This study is a 2 parallel armed, 2 parallel groups, randomized controlled trial, compared DNS exercise, to CS exercises in PWMS. This randomized controlled trial is with one to one allocation in two groups (group 1: DNS exercise, group 2: CS exercise). The time schedule of enrolment, interventions, and assessments is presented in the Table.
Women and men with multiple sclerosis aged between 30 to 50 years with moderate disabilities (EDSS between 2 and 5) will be included in the study from June 2020 to March 2021.
Inclusion and exclusion criteria:
Patients with a minimum score of 21 from the mini-mental scale examination, ability to walk, willingness to participate in the study, having sustained falling during the last three months, and at least high school graduation to filling out self-declaration questionnaires will be eligible. Patients with other neurological disorders, multiple sclerosis exacerbation during the last month, apraxia (due to inability to learn and practice the exercises), severe spasticity (score above three based on modified Ashworth scale), having a history of major surgery in the lower extremities, explicit postural abnormalities in the spine and lower limbs such as scoliosis and kyphosis and cardiovascular disease will be excluded.
Recruitment will take place in two steps: firstly, neurologists from Tehran hospitals will identify potentially eligible patients and refer them to the research center at the School of Rehabilitation Sciences at the Iran University of Medical Sciences. Secondly, the treatment practitioner who is a physiotherapist with five years of experience in the field of neurorehabilitation will conduct another screening for inclusion and exclusion criteria and make the final decision regarding the eligibility of the patients. If eligible, the patient will be provided with oral and written information about the study. Background information including name, contact number, height and weight, medical history, and medications used will be obtained from participants. Having signed a consent form, patients will be randomized to one of the two treatment groups. This study will be conducted in a clinical setting, and the assessment will be performed in the physiotherapy evaluation laboratory in the School of Rehabilitation Sciences at the Iran University of Medical Sciences, Tehran. Treatment sessions will be performed in participants’ houses because of COVID-19 pandemic.
Permuted block randomization method with block sizes of 4 will be used for randomization. According to the sample size of 66, 17 blocks will be generated using the online site (www.sealedenvelope.com).
For concealment in the randomization process, a unique code will be used on each envelope with the group number (1 or 2) specified inside which will be done by blind analyzer.
The treatment provider will assign participants to each group.
In this study, the assessor who evaluates the outcome of the study will be blind to the allocation of the treatment groups and doesn’t provide intervention. Additionally, the data will be evaluated by an analyzer who is blind to the allocation of the participant. The analyzer will make the final decision to terminate the trial.
Sample size calculation
This study, for the first time, compares DNS exercises with CS exercises in PWMS. Due to the lack of previous studies and considering the main goal of study as comparing two groups the day after the completion of the 15th sessions, the Cohen standardized effect size for comparing means of two independent groups was used in this study to calculate the sample size. Considering the probability of the first type error of 5%, the second type error of 20%, and the standard Cohen's effect size of 0.8, and using G-Power software the sample size was calculated for 26 subjects in each group which increased to 33 to assume the 20 % of dropout rate. This sample size will have enough power (0.83) considering effect size of 0.3 for repeated measure analysis.
At first, necessary explanations about the importance of exercise therapy in PWMS will be given to the participants. In addition, the participants or their companions are required to make the home environment as safe as possible to minimize the likelihood of falling. In both groups, exercise sessions will be delivered three times a week, over a course of 5 weeks, and the duration of each session will be 60 to 75 minutes. In two pamphlets, both groups will be given the exercises (DNS & CS) with the description required. In order to remind exercises to the participants, a reminder will be set on their cellphones. In addition, the participants will be instructed not to do any other exercises, nor receive other types of physiotherapy treatment, and the continuation of exercises will be recommended. If they don’t want to continue the treatment sessions or female participants get pregnant during the treatment plan, they will be excluded. Four barriers to exercise in PWMS are anticipated. The first is fatigue. Rest intervals are taken between specified exercises depending on one's condition. Participants will be highly recommended to stop any exercise movement when they feel a lack of energy. The second is menstruation in women. The treatment session will be canceled on the first day of menstruation. The third is the time of the treatment session. The exercises will be performed in the morning or evening based on the participant’s comfort and level of energy. The forth is medication. Treatment sessions will take place 48 hours after the participant’s multiple sclerosis related medications.
Dynamic Neuromuscular Stabilization Exercises (Group 1):
At first, the person learns the correct posture in sitting and standing position in front of a mirror. They recognize their abdominal muscles and learn how to contract them. Then, the performer will teach participants diaphragmatic breathing.
Diaphragmatic Breathing Training:
It is recommended to sit in an erect position. The shoulders and neck should be completely relaxing, and the upper abdominal muscles should not be active. The person is asked to push the anterior and lateral walls of the abdomen out during the inhale, and perform eccentric contraction of the abdominal muscles. During exhale, they need to maintain intra-abdominal pressure with abdominal muscle contraction. Exhale time should be longer than the inhale time (32).
During each step and in every situation, diaphragmatic breathing is emphasized so that the patient follows this type of breathing in each prescribed exercise.
The exercises will be performed in four positions: supine, prone, sitting, standing as follows:
One turns his head to one side, bending the hand and leg on the same side, then bending the hand and opposite leg.
The shoulders and elbows in 90–90 position, lifting the chest first from the floor and then getting the elbows closer to each other and bear weight on elbows. Next, they take forearms off the ground and bear the weight on the palms of the hands, and then take the pelvic off the ground to reach the quadruped position. To separate the upper trunk from the lower trunk, move hips to each side while maintaining the upper trunk (36).
The thigh and knee are positioned 90–90, and hips are slightly abducted and external rotated. The person is then asked to raise their hands to grab their knees first and then their toes. To separate the upper trunk from the lower trunk, the patient is asked to rotate the upper trunk to the left and right (without moving the lower trunk) while the arms are straight in front of the chest. Again to separate the upper trunk from the lower trunk, the lower trunk is rotated to the left and right (without moving the upper trunk) by rotating the bent knees to each side.
Simultaneous rotation of the upper trunk to one side and lower trunk to the other is the next step: changing of position from supine to side lying, with upper and lower limb flexion and adduction and trunk flexion and rotation. Then moving from side-lying to prone position while controlling the speed (36).
In long sitting position, participants put their hands out of their knees, slowly bend knees and hips, then with a slight external rotation of the hips, they try to grasp the toes. In an erect sitting position on a chair, the soles of feet on the floor, arms hooked, they rotate trunk to each side. In this position, they bend the trunk to each side to lift an object. Then they lift pelvis on each side while the trunk is fixed (37).
Sit to stand transformation:
They sit erect on the ground, one knee outward and one knee inward (side sitting). Then, with the help of a ladder, they put the foot of the in-warded knee on the ground to bring the knee forward.
In the knee-forward position, they do the forward/backward and lateral weight shifting and trunk rotation to the sides. Then bring the other leg forward and switch to Squat position, and then stand upright (31). During the first to the fifth week, the number of sets and their repetition will be increased based on one's performance.
Core Stability Exercises (Group 2):
Abdominal muscles contraction
Before starting, participants need to recognize their abdominal muscles and learn how to contract them. They will be asked to maintain abdominal contraction and normal breathing (squeeze abdomen while inhalation and exhalation) in all exercises (27).
In supine position, participants bend their knees and put soles of both feet on the ground (crook lying). While the spine is in proper position, they pull their navel inward (squeeze abdomen gently) and maintain this condition for 5 seconds. Then, they do the same exercise with straight knee position. In crook lying position, first participants take the sole of each foot off the ground alternately, then lift both legs simultaneously and take both knees to the abdomen. As they look at the ceiling, they gently take their shoulders off the ground (curl up). Next, while both feet are on the floor, they gently flex and extend their knees (heel slide). Participants do bridging exercises while they contract their abdominal and gluteal muscles (25).
At first, they do the abdominal contraction in the prone position. Then, they raise their chest so that they are in prone on elbow position. In the same position, they take the pelvis off the ground, while the knees and forearms are on the ground (semi plank). Next, they raise the pelvis to be in the quadruped position (26).
In this position, they contract abdominal muscles, then they do cat-camel exercise. After that, they raise their hands then their legs alternately. In the same position, participants raise the opposite hand and leg simultaneously (27).
While two knees are bent, they push the elbow on the ground to raise their trunk and pelvic off the ground (semi side bridge) (25).
While sitting on a chair and soles of the feet on the floor, they raise their knees to the abdomen alternately (26).
As they lean against the wall, they contract abdominal muscles and gently lower the trunk as the knees bend (27).
During these five weeks, the number of the sets and their repetition will be increased based on one's performance.
All primary and secondary outcome measures will be measured by the blind assessor, who is a physiotherapy PhD student and completed a training course of biomechanical assessment tools, at baseline (a day before the first treatment session), the day after final treatment session (15th session), and at a follow-up measurement after 3 months. A home-based exercise program will be recommended for 3 months’ follow-up based on their exercise group.
Primary outcome measures will be:
Trunk Impairment Scale
The Trunk Impairment Scale is a tool to assess trunk function ability in static, dynamic, and coordination conditions, with scores ranging from zero to 23. The scores for all items are summed, and a higher score indicates greater trunk function. In all cases, the person is in the sitting position without leaning back and without using their hands. Trunk Impairment Scale has been validated and tested for reliability in PWMS (38).
Berg Balance Scale
Berg Balance Scale is a validated tool to measure patient’s static and dynamic balance. It consists of 14 items (scores from zero to 56) and is a valid and reliable test for PWMS (39). Berg Balance Scale measures balance in sitting, standing, and most daily activities (such as sitting up, moving from chair to chair, standing with eyes closed).
Biodex Balance System
Biodex Balance System SD, 115 VAC (made in the United States) is a balance system consisting of a balance plate with 20 ° tilt range and various stability from 1 (least stable) to 12 (most stable). It is a valid and objective instrument to assesses balance performance (40). The study subjects will place their bare feet on the plate. Foot angle and location of the heel of each foot is recorded in the first session so that they will not change in subsequent sessions. The screen is adjusted to fit the individual height. Before starting the test, the individual will be familiarized with test’s performance (postural stability and falling risk tests). Participants will be instructed to keep the black circle on the screen in the middle of the screen. The number of repetitions in each test is set to three (20 seconds each with 10 seconds to rest interval). The plate stability starts at 12 and decreases by the end of the test based on each person's ability. Overall stability, anterior-posterior and medial-lateral index, and falling risk index for each individual will be recorded.
Secondary outcome measures will be:
Falling rate by asking the patient or their partner: “During the last 6 months, how many times have you fallen down?”
Fear of falling by filling out Activities-specific Balance Confidence questioner.
Patient mobility by filling out Multiple Sclerosis Walking Scale-12 questioner and measured by Time Up and Go test.
Spasticity scale by filling out Multiple Sclerosis Spasticity Scale-88 questioner and measured by Modified Aashworth Scale.
Activities-specific Balance Confidence
Activities-specific Balance Confidence is a questioner that contains 16 items and the participant rates his or her perceived level of balance confidence for each item. Scores range from 0 to 100 (best score). It is validated for PWMS (41).
Multiple Sclerosis Walking Scale-12
The Multiple Sclerosis Walking Scale Questionnaire is a subjective questionnaire with 12 items. It is a valid and reliable scale where participants rate the extent to which multiple sclerosis has limited their walking
ability during the past 2 weeks (maximum score = 100) (42).
Time Up and Go test
Time Up and Go test is a valid and reliable test to measure the mobility of PWMS. The tools needed in this test are a chair with proper height, a backrest, and a stopwatch. The person sits on the chair, and 3 meters in front of the person is marked. They will be instructed to get up from the chair as quickly as possible, go up to 3 meters, turn around and follow the same path and sit on the chair. (43). The assessor records the time spent with a stopwatch. The test is repeated three times, and the average is recorded.
Multiple Sclerosis Spasticity Scale-88
Multiple Sclerosis Spasticity Scale-88 measures patient's pexperience and perception of the impact of spasticity in Multiple Sclerosis with day-to-day symptoms and during functional activities over the previous two weeks. It contains 88 questions to quantify spasticity for a total score and in eight clinically relevant and stand-alone subscales: muscle stiffness, pain and discomfort, muscle spasms, activities of daily living, walking, body movements, emotional health, and social functioning (44). Summation of each item score will be recorded.
Modified Ashworth Scale
Modified Ashworth Scale is the most commonly used clinical measure of spasticity. Its validity has been proven in all muscle groups. In this study, the group of knee extensors and ankle plantar flexors will be evaluated. First, the inactive range of motion of the knee and ankle joints is measured by goniometer. To measure the tone of the knee extensors, the individual sleeps in the side-lying position so that hip and knee joints are in extension and head and trunk in a straight line, and the pelvis is supported from behind. The assessor stands behind the patient, with one hand above the knee outside the thigh, which stabilizes the femur. The other hand is above the ankle. Then, for 1 second (with the word one thousand one), the knee is passively moved from maximal extension to maximal flexion. The grade ranges from 0 to 4. To evaluate the tone of ankle plantar flexors, the person lies in the supine position, hip and knee are in extension, head and trunk in the midline. The assessor stands on the test side with one hand on the knee (to keep the lower limb fixed) and the other hand under the foot. He/she then lifts the ankle from maximum plantar flexion to maximal dorsiflexion within one second (45).
SPSS version 22 will be used for data analysis. Mean (standard deviation) or median (first quartile and third quartile) will be used to describe the quantitative variables according to the distribution of variables, and for categorical variables, frequency (percentages) will be used. Graphical methods, numerical indices, and Shapiro-Wilk’s tests will be used to check the normality of different measures.
To compare the mean of quantitative outcomes between two groups, independent t-test or nonparametric test, Mann-Whitney, and for within group comparisons, dependent t- test or the Wilcoxon signed-rank test will be used. Chi-squared or Fisher tests will be used to compare the categorical variables between the two groups. Repeated measure ANOVA tests will be used to compare performance at 3 months to baseline and post training performance. A 2-tailed P < .05 will be considered significant.