The Effects of Concurrent Resistance and Aerobic Exercise Training on Functional Status in Patients with Multiple Sclerosis

Abstract

Loss of balance and walking ability are two of the primary impairments in multiple sclerosis (MS), which leads to loss of autonomy, increased fatigue perception, and disease severity in patients. Physical activity has been shown to ameliorate MS functional impairments, but there is limited evidence of synergistic efficacy of exercise training interventions that have both a resistance and aerobic focus in these patients. We evaluated the effect of a 12-wk combined training intervention (resistance and aerobic exercise) on balance, walking ability, fatigue perception, quality of life, and severity of disease in patients with MS. The combined training was well tolerated by the patients and improved the quality of life of the patients as also reflected in the improvement in walking and balance ability as well as reduced depression, fatigue, and severity of disease. The results of this study confirm the beneficial effects of physical activity in patients with MS and support the use of a combination of resistance and aerobic exercise training to achieve functional and psychological therapeutic outcomes.

Introduction

Multiple sclerosis (MS) is a chronic disabling neurodegenerative disease characterized by extreme intervariability and intravariability in clinical course, with signs and symptoms that may affect functional, psychological, and cognitive area; some patients may rapidly lose their independence while others experience long periods without new symptoms. However, MS impairments may cause dysfunctions that lead to a progressive worsening of quality of life (QoL) (¹). A personalized approach to symptom management through an interdisciplinary approach that includes, in addition to pharmacological therapy, motor reeducation may determine a global path aimed to improve the living conditions of patients and their family (caregivers), allowing patients to maintain, as long as possible, their own autonomy (²). The primary functional impairments reported in these patients are loss of balance and mobility (³), which are characterized by increased swaying in quiet stance, delayed responses to postural perturbations, and reduced ability to move toward their limits of stability (⁴). Physical activity (PA) is a potentially modifiable behavior associated with several beneficial effects in patients with MS (^5,6). These patients are, however, less physically active than age-matched adults (⁷) as a result of a downward spiral which leads to sedentary behavior, loss of functional abilities, and increased depressive symptoms (⁸). Different types of physical activity have been suggested for patients with MS, such as aerobic exercise (⁹), progressive resistance training (¹⁰), and interval training (¹¹); combined training (CT) (endurance-strength training) seems to restore several functional impairments, and it is reported as more easily tolerated by patients, but its effects on balance and mental health are still poorly characterized (^12–14). Therefore, we performed a 12-wk randomized controlled trial to assess the effects of CT intervention (resistance and aerobic exercise) (24 sessions) on balance and walking ability in patients with MS. A secondary aim was to evaluate the impact of this approach on QoL, severity of disease, and fatigue perception to understand whether it could have positive effects on both functional and psychological areas in these patients. The same parameters were also evaluated in a conventional physiotherapy group (FKT).

Population

This was a pilot randomized controlled trial. We tested the effect of two different protocols on functional and psychological parameters in patients with MS. The total sample size (n = 20) was estimated through an a priori power analysis. The analysis was carried out with the G*Power software (G*Power V 3.1.3 Franz Faul, Universität Kiel, Germany), assuming a multivariate approach for between effects, within effects, and interactions. For the procedure the following parameters were considered: effect size f = 0.33 (calculated from η²p = 0.10 − medium effect), α =0.05, power = 0.80 (¹⁵). A flowchart of the study is shown in Figure. After approval by the Ethical Committee Policlinico Umberto I (RIF.CE:4520), the subjects were screened by a neurologist specializing in treatment of patients with MS. The inclusion criteria were: male or female; age, between 25 and 55 years; MS diagnosis according to the revised criteria (¹); a disability level assessed by Expanded Disability Status Scale (EDSS) (^16,17) score between 2.5 and 5.5; no clinical relapse within 1 month of the start of the protocol; authorization to practice sports after a specialized medical assessment. After screening, the patients were randomly assigned to either the CT group (n = 10) or the FKT group (n = 10), using a random computer program (Table 1). After the screening and randomization, all 20 patients (5 men, 15 women) signed the informed consent and started the physical and psychological evaluations. The same tests were proposed to all patients after the 24 sessions of activity.

Figure: Flowchart of the study.

Table 1: Baseline patients' characteristics.

Functional Assessment

• The Berg Balance Scale (¹⁸) (BBS) is a functional ordinary scale of static and dynamic balance, consisting of 14 items. It involves the execution of common movements of daily life.
• The Timed Up & Go Test (TUG) is a test that evaluates the muscular function and mobility. The National Institute of Clinical Evidence guidelines advocate the use the TUG test for assessment of gait and also are correlated to the balance and the prevention of falls in older people (¹⁹).
• The 6-min walking test (6MWT) (²⁰) is commonly used to assess endurance and cardiorespiratory fitness and has a strong correlation with subjective measures of walking ability and physical fatigue in patients with MS. The 10-m walking test (10MWT) (²¹) assesses walking speed in walking 10 m without assistance.

Psychological Assessment

Multiple Sclerosis Quality of Life-54 (MSQOL-54) (²²) is a questionnaire that evaluates both generic and MS-specific items in the physical and emotional spheres, the level of perceived health, social, cognitive and sexual functions, and the QoL. The summary scores are the physical health composite summary and the mental health composite summary.

The nine item Patient Health Questionnaire (PHQ9) (²³) is a self-reported questionnaire for screening, diagnosis, monitoring, and measuring severity of depression.

Fatigue Severity Scale (FSS) (²⁴) is a questionnaire that assesses the level of perceived fatigue. It is used to estimate the severity of the symptom, and it is composed by a list of nine entries with a score from 1 (completely in disagreement) to 9 (completely agree).

Intervention protocols

All patients, enrolled in the two intervention groups, performed 24 sessions of activity, twice a week, 1 h per session over 12 wk. Training sessions were conducted in a gym equipped for people with disabilities at the University Campus.

CT is a well-characterized strength and aerobic training program. This protocol provides an initial phase of warm-up followed by strength training consisting of three exercises for the lower limbs (Squat, Lateral Lunges, and Calf + Leg flexion), and three for the upper limbs (Biceps Curl + Arm Extension and Triceps push), at 50% of one-repetition max (1RM) evaluated after a familiarization phase. For each exercise, two series of 10 to 15 repetitions were carried out. The recovery between the two series was 30 s, while recovery between the different exercises was 1 min. After this phase, aerobic training was performed consisting of 10 min on a cycle ergometer at 65% of HRmax evaluated using the Karvonen formula: Exercise HR = % of target intensity (HRmax − HRrest) + HRrest (²⁵). Stretching exercises of major muscle groups and breathing exercises were performed during the final phase of the protocol. The sessions were performed in small groups of patients (4 to 5 patients with MS each time).

Conventional physiotherapy (FKT) is the therapy recommended by neurologists as supportive and specific to each patient. Patient were addressed in specialized centers near the hospital, where they participated in on-to-one interventions with the therapist performing passive and active exercises for the upper and lower limbs (i.e., Bobath and Vojta methods).

Statistical Analysis

The statistical package IBM SPSS version 20 (IBM, Chicago, IL) was used for the analysis. Data were presented as median (Mnd) and interquartile range (IQR) values. The Shapiro-Wilk test was applied, before the analysis, to test the normal distribution of the data. Due to the nonnormal distribution of the data, a nonparametric approach was chosen to test the effect of time (i.e., pre-post), and variables were examined by means of Wilcoxon Signed Rank tests conducted separately for the two groups (i.e., CT, FKT). The significance level for all comparisons was set at P ≤ 0.05.

Results

The BBS test reported a slight balance increase in the CT group (5%) after 24 sessions of training, while the FKT group showed a nonsignificant decrease after treatment (−2%). The impact of CT on balance is sustained by the TUG analysis, which reported an improvement in the test performance (pre = 8.01 ± 2.57; post = 6.17 ± 1.21; P = 0.012) in CT group, no differences were found in the FKT group. Data from endurance and speed walking tests reported a significant improvement in the CT group (6MWT pre = 413.33 ± 106.87; post = 498.75 ± 113.94; P = 0.003. 10MWT pre = 4.45 ± 1.51; post = 3.32 ± 0.55; P = 0.003 (Table 2). The same positive trends were found in the FKT group (6MWT = 5%; 10MWT = −7%), although not significant.

Table 2: Functional tests: Changes in strength and muscular functions before and after 12 wk of protocol.

The MSQOL-54 questionnaire (Table 3) showed a significant improvement of the Physical Health Score both in the CT group (physical pre = 28.71 ± 14.33; post = 45.94 ± 16.21; P = 0.003) and in the FKT group (physical pre = 50.30 ± 22.12; post = 60.05 ± 22.32 P = 0.007). While a significant improvement in the Mental Health composite summary score was found in the CT group only (mental pre = 31.29 ± 17.12; post = 49.97 ± 20.00; P = 0.004); data in the FKT group revealed a positive trend (15%). The same results were found for depressive symptoms. The 9PHQ score was significantly reduced after the CT protocol (pre = 14.69 ± 7.8; post = 7.36 ± 4.4 P = 0.02). Baseline data of these scores are extremely variable between groups, but the study is evaluating the effect within group, and both interventions seem to have positive impacts on psychological impairments, despite the disability level. As reported in the table, data on fatigue perception revealed a decrease of the score in both groups: the FSS score was significantly reduced after the CT protocol (pre = 5.93 ± 1.21; post = 4.59 ± 1.44; P = 0.019), as well as the FKT protocol (pre = 4.29 ± 2.25; post = 3.90 ± 2.04; P = 0.032). Data related to the general disability score showed a decreased EDSS after the interventions, suggesting a general positive effect of the protocols proposed (CT pre = 4.73 ± 0.90; post = 4.15 ± 1.18; P = 0.006).

Table 3: Psychological parameters analysis before and after 12 wk of protocol.

Discussion

All patients completed the protocols with no side effects reported. The CT intervention was well tolerated and improved several parameters in patients with MS. As previously reported by Cattaneo et al. (²⁶), data on this intervention seem promising, despite the small increase in the dynamic and static balance, as is evidenced by the TUG test, it could potentially reduce the risk of falls (²⁷). Our data suggest that this CT intervention, focused on improvements of lower limbs muscles through exercises, such as squats and lateral lunges, is able to restore the patient's ability to quickly respond to stimuli during the first walking meters, improving the patients' with MS autonomy. However, the clinical significance is not yet clear, and further research is necessary. Another test associated with healthy status and independence in patients with MS is the 6MWT (^28,29). Due to the impairments related to the disease, this was the most challenging test for patients with MS to complete, primarily during the preintervention evaluation. The results of this test suggest that a well-characterized adapted CT can lead to significant improvements in the patient's performance and general fitness. The 10MWT analysis confirmed the positive effect of a structured CT on walking autonomy in patients with MS, reporting a decreased time to perform this test after 24 CT sessions. These data underline that CT is a well-tolerated intervention able to improve several functional parameters in patients with MS (³⁰). According to several studies, balance and walking ability seem to be strictly linked with EDSS scores (^31,32). In the present study, the EDSS score of the patients decreased after both interventions, demonstrating a decline of the disease severity. Despite improvements in gait resistance, mobility, balance, and cognitive function after different types of physical activities have already been evaluated (^33–35), as far as the authors are aware, the present pilot study is the first to report on the potential impact of the CT intervention on the EDSS score. This corroborates the idea that a personalized protocol is able to improve balance and walking ability, and consequently on the course of MS disability level, helping patients with symptom management and restoring their autonomy. As previously reported in another study, physical activity has positive effects on patients' with MS QoL (³⁶), but little is known about the effect on other psychological parameters, such as depression and fatigue perception. Despite the variability between groups, our data on the MSQOL-54, PHQ9, and FSS questionnaires revealed a strong impact of CT on both mental and functional scores, as well as on the FSS score. This study suggests that, regardless the degree of psychological impairments, CT and FKT seem to have positive effects on this area. Probably the higher impact on CT group is due because the exercises were carried out in small group increasing the social activity, while the FKT protocol were performed one-to-one patient and physiotherapist. Adding to studies on older adults that suggest exercise as an important tool to counteract the mental health decline (^37,38), our preliminary results provide new data about the positive impact of structured physical activity on depression in these patients. Despite some studies reporting a negative correlation between physical activity level and depressive status (^8,39), there are limited data on interventional studies, which could provide evidence on the intensity, duration, and the type of exercise able to improve this parameter. The pilot protocol utilized in this study provides a good starting point to deepen this topic and provide physical activity guidance which may reduce different MS impairments. The FSS results reported that, despite the lower impact on functional parameters of FKT, patients in this group decreased their perception of fatigue probably due to the comfortable and relaxing nature of the exercises proposed. In keeping with the current literature, CT is associated with small or little reduction in fatigue (⁴⁰). Plow et al. (2009) and Smith et al. (2009) (^41,42) reported no change or a negative effect of the CT on fatigue. In contrast to these studies, the CT intervention used in the present study reduced fatigue relative to the control group. This finding further supports the idea that CT can induce important functional therapeutic outcomes and seems promising as a therapeutic protocol to restore patient mental health, improve the general QoL and fatigue that occurs in this patient group. Despite the outcomes across most domains reach the statistical significance that favor the CT group, there are some potential limitation in this study, the small sample size per group and the wide ranging symptoms of the patients generally did not allow to meet the threshold for minimal clinically important differences between group. This outcome has been aided by the use of objective and specific functional and psychological evaluations used to assess the interventions. Moreover, the FKT protocol was carried out by various physiotherapists reported by the hospital following the procedure of the Italian national health system for MS, in order to evaluate the difference between a structured physical training and the protocol proposed by the health system.

Conclusions

The results of this study confirm the beneficial effects of physical activity in patients with MS and support the use of a combination of resistance and aerobic exercise training to achieve functional and psychological therapeutic outcomes. Although additional investigations are needed to better understand the real potential of the CT intervention, this form of exercise training was well tolerated by the patients and improved the QoL of the patients as also reflected in the improvement in walking and balance ability as well as reduced depression, fatigue, and severity of disease. These positive results, interpreted in the context of the wider scientific literature (⁴³), should help promote the use of exercise training in patients with MS as exercise training can improve physical and neurological symptoms and, in doing so, contribute to long-term disease management, decreasing disease severity, perception of fatigue, and improving QoL. PA should be introduced at an early stage of the disease, if possible, to reduce disease progression, symptoms, and disabilities (⁴⁴).