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MS research update – Understanding how and why MS fatigue fluctuates throughout the day – 8 May 2017


In what they believe to be the first study of its kind, researchers asked participants - 38 with relapsing remitting MS and 38 without MS - to record levels of fatigue together with details of their mood, exposure to stress and physical activity at six time points during the day, for four consecutive weekdays. They hoped this would give a better understanding of how these factors contribute to fatigue fluctuations.

There were substantial moment-to-moment and day-to-day fluctuations in fatigue in people with MS. On average, their fatigue levels started higher and remained higher throughout the day, increasing more rapidly in the earlier part of the day, peaking in late afternoon then levelling off in the evening. People without MS started at a lower level and had a slower, steadier increase in fatigue levels across the day.

Many of the factors in daily life that influence fatigue were similar for both people with and without MS, but physical activity seemed to have a greater effect on people with MS, and a poor night's sleep had a greater effect on people without MS.

The researchers conclude that a better understanding of the changing levels of fatigue experienced by each person provides opportunities to develop personalised strategies for managing fatigue.


Fatigue is one of the most common symptoms of MS but the causes are not well understood. A wide range of factors can contribute to fatigue, including low mood and stress at work or in personal relationships. The combination of contributing factors means that fatigue levels can vary from day to day and within a day, making it particularly hard to cope with.

In what they believe to be the first study of its kind, UK researchers wanted to get a better picture of how fatigue levels vary from moment-to-moment and day-to-day and at the same time capture details of people's mood and their levels of stress and recent physical activity. By recording fatigue in the context of daily life, they hoped to get a better understanding of if, when and why fatigue levels fluctuate.

How this study was carried out

Over four weekdays, 76 participants - 38 with relapsing remitting MS and 38 without MS - were asked to record levels of fatigue together with details of their mood, exposure to stress and what they were doing at six time points during the day, between 10 am and 8 pm. At the start of the day, they were asked to rate the quality of the previous night's sleep and in the evening they were asked to score their overall fatigue level for the day.

What was found

As might be expected, there were substantial moment-to-moment and day-to-day fluctuations in fatigue in people with RRMS. On average, their fatigue levels started higher and remained higher throughout the day, increasing more rapidly in the earlier part of the day, peaking in late afternoon then leveling off in the evening. People without MS started at a lower level and had a slower, steadier increase in fatigue levels across the day.

In both groups, greater exposure to stress (for example deadlines at work or family conflict) and low mood were associated with higher fatigue levels, positive mood with lower fatigue levels. Increased fatigue was associated with recent physical activity in people with MS but not in those without MS. However, physical activity was recorded as a simple Yes/No score with no indication of intensity; this extra detail would have added more value to the data. Surprisingly, a poor night's sleep did not affect the next day's fatigue levels in people with MS but did increase fatigue levels in people without MS.

What does it mean?

This research highlights the variation in fatigue experienced by each person with MS and reinforces the need for personalised approaches to manage it effectively. Future studies of MS fatigue could explore ways to improve positive mood and respond to stress arising from personal relationships and the work environment. Ways to manage peak fatigue in the afternoon and after physical activity could also be explored.

Powell DJH, et al
Tracking daily fatigue fluctuations in multiple sclerosis: ecological momentary assessment provides unique insights
Journal of Behavioural Medicine 2017 Mar 9. [Epub ahead of print]
Read the full text of this paper

More about managing your fatigue

It's not possible to make fatigue go away completely but there are techniques that can be used to reduce the impact on your daily life. Health professionals, typically MS nurses, occupational therapists or physiotherapists, can help you find ways to manage fatigue. Perhaps more than any other symptom of MS, the most important person in the management of fatigue is yourself.

Keeping a fatigue diary is a good place to start. You could do this yourself using a notebook with columns ruled for date/time, current activity, fatigue score (1=low level of fatigue to 10=extreme fatigue) and notes about how you are feeling. If you do this for at least week, it will help you to see patterns in your fatigue levels and identify activities or incidents which are particularly draining. Knowing more about how your fatigue levels respond to the ups and downs of daily life will allow you to plan for times when you have more or less energy and look at ways to deal with low mood, stress within the family or at work or other factors you might identify from your diary.

You can learn more about techniques for managing fatigue in the A-Z of MS or in Living with fatigue which can be read online, downloaded as a pdf or ordered as a printed version.

You can read more about keeping a symptom diary in the A to Z of MS. Or you can read, download or order a printed copy of the book MS and Me: a self-management guide to living with MS. This book helps you learn more about your own MS and find the most effective ways to manage it.

Research by topic areas...

Causes of MS

Cortese M, Riise T, Bjørnevik K, et al.
Body size and physical exercise, and the risk of multiple sclerosis.
Mult Scler. 2017 Mar 1:1352458517699289. [Epub ahead of print]

Wesnes K, Myhr KM, Riise T, et al.
Physical activity is associated with a decreased multiple sclerosis risk: The EnvIMS study.
Mult Scler. 2017 Feb 1:1352458517694088. [Epub ahead of print]


Sadovnick AD, Yee IM, Attwell-Pope K, et al.
Patient-Reported Benefits of Extracranial Venous Therapy: British Columbia CCSVI Registry.
Can J Neurol Sci. 2017 Mar 8:1-9. [Epub ahead of print]

Co-existing conditions

Marrie RA.
Comorbidity in multiple sclerosis: implications for patient care.
Nat Rev Neurol. 2017 Mar 17. [Epub ahead of print]

Minár M, Petrleničová D, Valkovič P.
Higher prevalence of restless legs syndrome/Willis-Ekbom disease in multiple sclerosis patients is related to spinal cord lesions.
Mult Scler Relat Disord. 2017 Feb;12:54-58.

Disease modifying drugs

Havrdova E, Giovannoni G, Gold R, et al.
Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.
Eur J Neurol. 2017 Mar 22. [Epub ahead of print]
Read the full text of this paper

Elkjaer ML, Molnar T, Illes Z.
Teriflunomide for multiple sclerosis in real-world setting.
Acta Neurol Scand. 2017 Mar 20. [Epub ahead of print]

Reen GK, Silber E, Langdon DW.
Multiple sclerosis patients' understanding and preferences for risks and benefits of disease-modifying drugs: A systematic review.
J Neurol Sci. 2017 Apr 15;375:107-122.

Corvino FA, Oliveri D, Phillips AL.
The association of timing of disease-modifying drug initiation and relapse in patients with multiple sclerosis using electronic health records.
Curr Med Res Opin. 2017 Mar 20:1-14. [Epub ahead of print]

Freedman MS, Wolinsky JS, Comi G, et al.
The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies.
Mult Scler. 2017 Mar 1:1352458517695468. [Epub ahead of print]
Read the full text of this paper

Jongen PJ, Lemmens WA, Hoogervorst EL, et al.
Glatiramer acetate treatment persistence - but not adherence - in multiple sclerosis patients is predicted by health-related quality of life and self-efficacy: a prospective web-based patient-centred study (CAIR study).
Health Qual Life Outcomes. 2017 Mar 14;15(1):50.
Read the full text of this paper

Järvinen E, Multanen J, Atula S.
Subcutaneous Interferon β-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study.
Neurol Int. 2017 Feb 20;9(1):6957.
Read the full text of this paper

Fagius J, Feresiadou A, Larsson EM, et al.
Discontinuation of disease modifying treatments in middle aged multiple sclerosis patients. First line drugs vs natalizumab.
Mult Scler Relat Disord. 2017 Feb;12:82-87.

Berger JR.
Classifying PML risk with disease modifying therapies.
Mult Scler Relat Disord. 2017 Feb;12:59-63.

Li R, Sun X, Shu Y, et al.
Sex differences in outcomes of disease-modifying treatments for multiple sclerosis: A systematic review.
Mult Scler Relat Disord. 2017 Feb;12:23-28.

Edo Solsona MD, Monte Boquet E, Casanova Estruch B, et al.
Impact of adherence on subcutaneous interferon beta-1a effectiveness administered by Rebismart(®) in patients with multiple sclerosis.
Patient Prefer Adherence. 2017 Mar 2;11:415-421.
Read the full text of this paper

Zecca C, Merlini A, Disanto G, et al.
Half-dose fingolimod for treating relapsing-remitting multiple sclerosis: Observational study.
Mult Scler. 2017 Feb 1:1352458517694089. [Epub ahead of print]

Drugs in development

Nguyen AL, Gresle M, Marshall T, et al.
Monoclonal antibodies in the treatment of MS: emergence of B-cell targeted therapies".
Br J Pharmacol. 2017 Mar 20. [Epub ahead of print]

Herwerth M, Hemmer B.
Daclizumab for the treatment of relapsing-remitting multiple sclerosis.
Expert Opin Biol Ther. 2017 Mar 13. [Epub ahead of print]


Kobelt G, Thompson A, Berg J, et al.
New insights into the burden and costs of multiple sclerosis in Europe.
Mult Scler. 2017 Feb 1:1352458517694432. [Epub ahead of print]
Read the full text of this paper


Esposito S, Bonavita S, Sparaco M, et al.
The role of diet in multiple sclerosis: A review.
Nutr Neurosci. 2017 Mar 24:1-14. [Epub ahead of print]

Feinstein A, Pavisian B.
Multiple sclerosis and suicide.
Mult Scler. 2017 Mar 1:1352458517702553. [Epub ahead of print]

Altowaijri G, Fryman A, Yadav V.
Dietary Interventions and Multiple Sclerosis.
Curr Neurol Neurosci Rep. 2017 Mar;17(3):28.

Kalson-Ray S, Edan G, Leray E; SURVIMUS Study Group..
An excessive risk of suicide may no longer be a reality for multiple sclerosis patients.
Mult Scler. 2017 Mar 1:1352458517699873. [Epub ahead of print]

Marrie RA, Salter A, Tyry T, et al.
High hypothetical interest in physician-assisted death in multiple sclerosis.
Neurology. 2017 Mar 15. pii: 10.1212/WNL.0000000000003831. [Epub ahead of print]

Bell N, Brammer L.
A team approach to supporting the nutritional needs of patients living with multiple sclerosis.
Br J Community Nurs. 2017 Mar 2;22(3):124-128.

Other treatments

Keating GM.
Delta-9-Tetrahydrocannabinol/Cannabidiol Oromucosal Spray (Sativex(®)): A Review in Multiple Sclerosis-Related Spasticity.
Drugs. 2017 Apr;77(5):563-574.

Paediatric MS

Yeshokumar AK, Narula S, Banwell B.
Pediatric multiple sclerosis.
Curr Opin Neurol. 2017 Mar 20. [Epub ahead of print]

Charvet LE, Shaw M, Frontario A, et al.
Cognitive impairment in pediatric-onset multiple sclerosis is detected by the Brief International Cognitive Assessment for Multiple Sclerosis and computerized cognitive testing.
Mult Scler. 2017 Mar 1:1352458517701588. [Epub ahead of print]

Bourne T, Waltz M, Casper TC, et al.
Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.
J Neurol Sci. 2017 Apr 15;375:371-375.

Schwartz CE, Grover SA, Powell VE, et al.
Risk factors for non-adherence to disease-modifying therapy in pediatric multiple sclerosis.
Mult Scler. 2017 Feb 1:1352458517695469. [Epub ahead of print]

Physical activity

Fasczewski KS, Gill DL, Rothberger SM.
Physical activity motivation and benefits in people with multiple sclerosis.
Disabil Rehabil. 2017 Mar 14:1-7. [Epub ahead of print]

Aburub A, Khalil H, Al-Sharman A, et al.
The association between physical activity and sleep characteristics in people with multiple sclerosis.
Mult Scler Relat Disord. 2017 Feb;12:29-33.

Pregnancy and childbirth

Houtchens MK, Zapata LB, Curtis KM, et al.
Contraception for women with multiple sclerosis: Guidance for healthcare providers.
Mult Scler. 2017 Mar 1:1352458517701314. [Epub ahead of print]

Thone J, Thiel S, Gold R, et al.
Treatment of multiple sclerosis during pregnancy - safety considerations.
Expert Opin Drug Saf. 2017 Mar 23. [Epub ahead of print]

Río J, Rovira À, Tintoré M, et al.
Disability progression markers over 6-12 years in interferon-β-treated multiple sclerosis patients.
Mult Scler. 2017 Mar 1:1352458517698052. [Epub ahead of print]

Goldacre A, Pakpoor J, Goldacre M.
Perinatal characteristics and obstetric complications in mothers with multiple sclerosis: Record-linkage study.
Mult Scler Relat Disord. 2017 Feb;12:4-8.

Psychological aspects

Tietjen KM, Breitenstein S.
A Nurse-Led Telehealth Program to Improve Emotional Health in Individuals With Multiple Sclerosis.
J Psychosoc Nurs Ment Health Serv. 2017 Mar 1;55(3):31-37.

Murphy R, O'Donoghue S, Counihan T, et al.
Neuropsychiatric syndromes of multiple sclerosis.
J Neurol Neurosurg Psychiatry. 2017 Mar 11. pii: jnnp-2016-315367. [Epub ahead of print]

Camara-Lemarroy CR, Ibarra-Yruegas BE, Rodriguez-Gutierrez R, et al.
The varieties of psychosis in multiple sclerosis: A systematic review of cases.
Mult Scler Relat Disord. 2017 Feb;12:9-14.

Roy S, Drake AS, Eizaguirre MB, et al.
Trait neuroticism, extraversion, and conscientiousness in multiple sclerosis: Link to cognitive impairment?
Mult Scler. 2017 Feb 1:1352458517695467. [Epub ahead of print]

Golan D, Doniger GM, Wissemann K, et al.
The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.
Mult Scler. 2017 Feb 1:1352458517695470. [Epub ahead of print]

Bogosian A, Hughes A, Norton S, et al.
Potential treatment mechanisms in a mindfulness-based intervention for people with progressive multiple sclerosis.
Br J Health Psychol. 2016 Nov;21(4):859-880.


Cattaneo D, Lamers I, Bertoni R, et al.
Participation restriction in people with multiple sclerosis: prevalence and correlations with cognitive, walking, balance and upper limb impairments.
Arch Phys Med Rehabil. 2017 Mar 21. pii: S0003-9993(17)30160-0. [Epub ahead of print]

Kozlowski AJ, Fabian M, Lad D, et al.
Feasibility and safety of a powered exoskeleton for assisted walking for persons with multiple sclerosis: a single-group preliminary study.
Arch Phys Med Rehabil. 2017 Mar 15. pii: S0003-9993(17)30144-2. [Epub ahead of print]

Shahraki M, Sohrabi M, Taheri Torbati HR, et al.
Effect of rhythmic auditory stimulation on gait kinematic parameters of patients with multiple sclerosis.
J Med Life. 2017 Jan-Mar;10(1):33-37. Review.
Read the full text of this paper

Manca A, Dvir Z, Dragone D, et al.
Time course of strength adaptations following high-intensity resistance training in individuals with multiple sclerosis.
Eur J Appl Physiol. 2017 Apr;117(4):731-743.


Griffin N, Kehoe M.
A questionnaire study to explore the views of people with multiple sclerosis of using smartphone technology for health care purposes.
Disabil Rehabil. 2017 Mar 21:1-9. [Epub ahead of print]

Campbell E, Coulter E, Mattison P, et al.
Access, delivery and perceived efficacy of physiotherapy and use of complementary and alternative therapies by people with progressive multiple sclerosis in the United Kingdom: An online survey.
Mult Scler Relat Disord. 2017 Feb;12:64-69.

Wijnands JM, Kingwell E, Zhu F, et al.
Infection-related health care utilization among people with and without multiple sclerosis.
Mult Scler. 2016 Dec 1:1352458516681198. [Epub ahead of print]

Stem cells

Burman J, Kirgizov K, Carlson K, et al.
Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).
Bone Marrow Transplant. 2017 Mar 20. [Epub ahead of print]

Collins F, Kazmi M, Muraro PA.
Progress and prospects for the use and the understanding of the mode of action of autologous hematopoietic stem cell transplantation in the treatment of multiple sclerosis.
Expert Rev Clin Immunol. 2017 Mar 20:1-12. [Epub ahead of print]

Symptoms and symptom management

Scherder R, Kant N, Wolf E, et al.
Pain and Cognition in Multiple Sclerosis.
Pain Med. 2017 Mar 15. [Epub ahead of print]

González Gómez A, García-Ben A, Soler García A, et al.
Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.
Neurologia. 2017 Mar 15. pii: S0213-4853(17)30024-5. [Epub ahead of print]

Cockburn N, Pateman K, Taing MW, et al.
Managing the oral side effects of medications used to treat multiple sclerosis.
Aust Dent J. 2017 Mar 9. [Epub ahead of print]

Patel VP, Walker LA, Feinstein A.
Revisiting cognitive reserve and cognition in multiple sclerosis: A closer look at depression.
Mult Scler. 2017 Feb 1:1352458517692887. [Epub ahead of print]

Naro A, Leo A, Russo M, et al.
Breakthroughs in the spasticity management: Are non-pharmacological treatments the future?
J Clin Neurosci. 2017 May;39:16-27.

Özkan Tuncay F, Mollaoğlu M.
Effect of the cooling suit method applied to individuals with multiple sclerosis on fatigue and activities of daily living.
J Clin Nurs. 2017 Mar 2. [Epub ahead of print]

Vitamin D

Hartl C, Obermeier V, Gerdes LA, et al.
Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients.
J Neurol Sci. 2017 Apr 15;375:160-164.


Dorstyn D, Roberts R, Murphy G, et al.
Piloting an email-based resource package for job seekers with multiple sclerosis.
Disabil Rehabil. 2017 May;39(9):867-873.

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