Significant progress has been made in quantifying gait impairment in patients with multiple sclerosis, but clinician-friendly assessment techniques that are sensitive to mild levels of impairment are needed to facilitate early intervention and in turn improve patient outcomes.
By Douglas A. Wajda and Jacob J. Sosnoff, PhD
Multiple sclerosis (MS) is a chronic, potentially disabling neurologic disease common among adults in the US and worldwide.1 It has a heterogeneous prevalence, with higher prevalence in central and Northern Europe, North America, and Australia than in Asia, Africa, and South America.2 An estimated 450,000 persons in the US suffer from multiple sclerosis, with 2.2 million persons affected worldwide. The majority of people with MS are diagnosed between ages 20 and 50 years, and women are affected two to three times more often than men.3 The exact cause of MS is not clear, but it is believed to result from a combination of genetic and environmental factors.
MS involves intermittent bursts of focal inflammation in the central nervous system (CNS).4 The inflammatory process results in the demyelination and transection of axons throughout the CNS. The resulting damage leads to conduction delay and conduction block of electrical potentials along axons.5 This interference with neuronal conduction throughout the CNS is associated with a heterogeneous array of functional impairments and symptoms, including muscle weakness, cognitive impairment, sensory disturbances, and dysfunction in postural control and gait.1
Gait dysfunction represents one of the most debilitating symptoms experienced by persons with MS. Indeed, approximately 85% of individuals with MS report gait impairment as a major limitation in their daily lives.6 Additionally, gait function is predominately perceived as the most important bodily function domain by both those who have had MS for shorter (less than five years) and longer (more than 15 years) periods of time.7
Researchers believe gait impairment in MS is multifaceted. For instance, it has been linked to physiological functions such as leg strength,8,9 spasticity,10,11 aerobic capacity,8 and fatigue,12 and there is also growing evidence that even cognitive functioning is related to gait impairment.13-15
Gait impairment also factors greatly into the tracking and classification of the disease. The Expanded Disability Status Scale (EDSS) is the most common clinical standard for categorizing the disability level of persons with MS.16 Although the overall score is impacted by functioning in eight neurological domains, it relies heavily on the patient’s ability to walk and the need for assistive devices. Scores are given in a range from 0 to 10, where 0 represents no impairment and 10 represents death. Intermediate scores 4 and 6 relate to the onset of walking impairment and the use of a unilateral assistive device, respectively.
Apart from the clinical aspects of gait impairment, a large amount of research is dedicated to determining the relationships between gait impairment and activities of daily living. LaRocca reported that a majority of individuals with walking difficulty also indicated significant activity restrictions (about 80%), effects on emotional health (70%), and increased concerns about falling and other safety issues when moving around (70%).6 Other investigations have used wearable sensors to examine community ambulation, finding that decreases in activity and real-life walking were associated with higher levels of disability.17 Another possible impact of gait impairment in MS on daily life is its association with the risk of falling.18-20
Gait assessment in MS
Given the importance of gait impairment, assessment of gait is a prime topic of scientific inquiry within the MS research community. Gait analysis in MS represents a broad spectrum of techniques ranging from self-report to clinical assessments and the utilization of advanced measurement equipment. No one protocol, however, is considered the most effective for characterization of gait dysfunction.21 This lack of consensus is due to the range of settings and specificity of outcomes that have been used for clinical and research-based gait monitoring. This varied approach to assessment makes it critical to consider testing conditions and instructions when assessing the meaningful outcomes of a test and when extrapolating results across groups and interventions.22,23
Perhaps the simplest form of gait assessment involves patient-reported measures, or self-reports. These surveys are important as they give the patient’s own perspective on the impact of gait impairment on their lives. The most common of these self-reports in MS is the Multiple Sclerosis Walking scale 12 (MSWS-12). This 12-question survey assesses gait impairment in terms of perceived impacts on speed, distance, and activities of daily living. The MSWS-12 has been validated as a measure of walking function and as responsive to gait changes.24,25 Advantages of self-report measures are that they are easy to administer and relatively low in cost. Disadvantages of self-reports include the possibility that patients will prioritize specific aspects or symptoms of gait impairment and that their mood and emotional state may be potential influences during self-rating.24
To date, a large amount of gait-related research in MS has focused on timed performance tests as clinical measures of gait, a focus that reflects the low-cost and minimal equipment and training required for such tests.22,26 Common examples are the timed 25-foot walk, 2-minute walk, and 6-minute walk tests.
An advantage of timed performance tests is that they index different aspects of gait related to the varied distances and instructions employed. For instance, the timed 25-foot walk tests involves participants walking “as quickly, but safely” as possible, giving an indication of maximal walking velocity.27 By comparison, the instructions of the 6-minute walk ask participants to cover as much ground as possible in that time period, giving researchers an estimate of walking capacity and motor fatigue.28
In studies examining MS patients and healthy controls performing the timed 25-foot walk, the MS group had times ranging from 2.9 to 20.7 seconds, while times for the healthy controls ranged from 2.8 to 5.2 seconds. Overall, MS patients were slower than healthy controls, and the difference in performance was greatest in those with the highest amount of clinical disability.29 Investigations utilizing the 6-minute walk test displayed similar differences, specifically reduced walking distance in those with MS compared with matched controls. Multiple studies have shown this difference, as well as a comparable effect of disability level in the MS group.28,30
There is an ongoing debate within the MS rehabilitation community concerning the most clinically relevant performance measures.22,26 Arguments for the utilization of various performance tests focus on sensitivity to disability and underlying physiological mechanisms.31 Irrespective of these discussions, it appears that performance on a given test is tightly coupled with performance on other performance tests.22,32
Despite the low cost, minimal time, and simplicity of these clinical measures, drawbacks do exist. Noninstrumented performance tests do not capture gait differences between healthy individuals without MS and those with MS who have fairly mild impairment.26,33-35 This lack of sensitivity to mild gait impairment can lead to delays in intervention and gait rehabilitation.36
It’s possible to use advanced measurement tools of gait to gain a more in-depth analysis of spatiotemporal gait parameters in persons with MS. These techniques include body-worn inertial sensors, instrumented walkways, and motion-capture systems. Commonly, these methods are employed to determine stride-specific changes to gait parameters rather simply providing averaged values.37 Multiple studies using these measurement tools have shown differences between those with MS and healthy controls with regard to velocity, cadence, step length, step time, and duration of the gait cycle spent in double support, and that these impairments scale with disability level.36-40
Moreover, these technologies are also capable of detecting differences in spatiotemporal gait parameters between persons with MS who have mild impairment and healthy controls.36,38-40 This early detection of gait changes is an advantage in terms of providing early intervention.
Furthermore, advanced measurement techniques allow for quantification of gait variability, or the slight fluctuations in spatiotemporal parameters that occur throughout the duration of a walk. These slight variations are characterized using standard deviations and coefficients of variation of kinematic and spatiotemporal gait parameters.41-43 Multiple reports have shown significant differences in gait variability for persons with MS compared with healthy controls with regard to gait parameters including increased step time variability, step length variability, and single support time variability.33,44 Similar to other measures, gait variability has also been shown to scale with disability level.45 Moreover, variability-based metrics are more sensitive to fall status than traditional spatiotemporal parameters, and recurrent fallers have more gait variability than nonfallers.46
Like the previously described clinical tests, these more advanced procedures also have disadvantages. Potential issues relate to equipment costs, the need for dedicated laboratory space, and the time associated with processing of advanced walking data. Another limitation of these lab-based measures is that they do not assess walking in real-life settings. Several novel techniques have been employed in an attempt to quantify walking in real-life behavior, using accelerometers or similar activity monitors to assess ambulation in the community.47 Research has shown that real-world ambulation corresponds to lab-based measures of gait, walking impairment, and overall clinical disability.17,48,49 Ultimately, however, further research is needed to identify tests that have greater sensitivity to mild gait impairment but are simple enough to be performed in the clinical setting.
Currently the main rehabilitation options for gait impairment in MS consist of pharmacological treatment of symptoms and physical rehabilitation. The main goal of the pharmaceutical agents is to target specific symptoms that influence gait. For instance, it is well known that spasticity adversely impacts gait and can be managed with medications. Recently, pharmaceuticals that target nerve conduction have been approved for use in persons with MS. Fampridine, for example, acts to improve nerve conduction and has been shown to improve walking speed in some individuals with MS.50 There are downsides to these pharmacological tools, including adverse side effects and cost.
Prior to the introduction of pharmaceutical options, physical therapy and regimented exercise were the only effective means of restoring function in persons with MS.51 Indeed, exercise training has been proven to help mitigate and restore some of the declines in walking function associated with the progressing disability observed in MS.
One meta-analysis looking at the effects of exercise training on gait impairment in MS examined results from 22 previously published studies and found a small but positive effect of exercise on walking mobility.52 Additionally, this exercise effect was found to be approximately the same size as effects seen for medications acting on disease progression in MS, lending to its overall importance.
While this positive effect of exercise on walking function has been shown in general for a range of disability levels in MS, future analysis should consider examining its effects on individuals in the early stages of the disease. Previous trials of disease-modifying drugs have highlighted the importance of early intervention for slowing disease progression and thus it could be hypothesized that this same approach should be investigated with regard to gait impairment.52 Furthermore, research using advanced motion analysis techniques has shown that changes in the kinematics of gait do exist in the absence of any clinical disability in persons with MS.39 These early gait changes further highlight the importance of understanding the possible beneficial effects of gait therapies in those persons with MS showing minimal walking impairment.
Despite the vast amount of research that has been carried out quantifying gait impairment in MS, there is considerably more that can be done. As previously cited, there is a significant need for the development of tests that are low cost and clinically feasible, yet sensitive to mild impairment. These tests would allow for earlier detection of gait impairments and the possibility of early treatment, whether pharmaceutical, exercised-based, or educational. Moreover, continued research developing and testing interventional methods related to the distinct aspects of gait impairment in MS also represents a valuable topic area.
Gait impairment is one of the most prevalent symptoms of MS. In addition, gait is commonly perceived as the most important bodily function by those with MS, and gait impairment can have significant effects on everyday living. Measurement techniques vary from simplistic timed measures to those using advanced analysis tools and metrics. Continued understanding and investigation of gait impairment in MS can have a profound impact in this population.
Douglas A. Wajda is a doctoral student and Jacob J. Sosnoff, PhD, is an associate professor in the Department of Kinesiology and Community Health at the University of Illinois at Urbana-Champaign.
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