Does deep breathing significantly reduce fatigue in multiple sclerosis patients? A randomized, single-blind, controlled trial

INTERVENTION: Intervention 1: The deep breathing group (verum), which would perform deep breathing exercises. We will instruct the deep‐breathing group to inhale for 5 seconds and exhale for 5 seconds in the supine position. A block consists of 10 second breathing cycles that are repeated 6 times. There are a total of 10 blocks with a short break in between. Therefore, the deep breathing exercise is expected to take approximately 10 minutes in total. Patients should breathe continuously and regularly. Breathing movements should resemble a wave. Sudden inhalation and exhalation or holding of the breath should be avoided. Breathing should preferably be done through nostrils with your mouth closed. Intervention 2: The progressive muscle relaxation group on distal body parts. This group will be directed to increase muscle tension in distal areas of the body (arms and legs) and then release that tension to separate muscles in those parts of the body. CONDITION: Multiple Sclerosis‐related Fatigue PRIMARY OUTCOME: The primary endpoint is subjective state fatigue, which will be assessed using a visual analogue scale (VAS); ; We expect that the participants in the deep breathing group will recover more from subjective fatigue after the fatigue‐inducing alertness task than the participants in the progressive muscle relaxation group of distal body parts.; ; Participants' fatigue will be assessed thrice in the second sessions of the study, the first time before an alertness test, the second time after the alertness test and the last time after one of the biofeedback exercises (either deep breathing or progressive muscle relaxation of distal body parts). SECONDARY OUTCOME: The secondary outcome is the cardiovagal reflex. We will measure cardiogaval reflex with heart rate variability (HRV) analysis, which is an objective and non‐invasive quantitative autonomic testing tool for testing cardiovagal autonomic dysfunction, in tracking the natural fluctuations of autonomic function within minutes (Novak, 2011), and in predicting fatigue severity (Crosswell, Lockwood, Ganz & Bower, 2014). ; ; Participants' cardiovagal reflex will be assessed in the first session of the study. We will measure cardiovagal reflex through heart rate variability in conjunction with deep breathing (DB), with the Blood Volume Pulse Head Sensor of the NeXus 4 Biofeedback‐System of Hasomed (Inc. MM. Nexus 4), which evaluates changes in the instant heart rate that is provoked by DB at 6 breaths/min. Because heart responses to DB are mediated by the vagal nerve, the test is also referred to as cardiovagal testing. We will record a 5 minutes baseline before proceeding with the DB test. HRV analysis offers the important advantage that it can track dynamic changes of cardiac autonomic function within minutes and it is a reliable and sensitive clinical test for early detection of cardiovagal dysfunction in a wide range of autonomic disorders. We will repeat these recordings after the PMR and DB biofeedback training sessions. INCLUSION CRITERIA: ‐ a clinically diagnosed MS and; ‐ being at least 18 years old; ‐ suffering from at least weak fatigue (defined by the Multiple Sclerosis Functional Composite (MSFC)