Yoga Versus Physical Therapy In Multiple Sclerosis: Randomized Controlled Trial

Background. Yoga originated in the territory of modern India more than 3000 years ago and uses techniques for working with the musculoskeletal system, cardiorespiratory system and attention. Currently, the effectiveness and safety of yoga in patients with various neurological disorders, including MS, is of interest to many scientists and clinicians. The main aim of this study is to examine the effect of yoga on symptoms and quality of life in patients with MS versus physical therapy (exercise therapy) and no exercise. Methods. The patients were randomly assigned to 3 groups (yoga, PT, or waiting list), patients from the waiting list had an opportunity to enter the yoga program after the end of the trial period. After 12 weeks of regular exercises (or absence of them), the effect of yoga and PT on the functional status and quality of life of patients were evaluated. The MS treatment was a part of routine practice, as prescribed by the treating neurologist. The data was collected during the patients’ two visits to the study center - before the start of the study and at the end of the 12-week period. The in-person examination included a doctor's assessment of the EDSS, the SF-36 quality of life questionnaire, the fatigue scale, the Berg balance scale, the 6-minute walking test. Results. A total of 36 patients nished the clinical study: 30 women and 6 men. There was no statistically signicant difference between the groups in terms of improvement in MS symptoms as measured by the balance, walking test and fatigue scales. However, in the analysis of the 8 criteria of SF-36 quality-of-life questionnaire the covariation analysis statistically signicant differences were found in favor of the yoga group in terms of physical functioning (PF) (p=0.003), life activity (VT) (p<0.001), mental health (MH) (p=013), social functioning (SF) (p=0.028). Conclusions. Thus, regular yoga classes under the guidance of qualied staff are a promising method of non-drug rehabilitation of patients with MS with motor disorders. More research is needed to examine the impact of yoga on clinical patient improvement and quality of life indicators.


Background
Multiple sclerosis (MS) is a progressive, chronic disease of the central nervous system, which manifests itself in various neurological symptoms and their combinations, debuts more often at a young age, and may have different variants of the course. As a result, patients experience temporary or progressive disturbances of movement, walking function, balance, restriction of self-reliance, and a decrease in quality of life. The most common symptoms of multiple sclerosis are muscle weakness and instability in walking, spasticity, pathological fatigue, and other symptoms of CNS lesions may occur at various levels (Scierlo S. 2017). In this regard, MS is one of the frequent reasons for the increased disability length of different age groups of patients. Studies show that more than 65% of patients have trouble moving and up to 85% of patients have gait disorders (Rogers K. 2015). Thus, all MS patients need comprehensive rehabilitation and for many patients, it is required in the early stages of the disease. There is evidence that physical therapy programs (physical exercises) can improve MS patients' functionality (mobility, walking, endurance) and quality of life (Khan T. 2007, Alphonsus K. 2019, Motl RW. 2020). There is also evidence that more than 60% of patients are willing to use additional approaches to drug treatment, which can include exercise (Miller P. 2017). Among the actively studied methods of physical therapy used in the rehabilitation of patients with MS, there is physical therapy, yoga classes, dance therapy, aerobic exercises, and a combination of these approaches.
The effectiveness of physical therapy has beenexamined in many studies. A review of 26 randomized trials found a reduction in the risk of aggravation in the group of patients with MS performing exercise compared to the patients without gymnastics (6.3% At the same time, it is obvious that the correct comparison of these methods is of great interest for both researchers and specialists in the rehabilitation of patients with MS. This approach can expand our understanding of the mechanisms of functional disorders during MS and the ways to correct them. As a result, specialists will be able to combine the advantages of different approaches, improving the quality of rehabilitation. It should also be noted, that contrary to the well-de ned physical exercises protocols (Motl RW. 2020, Halabchi F. 2017), in most of the available at the moment studies, there is no detailed description for the performance of yoga protocols, i.e. those complexes of asanas, (special physical exercises), pranayama (breathing exercises) and techniques of mental relaxation, which were offered to patients, as well as the ways of their implementation. We can nd an exception only in some articles, where the images and names of poses and the sequence of their performance are given (Guner S. 2015, Kishiyama S. 2002, de Oliveira G 2016, Naja P. 2017). In other articles, the method of exercise and the use of yoga techniques are described only in general terms, such as hatha yoga, classical yoga, pranayama, yoga poses, breathing exercises. Typically, the frequency and duration of regular classes, the total number of classes, and the period of research are also speci ed.
However, our experience of teaching yoga, both in regular classes and for students with speci c health problems, including patients with MS shows that for each particular disease or symptom, yoga exercises should be performed according to specially developed techniques. At the same time, each component of this technique: the choice of a set of poses, sequence, duration, and correctness of their performance, plays a crucial role in achieving the goals and is extremely important for ensuring the reproduction, veri cation, and further practical use of the results.
Therefore, for this study we used B.K.S. Iyengar method of yoga training, which is one of the most In this regard, themain aim of this study is to examine the effect of Iyengar yoga on symptoms (such as walking, balance di culties) and quality of life in patients with MS, versus physical therapy (exercise therapy) and no exercise.

Methods
Patients.
This study involved adult patients with MS of both genders who had not performed regular physical exercises before. The patients were randomly assigned to 3 groups (yoga, physical therapy, or waiting list), patients from the waiting list had an opportunity to enter the yoga program after the end of the trial period. The observation group (1, 2 or 3) was known to both the patient and the doctor, but it was blinded for the rater. Participants were randomly divided into the yoga, physical therapy, or no exercise group.
After 12 weeks of regular exercises (or absence of them), the effect of yoga and physical therapy on the functional status and quality of life of patients were evaluated. The training programs were developed speci cally for MS patients. The MS treatment was a part of the routine practice, as prescribed by the treating neurologist. In the event of an exacerbation of MS or for other safety-related reasons (for example, side effects of an exercise), the patients were excluded from the study. The patients signed informed consent and got a patient information lea et.

Physical methods.
The yoga and exercise classes were held twice a week, for 12 weeks. Each session lasted about 60-75 minutes. The classes were held in a specially equipped hall, using supporting materials, under the guidance of experienced trainers and a trainer assistant. All exercises were performed by the study participants together, in accordance with the detailed instructions of the trainer.
In the exercise group, the class consisted of three parts: 10-15 minutes -a warm-up, which included exercises on stretching of the main muscle groups, exibility, in combination with breathing training; 25-35 minutes -endurance training, muscle strength, coordination and balance exercises, aerobic exercises; 10-15 minutes -relaxing techniques in combination with breathing exercises.
The yoga group practiced a special complex consisting of 13 basic and 4 alternative poses described in Appendix 1 and Appendix 2. The complex is basic, universal for patients with MS and is designed to ensure safety, but at the same time give practitioners the opportunity to progress and improve their condition. Alternative, lighter versions of those poses that may cause di culties were also suggested, and basic postures were performed using additional materials to ensure comfortable exercise. The names of poses and the basic principles of their implementation correspond to the classi cation given in B.K.S. Iyengar's book "Clari cation of Yoga" by Iyengar.
During the exercises, special attention was paid not only to the time of performance and the correct location of body parts, but also to the correct actions on tension, stretching and relaxation of the muscles of synergists and antagonists, as well as on getting patients' feedback after practicing a posture, increasing awareness and sensitivity of their body and its parts during the exercises. The alteration of activity and rest cycles was also an extremely important condition in the sequence, so that participants didnot get tired during the lessons. This is why the sequence involved both more active and more regenerative poses, with alternatives to some postures offered to the participants when fatigue or tension occured during the main exercise sequences. Throughout the study,the participants were also provided with the illustrated brochures with detailed descriptions and photographic illustrations of the exercises performed (Appendix 2).
Data and statistical analysis.
The data was collected during two visits to the research center: before the study began and at the end of the 12-week follow-up period. The survey on the visits included a doctor's assessment of the EDSS (Expanded Disability Scale Status), the SF-36 quality of life questionnaire, the fatigue scale, the Berg balance scale, the 6-minute walking test.
Descriptive statistics were used to describe demographics and all the data collected in the course of the study. For interval variables, the number of patients for each variable was calculated, the average arithmetic (with a 95% con dence interval on the average, where applicable, and calculating the absolute change relative to the original value), standard deviation, median, minimum and maximum values. For one-order variables, the values of the median, 25-and 75 percent were calculated. For nominal variables, the frequency of categories and con dence intervals for frequencies (95% con dence intervals by the Klopper-Pearson method) were calculated for each visit in the course of the study. The number of values missed was speci ed for each variable.
It was planned to use statistical analysis methods, including adjustment with account of the plurality of comparisons. When other methods of statistical analysis were necessary, an additional adjustment to the Bonferroni method was introduced and substantiated.
Statistical analysis was conducted using SPSS/PASW Statistics, SPSS Inc.

Results
The distribution of study participants is presented below (Figure 1). In total, 80 people contacted the organizers of the study. Of these, 61 people were screened and 56 patients with MS were included in the study: 26 in the yoga group, 16 in the PT group and 14 in the waiting list. The remaining 5 people had no neurological symptoms of MS and therefore were not included in the study. According to the protocol, the endpoint analysis was carried out regarding the patients who had undergone the rst and second examination (Per Protocol, PP). The number of the analyzed patients was 36 (15 in the rst group, 9 in the second group and 12 in the third group). The results of the scale assessment are presented in the Table 1. Of these, 30 werewomen and 6 were men. The number and proportion (%) of women in the groups was the following: 10/15 (66.7%) in the yoga group, 9/9 (100%) in the PT group and 11/12 (91.7%) in the waiting list.The average age of patients (average ± standard deviation) was 39±10.4 years in the yoga group, 46.1±11.3 years in the exercise group (PT) and 46.2±10.4 years in the no-exercise group (waiting list); the difference between the averages in the study groups is statistically insigni cant (by Student's t-test: (t-test value and df-value) 0,011023 and 40; 0,477188 and 28; 0,010097 and 38). The average MS duration prior to the study was 12.6±8.4 in the yoga group, 18.1±12.3 in the exercise group and 18.5±7.9 in the no exercise group. There were 14 patients with remitting MS, 1 patient with secondary-progressive MS in the yoga group; 6 patients with remitting MS, 2 patients with secondary-progressive MS and 1 patient with primary-progressive MS in the PT group; 7 patients with remitting MS, 5 patients with secondary-progressive MS in the waiting list. At the time of inclusion in the study, 15 (100%) patients in the yoga group, 5 (55.6%) patients in the PT group and 8 (66.7%) patients in the waiting list were taking DMT. The most commonly taken drug was glatyramer acetate. In second place in frequency was interferon beta-1b. According to thesurvey on previously done types of exercise, most often, the patients exercised at home or just walked. However, nobody did exercise regularly for rehabilitation purposes. The median of EDSS was 4 points, the same in the yoga and PT groups and 4,5 points in the waiting list group.  In the course of the study, only 2 patients with UP were registered as having: pain (without clari cation) and back pain, both cases in the PT group. There were no side effects during the yoga classes.

Discussion
This study has several unambiguous advantages: the group under research of non-drug rehabilitation (yoga) was compared not only with the control group without exercise, but also with the group treated by the standard method -PT. The su cient duration of observation (12 weeks) was planned to assess the effect. The focus group may not be fully representative of the general population of patients with MS, but it is close to the population, which is treated by the researched methods (yoga, PT) in routine practice. In addition, there were no demographic restrictions on inclusion in the study. In general, the plan of the study corresponded to its' goals. The main limitations of the plan of this study can be attributed to the relatively small sample size, which reduces the power of the statistical tests. In addition, the planned number of patients (75) was not recruited for organizational reasons, including the introduction of restrictions in connection with the COVID-19 pandemic.

Conclusions
Regular yoga classes under the guidance of quali ed staff are a promising method of non-drug rehabilitation of patients with MS with motor disorders. More research is needed to examine the impact of yoga on clinical patient improvement and quality of life indicators.