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Effects of Intermittent Versus Continuous Walking on Distance Walked and Fatigue in Persons With Multiple Sclerosis

A Randomized Crossover Trial

Karpatkin, Herb PT, DSc, NCS, MSCS; Cohen, Evan T. PT, MA, PhD, NCS; Rzetelny, Adam PhD; Parrott, J. Scott PhD; Breismeister, Breanne DPT; Hartman, Ryan DPT, C/NDT; Luu, Ronald DPT; Napolione, Danielle DPT

Journal of Neurologic Physical Therapy: July 2015 - Volume 39 - Issue 3 - p 172–178
doi: 10.1097/NPT.0000000000000091
Research Articles
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Background and Purpose: Fatigue is a common, disabling symptom experienced by persons with multiple sclerosis (MS). Evidence shows that intermittent exercise is associated in improved performance and negligible fatigue. The purpose of this study was to examine whether subjects with MS walk greater distances with less fatigue under intermittent (INT) or continuous (CONT) walking condition.

Methods: Twenty-seven subjects with MS (median Extended Disability Severity Scale 3.5, interquartile range 1.6) walked in the CONT (ie, 6 uninterrupted minutes) and INT (ie, three 2-minute walking bouts) conditions in a randomized crossover. Distance was measured for the entire 6-minute walking period and each 2-minute increment. Fatigue was measured as the difference in a visual analog scale of fatigue (ΔVAS-F) immediately preceding and following each trial.

Results: Participants walked greater distances in the INT condition compared to the CONT condition (P = 0.005). There was a significant interaction of walking condition and time (P < 0.001), indicating that the distances walked in the INT condition changed across time. ΔVAS-F was significantly lower in the INT condition than in the CONT condition (P = 0.036).

Discussion and Conclusion: Subjects with MS walked farther, and with less fatigue, when walking intermittently rather than continuously. Persons with MS may be able to tolerate a greater dose of walking training if the walking bouts are intermittent. Further study to determine the benefits of a walking exercise program using intermittent walking is recommended.

Video Abstract available for additional insights from the authors (Supplemental Digital Content 1,

Department of Physical Therapy, Hunter College, New York, New York (H.K.); Department of Rehabilitation and Movement Sciences—Doctor of Physical Therapy Program-South, Rutgers, The State University of New Jersey, Stratford (E.T.C.); Department of Psychology, Southern Illinois University at Carbondale (A.R.); Department of Interdisciplinary Studies, Rutgers, The State University of New Jersey, Newark (J.S.P.); Lutheran Medical Center, New York (B.B.); Texas Children's Hospital, Houston (R.H.); Union Square Rehabilitation and Sports Medicine, New York (R.L.); and Children's Rehabilitation Center, White Plains, New York (D.N.).

Correspondence: Evan T. Cohen, PT, MA, PhD, NCS, Department of Rehabilitation and Movement Sciences—Doctor of Physical Therapy Program-South, Rutgers, The State University of New Jersey, Stratford, NJ 08084 (

This manuscript reflects work previously presented at the 2012 Combined Sections Meeting of the American Physical Therapy Association.

None of the authors has any conflicts of interest to disclose pertaining to this research study.

This research study was not supported by any external funding sources.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

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Fatigue is the most common disabling symptom experienced by people with multiple sclerosis (MS)1 and may be so disabling that it interferes with activities of daily living (ADL).2Fatigue can be defined as “(t)he awareness of a decreased capacity for physical and/or mental activity due to an imbalance in the availability, utilization, and/or restoration of resources needed to perform activity.”3(p46) People with MS benefit from rehabilitation exercise programs; however, fatigue may limit their ability to engage in physical activity of sufficient dosing to achieve these benefits.4 An exercise program designed to limit the effects of fatigue could enable people with MS to exercise for a longer cumulative duration and with increased frequency. These gains may allow them to achieve higher levels of physical functioning and ADL.

Fatigue in MS is multifactorial and has negative consequences. Fatigue comes on easily, prevents sustained physical functioning, is worsened by heat, prevents fulfillment of responsibilities, and interferes with physical functioning.5 It may cause a sense of helplessness, depleted self-esteem, emotional distress, and neurologic impairment.6 Fatigue in MS can be divided into 2 categories: primary and secondary. Primary fatigue refers to fatigue due to the demyelination of motor tracts and can be subdivided into lassitude and motor fatigability. Lassitude is a general feeling of exhaustion, whereas motor fatigability is weakness due to repetitive use of muscle groups that recovers after rest.7 Secondary fatigue is due to inactivity and muscle disuse and can therefore be prevented, managed, or improved by an exercise program.8 Studies have shown that exercise can have fatigue-reducing effects in people with MS. Petajan and colleagues9 found significantly reduced fatigue and depression in a group of subjects with MS after a 10-week long exercise program compared with a nonexercising group. McCullagh and colleagues10 found that fatigue was reduced in subjects with MS at the completion of a 12-week exercise program, and also 3 months after the program's completion while a control group had no reduction.

Several studies have demonstrated the positive effects of exercise in subjects with MS on fatigue levels, and on walking speed and distance, all of which have been linked with the ability to perform ADL.11,12 Fatigue may, however, limit the ability of people with MS to engage in a sufficient volume of exercise to result in significant improvements. Previous studies have shown that subjects with MS learned to maintain mobility despite fatigue by taking frequent rest breaks.13 This suggests that resting during exercise, or intermittent exercise, may be a means of minimizing exercise-related fatigue and may allow people with MS to exercise more vigorously than when exercising continuously. Utilizing intermittent exercise methods could potentially reduce the effects of fatigue and improve exercise outcomes in people with MS.

There is one previously published study that supports the use of intermittent exercise for people with MS. Karpatkin and Rzetelny14 examined the effects of intermittent or continuous walking on fatigue in a group of subjects with MS with mild to moderate disability (Extended Disability Severity Scale [EDSS] 3-6). Postwalking fatigue was significantly less after the intermittent walking condition compared with the continuous walking condition; however, this study only compared the effects of intermittent and continuous walking on perceived fatigue. Performance measures, such as distance walked under the 2 conditions, were not examined.

The purpose of this study was to examine whether subjects with MS who engaged in 6 minutes of intermittent walking (ie, three 2-minute walking bouts) would ambulate longer cumulative distances and experience less fatigue than during a single 6-minute walking bout. The hypotheses were that subjects with MS would walk longer distances and experience lower levels of postwalking fatigue when walking intermittently compared to walking continuously for the same duration. The findings of this study will help inform the development of an exercise protocol for the population of persons with MS-related fatigue, with the goal of increasing their exercise endurance in order to improve their functional abilities.

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Following approval from the institutional review board of Hunter College, City University of New York, a sample of convenience was recruited from an MS specialty clinic (The Aspire Center for Health and Wellness, New York, New York). Inclusion criteria were that the person must be able to ambulate unassisted for 6 minutes, with or without assistive devices, and understand and sign an informed consent document. Prospective participants were excluded from the study if there was evidence of an MS exacerbation in the 4 weeks before testing as determined by a neurologist; they received methylprednisolone treatment within the 4 weeks before testing; they had orthopedic, cardiovascular, or pulmonary issues that would interfere with the person's ability to participate in the study; or they had cognitive issues such that the person would not be able to follow simple commands. Each participant completed the informed consent process prior to enrollment in the study. Participants were enrolled by members of the study team (H.K., B.B., R.H., R.L., and D.N.). All recruitment and data collection occurred between October 2010 and March 2011.

Demographic data for each participant were recorded at baseline and included age, gender, type of MS, years since diagnosis, EDSS scores, assistive device use, and use of antispasticity and antifatigue medications. Baseline fatigue was measured with the Fatigue Severity Scale (FSS). The FSS is a 9-item questionnaire with each item rated from 1 to 7 on a 7-point Likert scale.15 Mean scores of the 9 items were used resulting in a value that could range from 1 to 7 with a higher score indicating worse fatigue. The FSS has high validity, reliability, and internal consistency when measuring fatigue in people with MS.15

The study used a randomized crossover design to study the differences in distance walked and fatigue levels between the intermittent and continuous walking conditions. Simple randomization (odd/even number selection) was used to assign participants to 1 of the 2 test order groups. Those assigned to group A first performed the intermittent walking trial; those assigned to group B first performed the continuous walking trial. After a washout period of 7 to 14 days, each participant returned and performed the trial in the second condition. Walking distance was the linear distance in meters travelled during the 6 minutes of each trial. Fatigue was measured using a visual analog scale of fatigue (VAS-F) on which participants rated their fatigue by placing a mark on a 100-mm-long line.16 A mark on the extreme right of the scale indicated the worst fatigue possible, whereas a mark on the left indicated the least fatigue possible. Although the FSS and Fatigue Impact Scale17 have greater reliability, the VAS-F was chosen as the outcome measure for this study because it is more sensitive in detecting immediate changes in fatigue.18 The first recorded VAS-F measure was included in the baseline data.

Prior to the start of the first walking test, each participant completed the FSS. For each walking condition, participants rested for 15 minutes before testing. In each walking condition, participants were instructed to walk at their “best comfortable pace” back and forth along a 68.6-m pathway, making a 180-degree turn at each end for a total of 6 minutes. The pathway was located in the hallway of the physical therapy department of an academic center. The pathway was kept free of distractions during the testing period. Each participant's walking in each of the 2 conditions was measured at the same time of day and in the same footwear. Participants who used assistive devices for walking used them for both conditions. The standardized instructions that were read to each participant before each walk can be found in the Appendix.

In the continuous condition (CONT), participants walked for 6 minutes without rest breaks. In the intermittent condition (INT), participants walked three 2-minute increments with 2-minute seated rests between each increment. The 2-minute increment for walking was chosen on the basis of the authors' clinical observations, and evidence that most ambulatory people with MS maintain consistent walking speed in the first 2 minutes of a 6-minute walking test.19 The 2-minute rest period was selected on the basis of the authors' clinical judgment to match the walking time.

The primary outcome measures were walking distances (meters) and the VAS-F. Total walking distance and the distance walked during 3 increments of time: T1 (0-2 minutes), T2 (2-4 minutes), and T3 (4-6 minutes) were recorded. The VAS-F was completed 1 minute prior to, and within 1 minute after, each trial. The difference between the posttest VAS-F and pretest VAS-F was recorded as ΔVAS-F (millimeters).

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Statistical Analyses

Analyses were performed with SPSS version 21.0 (SPSS, Chicago, Illinois). Descriptive statistics were calculated for all variables and participant characteristics. Means and standard deviations were calculated for total meters walked during the 6 minutes, and each of the three 2-minute increments of walking during trials under the CONT and INT conditions.

Each participant provided his or her own control in this crossover design. The 2 test order groups were assessed for equivalence in terms of demographic (eg, sex) and baseline measures (eg, FSS scores) using independent t tests or nonparametric tests (Mann-Whitney U test) as appropriate for continuous variables, and chi-square or Fisher exact tests for categorical variables. Paired-samples t tests were used to examine within-individual differences in total walking distance and ΔVAS-F between conditions. To assess how distance walked changed over time a 2 (CONT and INT conditions) × 3 (time increments: T1, T2, and T3) repeated-measures analysis of variance (ANOVA) was conducted to examine the effects of CONT versus INT walking conditions on distance walked during each time increment. Planned pairwise comparisons were adjusted with Bonferroni adjustment. The more conservative approach of using only Greenhouse-Geisser–corrected degrees of freedom was utilized for all tests of significance involving repeated measures as sphericity was violated. For all tests, assumptions of normality were assessed, and when normality was in question, parametric findings were confirmed with the nonparametric equivalent tests. All tests were 2-tailed, with the significance level set at α ≤ 0.05.

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Twenty-nine participants completed the informed consent process and the first trial. Twenty-seven participants completed both trials; the data from these 27 participants were utilized for data analysis. Two participants withdrew from the study: one due to complications from a pregnancy, and the other due to a non–study-related fall. This minor attrition was treated as random and not imparting bias to the analysis. The study was terminated when the convenience sample was exhausted. No important harms or unintended effects were found during the study. No trials had to be halted for any reason.

There were no significant differences between test order groups in either demographic or baseline characteristics (P > 0.05). Thus, the 2 groups were combined for all further analyses. The demographic and baseline characteristics of each group and the whole sample are summarized in Table 1.

Table 1

Table 1

The main effect of the condition on total walking distance was significant (t = −3.03; P = 0.005; partial [Latin Small Letter Open E]2 = 0.261), indicating a greater total 6-minute walking distance in the INT condition compared with the CONT condition (334.3 ±111.85 m and 304.20 ±114.49 m, respectively) (Figure 1). Change in self-reported fatigue (ΔVAS-F) was significantly lower in the INT condition (20.7 mm ±23.0) versus the CONT (mean 30.2 mm, ±24.1) condition, indicating that participants experienced less fatigue in the INT condition than in the CONT condition (t = 2.22; P = 0.036; partial [Latin Small Letter Open E]2 = 0.159) (Figure 2).

Figure 1

Figure 1

Figure 2

Figure 2

To assess whether the change over time was different under each condition, the Condition × Time interaction was examined and found to be significant (F = 11.93; P < 0.001; partial [Latin Small Letter Open E]2 = 0.31), indicating that the difference in walking distance between the 2 groups increased across time (Figure 1). Pairwise comparisons revealed significant differences in distances walked between INT and CONT walking conditions at the T2 and T3 intervals (P = 0.006, partial [Latin Small Letter Open E]2 = 0.25, and P < 0.001, partial [Latin Small Letter Open E]2 = 0.42, respectively) but not at the T1 interval (P = 0.157). Pairwise comparisons within conditions indicated that while there was no difference in distance walked between time periods in the CONT condition (although there was a slight linear decline), the pattern was quite different in the INT condition. Under the INT condition, participants walked greater distances during T2 and T3 than during T1 (by 4.2 m, P = 0.001, partial [Latin Small Letter Open E]2 = 0.43, and by 3.7 m, P = 0.007, partial [Latin Small Letter Open E]2 = 0.30, respectively). There was no significant difference in distances walked between T2 and T3 (P = 1.00) (Figure 3).

Figure 3

Figure 3

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This study compared walking distance and change in perceived fatigue during intermittent and continuous walking over a 6-minute period in 27 subjects with MS. The participants walked significantly longer distances with less fatigue in the INT condition compared with the CONT condition. The difference in distance found between the 2 conditions (22.8 m) exceeded a patient-perceived minimally important change value of 21.6 m.20 This suggests that intermittent walking may be an appropriate intervention to increase walking distance in people with MS. Intermittent walking is a training method that can be achieved without the use of expensive and elaborate equipment and is therefore accessible to most persons with neurological conditions and to clinicians.

Many recent studies have examined gait and walking in subjects with MS, few have offered explicit recommendations for training methods to improve walking ability in this population. This study is an extension of previously reported work where subjects with MS reported intermittent walking to be less fatiguing than continuous walking, although distance walked was not measured.14 In the INT condition in this study, participants walked longer distances and, therefore, achieved a larger dose of training while avoiding some of the limiting effects of fatigue. It has been suggested that people with MS should limit exercise intensity to a low to moderate level to minimize detrimental effects to those with thermosensitivity.21 A shortcoming of this approach is that it limits the exercise dose, consequently limiting the benefit of that exercise. Intermittent exercise may allow for a greater dosing of exercise to occur by limiting the fatigue that is associated with the activity. If fatigue limits the quantity of walking that a people with MS can perform, intermittent walking training may be a means of addressing this limitation allowing people with MS to participate in a greater volume of training.

Intermittent training has been found to be helpful in both disabled and athletic populations, with differing reasons given for the improvement depending on the population examined. Gharbi and colleagues22 found that intermittent exercise resulted in improved lactate removal relative to continuous exercise in volunteers without disabilities during maximal exercise. However, comparison to the present study is difficult as Gharbi and colleagues used a 6×/week-for-6-weeks training program in persons who were physically fit. In addition, maximal aerobic speed and lactate clearance, rather than fatigue and distance walked, were the primary outcome measurements. It is unclear whether the same mechanism can be claimed for people with MS during 6-minute walks. Another study found improved functional capacity in persons with congestive heart failure who underwent intermittent training compared with continuous training.23 This study suggested that intermittent training is better tolerated by persons with diminished cardiac reserve due to its requiring diminished cardiac output.23 However, we examined persons with neurologic and not cardiac dysfunction making comparisons between the 2 studies difficult. These studies, although giving evidence of the efficacy of intermittent training, are difficult to compare to the present study as they used training programs as opposed to single bouts of exercise, did not measure fatigue or distance walked, and did not examine walking impairment in persons with neurologic dysfunction.

A possible reason for our findings may be related to the phenomenon of thermosensitivity in MS. Although thermosensitivity was not assessed in this study, as many as 60% to 80% of people with MS report clinical deterioration resulting from thermosensitivity.24 A core temperature increase of just 0.5°C can result in a slowing or blocking of nerve impulse conduction in demyelinated fibers.24 Increases in core temperature, either passively or by exercise, can cause a reduction in CNS activation thereby slowing down the central motor drive to the working muscles.25 It is possible that thermosensitivity is strongly related to motor fatigability, as core temperature is known to rise with exercise involving repetitive use of muscle groups.26 Although the effect of heat on people with MS is well known, its effect on physical performance has not been well examined. Van Diemen and colleagues27 found increased visual impairment in persons with MS after exercise. Fjeldstad and colleagues28 found that subjects with MS who complained of thermosensitivity had lower levels of physical participation than those who did not. The improved ambulation distances found in our study may have been due to the fact that as a result of the rests taken, core temperatures did not rise as high as they might have if the walking was done continually, thereby avoiding the decreased conduction through demyelinated fibers that normally occurs during exercise in people with MS. Future studies in which core temperature measurement is conducted during intermittent and continuous walking could confirm whether temperature changes differed between the 2 conditions, and if these were related to changes in distance walked and fatigue.

An alternative explanation for walking fatigue in people with MS is that limitations in oxidative capacity are responsible for impaired walking endurance.29 Oxidative muscle capacity was found to be more related to limited walking distance in people with MS than muscle strength. The effect of thermosensitivity was not examined. Although limitations in oxidative capacity may lead to impaired walking endurance, it is essentially a peripheral component unrelated to CNS dysfunction. It is therefore more likely to be a secondary complication of the disease due to a sedentary lifestyle. Although exercise programs that targeted oxidative capacity in people with MS may improve walking distance, it would only explain limitations in persons who have had time to develop diminished walking tolerance. Participants in this study had a mean disease duration of 11 years, suggesting that oxidative capacity loss due to the adoption of a sedentary lifestyle may have been responsible for the findings.

Another possible reason for our findings may simply have been that the rest breaks in the intermittent condition gave participants a psychologic boost that energized them so that they did not experience as much fatigue. Although it is possible that this might explain the difference in ΔVAS-F, it would be unlikely that all participants who walked greater distances in the INT condition did so primarily because of psychologic factors. This may be clarified in future studies by examining more objective and detailed measures of fatigue and its physiologic correlates.

Measurement of fatigue in people with MS is challenging. It is a subjective perception of multiple physiologic and psychologic properties, and determining which of these is principally responsible for the fatigue experienced by people with MS is difficult. Physiologic measurements such as heart and respiration rates may not be reliable because of the prevalence of autonomic dysfunction in people with MS.30 Although these data were not recorded, an increase in observable gait deviations was noted by the end of the walking trials; foot drag, circumduction, and widening base of support were all prevalent. Future studies could quantify these data through instrumented gait analysis at the end and beginning of a 6-minute walk.

The 6-minute continuous and intermittent walking test procedures we used were different from those described by Goldman and colleagues.31 To minimize the risk of falls, participants were instructed to perform a “U turn” at the end of the hallway rather than a pivot turn. Participants were instructed to perform each walking test at their “best comfortable pace” and not “as fast as possible.” This was done because of the clinical observation that some of the more participants with disabilities might have difficulty finishing a 6-minute-long walk at the speed suggested by Goldman and colleagues. In addition, walking at “best comfortable pace” is probably more reflective of causing the type of fatigue faced by the participants during their normal everyday walking. It is not clear whether different results would have been found if we had used these instructions. It is possible that walking at “best comfortable pace” may have resulted in walking at a slightly slower pace than walking “as fast as possible” and therefore resulted in a less fatiguing walk than if a different instruction had been used. However, this does not change the fact that participants walked greater distances with less fatigue in the intermittent walking condition than in the continuous walking condition.

Multiple sclerosis is a disease that is highly variable in presentation. The variability presents not only between, but also within individuals. For example, walking ability can vary depending on time of day, type of weather, whether they had just taken certain medications, as well as many other factors about which the person with MS or clinician may not be aware.32 The fact that this study examined only walking one time under each condition (INT and CONT) may therefore be considered a limitation of this study, as the true variability of people with MS may not have been fully captured. Future studies should consider having multiple trials under each condition to better examine the inherent variability of the population. A larger sample should be considered as there was insufficient statistical power to thoroughly analyze any covariation of MS-disease severity (EDSS) or fatigue (baseline FSS) of the reported outcomes.

Although studies in other populations have found improvements with intermittent training,22,23 the results of the study should not lead to the conclusion that intermittent walking will result in greater walking endurance in people with MS. It may be that the improvements in walking distance seen in intermittent walking do not transfer to overall walking endurance. Since outcomes of training can be specific to the trained task, it is possible that an intermittent walking training program may lead only to improvements in intermittent walking distance, with no improvement in continuous walking distance. To assess this, a study of the effects of an INT versus CONT training program on walking endurance should be undertaken.

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The clinical implications of our findings are that people with MS may be able to perform gait training at a greater dose if intermittent rests are taken than if they train continuously. If a greater overall amount of gait training can be performed, walking endurance may increase. Since fatigue is one of the most common reasons for limiting the amount of walking performed by persons with MS, intermittent training may offer a means by which this constraint may be avoided.

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APPENDIX: Standardized Instructions for the 6-Minute Walking Test for Continuous and Intermittent Conditions INSTRUCTIONS FOR THE CONTINUOUS CONDITION

We would like you to walk for 6 continuous minutes at your best comfortable pace. Do not run or jog. You will walk along this hallway for the entire walk, making a turn at the marked spot at the end of the hallway. When we ask you to stop, please come to a complete stop and sit down in the wheelchair that will be directly behind you. We will let you know when there are 5 seconds to walk by counting down those last 5 seconds. We will be recording the distance that you walk. We will be guarding you at all times and you will also be followed with a wheelchair so if you need to sit down at any time for any reason, let us know and we will have the wheelchair right behind you to sit in.

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We would like you to walk for 6 minutes, but you will take a seated rest every 2 minutes. Walk at your best comfortable pace, but do not run or jog. When there are 5 seconds to go in the 2-minute walk, we will count down those last 5 seconds, and then you will sit down in the wheelchair, which will be directly behind you. You will then sit in the wheelchair for 2 minutes. When there are 5 seconds to go in the 2-minute sitting period, we will count down those last 5 seconds and then you will get up and resume walking again for another 2 minutes. We will repeat this until you have completed a goal of 6 total minutes of walking, which will be three 2-minute walking periods. You will be guarded at all times and followed by a wheelchair so if you need to sit down at any time for any reason, let us know and we will have the wheelchair right behind you to sit in. You will walk along this hallway for the entire walk, making a turn at the marked spot at the end of the hallway. We will be recording the distance that you walk.




fatigue; gait and walking; intermittent training

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© 2015 Neurology Section, APTA