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Foot and Ankle Surgery: Silvia Valisena, MD, Gianfranco John Petri, MD, Andrea Ferrero, MD
Foot and Ankle Surgery: Silvia Valisena, MD, Gianfranco John Petri, MD, Andrea Ferrero, MD
Review
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 Morton’s neuroma (MN) can be operative, conservative and infiltrative. Our
Received 13 December 2016 aim was the evaluation of evidence on outcomes with different types of conservative, infiltrative 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
Morton’s 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
Infiltrative operative treatment.
Conservative Conclusions: The evaluated case series and few RCTs showed better results with invasive treatment. More
and better RCTs which evaluate risk-benefit ratio are required to confirm 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. Infiltrative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5.3. Operative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6. Secondary outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.1. Conservative treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.2. Infiltrative 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
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 Morton’s neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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FAS 1031 No. of Pages 11
1. Introduction 2. Methods
Morton’s neuroma (MN) is a degenerative neuropathy featuring 2.1. Criteria for considering studies for this review
fibrosis of the common interdigital nerve [1]. It is a common
pathology mainly affecting middle age women, although there is Studies were identified 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], inflammatory 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
infiltrations and then surgery, if the previous steps fail, according PROSPERO by combining “Morton’s neuroma”, “neuroma”, “sur-
to the therapeutical algorithm available in literature [2,9,10]. gery”, “infiltrative”, “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, infiltrative and operative treatments in patients with
The infiltrative 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 Morton’s (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 confirmed bursitis [16]. Many studies on primary
define 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 Morton’s neuroma treatment. Primary outcome on the basis of publication date or status.
defines 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 Johnson’s 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 infiltrative treatment have a mean follow-up
to 6 months, in case of infiltrations 6–12 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 defines 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 defined 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
first, 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 Morton’s neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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FAS 1031 No. of Pages 11
Please cite this article in press as: S. Valisena, et al., Treatment of Morton’s neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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FAS 1031 No. of Pages 11
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. (24–60) Open
2008 (Feb) [19] series
Plantar group: 69 29 (24–46) Nerve resection-plantar incision 68/73 4/69 0
Dorsal group: 56 37 (24–60) Nerve resection-dorsal incision 52/59 10/56 3/56
Bauer et al. 2015 Retrospective case Open: 26 24 (24–84) 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 (8–21) 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 (14–71) (+ adapted shoes/inner soles)
Faraj et al. 2010 Retrospective case 36 18 (13–54) 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 (120–240) (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 (120–146)
Pace et al. Retrospective case 78 54 (9–96) Open: neurectomy-dorsal incision 76/78 18/78 8/78
2010 [38] series
Park et al. 2013 Retrospective 84 n.s. (n.s.) Open: decompression–dorsal
[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) (24,7–27,7)
Osteotomy+ 26,3 Metatarsal shortening osteotomy and 40/40 2/40 0
release: 40 (No of (23,6–29) DTML release (Group B)
Morton)
Ruuskanen et al. Retrospective case 45 72 Open: neurectomy-dorsal incision 47/58 0 5/45
1994 [13] series (24–144)
Vito et al. 2003 Retrospective case 78 n.s. Open: Decompression with 78/82 n.a. 4/82
[24] series (n.s–128) relocation-dorsal incision
Akermark et al.. Prospective case 55 29 (24–46) Open: Nerve resection-plantar 55/59 3/55 0
2008 [44] series incision
Barrett et al. 1994 Prospective case 17 6 (9–12) 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 (6–72) Open: neurectomy-dorsal incision 17/25 n.a. 0
2008 [40] series
Akermark et al. RCT 76 34 (28–42) Open
2013 [45]
Plantar group: 35 34 (28–39) Nerve resection-plantar incision 32/35 5/35 n.a.
Dorsal group: 41 33 (28–42) Nerve resection-dorsal incision 38/41 6/41 2/41
Colgrove et al. RCT 44 n.s. (1–48) 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
Infiltrative 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 (24–55) 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 Morton’s neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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FAS 1031 No. of Pages 11
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 (3–36) Radiofrequency 26/29 1/29 2/29
[25] series thermoneurolysis
Mozena et al. Retrospective case 42 11 (2–24) Alcohol injection 30/49 3/42 12/42
2007 [26] series
Musson et al. Retrospective case 75 14,3 (6–26) 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 (7–15) 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 (13–34) 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 Morton’s 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 3–12 months, or infiltra-
studies with protocol analysis. tive therapy, with 1–3 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 benefit 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.
infiltrative [41–45] and 17 about operative treatment [37–40].
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 infiltrative treatment); 9 prospective case series
technique performed via plantar or dorsal approach, while the
(4 about operative and 5 about infiltrative 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 infiltrative 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 infiltrations 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 infiltrative [25,26] and one about conservative Study type Satisfaction Complication rate Failure rate
treatment [27]. In 6 other studies, all concerning infiltrative 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 finding [28–32].
Infiltrative 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.
Please cite this article in press as: S. Valisena, et al., Treatment of Morton’s neuroma: A systematic review, Foot Ankle Surg (2017), http://dx.doi.
org/10.1016/j.fas.2017.03.010
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FAS 1031 No. of Pages 11
3.5. Primary outcomes Regarding the attrition bias, we included only few studies in
which the over-estimation was not relevant for the general result
The most successful treatments were the operative ones with of the systematic review. For example two patients who missed the
89% success rate and the infiltrative ones with 85%. In Table 2 we follow-up were not included in the final count.
highlighted that operative treatment gives the best result. The recall bias, typically common in the retrospective case
series, was mentioned only in one of the included studies. Despite
3.5.1. Conservative treatment this, we suppose that this data is underestimated in the table of the
The use of the orthoses offered some improvement for the 48% methodology quality, due to the difficulty to detect it, unless the
of the patients included in the study. authors themselves point out this risk.
The presence of complications or recurrences was not always This review shows that operative and infiltrative treatments
highlighted. In some studies, instead, these data were specified but offer the best outcomes.
not properly described or enumerated. We grouped such data into The comparison per study design highlights that surgery has
the column “not available data”, as shown in Tables 1 and 2. better outcomes than infiltration.
The complication rate is higher with surgery, while the
3.6.1. Conservative treatment recurrence rate is higher with both infiltrative and conservative
The rate of complications was not available because only one treatments. These results look similar to those obtained by the Jain
study was included, while the rate of recurrences was 47%. et al. narrative review [2]. In that paper, just like in our study, the
authors highlighted the incomplete reporting of complications and
3.6.2. Infiltrative treatment recurrences. Differently from us, the authors labelled with the
The most frequent complications after infiltrative treatment were terms “complications” not only the proper complications, but also
haematoma and persistent pain, followed by temporary nerve cases of incorrect initial diagnosis, failure of non-operative
irritation, infection, severe pain and bruising at the injection site, intervention, inadequate resection and stump neuroma. We prefer
numbness. One case of allergic reaction to the injection was reported. to refer to these as “failures”. We deem important to make a clear
The global rate of complications was 3%, that is 5% for radio- distinction between the two because of the different impact that
frequency ablation and 3% for alcohol injections. The complication they have on the patients’ quality of life: while the majority of
rate for corticosteroid infiltrations was not available. complications can be resolved in a short time, failures require more
Symptoms recurred in 14% of patients, 23% after steroid time to be diagnosed and may require an additional intervention.
injection, 9% after radio-frequency and 12% after alcohol injections. For example, if post-surgical pain persists for many months, it
cannot be classified as “complication” anymore, but it could signal
3.6.3. Operative treatment a recurrence, or an incomplete, or missing MN resection.
The most common postoperative complications were wound Therapeutic algorithms available in literature recommend
infections, followed by hypersensitive scars, keloids, complex starting with conservative and infiltrative treatment and contem-
regional pain syndrome, persistent postoperative pain, numbness, plating surgery only secondarily [2,10]. According to some authors
restriction of physical activities, asymptomatic floating toes, mild this also helps in selecting those patients who would benefit from
stiffness of the metatarsophalangeal joints. surgery [10]. Others suggest that surgery should be chosen from
The global rate of postoperative complications was 21%, and the beginning in patients with symptoms for at least 6 months
specifically 25% for neurectomy, 6% for decompression (sectioning [34]. Nonetheless, data from these authors could be biased by
of the deep transverse intermetatarsal ligament with/without recall bias since their results are issued by retrospective studies.
osteotomy of the metatarsal heads) and 7% for mini-invasive Some authors have demonstrated that patients with symptoms for
decompression. more than a year do not necessarily benefit from surgery [10]. This
The whole rate of failures for both open and mini-invasive could depend on the accuracy of diagnosis and it is vital to exclude
resection and decompression procedures was 4%. causes of persistent post-operative pain other than a recurrent MN
[36], and use MRI to check the neuroma’s location and size [30,35].
3.7. Risk of bias in the included studies Diameters above 5 mm have been shown to fare better with
surgery [35], whereas those below 5 mm do better with infiltration
(Look at Table 3 for methodological appraisal). enjoying relief of symptoms up to 6 months [30].
Although our revision has a limit in the inclusion of case series,
3.7.1. Case series it is interesting to compare it to the Cochrane one [17]. This
The selection bias due to the dominant presence of case series included randomised and quasi-randomised controlled trials of
represented the more frequent type of bias in this systematic interventions which, after Consort [46], are now defined as
review. prospective or cohort studies and, as such, are not as strong as
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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
Infiltrative 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 specified 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 specified 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 specified 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 specified 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 Wilcoxon’s 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 specified 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 Fisher’s 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 specified 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 specified None No Outcome Mann–Whitney
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 specified 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 specified 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 specified Probably No Outcome None
2010 [38] case series exclusion if recall withdrawal coherently
criteria not consecutive bias described
stated series
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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 Mann–Whitney 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 specified None No Outcome Fisher’s 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 specified 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 Inclusion–exclusion Not specified 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 Inclusion–exclusion Not specified 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 Inclusion–exclusion Not specified 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 Inclusion–exclusion Not specified 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, Mann–Whitney 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 Fisher’s 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 final 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.: misclassification; n.s.: not stated; perform.: performance; report.: reporting;
retrosp.: retrospective; select.: selection; statist.: statistical.
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org/10.1016/j.fas.2017.03.010