The Effects of a Twelve-Week Home Walking Program on Cardiovascular Parameters and Fatigue Perception of Individuals with Multiple Sclerosis: A Pilot Study

Abstract

Purpose: To investigate the effects of a 12-week home walking program on cardiovascular parameters, fatigue perception, and walking distance in persons with multiple sclerosis (MS). Methods: Twelve ambulatory persons with MS, not currently participating in exercise were randomly assigned to control (C) or experimental groups (EX). Pretest data collection included resting HR, BP, fatigue perception (Fatigue Severity Scale), and 6-minute walk test. EX received a home walking program (30 min, 3 × week, × 12 weeks), using a modification of Karvonen's formula to calculate HR range. A HR monitor was used to adjust walking speed. The C group refrained from any regular exercise. Posttest data were collected at week 12 and analyzed using the Mann-Whitney U Test. Results: No statistically significant differences were noted between groups in any measured parameters; however, walking distance and Physiologic Cost Index did improve in the exercise group. Conclusion: No adverse events or increase in fatigue levels related to the exercise intervention were reported in this study. This home walking program may not be of sufficient intensity to elicit significant cardiovascular changes. Abnormal cardiac responses have been documented in this population, which may have affected the results. Clinicians may need to use alternate measures to assess fitness in this population.

INTRODUCTION

Multiple Sclerosis (MS) is a chronic, demyelinating disease of the central nervous system diagnosed in young adults between the ages of 20 and 40. The variable distribution of demyelination leads to a diverse clinical presentation. Individuals may exhibit weakness, numbness, spasticity, gait disturbances, ataxia, visual deficits, bowel and bladder dysfunction, cognitive changes, and fatigue which may result in a variety of functional limitations. The etiology of MS continues to remain unknown; however, current evidence suggests that MS occurs secondary to autoimmune dysfunction in individuals who are genetically susceptible.¹ Other major contributing factors include environment and immune dysregulation.^2,3

The Centers for Disease Control⁴ reported that the percent of total deaths in the general population attributed to heart disease in the United States in 2005 was 26.6%. Cardiovascular disease (ischemic heart disease and hypertension) is the second leading comorbid cause of death for those with MS in the US.⁵ It has been suggested that death rates associated with cardiovascular disease for those with MS may be secondary to inactivity associated with the disability.⁶ Stuifbergen⁷ has reported very low levels of physical activity for those with MS as compared to the general population.

It has been well documented that regular aerobic exercise reduces health risks in the general population.^8–10 Historically, health care professionals have been hesitant to prescribe aerobic exercise for individuals with MS due to fears of exacerbation from heat sensitivity; however, these concerns are unfounded.^11–14 A recent Cochrane Review¹⁵ of randomized-control trials of exercise therapy for MS concluded that exercise therapy improved muscle power, function, and mobility-related activity compared to no exercise in individuals with MS. However, there was no evidence to support one type of exercise program versus another. Although a number of published studies have addressed the effectiveness of rehabilitation^12,16 and physical therapy/exercise^17,18 on strength,¹¹ quality of life,^11,19 mobility,¹⁷ and fatigue,^16,20 for those with MS, only a few studies have isolated the type of intervention in a controlled fashion, making interpretation of the findings difficult.

Today, the seminal study by Petajan and colleagues¹¹ in 1996 along with earlier work by Ponichtera-Mulcare²¹ have set the standard guidelines for aerobic training in the MS population. Petajan et al¹¹ found significant improvements in maximal aerobic capacity (VO₂ max), physical work capacity, and isometric strength following a controlled, 15-week outpatient aerobic training program using arm and leg ergometry (60% VO₂ max, 3x/wk).

Since then, other researchers have found beneficial effects of aerobic training in this population using a variety of training intensities and methods: arm and leg ergometry,^11,22 leg ergometry alone,^19,23,24 treadmill walking,²⁵ and aqua class.^26,27 However, much of this research used institutionally-based programs, which lacked the convenience and cost effectiveness of a home program. Thus, the purpose of this study was to investigate the effects of a 12-week home exercise walking program on cardiovascular parameters, energy expenditure, and fatigue perception in individuals with mild to moderate MS. Outcome measures using simple instrumentation were chosen so the clinician could assess program effectiveness in any environment. Measures included resting heart rate (RHR), maximum heart rate during the 6-minute walk test (6MWT HR _max), blood pressure (BP), physiological cost index (PCI), fatigue perception, and walking endurance.

METHODS

Subjects

Fifteen subjects were recruited from 2 large metropolitan hospital centers with affiliated Multiple Sclerosis clinics, the National Multiple Sclerosis Chapter Web site and via flyers distributed at a MS Walkathon over a 2-year period. All subjects met the following inclusion criteria: adults between the ages of 18 and 65 with a diagnosis of MS greater than 1 year, no history of exacerbation within 6 months prior to study, no regular participation in an aerobic exercise program within 6 months prior to the study, the ability to walk independently 100 meters with or without resting (may use intermittent or constant unilateral assistance such as a cane, crutch, or a brace), and an Expanded Disability Status Score²⁸ (EDSS) ≤ 6.0. Subjects were excluded from the study if they had cardiovascular, pulmonary, or orthopedic conditions that precluded them from participating in an aerobic conditioning program. All subjects were medically cleared by their primary care provider or neurologist to participate in the study. The study received IRB approval at all affiliating institutions. Subjects allocated to the control group were offered the opportunity to participate in the home walking program with monitoring upon completion of the study.

Instruments

The Fatigue Severity Scale (FSS) was used to assess the fatigue level experienced by individuals before and after the exercise program. The FSS has been subjected to tests of internal consistency and validity²⁹ and is used frequently to quantify fatigue related to MS.^30–32

The six-minute walk test (6MWT) is a physical performance measure that is simple, self-paced, and measures global responses of all systems to submaximal exercise by measuring the distance walked on a flat surface in 6 minutes.³³ The reliability and validity of this test has been investigated extensively as it has been used as a functional outcome measure for children and adults with cardiopulmonary dysfunction.^34–38 It has also been used as a functional outcome measure for individuals with fibromyalgia³⁹ and the geriatric population.⁴⁰

The Physiological Cost Index was developed by McGregor⁴¹ as a simple and practical method to assess gait efficiency and energy expenditure. The PCI is based on Astrand and Rodahl's work,⁴² which showed that heart rate and speed of walking are linearly related to oxygen consumption at submaximal levels. The Physiological Cost Index has been used to assess energy expenditure in children and adults with functional impairments.^37,38,43 Research demonstrates a consistent correlation between energy expenditure, PCI, and level of functional disability.^44–46 The PCI was calculated as follows:

$$\text{PCI}=\frac{\text{Walking Heart Rate}-\text{Resting Heart Rate}(\text{beats}/\text{min})}{\text{Walking Speed}(\text{meters}/\text{min})}$$

Previous studies have found that the mean PCI for healthy adults is 0.35 beats/meter, with a range of 0.11 to 0.66 beats/meter.^47,48 A decrease in PCI reflects increased walking efficiency. Testing guidelines require that 3 conditions are met^41,45,49: (1) subjects walk at their self-selected speed, (2) the determination of a true resting heart rate, and (3) the use of a steady-state walking heart rate in the formula, which Astrand and Rodhal⁴² have identified as the heart rate at minute 3 during submaximal workloads in healthy individuals.

Rating of perceived exertion (RPE) was developed by Borg⁵⁰ as a subjective method of rating exercise intensity. It is highly correlated with heart rate and VO₂ max⁵¹ and is frequently used to monitor exercise intensity for those who have difficulty taking their own pulse and those taking cardiac medications which blunt normal heart rate responses.⁵² Rating of perceived exertion values range from 6 to 20 corresponding to the perception of “very, very light intensity” (RPE = 6) to “very, very hard intensity” (RPE = 20).

The heart rate reserve (HRR or Karvonen) method was developed by Karvonen⁵³ to prescribe exercise intensity based on a maximum heart rate (MHR) obtained from a progressive maximal exercise test. A training heart rate range is established based on resting heart rate (RHR), which is subtracted from the maximal heart rate (MHR) to obtain the heart rate reserve (HRR). A percentage of the HRR (usually 60% to 80% for healthy individuals) is then added to the RHR to obtain a target HR range.⁵¹ Safety during ambulation was of great concern in this study as balance impairments are a common complaint.⁵⁴ Hence, a modification of Karvonen's MHR was used to calculate a training heart rate range: [0.6 and 0.8 (6MWT HR_max – RHR) + RHR]; where MHR was operationally defined as MHR achieved during the 6MWT (6MWT HR_max).

Polar Fitwatch Heart Rate Monitors (Polar Electro Inc., Port Washington, NY) were used to obtain HR before, during, and after the 6MWT. In addition, the Polar Fitwatch was used by the exercise group during the walking program in order to maintain the training HR range. A standard aneroid sphygmomanometer and a stethoscope were used to measure resting and exercise blood pressure.

Procedure

A pretest-posttest, control group design was used in this study. Neither the researchers nor participants were blinded in the study. Participants were randomly assigned to a control or an experimental group by a coin toss. All subjects participated in a pretest session which included collection of demographic information and baseline data including: resting heart rate (RHR), resting blood pressure (RBP), and fatigue perception as measured by the Fatigue Severity Scale (FSS). Instructions in the use of the RPE scale (6-20 scale) and the procedure for the 6MWT were explained in detail. Ample opportunity was given to all subjects to ask questions.

All subjects completed a 6MWT using standardized language and guidelines as described in the American Thoracic Society guideline for the 6MWT.³³ Total distance in meters was recorded. In addition HR, BP, and RPE were obtained at minute 3 of the 6MWT, at the completion of the 6MWT, and 2 minutes after the walk test. To obtain BP at minute 3, the sphygmomanometer cuff was inflated during walking and the subject was asked to stop briefly (< 5 seconds) while the measurement was taken. Maximal HR during the 6MWT (6MWT HR_max) was also recorded. The subject's heart rate obtained at minute 3 of the 6MWT and the distance walked was used to calculate the PCI.

The exercise group received a home walking program that was individualized based on the results of the 6MWT. Walking speeds were determined by calculating a training HR range using a modification of Karvonen's formula described previously. The subjects then adjusted their walking speed to stay within their prescribed HR range using a Polar Fitwatch Heart Rate Monitor, which was supplied to the subject for their home use. The exercise group subjects were instructed to walk 3 times per week for 12 weeks. For the first 2 weeks, the subjects walked 5 minutes below the lower limits of their THR range, followed by 15 minutes of walking within their THR range, and then a 5-minute cool down below their THR range. During weeks 3 through 12, subjects increased their training time in the THR range to 20 to 30 minutes. The exercise group also maintained a weekly exercise log including RPE values and received biweekly telephone calls to monitor their exercise compliance. The control group was asked to refrain from any regular exercise during the 12-week period.

Posttesting occurred at 12 weeks and the aforementioned data were once again collected and recorded. Attempts were made to posttest subjects during the same time of day as the pretest. This occurred in all but one subject in the exercise group who had scheduling conflicts.

Data Analysis

The Mann-Whitney U Test was used to compare differences in the exercise and control group data due to the small and unequal sample size. Based on previous literature, the authors hypothesized that changes in distance walked, 6MWT HR_max, and PCI may occur following the completion of the home walking program. In addition to these variables, the following variables were also analyzed: RHR, resting SBP, resting DBP, and FSS. In order to provide a measure of the subject's baseline physical performance status, each subject's pretest 6MWT distance was compared to age and gender matched healthy norms⁵⁵ and is reported as a percentage. Group differences in age and pretest walking distance were analyzed using the Mann-Whitney U Test. Measures of central tendency and standard deviation were also noted. All analyses were two-tailed.

The minimal detectable difference for the PCI was calculated based on the following equation:⁵⁶ MDD = Z ∗ SEM ∗ √2; whereas the Z score represents the 95%CI.

RESULTS

Fifteen subjects were initially recruited into the study. Three subjects (2 control and 1 experimental) were excluded from data analysis due to poor compliance and failure to show for posttest assessment, resulting in 8 subjects in the exercise group and 4 subjects in the control group. Demographic information for the remaining 12 subjects is found in Table 1. The exercise group was comprised of 6 females and 2 males. The average age of the exercise group was 51.3 years (40-64). Two exercise subjects used some assistance during ambulation. Subject 1 occasionally held onto the walls or a hand rail while walking, and subject 6 regularly used a straight cane. The control group was comprised of 3 females and 1 male. The average age of the control group was 34.7 (22-50). Only one subject (#11) used a straight cane while ambulating. No orthosis was used in either group. Detailed medical information from the subject's neurologist or primary physician was not always available, therefore diagnostic classification systems were only provided in 30% of the subjects. The inclusion criteria required all subjects to have an EDSS of ≤ 6.0, however, individual EDSS scores were not provided by the referring physician. EDSS scores reported in Table 1 are a reflection of the history taken by the researchers and distance walked on the pretest 6MWT. Pretest 6MWT values were used to compare all subjects' physical performance to their age and gender matched healthy counterparts. These baseline 6MWT values are found in Table 1 (%6MWT) and ranged from 11% to 89% (mean = 50.38%) for the exercise group, and 35% to 65% for the control group (mean = 55%).

Table 1.

Subject Demographics

Subject #	Gender	Age in Years	MS Diagnosis (years since diagnosis)	EDSS	Current Medications	Assist ive device Yes No	% 6MWT for age/gender matched healthy at pretest
Experimental Group
1	F	64	Relapsing remitting	≤6.0	Avonex	Yes (rail)	11%
2	F	46	Not classified	≤5.0	None	No	39%
3	F	41	Not Classified (∼3 yrs)	≤4.0	Avonex Lipitor Vitamins	No	75%
4	F	40	Relapsing remitting (∼3 yrs)	≤4.0	Avonex	No	65%
5	F	40	Not classified (∼5 yrs)	≤3.5	Avonex	No	89%
6	M	62	Not classified (∼20 yrs)	≤6.0	Tegretol Elavil Xanax	Yes (straight cane)	24%
7	F	60	Primary progressive (∼30 yrs)	≤4.5	Imuran Zanaflex	No	55%
8	M	58	Not classified (∼12 yrs)	≤4.5	Synthroid Depakote	No	45%
Control Group
9	F	22	Not classified	≤4.5	Avonex Corticosteroids Copaxone	No	63%
10	F	50	Not classified	≤4.5	None	No	65%
11	M	35	Not classified	≤6.0	Avonex Corticosteroids	Yes (straight cane)	35%
12	F	32	Not classified	≤4.0	Avonex	No	57%

Descriptive statistics reporting pretest to posttest mean change based on group assignment are found in Table 2. No significant differences were noted between groups in any of the measured variables: distance walked, RHR, 6MWT HR_max, PCI, FSS, resting SBP, and resting DBP. The critical value for U for this sample size was 4 (p ≤_0.05). Calculated U values are reported in Table 2 and ranged from 10.5 to 13; p values ranged from 0.34 to 0.61. A significant difference in age was noted between groups (U=4; p = 0.041). No group differences were noted in pretest walking distance or the %6MWT at baseline.

Table 2.

Mean Change in Variables Based on Group Assignment and Calculated U Values

Group	Mean Distance Change (m) (SD)		Mean RHR Change (beats/min) (SD)		Mean 6MWT HRmax Change (beats/min) (SD)		Mean PCI Change (beats/meter) (SD)		Mean FSS Change (SD)		Mean SBP Change (mmHg) (SD)		Mean DBP Change (mmHg) (SD)
Control	46.75 (37.25)	U=13 p= 0.61	−2.0 (3.36)	U=10.5 p=0.34	0.75 (4.57)	U=12 p=0.49	−0.02 (0.04)	U=10.5 p=0. 34	−0.17 (0.49)	U=13 p=0.61	3.0 (2.38)	U=11 p=0.38	−4.25 (2.17)	U=11 p=0.37
Exercise		65.69 (24.36)		2.12 (2.79)		3.87 (3.17)		−0.09 (0.04)		−0.24 (0.72)		−0.25 (2.73)		−1.25 (3.87)

Nonstatistical, but perhaps clinically relevant changes were noted in the following variables: mean change in walking distance (EX = 65.69m vs. C = 46.75m) and mean change in PCI (EX = −0.09 beats/meter vs. C = −0.02 beats/meter (Table 2). Individual pretest and posttest values for walking distance and PCI are shown in Table 3. Both the exercise and control group mean walking distance and PCI scores improved on posttest. The minimal detectable difference (MDD) for the PCI (95% CI) was 0.15 beats/meter.

Table 3.

Pretest vs. Posttest Measurements: 6MWT and PCI

Subject #	Pretest 6MWT (m) (SD)	Posttest 6MWT (m) (SD)	Pretest PCI (beats/min) (SD)	Posttest PCI (beats/min) (SD)
Experimental Croup
1	213	251	0.79	0.57
2	256	264	0.82	0.77
3	503	724	0.23	0.22
4	438	532	0.57	0.57
5	599	650	0.58	0.56
6	162	171	0.81	0.49
7	335	402	0.70	0.73
8	311	349	0.54	0.43
Group Mean	352.2 (150.13)	417.9 (199.32)	0.63 (0.20)	0.54 (0.17)
Control Group
9	458	429	0.60	0.46
10	420	427	0.59	0.60
11	269	337	0.82	0.80
12	401	542	0.34	0.41
Group Mean	387 (82.15)	433.75 (83.95)	0.59 (0.20)	0.57 (0.17)

All 8 subjects in the experimental group returned their daily log calendars. The expected number of walking sessions in 12-week period, with a range of 12 to 42 sessions. Based on analysis of the exercise logs, the adherence rate for this exercise program was 75%.

The exercise group reported no incidence of falls, no increase in fatigue levels, and no adverse effects related to the exercise program. Individuals in both groups reported increased fatigue levels typically associated with warmer weather.

DISCUSSION

Although improvements in distance walked and PCI suggest that the exercise group may have demonstrated some physical performance gains as compared to the control group, statistical analysis did not support these findings. This may be due to a number of contributing factors. One reason may be that the established training heart rate guidelines used in this study was not of sufficient intensity to elicit true aerobic changes. Improvements in aerobic fitness have been reported in this population by a number of researchers^{11,22–24,57} using institutionally-based aerobic training programs, however, training heart rate ranges were based on VO₂ max graded exercise tests or a MHR calculated using 220-age. When comparing the mean MHR obtained by Petajan et al¹¹ during ergometric exercise testing of individuals with MS (175 beats/minute), to the mean 6MWT HR_max obtained in the exercise group in the present study (110 beats/minute) the differences are apparent.

Autonomic dysfunction may account for some of the lower maximum heart rates as the literature has demonstrated up to 50% of individuals diagnosed with MS may exhibit abnormal cardiovascular test responses.^58–61 Blunted heart rate^21,61 and systolic blood pressure responses to exercise⁶¹ have also been reported during maximal and submaximal aerobic exercise. Additionally, since the PCI is dependent on HR recordings, calculation of this parameter may also have been affected. However based on further data analysis, this appears unlikely as there was a significant difference in the exercise group average RHR as compared to their average 6MWT HR_max (p=.0001). Percent change of heart rates from resting to 6MWT HR_max ranged from 13.75% to 111%. Systolic BP responses to exercise were not as remarkable (p=.08).

The majority of subjects (11/12) demonstrated some improvement in distance walked on the posttest 6MWT regardless of group assignment; hence familiarity with the testing procedure may have contributed to improvements in walking distance in both groups and should be considered a limitation in the study. This issue could be addressed in the future by administering a practice test 1 hour earlier and taking the greater distance earned as the subject's baseline, as suggested by the American Thoracic Society Guidelines.³³

Large standard deviations for the 6MWT were seen in both groups during pretest and posttest situations (Table 3). Differing baseline physical performance levels may account for this factor. Using change scores in the data analysis should account for some of the baseline differences, however, performance gains are subject to the ceiling effect⁵⁶ and are dependent on baseline fitness level. Using the pretest distance as a covariate would address this issue; however, in the present study the sample size was too small to use this approach. Significant differences in age between groups may have also been a contributing factor in the outcome; again due to a small sample size we were unable to use age as a covariate during data analysis.

How functionally limited were the subjects as compared to a healthy population in terms of walking distance? Reference values for the 6MWT have been published based on best distance walked over 4 trials in a sample of 79 healthy individuals.⁵⁵ Distance walked reported for similar age groups as those in the current study averaged (mean ± SD) 699 ± 37m for women in the 20 to 40 year age group and 800 ± 83m for men. Best distance walked in the 41-60 age groups was 670 ± 85m for women and 671 ± 56m for men. On average, the exercise and control groups walked more than 200 meters less than their older healthier counterparts. Standing rests during the 6MWT or the home walking sessions may further explain some of the limitations in individual walking distances. Future studies of this nature should record number and length of rest periods during testing and training sessions.

Changes in PCI greater than 0.15 beats/meter (MDD) would suggest that the physical performance improvements reflected true change. Although the exercise group PCI mean change was −0.09 beats/meter, there was no clinical (MDD) or statistical difference.

Overall, study participants were able to consistently maintain their established training heart rate range during each walking session. Review of their daily logs revealed that the majority of the subjects (7/8) stayed within or slightly above the training heart rate ranges during most training sessions. Only 1 subject failed to record their HR data properly making review of their training data not feasible. Subject compliance is crucial when using a home program with self-report as part of a treatment intervention. In an attempt to increase adherence to the exercise program, biweekly phone calls from the researchers occurred to offer encouragement, answer questions, and check on progress. This study's adherence rate of 75% is slightly better than rates cited in a recent quantitative review which concluded adherence rates using self-report as 71.8%⁶² and adherence rates of 72% when exercise was the treatment choice. Frequent telephone contacts were well received by the subjects and may have contributed to their compliance rate.

Finally, no adverse events or reports of increased fatigue related to the exercise intervention were reported. These findings are consistent with current available evidence.^11–14,63

Limitations of this study include a small and unequal sample size. Although subjects were placed randomly into the control or exercise group, by chance the exercise group ended up with twice the amount of subjects. Lack of specific EDSS values also limits the generalizability of the findings.

The results of this pilot study warrant further research. A core set of outcome measures need to be identified and potential confounding variables such as age, type of MS, and disability level should be addressed.

CONCLUSIONS

Although results of this study were inconclusive, a number of important factors surfaced that require consideration as physical therapists prescribe aerobic training for those with MS. Although changes were noted in individuals who participated in a 12-week home walking exercise program, the submaximal intensity may not have been sufficient to elicit statistically significant cardiovascular changes in this population. Perhaps most importantly, a regular home exercise walking program of submaximal intensity appears to have no deleterious effects on an individual's perception of fatigue.