Lack of Evidence for a Temporal Relationship between Fatigue Perception and Physical Activity in Multiple Sclerosis ws

Research Article

Austin J Mult Scler & Neuroimmunol. 2015;2(3): 1019.

Lack of Evidence for a Temporal Relationship between Fatigue Perception and Physical Activity in Multiple Sclerosis

Selukar S¹, Moriello C², Andersen RE³, Reid RER³ and Mayo NE1,2*

¹School of Physical and Occupational Therapy, McGill University, Canada

²Division of Clinical Epidemiology, McGill University, Canada

³Department of Kinesiology and Physical Education, McGill University, Canada

*Corresponding author: Mayo NE, Division of Clinical Epidemiology, McGill University, Royal Victoria Hospital, 687 pine ave west (R4.17), Montreal, Quebec, H3A-1A1, Canada

Received: April 16, 2015; Accepted: July 01, 2015; Published: July 04, 2015


There is inconsistent evidence regarding daily variation of fatigue perception and its association with physical activity. While there is evidence that exercise can reduce fatigue it is not clear whether fatigue is a cause or consequence of physical inactivity.

The global aim of this study is to contribute evidence towards the daily variability in fatigue perception and to delineate the temporal sequence with physical activity in people with MS. This is a longitudinal predictive study over two time periods, immediately after trial entry and after the first exercise prescription (1 week later).

Fatigue perception was measured using a visual analogue scale for everyday at 8am, 12pm, 4pm and 9pm. Physical activity was recorded using an accelerometer for two continuous periods of 7 days.

Data was analyzed using Generalized Estimating Equations to adjust the variance for the clustering of measures within person. Odds ratio (OR) was used to identify peak times of the day for fatigue perception.

The results on 40 participants suggested that the odds of having maximum fatigue increased along the course of the day (lowest in morning, highest at night). Compared to 8:00 hours, the OR associated with having maximum fatigue at 21:00 hours was 5.57 (95% CI: 1.00, 2.44). At neither time period did end-of-day fatigue level impact on next day physical activity as measured by number of steps and the same for activity and perception of fatigue the next day. In this sample of low disability MS, there was no evidence linking fatigue and physical activity.

Keywords: Fatigue; Multiple sclerosis; Physical activity


MS: Multiple Sclerosis; OR: Odds Ratio; CI: Confidence Interval


Fatigue is the most studied symptom of Multiple Sclerosis (MS) in terms of measurement, impact, and treatment. A recent taxonomy of fatigue, separates perceived fatigue from performance fatigability [1], the former being measured using questionnaires, the latter measured with tests of muscle output. For patients, fatigue perception is what they report as distressing and is potentially what they can control by regulating activity and rest. Variation in perceived fatigue over time and with activity, and what this may mean in terms of etiology, impact, and treatment, has not been investigated systematically and evidence of a pattern is inconsistent [2-6].

People with MS consider fatigue as a barrier to take part in physical activity [7], yet the benefits of exercise are well established [8-11]. Despite this evidence, persons with MS show poor long term adherence in exercise programs and are reported to have high dropout rates [12]. The question remains, as to whether, exercise programs should be directed to improve physical activity in order to reduce fatigue, or should management of fatigue be considered first to improve physical activity. The relationship between fatigue and every day physical activity is a “chicken or egg” phenomenon, it is not clear whether fatigue is a cause or a consequence of physical inactivity.

The current longitudinal study aims: (i) to estimate the extent of variability in daily fatigue perception and identify the time of day where fatigue perception is the highest, and (ii) to estimate the temporal sequence between fatigue perception and physical activity.

Materials and Methods

Study design

This is a two-period longitudinal predictive study embedded within an ongoing randomized trial of exercise for people with MS “The Role of Exercise in Modifying outcomes of People with Multiple Sclerosis” (MSTEP) [13]. The fatigue monitoring component occurred over the first 14 days from study entry with the time divided into two consecutive periods of 7 days, one prior to exercise prescription and one after exercise prescription. Ethical consideration for this study was obtained from McGill University Health Centre (MUHC) at the Montreal Neurological Hospital.

Study population

Participants were those agreeing to the trial which recruited from two university hospital MS clinics. To be included, people had to be diagnosed with MS after 1994, aged 19 to 65 years, and capable of walking 100 meters without walking aid (PDDS stage: Early cane). Participants were excluded if they: (i) were already exercising three or more times per week; (ii) had any additional illness that restricted their function; (iii) had experienced a relapse during the past 30 days (included only if they were stable for more than 30 days after relapse); and (iv) showed difficulty reading, understanding, or speaking either English or French. We included only persons diagnosed after 1994 to have a more homogeneous group of people with respect to diagnostic criteria and access to disease modifying therapies (DMT) [14-16].


The demographic information such as age, gender, disability status was collected at baseline. The Patient Determined Disease Steps (PDDS) was used as a measure of disability. The PDDS is the patient version of the Expanded Disability Status Scale (EDSS) [17] and shows a high degree of correlation with the clinical measure [18].

Physical activity was measured using a uniaxial accelerometer, ActivPALTM. Accelerometers have been shown to have excellent psychometric properties in persons with MS and are considered a feasible and acceptable tool to measure physical activity in this population [19]. Reliability estimates are 0.85 for vigorous activities and 0.90 on rhythmic activities [19]. Information on average number of steps/day, energy expenditure, time spent sitting/lying, standing, stepping, number of transitions, and cadence was recorded.

Fatigue perception was measured using a 0 to 10 Visual Analogue Scale (VAS) with 0 indicating not at all fatigued and 10 worst fatigues. Participants were provided with a diary to record their VAS rating of fatigue perception on four times every day at 08:00, 12:00, 16:00, and 21:00 hours. As the accelerometer did not distinguish between sitting and lying, participants also recorded in this diary when they went to bed and when they got up to provide an estimate of hours spent lying down.


Eligible participants were identified from clinic records and were mailed a post-card about the study. Potential participants contacted the study centre directly or were telephoned by the research coordinator to be informed of the study and, for those interested, an appointment was made for an assessment. At this first visit, the consent was obtained, questionnaires and physical performance tests were completed, and an accelerometer was fixed to the thigh. At a second visit, 7 days later, the accelerometer was retrieved, randomization was carried out, the participants were given their exercise program, and a second accelerometer was put in place. This was to be worn for another seven days and then mailed back in a specially designed and addressed envelope. Thus, participants wore the accelerometer continuously, for a total of 14 days, 7 days pre-exercise prescription and 7 days post-exercise prescription. The analysis focused on linking fatigue perception to physical activity the next day and vice versa as shown in Figure 1.