Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by disturbances in nerve conduction and manifested by various clinical features. People with MS often complain of poor exercise tolerance and exertion fatigue that limit their daily living activities. (1,2) Peripheral factors (3-5) as well as central factors (2,6-8) may be involved in the pathogenesis of the reduced exercise tolerance and fatigue in people with MS. An abnormally high energy cost of walking has been suggested as an important contributing factor in leg fatigue during treadmill exercise. (3) Respiratory muscle dysfunction also has been related to the reduction in exercise tolerance in people with MS. (4) A recent study by Chetta et al (5) showed that subjects with MS who were mildly disabled had reduced limb endurance and an impaired cardio-respiratory response to self-paced walking that might have been related to deconditioning, cardiovascular autonomic dysfunction, and altered breathing control. Deconditioning may play a key role in the impaired exercise tolerance of people with MS. In order to minimize fatigue, people with MS limit their physical activity. (1,2) This limited physical activity, in turn, can lead to deconditioning and disuse that further worsens limb weakness and fatigue. (9) Furthermore, fatigue and limitation of physical activity may reduce the ability to participate in daily social and family activities. (9)

One of the primary aims of rehabilitation in people with MS is to maintain and improve functional independence. Review studies (10,11) suggest that exercise therapy may be beneficial for patients with MS in terms of physical fitness, activities of daily living, and outcomes related to mood. In particular, aerobic exercise seems to be a promising rehabilitative tool for patients with MS because it could positively affect both maximum exercise capacity (12) and dally physical activities. (13) In both the study by Petajan et al (12) and the study by Romberg et al, (13) however, the effect of aerobic exercise was compared with that of no treatment. In addition, in the study by Romberg et al, (13) aerobic exercise consisted of aquatic training, which was not tailored to meet the specific exercise capabilities of the subjects. Only one study (14) previously examined the effects of aerobic training (AT) on maximum exercise capacity, as compared with a physical therapy program. The analysis was restricted to within-group comparisons, and the results showed a significant increase in the anaerobic threshold but no changes in maximum aerobic capacity.

Therefore, the purpose of this randomized crossover controlled study was to assess the effects of an 8-week AT program on exercise capacity--in terms of walking capacity and maximum exercise tolerance, as well as its effects on fatigue and health-related quality of life--as compared with a neurological rehabilitation (NR) protocol in subjects with mild to moderate disability secondary to MS. We considered both the AT program and the NR protocol as 2 effective rehabilitative interventions for people with MS. Accordingly, we hypothesized that the 2 rehabilitation protocols could have similar effects on the functional status of subjects with MS.

Method

Subjects and Design

The subjects were screened from a waiting list for a rehabilitation program in the MS outpatient clinics at Parma University Hospital and Piacenza Hospital between January and May 2005. The inclusion criteria were: a diagnosis of MS according to the criteria of Poser et al, (15) a score of 6 or less on the Expanded Disability Status Scale (EDSS) (16) because individuals with an EDSS score greater than 6 need constant use of a bilateral aid while walking, and age between 20 and 55 years. Subjects were excluded if they had a relapse 4 weeks before the study; had a history of cardiac, pulmonary, orthopedic, metabolic, or other medical conditions precluding participation; were currently receiving steroid therapy or had been treated with steroids within 2 months prior to the study; or had engaged in a regular exercise program within 2 months before the study.

After screening, the subjects were randomly assigned, according to a computer-generated randomization list, and stratified by sex, age, and EDSS score to receive either an AT or NR 8-week parallel crossover intervention. To avoid any interference between the 2 interventions, all subjects waited 8 weeks before initiating the second intervention. During the 8-week washout period, the subjects were instructed to stop exercising. Clinical assessments, lung function and respiratory muscle strength (force-generating capacity) testing, 6-minute walk tests (6MWTs), and cardiopulmonary exercise tests (CPETs) were administered by the same examiner both prior to and after each 8-week treatment without knowledge of the subject's group assignment.

Out of 40 eligible subjects, 21 subjects were excluded because they did not meet the inclusion criteria or they declined to be enrolled (Fig. 1). Accordingly, we studied 19 subjects with MS (14 female, 5 male). The subjects' ages ranged from 22 to 51 years, and their disease duration ranged from 1 to 15 years. None of the subjects reported any history of cardiac or pulmonary disease, and all subjects had normal physical examinations of the chest, chest radiographs, and resting electrocardiograms. At the time of the study, 10 subjects were being treated with interferon beta, 4 with mitoxantrone, and 1 with glatiramer acetate. All subjects gave informed consent to participate in the study.

[FIGURE 1 OMITTED]

Clinical Assessment

The subjects' neurological impairment and degree of disability were assessed with the EDSS, which provides a score ranging from 0, indicating normal neurological findings, to 10, indicating death from MS. This scale is a reliable and valid measure of impairment and disability in people with MS. (17) The EDSS score was assigned without knowledge of the subjects' pulmonary function and exercise capacity test results.

The subjects' perceived effect of fatigue was assessed with the Modified Fatigue Impact Scale (MFIS), (18) which has been validated in people with MS. (19,20) The MFIS is a structured, self-report, 21-item questionnaire that provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functions. Scores on the MFIS range from 0 to 84, and all items are scaled so that higher scores indicate a greater effect of fatigue on a person's activities. Fatigue is defined as a self-reported lack of physical or mental energy that is perceived by the individual to interfere with usual and desired activities. (19)

The disease-specific Multiple Sclerosis Quality of Life-54 questionnaire (MSQOL-54) was used to assess health-related quality of life. (21,22) The 54 items are divided into 12 multiple-item scales and 2 single-item scales. The MSQOL-54 item results are transformed linearly to scores of 0 to 100, and final scale scores are created by averaging the scores of items within the scales. A higher score in each scale indicates a better health-related quality of life. Physical health composite (PHC) and mental health composite (MHC) scores were calculated as a weighted sum of selected scale scores. The reliability and validity of the MSQOL-54 scores have been confirmed in subjects with MS. (23)

Lung Function, Respiratory Muscle Strength, and Exercise Capacity Assessment

Pulmonary function was measured with a flow-sensing spirometer (Vmax 22)* and a body plethysmograph (Vmax 6200)* connected to a computer for data analysis. Baseline total lung capacity (TLC), forced expiratory volume in 1 second ([FEV.sub.1]), vital capacity (VC), and [FEV.sub.1]/VC ratio were recorded. All of these variables are expressed as a percentage of the predicted value. (24) The best out of 3 results was used in subsequent calculations.

Maximum inspiratory pressure and maximum expiratory pressure were performed against a valve, which could be closed by turning a tap. (25) Maximum inspiratory pressure and maximum expiratory pressure were measured (in centimeters of water) from TLC and residual volume (RV), respectively. The highest out of 5 recorded pressures maintained for 1 second were used for analysis.

Walking capacity was assessed with the 6MWT, according to a standard protocol. (26) The 6MWT is a symptom-limited exercise test, so subjects were allowed to stop if necessary, although they were instructed to resume walking as soon as possible. All subjects performed two 6MWTs, the second test performed the same as the first test, following a rest of at least 60 minutes. The walking distance was recorded in meters and expressed as a percentage of the predicted value, which accounted for age, sex, and height. (27) Additionally, the walking speed (in meters per minute) was calculated. Oxygen uptake ([??][O.sub.2], in milliliters per kilogram per minute) was continuously monitored with a portable lightweight system (VmaxST)* from 5 minutes before the walk until test completion, as well as 5 minutes after completion or until the return to the baseline level. The [??][O.sub.2] and the cost of walking during the walk (expressed as mL [O.sub.2] x [kg.sup.-1] x [m.sup.-1]) (3) were considered for analysis. Results from only the second walk were used for analysis to allow for any learning effect. (26,28)

Each subject performed a physician-supervised, standard, progressively increasing work rate CPET to maximum tolerance on an electromagnetically braked cycle ergometer. Gas exchange measurements (Vmax 229) * were taken for 3 minutes at rest, for 3 minutes of unloaded cycling at 60 rpm followed by a progressively increasing work rate exercise of 5 to 20 W x [min.sup.-1] to maximum tolerance, and for 2 minutes of recovery. Pulse oximetry, heart rate (HR), 12-lead electrocardiogram, and cuff blood pressure were monitored and recorded. Minute ventilation, [??][O.sub.2], and carbon dioxide production ([??]C[O.sub.2]) were computer-calculated breath by breath, interpolated second by second, and averaged over 10-second intervals. The maximum work rate (in watts), the [??][O.sub.2] at the peak of the exercise (in milliliters per minute and as a percentage of the predicted value), (29) and the [??][O.sub.2]/HR at the peak of the exercise (in milliliters divided by beats per minute and as a percentage of the predicted value) (29) were considered for analysis.

Rehabilitation Program

The AT program partially followed the protocol proposed by Petajan et al. (12) Briefly, the subjects participated in 3 training sessions per week on a leg cycle ergometer for 8 weeks. Each training session consisted of a 5-minute warm-up at 30% of maximum work rate, then 30 minutes at 60% of maximum work rate, which was followed by a 5-minute cool-down. Subjects then performed stretching exercises of their lower limbs and trunk muscles for 15 minutes. Workloads were calculated from the work rate obtained during the CPET and were progressively increased every week up to 80% of maximum work rate. Heart rate, blood pressure, pulse oximetry, and the subjects' perceived exertion, as assessed with a visual analog scale, were monitored during exercise.

During the NR program, subjects underwent 3 sessions per week for 8 weeks. Each session lasted 60 minutes and consisted of exercises aimed at improving respiratory-postural and respiratory-motor synergies and of stretching exercises. These exercises consisted of active movements of the trunk and upper limbs in a standing, sitting, or kneeling position, such as flexion and rotation movements of the trunk; gait exercises, including tandem gait or ambulation exercises combining advancement of one lower limb with raising of the opposite upper limb; and exercises for stretching the lower limbs and trunk muscles. During each exercise, much emphasis was placed on breathing, as the subjects were asked to inspire during active movements and to expire during relaxation. The exercises were grouped in 4 parts, separated by 3-minute pauses, and were all proposed with the same temporal sequence.

Trained physical therapists instructed the subjects individually on both AT and NR programs and supervised each exercise program session. Before and immediately after each exercise program session, subjects rated the magnitude of their perceived breathlessness and fatigue on a visual analog scale.

Data Analysis

We considered 2 outcome measures. The primary outcome measure was the effect of the rehabilitation programs on exercise capacity. The secondary outcome measure was the effect of the rehabilitation programs on fatigue and health-related quality of life.

Values are presented as mean [+ or -] standard deviation, unless otherwise specified. Between-group differences for all enrolled subjects, the subjects who completed the study, and the subjects who did not complete the study were examined using the chi-square test, the analysis of variance, and the Kruskal-Wallis test, when appropriate. In order to analyze the between-group and within-group interventions, the analysis of variance for repeated measures and the Newman-Keuls multiple comparison test were used for analysis of variables with Gaussian distribution, and the Friedman test was used for analysis of nonparametric variables. A P value [less than or equal to] 05 was taken as significant.

The clinical effect of the interventions on the primary outcomes was assessed by the effect size statistic, calculated as the mean change found in a variable divided by the standard deviation of that variable. (30) We used the criteria of Cohen (31) to interpret the effect size, where a value of 0.2 is considered a small effect, a value of 0.5 is considered a moderate effect, and a value of 0.8 is considered a large effect.

Results

Fourteen of the 19 subjects recruited for the investigation completed the AT program, and 16 subjects completed the NR program. Only 11 subjects, however, were able to complete the overall crossover controlled parallel study and were considered for analysis. Four subjects did not adhere to the study protocol and dropped out of the trial. In 2 of those subjects, the exercise program sessions induced a perception of breathlessness and fatigue, which persisted up to the beginning of the following session, thereby precluding the continuation of the rehabilitation program. The other 2 subjects withdrew from the rehabilitation program because they felt it was too stressful. Four subjects had a relapse of MS (2 subjects during the AT program and 2 subjects during the NR program) and were unable to complete the study (Fig. 1). Personal details and pulmonary function test results of the 19 subjects enrolled in the study, of the 11 subjects who completed the study, and of the 8 subjects who did not complete the study are reported in Table 1. No between-group differences were found. In addition, when baseline condition measurements of the 2 interventions were considered, no difference was found (Tabs. 2, 3, and 4).

Disease Progression and Exercise Adherence

No change over time was found in neurological status, as measured with the EDSS (P=1.0). All subjects who completed the study adhered very well to both the AT program and the NR program. Of 264 exercise sessions prescribed for either the AT program or the NR program, 230 and 238 exercise sessions, respectively, were completed, with an average adherence rate of 87%[+ or -]8% and of 90%[+ or -]6%, respectively. No exercise-related injuries were reported.

Primary and Secondary Outcomes

Lung function and respiratory muscle strength were not changed by participation in the AT program or the NR program (Tab. 2). MI subjects were able to complete a 6MWT without stopping. Due to technical problems, we recorded only preintervention and postintervention values for the 6MWT in 8 out of 11 subjects. Within-group analysis showed that subjects had significant improvements in walking distance (P=.02) and walking speed (P=.02) after the AT program, but not after the NR program. Cost of walking also did not change after completion of the AT program or the NR program (Tab. 2). When interventions were analyzed between groups, no difference was found. The effect size for walking distance and maximum work rate was small (0.2) in the AT program and negligible (0.09) in the NR program.

After the AT program, subjects showed a significant increase in peak [??][O.sub.2] (P=.01), maximum work rate (P=.01), and peak [??][O.sub.2]/HR at CPET (P=.04) when preintervention and postintervention values were compared. Moreover, after the AT program, 82% of the subjects had a percent increase in change of maximum work rate greater than 10% of the baseline value. After the NR program, subjects showed no significant increase in any CPET values (Tab. 2, Fig. 2). When interventions were analyzed between groups, peak [??][O.sub.2] and maximum work rate after the AT program were significantly increased compared with the corresponding values after the NR program (P=.025 and P=.02). The effect size for peak [??][O.sub.2] and maximum work rate was moderate in the AT program (0.6 and 0.5, respectively) and negligible in the NR program (0.02 and 0.07, respectively).

[FIGURE 2 OMITTED]

The MFIS and MSQOL-54 scores before and after AT and NR interventions are shown in Tables 3 and 4. After the AT program, the subjects showed a significant increase in 3 MSQOL-54 scale scores (emotional well-being, energy, and health distress). After the NR program, the subjects had significant improvements in health distress and mental health composite scores and a significant reduction in emotional well-being scores.

Discussion

Our study showed that, in subjects with mild to moderate disability secondary to MS, maximum exercise tolerance improved after completion of the 8-week AT and NT programs, as compared with baseline conditions. The change in walking capacity was significant after the AT program when compared with baseline conditions, but not after the NR program. Despite the effect of the AT program on physical performance, this rehabilitative approach did not differ from the NR intervention in terms of the perceived effect of fatigue and only partially affected the subjects' health-related quality of life.

Walking capacity can be assessed simply and reliably with the self-paced 6MWT, which can be considered to be a measure of limb endurance and reflects the submaximal functional exercise level of daily physical activities. (26) Restricted walking prevents people with MS from participating in family and social activities and is a major determinant of overall impairment in people with MS who are ambulatory. (32) Moreover, the walking distance covered during the 6MWT was found to be inversely related to the EDSS scores. (5) In the present study, we found that the walking capacity of patients with MS who were mildly to moderately disabled was substantially reduced, as expressed as a percentage of the predicted value, and was significantly increased after the AT program but not after the NR program. Furthermore, the change in walking capacity induced by AT did not significantly differ from the change induced by NR.

Previous studies, different in length and kind of exercise and in outcomes, showed discordant results of the effects of AT on walking capacity in subjects with MS. Rodgers et al, (33) in an uncontrolled study, found minimal effects on gait abnormalities (ie, decreased walking speed and cadence) after 6 months of AT. In contrast Romberg et al (13) showed that a 6-month AT program, including aquatic exercises, induced an increase in walking speed compared with no therapy. Recently, in an uncontrolled study, Kileff and Ashburn (34) found that 24 biweekly sessions of 30 minutes of cycling on a stationary bicycle improved walking distance. In that study, the mean improvement in 6MWT walking distance was 32 m.

In the present study, we found that the AT program induced a significant change in maximum aerobic capacity and work rate both over the study time and as compared with the NR program. Moreover, if we consider that a 10% increase in work rate on the cycle ergometer is indicative of an improvement in fitness, as suggested by Schapiro and colleagues, (35) we found that this outcome was achieved by most subjects undergoing AT. Our findings are consistent with those of Petajan et al, (12) who found a significant change in maximum aerobic capacity and work load in subjects who undertook AT compared with no therapy. Interestingly, we found a 20% increase in aerobic capacity, which is comparable to that found by Petajan et al, (12) despite a different duration of training (8 versus 15 weeks) and mode of aerobic exercise (leg cycle ergometer versus combined arm and leg cycle ergometer). By contrast, Mostert and Kesselring (14) did not find any change in maximum aerobic capacity in subjects with MS after a 4-week period of AT, despite findings of significant increases in [Vo.sub.2], anaerobic threshold, and maximum work rate. The shortness of the training period and the different degree of disability may explain the discrepancy between these results and those of Petajan et al (12) and our study.

In people with MS, the peak oxygen pulse during maximal incremental exercise on a cycle ergometer may be reduced when compared with subjects who are healthy. (36) This finding suggests that people with MS may have reduced cardiovascular fitness, which, in turn, may be related to deconditioning. In this study, we showed that the peak oxygen pulse increased after the AT program, but not after the NR program. To our knowledge, no data concerning the effect of rehabilitation programs on oxygen pulse have been available until now, except for the study by Mostert and Kesselring, (14) which demonstrated significant change in oxygen pulse measured at anaerobic threshold in subjects with MS who participated in an AT program.

Our results showed that both AT and NR intervention led to no significant change in the subjects' MFIS scores. The poor influence of physical exercise on perception of fatigue may be related to the multidimensional origin of fatigue, because central factors, (2,6-8) in addition to peripheral mechanisms, (3-5) are known to play a key role in the pathogenesis of this symptom. Furthermore, the MFIS may not be sensitive enough to detect changes in fatigue over time, and the duration of the rehabilitative program was too short to determine significant changes. Previous studies have shown discordant results on the effect of AT on fatigue. Some studies failed to demonstrate a significant effect of AT on fatigue, when comparing exercise training versus no exercise therapy (12) or "conventional" physical therapy. (14) In contrast, Surakka et al (37) found that 6 months of aerobic and strength exercises reduced motor fatigue in women, but not in men.

In this study, we showed that AT only partly affected the health perception of the subjects, particularly by significantly inducing increases in emotional well-being, energy, and health distress scores. In contrast, the NR program had a contradictory effect because it improved health distress and mental health composite scores while reducing emotional well-being. The mechanism of action of these changes is not completely clear and may not relate directly to the AT program or the NR program. Both intervention programs facilitate the patient's socialization, which, in itself, may have contributed to some of the beneficial effects. Moreover, it has been demonstrated that exercise may enhance psychological wellbeing via a strong placebo effect. (38)

We found a high rate of participant loss in this study. Among our subjects, a 26% dropout rate was observed, which was higher than dropout rates reported in previous studies. (13,14) Variations in the type and duration of the programs can explain the different adherence rates of the subjects with MS. Our rehabilitative protocol was an outpatient program that lasted 6 months, the study by Mostert and Kesselring (14) used a 4-week inpatient program, and the study by Romberg et al (13) used a combined 3-week inpatient program and a 23-week home-based rehabilitation program. However, our findings, together with previous findings, could imply that people with MS may have limited tolerance for traditional exercise training, and other rehabilitative strategies, such as pacing and energy conservation techniques, should be considered to improve their functional status.

We are aware of the numerous limitations of our study. First, a large number of subjects did not complete the study, and we are aware that a type II error may have occurred in our analysis of results. Moreover, the participant loss prevented a full intention-to-treat analysis being carried out. However, as far as we know, our study is the first randomized controlled study comparing 2 different rehabilitation interventions in patients with MS, which was conducted in a crossover way. In addition, we did not find any between-group (all subjects versus subjects who completed the study versus subjects who withdrew from the study) difference in baseline conditions.

This finding could likely minimize the bias due to the effect of attrition on the study sample. (39)

Second, it is well known that there is a learning effect when maximal or submaximal exercise testing, such as the 6MWT and the CPET, are performed. Thus, we cannot exclude the possibility that the positive results of our study might have been due, in part, to the expected variability in these measures. However, our subjects performed the 6MWT twice on the study day to minimize the learning effect of this exercise test because performance usually reaches a plateau after 2 tests are done within a week. (26) Moreover, in the assessment of maximum exercise capacity, we followed the same method as that applied in previous clinical trials in which subjects performed the CPET only once. (12-14)

Third, we arbitrarily choose an 8-week washout period between the 2 interventions. However, previous studies of subjects with MS showed beneficial effects on disability and health-related quality of life after rehabilitation, which lasted for 6 weeks (40) to 9 weeks. (41) Moreover, in our study, we can exclude a carryover effect between interventions because no significant difference was found in baseline measurements of the 2 interventions.

Lastly, we are aware that we compared the AT program with the NR program by using specific outcomes for the AT program. We, therefore, cannot exclude the possibility that the NR program could be superior to the AT program with regard to nonaerobic outcomes (eg, flexibility, balance) that were not measured in this study.

Conclusions

The findings demonstrated that 8 weeks of AT may be more effective than NR in improving maximum exercise tolerance and walking capacity in patients with MS and mild to moderate disability, leading to some positive effects on health-related quality of life. Our study supports the view that AT may be beneficial for patients with MS who are not experiencing an exacerbation of symptoms. However, the high rate of participant loss that occurred in our study also indicates that exercise programs may harm patients with MS. Further studies are needed to determine whether a more graded AT program can improve the adherence of patients with MS.

Invited Commentary

Carol Leiper

The authors should be congratulated for proposing this study to investigate the relationship between an aerobic cycling program and a functional activity outcome such as the cost of walking. As they point out, it is possible that the physical impairments that occur with the disease also may lead to a more sedentary lifestyle and deconditioning, resulting in further limitations in functional ability. For many years, limited knowledge of the pathophysiology of multiple sclerosis restricted our efforts to select the appropriate intensity of intervention and the prevention of accumulation of functional disability. Studies such as this help us to formulate better hypotheses for future interventions.

In summary, the authors found that an 8-week program of cycling on a lower-extremity ergometer with progressive resistance resulted in an increase in walking distance and speed for individuals with mild to moderate impairment related to multiple sclerosis. Improvements also were seen in measures of aerobic capacity. Similar changes did not occur when the subjects performed a "neurological rehabilitation" exercise program described as emphasizing active movements and gait exercises.

I would like to address 2 very different topics related to the study: (1) whether reported improvements represent real change and (2) the importance of continued physical activity for people with physical disability.

Measurement of Change

The measure of walking distance during the 6-minute walk tests will be used as the example to discuss the first question. The authors report a statistically significant improvement in walking distance of approximately 24 m following the aerobic training but not after the neurological training. However, the comparison between the 2 groups did not indicate the superiority of the aerobic training. How do we explain this discrepancy? One solution is to look at the size of the standard deviations of the measurements. The larger the standard deviation, the less likely the results will be significant unless the mean values are greatly different. The authors have used these variables to calculate the effect size and show us that for these 2 measures it is indeed small.

Another way to translate the results into meaningful values for the clinician would be to ask the question, "What is the minimal detectable change (MDC) of the measurements that would indicate a real change, indicating either improvement related to the intervention or, perhaps in a chronic disease, deterioration over time?" Because all measurements have some error associated with them, we would like to know that a reported change exceeded the likelihood of that due to errors of measurement. The MDC is frequently reported as the value of the standard error of measurement (SEM) multiplied by [+ or -] 1.96 ([+ or -]2 standard deviations) and therefore should be outside the range of measurement error. For example, Kennedy and colleagues (1) determined the stability of both the speed of fast self-paced walking and the distance of the 6-minute walk in a sample of individuals with osteoarthritis who were waiting for hip or knee arthroplasty. They reported the SEMs for the tests and then determined the MDC for a 90% confidence interval ([MDC.sub.90]). For their group with osteoarthritis, a change of 4.04 seconds for the fast self-paced walk and a change of 61.34 m for the 6-minute walk would be needed to represent real changes.

Flansbjer and colleagues (2) used a similar calculation referred to as the "smallest real difference" (SRD) when assessing the reliability of several gait performance measures in people with hemiparesis following stroke. The mean time since stroke in their sample was 16 months, but the range was 6 to 46 months. The authors reported the SEM for the 6-minute walk to be 18.6 m and the SRD to be 51.56 m. In both the study by Kennedy and colleagues (1) and the study by Flansbjer and colleagues, (2) the range of walking distances of the subjects was large (approximately 500 m in each case), and the means and standard deviations were similar to those of the study by Rampello et al. The authors may consider determining the SEM to further evaluate their results for this group of people with multiple sclerosis.

A potential cause of the wide standard deviations of the measures reported by Rampello et al might be the wide range of Expanded Disability Status Scale (EDSS) scores permitted for inclusion in the study, particularly because they cite another study showing an inverse relationship between distance walked and EDSS score. It may be necessary to limit the inclusion criteria to a smaller range on the EDSS scale or to use a different descriptor of disease severity. A similar comment could be made for the inclusion criteria in the studies of Kennedy et all and Flansbjer et al. (2) Kennedy et al included subjects who were waiting for either knee or hip arthroplasty, and Flansbjer et al included individuals who had a stroke between 6 and 46 months prior to testing. As we attempt to be more specific in the nature and intensity of prescription of intervention for individuals with neurologic diseases, we find the need for better classification of individuals with the same general disease diagnosis. More specific classification of functional activity may provide the opportunity to set better definitions for goals either for improvement or to show maintenance of status rather than decline. Delitto et al (3) have attempted to do this for individuals with low back syndrome, as has VanSwearingen and Brach (4) for those with facial neuromotor disorders.

Physical Activity and Fitness for Individuals With Disability

As Rampello et al point out, there is only a small body of literature at present that attempts to look at the need for and effects of specified forms of exercise for those with multiple sclerosis to maintain function and possibly retard accumulation of impairments. Since the preparation of their manuscript, another study (5) has been published in which aerobic treadmill training was the intervention of choice. Both treadmill and cycle ergometry are forms of exercise that can be carried out independently by the individuals described in the samples.

Physical therapists see only a small proportion of the individuals diagnosed with multiple sclerosis. In most instances, it is not until the person is in overt functional crisis that a referral is made. Some individuals have been advised to restrict exercise, others have tried to exercise and become fatigued, and still others have never thought about the need to work at maintaining flexibility, strength, and endurance.

In 1998, the US Department of Health and Human Services published a document titled Healthy People 2010 (6) in which goals for increasing the health of US citizens are given. There is a chapter devoted to physical activity and fitness in which the current percentages of participation are given for several types of activity. One of the comparisons is between people with and without disabilities. The Table specifies the goals for 2010 and shows the current percentages of people engaged in physical activity.

In 1999, Physical Therapy published a professional perspective article by Rimmer in which he discussed the need to develop programs of health promotion that would be designed to reduce secondary conditions, maintain functional independence, provide opportunity for leisure and enjoyment, and enhance the overall quality of life for individuals with disability. (7) Rimmer proposed a need for rehabilitation professionals to connect or partner with community-based fitness programs to create an environment that welcomes the inclusion of people with disabilities. Other authors (8,9) have written about the benefits of physical activity, and in particular, in group settings, on the quality of life. In recent years, the American Physical therapy Association has offered programming at national meetings to assist physical therapists who desire to make the community connection or to develop community fitness centers within their own practices. It seems to me that one of the needs in such programs are simple functional tests that would allow the client to document real change or the maintenance of current status in a standard way. Each client seems to have a different personal measure of status quo, improvement or decline. We need to select tests that are meaningful to the clients and determine the measurement properties for well-defined groups (classification).

Rampello et al focus our attention on a specific form of exercise that is prevalent in fitness centers, physical therapist practices, and at home--leg cycle ergometry. Their functional measures were distance walked and speed of walking, which could be predicted to change based on exercise for the cardiopulmonary system and the musculoskeletal components of the legs. Their comparison intervention appears to be a more traditional program that encompasses a wide variety of exercise crossing the dimensions of motor control, flexibility, balance, and possibly strength. What are the functional measures or tests that will be useful to record health status for these dimensions? How specific are the guidelines to document a change in status? Could a change in health status actually have been achieved with the comparison intervention, but was unrecognized because the chosen tests did not measure the function represented by these characteristics? In formulating and reporting their research, the authors have afforded us the opportunity to propose new hypotheses and advance the knowledge of the specificity of exercise testing and prescription for individuals with physical disability.

References

(1) Kennedy DM, Stratford PW, Wessel J, et al. Assessing stability and change of four performance measures: a longitudinal study evaluating outcome following total hip and knee arthroplasty. BMC Museuloskelet Disord. 2005;6:3.

(2) Flansbjer UB, Holmback AM, Downham D, et al. Reliability of gait performance tests in men and women with hemiparesis after stroke. J Rehabil Med. 2005;37:75-82.

(3) Delitto A, Erhard RE, Bowling RW. A treatment-based classification approach to low back syndrome: identifying and staging patients for conservative treatment. Phys Ther. 1995;75:470-489.

(4) VanSwearingen JM, Brach JS. Validation of a treatment-based classification system for individuals with facial neuromotor disorders. Phys Ther. 1998;78:678-689.

(5) Newman MA, Dawes H, van den Berg M, et al. Can aerobic treadmill training reduce the effort of walking and fatigue in people with multiple sclerosis: a pilot study. Mult Scler. 2007;13:113-119

(6) Objectives for Improving Health, Part B: Focus Area 22: Physical Activity and Fitness. Healthy People 2010. Available at: www. health.gov/healthypeople.

(7) Rimmer JH. Health promotion for people with disabilities: the emerging paradigm shift from disability prevention to prevention of secondary conditions. Phys Ther. 1999;79:495-502.

(8) Stuifbergen AK. Physical activity and perceived health status in persons with multiple sclerosis. J Neurosci Nuts. 1997;29: 238-243.

(9) Di Fabio RP, Choi T, Soderberg J, Hansen CR. Health-related quality of life for patients with progressive multiple sclerosis: influence of rehabilitation. Phys Ther. 1997;77: 1704-1716.

Cl Leiper, PT, PhD, is Adjunct Professor of Physical Therapy and Director, Dan Aaron Stay Fit Exercise Program for Individuals With Parkinson Disease or Multiple Sclerosis, Arcadia University, 450 S Easton Rd, Glenside, PA 19038 (USA). Address all correspondence to Dr Leiper at: [e-mail].

Anais Rampello, Alfredo Chetta

Author Response

Anais Rampello, Alfredo Chetta

We thank Leiper for her very kind commentary on our article. In addition, it gives us the opportunity to focus on some important topics related to our study. Two areas have been specifically addressed: the measurement of change and the importance of physical activity for people with disability.

Measurement of Change

We agree with Leiper about the importance of this first point. Our study showed that the change in walking capacity after aerobic training was statistically significant when compared with baseline walking capacity, but not when compared with walking capacity after neurological rehabilitation.

One possible explanation for this result is the size of the standard deviations of the measurements, which might be related to the wide range of Expanded Disability Status Scale (EDSS) scores permitted for patient inclusion. We are aware that a smaller range of EDSS scores would have selected a more homogeneous sample of subjects and probably would have reduced the size of the standard deviations. However, we chose to include subjects with mild to moderate disability subjects in the study in order to assess the effect and the feasibility of aerobic training in people with moderate disability as well. We also are aware that, in order to improve our ability to intervene in terms of mode and intensity of exercise, a better classification of subjects with multiple sclerosis as well as other diseases is needed. Although the EDSS is the most widely used rating scale for people with multiple sclerosis, it shows some limitations (1,2) because it appears to be poorly sensitive to clinical change and has limited ability to distinguish among individuals in terms of their disability. Thus, we need new measures to assess both impairment and disability in people with multiple sclerosis. Consequently, the Multiple Sclerosis Functional Composite (MSFC) has been proposed by Cutter et al, (3) and it recently has been found to be more sensitive than the EDSS in detecting changes in function as a result of regular exercise. (4) However, the MSFC requires further validation in rehabilitation trims.

We completely agree with Leiper that the functional status measurements often are difficult to interpret because small differences may be statistically, but not clinically, significant. As Leiper points out, the minimal detectable change in the measurements is frequently obtained by statistical data processing. An alternative approach for establishing the threshold for a noticeable difference in walking capacity would be to obtain qualitative and quantitative measurements of walking from many patients over an extended period. However, when a large number of patients with chronic obstructive pulmonary disease (COPD) were each asked to rate their walking ability relative to how it had been a few months prior, a poor correlation was found between actual and perceived changes in walking ability. (5)

Another interesting approach could rely on how individuals judge themselves relative to others with the same disease, rather than relative to their memories of past health. This approach has been successfully reported for analyzing functional status measurements in patients with arthritis (6) and has been used for establishing a threshold distance for the Six-Minute Walk Test in patients with COPD. (5) The latter study (5) showed that distances needed to differ by 54 m for "average" patients to stop rating themselves as "about the same" and to start rating themselves as either "a little bit better" or "a little bit worse" (95% confidence interval=37-71 m). This threshold distance is obviously disease specific, and further studies are needed to obtain a threshold distance in patients with multiple sclerosis.

Physical Activity and Fitness for Individuals With Disability

Continued physical activity undoubtedly should be encouraged for individuals with physical disability and for those with multiple sclerosis particularly. Limitation of physical activity secondary to multiple sclerosis-related fatigue can lead to deconditioning and thus to further worsening of exercise tolerance and functional ability, as well as to reduced participation in social and family activities.

Because leg cycle ergometry and treadmill exercise (as proposed by Newman et al (7) in their recent study) represent forms of exercise that can be carried out in physical therapist practices as well as in community fitness centers or at home, continuation of physical activity should be promoted. Thus, we decidedly agree with Leiper about the need for a strict collaboration between rehabilitation professionals and community fitness centers in order to involve people with disabilities in wider fitness programs besides physical therapy programs. Functional measures such as walked distance or speed of walking could be simple functional tests that would show a meaningful change in everyday life activity in terms of improvement in social participation and overall quality of life in individuals with disabilities.

Lastly, Leiper commented on the rehabilitation intervention that was compared with the aerobic training program. As discussed in our article, we are aware that the measured outcomes were specific for the aerobic protocol and were not appropriate to detect significant changes in nonaerobic outcomes. For instance, functional measurement of balance, flexibility, or strength (force-generating capacity) by using balance tests such as the Berg Balance Scale (8,9) and assessment of range of motion and isometric muscle strength (10) by means of a dynamometer would probably show the superiority of neurological rehabilitation in other dimensions as compared with aerobic training. Nevertheless, the purpose of our study was to assess the effect of the aerobic program on the exercise capacity of individuals with multiple sclerosis in terms of walking capacity and maximum exercise tolerance because data on this topic are scanty.

References

(1) Sharrack B, Hughes RA, Soudain S, Dunn G. The psychometric properties of clinical rating scales used in multiple sclerosis. Brain. 1999;122:141-159.

(2) Hobart J, Freeman J, Thompson A. Kurtzke scales revisited: the application of psychometric methods to clinical intuition. Brain. 2000;123:1027-1040.

(3) Cutter GR, Baler ML, Rudick RA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999;122:871-882.

(4) Romberg A, Virtanen A, Ruutiainen J. Long-term exercise improves functional impairment but not quality of life in multiple sclerosis. J Neurol. 2005;252: 839-845.

(5) Redelmeier DA, Bayoumi AM, Goldstein RS, Guyatt GH. Interpreting small differences in functional status: the Six-Minute Walk Test in chronic lung disease patients. Am J Respir Crit Care Med. 1997;155: 1278-1282.

(6) Redelmeier DA, Lorig K. Assessing the clinical importance of symptomatic improvements: an illustration in rheumatology. Arch Intern Med. 1993;153: 1337-1342.

(7) Newman MA, Dawes H, van den Berg M, et al. Can aerobic treadmill training reduce the effort of walking and fatigue in people with multiple sclerosis? A pilot study. Mult Scler. 2007;13:113-119.

(8) Berg K, Wood-Danphinee S, Williams JI, Maki B. Measuring balance in the elderly: preliminary development of an instrument. Physiother Can. 1989;41:304-311.

(9) Cattaneo D, Regola A, Meotti M. Validity of six balance disorders scales in persons with multiple sclerosis. Disabil Rehabil. 2006;28:789-795.

(10) White LJ, McCoy SC, Castellano V, et al. Resistance training improves strength and functional capacity in persons with multiple sclerosis. Mult Scler. 2004;10: 668-674.

The study protocol was approved by the ethics committees of University Hospital of Parma and of G da Saliceto Hospital.

This article was received March 15, 2006, and was accepted January 9, 2007.

References

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(27) Chetta A, Zanini A, Pisi G, et al. Reference values for 6-minute walk test in healthy subjects 20-50 years old. Respir Med. 2006;100:1573-1578.

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(29) Wasserman K, Hansen JE, Sue DY, et al. Principles of Exercise Testing and Interpretation. 3rd ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:143-164.

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(33) Rodgers MM, Mulcare JA, King DL, et al. Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program. J Rehabil Res Dev. 1999;36:183-188.

(34) Kileff J, Ashburn A. A pilot study of the effect of aerobic exercise on people with moderate disability multiple sclerosis. Clin Rehabil. 2005;19:165-169.

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(37) Surakka J, Romberg A, Ruutiainen J, et al. Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial. Clin Rehabil. 2004;18: 737-746.

(38) Desharnais R, Jobin J, Cote C, et al. Aerobic exercise and the placebo effect: a controlled study. Psychosom Med. 1993; 55:149-154.

(39) Dumville JC, Torgerson DJ, Hewitt CE. Reporting attrition in randomised controlled trials. BMJ. 2006;332:969-971.

(40) Patti F, Ciancio MR, Cacopardo M, et al. Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients: a randomised controlled trial. J Neurol. 2003;250:861-866.

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* SensorMedics Corp, 22705 Savi Ranch Pwy, Yorba Linda, CA 926674609.

A Rampello, MD, is Registrar, Department of Geriatrics and Rehabilitation, Unit of Rehabilitation, University Hospital of Parma, Parma, Italy.

M Franceschini, MD, is Consultant, Department of Geriatrics and Rehabilitation, Unit of Rehabilitation, University Hospital of Parma.

M Piepoli, MD, is Consultant, Heart Failure Unit, Department of Cardiology, G da Saliceto Hospital, Piacenza, Italy.

R Antenucci, MD, is Registrar, Unit of Rehabilitation, G da Saliceto Hospital.

G Lenti, MD, is Consultant, Unit of Rehabilitation, G da Saliceto Hospital.

D Olivieri, MD, is Full Professor, Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Parma, Italy.

A Chetta, MD, is Associate Professor, Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Viale G Rasori, 10-43100, Parma, Italy. Address all correspondence to Dr Chetta at: [e-mail].

[Rampello A, Franceschini M, Piepoli M, et al. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Phys Ther. 2007;87:545-555.]

Dr Rampello, Dr Franceschini, and Dr Chetta provided concept/idea/research design. Dr Rampello and Dr Chetta provided writing and data analysis. Dr Rampello and Dr Piepoli provided data collection. Dr Franceschini, Dr Olivieri, and Dr Chetta provided project management. Dr Franceschini and Dr Olivieri provided fund procurement. Dr Rampello, Dr Antenucci, and Dr Lenti provided subjects. Dr Piepoli, Dr Olivieri, and Dr Chetta provided consultation (including review of manuscript before submission).

Table 1.
Characteristics of the 19 Subjects With Multiple Sclerosis Enrolled
in the Study, of the 11 Subjects Who Completed the Study, and of the
8 Subjects Who Withdrew From the Study (a)

Variable                         All Subjects      Subjects
                                 (n = 19)          Who
                                                   Completed
                                                   Study
                                                   (n = 11)

Age (y)                           41 [+ or -] 8     44 [+ or -] 6
Sex (female/male)                 14/5               8/3
BMI (kg/[m.sup.2])                22 [+ or -] 3     23 [+ or -] 3
Disease duration (y)               8 [+ or -] 5      6 [+ or -] 4
Using disease-modifying drugs     15/4               8/3
  (yes/no)
EDSS score (0-10)                  3.5 (1-6)         3.5 (1-4)
[FEV.sub.1]/VC (% of predicted    82 [+ or -] 8     82 [+ or -] 8
  value)
[FEV.sub.1] (% of predicted      103 [+ or -] 13   105 [+ or -] 13
  value)
TLC (% of predicted value)       112 [+ or -] 11   112 [+ or -] 14
PImax (cm [H.sub.2]O)             83 [+ or -] 35    75 [+ or -] 42
PEmax (cm [H.sub.2]O)             93 [+ or -] 36    91 [+ or -] 37

Variable                         Subjects Who      P (b)
                                 Withdrew
                                 From Study
                                 (n = 8)

Age (y)                           37 [+ or -] 10   .21
Sex (female/male)                  6/2             .99
BMI (kg/[m.sup.2])                21 [+ or -] 3    .54
Disease duration (y)              10 [+ or -] 6    .34
Using disease-modifying drugs      7/1             .74
  (yes/no)
EDSS score (0-10)                  3.25 (1.5-6)    .96
[FEV.sub.1]/VC (% of predicted    83 [+ or -] 8    .99
  value)
[FEV.sub.1] (% of predicted      100 [+ or -] 13   .69
  value)
TLC (% of predicted value)       111 [+ or -] 8    .94
PImax (cm [H.sub.2]O)             95 [+ or -] 16   .46
PEmax (cm [H.sub.2]O)             96 [+ or -] 36   .94

(a) Values expressed as mean [+ or -] SD, except for Expanded
Disability Status Scale (EDSS) scores, which are expressed as
median (range). BMI = body mass index, [FEV.sub.1] = forced
expiratory volume in 1 second, VC = vital capacity, TLC = total
lung capacity, PImax = maximum inspiratory pressure, Pemax = maximum
expiratory pressure.

(b) P values assessed by chi-square test (sex, using disease-modifying
drugs), analysis of variance (age, BMI, disease duration, [FEV.sub.1]/
VC, [FEV.sub.1], TLC, PImax, PEmax), and Kruskal-Wallis test (EDSS
score).

Table 2.
Preintervention and Postintervention Values for Lung Function,
Respiratory Muscle Strength, 6-Minute Walk Tests, and Cardiopulmonary
Exercise Tests in Subjects With Multiple Sclerosis (a)

Variable                Aerobic Training Group

                        Preintervention      Postintervention     P (b)

[FEV.sub.1]/VC            84 [+ or -] 6        83 [+ or -] 8       .74
  (% of predicted
  value)
[FEV.sub.1] (% of        110 [+ or -] 11      108 [+ or -] 10      .66
  predicted value)
TLC (% of predicted      117 [+ or -] 14      116 [+ or -] 13      .86
  value)
PImax (cm [H.sub.2]O)     78 [+ or -] 45       80 [+ or -] 42      .91
PEmaX (cm [H.sub.2]O)     88 [+ or -] 38       90 [+ or -] 35      .89
Walking distance (m)     308 [+ or -] 98      332 [+ or -] 108     .02
Walking distance          55 [+ or -] 17       59 [+ or -] 19      .02
  (% of predicted
  value)
Walking speed             51 [+ or -] 16       55 [+ or -] 18      .02
  (m/min)
Cost of walking         0.20 [+ or -] 0.07   0.20 [+ or -] 0.07    .13
  (mL [O.sub.2] x
  [kg.sup.-1]
  x [m.sup.-1])
Peak V[O.sub.2]         17.1 [+ or -] 7.0    20.0 [+ or -] 6.6     .01
  (mL/min/kg)
Peak V[O.sub.2] (% of     58 [+ or -] 18       68 [+ or -] 18      .01
  predicted value)
Maximum work rate         82 [+ or -] 43      103 [+ or -] 48      .01
  (W)
Peak V[O.sub.2]/HR       7.8 [+ or -] 3.0     8.7 [+ or -] 3.2     .04
  (mL/bpm)
Peak V[O.sub.2]/HR        75 [+ or -] 19       84 [+ or -] 17      .04
  (% of predicted
  value)

Variable                Neurological Rehabilitation Group

                        Preintervention      Postintervention

[FEV.sub.1]/VC            82 [+ or -] 8        84 [+ or -] 7
  (% of predicted
  value)
[FEV.sub.1] (% of        105 [+ or -] 13      109 [+ or -] 11
  predicted value)
TLC (% of predicted      113 [+ or -] 14      115 [+ or -] 14
  value)
PImax (cm [H.sub.2]O)     75 [+ or -] 42       77 [+ or -] 41
PEmaX (cm [H.sub.2]O)     91 [+ or -] 37       92 [+ or -] 38
Walking distance (m)     298 [+ or -] 114     308 [+ or -] 110
Walking distance          53 [+ or -] 20       55 [+ or -] 20
  (% of predicted
  value)
Walking speed             50 [+ or -] 19       51 [+ or -] 18
  (m/min)
Cost of walking         0.23 [+ or -] 0.1    0.22 [+ or -] 0.09
  (mL [O.sub.2] x
  [kg.sup.-1]
  x [m.sup.-1])
Peak V[O.sub.2]         16.8 [+ or -] 6.5    16.9 [+ or -] 6.1
  (mL/min/kg)
Peak V[O.sub.2] (% of     57 [+ or -] 17       57 [+ or -] 18
  predicted value)
Maximum work rate         79 [+ or -] 45       82 [+ or -] 42
  (W)
Peak V[O.sub.2]/HR       7.8 [+ or -] 2.9     8.1 [+ or -] 3.5
  (mL/bpm)
Peak V[O.sub.2]/HR        76 [+ or -] 21       78 [+ or -] 25
  (% of predicted
  value)

Variable                Neurological
                        Rehabilitation Group

                        P (b)    P (b)    P (b)

[FEV.sub.1]/VC            .54      .51     .75
  (% of predicted
  value)
[FEV.sub.1] (% of         .44      .34     .82
  predicted value)
TLC (% of predicted       .74      .51     .86
  value)
PImax (cm [H.sub.2]O)     .91      .87     .86
PEmaX (cm [H.sub.2]O)     .95      .85     .89
Walking distance (m)      .17      .59     .18
Walking distance          .22      .67     .25
  (% of predicted
  value)
Walking speed             .14      .60     .23
  (m/min)
Cost of walking           .41      .42     .13
  (mL [O.sub.2] x
  [kg.sup.-1]
  x [m.sup.-1])
Peak V[O.sub.2]           .88      .66     .02
  (mL/min/kg)
Peak V[O.sub.2] (% of     .88      .89     .02
  predicted value)
Maximum work rate         .47      .53     .02
  (W)
Peak V[O.sub.2]/HR        .57      .96     .40
  (mL/bpm)
Peak V[O.sub.2]/HR        .67      .87     .49
  (% of predicted
  value)

(a) Values expressed as mean [+ or -] SD. [FEV.sub.1] = forced
expiratory volume in 1 second, VC = vital capacity, TLC = total lung
capacity, Pimax = maximum inspiratory pressure, PEmax = maximum
expiratory pressure, V[O.sub.2] = oxygen uptake, HR = heart rate. P
values assessed by means of analysis of variance for repeated measures
and Newman-Keuls multiple comparison test.

(b) Preintervention vs Postintervention.

(c) Preintervention vs Preintervention.

(d) Postintervention vs Postintervention.

Table 3.
Preintervention and Postintervention Modified Fatigue Impact Scale
(MFIS) Scores in Subjects With Multiple Sclerosis (a)

Variable       Aerobic Training Group

               Preintervention   Postintervention   P (b)

Total MFIS     3G (3-57)         29 (4-56)          .66
  score
Physical       17 (3-27)         14 (4-23)          .39
  subscale
Cognitive      11 (0-34)          8 (0-36)          .84
  subscale
Psychosocial    3 (0-6)           3 (0-7)           .89
  subscale

Variable       Neurological Rehabilitation Group

               Preintervention   Postintervention

Total MFIS     30 <6-52)         26 <3-67)
  score
Physical       19 <6-33)         13 <3-26)
  subscale
Cognitive      11 (0-31)         10 (0-40)
  subscale
Psychosocial    4 (0-G)           2 (0-G)
  subscale

Variable       Neurological
               Rehabilitation Group

               P (b)   P (b)   P (b)

Total MFIS     .64     .94     .86
  score
Physical       .55     .79     .89
  subscale
Cognitive      .97     .00     .71
  subscale
Psychosocial   .57     .G9     .92
  subscale

(a) Values are expressed as median (range). P values assessed by
means of Friedman test.

(b) Preintervention vs Postintervention.

(c) Preintervention vs Preintervention.

(d) Postintervention vs Postintervention.

Table 4.
Preintervention and Postintervention Multiple Sclerosis Quality of
Life-54 Questionnaire (MSQOL-54) Scores in Subjects With Multiple
Sclerosis (a)

Variable             Aerobic Training Group

                     Preintervention   Postintervention   P (b)

Physical function     68 (35-95)        60 (25-95)          .59
Role limitations-     25 (0-100)        75 (0-100)          .69
  physical
Role limitations-    100 (0-100)       100 (0-100)          .66
  emotional
Pain                  63 (23-100)       63 (32-100)         .59
Emotional well-       52 (4-84)         56 (28-84)          .02
  Being
Energy                36 (8-64)         44 (32-64)          .04
Health perception     40 (10-70)        35 (10-75)          .84
Social function       67 (33-100)       75 (50-100)         .45
Cognitive             70 (0-100)        75 (10-100)         .69
  function
Health distress       60 (40-95)        75 (60-95)          .03
Sexual function      100 (42-100)      100 (33-100)        1.00
Sexual                75 (50-75)        75 (50-75)          .66
  satisfaction
Change in health      50 (25-75)        50 (25-50)          .96
Overall quality       36 (5-77)         28 (10-82)         1.00
  of life
Physical health       50 (39-82)        59 (44-81)          .65
  composite
Mental health         60 (10-86)        66 (24-90)          .41
  composite

Variable             Neurological Rehabilitation Group

                     Preintervention   Postintervention

Physical function     70 (25-95)        55 (20-95)
Role limitations-     50 (0-100)        75 (0-100)
  physical
Role limitations-    100 (0-100)       100 (0-100)
  emotional
Pain                  68 (30-100)       77 (38-100)
Emotional well-       56 (4-76)         52 (28-76)
  being
Energy                44 (24-56)        40 (20-72)
Health perception     45 (5-70)         35 (15-65)
Social function       75 (8-92)         83 (38-100)
Cognitive             70 (5-100)        80 (25-100)
  function
Health distress       65 (15-90)        75 (55-100)
Sexual function      100 (50-100)      100 (33-100)
Sexual                75 (75-100)       75 (0-100)
  satisfaction
Change in health      50 (25-75)        75 (50-75)
Overall quality       28 (20-73)        36 (20-82)
  of life
Physical health       53 (43-81)        57 (41-81)
  composite
Mental health         63 (18-85)        66 (32-87)
  composite

Variable             Neurological
                     Rehabilitation Group

                     P (b)    P (b)   P (b)

Physical function      .92      .72     .84
Role limitations-      .71      .72     .97
  Physical
Role limitations-      .87     1.00     .76
  emotional
Pain                   .79      .77     .41
Emotional well-        .04      .59     .62
  being
Energy                 .86      .67     .14
Health perception      .76      .92     .92
Social function        .81      .74     .49
Cognitive              .77     1.00    1.00
  function
Health distress        .03      .83     .74
Sexual function        .61      .84     .76
Sexual                 .87      .97     .92
  satisfaction
Change in health       .66      .97     .68
Overall quality        .36      .59     .19
  of life
Physical health        .33      .55    1.00
  composite
Mental health          .03      .51     .89
  composite

(a) Values are expressed as median (range). P values assessed by means
of Friedman test.

(b) Preintervention vs postintervention.

(c) Preintervention vs preintervention.

(d) Postintervention vs postintervention.

Table.
Goals for 2010 and Current Percentages of People Engaged in Physical
Activity (a)

Goal                                     Current Level   Current Level
                                         Without         With
                                         Disability      Disability

22-1   Reduce the proportion of adults   36%             56%
         who engage in no leisure-time
         physical activity

22-2   Increase the proportion of        30 min          30 min
         adults who engage regularly       [greater        [greater
         in moderate physical activity     than or]        than or
         for at least 30 min per day       equal to] 5     equal to] 5
                                           days per        days per
                                           week = 16%      week = 12%

       Same goal                         20 min          20 min
                                           [greater]       [greater
                                           than or]        than or
                                           equal to] 3     equal to] 3
                                           days per        days per
                                           week = 33%      week = 23%

22-3   Increase the proportion of        25%             13%
         adults who engage in vigorous
         physical activity that
         promotes the development and
         maintenance of
         cardiorespiratory fitness
         [greater than or equal to] 3
         days per week for ?20 min

22-4   Increase the proportion of        20%             14%
         adults who perform physical
         activities that enhance and
         maintain muscular strength
         and endurance

22-5   Increase the proportion of        31%             29%
         adults who perform physical
         activities that enhance and
         maintain flexibility

(a) Adapted from: Objectives for Improving Health, Part B: Focus Area
22: Physical Activity and Fitness. Healthy People 2010. Available at:
www.health.gov/healthypeople.