Exercise therapy and multiple sclerosis a powerful non-pharmacological intervention

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1 Malmö, November 2014 Exercise therapy and multiple sclerosis a powerful non-pharmacological intervention Ulrik Dalgas, PhD Department of Public Health Section of Sport Science Aarhus University Denmark dalgas@ph.au.dk

2 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

3 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

4 Mult. Scler 2005; 11:4: Lowered physical activity level During recent years application of exercise therapy has become generally accepted in MS rehabilitation.

5 Lowered physical activity level - MS Phys Ther; 93:8: n=289, 2.5y

6 Muscle fiber atrophy

7 Background

8 JOSPT; 16:3:1992 Reduced muscle strength

9 Kjølhede et al. submitted Strength and walking

10 Reduced VO 2 -max VO 2 -max is an important health and performance marker ~20% lowering of VO 2 -max

11 Reduced VO 2 -max Duration of illness Neurological disablility (EDSS) Walking (T25FW, 6MWT) Body weight Accelerometer counts and GLTEQ Fatigue (FSS, MFIS) Aerobic capacity (VO 2 -max) Quality of life (SF36-MH, SF36) Plaque volume in brain POMS Vitamin D serum level SIP Strength / gripstrength Cognitive processing speed / PASAT Langeskov-Christensen et al. (Submitted)

12 Increased CVD risk

13 Walking speed and disability level EDSS score (a.u.) n 6MWT (m/s ± SD) 6MWT% (%expected ± SD) MSWS-12 (a.u. ± SD) ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 18.9 Langeskov et al. In preparation, n=473

14 MS patients vs. healthy controls Muscle strength Muscle mass Muscle activation Aerobic capacity (VO2-max) CVD risk Depression Fatigue Daily activity level Functional capacity Balance QoL Red arrow = Impaired in MS patients MS patients vs. healthy controls ê ê ê ê é é é ê ê ê ê ICF level Body Functions Activity Participation Motl & Pillutti, Nat Rev Neurol; Sep;8(9): Dalgas et al. Mult. Scler.14(35);35-53:2008

15 Rationale for exercise therapy Disease process Inactivity Rise and worsening of symptoms

16 Rationale for exercise therapy? Exercise therapy Disease process Inactivity? Positive effect on symptoms

17

18 Background Physical exercise is not for MS patients Rate of relapse Relative risk of relapse (vs. Control) Control 6.3% Exercise 4.6% 0.73 Exercise may protect against relapses in persons with MS.

19 Rationale for exercise therapy? Exercise therapy Disease process Inactivity? Positive effect on symptoms

20 Background Exercise therapy has been a controversial issue for many years Now an accepted part of MS rehabilitation

21 Background Research interest has increased dramatically Pubmed: "Multiple Sclerosis"[Mesh] AND "Exercise Therapy"[Mesh] Publications (n) Year

22 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

23 Definition Exercise therapy is an individualized exercise prescription (or plan) designed to restore health and prevent further disease or impairment. The prescription, written by a doctor or rehabilitation specialist, takes into account the current medical condition and provides advice regarding exercise type, intensity, duration and frequency.

24 What is exercise therapy? Resistance training Body building Basketball Soccer Swimming Rowing Running Cycling Endurance training Endurance training: Continous contractions against low loads ( Aerobic metabolism ) Resistance training: Few contractions against heavy loads ( Anaerobic metabolism )

25 Basic principles of exericse 1. Individual differences 2. Specificity 3. Progressive overload 4. Reversibility

26 Individual differences People respond differently to exercise because of differences in size and shape, genetics, past experience, chronic conditions, injuries and even gender 20 w, 3d/w, 30min/session HR: 65% of max N=481 Family Heritage Study, Bouchard et al.

27 Specificity To become better at a particular exercise or skill, it is necessary to perform that exercise or skill Fleck & Kraemer; Designing Resistance Training Programs RT for 6 weeks, 3 d/w

28 Progressive Basic principles Overload of exercise Performance Time

29 Reversibility Use it or lose it Change in performance from baseline Training Detraining

30 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

31 Background Physical exercise is not for MS patients Rate of relapse Relative risk of relapse (vs. Control) Rate of adverse events Control 6.3% 1.2% Exercise 4.6% % Evidence suggests that exercise training is generally safe for persons with MS.

32 Outline 40% experience symptom worsening during exercise Normalised for 85% within 30min after exercise cessation

33 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

34 Effects of exercise Exercise in a nonprogressive disease Exercise in a progressive disease Functional level Effect Functional level Same effect! Exercise may be an effective treatment Time Time

35 What is exercise therapy? Resistance training Body building Basketball Soccer Swimming Rowing Running Cycling Endurance training

36 Resistance training and muscle strength

37 Results from review 1. Safe intervention a. No adverse events b. No serious worsening of symptoms 2. Excellent adherance (90-100%) 3. Low drop out (0-13%) Kjølhede et al. Mult. Scler. Epub ahead of print, 2012

38 Results from review 4. No effects on EDSS 5. Improves muscle strength (7-21% for KE, KF and PF) 6. Holds the potential to improve muscle mass and neural activation Kjølhede et al. Mult. Scler. Epub ahead of print, 2012

39 Study design TRIAL Follow up 19 Exercise Resistance training No intervention 19 Control No intervention Resistance training Week 0 Test Week 12 Week 24 Test Test

40 Program Five leg exercises 2days/week

41 Study on resistance training Exercise Control * p<0.05 Change (%) Knee extensor KE MVC Functional Score Muscle strength Dalgas et al. Neurology:73: :2009

42 RT may improve neural activation

43 Typical EMG recording Nm µv µv µv KF MVC KF MVC Force VL RF ST KE MVC KE MVC VL RF ST Time [s] [s] Time [s]

44 Neural mechanisms % * +40% * Exercise (post-pre) Control (post-pre) +31% * Change in iemg (mv) VL iemg KE RF iemg KE ST iemg KF Dalgas et al. J Neurol 2013

45 Hypotese Før Styrketræning Before After

46 Results Walking velocity m/s 2 1 Healthy 2.2m/s MS after exercise 1.51m/s Crossing 1.5m/s MS before exercise1.29m/s 0

47 Changes of FSS (a.u.) Results Fatigue * CON EXE * p<0.05 Dalgas et al. Mult. Scler:16(4)480-90:2010

48 Results Mood * Changes of MDI (a.u.) * p<0.05 CON EXE Dalgas et al. Mult. Scler:16(4)480-90:2010

49 Results Quality of life * Changes of PCS (a.u.) * p<0.05 CON EXE Dalgas et al. Mult. Scler:16(4)480-90:2010

50 What is exercise therapy? Resistance training Body building Basketball Soccer Swimming Rowing Running Cycling Endurance training

51 Results from review 1. Safe intervention a. No adverse events b. No serious worsening of symptoms 2. Long term ET improve VO 2 -max Dalgas et al. Mult. Scler.14(35);35-53:2008

52 Aerobic capacity+15% Arm-leg ergometry 15 weeks 3 days/week QoL also improved Fatigue improved Mood improved Petajan et al. Annals of Neurology;39:4:1996

53 Endurance training and VO 2 -max Study or Subgroup Bjarnadottir 2007 Briken 2014 Golzari 2010 Hamburg group 2003/2004 Petajan 1996 Rasova 2006 Skjerbaek 2014 Experimental Control Std. Mean Difference Std. Mean Difference Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI 4 1, , , % 15.5% 14.2% 15.1% 15.3% 16.5% 11.6% 1.47 [0.30, 2.64] 0.31 [-0.40, 1.03] [-1.08, 0.68] 0.69 [-0.08, 1.46] 2.18 [1.43, 2.92] 0.10 [-0.49, 0.69] 0.23 [-0.97, 1.42] Total (95% CI) 125 Heterogeneity: Tau² = 0.58; Chi² = 26.30, df = 6 (P = ); I² = 77% Test for overall effect: Z = 2.03 (P = 0.04) % 0.67 [0.02, 1.32] Favours [control] Favours [experimental] Langeskov-Christensen et al. submitted

54 Results from review 3. ET can improve functional capacity but inconsistent findings exists Dalgas et al. Mult. Scler.14(35);35-53:2008

55 10m walk time: 17% improvement 3 days/week 4 weeks

56 NNR 2009 Feb;23(2): Mean ES = 0.19 Aerobic only = 0.25 Supervised exercise = 0.32

57 Results from review 4. ET seem to reduce fatigue but inconsistent findings exists Dalgas et al. Mult. Scler.14(35);35-53:2008

58 Psychosomatic Medicine 2013 Mean ES = 0.45

59 Results from review 5. ET can reduce depression score but inconsistent findings exists. 6. ET most often improves Quality of Life. Dalgas et al. Mult. Scler.14(35);35-53:2008

60 Eur J Neurol 2014 (in press) Mean ES = -0.37

61 Mean ES = 0.23

62 Exercise and cognition Two studies on MS identified Oken et al. 2004, Velikonja et al, 2010 Improved choice reaction time in MS Arch Phys Med Rehabil, 92, 1044:52;2011

63 Effects of Exercise therapy MS patients vs. healthy controls Muscle strength Muscle mass Muscle activation Aerobic capacity (VO2-max) CVD risk Depression Fatigue Daily activity level Functional capacity Balance ê ê ê ê é é é ê ê ê é é ê ê ê é é é é é é é ê ê ê é é é QoL ê é é Red arrow = Impaired in MS patients Green arrow = Improved after exercise in MS patients Motl & Pillutti, Nat Rev Neurol; Sep;8(9): Dalgas et al. Mult. Scler.14(35);35-53:2008

64 What about the severely disabled?

65 Særlige problemstillinger Int J MS Care, 12, 1, 6-12, 2010

66 Endurance training in EDSS>6 Skjerbæk et al. Mult Scler

67 Other types of training

68 Other types of training Yoga 6 mdr. Mindre træthed Samme effekt som cykling

69 J.Neurol.Phys.Ther; 33(3), : 2012 Climbing could improve muscle performance and balance for patients with Multiple Sclerosis; Jolk et al. and Valikonja et al. Mental tai chi-based exercise programme versus tai chi for multiple sclerosis patients; Kaur et al. (Poster ECTRIMS 2013)

70 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

71 Exercise prevalence How many patients with MS are exercising regularly?

72 Exercise and disease progression 45% exercised ( 2*30min/week; IPAQ) Australia, n=93 Population-based

73 Exercise and disease progression Disabil & Rehab; 35(5), , % exercised regularly (Are you exercising on a regular basis?) No difference between men and women Of those not exercising 79% were interested Canada, n=411, MS and CIS, EDSS<7, population based, single question (follow up questions)

74 Follow up effects How are the effects at follow up in exercise studies?

75 Results 180 KE MVC FS Functional Score Relative to pre value (%) Post Follow up Post Follow up

76 Results from review PT led FI led Yoga

77 Results from review

78 Reversibility Change in performance from baseline Training Detraining

79 Disabil & Rehab, 35(5), ; 2013 Perceived barriers n=417

80 Outline 1. Background and rationale 2. Definition and principles of exercise therapy 3. Safety 4. Effects of exercise therapy 5. Exercise in the community 6. Recommendations and conclusions

81 Exercise recommendations

82 Limitations to exercise studies 1. Small sample sizes 2. Short-term interventions (<26weeks) 3. Most studies applies supervised lab exercise not community based studies 4. Predominantly disability levels <EDSS 6 5. Predominantly studies on RRMS or mixed groups of patients 6. Patients with co-morbidities are excluded

83 Summary Exercise therapy is a safe and potent nonpharmacological intervention in MS (and other neurological pathologies) Effects cover symptoms at all ICF levels, but depend on exercise modality Knowledge on how to optimise long-term adherence are warranted Consensus recommendations exist

84 Thank you for your attention!

85 Trænings protokol Weeks Sets Reps Load 1 & RM 3 & RM 5 & RM 7 & RM 9 & RM 11 & RM

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