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Research on lower extremity health in patients with multiple sclerosis: a systematic scoping review



Multiple sclerosis (MS) often affects ambulation and the function of the lower limbs. However, little is known about how much research has been conducted on lower extremity health in patients with MS.


To analyse empirical studies and their evidence on lower extremity health in patients with MS, in order to identify the need for future studies in key areas.


A systematic scoping review was conducted. A literature search of Medline (PubMed), CINAHL (EBSCO) and the Cochrane Library databases was performed. The search covered the period up to 15 January 2020 from the earliest records available. This led to the inclusion of 42 empirical articles. The data were analysed using content analysis and quantification techniques.


The research on lower extremity health focused primarily on two main areas: gait and lower extremity muscle strength. Lower extremity health was assessed using a variety of methods, most of which consisted of objective physical tests and gait analysis. Patients with MS had many problems with the health of their lower extremities, which manifested in walking difficulties, balance problems, muscle weaknesses and spasticity. In the feet, pes cavus, claw toes, oedema and altered foot sensation were common.


MS affects lower limb and foot health, and these problems can affect patients’ daily lives. However, the extent of these problems is poorly understood, partly due to the dearth of research on lower limb and foot health. Therefore, further research is warranted in order to better understand the impact of MS on foot and lower limb health in everyday life.

Peer Review reports


Multiple sclerosis (MS) is an immune-mediated disease with a wide variation in its clinical course. Most patients with MS are initially diagnosed with a relapsing-remitting form of the illness, and the progression usually begins at around 40 years of age [1]. It is estimated that in 2016, there were more than 2.2 million prevalent cases of MS worldwide [2]. The highest estimates on prevalence per 100,000 people were for North America (167) and Western Europe (127) [2]. In a recent Finnish registry study, the mean age of patients with a new diagnosis of MS was 37.0 years (range: 15–69) and the female/male ratio was 2.6 [3].

Spasticity and weakness in the lower extremities are among the most common signs and symptoms of MS. As such, the validated Expanded Disability Status Scale (EDSS), [4] the most commonly used rating scale for disability in MS, is heavily based on the motor function of the lower limbs. Ambulatory impairment related to MS is a major factor in reducing patients’ quality of life and their ability to perform daily activities. Approximately 75% of patients with MS have limitations with walking [5] and balance [6,7,8]. Using prospective measures, fall rates of 56% have been reported in a recent meta-analysis of 537 individuals, with 37% of the study population falling recurrently [9]. Moreover fear of falling is associated with recurrent falls in patients with MS [10] thus impacting mobility and independent living. Also external factors like poorly fitting footwear increases risk for falls in patients with MS [11].

Investigations into the functional ability of patients with MS have focused on walking, postural control [7,8,9, 12] and gait abnormalities [13, 14]. Interventions including physical exercise, orthotic therapy and electrical stimulation have been shown to decrease the risk of falls, [15,16,17] although the evidence regarding the effects of these interventions is sparse and uncertain [18]. However, the majority of the research seems to focus on the musculoskeletal system as a whole, rather than the lower extremities in particular. In this review, ‘lower extremity health’ refers to the structure and functions of the lower extremities from the hips to the toes.

With regard to the lower extremities, muscle strength, optimal alignment of the joints, and foot and ankle stability form the basis for safe walking and motion [19]. However, despite the importance of lower extremity health, many persons have foot problems. In the general population, foot pain, [20, 21] hallux valgus, [22, 23] flat foot [24] and skin and nail problems [25] are the most common issues. Lower extremity health and the related problems have been considered in many patient groups with long-term health conditions such as diabetes, [26, 27] rheumatoid arthritis [28] and lupus [29]. For example, patients living with diabetes have an increased risk of developing foot problems such as neuropathic ulcers [30]; therefore, the number of foot problems in diabetic patients is higher than in the general population [31].

However, there seems to be a paucity of existing reviews examining foot problems in patients with MS.

Foot problems can add to a patient’s level of disability by causing changes in the structure and function of the body. Functional loss in the hips, knees, ankles or feet significantly increase the risk of falls, especially in older people [32]. Toe deformities, such as hallux valgus, hammer toe and claw toes, reduce the area used for balance in the sole of the foot, increasing postural sway and risk of falls [32, 33] and decreasing gait velocity [34]. In addition, reduced medial arch height and forefoot disorders (such as splay foot) change the kinematics and muscle activation of the foot, leading to altered gait patterns [35, 36]. Prolonged foot pain is also a strong risk factor for falls [37] and is associated with functional limitation, resulting in challenges conducting activities of daily living [38]. Among patients with MS, foot drop symptom where dorsiflexion of the ankle joint is reduced during gait is common [39]. Foot drop leads to poor foot clearance during gait and significantly elevates the risk of trips and falls [39]. Overall, foot problems negatively impact daily life and reduce quality of life [20, 40].

Although it is understood that MS causes ambulatory impairment, little is known about lower extremity health of those living with the disease. Investigations into lower extremity health will create opportunities to develop interventions that support functional ability. The research on lower extremity health among patients with MS seems to be fragmented, however, and a thorough synthesis of the research evidence is lacking. Therefore, a systematic scoping review was conducted in order to identify the potential size and scope of the available research evidence on lower extremity health in patients with MS.


The aim of this review was to analyse empirical studies and their evidence on lower extremity health in patients with MS, in order to identify the need for future studies in key areas.

The following research questions were formulated:

  1. 1)

    What is the focus of lower extremity health research in patients with MS?

  2. 2)

    What methods have been used to study lower extremity health in patients with MS?

  3. 3)

    What are the main lower extremity problems in patients with MS?


A systematic scoping review [41] was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews [42] was used to outline this review. The review followed predetermined, unpublished, protocol.

Literature search

A literature search was performed in three international scientific databases – Medline (PubMed) and CINAHL (EBSCO) – and the Cochrane Library. The search covered the period between 15 January 2020 and the earliest records available: from 1966 for Medline/PubMed, from 1988 for CINAHL and from 1992 for the Cochrane Library. Medical Subject Headings (MeSH terms, in Medline and Cochrane Library) and Major Headings (in CINAHL) were used to identify studies focusing on MS. Multiple search terms were used in order to cover the topic of lower extremity health as widely as possible. The final search sentence was as follows: Multiple sclerosis[MeSH] AND (foot OR feet OR “lower extremity” OR “lower extremities” OR “lower leg” OR “lower legs” OR “lower limb” OR “lower limbs”) AND (health OR problem* OR disorder* OR complaint* OR deformit* OR disabilit* OR condition*). The search was limited to title and abstract levels and to studies published in English. The literature search produced a total of 446 hits (n = 387/Medline, n = 56/CINAHL, n = 3/Cochrane).

Study retrieval process

The studies were assessed against predetermined eligibility criteria (Table 1). The study retrieval process was carried out by two researchers (A-ML, MS) in two phases (Fig. 1). First, the titles and abstracts of the studies were screened against the inclusion and exclusion criteria. The researchers worked independently and discussed their choices before the next phase. In the case of a disagreement, this was discussed and a consensus was achieved within the research team. In total, 328 studies were excluded because they did not focus on lower extremity health or they were instrument-development or instrument-validation studies. The remaining 73 studies were included in the second phase, which entailed a full inspection of the text. After careful reading of the full texts and achieving a consensus, 31 studies were excluded. This resulted in 42 studies being included in the review and the final analysis.

Table 1 Eligibility criteria
Fig. 1

Data extraction flowchart

Data extraction and analysis

For the data extraction, detailed information from the studies were collected and entered on a data extraction spreadsheet. The information consisted of the following: author names, year of publication, country of origin, study aim, study setting, study design, methods of data collection and analysis, participants (sample size, mean age), and main results. The data were analysed using content analysis and quantification. The original expressions in the studies were used, which removed the need for any interpretation.

Critical appraisal of individual sources of evidence

Critical appraisal of included studies was performed using the Mixed Methods Appraisal Tool (MMAT) [43] by two authors (MS, A-ML). The MMAT is applicable for empirical studies using different research designs namely qualitative research, randomized controlled trials, non-randomized studies, quantitative descriptive studies, and mixed methods studies. Each study was evaluated against five items focusing on methodological quality of the study with response scale yes/no/can’t tell.


Description of the studies

The studies were published between 1978 and 2019, predominantly in the 2010s (n = 32). They were published in the United States (n = 15), Italy (n = 5), Australia (n = 2), Denmark (n = 2), Israel (n = 2), Romania (n = 2), Switzerland (n = 2), Turkey (n = 2) and the United Kingdom (UK) (n = 2). In each of the following countries, one study was published: Belgium, Brazil, Finland, France, Greece, Qatar and Spain. In addition, one study [44] included participants from five countries: France, Germany, Italy, Spain and the UK. The number of participants in each study ranged from 8 to 2171 (mean 97, median 29, SD 335). Only four of the studies included more than 100 subjects. All of the participants were patients who had been diagnosed with MS, and more information about the participants was provided in some of the studies, such as the stage of MS (relapsing-remitting or progressive) or their level on the EDSS (e.g., 2.5–5.5 or 4.0–6.0). Most of the studies used some sort of intervention design (n = 16) (such as randomized controlled trials, clinical trials or pretest-posttest studies) or cross-sectional design (n = 13). In 15 of the studies, no information was provided about the study design.

Based on critical appraisal the methodological quality of studies was acceptable. Studies with randomized controlled trial designs fulfilled all five criteria in three studies and seven studies met four criteria. In non-randomized studies one study fulfilled all five criteria and seven studies four criteria. For quantitative descriptive studies four studies met all five criteria, sixteen studies met four and three studies met three criteria.

The focus of lower extremity health research in patients with MS

The research on lower extremity health focused primarily on two main areas: gait and lower extremity muscle strength (Table 2). The topics within the area of gait included walking endurance, gait parameters, foot placement during walking, balance and falls. The research on lower extremity muscle strength concentrated on analysing the muscle performance and capacity of the lower extremities during exercise or resistance training. There were single studies focusing on foot sensation, [50] foot vibration perception, [50, 60] neuropathic foot pain, [60] foot deformities, [75] lower limb oedema [80] and foot sudomotor function [60].

Table 2 Summary of the studies (n = 42) included on the review in the alphabetical order

Methods used to study lower extremity health in patients with MS

Lower extremity health was assessed using several different methods, most of which consisted of objective physical tests and gait analysis (Table 3). Mobility was assessed by conducting validated performance tests, such as a timed up-and-go test (n = 9), a timed 25-ft walk (n = 14) or a 500-m walk (n = 1). Aerobic capacity and endurance were measured with a 6-min walk test (n = 8) or a one-legged cycling test (n = 1). Gait was assessed from the perspective of gait biomechanics conducted using 3D or visual gait analysis methods. The gait analysis focused on walking speed (n = 15) including pelvic and hip kinematics, step width and walking velocity. Gait ability was assessed using a 2-min walk test (n = 5), a 10-m walk (n = 2), a stair climb test (n = 2) and Bessou’s locometer (n = 1), or by using the patient-reported Multiple Sclerosis Walking Scale (n = 6).

Table 3 Methods of assessing lower extremity health in patients with MS

Lower extremity muscle strength was assessed using clinical strength tests (Table 3). These included isokinetic (n = 3) or isometric (n = 9) dynamometry measures and the sit-to-stand test (n = 1). Three studies used a dynamometer to assess muscle strength without specifying the measurement focus. Muscle endurance was assessed by counting the repetitions conducted during a 3-min stepping test (n = 1) or on a seated leg-press machine. Muscle stiffness and spasticity were assessed using validated instruments, such as the Ashworth Scale (n = 3). Tests focusing on tendon reflexes, passive and dynamic range of motion in ankle and knee joints and resistance were also used to test muscle spasticity.

Balance was assessed using clinical tests and instruments (Table 3). Dynamic and static balance were measured with stabilometry and posturography (n = 4). Obstacle negotiation was used to measure balance in obstacle-crossing (n = 1). Postural control was measured by timing the duration of standing on one leg (n = 1). The centre of pressure in the sole of the foot was analysed in order to detect changes in plantar pressure (n = 2). The Activities-specific Balance Confidence Scale (n = 3) and the Berg Balance Scale (n = 4) were used as objective measures of balance problems in daily life.

Specific foot assessments (Table 3) focused on vibration perception in the sole of the foot (n = 3), foot biomechanics (n = 2), plantar pressure (n = 2), neuropathic pain (n = 1), sudomotor function (n = 1), oedema (n = 1), foot sensation (n = 1) and foot deformities (n = 1).

Lower extremity problems in patients with MS

There were many lower extremity health problems in patients with MS (Table 4). Their lower extremities had undergone many biomechanical changes, which could be seen as a functional discrepancy of the load on the lower limbs and walking asymmetry [78].

Table 4 Lower extremity health problems in patients with MS

Changes lower extremity biomechanics and muscle strength caused lower extremity problems which were affecting gait in many ways [48, 54, 56]. The lower extremity problems caused walking difficulties which were seen in the length of the step or the walking speed [44, 47, 48, 54, 73]. Walking and mobility problems and a limited range of motion in the lower limb joints were the most bothersome symptoms in patients with MS [44]. Perceived fatigue shortened the walking distance, [63, 67] and obesity was linked to a slower walking speed with shorter step lengths in patients with MS [58]. The altered lower extremity mechanics in these patients reflected a strength deficit compared with healthy controls during walking [56]. Patients with MS had increased coactivation in the knee and ankle muscles during the single or double support phases of the gait. This increased coactivation of muscles was associated with impaired postural stability and was a compensatory mechanism, where a patient with MS tried to walk as safely as possible [46]. Impaired postural balance resulted in decreased maximal walking performance and walking speed [48, 54].

Spasticity in the lower extremities was common (Table 4), [75] resulting in reduced balance [81] and creating an altered gait pattern characterised by reduced speed, rhythm, stride length and swing phase and increased double support time [68]. Muscle weaknesses in the lower limbs was prevalent in patients with MS and resulted in a slower sitting-to-standing time [47] and reduced balance [51]. Thus, reduced balance was related to slower walking velocity [54]. In the foot and ankle, pes cavus, claw toes, ankle equinus [75] and lower extremity oedema were prevalent [80]. Neuropathic pain and sudomotor dysfunction and elevated vibration perception of the feet were also common and associating with neurological disability caused by MS [60].

Some interventions aimed to support lower extremity health in patients with MS. Most of the intervention studies (n = 12) were focused on improving lower extremity muscle strength, [52, 53, 64, 83] walking, [53, 55, 65, 69, 70, 74, 76, 77, 83] balance, [51, 52] mobility [52] or kinematics in the lower extremities [76]. The interventions varied from various physical training methods to foot orthoses. Eight week progressive lower body resistance training significantly improved leg extensor power, [52] knee extension, plantarflexion and stepping performance, [83] and it also had positive effects on walking ability [55]. Supervised muscle power training for the knee extensors lasting 12 weeks improved peak muscle power and maximal voluntary isometric contraction of the knee extensors [64]. Physical activity program for 24 weeks consisting of aerobic and strength training resulted improvements is gait stride length, speed and cadence [65] and muscle endurance [69]. Aerobic training improved the passive range of movement in the hips, but it had only a minimal effect on gait abnormalities [76]. Virtual reality treadmill training for 6 weeks improved balance, walking endurance and gait kinematics [70]. Mixed evidence was found for the effects of foot orthoses [45, 72, 74] and whole-body vibration [49, 57] as interventions. Ankle-foot orthoses and functional electrical stimulation improved walking speed in patients with MS with foot drop [74]. Whereas dynamic foot orthoses increased body sway and changed the centre of pressure position [72]. Powered ankle-foot orthosis did not improve walking endurance of patients with MS [45].


Research on lower extremity health in patients with MS is an important and necessary aspect of rehabilitation research. This review highlights the importance of future research on the topic. On the basis of the results, it is evident that lower extremity research among patients with MS has focused strongly on gait and lower extremity muscle strength. Little emphasis has been placed on foot or ankle problems. It is understandable that the focus has been on lower extremity strength, as maintaining the ability to move is important for functional ability. However, sometimes relatively small changes in foot or ankle biomechanics and in foot health can affect walking ability; thus, more attention on this is needed in future.

The research methods applied in the studies were varied. Performance assessments were undertaken with validated and widely used methods such as timed 25-Foot Walk and 6-Minute Walk Test. The methods were strongly focusing on objective assessment of lower extremity health. Patients’ subjective perspective to lower extremity health was rarely under investigation. The use of qualitative methods such as interviews or written diaries could provide useful information about patients’ experiences of living with MS and lower extremity problems including how they manage in daily life in terms of walking, foot self-care and footwear which all are important while maintaining or promoting lower extremities. In addition, the use of information technology, such as active wristbands, could produce detailed follow-up information about level of physical activity and this information could be analysed against lower extremity health status.

The design of the research reviewed was traditional and in line with the research methods. Future studies could focus on more versatile research designs. Follow-up studies with many measurement points could provide evidence of how lower extremity health, specifically foot health, alters over time or in relation to MS disease activity. In addition, observational studies could provide important information how patients with MS care for their feet. With this kind of information, targeted interventions could be developed and tested in order to support patients with MS during the trajectory of the disease.

Many patients with MS have problems with the lower extremities of which the most widespread problems relate to reduced lower limb muscle strength, impaired balance and walking dysfunction. Moreover, pes cavus, claw toes, oedema and altered foot sensation were common. All these problems have a direct effect on quality of life [85]; thus, it is important to study them. In future, the use of wearable technology [86] or other new technologies could provide a new way to assess walking ability, balance and muscle strength in patients’ actual everyday circumstances. This kind of information could be used as the basis for future interventions and technological innovations.

One important aspect of lower extremity health is foot self-care, but there is limited evidence of how patients with MS manage this. Therefore, it is important to identify potential gaps in foot care knowledge and habits among patients with MS, which could be done by using, for example, information technology for communication. Moreover, the hindering and promoting factors for lower extremity health, including foot health, should be investigated in order to help develop interventions that support foot self-care.

Future research needs to investigate the foot problems experienced by patients with MS. There is limited evidence of foot health in patients with MS as only one study identified in this review focused directly on foot health revealing pes cavus and claw toes common in patients with MS [75]. The particular study focused only foot structural deformities omitting for example skin and nail problems and foot pain. Therefore in order to gain a full picture of foot health status in patients with MS a large scale foot health assessment studies are needed. Changes in foot and ankle biomechanics or muscle strength in the foot can alter gait [66] and decrease functional ability. More specifically, changes in foot biomechanics can cause changes in the skin, such as corns and calluses, which, because they may be painful, can lead to altered foot biomechanics increasing tissue stress and thus impacting on gait [87]. Therefore, a systematic and thorough foot and lower extremity assessment is needed to conduct with methods combining the assessment of mechanically-based pathologies in the skin, tissue stress and foot, ankle and lower extremity biomechanics.

Assessment of foot problems and timely provided care is important in patients with MS. If foot problems are left uncared they can have long-term consequences on a person’s overall health. To support identification of foot problems, there is a need to develop a systematic assessment framework for evaluating the impact of MS on the lower limbs and feet. This information could then be used in both clinical and research contexts. The impact of assessing foot problems, and the resulting foot-health interventions, needs to be evaluated in the clinical and research contexts. Patients with MS could benefit from an intervention study where the effectiveness of professional foot care and individual foot self-care outcomes are assessed in order to improve foot health.

Strengths and limitations

This review has some strengths and limitations that must be considered when interpreting the results. The literature search was conducted in the Medline (PubMed), CINAHL and Cochrane Library databases. Both of these databases are scientific, international and widely used, and their coverage of research in the field of health sciences is comprehensive [88]. The literature search was conducted using a combination of MeSH terms (in Medline) and Major Headings (in CINAHL) related to MS and keywords related to lower extremity health. The use of MeSH or Major Headings was considered appropriate because MS is a universally agreed term and there is no synonym for the disease. On the other hand, several synonyms were used for lower extremity health in order to ensure a comprehensive approach to the topic. Despite the careful search term planning, some terms might have been missed; thus, the coverage of the review could have been limited. However, the search produced more than 400 hits, the vast majority of which focused on MS.

The major limitation of this review relates to the analysis of the studies that were included. The studies were heterogeneous and were conducted using different study designs. The variation in the research methods and the results posed challenges for the analysis. Instead of searching for in-depth information about lower extremity health in patients with MS, a decision to remain at the general descriptive level was made within the research team. This decision was in line with the general definition of systematic scoping reviews, which usually focus on identifying the potential size and scope of the available research literature [89]. Moreover, the heterogeneous nature and methodological diversity of the studies restricted the possibility to conduct meta-analysis. In future, a review focusing on studies with similar designs could be conducted in order to advance in-depth knowledge of lower extremity health in patients with MS. Despite these limitations, this review produced a summary and evidence of current research and demonstrated the need for further research.


This systematic scoping review revealed that MS affects lower limb and foot health in ways that have the potential to affect patients’ daily life. However, the extent of these problems is unclear, and this is in due to a dearth of research that focuses on lower limb and foot health in this patient group. It is important to identify foot problems at an early stage to facilitate the provision of appropriate interventions in a timely manner. It is evident that there needs to be more focus on foot problems, both in the clinical environment and in the context of research.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.



The Cumulative Index of Nursing and Allied Health Literature


Expanded Disability Status Scale


Medical Subject Headings


Multiple sclerosis


The Preferred Reporting Items for Systematic Reviews and Meta-Analyses


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MS designed the study. MS and A-ML collected and analysed the data. MS A-ML drafted the article. JR and HL-K critically revised the article for important intellectual content. All authors read and approved the final version of the manuscript.

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Correspondence to Minna Stolt.

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Stolt, M., Laitinen, AM., Ruutiainen, J. et al. Research on lower extremity health in patients with multiple sclerosis: a systematic scoping review. J Foot Ankle Res 13, 54 (2020).

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  • Multiple sclerosis
  • Lower extremity
  • Research
  • Review