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Mobility Concerns in Multiple Sclerosis—Studies and Surveys on US Patient Populations of Relevance to Nurses

Jong-mi Lee, Jeffrey Dunn
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Published Online: Oct 26th 2013 US Neurology, 2013;9(1):17–23 DOI: http://doi.org/10.17925/USN.2013.09.01.17
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1

Abstract

Overview

Despite significant advances in treatments and therapies for multiple sclerosis (MS) over the last two decades, there remains no effective
treatment that can definitively halt the progression of functional impairments in MS. Impaired mobility, walking in particular, has been observed
in early MS disease, and cross-sectional surveys according to MS clinical criteria have shown that approximately 50 % of existing patient
populations with MS require mobility support, such as wheelchairs or walking aids, some or all of the time. Loss of mobility is one of the most
disabling effects of MS, and adversely affects independence, employment, and quality of life. Additionally, as patients experience mobility
loss, their ability to perform activities of daily living (ADL) decreases and dependence on the assistance of others increases. The stress and
physical burden of caring for a friend or relative with MS may affect the health of caregivers and increase their own requirement for healthcare
resources. The identification of therapeutic options for improving impaired mobility and coping with disability represents an important aspect
of patient management. This review will discuss current published literature on mobility matters in MS, how they affect the patient, and how
they are measured and treated, with inclusion of the perspective of a MS nurse specialist.

Acknowledgments: Editorial assistance was provided by James Gilbart at Touch Medical Media.

Keywords

Multiple sclerosis, impaired mobility, assessment, therapeutic options for mobility, nurse practitioners, caregivers

2

Article

Multiple sclerosis (MS) is a chronic inflammatory-demyelinating disease caused by intermittent and recurrent episodes of multifocal inflammation in the central nervous system (CNS), which results in the demyelination and transection of axons in the brain, optic nerve, and spinal cord. This damage to the neuronal pathways affects signal conduction, causing neurologic disabilities, such as vision problems, difficulty walking, weakness, imbalance, sensory loss, pain, cognitive changes, spasticity, and bladder or bowel dysfunction.1 MS affects approximately 2.5 million people worldwide,2 with the majority of people diagnosed between the ages of 20 and 50.3 Women are more often affected by MS than men, and it is more prevalent in people of northern European descent than in those of other ancestries.3 In many people with MS, mobility is affected early in the disease, even when clinical measures of disability are minimally altered.4

Mobility is defined by the International Classification of Functioning, Disability, and Health (ICF) as “… moving by changing body position or location or by transferring from one place to another by carrying, moving, or manipulating objects, by walking, running or climbing, and by using various forms of transportation …” It has been estimated that 80 % of people with MS (as defined by a previous version of the McDonald diagnostic criteria of 2005)5 will experience impaired mobility to some degree, within 10–15 years of their initial diagnosis6 although this figure is decreasing with the widespread use of disease-modifying therapies (DMTs) that delay disability progression. Difficulty with walking is the primary factor contributing to loss of mobility in MS, is often the most visible sign of MS,7,8 and constitutes one of the most feared and disabling neuromuscular deficits associated with the disease.8–10 Walking impairment represents a particular concern of those living with this disease, as continued impairment increases physical inactivity in a positive feedback loop (see Figure 1). Loss of mobility in people with MS adversely affects independence, employment, and quality of life (QoL). In this article, we will examine mobility concerns in MS, discuss how they affect patients and their caregivers, and how they are measured and treated. Additionally, we will review the main experiences of mobility and walking concerns provided by a MS nurse practitioner and a neurologist, and briefly examine current and future improvements and developments in the management of people with MS that may reduce the impact of reduced mobility.

Impact of Impaired Mobility on People with Multiple Sclerosis and their Caregivers
Regardless of disability level or disease duration, maintaining mobility is ranked as one of the highest priorities among people with MS,8 and as the most concerning aspect of the disease.11 Impaired mobility is closely associated with low self-reported QoL in people with MS, and can profoundly affect the ability of individuals to live independently.12 In a recent study evaluating the prevalence, severity, and burden of walking and mobility problems (WMPs) in five European countries, WMPs were regarded as the most bothersome MS symptom by almost half of patients (43 %) of the 683 who responded.7 Multiple studies have reported a correlation between impaired mobility and reduced activities of daily living (ADL), reduced participation in life tasks and community, and decreased QoL.13–18

The impact of mobility impairment on daily life is substantial, with walking difficulties reported in 79 % of people with MS in the US.19 One longitudinal study estimated that by 15 years post MS diagnosis, there is an approximately 40 % probability of a patient with MS needing some type of walking aid and a 25 % probability of them needing a wheelchair.20 In this study the cohort was defined using the Poser criteria;21 using the more recently revised 2010 McDonald criteria,22 the numbers diagnosed would have been greater than the earlier diagnostic potential and applicability to wider populations of the later revisions. In a more recent survey of 703 community-dwelling, working-age adults with MS, 60.5 % were found to own at least one mobility aid, most commonly manual wheelchairs (38.4 %), followed by canes or crutches (35.7 %).23 People with MS often have difficulty continuing to work, and lost income due to loss of employment or early retirement is the largest single factor contributing to the economic cost of MS.24 In a recent survey involving 8,681 participants from 125 countries, fatigue (85 %) and mobility factors (72 %) were reported as the symptoms most detrimental to their ability to remain in work.25 The impact of impaired mobility on employment is marked,26 correlating with decreased instrumental ADL (IADL) scores, decreased employment, and decreased income. Moreover, an online survey of 1,011 people with MS found that only 34 % who had difficulty walking were employed.27

The Expanded Disability Status Scale (EDSS) is the primary disease-specific health measure for MS,28 and is heavily weighted toward mobility.29 EDSS scores of 4.0 (severe disability in one of the functional systems but able to walk more than 500 m without aid or rest) and 6.0 (ability to walk with stick, crutch, or other aid no more than 100 m without rest) represent the onset and progression of significant mobility limitations.30,31 A European study by Kobelt et al. found that, among patients with EDSS scores of 0–1.0, about 70–80 % of those aged 65 years or below were employed.24,32 For patients with EDSS scores of 4.0, employment varied between countries from 40–76 %; however, for patients with EDSS scores of 6.0, the proportion employed was much lower ranging from 17–44 %.24 Similarly, in a Canadian study of unemployment determinants among people with MS, participants who were unemployed had significantly more walking limitations than those in employment.33 Mobility limitations were frequently cited as the reason for unemployment in this study. As patients experience mobility loss, their ability to perform ADL decreases and dependence upon the assistance of others increases. Informal caregivers, such as family members, friends, or neighbors, often provide this necessary assistance.

A study of 302 caregivers of people with MS determined that assistance was most often provided for mobility-related activities.34 The stress and physical burden of caring for a friend or relative with MS may affect the health of caregivers and increase their own requirement for healthcare resources. Informal caregivers have been described as the ‘hidden patient’, due to the physical, emotional, psychologic, social, and economic burdens that are assumed in their role as caregiver.35 In one survey on the level of MS caregiver strain, 12 % of caregivers reported receiving treatment for depression.36 In another study, disease impact was found to be correlated with health problems in caregivers that affected both their physical and mental health status, including anxiety, depression, back pain, and insomnia.37 Caregivers of people with MS experience a substantial burden and reductions in QoL, but this is less well recognized or studied than the effects on the patient.38

In addition to the stress and physical burden felt by the caregivers of people with MS, there is also an economic cost to their role. The adverse effect of MS on the patient’s employment and the employment of others in the household invariably decreases the household’s income and standard of living through reductions in salary or loss of future earnings.12 The number of working days lost by caregivers is often similar to that lost by the MS patient. Kahn et al. found that 64.5 % of MS caregivers reported having to make work adjustments, such as taking time off.36 An Italian study found that 39.3 % of caregivers lost an average 7.8 working days during a 3-month period,39 and another found that female gender and advanced age were the main predictors of lower QoL in caregivers.40 A more recent study in the US reported that 53 % of caregivers lost an average 7.3 work days in last year.41

Impaired Mobility Assessment Tools
There is increasing recognition of the importance of walking limitations in the lives of people with MS. Measuring mobility limitations in people with MS is essential to enable evaluation of disability and disease progression. Moreover, such measurements can provide valuable information on the efficacy of disease-modifying drugs, symptomatic agents, and rehabilitation strategies in people with MS. A variety of scales has been used for the measurement of mobility, ambulation, walking, and gait in MS. These include clinical rating scales, performance and physiologic markers, and alterations in spatial and temporal gait parameters. The EDSS is the gold standard for the measurement of MS disease severity, and although it is weighted toward ambulation at and above a score of 4.0, it is only marginally useful for measuring changes in mobility.42 Table 1 offers a summary of the mobility assessment tools used to characterize mobility impairment in people with MS. The Hauser Ambulation Index (HAI),43 similar to the EDSS, has a high reliability and is effective in classifying patients based on their current walking ability; however, it demonstrates a low responsiveness to change, making it of limited use for measuring changes in mobility. Other clinical rating scales include the Functional Independence Measure (FIM) (an 18-item scale of physical and cognitive disability)44 and the Barthel Index (a 10-component scale that measures ADL, widely used to assess disabilities caused by neurologic disease, especially stroke).45 The FIM showed no superiority over the Barthel Index in people with MS undergoing neurorehabilitation,46 and although the FIM is a reliable and valid tool, like the EDSS and AI, it exhibits low responsiveness to change.

The Dynamic Gain Index (DGI) relies on an observer’s rating of the patient’s limitations while performing specific tasks, and measures walking, stair climbing, and balance.47 Although it has demonstrated good reliability and has been found to inversely correlate with timed walk tests, the major limitation of this assessment is that a trained evaluator must run the test. Similarly, the Rivermead Visual Gait Assessment (RVGA), while providing qualitative information on the walking ability of a patient, is time consuming, has complex scoring, and must be performed by a clinician with experience in gait analysis.48

The self-reported 12-item MS walking (MSWS-12) scale was specifically developed to measure walking ability in MS,49 and has since been adapted into a generic measure of walking and mobility, renamed the Walk-12.50 The MSWS-12 is a patient-rated measure of walking, and contains 12 questions with Likert-type responses. It has been demonstrated to be more responsive than the Timed 25-Foot Walk (T25FW) test,49 and multiple studies have confirmed the validity of the MSWS-12 as a measure of the impact of MS on walking.49,51,52

Timed walk tests are objective, quantitative measures of walking, and many have the advantage of requiring minimum time and space.42 In general, shorter timed walking tests, such as the T25FW, the 10 m timed walk (10MTW), and the 30 m timed walk (30MTW), assess the patient’s overall walking disability. Longer-distance walking tests, such as the 6-minute walk (6MW), the 2-minute walk (2MW), and the 100 m timed walk (100MTW) are better at assessing fatigue during walking, and limitations in walking distance. The T25FW, which measures the time taken for the patient to walk 25 feet, has shown good reliability and reproducibility in multiple studies, has been extensively validated, and is often used as a standard for evaluating other walking and mobility assessments.53 The 6MW measures the maximum distance that a patient can walk in 6 minutes, is reproducible,54 and has been shown to correlate well with other disability measures.53 The 6MW requires more space than other timed walked tests and is more a measure of walking endurance than walking speed. An alternative to the 6MW is the 2MW test (measuring the maximum distance that a patient can walk in 2 minutes), which has reduced patient burden, especially for those with high levels of fatigue.55 Other timed mobility tests include the Timed Up and Go Test (TUGT),56 and Six Spot Step Test (SSST).57 The TUGT is easy to administer and measures the time taken for a patient to rise from a chair, walk 3 m, turn around, walk back to the chair, and sit down. The TUGT has been demonstrated to correlate with motor, cognitive, and behavioral functioning in relapsing-remitting MS.58 The SSST measures lower-extremity function more than the other walking tests, and also measures coordination and balance.57 In this test, the patient is asked to walk between cylindrical blocks placed on the floor in a set pattern; each cylinder is stood in marked circle. As the patient walks, he or she is required to kick the block out of each circle with a specified foot until all the cylinders have been knocked over. Patients repeat the process four times (twice using each foot).

While timed tests can measure changes in walking speed, they are unable to measure differences in gait pattern. The RVGA assesses gait pattern but, as mentioned previously, requires a clinician with experience in gait analysis. A recent study assessed the biomechanical characteristics of gait among people with MS with varying degrees of severity using kinetic and kinematic analysis (KKA)59 and there is increasing interest in these types of measures for assessing mobility in people with MS. Motion analysis systems can provide a 3D assessment of gait kinetics and kinematics; however, they require large amounts of space, analysis is time consuming, and the equipment needed has a high cost.42 The GAITrite® (Sparta NJ, US) electronic pathway appears to be a promising tool for gait analysis has been demonstrated to identify mobility impairment in people with MS with a relatively short disease duration.60 Recently, accelerometry has been recognized as a tool for the assessment of real-life walking ability in people with MS,61 and similarly pedometry can also be used outside of the clinic to measure changes in patient mobility.

In summary, there are many measurement tools for mobility impairment in MS; however, they have varying degrees of responsiveness to change, ease of use, and cost. The T25FW and the MSWS-12 are both feasible for use in clinical practice, while also displaying satisfactory reliability and responsiveness.42 The T25FW is the best characterized measure of mobility in people with MS, and it was recently proposed that the T25FW and the 2MW test be used as standards for measuring walking capacity in MS.62

Therapeutic Options for Treating Mobility in Multiple Sclerosis
One therapeutic option for treating mobility in people with MS is exercise and physical therapy. People with MS often have decreased physical activity, leading to physical deconditioning, which may in turn influence the start and progression of mobility impairment (see Figure 1).63–65 Decreased physical activity leads to reduced aerobic capacity, balance, and muscle strength, which feeds back to further reduce physical activity (stage 1 of Figure 1).63 At some point in this feedback loop a threshold is met, resulting in an impact on the patient’s mobility (stage 2 of Figure 1). Evidence from several studies indicates that exercise and physical therapy may have a beneficial effect on mobility, while also improving fitness, muscle strength, fatigue, mood, and QoL.63,65–69 A meta-analysis examining the overall effect of exercise on QoL in people with MS, found that exercise training is associated with a small but statistically significant improvement in QoL.66 Furthermore, a Cochrane systematic review concluded that exercise therapy can be beneficial for people with MS in terms of isometric strength, physical fitness, and mobility-related ADL.67 A recent pilot study examined changes in walking function in people with MS following aerobic, resistance, and balance-related exercise training, and improved walking mobility following exercise training was demonstrated, as determined by improvements in MSWS-12 score, T26FW, and TUGT.70 Further research is needed to fully determine the effects of exercise on mobility in people with MS. Although this field of study is not sufficiently developed, the preliminary evidence is promising.

Impaired walking in MS can be considered a disease-specific disability resulting from the conduction blockade that is a consequence of axonal demyelination. While current immunomodulatory therapies for MS slow disease progression and reduce relapse rates in clinically isolated syndrome and remitting forms of MS,71–73 immunomodulatory treatments do not necessarily provide any improvement in mobility. Approximately 50 % of people with MS report no improvement in mobility following DMT.13,74 Current medications that target mobility impairment in people with MS include US Food and Drug Administration (FDA)-approved dalfampridine extended-release (dalfampridine-ER) tablets, known as sustained-, prolonged-, or modified-release fampridine outside the US. Dalfampridine is not an immunomodulatory treatment, but it can be used in combination with DMTs, and specifically targets walking impairment.

Dalfampridine, a broad-spectrum inhibitor of potassium channels, is believed to exert its effects by binding to potassium channels in the cellular membranes of CNS nerve fibers, particularly in the areas of demyelination.75 The blockade of potassium channels has been shown to increase conduction in demyelinated nerve fibers.76 Dalfampridine improves action potential propagation by binding to the open potassium channel transmembrane pore region, which delays repolarization of the nerve cell, and in turn increases the duration of the action potential.10,76

Dalfampridine-ER has been demonstrated to improve walking in people with MS.77,78 Two phase III trials assessing the effects of dalfampridine on walking in people with MS demonstrated that dalfampridine has a positive effect on walking speed.79,80 In both studies, the primary outcome was percentage of T25FW responders, defined as patients who had a consistent improvement in T25FW speed relative to baseline. A 2009 phase III randomized trial of dalfampridine-ER 10 mg twice daily compared with placebo, found that 35 % of patients in the intent-to-treat (ITT) population (n=224) were responders to dalfampridine-ER, whereas 8% of patients taking placebo demonstrated T25FW improvement.80 Additionally, walking speed in dalfampridine responders increased by 25.2 % from baseline, and leg strength (as measured by the lower extremity manual muscle test [LEMMT]) was also significantly increased in this group compared with placebo (0.18 versus 0.04 [p=0.0002]). In a second randomized double-blind phase III trial, 42.9 % responded to dalfampridine compared with 9.3 % of those in the placebo group. The average improvement in walking speed in the dalfampridine-responder group was 24.7 % from baseline.79 Dalfampridine is generally well tolerated and most adverse events are mild.77,81

Mobility-related Assistive Technology
When mobility deficits do not respond to other interventions, mobility-related assistive technology (MAT) may be helpful. Despite best treatment efforts, assistance with walking will eventually be required by 75–80 % of all people with MS (with relapsing-remitting or primary progressive MS).31 The use of MAT can greatly improve ADL and the independence of people with MS.82 Common MATs used by people with MS are summarized in Table 2.

A survey of 703 self-reporting working-age adults with MS reported significant mobility problems, including an increased level of concentration required to walk and difficulty in standing.19 The same survey indicated that 60.5 % of patients required a mobility aid, with manual wheelchairs the most common,19 and that patients often alternated between mobility aids to suit their specific mobility requirements. Several studies have found that manual wheelchairs are the most common MATs utilized by people with MS.9,83,84 Caution should be used when prescribing MATs because if the device does not fit the patient’s needs it is often abandoned. A retrospective study found that MAT devices were abandoned in people with MS for several main reasons: worsening in physical status (36.4 %), nonacceptance by the user (30.3 %), inappropriateness (24.2 %), and insufficient/lack of information and training given to the patient (9.0 %).83 To be adopted successfully, the MAT must increase QoL in people with MS.6 The challenge for rehabilitation specialists is to find an appropriate device that meets the user’s needs, such as level of fatigue, degree of mobility impairment, and the activities they wish to participate in. Successful adoption of MAT devices involves a high level of communication between the patient, the rehabilitation team, family members, and caregivers.

Experiences with Mobility from a Multiple Sclerosis Nurse Practitioner and a Neurologist
The Stanford Multiple Sclerosis Center sees approximately 800 people with MS each year. It is a specialty clinic within the larger neurosciences clinic and therefore often sees patients for second and third opinions on diagnosis and treatment of MS. Of this population seen each year, more than 75 % complain of some difficulty with walking. Among patients in this population who have difficulty with walking, more than 90 % have resorted to using a walking aid. The walking aid serves the purpose of maintaining safety through assistance, but is inadequate in serving the patient’s need for independence and efficacy. The center proactively treats the disease course with DMTs to hopefully reduce relapses and further delay disease progression. But, as has been seen, patients will continue to progress in disability over time.

In combination with DMTs, the Stanford Multiple Sclerosis Center team looks for patient-specific complementary approaches to treat the symptoms of MS. Patients with a walking impairment also struggle with symptoms that can worsen their gait. Fatigue is one of the most common symptoms and, combined with walking impairment, is a significant disabling feature in the patient population. The Stanford Multiple Sclerosis Center providers consider various agents to address fatigue including antidepressants, stimulants, and other complementary therapies. In addition, the importance of body conditioning, exercise, stretching, and stress reduction is emphasized to help with symptoms. Dalfampridine-ER is frequently prescribed to help with walking impairment and the patient response has paralleled that observed in clinical trials. In anecdotal reports, those patients who benefit from dalfampridine-ER have remarked that their QoL has substantially improved with its use, which they were unable to perceive with the use of walking aids.

A patient’s perception of wellness is complicated by not only their neurologic status, but also by their physical appearance and emotional tolerance to their disability. In general, patients appear to have a harder time accepting the use of a walking aid rather than a medication that can potentially help their walking outcome. Given this, the patient’s perceived sense of wellness is improved by reduced dependence on walking aids. Nevertheless, the nature of this disorder will evolve into disability progression. Addressing the concerns of walking impairment and MS symptoms early has helped provide better patient outcomes in the longterm management of MS. In the future, the Stanford Multiple Sclerosis Center team hopes to see additional treatments and mobility assistance become available to help patients function and live independently.

Conclusions
Loss of mobility is among the most disabling effects of MS, and it adversely affects independence, employment, and QoL. As mobility decreases, informal caregivers such as family members, friends, and neighbors provide an important role in assisting with mobility-related activities. Physical, emotional, psychologic, social, and economic burdens, however, are often a consequence of their caregiving role. Measuring mobility limitations in people with MS is essential to enable evaluation of disability and disease progression, and can provide valuable information on the efficacy of disease-modifying drugs, symptomatic agents, and rehabilitation strategies in people with MS. Current treatments that target walking impairment in MS include dalfampridine-ER which has been demonstrated in clinical trials and in regular clinical use to have beneficial effects on walking in people with MS. Other approaches involve physical therapy and exercise. If walking impairments do not respond to therapeutic interventions, MAT may be helpful. To be adopted successfully, the MAT must increase the QoL in people with MS, and must involve a high level of communication between the patient, the rehabilitation team and family members and caregivers.

2

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Article Information

Disclosure

Jong-Mi Lee, NP, has served on nursing advisory boards for Biogen Idec, Teva Neuroscience, and Genzyme. Jeffrey Dunn, MD, has a patent pending for a biomarker to predict treatment response in multiple sclerosis (MS). He has received grant support for clinical research from the Accelerated Cure Project, Genzyme, Roche/Genentech, and Actelion. He has served on scientific advisory boards for Biogen Idec, Teva Neuroscience, and Genzyme. He has received honoraria from the National MS Society and from PRIME® Continuing Medical Education.

Correspondence

Jeffrey Dunn, MD, Stanford Multiple Sclerosis Center, Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA 94305-5235, US. E: jeffdunn@stanford.edu

Support

The publication of this article was funded by Acorda. The views and opinions expressed are those of the authors and not necessarily those of Acorda.

Received

2013-05-31T00:00:00

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