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BMC Neurology
Published in: BMC Neurology 1/2019

Open Access 01-12-2019 | Spinal Muscular Atrophy | Research article

Assessment of fatigability in patients with spinal muscular atrophy: development and content validity of a set of endurance tests

Authors: Bart Bartels, Laura E. Habets, Marloes Stam, Renske I. Wadman, Camiel A. Wijngaarde, Marja A. G. C. Schoenmakers, Tim Takken, Erik H.J. Hulzebos, W. Ludo van der Pol, Janke F. de Groot

Published in: BMC Neurology | Issue 1/2019

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Abstract

Background

Fatigability has emerged as an important dimension of physical impairment in patients with Spinal Muscular Atrophy (SMA). At present reliable and valid outcome measures for both mildly and severely affected patients are lacking. Therefore the primary aim of this study is the development of clinical outcome measures for fatigability in patients with SMA across the range of severity.

Methods

We developed a set of endurance tests using five methodological steps as recommended by the ‘COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). In this iterative process, data from multiple sources were triangulated including a scoping review of scientific literature, input from a scientific and clinical multidisciplinary expert panel and three pilot studies including healthy persons (N = 9), paediatric patients with chronic disorders (N = 10) and patients with SMA (N = 15).

Results

Fatigability in SMA was operationalised as the decline in physical performance. The following test criteria were established; one method of testing for patients with SMA type 2–4, a set of outcome measures that mimic daily life activities, a submaximal test protocol of repetitive activities over a longer period; external regulation of pace. The scoping review did not generate suitable outcome measures.
We therefore adapted the Endurance Shuttle Walk Test for ambulatory patients and developed the Endurance Shuttle Box and Block Test and the - Nine Hole Peg Test for fatigability testing of proximal and distal arm function. Content validity was established through input from experts and patients. Pilot testing showed that the set of endurance tests are comprehensible, feasible and meet all predefined test criteria.

Conclusions

The development of this comprehensive set of endurance tests is a pivotal step to address fatigability in patients with SMA.
Appendix
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Literature
1.
Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P. Identification and characterization of a apinal muscular atrophy-determining gene. Cell. 1995;80:155–65.CrossRef
2.
Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. The Lancet Neurology. 2012;11(5):443–52.CrossRef
3.
Wadman RI, Wijngaarde CA, Stam M, Bartels B, Otto LAM, Lemmink HH, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2018;25(3):512–8.CrossRef
4.
Noto Y, Misawa S, Mori M, Kawaguchi N, Kanai K, Shibuya K, et al. Prominent fatigue in spinal muscular atrophy and spinal and bulbar muscular atrophy: evidence of activity-dependent conduction block. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2013;124(9):1893–8.CrossRef
5.
Wadman RI, Vrancken AFJE, van den Berg LH, Van der Pol WL. Dysfunction of the neuromuscular junciton in spinal muscular atrophy types 2 and 3. Neurology. 2012;79:2050–5.CrossRef
6.
Pageaux B, Lepers R. Fatigue induced by physical and mental exertion increases perception of effort and impairs subsequent endurance performance. Front Physiol. 2016;7:587.CrossRef
7.
Kluger BM, Krupp LB, Enoka RM. Fatigue and fatigability in neurologic. Neurology. 2013;80:409–16.CrossRef
8.
Kariya S, Park GH, Maeno-Hikichi Y, Leykekhman O, Lutz C, Arkovitz MS, et al. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet. 2008;17(16):2552–69.CrossRef
9.
Kong L, Wang X, Choe DW, Polley M, Burnett BG, Bosch-Marce M, et al. Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. J Neurosci. 2009;29(3):842–51.CrossRef
10.
Arnold AS, Gueye M, Guettier-Sigrist S, Courdier-Fruh I, Coupin G, Poindron P, et al. Reduced expression of nicotinic AChRs in myotubes from spinal muscular atrophy I patients. Laboratory investigation; a journal of technical methods and pathology. 2004;84(10):1271–8.CrossRef
11.
Goulet B, Kothary R, Parks RJ. At the junction of spinal muscular atrophy pathogenesis: the role of neuromuscular junction dysfunction in SMA disease progression. Curr Mol Med. 2013;13(1–15).
12.
Pera MC, Luigetti M, Pane M, Coratti G, Forcina N, Fanelli L, et al. 6MWT can identify type 3 SMA patients with neuromuscular junction dysfunction. Neuromuscular disorders : NMD. 2017;27(10):879–82.CrossRef
13.
14.
Stam M, Wadman RI, Wijngaarde CA, Bartels B, Asselman FL, Otto LAM, et al. Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2-4 (SPACE trial). BMJ Open. 2018;8(7):e019932.CrossRef
15.
Health USDo, Human Services FDACfDE, Research, Health USDo, Human Services FDACfBE, Research, et al. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006;4:79.CrossRef
16.
(CHMP) Cfmpfhu. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. European Medicines Agency website, 2005.
17.
de Vet HC, Terwee CB, Mokkink LB, Knol DL. Measurement in medicine: practical guides to biostatistics and epidemiology. 4th ed. Cambride: Cambride University Press; 2011.CrossRef
18.
Mokkink LB, Terwee CB, Knol DL, Stratford PW, Alonso J, Patrick DL, et al. Protocol of the COSMIN study: COnsensus-based standards for the selection of health measurement INstruments. BMC Med Res Methodol. 2006;6:2.CrossRef
19.
Lou J-S. Techniques in assessing fatigue in neuromuscular diseases. Phys Med Rehabil Clin N Am. 2012;23:11–22.CrossRef
20.
Alexander NB, Taffet GE, Horne FM, Eldadah BA, Ferrucci L, Nayfield S, et al. Bedside-to-bench conference: research agenda for idiopathic fatigue and aging. J Am Geriatr Soc. 2010;58(5):967–75.CrossRef
21.
Vollestad NK. Measurement of human fatigue. J Neurosci Methods. 1997;74(219/27).
22.
Finsterer J. Biomarkers of peripheral muscle fatigue during exercise. BMC Musculoskelet Disord. 2012;13:218.CrossRef
23.
Bar-Or O. Role of exercise in the assessment and management of neuromuscular disease in children. Med Sci Sports Exerc. 1996;28(4):421–7.CrossRef
24.
Jones D, Round J, de Haan A. Skeletal muscle from molecules to movement. In: A textbook of muscle physiology for sports, exercise,physiotherapy and medicine. London: Churchill Livingstone; 2004.
25.
Féasson L, Camdessanché JP, El Mhandi L, Calmels P, Millet GY. Fatigue and neuromuscular diseases. Ann Readapt Med Phys. 2006;49(6):375–84.CrossRef
26.
Straver CG, van den Berg LH, van Doorn PA, Franssen H. Symptoms of activity induced weakness in peripheral nervous system disorders. J Peripher Nerv Syst. 2011;16:108–12.CrossRef
27.
van Mater HA, Williams JW Jr, Coeytaux RR, Sanders GD, Kemper AR. Psychometric characteristics of outcome measures in juvenile idiopathic arthritis: a systematic review. Arthritis care & research. 2012;64(4):554–62.CrossRef
28.
Wadman RI, Stam M, Gijzen M, Lemmink HH, Snoeck IN, Wijngaarde CA, et al. Association of motor milestones, SMN2 copy and outcome in spinal muscular atrophy types 0-4. J Neurol Neurosurg Psychiatry. 2017;88(4):365–7.CrossRef
29.
Bowen DJ, Kreuter M, Spring B, Cofta-Woerpel L, Linnan L, Weiner D, et al. How we design feasibility studies. Am J Prev Med. 2009;36(5):452–7.CrossRef
30.
Utter AC, Robertson RJ, Nieman DC, Kang J. Children's OMNI scale of perceived exertion: walking/running evaluation. Med Sci Sports Exerc. 2002;34(1):139–44.CrossRef
31.
Moller MC, Nygren de Boussard C, Oldenburg C, Bartfai A. An investigation of attention, executive, and psychomotor aspects of cognitive fatigability. J Clin Exp Neuropsychol. 2014;36(7):716–29.CrossRef
32.
Hart R, Ballaz L, Robert M, Pouliot A, D'Arcy S, Raison M, et al. Impact of exercise-induced fatigue on the strength, postural control, and gait of children with a neuromuscular disease. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists. 2014.
33.
Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. The Lancet Neurology. 2009;8(5):475–90.CrossRef
34.
Milner-Brown HS, Miller RG. Increased muscular fatigue in patients with neurogenic muscle weakness: quantification and pathophysiology. Arch Phys Med Rehabil. 1989;70(5):361–6.PubMed
35.
Iannaccone ST, White M, Browne R, Russman B, Buncher R, Samaha FJ. Muscle fatigue in spinal muscular atrophy. J Child Neurol. 1997;12(5):321–6.CrossRef
36.
Granger MW, Buschang PH, Throckmorton GS, Iannaccone ST. Masticatory muscle function in patients with spinal muscular atrophy. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics. 1999;115(6):697–702.CrossRef
37.
Montes J, McDermott MP, Martens WB, Dunaway S, Glanzman AM, Riley S, et al. Six-minute walk test demonstrates motor fatigue in spinal muscular atrophy. Neurology. 2010;75(12):833–8.CrossRef
38.
Montes J, Dunaway S, Montgomery MJ, Sproule D, Kaufmann P, De Vivo DC, et al. Fatigue leads to gait changes in spinal muscular atrophy. Muscle Nerve. 2011;43(4):485–8.CrossRef
39.
Montes J, Blumenschine M, Dunaway S, Alter AS, Engelstad K, Rao AK, et al. Weakness and fatigue in diverse neuromuscular diseases. J Child Neurol. 2013;28(10):1277–83.CrossRef
40.
Montes J, Dunaway S, Garber CE, Chiriboga CA, De Vivo DC, Rao AK. Leg muscle function and fatigue during walking in spinal muscular atrophy type 3. Muscle Nerve. 2013.
41.
Stam M, 'Wadman RI, Leeuw M, Wijngaarde CA, van den Berg LH, van der Pol WL. The repeated nine hole peg test as outcome measure for fatigability in SMA. Orphanet journal of rare diseases 2018.
42.
Lammers AE, Diller GP, Odendaal D, Tailor S, Derrick G, Haworth SG. Comparison of 6-min walk test distance and cardiopulmonary exercise test performance in children with pulmonary hypertension. Arch Dis Child. 2011;96(2):141–7.CrossRef
43.
Dunaway Young S, Montes J, Kramer SS, Marra J, Salazar R, Cruz R, et al. Six-minute walk test is reliable and valid in spinal muscular atrophy. Muscle Nerve. 2016;54(5):836–42.CrossRef
44.
Revill SM, Morgan MDL, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk test: a new field exercise test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax. 1999;54:213–22.CrossRef
45.
Grice KO, Vogel KA, Le V, Mitchell A, Muniz S, Vollmer MA. Adult norms for a comercially available nine hole peg test for finger dexterity. Am J Occup Ther. 2003;57:570–3.CrossRef
46.
Poole JL, Burtner PA, Torres TA, McMullen CK, Markham A, Marcum ML, et al. Measuring dexterity in children using the nine-hole peg test. Journal of hand therapy : official journal of the American Society of Hand Therapists. 2005;18(3):348–51.CrossRef
47.
Mathiowetz V, Federman S, Box WD. Block test of manual dexterity norms for 6-19 years old. Can J Occup Ther. 1985;52(5).
48.
Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and block test of manual dexterity. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 1985;39(6):386–91.CrossRef
49.
Terwee CB, Prinsen CAC, Chiarotto A, Westerman MJ, Patrick DL, Alonso J, et al. COSMIN methodology for evaluating the content validity of patient-reported outcome measures: a Delphi study. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2018;27(5):1159–70.CrossRef
50.
Hill K, Dolmage TE, Woon L, Coutts D, Goldstein R, Brooks D. A simple method to derive speed for the endurance shuttle walk test. Respir Med. 2012;106(12):1665–70.CrossRef
51.
Qin J, Lin JH, Buchholz B, Xu X. Shoulder muscle fatigue development in young and older female adults during a repetitive manual task. Ergonomics. 2014:1–12.
52.
Qin J, Lin JH, Faber GS, Buchholz B, Xu X. Upper extremity kinematic and kinetic adaptations during a fatiguing repetitive task. Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology. 2014;24(3):404–11.CrossRef
53.
Conceicao A, Silva AJ, Barbosa T, Karsai I, Louro H. Neuromuscular fatigue during 200 m breaststroke. Journal of sports science & medicine. 2014;13(1):200–10.
54.
Enoka RM, Duchateau J. Translating fatigue to human performance. Med Sci Sports Exerc. 2016;48(11):2228–38.CrossRef
55.
Schillings ML, Kalkman JS, Janssen HM, van Engelen BG, Bleijenberg G, Zwarts MJ. Experienced and physiological fatigue in neuromuscular disorders. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2007;118(2):292–300.CrossRef
56.
Taylor JL, Amann M, Duchateau J, Meeusen R, Rice CL. Neural contributions to muscle fatigue: from the brain to the muscle and Back again. Med Sci Sports Exerc. 2016;48(11):2294–306.CrossRef
57.
Allen DG, Lamb GD, Westerblad H. Skeletal muscle fatigue: cellular mechanisms. Physiol Rev. 2008;88(1):287–332.CrossRef
58.
Gandevia SC. Spinal and supraspinal factors in human muscle fatigue. Physiol Rev. 2001;81(4):1725–89.CrossRef
59.
Van Cutsem J, Marcora S, De Pauw K, Bailey S, Meeusen R, Roelands B. The effects of mental fatigue on physical performance: a systematic review. Sports Med. 2017;47(8):1569–88.CrossRef
60.
Ripolone M, Ronchi D, Violano R, Vallejo D, Fagiolari G, Barca E, et al. Impaired muscle mitochondrial biogenesis and Myogenesis in spinal muscular atrophy. JAMA neurology. 2015;72(6):666–75.CrossRef
61.
Shababi M, Lorson CL, Rudnik-Schoneborn SS. Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease? J Anat. 2014;224(1):15–28.CrossRef
62.
CMW Gaasterland, Jansen-van der Weide MC, Vroom E, Leeson-Beevers K, Kaatee M, Kaczmarek R, et al. The POWER-protocol: recommendations for involving patient representatives in choosing relevant outcome measures during rare diseases clinical trial design journal health policy. 2018;accepted.
63.
Gastin PB. Energy system interaction and relative contribution during maximal exercise. Sports Med. 2001;31(10):725–41.CrossRef
Metadata
Title
Assessment of fatigability in patients with spinal muscular atrophy: development and content validity of a set of endurance tests
Authors
Bart Bartels
Laura E. Habets
Marloes Stam
Renske I. Wadman
Camiel A. Wijngaarde
Marja A. G. C. Schoenmakers
Tim Takken
Erik H.J. Hulzebos
W. Ludo van der Pol
Janke F. de Groot
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2019
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-019-1244-3

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