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Muscle Biology of Contractures in Children with Cerebral Palsy

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Cerebral Palsy

Abstract

Muscular contractures are routinely observed in children with cerebral palsy. The natural progression of gait leads to a reduction in passive range of motion. Here we discuss the physiological properties of skeletal muscle tissue and the recent advances in the biological basis of contractures. Skeletal muscles are highly organized structures composed of muscle cells, i.e., myofibers, arranged in parallel and series. Myofibers in turn are made up of the basic contractile proteins, actin, and myosin that form sarcomeres. Sarcomere length and force production are intricately associated such that at very long and short sarcomere lengths, there is a reduction in force-generating capacity. During normal postnatal development, stretch-induced longitudinal skeletal muscle growth by addition of sarcomeres is mediated by bone growth. In children with cerebral palsy, sarcomere lengths are overstretched, and sarcomere number is lower, associated with a limitation in joint range of motion, suggesting reduced ability for muscle growth. Increase in muscle extracellular matrix content and increase in passive mechanical stiffness of fibers and fiber bundles are also observed. Satellite cells are resident stem cells indispensible for postnatal development, repair, and regeneration of skeletal muscles. The satellite cell population is dramatically reduced in contractured muscles. Overall these findings suggest that impaired muscle growth and contractures in children with cerebral palsy are related to a reduced muscle stem cell number.

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References

  1. Hirtz D, Thurman DJ, Gwinn-Hardy K, et al. How common are the "common" neurologic disorders? Neurology. 2007;68:326–37.

    Article  CAS  PubMed  Google Scholar 

  2. Palisano R, Rosenbaum P, Walter S, et al. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol. 1997;39:214–23.

    Article  CAS  PubMed  Google Scholar 

  3. Van Naarden Braun K, Doernberg N, Schieve L, et al. Birth prevalence of cerebral palsy: a population-based study. Pediatrics. 2016;137:1–9.

    Article  Google Scholar 

  4. Graham HK, Rosenbaum P, Paneth N, et al. Cerebral palsy. Nat Rev Dis Primers. 2016;2:15082.

    Article  PubMed  Google Scholar 

  5. Rodda JM, Graham HK, Carson L, et al. Sagittal gait patterns in spastic diplegia. J Bone Joint Surg. (British Volume). 2004;86-B:251–8.

    Article  Google Scholar 

  6. Leafblad ND, Van Heest AE. Management of the Spastic Wrist and Hand in cerebral palsy. J Hand Surg Am. 2015;40:1035–40.

    Article  PubMed  Google Scholar 

  7. Hagglund G, Wagner P. Development of spasticity with age in a total population of children with cerebral palsy. BMC Musculoskelet Disord. 2008;9:150.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nordmark E, Hagglund G, Lauge-Pedersen H, et al. Development of lower limb range of motion from early childhood to adolescence in cerebral palsy: a population-based study. BMC Med. 2009;7:65.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Willerslev-Olsen M, Lorentzen J, Sinkjær T, Nielsen JBO. Passive muscle properties are altered in children with cerebral palsy before the age of 3 years and are difficult to distinguish clinically from spasticity. Dev Med Child Neurol. 2013;55:617–23.

    Article  PubMed  Google Scholar 

  10. Tedroff K, Löwing K, Jacobson D, Åström E. Does loss of spasticity matter? A 10-year follow-up after selective dorsal rhizotomy in cerebral palsy. Dev Med Child Neurol. 2011;53:724–9.

    Article  PubMed  Google Scholar 

  11. Tedroff K, Granath F, Forssberg H, Haglund-Akerlind Y. Long-term effects of botulinum toxin a in children with cerebral palsy. Dev Med Child Neurol. 2009;51:120–7.

    Article  PubMed  Google Scholar 

  12. Bell KJ, Ounpuu S, DeLuca PA, Romness MJ. Natural progression of gait in children with cerebral palsy. J Pediatr Orthoped. 2002;22:677–82.

    Google Scholar 

  13. Johnson DC, Damiano DL, Abel MF. The evolution of gait in childhood and adolescent cerebral palsy. J Pediatr Orthop. 1997;17:392–6.

    CAS  PubMed  Google Scholar 

  14. Barber LA, Read F, Lovatt Stern J, et al. Medial gastrocnemius muscle volume in ambulant children with unilateral and bilateral cerebral palsy aged 2 to 9 years. Dev Med Child Neurol. 2016;58:1146–52.

    Article  PubMed  Google Scholar 

  15. Herskind A, Ritterband-Rosenbaum A, Willerslev-Olsen M, et al. Muscle growth is reduced in 15-month-old children with cerebral palsy. Dev Med Child Neurol. 2016;58:485–91.

    Article  PubMed  Google Scholar 

  16. Oeffinger D, Conaway M, Stevenson R, et al. Tibial length growth curves for ambulatory children and adolescents with cerebral palsy. Dev Med Child Neurol. 2010;52:e195–201.

    Article  PubMed  Google Scholar 

  17. Rethlefsen SA, Healy BS, Wren TA, et al. Causes of intoeing gait in children with cerebral palsy. J Bone Joint Surg Am. 2006;88:2175–80.

    PubMed  Google Scholar 

  18. Lieber RL. Skeletal muscle adaptability. I: review of basic properties. Dev Med Child Neurol. 1986;28:390–7.

    Article  CAS  PubMed  Google Scholar 

  19. Gordon AM, Huxley AF, Julian FJ. The variation in isometric tension with sarcomere length in vertebrate muscle fibres. J Physiol. 1966;184:170–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gokhin DS, Ward SR, Bremner SN, Lieber RL. Quantitative analysis of neonatal skeletal muscle functional improvement in the mouse. J Exp Biol. 2008;211:837–43.

    Article  CAS  PubMed  Google Scholar 

  21. Lieber RL, Friden J. Functional and clinical significance of skeletal muscle architecture. Muscle Nerve. 2000;23:1647–66.

    Article  CAS  PubMed  Google Scholar 

  22. Montgomery RD. Growth of human striated muscle. Nature. 1962;195:194–5.

    Google Scholar 

  23. Goldspink G. The proliferation of myofibrils during muscle fibre growth. J cell. Science. 1970;6:593–603.

    CAS  Google Scholar 

  24. Griffin GE, Williams PE, Goldspink G. Region of longitudinal growth in striated muscle fibres. Nat New Biol. 1971;232:28–9.

    Article  CAS  PubMed  Google Scholar 

  25. Williams PE, Goldspink G. Longitudinal growth of striated muscle fibres. J Cell Sci. 1971;9:751–67.

    CAS  PubMed  Google Scholar 

  26. Williams PE, Goldspink G. The effect of immobilization on the longitudinal growth of striated muscle fibres. J Anat. 1973;116:45–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Boakes JL, Foran J, Ward SR, Lieber RL. Muscle adaptation by serial sarcomere addition 1 year after femoral lengthening. Clin Orthop Relat Res. 2007;456:250–3.

    Article  PubMed  Google Scholar 

  28. McNee AE, Will E, Lin JP, et al. The effect of serial casting on gait in children with cerebral palsy: preliminary results from a crossover trial. Gait Posture. 2007;25:463–8.

    Article  CAS  PubMed  Google Scholar 

  29. Lieber RL, Fridén J. Spasticity causes a fundamental rearrangement of muscle-joint interaction. Muscle Nerve. 2002;25:265–70.

    Article  PubMed  Google Scholar 

  30. Pontén E, Gantelius S, Lieber RL. Intraoperative muscle measurements reveal a relationship between contracture formation and muscle remodeling. Muscle Nerve. 2007;36:47–54.

    Article  PubMed  Google Scholar 

  31. Mathewson MA, Ward SR, Chambers HG, Lieber RL. High resolution muscle measurements provide insights into equinus contractures in patients with cerebral palsy. J Orthop Res. 2015;33:33–9.

    Article  PubMed  Google Scholar 

  32. Smith LR, Lee KS, Ward SR, Chambers HG, Lieber RL. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length. J Physiol. 2011;589:2625–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Smith LR, Chambers HG, Subramaniam S, Lieber RL. Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy. PLoS One. 2012;7:e40686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Smith LR, Pontén E, Hedström Y, et al. Novel transcriptional profile in wrist muscles from cerebral palsy patients. BMC Med Genet. 2009;2:44.

    Google Scholar 

  35. Gillies AR, Lieber RL. Structure and function of the skeletal muscle extracellular matrix. Muscle Nerve. 2011;44:318–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Patel TJ, Lieber RL. Force transmission in skeletal muscle: from actomyosin to external tendons. Exerc Sport Sci Rev. 1997;25:321–63.

    Article  CAS  PubMed  Google Scholar 

  37. Zogby AM, Dayanidhi S, Chambers HG, Schenk S, Lieber RL. Skeletal muscle fiber-type specific succinate dehydrogenase activity in cerebral palsy. Muscle Nerve. 2017;55:122–4.

    Article  CAS  PubMed  Google Scholar 

  38. de Bruin M, Smeulders MJ, Kreulen M, et al. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study. PLoS One. 2014;9:e101038.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Booth CM, Cortina-Borja MJF, Theologis TN. Collagen accumulation in muscles of children with cerebral palsy and correlation with severity of spasticity. Dev Med Child Neurol. 2001;43:314–20.

    Article  CAS  PubMed  Google Scholar 

  40. Meyer GA, Lieber RL. Elucidation of extracellular matrix mechanics from muscle fibers and fiber bundles. J Biomech. 2011;44:771–3.

    Article  PubMed  Google Scholar 

  41. Lieber RL, Runesson E, Einarsson F, Friden J. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle Nerve. 2003;28:464–71.

    Article  PubMed  Google Scholar 

  42. Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiol Rev. 2013;93:23–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mauro A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961;9:493–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dayanidhi S, Dykstra PB, Lyubasyuk V, et al. Reduced satellite cell number in situ in muscular contractures from children with cerebral palsy. J Orthop Res. 2015;33:1039–45.

    Article  PubMed  Google Scholar 

  45. Dayanidhi S, Lieber RL. Skeletal muscle satellite cells: mediators of muscle growth during development and implications for developmental disorders. Muscle Nerve. 2014;50:723–32.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Smith LR, Chambers HG, Lieber RL. Reduced satellite cell population may lead to contractures in children with cerebral palsy. Dev Med Child Neurol. 2013;55:264–70.

    Article  PubMed  Google Scholar 

  47. Enesco M, Puddy D. Increase in the number of nuclei and weight in skeletal muscle of rats of various ages. Am J Anat. 1964;114:235–44.

    Article  CAS  PubMed  Google Scholar 

  48. Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. Anatom Rec. 1971;170:421–35.

    Article  CAS  Google Scholar 

  49. Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000;100:157–68.

    Article  CAS  PubMed  Google Scholar 

  50. Seale P, Sabourin LA, Girgis-Gabardo A, et al. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;102:777–86.

    Article  CAS  PubMed  Google Scholar 

  51. Collins CA, Olsen I, Zammit PS, et al. Stem cell function, self-renewal, and Behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;122:289–301.

    Article  CAS  PubMed  Google Scholar 

  52. Kuang S, Gillespie MA, Rudnicki MA. Niche regulation of muscle satellite cell self-renewal and differentiation. Cell Stem Cell. 2008;2:22–31.

    Article  CAS  PubMed  Google Scholar 

  53. Lepper C, Conway SJ, Fan CM. Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements. Nature. 2009;460:627–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Oustanina S, Hause G, Braun T. Pax7 directs postnatal renewal and propagation of myogenic satellite cells but not their specification. EMBO J. 2004;23:3430–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Günther S, Kim J, Kostin S, et al. Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells. Cell Stem Cell. 2013;13:590–601.

    Article  PubMed  PubMed Central  Google Scholar 

  56. von Maltzahn J, Jones AE, Parks RJ, Rudnicki MA. Pax7 is critical for the normal function of satellite cells in adult skeletal muscle. Proc Nation Acad Sci USA. 2013;110:16474–9.

    Article  Google Scholar 

  57. Keefe AC, Lawson JA, Flygare SD, et al. Muscle stem cells contribute to myofibres in sedentary adult mice. Nat Commun. 2015;6:7087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bentzinger CF, Wang YX, Dumont NA, Rudnicki MA. Cellular dynamics in the muscle satellite cell niche. EMBO Rep. 2013;14:1062–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Murphy MM, Lawson JA, Mathew SJ, et al. Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration. Development. 2011;138:3625–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Fry CS, Lee JD, Mula J, et al. Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. Nat Med. 2015;21:76–80.

    Article  CAS  PubMed  Google Scholar 

  61. Pallafacchina G, Francois S, Regnault B, et al. An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells. Stem Cell Res. 2010;4:77–91.

    Article  CAS  PubMed  Google Scholar 

  62. Kinney MC, Dayanidhi S, Dykstra PB, et al. Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition. Muscle Nerve. 2017;55(3):384–92.

    Google Scholar 

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Authors and Affiliations

  1. Shirley Ryan AbilityLab (formerly the Rehabilitation Institute of Chicago), Chicago, IL, USA

    Sudarshan Dayanidhi P.T., Ph.D. & Richard L. Lieber Ph.D.

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  1. Sudarshan Dayanidhi P.T., Ph.D.
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  2. Richard L. Lieber Ph.D.
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Correspondence to Richard L. Lieber Ph.D. .

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  1. Division of Paediatric Neurology, Aristotle University of Thessaloniki Division of Paediatric Neurology, Thessaloniki, Greece

    Christos P. Panteliadis

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Dayanidhi, S., Lieber, R.L. (2018). Muscle Biology of Contractures in Children with Cerebral Palsy. In: Panteliadis, C. (eds) Cerebral Palsy. Springer, Cham. https://doi.org/10.1007/978-3-319-67858-0_15

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  • DOI: https://doi.org/10.1007/978-3-319-67858-0_15

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