Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 Sep 11;2015(9):CD009956.
doi: 10.1002/14651858.CD009956.pub2.

Exercise therapy for fatigue in multiple sclerosis

Martin Heine  1 , Ingrid van de Port, Marc B Rietberg, Erwin E H van Wegen, Gert Kwakkel
Affiliations
Meta-Analysis

Exercise therapy for fatigue in multiple sclerosis

Martin Heine et al. Cochrane Database Syst Rev. .

Abstract

Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS.

Objectives: To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS.

Search methods: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews.

Selection criteria: We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such.

Data collection and analysis: Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so.

Main results: Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing-remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value < 0.01). However, there was significant heterogeneity between trials (I(2) > 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to -0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non-exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly.

Authors' conclusions: Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome.

PubMed Disclaimer

Conflict of interest statement

MH reported no competing interest.

IP reported no competing interest.

MB reported no competing interest.

EW reported no competing interest.

GK reported no competing interest.

No commercial party having a direct financial interest in the results of the research supporting this article has, or will, confer a benefit on the authors, or on any organization with which the authors are associated. None of the authors were involved in trials included in the present review.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included trials.
3
3
Funnel plot of trials comparing exercise versus a non‐exercise control condition.
1.1
1.1. Analysis
Comparison 1 Overall analysis, Outcome 1 Fatigue.
2.1
2.1. Analysis
Comparison 2 Sensitivity analysis (Intervention contrast), Outcome 1 Fatigue.
3.1
3.1. Analysis
Comparison 3 Per fatigue measure, Outcome 1 Fatigue.
4.1
4.1. Analysis
Comparison 4 Per exercise group (random‐effects model), Outcome 1 Fatigue.
5.1
5.1. Analysis
Comparison 5 Per exercise group (fixed‐effect model), Outcome 1 Fatigue.
6.1
6.1. Analysis
Comparison 6 Sensitivity analysis (methodological quality), Outcome 1 Fatigue.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009956

References

References to studies included in this review

Ahmadi 2013 {published data only}
    1. Ahmadi A, Arastoo AA, Nikbakht M, Zahednejad S, Rajabpour M. Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients. Iranian Red Cresent Medical Journal 2013;15(6):449‐54. - PMC - PubMed
Aydin 2014 {published data only}
    1. Aydin T, Akif Sariyildiz M, Guler M, Celebi A, Seyithanoglu H, Mirzayev I, et al. Evaluation of the effectiveness of home based or hospital based calisthenic exercises in patients with multiple sclerosis. European Review for Medical and Pharmacological Sciences 2014;18(8):1189‐98. - PubMed
Bansi 2013 {published data only}
    1. Bansi J, Bloch W, Gamper U, Kesselring J. Training in MS: influence of two different endurance training protocols (aquatic versus overland) on cytokine and neurotrophin concentrations during three week randomized controlled trial. Multiple Sclerosis 2013;19(5):613‐21. - PubMed
Brichetto 2013 {published data only}
    1. Brichetto G, Spallarossa P, Carvalho ML, Battaglia MA. The effect of Nintendo(R) Wii(R) on balance in people with multiple sclerosis: a pilot randomized control study. Multiple Sclerosis 2013;19(9):1219‐21. - PubMed
Briken 2014 {published data only}
    1. Briken S, Gold S, Patra S, Vettorazzi E, Harbs D, Tallner A, et al. Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial. Multiple Sclerosis 2014;20(3):382‐90. - PubMed
Burschka 2014 {published data only}
    1. Burschka JM, Keune PM, Oy UH, Oschmann P, Kuhn P. Mindfulness‐based interventions in multiple sclerosis: beneficial effects of Tai Chi on balance, coordination, fatigue and depression. BMC Neurology 2014;14:165. - PMC - PubMed
Cakt 2010 {published data only}
    1. Cakt BD, Nacir B, Genc H, Saracoglu M, Karagoz A, Erdem HR, et al. Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study. American Journal of Physical Medicine & Rehabilitation 2010;89(6):446‐57. - PubMed
Carter 2014 {published data only}
    1. Carter A, Daley A, Humphreys L, Snowdon N, Woodroofe N, Petty J, et al. Pragmatic intervention for increasing self‐directed exercise behaviour and improving important health outcomes in people with multiple sclerosis: a randomised controlled trial. Multiple Sclerosis 2014;20(8):1112‐22. - PubMed
Castro‐Sanchez 2012 {published data only}
    1. Castro‐Sanchez AM, Mataran‐Penarrocha GA, Lara‐Palomo I, Saavedra‐Hernandez M, Arroyo‐Morales M, Moreno‐Lorenzo C. Hydrotherapy for the treatment of pain in people with multiple sclerosis: a randomized controlled trial. Evidence‐based Complementary and Alternative Medicine 2012;2012:1‐8. - PMC - PubMed
Collett 2011 {published data only}
    1. Collett J, Dawes H, Meaney A, Sackley C, Barker K, Wade D, et al. Exercise for multiple sclerosis: a single‐blind randomized trial comparing three exercise intensities. Multiple Sclerosis 2011;17(5):594‐603. - PubMed
Coote 2015 {published data only}
    1. Coote S, Hughes L, Rainsford G, Minogue C, Donnelly A. A pilot randomized trial of progressive resistance exercise augmented by neuromuscular electrical stimulation for people with multiple sclerosis who use walking aids. Archives of Physical Medicine and Rehabilitation 2015;96:197‐204. [PUBMED: 25308884] - PubMed
Dalgas 2010 {published data only}
    1. Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen H, Knudsen C, et al. Fatigue, mood and quality of life improve in MS patients after progressive resistance training. Multiple Sclerosis 2010;16(4):480‐90. - PubMed
Dettmers 2009 {published data only}
    1. Dettmers C, Sulzmann M, Ruchay‐Plossl A, Gutler R, Vieten M. Endurance exercise improves walking distance in MS patients with fatigue. Acta Neurologica Scandinavica 2009;120(4):251‐7. - PubMed
Dodd 2011 {published data only}
    1. Dodd KJ, Taylor NF, Shields N, Prasad D, McDonald E, Gillon A. Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial. Multiple Sclerosis 2011;17(11):1362‐74. - PubMed
Frevel 2015 {published data only}
    1. Frevel D, Maurer M. Internet‐based home training is capable to improve balance in multiple sclerosis: a comparative trial with hippotherapy. European Journal of Physical and Rehabilitation Medicine 2015;51:23‐30. - PubMed
Fry 2007 {published data only}
    1. Fry DK, Pfalzer LA, Chokshi AR, Wagner MT, Jackson ES. Randomized control trial of effects of a 10‐week inspiratory muscle training program on measures of pulmonary function in persons with multiple sclerosis. Journal of Neurologic Physical Therapy 2007;31(4):162‐72. - PubMed
Gandolfi 2014 {published data only}
    1. Gandolfi M, Geroin C, Picelli A, Munari D, Waldner A, Tamburin S, et al. Robot‐assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial. Frontiers in Human Neuroscience 2014;8:318. - PMC - PubMed
Garrett 2013 {published data only}
    1. Garrett M, Hogan N, Larkin A, Saunders J, Jakeman P, Coote S. Exercise in the community for people with minimal gait impairment due to MS: an assessor‐blind randomized controlled trial. Multiple sclerosis 2013;19(6):782‐9. - PubMed
    1. Garrett M, Hogan N, Larkin A, Saunders J, Jakeman P, Coote S. Exercise in the community for people with multiple sclerosis ‐ a follow‐up of people with minimal gait impairment. Multiple Sclerosis 2013;19(6):790‐8. - PubMed
Geddes 2009 {published data only}
    1. Geddes EL, Costello E, Raivel K, Wilson R. The effects of a twelve‐week home walking program on cardiovascular parameters and fatigue perception of individuals with multiple sclerosis: a pilot study. Cardiopulmonary Physical Therapy Journal 2009;20(1):5‐12. - PMC - PubMed
Hayes 2011 {published data only}
    1. Hayes HA, Gappmaier E, Lastayo PC. Effects of high‐intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial. Journal of Neurologic Physical Therapy 2011;35(1):2‐10. - PubMed
Hebert 2011 {published data only}
    1. Hebert JR, Corboy JR, Manago MM, Schenkman M. Effects of vestibular rehabilitation on multiple sclerosis‐related fatigue and upright postural control: a randomized controlled trial. Physical Therapy 2011;91(8):1166‐83. - PubMed
Hogan 2014 {published data only}
    1. Hogan N, Kehoe M, Larkin A, Coote S. The effect of community exercise interventions for people with ms who use bilateral support for gait. Multiple Sclerosis International 2014;109142:2‐12. [DOI: 10.1155/2014/109142] - DOI - PMC - PubMed
Kargarfard 2012 {published data only}
    1. Kargarfard M, Etemadifar M, Baker P, Mehrabi M, Hayatbakhsh MR. Effect of aquatic exercise training on fatigue and health‐related quality of life in patients with multiple sclerosis. Archives of Physical Medicine and Rehabilitation 2012;93(10):1701‐8. - PubMed
Klefbeck 2003 {published data only}
    1. Klefbeck B, Hanrah NJ. Effect of inspiratory muscle training in patients with multiple sclerosis. Archives of Physical Medicine and Rehabilitation 2003; Vol. 84, issue 7:994‐9. - PubMed
Learmonth 2012 {published data only}
    1. Learmonth YC, Paul L, Miller L, Mattison P, McFadyen AK. The effects of a 12‐week leisure centre‐based, group exercise intervention for people moderately affected with multiple sclerosis: a randomized controlled pilot study. Clinical Rehabilitation 2012;26(7):579‐93. - PubMed
McCullagh 2008 {published data only}
    1. McCullagh R, Fitzgerald AP, Murphy RP, Cooke G. Long‐term benefits of exercising on quality of life and fatigue in multiple sclerosis patients with mild disability: a pilot study. Clinical Rehabilitation 2008;22(3):206‐14. - PubMed
Mori 2011 {published data only}
    1. Mori F, Ljoka C, Magni E, Codeca C, Kusayanagi H, Monteleone F, et al. Transcranial magnetic stimulation primes the effects of exercise therapy in multiple sclerosis. Journal of Neurology 2011;258(7):1281‐7. - PubMed
Mostert 2002 {published data only}
    1. Mostert S, Kesselring J. Effects of a short‐term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Multiple Sclerosis 2002;8(2):161‐8. - PubMed
Negahban 2013 {published data only}
    1. Negahban H, Rezaie S, Goharpey S. Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study. Clinical Rehabilitation 2013;27(12):1126‐36. - PubMed
Oken 2004 {published data only}
    1. Oken BS, Kishiyama S, Zajdel D, Bourdette D, Carlsen J, Haas M, et al. Randomized controlled trial of yoga and exercise in multiple sclerosis. Journal of Neurology 2004;62(11):2058‐64. - PubMed
    1. Sherman KJ. Yoga and exercise may reduce fatigue in multiple sclerosis patients. Focus on Alternative & Complementary Therapies 2004;9(4):312‐3.
Petajan 1996 {published data only}
    1. Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Annals of Neurology 1996; Vol. 39, issue 4:432‐41. - PubMed
Plow 2009 {published data only}
    1. Plow MA, Mathiowetz V, Lowe DA. Comparing individualized rehabilitation to a group wellness intervention for persons with multiple sclerosis. American Journal of Health Promotion 2009; Vol. 24, issue 1:23‐6. - PubMed
Rampello 2007 {published data only}
    1. Rampello A, Franceschini M, Piepoli M, Antenucci R, Lenti G, Olivieri D, et al. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Physical Therapy 2007; Vol. 87, issue 5:545‐55. - PubMed
Sabapathy 2011 {published data only}
    1. Sabapathy NM, Minahan CL, Turner GT, Broadley S. Comparing endurance and resistance exercise training in people with multiple sclerosis: a randomized pilot study. Clinical Rehabilitation 2011;25(1):14‐24. - PubMed
Sangelaji 2014 {published data only}
    1. Sangelaji B, Nabavi SM, Estebsari F, Banshi MR, Rashidian H, Jamshidi E, et al. Effect of combination exercise therapy on walking distance, postural balance, fatigue and quality of life in multiple sclerosis patients: a clinical trial study. Iranian Red Crescent Medical Journal 2014;16(6):e17173. - PMC - PubMed
Schulz 2004 {published data only}
    1. Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, et al. Impact of aerobic training on immune‐endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. Journal of Neurological Sciences 2004;225(1‐2):11‐8. - PubMed
Skjerbaek 2014 {published data only}
    1. Skjerbaek AG, Naesby M, Lutzen K, Moller AB, Jensen E, Lamers I, et al. Endurance training is feasible in severely disabled patients with progressive multiple sclerosis. Multiple Sclerosis 2014;20(5):627‐30. - PubMed
Smedal 2011 {published and unpublished data}
    1. Smedal T, Myhr KM, Aarseth JH, Gjelsvik B, Beiske AG, Glad SB, et al. The influence of warm versus cold climate on the effect of physiotherapy in multiple sclerosis. Acta Neurologica Scandinavica 2011;124:45‐52. - PubMed
Straudi 2014 {published data only}
    1. Straudi S, Martinuzzi C, Pavarelli C, Sabbagh Charabati A, Benedetti MG, Foti C, et al. A task‐oriented circuit training in multiple sclerosis: a feasibility study. BMC Neurology 2014;14(1):124. - PMC - PubMed
Surakka 2004 {published data only}
    1. Surakka J, Romberg A, Ruutiainen J, Aunola S, Virtanen A, Karppi S, et al. Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial. Clinical Rehabilitation 2004;18(7):737‐46. - PubMed
Sutherland 2001 {published data only}
    1. Sutherland G, Andersen MB, Stoove MA. Can aerobic exercise training affect health‐related quality of life for people with multiple sclerosis?. Journal of Sports & Exercise Psychology 2001;32(2):122‐35.
Tarakci 2013 {published data only}
    1. Tarakci E, Yeldan I, Huseyinsinoglu BE, Zenginler Y, Eraksoy M. Group exercise training for balance, functional status, spasticity, fatigue and quality of life in multiple sclerosis: a randomized controlled trial. Clinical Rehabilitation 2013;27(9):813‐22. - PubMed
van den Berg 2006 {published data only}
    1. Berg M, Dawes H, Wade DT, Newman M, Burridge J, Izadi H, et al. Treadmill training for individuals with multiple sclerosis: a pilot randomised trial. Journal of Neurology, Neurosurgery & Psychiatry 2006;77(4):531‐3. - PMC - PubMed
Velikonja 2010 {published and unpublished data}
    1. Velikonja O, Curic K, Ozura A, Jazbec SS. Influence of sports climbing and yoga on spasticity, cognitive function, mood and fatigue in patients with multiple sclerosis. Clinical Neurology and Neurosurgery 2010; Vol. 112, issue 7:597‐601. - PubMed
Wier 2011 {published data only}
    1. Wier LM, Hatcher MS, Triche EW, Lo AC. Effect of robot‐assisted versus conventional body‐weight‐supported treadmill training on quality of life for people with multiple sclerosis. Journal of Rehabilitation Research & Development 2011;48(4):483‐92. - PubMed

References to studies excluded from this review

Barrett 2009 {published data only}
    1. Barrett CL, Mann GE, Taylor PN, Strike P. A randomized trial to investigate the effects of functional electrical stimulation and therapeutic exercise on walking performance for people with multiple sclerosis. Multiple Sclerosis 2009; Vol. 15, issue 4:493‐504. - PubMed
Bayraktar 2013 {published data only}
    1. Bayraktar D, Guclu‐Gunduz A, Yazici G, Lambeck J, Batur‐Caglayan HZ, Irkec C, et al. Effects of Ai‐Chi on balance, functional mobility, strength and fatigue in patients with multiple sclerosis: a pilot study. Neurorehabilitation 2013;33(3):431‐7. - PubMed
Bjarnadottir 2007 {published data only}
    1. Bjarnadottir OH, Konradsdottir AD, Reynisdottir K, Olafsson E. Multiple sclerosis and brief moderate exercise. A randomised study. Multiple Sclerosis 2007; Vol. 13, issue 6:776‐82. - PubMed
Broekmans 2010 {published data only}
    1. Broekmans T, Roelants M, Alders G, Feys P, Thijs H, Eijnde BO. Exploring the effects of a 20‐week whole‐body vibration training programme on leg muscle performance and function in persons with multiple sclerosis. Journal of Rehabilitation Medicine 2010; Vol. 42, issue 9:866‐72. - PubMed
Broekmans 2011 {published data only}
    1. Broekmans T, Roelants M, Feys P, Alders G, Gijbels D, Hanssen I, et al. Effects of long‐term resistance training and simultaneous electro‐stimulation on muscle strength and functional mobility in multiple sclerosis. Multiple Sclerosis 2011; Vol. 17, issue 4:468‐77. - PubMed
Carter 2013a {published data only}
    1. Carter AM, Daley AJ, Kesterton SW, Woodroofe NM, Saxton JM, Sharrack B. Pragmatic exercise intervention in people with mild to moderate multiple sclerosis: a randomised controlled feasibility study. Contemporary Clinical Trials 2013;35(2):40‐7. - PubMed
Carter 2013b {published data only}
    1. Carter AM, Daley AJ, Kesterton SW, Woodroofe NM, Saxton JM, Sharrack B. Pragmatic exercise intervention in people with mild to moderate multiple sclerosis: a randomised controlled feasibility study. Contemporary Clinical Trials 2013; Vol. 35, issue 2:40‐7. - PubMed
Castellano 2008 {published data only}
    1. Castellano V, White LJ. Serum brain‐derived neurotrophic factor response to aerobic exercise in multiple sclerosis. Journal of Neurological Sciences. 2008/02/16 2008; Vol. 269, issue 1‐2:85‐91. - PubMed
Cattaneo 2007 {published data only}
    1. Cattaneo D, Jonsdottir J, Zocchi M, Regola A. Effects of balance exercises on people with multiple sclerosis: a pilot study. Clinical Rehabilitation. 2007/09/19 2007; Vol. 21, issue 9:771‐81. - PubMed
Claerbout 2012 {published data only}
    1. Claerbout M, Gebara B, Ilsbroukx S, Verschueren S, Peers K, Asch P, et al. Effects of 3 weeks' whole body vibration training on muscle strength and functional mobility in hospitalized persons with multiple sclerosis. Multiple Sclerosis. 2011/11/16 2012; Vol. 18, issue 4:498‐505. - PubMed
Dalgas 2009 {published data only}
    1. Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen HJ, Knudsen C, et al. Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology. 2009/11/04 2009; Vol. 73, issue 18:1478‐84. - PubMed
DeBolt 2004 {published data only}
    1. DeBolt LS, McCubbin JA. The effects of home‐based resistance exercise on balance, power, and mobility in adults with multiple sclerosis. Archives of Physical Medicine and Rehabilitation. 2004/02/18 2004; Vol. 85, issue 2:290‐7. - PubMed
Fimland 2010 {published data only}
    1. Fimland MS, Helgerud J, Gruber M, Leivseth G, Hoff J. Enhanced neural drive after maximal strength training in multiple sclerosis patients. European Journal of Applied Physiology. 2010/06/01 2010; Vol. 110, issue 2:435‐43. - PubMed
Gosselink 2000 {published data only}
    1. Gosselink R, Kovacs L, Ketelaer P, Carton H, Decramer M. Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Archives of Physical Medicine and Rehabilitation. 2000/06/17 2000; Vol. 81, issue 6:747‐51. - PubMed
Grossman 2010 {published data only}
    1. Grossman P, Kappos L, Gensicke H, D'Souza M, Mohr DC, Penner I K, et al. MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial. Journal of Neurology 2010;75(13):1141‐9. - PMC - PubMed
Guerra 2014 {published data only}
    1. Guerra E, Cagno A, Mancini P, Sperandii F, Quaranta F, Ciminelli E, et al. Physical fitness assessment in multiple sclerosis patients: a controlled study. Research in Developmental Disabilities 2014;35(10):2527‐33. [PUBMED: 25000308] - PubMed
Heesen 2003 {published data only}
    1. Heesen C, Gold SM, Hartmann S, Mladek M, Reer R, Braumann KM, et al. Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. Brain, Behavior, and Immunity. 2003/10/30 2003; Vol. 17, issue 6:473‐81. - PubMed
Hilgers 2013 {published data only}
    1. Hilgers C, Mundermann A, Riehle H, Dettmers C. Effects of whole‐body vibration training on physical function in patients with multiple sclerosis. NeuroRehabilitation. 2013/05/08 2013; Vol. 32, issue 3:655‐63. - PubMed
Hojjatollah 2012 {published data only}
    1. Hojjatollah NB, Khosrow E, Reza RS, Monire MN. Effects of selected combined training on muscle strength in multiple sclerosis patients. HealthMED 2012; Vol. 6, issue 1:96‐102.
Jackson 2008 {published data only}
    1. Jackson KJ, Merriman HL, Vanderburgh PM, Brahler CJ. Acute effects of whole‐body vibration on lower extremity muscle performance in persons with multiple sclerosis. Journal of Neurological Physical Therapy. 2009/03/07 2008; Vol. 32, issue 4:171‐6. - PubMed
Keser 2011 {published data only}
    1. Keser I, Meric A, Kirdi N, Kurne A, Karabudak R. Comparing routine neurorehabilitation programme with callisthenic exercises in multiple sclerosis. NeuroRehabilitation. 2011/08/31 2011; Vol. 29, issue 1:91‐8. - PubMed
Keser 2013 {published data only}
    1. Keser I, Kirdi N, Meric A, Kurne AT, Karabudak R. Comparing routine neurorehabilitation program with trunk exercises based on Bobath concept in multiple sclerosis: pilot study. Journal of Rehabilitation Research and Development. 2013/03/22 2013; Vol. 50, issue 1:133‐40. - PubMed
Marandi 2013a {published data only}
    1. Marandi SM, Shahnazari Z, Minacian V, Zahed A. A comparison between pilates exercise and aquatic training effects on muscular strength in women with multiple sclerosis. Pakistan Journal of Medical Sciences 2013;29(1 Suppl):285‐9.
Marandi 2013b {published data only}
    1. Marandi SM, Nejad VS, Shanazari Z, Zolaktaf V. A comparison of 12 weeks of pilates and aquatic training on the dynamic balance of women with multiple sclerosis. International Journal of Preventive Medicine 2013;4(Suppl 1):S110‐7. - PMC - PubMed
McAuley 2007 {published data only}
    1. McAuley E, Motl RW, Morris KS, Hu L, Doerksen SE, Elavsky S, et al. Enhancing physical activity adherence and well‐being in multiple sclerosis: a randomised controlled trial. Multiple Sclerosis. 2007/06/06 2007; Vol. 13, issue 5:652‐9. - PubMed
Miller 2011 {published data only}
    1. Miller L, Paul L, Mattison P, McFadyen A. Evaluation of a home‐based physiotherapy programme for those with moderate to severe multiple sclerosis: a randomized controlled pilot study. Clinical Rehabilitation 2011;25(8):720‐30. - PubMed
Mutluay 2007 {published data only}
    1. Mutluay FK, Demir R, Ozyilmaz S, Caglar AT, Altintas A, Gurses HN. Breathing‐enhanced upper extremity exercises for patients with multiple sclerosis. Clinical Rehabilitation 2007; Vol. 21, issue 7:595‐602. - PubMed
Nilsagard 2013 {published data only}
    1. Nilsagard YE, Forsberg AS, Koch L. Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi‐centre study. Multiple Sclerosis. 2012/06/08 2013; Vol. 19, issue 2:209‐16. - PubMed
Patti 2003 {published data only}
    1. Patti F, Ciancio MR, Cacopardo M, Reggio E, Fiorilla T, Palermo F, et al. Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients ‐ a randomised controlled trial. Journal of Neurology 2003; Vol. 250, issue 7:861‐6. - PubMed
Paul 2014 {published data only}
    1. Paul L, Coulter EH, Miller L, McFadyen A, Dorfman J, Mattison GG. Web‐based physiotherapy for people moderately affected with multiple sclerosis; quantitative and qualitative data from a randomized, controlled pilot study. Clinical Rehabilitation 2014;28(9):924‐35. - PubMed
Rasova 2006 {published data only}
    1. Rasova K, Havrdova E, Brandejsky P, Zalisova M, Foubikova B, Martinkova P. Comparison of the influence of different rehabilitation programmes on clinical, spirometric and spiroergometric parameters in patients with multiple sclerosis. Multiple Sclerosis. 2006/04/25 2006; Vol. 12, issue 2:227‐34. - PubMed
Rodrigues 2008 {published data only}
    1. Rodrigues IF, Nielson MBP, Marinho AR. Evaluation of the physical therapy on the balance and on the quality of life in multiple sclerosis patients. Revista Neurosciecias 2008;16(4):269‐74.
Romberg 2005 {published data only}
    1. Romberg A, Virtanen A, Ruutiainen J. Long‐term exercise improves functional impairment but not quality of life in multiple sclerosis. Journal of Neurology 2005;252(7):839‐45. - PubMed
Schwartz 2012 {published data only}
    1. Schwartz I, Sajin A, Moreh E, Fisher I, Neeb M, Forest A, et al. Robot‐assisted gait training in multiple sclerosis patients: a randomized trial. Multiple Sclerosis 2012;18(6):881‐90. - PubMed
Shanazari 2013 {published data only}
    1. Shanazari Z, Marandi SM, Minasian V. Effect of 12‐week pilates and aquatic training on fatigue in women with multiple sclerosis. Journal of Mazandaran University of Medical Sciences 2013;23(98):257‐64.
Solari 1999 {published data only}
    1. Solari A, Filippini G, Gasco P, Colla L, Salmaggi A, Mantia L, et al. Physical rehabilitation has a positive effect on disability in multiple sclerosis patients. Journal of Neurology 1999;52(1):57‐62. - PubMed
Stephens 2001 {published data only}
    1. Stephens J, DuShuttle D, Hatcher C, Shmunes J, Slaninka C. Use of awareness through movement improves balance and balance confidence in people with multiple sclerosis: a randomized controlled study. Journal of Neurological Physical Therapy 2001; Vol. 25, issue 2:39‐49.

References to studies awaiting assessment

Pazokian 2013 {published data only}
    1. Pazokian M, Shaban M, Zakermoghdam M, Mehran A, Sangelagi B. A comparison between the effect of stretching with aerobic and aerobic exercises on fatigue level in multiple sclerosis patients. Qom University of Medical Sciences Journal 2013;7(1):8.
Summers 2000 {published data only}
    1. Summers L. The Effects of Resistance Exercise on Lower Extremity Power in Women with Multiple Sclerosis. Oregon State University, 2000.

Additional references

Ahlberg 2003
    1. Ahlberg K, Ekman T, Gaston‐Johansson F, Mock V. Assessment and management of cancer‐related fatigue in adults. Lancet 2003;362(9384):640‐50. - PubMed
Andreasen 2011
    1. Andreasen AK, Stenager E, Dalgas U. The effect of exercise therapy on fatigue in multiple sclerosis. Multiple Sclerosis 2011;17(9):1041‐54. - PubMed
Asano 2009
    1. Asano M, Dawes DJ, Arafah A, Moriello C, Mayo NE. What does a structured review of the effectiveness of exercise interventions for persons with multiple sclerosis tell us about the challenges of designing trials?. Multiple Sclerosis 2009;15(4):412‐21. - PubMed
Chaudhuri 2004
    1. Chaudhuri A, Behan PO. Fatigue in neurological disorders. Lancet 2004;363(9413):978‐88. - PubMed
Cohen 1977
    1. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd Edition. New York: Academic Press, 1977.
Cooke 2006
    1. Cooke SF, Bliss TV. Plasticity in the human central nervous system. Brain 2006;129(7):1659‐73. - PubMed
Cooney 2013
    1. Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, et al. Exercise for depression. Cochrane Database of Systematic Reviews 2013, Issue 9. [DOI: 10.1002/14651858.CD004366.pub6] - DOI - PMC - PubMed
Cramer 2014
    1. Cramer H, Lauche R, Azizi H, Dobos G, Langhorst J. Yoga for multiple sclerosis: a systematic review and meta‐analysis. PLoS One 2014;9(11):e112414. - PMC - PubMed
Dalgas 2008
    1. Dalgas U, Stenager E, Ingemann‐Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance‐, endurance‐ and combined training. Multiple Sclerosis 2008;14(1):35‐53. - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34. - PMC - PubMed
Elbers 2012
    1. Elbers RG, Rietberg MB, Wegen EE, Verhoef J, Kramer SF, Terwee CB, et al. Self‐report fatigue questionnaires in multiple sclerosis, Parkinson's disease and stroke: a systematic review of measurement properties. Quality of Life Research 2012;21(6):925‐44. - PMC - PubMed
Fisk 1994
    1. Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clinical Infectious Diseases 1994;18(Suppl 1):S79‐83. - PubMed
Garber 2011
    1. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medical Science in Sports & Exercise 2011;43(7):1334‐59. - PubMed
Gottschalk 2005
    1. Gottschalk M, Kumpfel T, Flachenecker P, Uhr M, Trenkwalder C, Holsboer F, et al. Fatigue and regulation of the hypothalamo‐pituitary‐adrenal axis in multiple sclerosis. Archives of Neurology 2005;62(2):277‐80. - PubMed
Higgins 2011a
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Higgins 2011b
    1. Higgins JPT, Altman DG, Sterne JAC. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Higgins 2011c
    1. Higgins JPT, Deeks JJ, Altman DG. Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org..
Kehoe 2014
    1. Kehoe M, Saunders J, Jakeman P, Coote S. Predictors of the physical impact of multiple sclerosis following community‐based, exercise trial. Multiple Sclerosis Journal 2014;21(5):590‐8. - PubMed
Kjølhede 2012
    1. Kjølhede T, Vissing K, Dalgas U. Multiple sclerosis and progressive resistance training: a systematic review. Multiple Sclerosis 2012;18(9):1215‐28. - PubMed
Koch‐Henriksen 2010
    1. Koch‐Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurology 2010;9(5):520‐32. - PubMed
Krupp 1989
    1. Krupp LB, LaRocca NG, Muir‐Nash J, Steinberg AD. The Fatigue Severity Scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of Neurology 1989;46(10):1121‐3. - PubMed
Latimer‐Cheung 2013
    1. Latimer‐Cheung AE, Pilutti LA, Hicks AL, Martin Ginis KA, Fenuta AM, MacKibbon KA, et al. Effects of exercise training on fitness, mobility, fatigue, and health‐related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Archives of Physical Medicine and Rehabilitation 2013;94(9):1800‐28. - PubMed
Learmonth 2013
    1. Learmonth YC, Dlugonski D, Pilutti LA, Sandroff BM, Klaren R, Motl RW. Psychometric properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale. Journal of Neurological Sciences 2013;331(1‐2):102‐7. - PubMed
Maher 2003
    1. Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Physical Therapy 2003;83(3):713‐21. - PubMed
McDonald 2001
    1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International panel on the diagnosis of multiple sclerosis. Annals of Neurology 2001;50(1):121‐7. - PubMed
Mills 2009
    1. Mills R, Young C, Nicholas R, Pallant J, Tennant A. Rasch analysis of the Fatigue Severity Scale in multiple sclerosis. Multiple Sclerosis 2009;15(1):81‐7. - PubMed
Mills 2010
    1. Mills RJ, Young CA, Pallant JF, Tennant A. Rasch analysis of the Modified Fatigue Impact Scale (MFIS) in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry 2010;81(9):1049‐51. - PubMed
Motl 2008
    1. Motl RW, Gosney JL. Effect of exercise training on quality of life in multiple sclerosis: a meta‐analysis. Multiple Sclerosis 2008;14(1):129‐35. - PubMed
Motl 2012
    1. Motl RW, Pilutti LA. The benefits of exercise training in multiple sclerosis. Nature Review Neurology 2012;8(9):487‐97. - PubMed
Motl 2013
    1. Motl RW. Physical activity in MS: theory, determinants, and behavioral interventions. Multiple Sclerosis. 2013; Vol. 19 (S1):40.
MS Council 1998
    1. Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis: Evidence‐Based Management Strategies for Fatigue in Multiple Sclerosis. Washington: DC Paralyzed Veterans of America, 1998.
Nuesch 2010
    1. Nuesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta‐analyses of osteoarthritis trials: meta‐epidemiological study. BMJ 2010;341:c3515. [PUBMED: 20639294] - PMC - PubMed
Olascoaga 2010
    1. Olascoaga J. Quality of life and multiple sclerosis [Calidad de vida y esclerosis multiple]. Revista de Neurologia 2010;51(5):279‐88. - PubMed
Packer 1995
    1. Packer T, Brink N, Sauriol A. Managing Fatigue: A Six‐Week Course for Energy Conservation. Tucson, Arizona: Therapy Skill Builders, 1995.
Pilutti 2013
    1. Pilutti LA, Greenlee TA, Motl RW, Nickrent MS, Petruzzello SJ. Effects of exercise training on fatigue in multiple sclerosis: a meta‐analysis. Psychosomatic Medicine 2013;75(6):575‐80. - PubMed
Pilutti 2014
    1. Pilutti LA, Platta ME, Motl RW, Latimer‐Cheung AE. The safety of exercise training in multiple sclerosis: a systematic review. Journal of the Neurological Sciences 2014;343:3‐7. - PubMed
Polman 2005
    1. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Annals of Neurology 2005;58(6):840‐6. - PubMed
Polman 2011
    1. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of Neurology 2011;69(2):292‐302. - PMC - PubMed
Poser 1983
    1. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Annals of Neurology 1983;13(3):227‐31. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rietberg 2005
    1. Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. Cochrane Database of Systematic Reviews 2005, Issue 1. [DOI: 10.1002/14651858.CD003980.pub2] - DOI - PMC - PubMed
Rietberg 2010
    1. Rietberg MB, Wegen EE, Kwakkel G. Measuring fatigue in patients with multiple sclerosis: reproducibility, responsiveness and concurrent validity of three Dutch self‐report questionnaires. Disability and Rehabilitation 2010;32(22):1870‐6. - PubMed
Schulz 2010
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Medicine 2010;7(3):e1000251. - PMC - PubMed
Schumacher 1965
    1. Schumacher GA, Beebe G, Kibler RF, Kurland LT, Kurtzke JF, McDowell F, et al. Problems of experimental trials of therapy in multiple sclerosis: report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis. Annals of the New York Academy of Sciences 1965;122:552‐68. - PubMed
Smets 1995
    1. Smets EM, Garssen B, Bonke B, Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. Journal of Psychosomatic Research 1995;39(3):315‐25. - PubMed
Vickrey 1995
    1. Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health‐related quality of life measure for multiple sclerosis. Quality of Life Research 1995;4(3):187‐206. - PubMed
Ware 1992
    1. Ware JE Jr, Sherbourne CD. The MOS 36‐item Short‐Form Health Survey (SF‐36). I. Conceptual framework and item selection. Medical Care 1992;30(6):473‐83. - PubMed
Webster's New World Dictionary 1982
    1. Guralnik DB. Webster's New World Dictionary. New York: Simon and Schuster, 1982.
White 2008a
    1. White LJ, Castellano V. Exercise and brain health ‐ implications for multiple sclerosis: part 1 ‐ neuronal growth factors. Sports Medicine 2008;38(2):91‐100. - PubMed
White 2008b
    1. White LJ, Castellano V. Exercise and brain health ‐ implications for multiple sclerosis: part II ‐ immune factors and stress hormones. Sports Medicine 2008;38(3):179‐86. - PubMed
White 2011
    1. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011;377(9768):823‐36. - PMC - PubMed
WHO 2008
    1. World Health Organization. MS Atlas. Geneva: World Health Organization, 2008.
WHO 2012
    1. World Health Organization. International classification of functioning, disability and health (ICF). www.who.int/classifications/icf/en/ (accessed 9 April 2015).
Wynia 2008
    1. Wynia K, Middel B, Dijk JP, Keyser JH, Reijneveld SA. The impact of disabilities on quality of life in people with multiple sclerosis. Multiple Sclerosis 2008;14(7):972‐80. - PubMed
Zajicek 2010
    1. Zajicek JP, Ingram WM, Vickery J, Creanor S, Wright DE, Hobart JC. Patient‐orientated longitudinal study of multiple sclerosis in south west England (The South West Impact of Multiple Sclerosis Project, SWIMS) 1: protocol and baseline characteristics of cohort. BMC Neurology 2010;10:88. - PMC - PubMed
Zedlitz 2012
    1. Zedlitz AM, Rietveld TC, Geurts AC, Fasotti L. Cognitive and graded activity training can alleviate persistent fatigue after stroke: a randomized, controlled trial. Stroke 2012;43(4):1046‐51. - PubMed

References to other published versions of this review

Heine 2012
    1. Heine M, Rietberg MB, Wegen EEH, Port IVD, Kwakkel G. Exercise therapy for fatigue in multiple sclerosis. Cochrane Database of Systematic Reviews 2012, Issue 7. [DOI: 10.1002/14651858.CD009956] - DOI - PMC - PubMed

Publication types