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FAS 1031 No. of Pages 11

Foot and Ankle Surgery xxx (2017) xxxxxx

Contents lists available at ScienceDirect

Foot and Ankle Surgery

journal homepage: www.elsevier.com/locate/fas

Review

Treatment of Mortons neuroma: A systematic review

Silvia Valisena, MDa,* , Gianfranco John Petri, MDb , Andrea Ferrero, MDb
a
Service of Traumatology, Regional Hospital of Bellinzona, Via Ospedale, Bellinzona, Switzerland
b
Clinica Luganese Moncucco, Via Moncucco 10, Lugano, Switzerland

A R T I C L E I N F O A B S T R A C T

Article history: Background: The treatment of Mortons neuroma (MN) can be operative, conservative and inltrative. Our
Received 13 December 2016 aim was the evaluation of evidence on outcomes with different types of conservative, inltrative and
Received in revised form 17 February 2017 surgical treatment in patients affected by primary MN.
Accepted 28 March 2017
Methods: The bibliographic search was conducted in MEDLINE, Cochrane Library, DARE. Only studies in
Available online xxx
English were collected. The last search was in August 2015. Case series and randomized controlled trials
(RCTs) assessing patients satisfaction or pain improvement at an average follow-up of at least 6 months
Keywords:
after treatment of primary MN were included. Two reviewers selected the studies, evaluated their
Mortons neuroma
Treatment
methodological quality, and retrieved data independently.
Surgery Results: Of 283 titles found, only 29 met the inclusion criteria. Data showed better outcomes with
Inltrative operative treatment.
Conservative Conclusions: The evaluated case series and few RCTs showed better results with invasive treatment. More
and better RCTs which evaluate risk-benet ratio are required to conrm these results.
2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1. Criteria for considering studies for this review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.2. Data collection and analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.3. Assessment of risk of bias in included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.4. Data synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Papers selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Description of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.3. Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.4. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5. Primary outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5.1. Conservative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5.2. Inltrative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5.3. Operative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6. Secondary outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.1. Conservative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.2. Inltrative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.3. Operative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7. Risk of bias in the included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7.1. Case series . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7.2. Randomized controlled trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

* Corresponding author at: Viale Stazione 30, Bellinzona 6500, Switzerland.

E-mail address: silvia.valisena@gmail.com (S. Valisena).

http://dx.doi.org/10.1016/j.fas.2017.03.010
1268-7731/ 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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2 S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx

4.1. Summary of the evidences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

4.2. Limitations of the studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Conict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction 2. Methods

Mortons neuroma (MN) is a degenerative neuropathy featuring 2.1. Criteria for considering studies for this review
brosis of the common interdigital nerve [1]. It is a common
pathology mainly affecting middle age women, although there is Studies were identied by searches in electronic libraries, trial
lack of data on its frequency [2]. Its incidence in UK was 50.2% for registries and bibliographic quotations. Two reviewers (A.F. and S.
men and 87.2% for women per 100,000 of patients presenting to V.) independently carried out the bibliographic searches and
primary care [3]. studies selections, holding into account the inclusion and
Four aetiopathogenetic theories have been proposed [4], exclusion criteria (described later). Cases of disagreement were
chronic traction damage [2], inammatory environment due to arbitrated by a third reviewer (G.J.P.). The authors of the selected
intermetatarsal bursitis [5], compression by the deep transverse studies were never contacted. Searches were carried out on
intermetatarsal ligament [6,7], and ischemia of vasa nervorum [8]. MEDLINE (1946 to August 2015), Cochrane Library (1979 to August
The treatment for MN is initially conservative, progressing to 2015), DARE (1995 to August 2015), ClinicalTrials.gov and
inltrations and then surgery, if the previous steps fail, according PROSPERO by combining Mortons neuroma, neuroma, sur-
to the therapeutical algorithm available in literature [2,9,10]. gery, inltrative, conservative, treatment.
The treatments considered as conservative consist in patients We have included prospective and retrospective case series and
education on avoidance of tight shoes, manipulation and use of randomized controlled trials (RCTs) which assess the results of
insoles or other special orthotic appliances. conservative, inltrative and operative treatments in patients with
The inltrative treatments include injections of local anaes- diagnosis of primary MN, excluding stump neuroma and recur-
thetics, steroids or alcohol and percutaneous radio-frequency rences, with a mean follow-up of at least 6 months.
ablation. We excluded papers in languages other than English, case
The surgical treatments consist of neurectomy or neurolysis, reports and animal studies.
which can be performed open, either via a dorsal or plantar We excluded studies in which X-rays and histology showed that
approach, or mini-invasive. The latter is aimed at decompressing a sizable proportion of patients presented pathologies other than
the nerve by division of the deep intermetatarsal ligament, either Mortons (usually bursitis and synovitis) and in which the results
endoscopically or percutaneously. were cumulative and did not differentiated the neuroma from the
The studies, which assess the results of treatment, have a other forms of metatarsalgia. One such study, even if excellent
follow-up from one week [11] to 10 years [12,13]. from a methodological point of view, was excluded on account of
The length of follow-up allows to identify durable results and to 31% ultrasound conrmed bursitis [16]. Many studies on primary
dene complications of treatment, failures and recurrences. MN exclude patients with rheumatoid arthritis, diabetes mellitus
According to Mann, it takes one year following neurectomy to and foot deformities. Many others do not state whether such
develop a symptomatic amputation neuroma, after a pain-free conditions are cause for exclusion. A few studies do include some
postoperative period [14]. such patients. Because of such disparity we decided not to consider
The aim of this review is to compare the outcomes of the those conditions as exclusion criteria. We did not exclude papers
different types of Mortons neuroma treatment. Primary outcome on the basis of publication date or status.
denes which treatment provides the best result at an average We excluded studies which presented bias with overestimation
follow-up of at least 6 months in terms of patients satisfaction, of results, as for protocol analysis in controlled randomized trials.
improvement of pain and other symptoms. Patients satisfaction is One important requirement for inclusion was that the primary
based on Johnsons scale [15] and other scales. Pain was measured outcome be assessed after a mean follow-up of 6 months. This was
with VAS and other scales (number rating scale, NRS). The follow- an arbitrary choice based on the observation that studies on
up of studies on conservative treatment usually lasts for few weeks conservative and inltrative treatment have a mean follow-up
to 6 months, in case of inltrations 612 months, for surgical usually inferior to 6 months. Therefore our choice of 6 months
studies it can last for years. To compare the results of all types of allowed us to compare studies on the three types of treatment.
therapy we have chosen a 6-month follow-up. Furthermore, it is twice the length of follow-up reported in a
Secondary outcome denes the evaluation of complications, previous Cochrane Review [17]. Studies with follow-up periods
recurrences and failures for each type of treatment. Such events and outcomes not clearly dened were excluded.
are complementary to the primary outcome. It is important to The evaluation of the secondary outcome was added to our
distinguish between mere adverse events and recurrences. The protocol secondarily because, during selection of the articles, we
rst, such as haematoma, infection, postoperative pain, allergic often noticed that complications and recurrences were either
reactions to injected drugs are only a temporary setback, unreported or cumulated as adverse events. Moreover, some
whereas the second can have a long-term impact on patients authors report reoperation rates without naming their causes.
quality of life. Assessing the correct reporting of complications and recurrences is
useful to identify cases of excessively positive reporting of results.

Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
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For every bias, we dened the level of risk as high, low or

283 titles/abstracts 260 MEDLINE indenite.
13 Cochrane Library
1 DARE We drew up a table to evaluate:
8 ClinicalTrials.gov
1 PROSPERO  the suitability of the study design;
 any misclassication bias due to the diagnosis used to dene the
sample;
7 redundant studies eliminated  information bias, checking if the inclusion and exclusion criteria
were described for all the patients;
 selection bias, dened as a sequential ordering bias of the
276 titles/abstracts examined patients for the case series and according to the variables pointed
out by the Cochrane Handbook for the randomized control trials
(RCTs);
235 studies eliminated  performance and detection bias for the RCTs and even for the
37 full texts not available case series, when they indicated if the blinding for the outcome
198 not meeting inclusion criteria assessors had been performed for the patients or for the medical
staff;
 recall bias, evaluation of any patients mistake in reporting
41 full texts examined clinical data;
 reporting bias, reporting not in line with the specic statement of
the study or omission of any clinical data or results;
12 studies not meeting inclusion criteria  attrition bias: this term was used both for RCTs and observational
studies; consequently, when this bias was present, the term used
in the table was for protocol analyses.
29 studies included in the qualitative
analysis
Case series do not use a rigorous methodology, according to
Fig. 1. Flow chart: procedure for paper selection. their low level of evidence. Case series with a low risk of results
overestimation and with suitable methodological characteristics
were included.
Patients with recurrence or needing further injections or
reoperation were dened as failures. 2.4. Data synthesis
The procedure used for the papers selection is described in the
ow chart in Fig. 1. We presented the outcome (in Tables 1 and 2) as an absolute
number to perform the weighted average for every column. For this
2.2. Data collection and analysis reason, we performed proportions to convert the frequency from
relative to absolute when the paper reported the result only in
We created a chart for data extraction; it was tested at interim percentage.
analysis and subsequently implemented with the secondary This conversion was possible only for the papers in which the
outcome related columns. general number of the studied population was known and a
The extraction of the data has been performed by two authors in protocol analysis was not performed.
independent way. We did not perform a meta-analysis to the interim analyses,
There have not been cases of disagreements among the analyses because most of the studies were observational. It was not possible
of the two authors. to perform a meta-analysis for the included RCTs either, because of
From every included study we have drawn out information the high degree of heterogeneity, as already found by other authors
related to: [17].

 demographic data (number of participants, number of MNs 3. Results

affected feet, median age and range for every sample of patients);
 clinical data (duration of the symptoms before treatment, type
and duration of any previous treatment, average duration and
range of the follow-up, type of treatment, numbers of conrmed
MNs, numbers of cases conrmed by histological examination,
clinical outcomes, complications, therapeutical failures).
From the original data set, only the following items were
selected: information related to the number of participants,
average duration and range of the follow-up, type of surgery,
outcomes, complications, failures.
We have performed a weighted average in order to reduce the
inuence of the sample size on the frequency of the outcome for
every type of treatment.
2.3. Assessment of risk of bias in included studies
We followed the bias assessment process as described in the
Cochrane Handbook [18], making it suitable for the case series.
3.1. Papers selection
At the beginning of our sensitive research, we had 283 papers.
After a rst screening we examined 41 full texts.
In a second phase, we excluded studies with a high number of
patients affected by non-Mortons metatarsalgia in which the
demarcation between the sub-populations was not possible. We
only kept the papers in which the number of patients potentially
affected by a non-Mortons metatarsalgia was thought to be very
low (less than 5 patients).
Some other papers were excluded for different reasons:
 studies that described a treatment algorithm without specifying
the duration of each stage;
 studies that did not describe the outcome in terms of patients
satisfaction and improving symptoms;
 studies that did not use the same outcome measures described in
methods;

Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
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Table 1
Clinical data: outcomes of the included studies (presented as absolute numbers).

Study and year Study design Participant No. Mean F-U in Treatment Overall Complicationsa Failuresa
months (F-U satisfactiona
range)
Surgical treatment
Akermark et al. Retrospective case 145 n.s. (2460) Open
2008 (Feb) [19] series
Plantar group: 69 29 (2446) Nerve resection-plantar incision 68/73 4/69 0
Dorsal group: 56 37 (2460) Nerve resection-dorsal incision 52/59 10/56 3/56
Bauer et al. 2015 Retrospective case Open: 26 24 (2484) Open neurectomy 24/26 1/26 1/26
[36] series dorsal incision
M.I.S.: 26 M.I.S.: Percutaneous metatarsal 23/26 1/26 1/26
osteotomies and ligament release
Biasca et al. 1999 Retrospective case 19 15 (821) Partial neurectomy-dorsal incision 14/19 n.a. n.a.
[35] series
Dereymaeker Retrospective case 31 44,7 Open: excision-dorsal incision 26/32 0 1/31
et al. 1996 [21] series (1471) (+ adapted shoes/inner soles)
Faraj et al. 2010 Retrospective case 36 18 (1354) Open: neurectomy 30/36
[37] series
Plantar group: 20 (Feet Plantar incision 11/36 1/36
No)
Dorsal group: 22 (Feet Dorsal incision 6/36 0
No)
Kasparek et al. Retrospective case 81 180 Open: excision-dorsal incision 90/98 73/111 n.a.
2013 [22] series (120240) (55 cases with DTML transection;
56 without DTML transection)
Lee et al. Retrospective case 13 126 Open neurectomy-dorsal incision 13/13 11/13 n.a.
2011 [12] series (120146)
Pace et al. Retrospective case 78 54 (996) Open: neurectomy-dorsal incision 76/78 18/78 8/78
2010 [38] series
Park et al. 2013 Retrospective 84 n.s. (n.s.) Open: decompressiondorsal
[39] comparative series incision for both groups
DTML release: 46 (No of 26,2 DTML release (Group A) 42/46 3/46 2/46
Morton) (24,727,7)
Osteotomy+ 26,3 Metatarsal shortening osteotomy and 40/40 2/40 0
release: 40 (No of (23,629) DTML release (Group B)
Morton)
Ruuskanen et al. Retrospective case 45 72 Open: neurectomy-dorsal incision 47/58 0 5/45
1994 [13] series (24144)
Vito et al. 2003 Retrospective case 78 n.s. Open: Decompression with 78/82 n.a. 4/82
[24] series (n.s128) relocation-dorsal incision
Akermark et al.. Prospective case 55 29 (2446) Open: Nerve resection-plantar 55/59 3/55 0
2008 [44] series incision
Barrett et al. 1994 Prospective case 17 6 (912) M.I.S.: Endoscopic decompression 15/17 2/17 n.a.
[20] series
Nashi et al. 1997 Prospective case 52 36 (n.s.) Open neurectomy
[23] series
Plantar: 26 Plantar incision 17/26 7/26 1/26
Dorsal: 26 Dorsal incision 21/26 4/26 1/26
Valente et al. Prospective case 25 45 (672) Open: neurectomy-dorsal incision 17/25 n.a. 0
2008 [40] series
Akermark et al. RCT 76 34 (2842) Open
2013 [45]
Plantar group: 35 34 (2839) Nerve resection-plantar incision 32/35 5/35 n.a.
Dorsal group: 41 33 (2842) Nerve resection-dorsal incision 38/41 6/41 2/41
Colgrove et al. RCT 44 n.s. (148) Open-dorsal incision 1/44 0
2000 [14]
Resection: 22 Resection 19/22 n.a. 0
Neuroma intermuscular Neuroma intermuscular 21/22 1/22 0
transposition: 22 transposition

Study and year Study Participant No Mean F-U in months (F-U Treatment Overall Complications Failures
design range) satisfaction
Conservative treatment
Kilkmartin et al. RCT 23 n.s. (n.s.) Orthosis n.a. 11/23
1994 [27] Supination 10,1 Supination with cobra orthosis 5/10
orthosis: 10 (treatment A)
Pronation 11,09 Pronation with reverse cobra orthosis 5/11
orthosis: 11 (treatment B)

Study and year Study design Participant No Mean F-U in months Treatment Overall Complicationsa Failuresa
(F-U range) satisfactiona
Inltrative treatment
Chuter et al. 2013 Retrospective case 25 6 (6) US-guided radiofrequency 26/30 1/25 3/25
[41] series ablation
Magnan et al. Retrospective case 65 36 (2455) Phenol injection-dorsal 57/71 0 4/65
2005 [42] series approach

Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
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Table 1 (Continued)
Study and year Study design Participant No Mean F-U in months Treatment Overall Complicationsa Failuresa
(F-U range) satisfactiona
Moore et al. 2012 Retrospective case 29 13 (336) Radiofrequency 26/29 1/29 2/29
[25] series thermoneurolysis
Mozena et al. Retrospective case 42 11 (224) Alcohol injection 30/49 3/42 12/42
2007 [26] series
Musson et al. Retrospective case 75 14,3 (626) US-guided alcohol ablation 55/85 1/75 17/75
2012 [32] series
Pasquali et al. Retrospective case 508 12 (12) US-guided alcohol injection 400/540 0 n.a.
2015 [33] series
Deniz et al. 2015 Prospective case 20 9 (715) US-guided pulsed 12/20 2/20 n.a.
[43] series radiofrequency ablation
Fanucci et al. Prospective case 40 10 (n.s.) US-guided alcohol injection 36/40 6/40 4/40
2004 [28] series
Hughes et al. Prospective case 101 21,1 (1334) US-guided alcohol injection 91/100 17/101 3/101
2007 [29] series
Makki et al. 2012 Prospective 43 n.s. (12) Corticosteroid injections
[30] comparative study
G1 (small neuromas): 5/16 n.a. 2/17
17 Morton
G2 (large neuromas): 8/22 n.a. 4/22
22 Morton
Markovic et al. Prospective case 35 9 (9) US-guided corticosteroid 26/39 0 12/39
2008 [31] series injections

M.I.S.: mini-invasive surgery; n.a.: not available (referred to the columns complications, failures: one of these was not mentioned nor rated); No: number; n.s.: not stated;
a
For these columns, satisfaction and symptoms improvement, complications and failure are referred to the number of participant or to the number of feet or to the number
of neuromas. This is why the denominator of the fractions can be different from the number of participant. In other cases, if the number of participant includes few bursitis, the
denominator of these columns differs because it is referred only to Mortons neuromas.

 studies that provided data that we could not use to perform Most of the operated patients (10/17 studies) had formerly
weighted average; experienced conservative treatment for 312 months, or inltra-
 studies with protocol analysis. tive therapy, with 13 corticosteroid injections. The patients
treated with corticosteroid had previously undergone conservative
At the end of the skim process, our systematic review was based treatment without improvements. Some of them had received
on 29 studies. corticosteroid injections without benet before undergoing radio
ablation.
3.2. Description of included studies
3.4. Treatment
As shown in Table 1, the 29 studies concerned different
Sixteen studies about operative treatment focused on open and
approaches to MN: 1 was about the conservative, 11 were about
2 on mini-invasive technique.
inltrative [4145] and 17 about operative treatment [3740].
Seven of the 16 studies about open techniques were compara-
They included 17 retrospective case series (11 about operative
tive; 4 of these compared the results of the same operative
and 6 about inltrative treatment); 9 prospective case series
technique performed via plantar or dorsal approach, while the
(4 about operative and 5 about inltrative treatment); 3 RCTs
other 3 evaluated different operative approaches. The most
(2 about operative and 1 about conservative treatment).
frequent was dorsal. In 14 studies the nerve was excised, whereas
The inclusion of only one study on conservative treatment is a
in 4 studies it was decompressed by division of the intermetatarsal
limitation, but it must be stressed that most such studies have a
transverse deep ligament. The follow-up period was 46 months.
follow-up of one month.
Six studies concerning inltrative treatment focused on alcohol
injections, 3 on radio-frequency ablation and 2 on corticosteroid
3.3. Participants injections. The follow-up period was 14 months.
The study concerning conservative treatment focused on the
The total number of participants affected by primary MN was use of the orthoses. The follow-up period was about 10.5 months.
2021, of which 21 treated conservatively, 1041 by inltrations and
959 surgically.
Median age was 43 for conservative and 51,4 for operative
Table 2
treatment.
Primary and secondary outcomes of the included studies.
The diagnosis was clinical for 9 studies: 6 about operative [19
24], 2 about inltrative [25,26] and one about conservative Study type Satisfaction Complication rate Failure rate
treatment [27]. In 6 other studies, all concerning inltrative Conservative Overall 48% Not available 47%
treatment, the diagnosis was clinical-radiological; in these works, 1 study (C)
Ultra Sound (US) were used to verify the clinical nding [2832].
Inltrative Overall 85% 3% 14%
In some studies about operative treatment, the differential 11 studies (A, B) A 74, B 75% 10 studies 10 studies
diagnosis (DD) was supported by X-rays. In some others, patients
underwent X-rays, US and/or MRI for the DD. The ex juvantibus Surgical Overall 89% 21% 4%
diagnosis, with corticosteroid injection, was used in just one case. 17 studies (A, B, C) A 91, B 82, C 92% 14 studies 13 studies
In 3 studies the diagnostic method was not mentioned. A: retrospective studies, B: prospective studies, C: RCT.

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6 S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx
3.5. Primary outcomes
The most successful treatments were the operative ones with
89% success rate and the inltrative ones with 85%. In Table 2 we
highlighted that operative treatment gives the best result.
3.5.1. Conservative treatment
The use of the orthoses offered some improvement for the 48%
of the patients included in the study.
3.5.2. Inltrative treatment
We found 81% success rate for radio-frequency ablation versus
71% success rate for alcohol injections and 51% success rate for
corticosteroid injections.
3.5.3. Operative treatment
We found 88% success rate for neurectomy versus 94% success
rate for the decompression performing weighted averages. No
great difference was statistically revealed between dorsal or
plantar neurectomy (88% versus 89%). The success rate in the
2 studies on mini-invasive decompression surgery was 88%.
3.6. Secondary outcomes
The presence of complications or recurrences was not always
highlighted. In some studies, instead, these data were specied but
not properly described or enumerated. We grouped such data into
the column not available data, as shown in Tables 1 and 2.
3.6.1. Conservative treatment
The rate of complications was not available because only one
study was included, while the rate of recurrences was 47%.
3.6.2. Inltrative treatment
The most frequent complications after inltrative treatment were
haematoma and persistent pain, followed by temporary nerve
irritation, infection, severe pain and bruising at the injection site,
numbness. One case of allergic reaction to the injection was reported.
The global rate of complications was 3%, that is 5% for radio-
frequency ablation and 3% for alcohol injections. The complication
rate for corticosteroid inltrations was not available.
Symptoms recurred in 14% of patients, 23% after steroid
injection, 9% after radio-frequency and 12% after alcohol injections.
3.6.3. Operative treatment
The most common postoperative complications were wound
infections, followed by hypersensitive scars, keloids, complex
regional pain syndrome, persistent postoperative pain, numbness,
restriction of physical activities, asymptomatic oating toes, mild
stiffness of the metatarsophalangeal joints.
The global rate of postoperative complications was 21%, and
specically 25% for neurectomy, 6% for decompression (sectioning
of the deep transverse intermetatarsal ligament with/without
osteotomy of the metatarsal heads) and 7% for mini-invasive
decompression.
The whole rate of failures for both open and mini-invasive
resection and decompression procedures was 4%.
3.7. Risk of bias in the included studies
(Look at Table 3 for methodological appraisal).
3.7.1. Case series
The selection bias due to the dominant presence of case series
represented the more frequent type of bias in this systematic
review.
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org/10.1016/j.fas.2017.03.010
Regarding the attrition bias, we included only few studies in
which the over-estimation was not relevant for the general result
of the systematic review. For example two patients who missed the
follow-up were not included in the nal count.
The recall bias, typically common in the retrospective case
series, was mentioned only in one of the included studies. Despite
this, we suppose that this data is underestimated in the table of the
methodology quality, due to the difculty to detect it, unless the
authors themselves point out this risk.
3.7.2. Randomized controlled trials
The randomization was done, but the technique was not
properly described.
The concealment of allocation list was not specied in any of the
studies.
The analysis for protocol was done in few studies.
The report of patients withdrawal from the study was not
always available.
The outcome assessors blinding was done in two of the trials.
4. Discussion
4.1. Summary of the evidences
This review shows that operative and inltrative treatments
offer the best outcomes.
The comparison per study design highlights that surgery has
better outcomes than inltration.
The complication rate is higher with surgery, while the
recurrence rate is higher with both inltrative and conservative
treatments. These results look similar to those obtained by the Jain
et al. narrative review [2]. In that paper, just like in our study, the
authors highlighted the incomplete reporting of complications and
recurrences. Differently from us, the authors labelled with the
terms complications not only the proper complications, but also
cases of incorrect initial diagnosis, failure of non-operative
intervention, inadequate resection and stump neuroma. We prefer
to refer to these as failures. We deem important to make a clear
distinction between the two because of the different impact that
they have on the patients quality of life: while the majority of
complications can be resolved in a short time, failures require more
time to be diagnosed and may require an additional intervention.
For example, if post-surgical pain persists for many months, it
cannot be classied as complication anymore, but it could signal
a recurrence, or an incomplete, or missing MN resection.
Therapeutic algorithms available in literature recommend
starting with conservative and inltrative treatment and contem-
plating surgery only secondarily [2,10]. According to some authors
this also helps in selecting those patients who would benet from
surgery [10]. Others suggest that surgery should be chosen from
the beginning in patients with symptoms for at least 6 months
[34]. Nonetheless, data from these authors could be biased by
recall bias since their results are issued by retrospective studies.
Some authors have demonstrated that patients with symptoms for
more than a year do not necessarily benet from surgery [10]. This
could depend on the accuracy of diagnosis and it is vital to exclude
causes of persistent post-operative pain other than a recurrent MN
[36], and use MRI to check the neuromas location and size [30,35].
Diameters above 5 mm have been shown to fare better with
surgery [35], whereas those below 5 mm do better with inltration
enjoying relief of symptoms up to 6 months [30].
Although our revision has a limit in the inclusion of case series,
it is interesting to compare it to the Cochrane one [17]. This
included randomised and quasi-randomised controlled trials of
interventions which, after Consort [46], are now dened as
prospective or cohort studies and, as such, are not as strong as
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S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx 7

Table 3
Methodological appraisal: risk of bias in included studies.

Study and Study Appropr. Miscl. Inform. Select. bias Perform. Detect. bias Attrition bias Report. bias Statist.
year design study bias bias bias analysis
design
Conservative treatment
Kilkmartin RCT Yes Clinical Inclusion Type of randomization and No Not stated if Lost to follow All outcomes reported; for p
et al. diagn. exclusion sequence reported; blinding blinded up reported; protocol analysis (few
1994 criteria concealment of allocation of outcome per protocol withdrawals hence not
[27] state list n.s. patient/ assessors analysis relevant)
personnel
Low risk Low Low risk of Unclear risk of bias Low risk Unclear risk Unclear risk of High risk of bias
of bias risk of bias of bias of bias bias
bias

Study Study Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition bias Report. bias Statist.
and year design study bias analysis
design
Inltrative treatment
Chuter Retrosp. Yes clinical diagnosis Inclusion Probably none No withdrawals Outcome p
et al. case and MRI for some exclusion criteria consecutive coherently
2013 series pt stated series described
[41]
Low risk Low risk of bias Low risk of bias Low risk of bias Low Low risk of bias Low risk of
of bias risk of bias
bias
Magnan Retrosp. Yes clinical diagnosis, Inclusion Probably none No withdrawals Outcome None
et al. case X-ray and US exclusion criteria consecutive coherently
2005 series not stated series described
[42]
Low risk Low risk of bias Unclear risk of Low risk of bias Low Low risk of bias Low risk of
of bias bias risk of bias
bias
Moore Retrosp. Yes clinical diagnosis Inclusion Not specied if None No per protocol analysis Outcome None
et al. case exclusion criteria consecutive coherently
2012 series not stated series described
[25]
Low risk Low risk of bias Unclear risk of High risk of Low Low risk of bias Low risk of
of bias bias bias risk of bias
bias
Mozena Retrosp. Yes clinical diagnosis Inclusion Not specied if None No withdrawals Outcome p
et al. case exclusion criteria consecutive coherently
2007 series stated series described
[26]
Low risk Low risk of bias Low risk of bias High risk of Low Low risk of bias Low risk of
of bias bias risk of bias
bias
Musson Retrosp. Yes clinical diagnosis Inclusion Probably None Reasons for withdrawal stated; per Outcome None
et al. case and US exclusion criteria consecutive protocol analysis (few withdrawals, hence coherently
2012 series stated series not relevant) described
[32]
Low risk Low risk of bias Low risk of bias Low risk of bias Low Low risk of bias Low risk of
of bias risk of bias
bias
Pasquali Retrosp. Yes clinical diagnosis Inclusion Not specied if None Reasons for withdrawal not stated; no per Outcome p
et al. case and US exclusion criteria consecutive protocol analysis coherently
2015 series stated series described
[33]
Low risk Low risk of bias Low risk of bias High risk of Low Low risk of bias Low risk of
of bias bias risk of bias
bias

Study and Study design Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition bias Report. bias Statist. analysis
year study bias
design
Deniz Prospective Yes clinical Inclusion Not specied None No withdrawals Outcome p
et al. case series diagnosis and exclusion if coherently
2015 MRI for some criteria consecutive described
[43] pt stated series
Low risk Low risk of bias Low risk of High risk of Low Low risk of bias Low risk of
of bias bias bias risk of bias
bias
Fanucci Prospective Yes clinical Inclusion Probably None No withdrawals Outcome None
et al. case series diagnosis and exclusion consecutive coherently
2004 US criteria series described
[28] stated
Low risk Low risk of bias Low risk of Low risk of Low risk of bias Low risk of
of bias bias bias bias

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Table 3 (Continued)
Study and Study design Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition bias Report. bias Statist. analysis
year study bias
design
Low
risk of
bias
Hughes Prospective Yes Clinical Inclusion Probably None Reasons for withdrawal stated; per Outcome Kolmogorov
et al. case series diagnosis and exclusion consecutive protocol analysis (few withdrawals, coherently Smirnov test,
2007 US criteria series hence not relevant) described Wilcoxons signed
[29] stated rank
Low risk Low risk of bias Low risk of Low risk of Low Low risk of bias Low risk of
of bias bias bias risk of bias
bias
Makki Prospective Yes Clinical Inclusion Probably None Per protocol analysis (few Outcome Student t test
et al. comparative diagnosis and exclusion consecutive withdrawals, hence not relevant) coherently
2012 study US criteria series described
[30] stated
Low risk Low risk of bias Low risk of Low risk of Low Low risk of bias Low risk of
of bias bias bias risk of bias
bias
Markovic Prospective Yes Clinical Inclusion Probably None No withdrawals Outcome None
et al. case series diagnosis and exclusion consecutive coherently
2008 US criteria series described
[31] stated
Low risk Low risk of bias Low risk of Low risk of Low Low risk of bias Low risk of
of bias bias bias risk of bias
bias

Study and Study design Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition Report. bias Statist. analysis
year study bias bias
design
Surgical treatment
Akermark Retrospective Yes Clinical Inclusion Probably None Reasons for Outcome p, SD
et al. 2008 case series diagnosis exclusion consecutive withdrawal coherently
(Feb) [19] series
criteria stated stated described
Low risk Low risk of bias Low risk of bias
Low risk of Low risk Low risk of Low risk of
of bias bias of bias bias bias
Bauer et al. Retrospective Yes Clinical Inclusion Not specied None No Outcome p, univariate analysis, logistic
2015 [36] case series diagnosis and exclusion if withdrawal coherently regression
MRI for all pt criteria stated consecutive described
series
Low risk Low risk of bias Low risk of bias High risk of Low risk Low risk of Low risk of
of bias bias of bias bias bias
Biasca et al. Retrospective Yes Clinical Inclusion Probably None No Outcome Fishers exact test
1999 [35] case series diagnosis, X-ray exclusion consecutive withdrawal coherently
and MRI for all pt criteria stated series described
Low risk Low risk of bias Low risk of bias Low risk of Low risk Low risk of Low risk of
of bias bias of bias bias bias
Dereymaeker Retrospective Yes Clinical Inclusion Not specied None No Outcome None
et al. 1996 case series diagnosis exclusion if withdrawal coherently
[21] criteria not consecutive described
stated series
Low risk Low risk of bias Unclear risk of High risk of Low risk Low risk of Low risk of
of bias bias bias of bias bias bias
Faraj et al. Retrospective Yes Clinical Inclusion Not specied None No Outcome MannWhitney
2010 [37] case series diagnosis and X- exclusion if withdrawal coherently
ray criteria not consecutive described
stated series
Low risk Low risk of bias Unclear risk of High risk of Low risk Low risk of Low risk of
of bias bias bias of bias bias bias
Kasparek Retrospective Yes Clinical Inclusion Not specied None No Outcome p, SD
et al. 2013 case series diagnosis exclusion if withdrawal coherently
[22] criteria stated consecutive described
series
Low risk Low risk of bias Low risk of bias High risk of Low risk Low risk of Low risk of
of bias bias of bias bias bias
Lee et al. 2011 Retrospective Yes Clinical Inclusion Not specied None No Outcome Chi quadro
[12] case series diagnosis and US exclusion if withdrawal coherently
for some pt criteria not consecutive described
stated series
Low risk Low risk of bias Unclear risk of High risk of Low risk Low risk of Low risk of
of bias bias bias of bias bias bias
Pace et al. Retrospective Yes n.s. Inclusion Not specied Probably No Outcome None
2010 [38] case series exclusion if recall withdrawal coherently
criteria not consecutive bias described
stated series

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S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx 9

Table 3 (Continued)
Study and Study design Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition Report. bias Statist. analysis
year study bias bias
design
Low risk Unclear risk of Unclear risk of High risk of High risk Low risk of Low risk of
of bias bias bias bias of bias bias bias
Park et al. Retrospective Yes Clinical Inclusion Probably None No Outcome Wilcoxon signed-rank test,
2013 [39] comparative diagnosis and exclusion consecutive withdrawal coherently MannWhitney U test,
series MRI for all pt criteria stated series described multivariate linear regression
Low risk Low risk of bias Low risk of bias Low risk of Low risk Low risk of Low risk of
of bias bias of bias bias bias
Ruuskanen et. Retrospective Yes n.s. Inclusion Not specied None No Outcome Fishers exact test
al 1994 [13] case series exclusion if withdrawal coherently
criteria stated consecutive described
series
Low risk Unclear risk of Low risk of bias High risk of Low risk Low risk of Low risk of
of bias bias bias of bias bias bias
Vito et al. Retrospective Yes Clinical Inclusion Not specied None No Outcome None
2003 [24] case series diagnosis exclusion if withdrawal coherently
criteria not consecutive described
stated series
Low risk Low risk of bias Unclear risk of High risk of Low risk Low risk of Low risk of
of bias bias bias of bias bias bias

Study and Study Appropr. Miscl. bias Inform. bias Select. bias Recall Attrition bias Report. bias Statist.
year design study bias analysis
design
Akermark et. Prospective Yes Clinical diagnosis and Inclusionexclusion Not specied if None No withdrawal Outcome p, SD
al. 2008 case series X-ray for some pt criteria stated consecutive series coherently
[44] described
Low risk of Low risk of bias Low risk of bias High risk of bias Low risk Low risk of bias Low risk of bias
bias of bias
Barrett et al. Prospective Yes Clinical diagnosis Inclusionexclusion Not specied if None Reasons for Outcome None
1994 [20] case series criteria not stated consecutive series withdrawal not coherently
stated described
Low risk of Low risk of bias Unclear risk of bias High risk of bias Low risk Low risk of bias Low risk of bias
bias of bias
Nashi et al. Prospective Yes Clinical diagnosis Inclusionexclusion Not specied if None Unknown if Outcome None
1997 [23] case series criteria not stated consecutive series withdrawal coherently
described
Low risk of Low risk of bias Unclear risk of bias High risk of bias Low risk Unclear risk of Low risk of bias
bias of bias bias
Valente et al. Prospective Yes Clinical diagnosis and Inclusionexclusion Not specied if None No withdrawal Outcome None
2008 [40] case series X-ray criteria not stated consecutive series coherently
described
Low risk of Low risk of bias Unclear risk of bias High risk of bias Low risk Low risk of bias Low risk of bias
bias of bias

Study and Study Appropr. Miscl. bias Inform. Select. bias Perform. Detect. Attrition bias Report. Statist. analysis
year design study bias bias bias bias
design
Akermark RCT Yes clinical Inclusion Randomiza-tion No Blinding Reasons for withdrawal Outcome p, SD, MannWhitney U
et al. diagnosis, exclusion method blinding of of stated; no per protocol coherently test, chi-square test,
2013 X-ray and criteria explained; patients/ outcome analysis (except pt described Fishers exact test, sign
[45] MRI for all stated number of personnel, assessors satisfaction); pt test for ordered
pt participant in each except for switched from a group to categorical data and the
block n.s.; outcome the other not included in McNemar test for
concealment of assessor nal count nominal data
allocation list n.s.
Low risk Low risk Low risk Low risk of bias Low risk of Low risk Unclear risk of bias Low risk of
of bias of bias of bias bias of bias bias
Colgrove RCT Yes n.s. Inclusion Randomization No Blinding No per protocol analysis Outcome Wilcoxon Rank Sum
et al. exclusion method blinding of of coherently
2000 criteria explained; patients/ outcome described
[14] stated number of personnel, assessors
participant in each except for
block n.s.; outcome
concealment of assessor
allocation list n.s.
Low risk Unclear Low risk Low risk of bias Low risk of Low risk Low risk of bias Low risk of
of bias risk of bias of bias bias of bias bias

Appropr.: appropriate; detect.: detection; diagn.: diagnosis; inform.: information; miscl.: misclassication; n.s.: not stated; perform.: performance; report.: reporting;
retrosp.: retrospective; select.: selection; statist.: statistical.

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10 S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx
randomised controlled trials. Their inclusion criteria do not
contain a time limit for follow-up. We chose a length of at least
6 months, which is a limit but is still useful. This choice allowed us
to compare the three types of treatment and, although the possible
appearance of amputation neuromas after one year make it short,
all the studies on surgical treatment we included, except one, have
follow-ups well above one year. This allowed us not to underesti-
mate this complication. The Cochrane review evaluates three
studies, each dealing with a different type of treatment:
transposition and resection; supinatory and pronatory insoles;
neurectomy through dorsal and plantar incision. The authors
admit how difcult it is to draw conclusions and deem the
evidence as insufcient for evaluating the effectiveness of surgical
versus non-surgical treatments and highlight that controlled
randomised studies are necessary for this purpose. We would
add that it is vital to standardise outcome measures, which are too
varied at present.
4.2. Limitations of the studies
The studies about the MNs treatment share similar limitations
related to the risk of an overestimation of the results.
The clinical outcome is not described by using a standardized
system, but it is often dened with an empirical scale, instead of
the American Orthopaedics Foot and Ankle Society score (AOFAS)
or the Johnson scale.
Most of the available studies about MN are case series, for
which the researchers do not have the obligation to reduce the
selection bias. The inclusion and exclusion criteria, as well as the
diagnostic methods, are not always mentioned; consequently, the
population at study can potentially comprise not only patients
with Morton, but also patients with other types of metatarsalgia,
and this cannot be traced unless mentioned by the authors. Since
a wrong diagnosis, which could account for the treatment failure,
is often not mentioned by authors we decided not to exclude
studies in which very few patients (less than ve), compared to
the total sample, proved to be affected by a non-Morton
metatarsalgia.
Our systematic review has its main limitation in the inclusion of
only one paper about conservative therapy responding to our
inclusion and exclusion criteria. This is due to the paucity of such
studies, which tend to have a follow-up of one month.
A weighted average was performed in order to reduce the
inuence of the sample size of every study on the results of the
review. Nevertheless, the results of our systematic review may
have been inuenced by the number of the included studies.
5. Conclusions
This systematic review suggests that operative treatment leads
to better results, followed by inltrative treatment. The effective-
ness of conservative treatments seems less but the paucity of
adequate studies makes it hard to assess.
It is important to evaluate the risk/benet ratio through an
appropriate reporting of complications and failures for every
treatment, in order to decide if it is more suitable to begin
treatment with surgery or if its better to follow therapeutic
algorithms and begin with conservative and inltrative
treatment. Patients should be involved in the choice and
physicians should explain clearly the risk/benet ratio for every
treatment.
Further studies with high level of evidence, preferably RCTs, are
needed. It is also recommended that, in future, researches focus
their attentions on identifying the risk and prognosis factors, in
order to make the choice of the therapeutical approach less
empirical.
Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
Conict of interest
We conrm that this manuscript has not been published
elsewhere and is not under consideration by any other journal. All
of the authors agree with submission to Foot and Ankle Surgery. We
have no conict of interest to declare.
This research did not receive any specic grant from funding
agencies in the public, commercial, or not-for-prot sectors.
Acknowledgements
We thank Dr. Daniela Vecchio (University of Genoa) for
epidemiological consultation and Dr. Roberto Giovannini (Uni-
versity of Milan- Bicocca) for helping in data collection and
analysis.
References
[1] Wu KK. Mortons interdigital neuroma: a clinical review of its etiology,
treatment, and results. J Foot Ankle Surg 1996;35(2)1129 discussion 187-8.
[2] Jain S, Mannan K. The diagnosis and management of Mortons neuroma: a
literature review. Foot Ankle Spec 2013;6(4):30717, doi:http://dx.doi.org/
10.1177/1938640013493464.
[3] Latinovic R, Gulliford MC, Hughes RAC. Incidence of common compressive
neuropathies in primary care. J Neurol Neurosurg Psychiatry 2006;77(2):263
5, doi:http://dx.doi.org/10.1136/jnnp.2005.066696.
[4] Hassouna H, Singh D. Mortons metatarsalgia: pathogenesis, aetiology and
current management. Acta Orthop Belg 2005;71(6):64655.
[5] Bossley CJ, Cairney PC. The intermetatarsophalangeal bursaits signicance in
Mortons metatarsalgia. J Bone Joint Surg Br 1980;62-B(2):1847.
[6] Root ML, Orien WP, Weed JH. Normal and abnormal function of the foot, vol II.
Los Angeles, CA: Clinical Biomechanics Corp.; 1977.
[7] Gauthier G. Thomas Mortons disease: a nerve entrapment syndrome. A new
surgical technique. Clin Orthop Relat Res 1979;142:902.
[8] Nissen KI. Plantar digital neuritis; Mortons metatarsalgia. J Bone Joint Surg Br
1948;30B(1):8494.
[9] Genon MP, Chin TY, Bedi HS, Blackney MC. Radio-frequency ablation for the
treatment of Mortons neuroma. ANZ J Surg 2010;80(9):5835.
[10] Bennett GL, Graham CE, Mauldin DM. Mortons interdigital neuroma: a
comprehensive treatment protocol. Foot Ankle Int 1995;16(12):7603.
[11] Sofka CM, Adler RS, Ciavarra GA, Pavlov H. Ultrasound-guided interdigital
neuroma injections: short-term clinical outcomes after a single percutaneous
injectionpreliminary results. HSS J 2007;3(1):449, doi:http://dx.doi.org/
10.1007/s11420-006-9029-9.
[12] Lee KT, Kim JB, Young KW, Park YU, Kim JS, Jegal H. Long-term results of
neurectomy in the treatment of Mortons neuroma: more than 10 years
follow-up. Foot Ankle Spec 2011;4(6):34953, doi:http://dx.doi.org/10.1177/
1938640011428510.
[13] Ruuskanen MM, Niinimki T, Jalovaara P. Results of the surgical treatment of
Mortons neuralgia in 58 operated intermetatarsal spaces followed over 6 (2
12) years. Arch Orthop Trauma Surg 1994;113(2):7880.
[14] Colgrove RC, Huang EY, Barth AH, Greene MA. Interdigital neuroma:
intermuscular neuroma transposition compared with resection. Foot Ankle
Int 2000;21(3):20611.
[15] Johnson JE, Johnson KA, Unni KK. Persistent pain after excision of an
interdigital neuroma. Results of reoperation. J Bone Joint Surg Am 1988;70
(June (5)):6517.
[16] Hassouna H, Singh D, Taylor H, Johnson S. Ultrasound guided steroid injection
in the treatment of interdigital neuralgia. Acta Orthop Belg 2007;73(2):2249.
[17] Thomson CE, Gibson JN, Martin D. Interventions for the treatment of Mortons
neuroma. Cochrane Database Syst Rev 2004;3:CD003118, doi:http://dx.doi.
org/10.1002/14651858.CD003118.pub2.
[18] Higgins JPT, Green S. Cochrane handbook for systematic reviews of
interventions. Version 5.0.0. The Cochrane Collaboration; 2011.
[19] Akermark C, Crone H, Saartok T, Zuber Z. Plantar versus dorsal incision in the
treatment of primary intermetatarsal Mortons neuroma. Foot Ankle Int
2008;29(2):13641, doi:http://dx.doi.org/10.3113/FAI.2008.0136.
[20] Barrett SL, Pignetti TT. Endoscopic decompression for intermetatarsal nerve
entrapmentthe EDIN technique: preliminary study with cadaveric speci-
mens; early clinical results. J Foot Ankle Surg 1994;33(5):5038.
[21] Dereymaeker G, Schroven I, Steenwerckx A, Stuer P. Results of excision of the
interdigital nerve in the treatment of Mortons metatarsalgia. Acta Orthop Belg
1996;62(1):225.
[22] Kasparek M, Schneider W. Surgical treatment of Mortons neuroma: clinical
results after open excision. Int Orthop 2013;37(9):185761, doi:http://dx.doi.
org/10.1007/s00264-013-2002-6.
[23] Nashi M, Venkatachalam AK, Muddu BN. Surgery of Mortons neuroma: dorsal
or plantar approach? J R Coll Surg Edinb 1997;42:367.
[24] Vito GR, Talarico LM. A modied technique for Mortons neuroma:
decompression with relocation. J Am Podiatr Med Assoc 2003;93(3):1904.
G Model
FAS 1031 No. of Pages 11
S. Valisena et al. / Foot and Ankle Surgery xxx (2017) xxxxxx
[25] Moore JL, Rosen R, Cohen J, Rosen B. Radiofrequency thermoneurolysis for the
treatment of Mortons neuroma. J Foot Ankle Surg 2012;51(1):202, doi:http://
dx.doi.org/10.1053/j.jfas.2011.10.007.
[26] Mozena JD, Clifford JT. Efcacy of chemical neurolysis for the treatment of
interdigital nerve compression of the foot: a retrospective study. J Am Podiatr
Med Assoc 2007;97(3):2036.
[27] Kilmartin TE, Wallace WA. Effect of pronation and supination orthosis on
Mortons neuroma and lower extremity function. Foot Ankle Int 2016;15(May
(5)):25662.
[28] Fanucci E, Masala S, Fabiano S, Perugia D, Squillaci E, Varrucciu V, et al.
Treatment of intermetatarsal Mortons neuroma with alcohol injection under
US guide: 10-month follow-up. Eur Radiol 2004;14(3):5148.
[29] Hughes RJ, Ali K, Jones H, Kendall S, Connell DA. Treatment of Mortons
neuroma with alcohol injection under sonographic guidance: follow-up of
101 cases. AJR Am J Roentgenol 2007;188(6):15359.
[30] Makki D, Haddad BZ, Mahmood Z, Shahid MS, Pathak S, Garnham I. Efcacy of
corticosteroid injection versus size of plantar interdigital neuroma. Foot Ankle
Int 2012;33(9):7226, doi:http://dx.doi.org/10.3113/FAI.2012.0722.
[31] Markovic M, Crichton K, Read JW, Lam P, Slater HK. Effectiveness of ultrasound-
guided corticosteroid injection in the treatment of Mortons neuroma. Foot
Ankle Int 2008;29(5):4837, doi:http://dx.doi.org/10.3113/FAI.2008.0483.
[32] Musson RE, Sawhney JS, Lamb L, Wilkinson A, Obaid H. Ultrasound guided
alcohol ablation of Mortons neuroma. Foot Ankle Int 2012;33(3):196201.
[33] Pasquali C, Vulcano E, Novario R, Varotto D, Montoli C, Volpe A. Ultrasound-
guided alcohol injection for Mortons neuroma. Foot Ankle Int 2015;36(1):
559, doi:http://dx.doi.org/10.1177/1071100714551386.
[34] Gaynor R, Hake D, Spinner SM, Tomczak RL. A comparative analysis of
conservative versus surgical treatment of Mortons neuroma. J Am Podiatr
Med Assoc 1989;79(1):2730.
[35] Biasca N, Zanetti M, Zollinger H. Outcomes after partial neurectomy of
Mortons neuroma related to preoperative case histories, clinical ndings, and
ndings on magnetic resonance imaging scans. Foot Ankle Int 1999;20
(9):56875.
[36] Bauer T, Gaumetou E, Klouche S, Hardy P, Maffulli N. Metatarsalgia and
Mortons disease: comparison of outcomes between open procedure and
Please cite this article in press as: S. Valisena, et al., Treatment of Mortons neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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neurectomy versus percutaneous metatarsal osteotomies and ligament
release with a minimum of 2 years of follow-up. J Foot Ankle Surg 2015;54
(3):3737, doi:http://dx.doi.org/10.1053/j.jfas.2014.08.009.
[37] Faraj AA, Hosur A. The outcome after using two different approaches for
excision of Mortons neuroma. Chin Med J (Engl). 2010;123(16):21958.
[38] Pace A, Scammell B, Dhar S. The outcome of Mortons neurectomy in the
treatment of metatarsalgia. Int Orthop 2010;34(4):5115.
[39] Park EH, Kim YS, Lee HJ, Koh YG. Metatarsal shortening osteotomy for
decompression of Mortons neuroma. Foot Ankle Int 2013;34(12):165460,
doi:http://dx.doi.org/10.1177/1071100713499905.
[40] Valente M, Crucil M, Alecci V. Operative treatment of interdigital Mortons
neuroma. Chir Organi Mov 2008;92(1):3943, doi:http://dx.doi.org/10.1007/
s12306-008-0039-2.
[41] Chuter GS, Chua YP, Connell DA, Blackney MC. Ultrasound-guided radio-
frequency ablation in the management of interdigital (Mortons) neuroma.
Skeletal Radiol 2013;42(1):10711, doi:http://dx.doi.org/10.1007/s00256-012-
1527-x.
[42] Magnan B, Marangon A, Frigo A, Bartolozzi P. Local phenol injection in the
treatment of interdigital neuritis of the foot (Mortons neuroma). Chir Organi
Mov 2005;90(4):3717.
[43] Deniz S, Purtuloglu T, Tekindur S, Cansz KH, Yetim M, Klckaya O, et al.
Ultrasound-guided pulsed radio frequency treatment in Mortons neuroma. J
Am Podiatr Med Assoc 2015;105(4):3026, doi:http://dx.doi.org/10.7547/13-
128.1.
[44] Akermark C, Saartok T, Zuber Z. A prospective 2-year follow-up study of
plantar incision in the treatment of primary intermetatarsal neuromas
(Mortons neuroma). Foot and Ankle Surg 2008;14:6773.
[45] Akermark C, Crone H, Skoog A, Weidenhielm L. A prospective randomized
controlled trial of plantar versus dorsal incision for operative treatment of
primary Mortons neuroma. Foot and Ankle Int 2013;34(9):1198204.
[46] Moher D, Hopewell S, Schulz KF, Montori V, Gtzsche PC, Devereaux PJ, et al.
Consort 2010 explanation and elaboration: updated guidelines for reporting
parallel group randomised trials. BMJ 2010;340:c869.