[en] [en] BACKGROUND: Measurement of muscle strength and motor function is recommended in clinical trials of neuromuscular diseases, but the loss of hand strength at which motor function is impacted is not documented.
OBJECTIVES: To establish the relationship between hand strength and function, and to determine the strength threshold that differentiates normal and abnormal hand function in individuals with Duchenne Muscular Dystrophy (DMD) or Spinal Muscular Atrophy (SMA).
METHODS: Maximal handgrip and key pinch strength were measured with the MyoGrip and MyoPinch dynamometers, respectively. Hand function was assessed using the MoviPlate, the Motor Function Measure items for distal upper limb (MFM-D3-UL) and the Cochin Hand Function Scale (CHFS).
RESULTS: Data from 168 participants (91 DMD and 77 SMA, age 6-31 years) were analyzed. Relationships between strength and function were significant (P < 0.001). Hand function was generally preserved when strength was above the strength threshold determined by Receiver-Operating Characteristic (ROC) analysis: For MFM-D3-UL, the calculated handgrip strength thresholds were 41 and 13% of the predicted strength for a healthy subject (% pred) and the key pinch strength thresholds were 42 and 26% pred for DMD and SMA, respectively. For the MoviPlate, handgrip strength thresholds were 11 and 8% pred and key pinch strength thresholds were 21 and 11% pred for DMD and SMA, respectively. For participants with sub-threshold strength, hand function scores decreased with decreasing strength. At equal % pred strength, individuals with SMA had better functional scores than those with DMD.
CONCLUSIONS: Hand function is strength-dependent for most motor tasks. It declines only when strength falls below a disease-specific threshold. Therefore, therapies capable of maintaining strength above this threshold should preserve hand function.
Disciplines :
Pediatrics
Author, co-author :
Decostre, Valérie ; Institut de Myologie, GH Pitié-Salpêtrière, Paris, France
De Antonio, Marie; Institut de Myologie, GH Pitié-Salpêtrière, Paris, France ; Present address: Direction de la Recherche Clinique et de l'Innovation, Centre hospitalier universitaire de Clermont-Ferrand, Clermont-Ferrand, France
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; Institut de Myologie, GH Pitié-Salpêtrière, Paris, France ; Present address: Department of Paediatrics, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
Hogrel, Jean-Yves; Institut de Myologie, GH Pitié-Salpêtrière, Paris, France
Language :
English
Title :
Relationship Between Hand Strength and Function in Duchenne Muscular Dystrophy and Spinal Muscular Atrophy: Implications for Clinical Trials.
The ULENAP and PreU7 projects were supported by the Association Fran\u00E7aise contre les Myopathies (AFM) and by the Advanced Diagnostics for New Therapeutic Approaches (ADNA), a program dedicated to personalized medicine, coordinated by Institut M\u00E9rieux and supported by research and innovation aid from the French public agency, OSEO. The NatHis-SMA study was co-funded by Institut Roche and Association Institut de Myologie.
Duruoz MT, Poiraudeau S, Fermanian J, Menkes CJ, Amor B, Dougados M, et al. Development and validation of a rheumatoid hand functional disability scale that assesses functional handicap. J Rheumatol. 1996;23(7): 1167-72.
Klingels K, Mayhew AG, Mazzone ES, Duong T, Decostre V, Werlauff U, et al. Development of a patient-reported outcome measure for upper limb function in Duchenne muscular dystrophy:DMDUpper Limb PROM. Dev Med Child Neurol. 2017;59(2):224-31.
Poole JL. Measures of hand function: Arthritis Hand Function Test (AHFT), Australian Canadian Osteoarthritis Hand Index (AUSCAN), Cochin Hand Function Scale, Functional Index for Hand Osteoarthritis (FIHOA), Grip Ability Test (GAT), Jebsen Hand Function Test (JHFT), and Michigan Hand Outcomes Questionnaire (MHQ). Arthritis Care Res (Hoboken). 2011;63(Suppl 11):S189-99.
Berard C, Payan C, Hodgkinson I, Fermanian J. A motor function measure for neuromuscular diseases. Construction and validation study. Neuromuscul Disord. 2005;15(7):463-70.
Mayhew A, Mazzone ES, Eagle M, Duong T, Ash M, Decostre V, et al. Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy. Dev Med Child Neurol. 2013;55(11):1038-45.
Servais L, Deconinck N, Moraux A, Benali M, Canal A, Van Parys F, et al. Innovative methods to assess upper limb strength and function in non-ambulant Duchenne patients. Neuromuscul Disord. 2013;23(2):139-48.
Seferian AM, Moraux A, Annoussamy M, Canal A, Decostre V, Diebate O, et al. Upper limb strength and function changes during a one-year follow-up in nonambulant patients with Duchenne Muscular Dystrophy: An observational multicenter trial. PLoS One. 2015;10(2): e0113999.
Seferian AM, Moraux A, Canal A, Decostre V, Diebate O, Le Moing AG, et al. Upper limb evaluation and one-year follow up of non-ambulant patients with spinal muscular atrophy: An observational multicenter trial. PLoS One. 2015;10(4):e0121799.
Chabanon A, Seferian AM, Daron A, Pereon Y, Cances C, Vuillerot C, et al. Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: Baseline data NatHis-SMA study. PLoS One. 2018;13(7):e0201004.
Annoussamy M, Seferian AM, Daron A, Pereon Y, Cances C, Vuillerot C, et al. Natural history of Type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol. 2020.
DeWel B, De Schaepdryver M, Poesen K, Claeys KG. Biochemical and clinical biomarkers in adult SMA 3-4 patients treated with nusinersen for 22 months. Ann Clin Transl Neurol. 2022;9(8):1241-51.
Hogrel JY, Wary C, Moraux A, Azzabou N, Decostre V, Ollivier G, et al. Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy. Neurology. 2016;86(11):1022-30.
Servais L, Montus M, Guiner CL, Ben Yaou R, Annoussamy M, Moraux A, et al. Non-Ambulant Duchenne Patients Theoretically Treatable by Exon 53 Skipping have Severe Phenotype. J Neuromuscul Dis. 2015;2(3):269-79.
Lilien C, Reyngoudt H, Seferian AM, Gidaro T, Annoussamy M, Che V, et al. Upper limb disease evolution in exon 53 skipping eligible patients with Duchenne muscular dystrophy. Ann Clin Transl Neurol. 2021.
Annoussamy M, Lilien C, Gidaro T, Gargaun E, Che V, Schara U, et al. X-linked myotubular myopathy: A prospective international natural history study. Neurology. 2019;92(16):e1852-e67.
Duong T, Braid J, Staunton H, Barriere A, Petridis F, Reithinger J, et al. Understanding the relationship between the 32-item motor function measure and daily activities from an individual with spinal muscular atrophy and their caregivers' perspective: A two-part study. BMC Neurol. 2021;21(1):143.
Florkowski CM. Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: Communicating the performance of diagnostic tests. Clin Biochem Rev. 2008;29(Suppl 1):S83-7.
Pepe MS. The statistical evaluation of medical tests for classification and prediction. Oxford: Oxford University Press; 2003.
de Lattre C, Payan C, Vuillerot C, Rippert P, de Castro D, Berard C, et al. Motor function measure: Validation of a short form for young children with neuromuscular diseases. Arch Phys Med Rehabil. 2013;94(11):2218-26.
Yildirim MH, Yildirim EA, Carpar E, Coskun T, Ipekcioglu D, Canturk G. Hand functions in patients with schizophrenia: Aclinical comparison with bipolar disorder and healthy subjects. Compr Psychiatry. 2018;87:53-8.
Brooke MH, Griggs RC, Mendell JR, Fenichel GM, Shumate JB, Pellegrino RJ. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981;4(3):186-97.
Hogrel JY, Decostre V, Ledoux I, de Antonio M, Niks EH, de Groot I, et al. Normalized grip strength is a sensitive outcome measure through all stages of Duchenne muscular dystrophy. J Neurol. 2020;267(7):2022-8.
Pane M, Mazzone ES, Sivo S, Fanelli L, De Sanctis R, D'Amico A, et al. The 6 minute walk test and performance of upper limb in ambulant duchenne muscular dystrophy boys. PLoS Curr. 2014;6.
Pera MC, Coratti G, Mazzone ES, Montes J, Scoto M, De Sanctis R, et al. Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve. 2019;59(4):426-30.
Salazar R, Montes J, Dunaway Young S, McDermott MP, Martens W, Pasternak A, et al. Quantitative Evaluation of Lower Extremity Joint Contractures in Spinal Muscular Atrophy: Implications for Motor Function. Pediatr Phys Ther. 2018;30(3):209-15.
Johnson ER, Fowler WM, Jr., Lieberman JS. Contractures in neuromuscular disease. Arch Phys Med Rehabil. 1992;73(9):807-10.
Wang HY, Ju YH, Chen SM, Lo SK, Jong YJ. Joint range of motion limitations in children and young adults with spinal muscular atrophy. Arch Phys Med Rehabil. 2004;85(10):1689-93.
Bergsma A, Janssen M, Geurts ACH, Cup EHC, de Groot IJM. Different profiles of upper limb function in four types of neuromuscular disorders. Neuromuscul Disord. 2017;27(12):1115-22.
Ingram LA, Butler AA, Walsh LD, Brodie MA, Lord SR, Gandevia SC. The upper limb Physiological Profile Assessment: Description, reliability, normative values and criterion validity. PLoS One. 2019;14(6):e0218553.
Bulut N, Alemdaroglu-Gurbuz I, Topaloglu H, Yilmaz O, Karaduman A. The association between trunk control and upper limb functions of children with Duchenne muscular dystrophy. Physiother Theory Pract. 2020:1-9.
Davoli GBQ, Cardoso J, Silva GC, Moreira RFC, Mattiello-Sverzut AC. Instruments to assess upper-limb function in children and adolescents with neuromuscular diseases: A systematic review. Dev Med Child Neurol. 2021.
Brogna C, Pane M, Coratti G, D'Amico A, Pegoraro E, Bello L, et al. Upper limb changes in DMD patients amenable to skipping exons 44, 45, 51 and 53: A 24-month study. Children (Basel). 2023;10(4).
