Home > News > Physical Activity in Pediatric Multiple Sclerosis— Can Lifestyle Factors Affect Disease Outcomes?
Multiple Sclerosis
Read Time: 5 mins

Physical Activity in Pediatric Multiple Sclerosis— Can Lifestyle Factors Affect Disease Outcomes?

Published Online: March 27th 2015 US Neurology, 2015;11(1):19–22 DOI: http://doi.org/10.17925/USN.2015.11.01.19
Authors: E Ann Yeh, Robert W Motl
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

Currently, little to no information is available about interventions that can ameliorate symptoms such as depression and fatigue in children and adolescents with multiple sclerosis (MS), nor is there clear information on modifiable factors that can provide neuroprotection in this population. However, physical activity (PA) may have significant effects on disease activity, future disability, cognition, and symptoms of depression and fatigue in pediatric MS. The extent of this effect is unknown. In this paper, after providing an overview of definitions of and outcomes in pediatric MS, we provide a review of existing literature relating PA to outcomes in MS, and then turn to a review of the complex relationship between PA, neuroinflammation, and outcomes in the pediatric population.

Keywords

Pediatric, multiple sclerosis, physical activity, outcome, fatigue, depression, exercise, review

Article:

Demyelinating disorders of the central nervous system (CNS) occur in approximately 1/100,000 children. About one-fifth of these children will eventually receive a diagnosis of multiple sclerosis (MS).1 These cases constitute approximately 2–5 % of all cases of MS.2 Of these children, up to three-quarters will experience cognitive decline, depression, and/or fatigue, and irreversible motor disability occurs at a young age, on average 2 decades after disease onset, or in the fourth decade of life. Currently, little to no information is available about interventions that can ameliorate symptoms such as depression and fatigue in children and adolescents with MS. Cross-sectional studies in healthy adolescents have suggested relationships between higher levels of physical activity (PA) and cognitive outcomes, brain volumes, psychosocial outcomes, and academic achievement. Adult MS studies have shown PA to benefit cognition and psychosocial outcomes. Improvement in levels of PA in this population may provide a simple, nonpharmacologic means by which to reach this goal. In this paper, after providing background information on pediatric demyelinating disorders, we will move on to an overview of studies focused on the relationship between physical activity, neuroinflammation, and outcomes in MS and in the pediatric population.

Background—Pediatric Demyelinating Disorders
Definitions
Pediatric demyelinating disorders can be divided broadly into recurrent and monophasic entities, including acute disseminated encephalomyelitis (ADEM), clinically isolated syndrome (CIS), and MS, in addition to entities such as neuromyelitis optica and recurrent optic neuritis/chronic relapsing inflammatory optic neuropathy. Currently, magnetic resonance imaging (MRI) and clinical parameters fulfilling criteria for dissemination in space and time appear to be suitable for diagnosing MS in childhood. While the 2005 McDonald criteria were found to have poor specificity and sensitivity for pediatric MS,3,4 the revised McDonald MRI Criteria5 are sensitive and specific for the diagnosis of MS in children >11 years of age.6 In brief, in children over 11 years of age, demonstration of dissemination in time can be accomplished by using a single MRI timepoint with evidence for enhancing and nonenhancing lesions in areas typical for MS, whereas dissemination in space can be demonstrated by greater or equal to one lesion in at least two of the four following regions: periventricular, juxtacortical, infratentorial, spinal cord. Younger children who present with multifocal demyelination diagnosed as ADEM should have two or more non-ADEM attacks or one ADEM attack followed by a nonencephalopathic clinical attack and accrual of lesions satisfying McDonald Criteria.5,7

Increased Disease Burden in Children with Multiple Sclerosis
Pediatric onset MS is characterized by greater MRI disease burden both early on in the disease and at later stages,8,9 with evidence for accelerated disease burden in comparison with the adult population. Children with MS have a higher T1 lesion volume on brain MRI, a higher T1 lesion volume to brain parenchymal volume ratio, and a lower magnetization transfer in T2 lesions as well as in normal appearing gray matter (GM) and white matter compared with adults with similar disease duration. Patients with longstanding pediatric-onset disease compared with those with longstanding adult onset disease of similar duration have no significant differences in quantitative measures including GM fraction, white matter fraction, T1 lesion volume, T2 lesion volume, and brain parenchymal fraction.9 As a brain volume loss of 0.2 % per year between the ages of 30–50 is anticipated as part of the normal aging process,10 the presence of similar brain parenchymal fraction in these two groups suggests more aggressive disease in pediatric-onset compared with adult-onset MS. This has been further supported by studies reporting decreased head size in children with MS.11

As in adult MS, GM atrophy can occur early in the course of pediatric onset MS.9,12 GM atrophy in the thalamus has been described in pediatric onset MS after a mean disease duration of 3 years. However, unlike the adult population, where correlations between GM atrophy and disability have been found,10 there appears to be no correlation between GM volume loss and disease duration or physical disability in pediatric onset MS with relatively short disease duration.9,12 Importantly, while at onset GM involvement in pediatric populations may be limited,13,14 the rate of progression of GM atrophy is similar between adult onset and pediatric onset relapsing-remitting-MS (RR-MS) patients.14 This is corroborated by findings in a long-term follow-up study, in which no differences were seen in regional GM atrophy between age- and disease-duration-matched adult- and pediatric-onset MS patients.15 Thus, multiple MRI studies have demonstrated clear evidence for high disease activity and progressive atrophy in individuals with pediatric onset MS.

Finally, clinical relapses in pediatric MS are reported to be more frequent than in the adult population, occurring at a rate of 1.13 relapses per year compared with 0.4 relapses per year in the adult population.16 Indeed, a first interattack interval of less than a year is reported in 60 % of patients with pediatric MS.16 An interattack interval of less than a year in addition to high relapse frequency in the first 2 years after diagnosis is predictive of secondary progression and earlier progression to irreversible disability in pediatric patients.17

Psychosocial and Physical Burden of Pediatric Multiple Sclerosis
Despite evidence for greater disease severity in pediatric MS, natural history studies have suggested a relatively slow accrual of physical disability in this population. On average, the patient with pediatric onset MS will reach a point of irreversible disability (Expanded Disability Severity Scale [EDSS] ≥4) approximately 20 years after disease onset compared with 10 years in adult-onset patients.18 Nonetheless, the burden of non-motor disability is high as the majority of children and adolescents with MS may suffer from depression, fatigue, or cognitive impairment.19,20

Cognitive impairment may occur early on in the disease course, with one study suggesting a deterioration on neurocognitive testing in 75 % of pediatric onset patients within 2 years of disease onset.21 At 5 years, a small number of children in the same cohort were noted to have improvements in performance (25 %), with over half (56 %) of these patients experiencing deterioration from onset.22

Depression is seen in almost one-third of children with acquired demyelinating syndromes, with fatigue in one-quarter.19,23 No large-scale studies evaluating longer-term occupational and social outcomes of this population have been published, but one small cohort of MS patients (n=19) with pediatric onset disease suggests a downward educational trajectory, as represented by greater need for school supports and worsening academic performance.24

Currently, little to no information is available about interventions that can ameliorate symptoms, such as depression and fatigue in children and adolescents with MS, nor is there clear information on modifiable factors that can provide neuroprotection in this population. However, growing literature supports an association between higher levels of PA and improved outcomes in both pediatric populations and adults with MS. The remainder of this review paper will be devoted to a brief consideration of the literature on PA in MS and pediatric populations.

Physical Activity in Pediatric Populations— Effect on Inflammation, Fatigue, Depression, and Cognition
Researchers have examined relationships between PA and neurocognitive and psychosocial outcomes in both healthy children and children with chronic illnesses such as chronic fatigue syndrome, pediatric cancer (acute lymphoblastic leukemia [ALL]), pediatric lupus, and juvenile idiopathic arthritis (JIA). This work has suggested that exercise interventions may lead to improvements in well-being, fatigue, and depression, as has adult literature focusing on MS25–30 and chronic illnesses.31 For example, in JIA, an 8-week dedicated program of aerobic training has led to increases in aerobic capacity, as well as improvements in a health index (childhood health assessment questionnaire, [CHAQ] [0.77 ± 0.61 to 0.20 ± 0.28; p<0.001]).32 However, another study has suggested that improvements in well being (CHAQ) after an exercise intervention may be small.33 In terms of depression in children, several studies have suggested improvements in self-reported measures of depression and self-worth in obese children, including a randomized controlled trial (RCT) comparing usual care to an exercise intervention (n=81),34 and another RCT comparing two different prescribed exercise lengths (0 versus 20 minutes versus 40 minutes, n=207).35

Much research on the effects of exercise as an intervention for cancerrelated fatigue in adults has been published, showing moderate effects on sleep, depression, and fatigue.36 Studies in the pediatric cancer population have indicated low levels of fitness and high levels of fatigue, but only one study has assessed the specific effects of exercise on wellbeing, fatigue, and depression in this population, and did not report significant effects.37

As for effects on cognition, multicomponent interventions focusing on increasing PA have resulted in improvements in cognition, mathematics, and reading scores in healthy children,38,39 while effects on executive function40 have been reported in a randomized exercise trial in an obese pediatric population. Furthermore, healthy children (n=221) exhibited both increased fitness and improvements in cognitive flexibility (4.8 %, 95 % confidence interval [CI] 1.1 to 8.4; d=0.35 for group difference in pre-topost change score) and inhibition (3.2 %, 95 % CI 0.0 to 6.5; d=0.27) after undergoing a school-based PA intervention.41 Structural and functional changes, namely changes in hippocampal size and memory, have been found in older adults after an exercise intervention,42 while in healthy adolescents, children with greater fitness levels have been found to have greater volumes in the deep GM.43

Finally, PA and fitness may mediate inflammation in children. While exercise may acutely increase systemic inflammation in the pediatric population,44 it has been found to be well tolerated in children with chronic inflammatory conditions, such as JIA and systemic lupus erythematosis (SLE).25 Moreover, the long-term effects of exercise and increased fitness may be anti-inflammatory: one study of a 9-month fitness-based curriculum in non-obese middle school students demonstrated both increased fitness and lowered tumor necrosis factor (TNF)-alpha levels (–2.55 ± 1.79 pg/ml; p<0.001).45

Physical Activity in Adult Multiple Sclerosis
Studies from North America have documented lower rates of PA in people with MS than healthy controls via survey data46,47 and using objective measures (accelerometry data: d=0.68, F=47.2; p<0.001).48 Furthermore, a meta-analysis of studies of PA in MS has reported that PA levels in the adult MS population are 1 standard deviation (SD) below that of healthy controls.49

Higher levels of PA may have effects on disease activity and common symptoms associated with MS. For example, in the adult MS population, level of premorbid PA predicts worsening of disability scores over 2-year follow-up.50 One large survey suggests associations between increased PA and both overall health-related quality of life (HRQOL) and HRQOL subscales (physical health, improvements in health, energy subscale, social function subscale) as well as decreased relapse rate (p=0.009).51 The relationship between HRQOL and PA is complex, and the relationship may be indirect. In another study of 292 MS patients that evaluated QOL, disability, PA (selfreported and accelerometer), mood, pain, self-efficacy and self-report, lower levels of fatigue, depression, anxiety and pain, and higher levels of social support and MS self-efficacy had higher levels of QOL.52

In adult MS, aerobic training has improved fatigue, depression, and anger scores over the course of 10 to 12 weeks.30,53 Another study evaluating the effects of two exercise training programs in MS over the course of 2 months (patients n=30; controls n=15) suggests that both patients undergoing resistance training and those undergoing lower limb strengthening and balancing exercises benefitted in several areas whereas controls showed no improvement.54 In addition, patients undergoing either form of exercise training were found to have improvements in fatigue and depression.

These benefits may last beyond the intervention period: one study found that improvements in QOL and fatigue persisted 3 months after discontinuation of the program.30 Shorter-term programs may have benefits: one 4-week program showed an improvement in aerobic capacity in addition to an improvement of health perception and a tendency to less fatigue. Symptom exacerbation was low (6 %).55

It is possible that PA in any form may be beneficial in the MS population. A longer-term study evaluating yoga and exercise has suggested benefits of a 6-month yoga or exercise class on fatigue compared with a control condition.56 This is supported by recent studies focusing on sedentary behavior in MS57 and active commuting in healthy pediatric and adult populations,58,59 suggesting a beneficial effect related to overall increase in PA regardless of level of aerobic activity. The relationship between frequent symptoms such as fatigue and physical activity, however, is complex, as one study has suggested only a weak relationship between fatigue and PA, while age, type of MS, anxiety, and depression mitigated this relationship.60

Physical Activity in Pediatric Multiple Sclerosis
Information regarding exercise and PA in pediatric MS is lacking, but some data suggesting conditions associated with decreased PA may have an effect on MS in children. Obesity has been identified as a major problem in pediatric onset MS, with an odds ratio for receiving the diagnosis of MS/CIS of 3.76 (1.54–9.16) in extremely obese (BMI ≥35 kg/m2) girls in California.61 In other work, obesity at age 18 was associated with a twofold increased risk for MS in two large cohorts of women (Nurses’ Health Study).62 Indirect support for the role of exercise, physical activity, and fitness on systemic inflammation can be seen in research demonstrating an elevation of inflammatory markers in non-obese children with higher body fat and lower fitness levels.63

Our preliminary data evaluating levels of PA in pediatric MS compared with children with monophasic demyelinating disorders suggests significantly lower participation in strenuous activities in the MS population (n=23) in comparison to children with monophasic demyelination (n=52) (70 % versus 90 %; p=0.03).64 In our study, moderate PA had no correlation with depression and fatigue, but strenuous PA significantly correlated with lower levels of general fatigue (r=–0.45), suggesting a possible relationship between common symptoms associated with MS and higher-intensity PA. Children with longer disease duration were less likely to participate in strenuous PA (r=–0.51). We have demonstrated correlations between low levels of PA self-efficacy and mild PA, and high levels of PA self-efficacy and participation in strenuous PA, suggesting a relationship between higher rates of PA self-efficacy and greater engagement in strenuous types of PA in this population.65

While the associations between PA and psychosocial outcomes in pediatric MS have not been investigated, research in healthy Canadian children demonstrating associations between PA and increased risk for obesity and poor HRQOL66 suggests the need for close examination of this matter in children with MS.

Conclusions
Pediatric MS carries with it a high disease burden and poor cognitive and psychosocial outcomes. Development of interventions focused on preventing, slowing, and remediating these outcomes is imperative. We believe that participation in PA holds considerable promise as a behavior intervention. Our preliminary cross-sectional work suggests that children with MS engage in less PA than children who have recovered from a monophasic demyelinating attack. Further, there is a strong basis for PA as a behavioral intervention based on research reviewed for adolescent populations with and without disease, and in adults with MS. Further studies should examine the potential neuroprotective effects of PA and establish the level of PA and fitness that may be effective for an interventional program. If, indeed, higher levels of general PA can help to ameliorate MS-related symptoms and, potentially, affect disease progression, flexible, home-/distance-based interventions that would be feasible for this population could be crafted. Such strategies would have the potential to translate to other flexible, potentially technology-based patient-centered interventions, including those focused on medication adherence and symptom management. This is an important next step in research involving pediatric MS.

Article Information:
Disclosure

E Ann Yeh receives funding from the National MS Society, the Canadian Institutes of Health Research, the Dairy Farmers of Ontario, SickKids Foundation, SickKids
Innovation Fund, Canadian Multiple Sclerosis Monitoring System/Public Health Agency of Canada (CMSMS/PHAC), the Canadian Multiple Sclerosis Scientific Research Foundation, and the MS Society of Canada. Robert Motl has received speaker honoraria from EMD Serono. No funding was received for the publication of this article.

Correspondence

E Ann Yeh, Division of Neurology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5B 1X8 Canada. E: ann.yeh@sickkids.ca

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Received

2015-01-26T00:00:00

References

  1. Banwell B, Bar-Or A, et al., Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study, Lancet Neurology, 2011;10:436–45.
  2. Chitnis T, Glanz B, Jaffin S, Healy B, Demographics of pediatriconset multiple sclerosis in an MS center population from the Northeastern United States, Mult Scler, 2009;15:627–31.
  3. Callen DJ, Shroff MM, Branson HM, et al., MRI in the diagnosis of pediatric multiple sclerosis, Neurology, 2009;72:961–7.
  4. Yeh EA, Chitnis T, Krupp L, et al., Pediatric multiple sclerosis, Nat Rev Neurol, 2009;5:621–31.
  5. Polman CH, Reingold SC, Banwell B, et al., Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, Ann Neurol, 2011;69:292–302.
  6. Sadaka Y, Verhey LH, Shroff MM, et al., 2010 McDonald criteria for diagnosing pediatric multiple sclerosis, Ann Neurol, 2012;72:211–23.
  7. Krupp LB, Tardieu M, Amato MP, et al., International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions, Mult Scler, 2013;19:1261–7.
  8. Waubant E, Chabas D, Okuda DT, et al., Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults, Arch Neurol, 2009;66:967–71.
  9. Yeh EA, Weinstock-Guttman B, Ramanathan M, et al., Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis, Brain, 2009;132(Pt 12): 3392–400.
  10. Zivadinov R, Bakshi R, Central nervous system atrophy and clinical status in multiple sclerosis, J Neuroimaging, 2004;14:S27–S35.
  11. Kerbrat A, Aubert-Broche B, Fonov V, et al., Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS, Neurology, 2012;78:194–201.
  12. Mesaros S, Rocca MA, Absinta M, et al., Evidence of thalamic gray matter loss in pediatric multiple sclerosis, Neurology, 2008;70(13 Pt 2):1107–12.
  13. Absinta M, Rocca MA, Moiola L, et al., Cortical lesions in children with multiple sclerosis, Neurology, 2011;76:910–3.
  14. Calabrese M, Seppi D, Romualdi C, et al., Gray matter pathology in MS: a 3-year longitudinal study in a pediatric population, AJNR Am J Neuroradiol, 2012;33:1507–11.
  15. Donohue K, Cox JL, Dwyer MG, et al., No regional gray matter atrophy differences between pediatric- and adult-onset relapsing-remitting multiple sclerosis, J Neuroimaging, 2014;24:63–7.
  16. Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T, Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis, Arch Neurol, 2009;66:54–9.
  17. Simone IL, Carrara D, Tortorella C, Liguori M, et al., Course and prognosis in early-onset MS: comparison with adult-onset forms, Neurology, 2002;59:1922–8.
  18. Renoux C, Vukusic S, Mikaeloff Y, et al., Natural history of multiple sclerosis with childhood onset, N Engl J Med, 2007;356:2603–13.
  19. Parrish JB, Weinstock-Guttman B, Smerbeck A, et al., Fatigue and depression in children with demyelinating disorders, J Child Neurol, 2013;28:713–8.
  20. Amato MP, Goretti B, Ghezzi A, et al., Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up, Neurology, 2010;75:1134–40.
  21. Amato M, Gordetti B, Ghezzi A, et al., Cognitive and psychosocial features of childhood and juvenile MS: a reappraisal after 2 years, Neurology, 2009;72(Suppl. 1):A97.
  22. Amato MP, Goretti B, Ghezzi A, et al., Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up, Neurology, 2014;83:1432–8.
  23. Goretti B, Portaccio E, Ghezzi A, et al., Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis, Mult Scler, 2012;18:329–34.
  24. Grover S, Sye A, Aubert-Broche B, et al., ACTRIMS-ECTRIMS MS Boston 2014: Poster Sessions 2: Young adults with pediatriconset MS have a downward educational trajectory, Mult Scler, 2014;20(Suppl. 1):394.
  25. Gualano B, Sa Pinto AL, Perondi B, et al., Evidence for prescribing exercise as treatment in pediatric rheumatic diseases, Autoimmun Rev, 2010;9:569–73.
  26. Houghton KM, Tucker LB, Potts JE, McKenzie DC, Fitness, fatigue, disease activity, and quality of life in pediatric lupus, Arthritis Rheum, 2008;59:537–45.
  27. White PD, Goldsmith KA, Johnson AL, 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;377:823–36.
  28. Gordon BA, Knapman LM, Lubitz L, Graduated exercise training and progressive resistance training in adolescents with chronic fatigue syndrome: a randomized controlled pilot study, Clin Rehabil, 2010;24:1072–9.
  29. Nunez M, Fernandez-Sola J, Nunez E, et al., Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of followup, Clin Rheumatol, 2011;30:381–9.
  30. 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, Clin Rehabil, 2008;22:206–14.
  31. Herring MP, Puetz TW, O’Connor PJ, Dishman RK, Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials, Arch Int Med, 2012;172:101–11.
  32. Dog˘ ru Apti M, Kasapçopur Ö, Mengi M, et al., Regular aerobic training combined with range of motion exercises in juvenile idiopathic arthritis, BioMed Research International, 2014;2014:748972.
  33. Sandstedt E, Fasth A, Week MN, Beckung E, Muscle strength, physical fitness and well-being in children and adolescents with juvenile idiopathic arthritis and the effect of an exercise programme: a randomized controlled trial, Pediatr Rheumatol Online J, 2013;11:7.
  34. Daley AJ, Copeland RJ, Wright NP, et al., Exercise therapy as a treatment for psychopathologic conditions in obese and morbidly obese adolescents: a randomized, controlled trial, Pediatrics, 2006;118:2126–34.
  35. Petty KH, Davis CL, Tkacz J, et al., Exercise effects on depressive symptoms and self-worth in overweight children: a randomized controlled trial, J Pediatr Psychol, 2009;34:929–39.
  36. Tomlinson D, Diorio C, Beyene J, Sung L, Effect of exercise on cancer-related fatigue: a meta-analysis, Am J Phys Med Rehabil, 2014;93:675–86.
  37. Braam KI, van der Torre P, Takken T, et al., Physical exercise training interventions for children and young adults during and after treatment for childhood cancer, Cochrane Database Syst Rev, 2013;4:CD008796.
  38. Nansel TR, Huang TT, Rovner AJ, Sanders-Butler Y, Association of school performance indicators with implementation of the healthy kids, smart kids programme: case study, Public Health Nutr, 2010;13:116–22.
  39. Shilts MK, Lamp C, Horowitz M, Townsend MS, Pilot study: EatFit impacts sixth graders’ academic performance on achievement of mathematics and english education standards, J Nutr Educ Behav, 2009;41:127–31.
  40. Davis CL, Tomporowski PD, McDowell JE, et al., Exercise improves executive function and achievement and alters brain activation in overweight children: a randomized, controlled trial, Health Psychol, 2011;30:91–8.
  41. Hillman CH, Pontifex MB, Castelli DM, et al., Effects of the FITKids randomized controlled trial on executive control and brain function, Pediatrics, 2014;134:e1063–71.
  42. Erickson KI, Voss MW, Prakash RS, et al., Exercise training increases size of hippocampus and improves memory, Proc Natl Acad Sci U S A, 2011;108:3017–22.
  43. Chaddock L, Erickson KI, Prakash RS, et al., Basal ganglia volume is associated with aerobic fitness in preadolescent children, Dev Neurosci, 2010;32:249–56.
  44. Timmons BW, Raha S, A pediatric perspective on inflammation and oxidative stress in response to exercise, Appl Physiol Nutr Metab, 2008;33:411–9.
  45. Carrel AL, McVean JJ, Clark RR, et al., School-based exercise improves fitness, body composition, insulin sensitivity, and markers of inflammation in non-obese children, J Pediatr Endocrinol Metab, 2009;22:40–15.
  46. Ploughman M, Beaulieu S, Harris C, et al., The Canadian survey of health, lifestyle and ageing with multiple sclerosis: methodology and initial results, BMJ Open, 2014;4:e005718.
  47. Motl RW, McAuley E, Sandroff BM, Hubbard EA, Descriptive epidemiology of physical activity rates in multiple sclerosis, Acta Neurol Scand, 2015 [Epub ahead of print].
  48. Klaren RE, Motl RW, Dlugonski D, et al., Objectively quantified physical activity in persons with multiple sclerosis, Arch Phys Med Rehabil, 2013;94:2342–8.
  49. Motl RW, McAuley E, Snook EM, Physical activity and multiple sclerosis: a meta-analysis, Mult Scler, 2005;11:459–63.
  50. Motl RW, Dlugonski D, Pilutti L, et al., Premorbid physical activity predicts disability progression in relapsing-remitting multiple sclerosis, J Neurol Sci, 2012;323(1–2):123–7.
  51. Marck CH, Hadgkiss EJ, Weiland TJ, et al., Physical activity and associated levels of disability and quality of life in people with multiple sclerosis: a large international survey, BMC Neurol, 2014;14:143.
  52. Motl RW, McAuley E, Snook EM, Gliottoni RC, Physical activity and quality of life in multiple sclerosis: intermediary roles of disability, fatigue, mood, pain, self-efficacy and social support, Psychol Health Med, 2009;14:111–24.
  53. Petajan JH, Gappmaier E, White AT, et al., Impact of aerobic training on fitness and quality of life in multiple sclerosis, Ann Neurol, 1996;39:432–41.
  54. Cakt BD, Nacir B, Genç H, et al., Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study, Am J Phys Med Rehabil, 2010;89:446–57.
  55. 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, Mult Scler, 2002;8:161–8.
  56. Oken BS, Kishiyama S, Zajdel D, et al., Randomized controlled trial of yoga and exercise in multiple sclerosis, Neurology, 2004;62:2058–64.
  57. Klaren RE, Hubbard EA, Motl RW, Efficacy of a behavioral intervention for reducing sedentary behavior in persons with multiple sclerosis: A pilot examination, Am J Prev Med, 2014;47:613–6.
  58. Martinez-Gomez D, Ruiz JR, Gomez-Martinez S, et al., Active commuting to school and cognitive performance in adolescents: the AVENA study, Am J Prev Med, 2014;47:613–6.
  59. Andersen LB, Schnohr P, Schroll M, Hein HO, All-cause mortality associated with physical activity during leisure time, work, sports, and cycling to work, Arch Int Med, 2000;160:1621–8.
  60. Rietberg MB, van Wegen EE, Uitdehaag BM, Kwakkel G, The association between perceived fatigue and actual level of physical activity in multiple sclerosis, Mult Scler, 2011;17:1231–7.
  61. Langer-Gould A, Brara SM, Beaber BE, Koebnick C, Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome, Neurology, 2013;80:548–52.
  62. Munger KL, Chitnis T, Ascherio A, Body size and risk of MS in two cohorts of US women, Neurology, 2009;73:1543–50.
  63. McVean JJ, Carrel AL, Eickhoff JC, Allen DB, Fitness level and body composition are associated with inflammation in nonobese children, J Pediatr Endocrinol Metab, 2009;22:153–9.
  64. Grover SA, Banwell B, Khan S, Yeh EA, Exercise, Fatigue and Depression in a Pediatric Multiple Sclerosis Population, Abstracts of ECTRIMS (Congress of the European Committee for Treatment and Research in Multiple Sclerosis), 2013. October 2–5, 2013. Copenhagen, Denmark, Mult Scler, 2013; 19(Suppl. 11):8–597.
  65. Sawicki C, Grover S, Kinnette-Hopkins D, et al., (editors), Self-efficacy and functional disability as barriers to physical activity participation in paediatric multiple sclerosis, American Academy of Neurology, 2015.
  66. Wu XY, Ohinmaa A, Veugelers PJ, Diet quality, physical activity, body weight and health-related quality of life among grade 5 students in Canada, Public Health Nutr, 2012;15:75–81.

Further Resources

Share this Article
Related Content In Multiple Sclerosis
  • Copied to clipboard!
    accredited arrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-whiteticktimetranscriptup-arrowwebinar Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72