Is Exercise-Induced Fatigue a Problem in Children with Duchenne Muscular Dystrophy?
Objective Duchenne muscular dystrophy (DMD) is a devastating X-linked muscular disorder. The number of studies investigating new therapeutic approaches is substantially increasing. This study aims to investigate the impact and diagnostic value of exercise-induced fatigue in DMD, which has been proposed as a suitable outcome parameter in other conditions like spinal muscular atrophy.
Patients and Methods A cohort of 55 DMD patients (49 of them treated with steroids and 9 with ataluren) underwent a total of 241 6MWT (mean 4.4 tests/patient) which were retrospectively analyzed. Exercise-induced fatigue was assessed by the ratio between the distance achieved in the sixth minute and the distance in the second minute of the 6MWT. In previous studies a quotient above 1 was defined as a sign of fatigue.
Results The average fatigue quotient in the whole cohort of patients was 1.0. In a further analysis no impact of age, steroid therapy, ataluren therapy, overall disability, and distance in the 6-minute walk test (6MWT) on fatigue in DMD patients could be shown.
Conclusion Our data show that fatigue does not play a relevant role in DMD. Analysis of fatigue is not a useful outcome parameter in DMD studies. For this reason we suggest the 2MWT, which is better accepted by the patients, as an alternative to the commonly 6MWT.
KeywordsDuchenne muscular dystrophy - outcome measures - clinical trials - 6-minute walk test - fatigue
* The authors contributed equally to the manuscript.
Received: 09 November 2019
Accepted: 12 February 2020
05 May 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Stuttgart · New York
- 1 Emery AE. The muscular dystrophies. Lancet 2002; 359 (9307): 687-695
- 2 Zubrzycka-Gaarn EE, Bulman DE, Karpati G. , et al. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 1988; 333 (6172): 466-469
- 3 Brooke MH, Fenichel GM, Griggs RC. , et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology 1989; 39 (04) 475-481
- 4 McDonald CM, Abresch RT, Carter GT. , et al. Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med Rehabil 1995; 74 (Suppl. 05) S70-S92
- 5 Kohler M, Clarenbach CF, Bahler C, Brack T, Russi EW, Bloch KE. Disability and survival in Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry 2009; 80 (03) 320-325
- 6 Villanova M, Kazibwe S. New survival target for Duchenne muscular dystrophy. Am J Phys Med Rehabil 2017; 96 (02) e28-e30
- 7 El-Aloul B, Altamirano-Diaz L, Zapata-Aldana E. , et al. Pharmacological therapy for the prevention and management of cardiomyopathy in Duchenne muscular dystrophy: a systematic review. Neuromuscul Disord 2017; 27 (01) 4-14
- 8 Brooke MH, Fenichel GM, Griggs RC. , et al. Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone. Arch Neurol 1987; 44 (08) 812-817
- 9 Le Guiner C, Servais L, Montus M. , et al. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun 2017; 8: 16105
- 10 Robinson-Hamm JN, Gersbach CA. Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy. Hum Genet 2016; 135 (09) 1029-1040
- 11 Reinig AM, Mirzaei S, Berlau DJ. Advances in the treatment of Duchenne muscular dystrophy: new and emerging pharmacotherapies. Pharmacotherapy 2017; 37 (04) 492-499
- 12 McDonald CM, Henricson EK, Han JJ. , et al. The 6-minute walk test as a new outcome measure in Duchenne muscular dystrophy. Muscle Nerve 2010; 41 (04) 500-510
- 13 Davidson ZE, Ryan MM, Kornberg AJ, Walker KZ, Truby H. Strong correlation between the 6-minute walk test and accelerometry functional outcomes in boys with Duchenne muscular dystrophy. J Child Neurol 2015; 30 (03) 357-363
- 14 Montes J, Blumenschine M, Dunaway S. , et al. Weakness and fatigue in diverse neuromuscular diseases. J Child Neurol 2013; 28 (10) 1277-1283
- 15 Montes J, Dunaway Young S, Mazzone ES. , et al. Nusinersen improves walking distance and reduces fatigue in later-onset SMA. Muscle Nerve 2019; 60 (04) 409-414
- 16 Witherspoon JW, Vuillerot C, Vasavada RP. , et al. Motor function performance in individuals with RYR1-related myopathies. Muscle Nerve 2019; 60 (01) 80-87
- 17 ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166 (01) 111-117
- 18 Vill K, Ille L, Schroeder SA, Blaschek A, Müller-Felber W. Six-minute walk test versus two-minute walk test in children with Duchenne muscular dystrophy: is more time more information?. Eur J Paediatr Neurol 2015; 19 (06) 640-646
- 19 Bartels B, de Groot JF, Terwee CB. The six-minute walk test in chronic pediatric conditions: a systematic review of measurement properties. Phys Ther 2013; 93 (04) 529-541
- 20 McDonald CM, Campbell C, Torricelli RE. , et al; Clinical Evaluator Training Group; ACT DMD Study Group. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390 (10101): 1489-1498
- 21 Shieh PB, Mcintosh J, Jin F. , et al; THE ACT DMD STUDY GROUP. Deflazacort versus prednisone/prednisolone for maintaining motor function and delaying loss of ambulation: a post HOC analysis from the ACT DMD trial. Muscle Nerve 2018; 58 (05) 639-645
- 22 Victor RG, Sweeney HL, Finkel R. , et al; Tadalafil DMD Study Group. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology 2017; 89 (17) 1811-1820
- 23 McDonald CM, Henricson EK, Abresch RT. , et al; PTC124-GD-007-DMD Study Group. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve 2013; 48 (03) 343-356
- 24 McDonald CM, Henricson EK, Abresch RT. , et al; PTC124-GD-007-DMD Study Group. The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study. Muscle Nerve 2013; 48 (03) 357-368
- 25 Nardes F, Araújo AP, Ribeiro MG. Mental retardation in Duchenne muscular dystrophy. J Pediatr 2012; 88 (01) 6-16
- 26 Witherspoon JW, Vasavada R, Logaraj RH. , et al. Two-minute versus 6-minute walk distances during 6-minute walk test in neuromuscular disease: is the 2-minute walk test an effective alternative to a 6-minute walk test?. Eur J Paediatr Neurol 2019; 23 (01) 165-170
- 27 Morice A, Smithies T. The 100 m walk: a simple and reproducible exercise test. Br J Dis Chest 1984; 78 (04) 392-394