AccScience Publishing / AN / Volume 3 / Issue 2 / DOI: 10.36922/an.2576

Fatigue: Pharmacological and non-pharmacological management in patients with multiple sclerosis

Kubra Yeni1*
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1 Department of Nursing, Faculty of Health Sciences, Ondokuz Mayis University, Samsun, Turkey
Advanced Neurology 2024, 3(2), 2576
Submitted: 29 December 2023 | Accepted: 20 March 2024 | Published: 30 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Multiple sclerosis (MS) is a neurological disease that causes inflammation and demyelination of the central nervous system. It progresses with episodic attacks and is particularly disabling in young adults. Among the many symptoms experienced by MS patients, fatigue is one of the most commonly reported. Approximately 75 – 90% of patients experience fatigue, with the vast majority reporting it as one of their top three symptoms. Over half of MS patients find fatigue to be a debilitating symptom that interferes with their work, family, and social life, significantly affecting their overall quality of life. Despite its prevalence, fatigue is often overlooked due to its subjective nature. Although the pathophysiology of fatigue is not fully understood, it has been associated with various variables such as stress, vigorous exercise, anxiety, depression, insomnia, pain, spasticity, medication side effects, anemia, and temperature elevation. Effective management of multifactorial fatigue requires a multidisciplinary approach, incorporating both pharmacological and non-pharmacological modalities. An analysis of studies conducted over the last decade indicates that the efficacy of pharmacological methods is controversial, with a high side effect profile. Among non-pharmacological methods, exercise has proven to be one of the most effective interventions. In addition, dietary modifications and vitamin supplementation have demonstrated effectiveness. Cognitive behavioral therapy, acupressure, acupuncture, the application of cooling garments, transcranial stimulation, web-based education and counseling, and guided imagery have also reported positive results. However, further studies with larger sample sizes are necessary to objectively evaluate their effectiveness. In conclusion, fatigue is a prevalent symptom among MS patients. While the management of fatigue through pharmacological methods remains controversial, non-pharmacological methods have demonstrated effectiveness, are low-cost, and have no side effects.

Multiple sclerosis
Pharmacological management
Non-pharmacological management
  1. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis. JAMA. 2021;325(8):765. doi: 10.1001/jama.2020.26858


  1. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: Pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J. 2017;19(1):1-10. doi: 10.22074/cellj.2016.4867


  1. Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments. Exp Ther Med. 2017;13(6):3163-3166. doi: 10.3892/etm.2017.4410


  1. Hauser SL, Cree BAC. Treatment of multiple sclerosis: A review. Am J Med. 2020;133(12):1380-1390.e2. doi: 10.1016/j.amjmed.2020.05.049


  1. Lakin L, Davis BE, Binns CC, Currie KM, Rensel MR. Comprehensive approach to management of multiple sclerosis: Addressing invisible symptoms-a narrative review. Neurol Ther. 2021;10(1):75-98. doi: 10.1007/s40120-021-00239-2


  1. Ayache SS, Chalah MA. Fatigue in multiple sclerosis - insights into evaluation and management. Neurophysiol Clin. 2017;47(2):139-171. doi: 10.1016/j.neucli.2017.02.004


  1. Dilek F, Bitek DE, Erol Ö, Ünsar S. Three symptoms and nursing management of multiple sclerosis: Fatigue, bladder problems and sexuality. J Anatolia Nurs Health Sci. 2019;22(4):300-305. doi: 10.17049/ataunihem.431464


  1. Derle E, Uzuner N, Canbaz Kabay S, Tuncer MA. Multipl skleroz sürecinde izlenen semptomlar ve tedavi yaklaşimlari (Symptoms and treatment approaches during the multiple sclerosis process). In: Efendi H, Yandım Kuşcu D, editors. Multipl Skleroz Tanı ve Tedavi Kılavuzu (Multiple Sclerosis Diagnosis and Treatment Guide). Türkiye: Galenos Yayınevi; 2018. p. 152-153.


  1. Patejdl R, Zettl UK. The pathophysiology of motor fatigue and fatigability in multiple sclerosis. Front Neurol. 2022;13:891415. doi: 10.3389/fneur.2022.891415


  1. Ayache SS, Serratrice N, Abi Lahoud GN, Chalah MA. Fatigue in multiple sclerosis: A review of the exploratory and therapeutic potential of non-invasive brain stimulation. Front Neurol. 2022;13:813965. doi: 10.3389/fneur.2022.813965


  1. Jhonson SL. The concept of fatigue in multiple sclerosis. J Neurosci Nurs. 2008;40(2):77-78. doi: 10.1097/01376517-200804000-00005


  1. Manjaly ZM, Harrison NA, Critchley HD, et al. Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(6):642-651. doi: 10.1136/jnnp-2018-320050


  1. Nourbakhsh B, Azevedo C, Nunan-Saah J, et al. Longitudinal associations between brain structural changes and fatigue in early MS. Mult Scler Relat Disord. 2016;5:29-33. doi: 10.1016/j.msard.2015.10.006


  1. Rocca MA, Parisi L, Pagani E, et al. Regional but not global brain damage contributes to fatigue in multiple sclerosis. Radiology. 2014;273(2):511-520. doi: 10.1148/radiol.14140417


  1. Calabrese M, Rinaldi F, Grossi P, et al. Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing- remitting multiple sclerosis. Mult Scler J. 2010;16(10):1220-1228. doi: 10.1177/1352458510376405


  1. Cruz Gómez ÁJ, Ventura Campos N, Belenguer A, Ávila C, Forn C. Regional brain atrophy and functional connectivity changes related to fatigue in multiple sclerosis. PLoS One. 2013;8(10):e77914. doi: 10.1371/journal.pone.0077914


  1. Qiu W, Raven S, Wu JS, et al. Hypothalamic lesions in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2011;82(7):819-822. doi: 10.1136/jnnp.2009.198192


  1. Huitinga I, Erkut ZA, van Beurden D, Swaab DF. Impaired hypothalamus‐pituitary‐adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions. Ann Neurol. 2004;55(1):37-45. doi: 10.1002/ana.10766


  1. Oliva Ramirez A, Keenan A, Kalau O, Worthington E, Cohen L, Singh S. Prevalence and burden of multiple sclerosis-related fatigue: A systematic literature review. BMC Neurol. 2021;21(1):468. doi: 10.1186/s12883-021-02396-1


  1. Rottoli M, La Gioia S, Frigeni B, Barcella V. Pathophysiology, assessment and management of multiple sclerosis fatigue: An update. Expert Rev Neurother. 2017;17(4):373-379. doi: 10.1080/14737175.2017.1247695


  1. Krupp LB, Larocca NG, Muir Nash J, Steinberg AD. The fatigue severity scale: Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-1123. doi: 10.1001/archneur.1989.00520460115022


  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. Clin Infect Dis. 1994;18(Suppl 1):S79-S83. doi: 10.1093/clinids/18.Supplement_1.S79


  1. Tarasiuk J, Kapica-Topczewska K, Czarnowska A, Chorąży M, Kochanowicz J, Kułakowska A. Co-occurrence of fatigue and depression in people with multiple sclerosis: A mini-review. Front Neurol. 2022;12:817256. doi: 10.3389/fneur.2021.817256


  1. Sheng P, Hou L, Wang X, et al. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: A systematic review and meta-analysis. PLoS One. 2013;8(12):e81802. doi: 10.1371/journal.pone.0081802


  1. Generali JA, Cada DJ. Amantadine: Multiple sclerosis-related fatigue. Hosp Pharm. 2014;49(8):710-712. doi: 10.1310/hpj4908-710


  1. Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol. 2009;256(4):645-650. doi: 10.1007/s00415-009-0152-7


  1. Zifko UA, Rupp M, Schwarz S, Zipko HT, Maida EM. Modafinil in treatment of fatigue in multiple sclerosis. J Neurol. 2002;249(8):983-987. doi: 10.1007/s00415-002-0765-6


  1. Littleton ET, Hobart JC, Palace J. Modafinil for multiple sclerosis fatigue: Does it work? Clin Neurol Neurosurg. 2010;112(1):29-31. doi: 10.1016/j.clineuro.2009.09.004


  1. Nourbakhsh B, Revirajan N, Morris B, et al. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: A randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021;20(1):38-48. doi: 10.1016/S1474-4422(20)30354-9


  1. Pucci E, Brañas Tato P, D’Amico R, Giuliani G, Solari A, Taus C. Amantadine for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2007;2007:CD002818. doi: 10.1002/14651858.CD002818.pub2


  1. Falsafi Z, Tafakhori A, Agah E, et al. Safety and efficacy of memantine for multiple sclerosis-related fatigue: A pilot randomized, double-blind placebo-controlled trial. J Neurol Sci. 2020;414:116844. doi: 10.1016/j.jns.2020.116844


  1. de Almeida GM, Scola RH, Ducci RDP, et al. Does oral salbutamol improve fatigue in multiple sclerosis? A pilot placebo-controlled study. Mult Scler Relat Disord. 2020;46:102586. doi: 10.1016/j.msard.2020.102586


  1. Fitzgerald KC, Morris B, Soroosh A, et al. Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis-related fatigue. Mult Scler J. 2021;27(6):942-953. doi: 10.1177/1352458520936226


  1. Morrow SA, Rosehart H, Johnson AM. The effect of Fampridine-SR on cognitive fatigue in a randomized double-blind crossover trial in patients with MS. Mult Scler Relat Disord. 2017;11:4-9. doi: 10.1016/j.msard.2016.10.011


  1. Broicher SD, Filli L, Geisseler O, et al. Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years. J Neurol. 2018;265(5):1016-1025. doi: 10.1007/s00415-018-8796-9


  1. Natsheh JY, DeLuca J, Costa SL, Chiaravalloti ND, Dobryakova E. Methylphenidate may improve mental fatigue in individuals with multiple sclerosis: A pilot clinical trial. Mult Scler Relat Disord. 2021;56:103273. doi: 10.1016/j.msard.2021.103273


  1. Kooshiar H, Moshtagh M, Sardar M, Foroughipour M, Shakeri M, Vahdatinia B. Fatigue and quality of life of women with multiple sclerosis: A randomized controlled clinical trial. J Sports Med Phys Fitness. 2014;55(6):668-674.


  1. Kerling A, Keweloh K, Tegtbur U, et al. Effects of a short physical exercise intervention on patients with multiple sclerosis (MS). Int J Mol Sci. 2015;16(7):15761-15775. doi: 10.3390/ijms160715761


  1. Razazian N, Yavari Z, Farnia V, et al. Exercising impacts on fatigue, depression, and paresthesia in female patients with multiple sclerosis. Med Sci Sport Exerc. 2016;48(5):796-803. doi: 10.1249/MSS.0000000000000834


  1. Dehkordi AH. Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: A randomized trial. J Sports Med Phys Fitness. 2016;56(11):1417-1422.


  1. Bulguroglu I, Guclu-Gunduz A, Yazici G, et al. The effects of mat pilates and reformer pilates in patients with multiple sclerosis: A randomized controlled study. NeuroRehabilitation. 2017;41(2):413-422. doi: 10.3233/NRE-162121


  1. Heine M, Verschuren O, Hoogervorst EL, et al. Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial. Mult Scler J. 2017;23(11):1517-1526. doi: 10.1177/1352458517696596


  1. Kargarfard M, Shariat A, Ingle L, Cleland JA, Kargarfard M. Randomized controlled trial to examine the impact of aquatic exercise training on functional capacity, balance, and perceptions of fatigue in female patients with multiple sclerosis. Arch Phys Med Rehabil. 2018;99(2):234-241. doi: 10.1016/j.apmr.2017.06.015


  1. Grazioli E, Tranchita E, Borriello G, Cerulli C, Minganti C, Parisi A. The effects of concurrent resistance and aerobic exercise training on functional status in patients with multiple sclerosis. Int Fed Sport Med. 2019;18(12):452-457. doi: 1537-890X/1812/452–457


  1. Callesen J, Cattaneo D, Brincks J, Kjeldgaard Jørgensen ML, Dalgas U. How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study. Mult Scler. 2020;26(11):1420-1432. doi: 10.1177/1352458519865740


  1. Feys P, Moumdjian L, Van Halewyck F, et al. Effects of an individual 12-week community-located “start-to-run” program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis. Mult Scler J. 2019;25(1):92-103. doi: 10.1177/1352458517740211


  1. Plow M, Finlayson M, Liu J, Motl RW, Bethoux F, Sattar A. Randomized controlled trial of a telephone-delivered physical activity and fatigue self-management interventions in adults with multiple sclerosis. Arch Phys Med Rehabil. 2019;100(11):2006-2014. doi: 10.1016/j.apmr.2019.04.022


  1. Young HJ, Mehta TS, Herman C, Wang F, Rimmer JH. The effects of M2M and adapted yoga on physical and psychosocial outcomes in people with multiple sclerosis. Arch Phys Med Rehabil. 2019;100(3):391-400. doi: 10.1016/j.apmr.2018.06.032


  1. Kratz AL, Atalla M, Whibley D, Myles A, Thurston T, Fritz NE. Calling out MS fatigue: Feasibility and preliminary effects of a pilot randomized telephone-delivered exercise intervention for multiple sclerosis fatigue. J Neurol Phys Ther. 2020;44(1):23-31. doi: 10.1097/NPT.0000000000000296


  1. Abonie US, Hettinga FJ. Effect of a tailored activity pacing intervention on fatigue and physical activity behaviours in adults with multiple sclerosis. Int J Environ Res Public Health. 2020;18(1):17. doi: 10.3390/ijerph18010017


  1. Akbar N, Sandroff BM, Wylie GR, et al. Progressive resistance exercise training and changes in resting-state functional connectivity of the caudate in persons with multiple sclerosis and severe fatigue: A proof-of-concept study. Neuropsychol Rehabil. 2020;30(1):54-66. doi: 10.1080/09602011.2018.1449758


  1. Ozdogar AT, Ertekin O, Kahraman T, Yigit P, Ozakbas S. Effect of video-based exergaming on arm and cognitive function in persons with multiple sclerosis: A randomized controlled trial. Mult Scler Relat Disord. 2020;40:101966. doi: 10.1016/j.msard.2020.101966


  1. Fleming KM, Coote SB, Herring MP. Home-based Pilates for symptoms of anxiety, depression and fatigue among persons with multiple sclerosis: An 8-week randomized controlled trial. Mult Scler J. 2021;27(14):2267-2279. doi: 10.1177/13524585211009216


  1. Alketbi A, Basit S, Hamza N, Walton LM, Moustafa IM. The added value of cognition-targeted exercise versus symptom-targeted exercise for multiple sclerosis fatigue: A randomized controlled pilot trial. PLoS One. 2021;16(11):e0258752. doi: 10.1371/journal.pone.0258752


  1. Langeskov‐Christensen M, Hvid LG, Jensen HB, et al. Efficacy of high‐intensity aerobic exercise on common multiple sclerosis symptoms. Acta Neurol Scand. 2022;145(2):229-238. doi: 10.1111/ane.13540


  1. Bilek F, Cetisli-Korkmaz N, Ercan Z, Deniz G, Demir CF. Aerobic exercise increases irisin serum levels and improves depression and fatigue in patients with relapsing remitting multiple sclerosis: A randomized controlled trial. Mult Scler Relat Disord. 2022;61:103742. doi: 10.1016/j.msard.2022.103742


  1. Karpatkin H, Rachwani J, Rhodes R, et al. The effect of intermittent vs. continuous walking on distance to fatigue in persons with multiple sclerosis. Disabil Rehabil. 2022;44(26):8429-8435. doi: 10.1080/09638288.2021.2018055


  1. Pan Y, Huang Y, Zhang H, Tang Y, Wang C. The effects of Baduanjin and yoga exercise programs on physical and mental health in patients with Multiple Sclerosis: A randomized controlled trial. Complement Ther Med. 2022;70:102862. doi: 10.1016/j.ctim.2022.102862


  1. Hashemi Rad YS, Aghayari A. Effect of a 6-Wk sensory-motor exercise program on the balance and fatigue severity in women with multiple sclerosis. Am J Phys Med Rehabil. 2024;103(1):13-17. doi: 10.1097/PHM.0000000000002295


  1. Wolf F, Nielsen J, Saliger J, et al. Multimodal agility-based exercise training (MAT) versus strength and endurance training (SET) to improve multiple sclerosis-related fatigue and fatigability during inpatient rehabilitation: A randomized controlled pilot and feasibility study [ReFEx]. BMC Neurol. 2023;23(1):388. doi: 10.1186/s12883-023-03436-8


  1. Marchiò M, Roli L, Lucchi C, et al. Ghrelin plasma levels after 1 year of ketogenic diet in children with refractory epilepsy. Front Nutr. 2019;6:112. doi: 10.3389/fnut.2019.00112


  1. Achiron A, Givon U, Magalashvili D, et al. Effect of alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study. Mult Scler J. 2015;21(6):767-775. doi: 10.1177/1352458514554053


  1. Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial. Nutr Neurosci. 2016;19(3):138-143. doi: 10.1179/1476830515Y.0000000002


  1. Bertoglio JC, Baumgartner M, Palma R, et al. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: A 12-month double-blind placebo-controlled pilot study. BMC Neurol. 2016;16(1):77. doi: 10.1186/s12883-016-0595-2


  1. Coe S, Axelsson E, Murphy V, et al. Flavonoid rich dark cocoa may improve fatigue in people with multiple sclerosis, yet has no effect on glycaemic response: An exploratory trial. Clin Nutr ESPEN. 2017;21:20-25. doi: 10.1016/j.clnesp.2017.07.002


  1. Bitarafan S, Mohammadpour Z, Jafarirad S, Harirchian MH, Yekaninejad MS, Saboor-Yaraghi AA. The effect of retinyl-palmitate on the level of pro and anti-inflammatory cytokines in multiple sclerosis patients: A randomized double blind clinical trial. Clin Neurol Neurosurg. 2019;177:101-105. doi: 10.1016/j.clineuro.2019.01.003


  1. Albrechtsen MT, Langeskov-Christensen M, Jørgensen MLK, Dalgas U, Hansen M. Is diet associated with physical capacity and fatigue in persons with multiple sclerosis? Results from a pilot study. Mult Scler Relat Disord. 2020;40:101921. doi: 10.1016/j.msard.2019.101921


  1. Coe S, Cossington J, Collett J, et al. A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(5):507-513. doi: 10.1136/jnnp-2018-319496


  1. Katz Sand I, Benn EKT, Fabian M, et al. Randomized-controlled trial of a modified Mediterranean dietary program for multiple sclerosis: A pilot study. Mult Scler Relat Disord. 2019;36:101403. doi: 10.1016/j.msard.2019.101403


  1. Bahr LS, Bock M, Liebscher D, et al. Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): Protocol of a randomized controlled study. Trials. 2020;21(1):3. doi: 10.1186/s13063-019-3928-9


  1. Lee JE, Titcomb TJ, Bisht B, Rubenstein LM, Louison R, Wahls TL. A modified MCT-based ketogenic diet increases plasma β-hydroxybutyrate but has less effect on fatigue and quality of life in people with multiple sclerosis compared to a modified paleolithic diet: A waitlist-controlled, randomized pilot study. J Am Coll Nutr. 2021;40(1):13-25. doi: 10.1080/07315724.2020.1734988


  1. Mousavi-Shirazi-Fard Z, Mazloom Z, Izadi S, Fararouei M. The effects of modified anti-inflammatory diet on fatigue, quality of life, and inflammatory biomarkers in relapsing-remitting multiple sclerosis patients: A randomized clinical trial. Int J Neurosci. 2021;131(7):657-665. doi: 10.1080/00207454.2020.1750398


  1. Wahls TL, Titcomb TJ, Bisht B, et al. Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial. Mult Scler J Exp Transl Clin. 2021;7(3):1-11. doi: 10.1177/20552173211035399


  1. Motaghi N, Tajadini H, Shafiei K, et al. Lavender improves fatigue symptoms in multiple sclerosis patients: A double-blind, randomized controlled trial. Mult Scler Relat Disord. 2022;65:104000. doi: 10.1016/j.msard.2022.104000


  1. Bohlouli J, Namjoo I, Borzoo-Isfahani M, et al. Modified Mediterranean diet v. traditional Iranian diet: Efficacy of dietary interventions on dietary inflammatory index score, fatigue severity and disability in multiple sclerosis patients. Br J Nutr. 2022;128(7):1274-1284. doi: 10.1017/S000711452100307X


  1. Chase E, Chen V, Martin K, et al. A low-fat diet improves fatigue in multiple sclerosis: Results from a randomized controlled trial. Mult Scler. 2023;29(13):1659-1675. doi: 10.1177/13524585231208330


  1. Moravejolahkami AR, Chitsaz A, Hassanzadeh A, Paknahad Z. Anti-inflammatory-antioxidant modifications and synbiotics improved health-related conditions in patients with progressive forms of multiple sclerosis: A single-center, randomized clinical trial. Complement Ther Clin Pract. 2023;53:101794. doi: 10.1016/j.ctcp.2023.101794


  1. Asghari KM, Dolatkhah N, Ayromlou H, Mirnasiri F, Dadfar T, Hashemian M. The effect of probiotic supplementation on the clinical and para-clinical findings of multiple sclerosis: A randomized clinical trial. Sci Rep. 2023;13(1):18577. doi: 10.1038/s41598-023-46047-6


  1. Chen V, Chase E, Lane M, et al. A randomized, controlled trial of low-fat diet for fatigue in multiple sclerosis (P6- 3.008). Neurology. 2023;100(17 Suppl 2). doi: 10.1212/WNL.0000000000202450


  1. Blikman LJ, van Meeteren J, Twisk JW, et al. Effectiveness of energy conservation management on fatigue and participation in multiple sclerosis: A randomized controlled trial. Mult Scler. 2017;23(11):1527-1541. doi: 10.1177/1352458517702751


  1. Silva T, Alencar RC, de Souza Silva BC, et al. Effect of photobiomodulation on fatigue in individuals with relapsing-remitting multiple sclerosis: A pilot study. Lasers Med Sci. 2022;37(8):3107-3113. doi: 10.1007/s10103-022-03567-3


  1. Bastani F, Sobhani M, Emamzadeh Ghasemi HS. Effect of acupressure on fatigue in women with multiple sclerosis. Glob J Health Sci. 2015;7(4):375-381. doi: 10.5539/gjhs.v7n4p375


  1. Choobforoushzadeh A, Neshat-Doost HT, Molavi H, Abedi MR. Effect of neurofeedback training on depression and fatigue in patients with multiple sclerosis. Appl Psychophysiol Biofeedback. 2015;40(1):1-8. doi: 10.1007/s10484-014-9267-4


  1. van den Akker LE, Beckerman H, Collette EH, et al. Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial. Mult Scler. 2017;23(11):1542-1553. doi: 10.1177/1352458517709361


  1. Gonzales B, Chopard G, Charry B, et al. Effects of a training program involving body cooling on physical and cognitive capacities and quality of life in multiple sclerosis patients: A pilot study. Eur Neurol. 2017;78(1-2):71-77. doi: 10.1159/000477580


  1. Pöttgen J, Moss-Morris R, Wendebourg JM, et al. Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018;89(9):970-976. doi: 10.1136/jnnp-2017-317463


  1. Cancelli A, Cottone C, Giordani A, et al. Personalized, bilateral whole-body somatosensory cortex stimulation to relieve fatigue in multiple sclerosis. Mult Scler. 2018;24(10):1366-1374. doi: 10.1177/1352458517720528


  1. Charvet LE, Dobbs B, Shaw MT, Bikson M, Datta A, Krupp LB. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: Results from a randomized, sham-controlled trial. Mult Scler J. 2018;24(13):1760-1769. doi: 10.1177/1352458517732842


  1. Chalah MA, Grigorescu C, Padberg F, Kümpfel T, Palm U, Ayache SS. Bifrontal transcranial direct current stimulation modulates fatigue in multiple sclerosis: A randomized sham-controlled study. J Neural Transm (Vienna). 2020;127(6):953-961. doi: 10.1007/s00702-020-02166-2


  1. Mortezanejad M, Ehsani F, Masoudian N, Zoghi M, Jaberzadeh S. Comparing the effects of multi-session anodal trans-cranial direct current stimulation of primary motor and dorsolateral prefrontal cortices on fatigue and quality of life in patients with multiple sclerosis: A double-blind, randomized, sham-controlled trial. Clin Rehabil. 2020;34(8):1103-1111. doi: 10.1177/0269215520921506


  1. Mateen FJ, Vogel AC, Kaplan TB, et al. Light therapy for multiple sclerosis-associated fatigue: A randomized, controlled phase II trial. J Neurol. 2020;267(8):2319-2327. doi: 10.1007/s00415-020-09845-w


  1. Radecka A, Knyszyńska A, Łuczak J, Lubkowska A. Adaptive changes in muscle activity after cryotherapy treatment: Potential mechanism for improvement the functional state in patients with multiple sclerosis. NeuroRehabilitation. 2021;48(1):119-131. doi: 10.3233/NRE-201535


  1. Ghannadi S, Noormohammadpour P, Mazaheri R, et al. Effect of eight weeks respiratory muscle training on respiratory capacity, functional capacity and quality of life on subjects with mild to moderate relapsing-remitting multiple sclerosis: A single-blinded randomized controlled trial. Mult Scler Relat Disord. 2022;68:104208. doi: 10.1016/j.msard.2022.104208


  1. Yeni K, Tulek Z, Terzi M. Effect of self-acupressure on fatigue in patients with multiple sclerosis. Complement Ther Clin Pract. 2022;47:101572. doi: 10.1016/j.ctcp.2022.101572


  1. Moustafaa EBS, Darwish MH, El-Tamawy MS, Abu Elkasem ST. Fatigue, cognition and inflammatory biomarkers changes in response to computer-based cognitive training in multiple sclerosis patients: A randomized controlled trial. NeuroRehabilitation. 2022;51(2):315-324. doi: 10.3233/NRE-220001


  1. Askari S, Kessler D, Smyth P, Finlayson M. Evaluating occupational performance coaching to support fatigue management for people with multiple sclerosis: A feasibility study. Clin Rehabil. 2022;36(9):1244-1256. doi: 10.1177/02692155221107074


  1. Granja-Domínguez A, Hochsprung A, Luque-Moreno C, et al. Effects of pulsed electromagnetic field therapy on fatigue, walking performance, depression, and quality of life in adults with multiple sclerosis: A randomized placebo-controlled trial. Braz J Phys Ther. 2022;26(5):100449. doi: 10.1016/j.bjpt.2022.100449


  1. Kesik G, Ozdemir L, Mungan Ozturk S. The effects of relaxation techniques on pain, fatigue, and kinesiophobia in multiple sclerosis patients: A 3-arm randomized trial. J Neurosci Nurs. 2022;54(2):86-91. doi: 10.1097/JNN.0000000000000620


  1. de Gier M, Beckerman H, Twisk J, Knoop H, de Groot V. Blended versus face-to-face cognitive behavioural therapy for severe fatigue in patients with multiple sclerosis: A non-inferiority RCT. Mult Scler. 2023;29(10):1316-1326. doi: 10.1177/13524585231185462


  1. Qomi M, Rakhshan M, Ebrahimi Monfared M, Khademian Z. The effect of distance nurse-led fatigue management on fatigue, sleep quality, and self-efficacy in patients with multiple sclerosis: A quasi-experimental study. BMC Neurol. 2023;23(1):71. doi: 10.1186/s12883-023-03115-8


  1. Khodaie F, Naser Moghadasi A, Kazemi AH, Zhao B. Effectiveness of acupuncture for fatigue in patients with relapsing-remitting multiple sclerosis: A randomized controlled trial. Acupunct Med. 2023;41(4):199-205. doi: 10.1177/09645284221150824


  1. Titcomb TJ, Sherwood M, Ehlinger M, et al. Evaluation of a web-based program for the adoption of wellness behaviors to self-manage fatigue and improve quality of life among people with multiple sclerosis: A randomized waitlist-control trial. Mult Scler Relat Disord. 2023;77:104858. doi: 10.1016/j.msard.2023.104858


  1. Motl RW, Sandroff BM, Pilutti LA, et al. Randomized controlled trial of the ehavioral ntervention for increasing hysical ctivity in ultiple clerosis project: Secondary, patient-reported outcomes. Contemp Clin Trials. 2023;125:107056. doi: 10.1016/j.cct.2022.107056


  1. Gay MC, Cassedanne F, Barbot F, et al. Long-term effectiveness of a cognitive behavioural therapy (CBT) in the management of fatigue in patients with relapsing remitting multiple sclerosis (RRMS): A multicentre, randomised, open-label, controlled trial versus standard care. J Neurol Neurosurg Psychiatry. 2024;95(2):158-166. doi: 10.1136/jnnp-2023-331537
Conflict of interest
The author declares that she has no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing