. Veronica Macchi: imaging study. Andrea Porzionato: data analysis. Mario Del Borrello: imaging study. Carlo Biz: data interpretation. Raffaele De Caro: critical revision and approval of manuscript.

Conflict of interest

The authors declared no conflicts of interest.