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Cerebral palsy

An Erratum to this article was published on 28 January 2016

Abstract

Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging.

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Figure 1: Gross Motor Function Classification System expanded and revised for children with cerebral palsy, 6–12 years of age.
Figure 2: Topographical description in cerebral palsy: unilateral and bilateral cerebral palsy.
Figure 3: Association between gestational age and the prevalence of cerebral palsy.
Figure 4: Brain lesions in cerebral palsy.
Figure 5: Cell death signalling pathways.
Figure 6: Structural changes observed in muscle of children with cerebral palsy compared with typically developing children.
Figure 7: Movement disorders in cerebral palsy.
Figure 8: Stance phase and sagittal ankle kinematics: typically developing gait.
Figure 9: Upper motor neuron syndrome.
Figure 10: The role of ankle foot orthoses in ambulant children with cerebral palsy.
Figure 11: Quality-of-life scores by domain of the KIDSCREEN questionnaire.

References

  1. 1

    Rosenbaum, P. et al. A report: the definition and classification of cerebral palsy April 2006. Dev. Med. Child Neurol. Suppl. 109, 8–14 (2007). This paper contains the agreed definition of cerebral palsy and the rationale behind each of the words in the definition.

    PubMed  Google Scholar 

  2. 2

    Brooks, J. C. et al. Recent trends in cerebral palsy survival. Part I: period and cohort effects. Dev. Med. Child Neurol. 56, 1059–1064 (2014).

    Article  PubMed  Google Scholar 

  3. 3

    Brooks, J. C. et al. Recent trends in cerebral palsy survival. Part II: individual survival prognosis. Dev. Med. Child Neurol. 56, 1065–1071 (2014).

    Article  PubMed  Google Scholar 

  4. 4

    Rosenbaum, P. & Gorter, J. W. The ‘F-words’ in childhood disability: I swear this is how we should think! Child Care Health Dev. 38, 457–463 (2012). This paper has become very popular, combining the WHO's important ideas about health with some specific but tongue-in-cheek ‘words’ with which to think about life-course issues for children with cerebral palsy (and in fact many other developmental conditions).

    Article  CAS  PubMed  Google Scholar 

  5. 5

    Little, W. J. On the incidence of abnormal parturition, difficult labour, premature birth and asphyxia neonatorum on the mental and physical condition of the child, especially in relation to deformities. Trans. Obstet. Soc. 3, 293–344 (1862). William J. Little provided the first clear description of the cerebral palsy syndrome and set the tone for thinking about aetiology for the next 100 years by identifying premature birth and asphyxia neonatorum as key underlying factors.

    Google Scholar 

  6. 6

    Rosenbaum, P. Cerebral Palsy (Mac Keith Press, 2014).

    Google Scholar 

  7. 7

    Jahnse, R. Being Adult With a Childhood Disease — a Survey on Adults With Cerebral Palsy in Norway (Unipub AS, 2004).

    Google Scholar 

  8. 8

    Surveillance of Cerebral Palsy in Europe. Prevalence and characteristics of children with cerebral palsy in Europe. Dev. Med. Child Neurol. 44, 633–640 (2002).

    Google Scholar 

  9. 9

    Christensen, D. et al. Prevalence of cerebral palsy, co-occurring autism spectrum disorders, and motor functioning — Autism and Developmental Disabilities Monitoring Network, USA, 2008. Dev. Med. Child Neurol. 56, 59–65 (2014).

    Article  PubMed  Google Scholar 

  10. 10

    Chang, M.-J., Ma, H.-I. & Lu, T.-H. Estimating the prevalence of cerebral palsy in Taiwan: a comparison of different case definitions. Res. Dev. Disabil. 36C, 207–212 (2014).

    PubMed  Google Scholar 

  11. 11

    El-Tallawy, H. N. et al. Cerebral palsy in Al-Quseir City, Egypt: prevalence, subtypes, and risk factors. Neuropsychiatr. Dis. Treat. 10, 1267–1272 (2014).

    PubMed  PubMed Central  Google Scholar 

  12. 12

    Paneth, N., Hong, T. & Korzeniewski, S. The descriptive epidemiology of cerebral palsy. Clin. Perinatol. 33, 251–267 (2006).

    Article  PubMed  Google Scholar 

  13. 13

    Freud, S. Die Infantile Cerebrallähmung (Alfred Holder, 1897).

    Google Scholar 

  14. 14

    Dammann, O. & Leviton, A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr. Res. 42, 1–8 (1997).

    Article  CAS  Google Scholar 

  15. 15

    Frid, C., Drott, P., Otterblad Olausson, P., Sundelin, C. & Annerén, G. Maternal and neonatal factors and mortality in children with Down syndrome born in 1973–1980 and 1995–1998. Acta Paediatr. 93, 106–112 (2004).

    Article  CAS  PubMed  Google Scholar 

  16. 16

    Moster, D., Wilcox, A. J., Vollset, S. E., Markestad, T. & Lie, R. T. Cerebral palsy among term and postterm births. JAMA 304, 976–982 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Kuban, K. C. K. et al. Cranial ultrasound lesions in the NICU predict cerebral palsy at age 2 years in children born at extremely low gestational age. J. Child Neurol. 24, 63–72 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18

    Pinto-Martin, J. A. et al. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics 95, 249–254 (1995).

    CAS  PubMed  Google Scholar 

  19. 19

    Kuban, K. C. K. et al. The breadth and type of systemic inflammation and the risk of adverse neurological outcomes in extremely low gestation newborns. Pediatr. Neurol. 52, 42–48 (2015).

    Article  PubMed  Google Scholar 

  20. 20

    Reuss, M. L., Paneth, N., Pinto-Martin, J. A., Lorenz, J. M. & Susser, M. The relation of transient hypothyroxinemia in preterm infants to neurologic development at two years of age. N. Engl. J. Med. 334, 821–827 (1996).

    Article  CAS  PubMed  Google Scholar 

  21. 21

    Collins, M. P., Lorenz, J. M., Jetton, J. R. & Paneth, N. Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants. Pediatr. Res. 50, 712–719 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. 22

    Leviton, A. et al. Two-hit model of brain damage in the very preterm newborn: small for gestational age and postnatal systemic inflammation. Pediatr. Res. 73, 362–370 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Rouse, D. J. et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N. Engl. J. Med. 359, 895–905 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Jacquemyn, Y., Zecic, A., Van Laere, D. & Roelens, K. The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection. Arch. Gynecol. Obstet. 291, 969–975 (2015).

    Article  CAS  PubMed  Google Scholar 

  25. 25

    Conde-Agudelo, A. & Romero, R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am. J. Obstet. Gynecol. 200, 595–609 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Costantine, M. M. & Weiner, S. J. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants: a meta-analysis. Obstet. Gynecol. 114, 354–364 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Nelson, K. B. & Ellenberg, J. H. Apgar scores as predictors of chronic neurologic disability. Pediatrics 68, 36–44 (1981). The first comprehensive modern day exploration of obstetric factors and birth asphyxia in cerebral palsy came from the National Collaborative Perinatal Project in the United States. This paper (one of several from that study) showed that, although birth depression, as assessed by Apgar score, was a potent correlate of cerebral palsy, most normal-birth-weight children with cerebral palsy had 5-minute Apgar scores in the normal range.

    CAS  PubMed  Google Scholar 

  28. 28

    Nelson, K. B. & Ellenberg, J. H. Obstetric complications as risk factors for cerebral palsy or seizure disorders. JAMA 251, 1843–1848 (1984).

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Ellenberg, J. H. & Nelson, K. B. The association of cerebral palsy with birth asphyxia: a definitional quagmire. Dev. Med. Child Neurol. 55, 210–216 (2013).

    Article  PubMed  Google Scholar 

  30. 30

    McIntyre, S. et al. A systematic review of risk factors for cerebral palsy in children born at term in developed countries. Dev. Med. Child Neurol. 55, 499–508 (2013).

    Article  PubMed  Google Scholar 

  31. 31

    Garne, E., Dolk, H., Krägeloh-Mann, I., Holst Ravn, S. & Cans, C. Cerebral palsy and congenital malformations. Eur. J. Paediatr. Neurol. 12, 82–88 (2008).

    Article  PubMed  Google Scholar 

  32. 32

    Jacobs, S. E. et al. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev. 1, CD003311 (2013). The first treatment for newborns to successfully prevent cerebral palsy in term infants is the application of head or body cooling for 72 hours in those diagnosed with hypoxic–ischaemic encephalopathy, which lowers both mortality and risk of cerebral palsy by 25%.

    Google Scholar 

  33. 33

    Nelson, K. B. & Grether, J. K. Causes of cerebral palsy. Curr. Opin. Pediatr. 11, 487–491 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Brites, D. & Bhutani, V. in Cerebral Palsy: Science and Clinical Practise (eds Dan, B., Mayston, M., Paneth, N. & Rosenbloom, L. ) 131–149 (Mac Keith Press, 2014).

    Google Scholar 

  35. 35

    Korzeniewski, S. J., Birbeck, G., DeLano, M. C., Potchen, M. J. & Paneth, N. A systematic review of neuroimaging for cerebral palsy. J. Child Neurol. 23, 216–227 (2008).

    Article  PubMed  Google Scholar 

  36. 36

    Kirton, A. in Cerebral Palsy: Science and Clinical Practise (eds Dan, B., Mayston, M., Paneth, N. & Rosenbloom, L. ) 91–107 (Mac Keith Press, 2014).

    Google Scholar 

  37. 37

    Wu, Y. W. et al. Racial, ethnic, and socioeconomic disparities in the prevalence of cerebral palsy. Pediatrics 127, e674–e681 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38

    Oskoui, M., Messerlian, C., Blair, A., Gamache, P. & Shevell, M. Variation in cerebral palsy profile by socio-economic status. Dev. Med. Child Neurol. http://dx.doi.org/10.1111/dmcn.12808 (2015).

  39. 39

    Durkin, M. S. et al. The role of socio-economic status and perinatal factors in racial disparities in the risk of cerebral palsy. Dev. Med. Child Neurol. 57, 835–843 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Durkin, M. S. in Cerebral Palsy: Science and Clinical Practise (eds Dan, B., Mayston, M., Paneth, N. & Rosenbloom, L. ) 63–71 (Mac Keith Press, 2014).

    Google Scholar 

  41. 41

    Pharoah, P. O., Buttfield, I. H. & Hetzel, B. S. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 1, 308–310 (1971).

    Article  CAS  PubMed  Google Scholar 

  42. 42

    Bax, M., Tydeman, C. & Flodmark, O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA 296, 1602–1608 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. 43

    Dan, B., Mayston, M., Paneth, N. & Rosenbloom, L. (eds) Cerebral Palsy: Science and Clinical Practice (Mac Keith Press, 2014).

    Google Scholar 

  44. 44

    Raybaud, C. Destructive lesions of the brain. Neuroradiology 25, 265–291 (1983).

    Article  CAS  PubMed  Google Scholar 

  45. 45

    Talos, D. M. et al. Developmental regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. II. Human cerebral white matter and cortex. J. Comp. Neurol. 497, 61–77 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Back, S. A. et al. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J. Neurosci. 21, 1302–1312 (2001).

    Article  CAS  Google Scholar 

  47. 47

    Thornton, C. et al. Molecular mechanisms of neonatal brain injury. Neurol. Res. Int. 2012, 1–16 (2012).

    Article  Google Scholar 

  48. 48

    Jensen, A., Garnier, Y., Middelanis, J. & Berger, R. Perinatal brain damage — from pathophysiology to prevention. Eur. J. Obstet. Gynecol. Reprod. Biol. 110, S70–S79 (2003).

    Article  CAS  PubMed  Google Scholar 

  49. 49

    Biran, V. et al. Is melatonin ready to be used in preterm infants as a neuroprotectant? Dev. Med. Child Neurol. 56, 717–723 (2014).

    Article  PubMed  Google Scholar 

  50. 50

    Capani, F. et al. Changes in reactive oxygen species (ROS) production in rat brain during global perinatal asphyxia: an ESR study. Brain Res. 914, 204–207 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. 51

    Saugstad, O. D., Sejersted, Y., Solberg, R., Wollen, E. J. & Bjørås, M. Oxygenation of the newborn: a molecular approach. Neonatology 101, 315–325 (2012).

    Article  CAS  PubMed  Google Scholar 

  52. 52

    Babcock, M. A. et al. Injury to the preterm brain and cerebral palsy: clinical aspects, molecular mechanisms, unanswered questions, and future research directions. J. Child Neurol. 24, 1064–1084 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53

    Herrera-Marschitz, M. et al. Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins. Neurotox. Res. 19, 603–627 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Thoresen, M. Who should we cool after perinatal asphyxia? Semin. Fetal Neonatal Med. 2, 66–71 (2015).

    Article  Google Scholar 

  55. 55

    Kaur, C. & Ling, E. A. Periventricular white matter damage in the hypoxic neonatal brain: role of microglial cells. Prog. Neurobiol. 87, 264–280 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. 56

    Carr, L. J., Harrison, L. M., Evans, A. L. & Stephens, J. A. Patterns of central motor reorganization in hemiplegic cerebral palsy. Brain 116, 1223–1247 (1993).

    Article  PubMed  Google Scholar 

  57. 57

    Leonard, C. T. & Hirschfeld, H. Myotatic reflex responses of non-disabled children and children with spastic cerebral palsy. Dev. Med. Child Neurol. 37, 783–799 (1995).

    Article  CAS  PubMed  Google Scholar 

  58. 58

    Fazzi, E. et al. Neuro-ophthalmological disorders in cerebral palsy: ophthalmological, oculomotor, and visual aspects. Dev. Med. Child Neurol. 54, 730–736 (2012).

    Article  PubMed  Google Scholar 

  59. 59

    Rose, J. et al. Muscle pathology and clinical measures of disability in children with cerebral palsy. J. Orthop. Res. 12, 758–768 (1994).

    Article  CAS  PubMed  Google Scholar 

  60. 60

    Schiaffino, S. & Reggiani, C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol. Rev. 76, 371–423 (1996).

    Article  CAS  PubMed  Google Scholar 

  61. 61

    Castle, M. E., Reyman, T. A. & Schneider, M. Pathology of spastic muscle in cerebral palsy. Clin. Orthop. Relat. Res. 142, 223–232 (1979).

    Google Scholar 

  62. 62

    Tirrell, T. F. et al. Human skeletal muscle biochemical diversity. J. Exp. Biol. 215, 2551–2559 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Powell, P. L., Roy, R. R., Kanim, P., Bello, M. A. & Edgerton, V. R. Predictability of skeletal muscle tension from architectural determinations in guinea pig hindlimbs. J. Appl. Physiol. 57, 1715–1721 (1984).

    Article  CAS  PubMed  Google Scholar 

  64. 64

    Gordon, A. M., Huxley, A. F. & Julian, F. J. The variation in isometric tension with sarcomere length in vertebrate muscle fibres. J. Physiol. 184, 170–192 (1966).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Lieber, R. L., Loren, G. J. & Fridén, J. In vivo measurement of human wrist extensor muscle sarcomere length changes. J. Neurophysiol. 71, 874–881 (1994).

    Article  CAS  PubMed  Google Scholar 

  66. 66

    Lieber, R. L. & Fridén, J. Spasticity causes a fundamental rearrangement of muscle–joint interaction. Muscle Nerve 25, 265–270 (2002).

    Article  PubMed  Google Scholar 

  67. 67

    Smith, L. R., Lee, K. S., Ward, S. R., Chambers, H. G. & Lieber, R. L. Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length. J. Physiol. 589, 2625–2639 (2011). This is the most complete analysis of human muscle from 40 children demonstrating the in vivo, in vitro and biochemical changes in muscle from patients with cerebral palsy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Mathewson, M. A., Ward, S. R., Chambers, H. G. & Lieber, R. L. High resolution muscle measurements provide insights into equinus contractures in patients with cerebral palsy. J. Orthop. Res. 33, 33–39 (2015). This report highlights the weakness in the use of ultrasound, which is very common in studies of children with cerebral palsy. The report demonstrates that, although fascicle length of children with cerebral palsy and typically developing children may be the same, their serial sarcomere number is dramatically different.

    Article  PubMed  Google Scholar 

  69. 69

    Lieber, R. L., Runesson, E., Einarsson, F. & Fridén, J. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle Nerve 28, 464–471 (2003).

    Article  PubMed  Google Scholar 

  70. 70

    Gillies, A. R. & Lieber, R. L. Structure and function of the skeletal muscle extracellular matrix. Muscle Nerve 44, 318–331 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Lieber, R. L. & Ward, S. R. Cellular mechanisms of tissue fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis. Am. J. Physiol. Cell Physiol. 305, C241–C252 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Mathewson, M. A. et al. Stiff muscle fibers in calf muscles of patients with cerebral palsy lead to high passive muscle stiffness. J. Orthop. Res. 32, 1667–1674 (2014).

    Article  PubMed  Google Scholar 

  73. 73

    Labeit, S. & Kolmerer, B. Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science 270, 293–296 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. 74

    Smith, L. R. et al. Novel transcriptional profile in wrist muscles from cerebral palsy patients. BMC Med. Genomics 2, 44 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Smith, L. R., Chambers, H. G., Subramaniam, S. & Lieber, R. L. Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy. PLoS ONE 7, e40686 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Goldsmith, E. C., Bradshaw, A. D. & Spinale, F. G. Cellular mechanisms of tissue fibrosis. 2. Contributory pathways leading to myocardial fibrosis: moving beyond collagen expression. Am. J. Physiol. Cell Physiol. 304, C393–C402 (2013).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Dayanidhi, S. & Lieber, R. L. Skeletal muscle satellite cells: mediators of muscle growth during development and implications for developmental disorders. Muscle Nerve 50, 723–732 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78

    Lepper, C., Partridge, T. A. & Fan, C.-M. An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration. Development 138, 3639–3646 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Smith, L. R., Chambers, H. G. & Lieber, R. L. Reduced satellite cell population may lead to contractures in children with cerebral palsy. Dev. Med. Child Neurol. 55, 264–270 (2013).

    Article  PubMed  Google Scholar 

  80. 80

    Williams, P. E. & Goldspink, G. Longitudinal growth of striated muscle fibres. J. Cell Sci. 9, 751–767 (1971).

    CAS  PubMed  Google Scholar 

  81. 81

    Fry, C. S. et al. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. FASEB J. 28, 1654–1665 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Brack, A. S. et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317, 807–810 (2007).

    Article  CAS  Google Scholar 

  83. 83

    Lotersztajn, S. & Insel, P. A. AJP-cell begins a theme series on tissue fibrosis. Am. J. Physiol. Cell Physiol. 304, C215 (2013).

    Article  CAS  PubMed  Google Scholar 

  84. 84

    Johnston, M. V., Ferriero, D. M., Vannucci, S. J. & Hagberg, H. Models of cerebral palsy: which ones are best? J. Child Neurol. 20, 984–987 (2005).

    Article  PubMed  Google Scholar 

  85. 85

    Clowry, G. J., Basuodan, R. & Chan, F. What are the best animal models for testing early intervention in cerebral palsy? Front. Neurol. 5, 258 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  86. 86

    Friel, K. M., Williams, P. T. J. A., Serradj, N., Chakrabarty, S. & Martin, J. H. Activity-based therapies for repair of the corticospinal system injured during development. Front. Neurol. 5, 229 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  87. 87

    Martin, J. H., Friel, K. M., Salimi, I. & Chakrabarty, S. Activity- and use-dependent plasticity of the developing corticospinal system. Neurosci. Biobehav. Rev. 31, 1125–1135 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  88. 88

    Alisky, J. M., Swink, T. D. & Tolbert, D. L. The postnatal spatial and temporal development of corticospinal projections in cats. Exp. Brain Res. 88, 265–276 (1992).

    Article  CAS  PubMed  Google Scholar 

  89. 89

    Derrick, M. et al. Preterm fetal hypoxia-ischemia causes hypertonia and motor deficits in the neonatal rabbit: a model for human cerebral palsy? J. Neurosci. 24, 24–34 (2004).

    Article  CAS  PubMed  Google Scholar 

  90. 90

    Lin, J.-P. The cerebral palsies: a physiological approach. J. Neurol. Neurosurg. Psychiatry 74 (Suppl. 1), i23–i29 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  91. 91

    Lin, J.-P. The contribution of spasticity to the movement disorder of cerebral palsy using pathway analysis: does spasticity matter? Dev. Med. Child Neurol. 53, 7–9 (2011).

    Article  PubMed  Google Scholar 

  92. 92

    Albanese, A. et al. Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 28, 863–873 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  93. 93

    Fish, D. R. et al. The effect of sleep on the dyskinetic movements of Parkinson's disease, Gilles de la Tourette syndrome, Huntington's disease, and torsion dystonia. Arch. Neurol. 48, 210–214 (1991).

    Article  CAS  PubMed  Google Scholar 

  94. 94

    Berardelli, A. et al. The pathophysiology of primary dystonia. Brain 121, 1195–1212 (1998).

    Article  PubMed  Google Scholar 

  95. 95

    Brown, J. K., Omar, T. & O'Regan, M. in Neurophysiology and Neuropsychology of Motor Development. Clinics in Developmental Medicine (eds Connolly, K. C. & Forssberg, H. ) 1–41 (Mac Keith Press, 1997).

    Google Scholar 

  96. 96

    Bennett, M. R. & Pettigrew, A. G. The formation of synapses in reinnervated and cross-reinnervated striated muscle during development. J. Physiol. 241, 547–573 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    Myklebust, B. M., Gottlieb, G. L. & Agarwal, G. C. Stretch reflexes of the normal infant. Dev. Med. Child Neurol. 28, 440–449 (1986).

    Article  CAS  PubMed  Google Scholar 

  98. 98

    Benoit, P. & Changeux, J. P. Consequences of tenotomy on the evolution of multiinnervation in developing rat soleus muscle. Brain Res. 99, 354–358 (1975).

    Article  CAS  PubMed  Google Scholar 

  99. 99

    Lin, J.-P., Brown, J. K. & Walsh, E. G. Physiological maturation of muscles in childhood. Lancet 343, 1386–1389 (1994). This is the first paper to study the physiological muscle twitch characteristics and muscle–tendon compliance in children and adults. Slow twitches and very high compliance of muscles in infancy partly explain why co-contraction is a necessary adaptation in early life.

    Article  CAS  PubMed  Google Scholar 

  100. 100

    Sutherland, D., Olshen, R., Biden, E. & Wyatt, M. (eds) The Development of Mature Walking. Clinics in Developmental Medicine (Mac Keith Press, 1988).

    Google Scholar 

  101. 101

    Leonard, C. T., Hirschfeld, H. & Forssberg, H. The development of independent walking in children with cerebral palsy. Dev. Med. Child Neurol. 33, 567–577 (1991). This classic paper linked the co-contraction of early walking in cerebral palsy to the common pattern of co-contraction in all supported walking in typically developing children.

    Article  CAS  PubMed  Google Scholar 

  102. 102

    Fog, E. & Fog, M. in Minimal Cerebral Dysfunction (eds Mac Keith, R. & Bax, M. ) 52–57 (SIMP, 1963). This is the first study, published in a now out of print book, describing overflow co-contraction in typically developing children when asked to perform unfamiliar tasks. It should be obligatory reading for all paediatricians.

    Google Scholar 

  103. 103

    Detrembleur, C., Willems, P. & Plaghki, L. Does walking speed influence the time pattern of muscle activation in normal children? Dev. Med. Child Neurol. 39, 803–807 (1997).

    CAS  PubMed  Google Scholar 

  104. 104

    Tedroff, K., Knutson, L. M. & Soderberg, G. L. Synergistic muscle activation during maximum voluntary contractions in children with and without spastic cerebral palsy. Dev. Med. Child Neurol. 48, 789–796 (2006).

    Article  PubMed  Google Scholar 

  105. 105

    Graziadio, S. et al. Developmental tuning and decay in senescence of oscillations linking the corticospinal system. J. Neurosci. 30, 3663–3674 (2010).

    Article  CAS  PubMed  Google Scholar 

  106. 106

    Quartarone, A., Rizzo, V. & Morgante, F. Clinical features of dystonia: a pathophysiological revisitation. Curr. Opin. Neurol. 21, 484–490 (2008).

    Article  PubMed  Google Scholar 

  107. 107

    Mink, J. W. Special concerns in defining, studying, and treating dystonia in children. Mov. Disord. 28, 921–925 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  108. 108

    Draganski, B. et al. Evidence for segregated and integrative connectivity patterns in the human basal ganglia. J. Neurosci. 28, 7143–7152 (2008). This is essential reading for anyone interested in the role of the basal ganglia in motor function and dysfunction.

    Article  CAS  PubMed  Google Scholar 

  109. 109

    Nashner, L. M., Shumway-Cook, A. & Marin, O. Stance posture control in select groups of children with cerebral palsy: deficits in sensory organization and muscular coordination. Exp. Brain Res. 49, 393–409 (1983). This is one of the first papers to define non-spastic abnormal motor patterns in children with cerebral palsy.

    Article  CAS  PubMed  Google Scholar 

  110. 110

    Lin, J.-P., Lumsden, D. E., Gimeno, H. & Kaminska, M. The impact and prognosis for dystonia in childhood including dystonic cerebral palsy: a clinical and demographic tertiary cohort study. J. Neurol. Neurosurg. Psychiatry 85, 1239–1244 (2014). This very large study is the first of its kind exploring the common issues facing children with dystonic cerebral palsy and genetic dystonias, looking at early development and motor severity using the GMFCS.

    Article  PubMed  Google Scholar 

  111. 111

    Lumsden, D. E., Gimeno, H., Tustin, K., Kaminska, M. & Lin, J.-P. Interventional studies in childhood dystonia do not address the concerns of children and their carers. Eur. J. Paediatr. Neurol. 19, 327–336 (2015).

    Article  PubMed  Google Scholar 

  112. 112

    Lance, J. in Spasticity: Disordered Motor Control (eds Feldman, R. G., Young, R. R. & Koella, W. P. ) 185–203 (Year Book Medical Publishers, 1983).

    Google Scholar 

  113. 113

    Kim, H. S. et al. Effect of muscle activity and botulinum toxin dilution volume on muscle paralysis. Dev. Med. Child Neurol. 45, 200–206 (2003).

    Article  PubMed  Google Scholar 

  114. 114

    McClellan, D. L., Hassan, N. & Hodgson, J. A. in Clinical Neurophysiology in Spasticity (eds Delwaide, P. J. & Young, R. R. ) 131–139 (Elsevier Science, 1985).

    Google Scholar 

  115. 115

    Lin, J.-P. & Brown, J. K. Peripheral and central mechanisms of hindfoot equinus in childhood hemiplegia. Dev. Med. Child Neurol. 34, 949–965 (1992). An early systematic exploration of the dysfunctional equinus foot posture in cerebral palsy.

    Article  CAS  PubMed  Google Scholar 

  116. 116

    Price, G. W., Wilkin, G. P., Turnbull, M. J. & Bowery, N. G. Are baclofen-sensitive GABAB receptors present on primary afferent terminals of the spinal cord? Nature 307, 71–74 (1984).

    Article  CAS  PubMed  Google Scholar 

  117. 117

    Lin, J.-P., Brown, J. K. & Walsh, E. G. Continuum of reflex excitability in hemiplegia: influence of muscle length and muscular transformation after heel-cord lengthening and immobilization on the pathophysiology of spasticity and clonus. Dev. Med. Child Neurol. 41, 534–548 (1999).

    Article  CAS  PubMed  Google Scholar 

  118. 118

    Dietz, V. & Berger, W. Cerebral palsy and muscle transformation. Dev. Med. Child Neurol. 37, 180–184 (1995).

    Article  CAS  PubMed  Google Scholar 

  119. 119

    Hufschmidt, A. & Mauritz, K. H. Chronic transformation of muscle in spasticity: a peripheral contribution to increased tone. J. Neurol. Neurosurg. Psychiatry 48, 676–685 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. 120

    Bar-On, L. et al. Spasticity and its contribution to hypertonia in cerebral palsy. Biomed. Res. Int. 2015, 317047 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  121. 121

    Surveillance of Cerebral Palsy in Europe. A collaboration of cerebral palsy surveys and registers. Dev. Med. Child Neurol. 42, 816–824 (2000).

    Article  Google Scholar 

  122. 122

    Towsley, K., Shevell, M. I. & Dagenais, L. Population-based study of neuroimaging findings in children with cerebral palsy. Eur. J. Paediatr. Neurol. 15, 29–35 (2011).

    Article  PubMed  Google Scholar 

  123. 123

    Hoon, A. H. et al. Diffusion tensor imaging of periventricular leukomalacia shows affected sensory cortex white matter pathways. Neurology 59, 752–756 (2002). This study clearly shows why periventricular leukomalacia might exist with intact corticospinal tracts and why periventricular leukomalacia does not always equate with ‘spasticity’. References 124 and 125 take this issue further with detailed neurophysiological evidence.

    Article  PubMed  Google Scholar 

  124. 124

    McClelland, V., Mills, K., Siddiqui, A., Selway, R. & Lin, J.-P. Central motor conduction studies and diagnostic magnetic resonance imaging in children with severe primary and secondary dystonia. Dev. Med. Child Neurol. 53, 757–763 (2011).

    Article  PubMed  Google Scholar 

  125. 125

    Lumsden, D. E. et al. Central motor conduction time and diffusion tensor imaging metrics in children with complex motor disorders. Clin. Neurophysiol. 126, 140–146 (2015).

    Article  PubMed  Google Scholar 

  126. 126

    Gainsborough, M., Surman, G., Maestri, G., Colver, A. & Cans, C. Validity and reliability of the guidelines of the surveillance of cerebral palsy in Europe for the classification of cerebral palsy. Dev. Med. Child Neurol. 50, 828–831 (2008). This study reveals that clinicians do not necessarily classify cerebral palsy in the same way, even when provided with definitions to follow. Consequently, dystonia continues to be under-recognized.

    Article  PubMed  Google Scholar 

  127. 127

    Liow, N. Y.-K. et al. Gabapentin can significantly improve dystonia severity and quality of life in children. Eur. J. Paediatr. Neurol. 20, 100–107 (2016).

    Article  PubMed  Google Scholar 

  128. 128

    Elze, M. et al. Burke–Fahn–Marsden dystonia severity, gross motor, manual ability, and communication function classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a Rosetta Stone study. Dev. Med. Child Neurol. http://dx.doi.org/10.1111/dmcn.12965 (2015). This is the first study to compare the severity of dystonia and motor function in children with isolated monogenetic dystonia, progressive dystonias and dystonic cerebral palsy.

  129. 129

    Ashwal, S. et al. Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 62, 851–863 (2004). This paper is important to the diagnosis and management of cerebral palsy and is highly influential for clinical decision making.

    Article  CAS  PubMed  Google Scholar 

  130. 130

    Prechtl, H. F. et al. An early marker for neurological deficits after perinatal brain lesions. Lancet 349, 1361–1363 (1997).

    Article  CAS  PubMed  Google Scholar 

  131. 131

    Spittle, A. J., Boyd, R. N., Inder, T. E. & Doyle, L. W. Predicting motor development in very preterm infants at 12 months' corrected age: the role of qualitative magnetic resonance imaging and general movements assessments. Pediatrics 123, 512–517 (2009).

    Article  PubMed  Google Scholar 

  132. 132

    Hoffer, M. M. & Perry, J. Pathodynamics of gait alterations in cerebral palsy and the significance of kinetic electromyography in evaluating foot and ankle problems. Foot Ankle 4, 128–134 (1983).

    Article  CAS  PubMed  Google Scholar 

  133. 133

    Rodda, J. M., Graham, H. K., Carson, L., Galea, M. P. & Wolfe, R. Sagittal gait patterns in spastic diplegia. J. Bone Joint Surg. Br. 86, 251–258 (2004).

    Article  CAS  PubMed  Google Scholar 

  134. 134

    Skiöld, B., Eriksson, C., Eliasson, A.-C., Adén, U. & Vollmer, B. General movements and magnetic resonance imaging in the prediction of neuromotor outcome in children born extremely preterm. Early Hum. Dev. 89, 467–472 (2013).

    Article  PubMed  Google Scholar 

  135. 135

    Reid, S. M., Dagia, C. D., Ditchfield, M. R., Carlin, J. B. & Reddihough, D. S. Population-based studies of brain imaging patterns in cerebral palsy. Dev. Med. Child Neurol. 56, 222–232 (2014).

    Article  PubMed  Google Scholar 

  136. 136

    Alfirevic, Z., Stampalija, T., Roberts, D. & Jorgensen, A. L. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst. Rev. 4, CD008991 (2012).

    Google Scholar 

  137. 137

    van Vliet, E. O. G., Boormans, E. M., de Lange, T. S., Mol, B. W. & Oudijk, M. A. Preterm labor: current pharmacotherapy options for tocolysis. Expert Opin. Pharmacother. 15, 787–797 (2014).

    Article  CAS  PubMed  Google Scholar 

  138. 138

    Vogel, J. P., Nardin, J. M., Dowswell, T., West, H. M. & Oladapo, O. T. Combination of tocolytic agents for inhibiting preterm labour. Cochrane Database Syst. Rev. 7, CD006169 (2014).

    Google Scholar 

  139. 139

    Sotiriadis, A. et al. Neurodevelopmental outcome after a single course of antenatal steroids in children born preterm: a systematic review and meta-analysis. Obstet. Gynecol. 125, 1385–1396 (2015).

    Article  CAS  PubMed  Google Scholar 

  140. 140

    Damiano, D. L. Activity, activity, activity: rethinking our physical therapy approach to cerebral palsy. Phys. Ther. 86, 1534–1540 (2006).

    Article  PubMed  Google Scholar 

  141. 141

    Novak, I. et al. A systematic review of interventions for children with cerebral palsy: state of the evidence. Dev. Med. Child Neurol. 55, 885–910 (2013).

    Article  PubMed  Google Scholar 

  142. 142

    Kleim, J. A. & Jones, T. A. Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J. Speech Lang. Hear. Res. 51, S225–S239 (2008).

    Article  PubMed  Google Scholar 

  143. 143

    Huang, H., Fetters, L., Hale, J. & McBride, A. Bound for success: a systematic review of constraint-induced movement therapy in children with cerebral palsy supports improved arm and hand use. Phys. Ther. 89, 1126–1141 (2009).

    Article  PubMed  Google Scholar 

  144. 144

    Tinderholt Myrhaug, H., Ostensjø, S., Larun, L., Odgaard-Jensen, J. & Jahnsen, R. Intensive training of motor function and functional skills among young children with cerebral palsy: a systematic review and meta-analysis. BMC Pediatr. 14, 292 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  145. 145

    Lohse, K. R., Hilderman, C. G. E., Cheung, K. L., Tatla, S. & Van der Loos, H. F. M. Virtual reality therapy for adults post-stroke: a systematic review and meta-analysis exploring virtual environments and commercial games in therapy. PLoS ONE 9, e93318 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. 146

    Peterson, M. D., Gordon, P. M. & Hurvitz, E. A. Chronic disease risk among adults with cerebral palsy: the role of premature sarcopoenia, obesity and sedentary behaviour. Obes. Rev. 14, 171–182 (2013).

    Article  CAS  PubMed  Google Scholar 

  147. 147

    Wiley, M. E. & Damiano, D. L. Lower-extremity strength profiles in spastic cerebral palsy. Dev. Med. Child Neurol. 40, 100–107 (1998).

    Article  CAS  PubMed  Google Scholar 

  148. 148

    Balemans, A. C. J. et al. Maximal aerobic and anaerobic exercise responses in children with cerebral palsy. Med. Sci. Sports Exerc. 45, 561–568 (2013).

    Article  PubMed  Google Scholar 

  149. 149

    Moreau, N. G., Li, L., Geaghan, J. P. & Damiano, D. L. Fatigue resistance during a voluntary performance task is associated with lower levels of mobility in cerebral palsy. Arch. Phys. Med. Rehabil. 89, 2011–2016 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  150. 150

    Franki, I. et al. The evidence-base for basic physical therapy techniques targeting lower limb function in children with cerebral palsy: a systematic review using the International Classification of Functioning, Disability and Health as a conceptual framework. J. Rehabil. Med. 44, 385–395 (2012).

    Article  PubMed  Google Scholar 

  151. 151

    Damiano, D. L. Progressive resistance exercise increases strength but does not improve objective measures of mobility in young people with cerebral palsy. J. Physiother. 60, 58 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  152. 152

    Scholtes, V. A. et al. Effectiveness of functional progressive resistance exercise training on walking ability in children with cerebral palsy: a randomized controlled trial. Res. Dev. Disabil. 33, 181–188 (2012).

    Article  PubMed  Google Scholar 

  153. 153

    Taylor, N. F. et al. Progressive resistance training and mobility-related function in young people with cerebral palsy: a randomized controlled trial. Dev. Med. Child Neurol. 55, 806–812 (2013).

    Article  PubMed  Google Scholar 

  154. 154

    Van Wely, L., Balemans, A. C., Becher, J. G. & Dallmeijer, A. J. Physical activity stimulation program for children with cerebral palsy did not improve physical activity: a randomised trial. J. Physiother. 60, 40–49 (2014).

    Article  PubMed  Google Scholar 

  155. 155

    Graham, H. K. & Selber, P. Musculoskeletal aspects of cerebral palsy. J. Bone Joint Surg. Br. 85, 157–166 (2003).

    Article  Google Scholar 

  156. 156

    Leonard, J. & Graham, H. K. in Botulinum Toxin: Therapeutic Clinical Practice and Science (ed. Jankovic, J. ) 172–191 (Saunders Elsevier, 2009).

    Book  Google Scholar 

  157. 157

    Graham, H. K. Management of the Motor Disorders of Children with Cerebral Palsy (Mac Keith Press, 2004).

    Google Scholar 

  158. 158

    Rang, M. in Lovell & Winter's Pediatric Orthopaedics (ed. Morrissy, R. T. ) 465–506 (JB Lippincott, 1990).

    Google Scholar 

  159. 159

    Gage, J. R. & Schwartz, M. H. in The Identification and Treatment of Gait Problems in Cerebral Palsy (eds Gage, J. R., Schwartz, M. H., Koop, S. E. & Novacheck, T. F. ) 107–129 (Mac Keith Press, 2009).

    Google Scholar 

  160. 160

    Thomason, P. & Rodda, J. in Cerebral Palsy: Science and Clinical Practise (eds Dan, B., Mayston, M., Paneth, N. & Rosenbloom, L. ) 287–312 (Mac Keith Press, 2014).

    Google Scholar 

  161. 161

    Hägglund, G. & Wagner, P. Development of spasticity with age in a total population of children with cerebral palsy. BMC Musculoskelet. Disord. 9, 150 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  162. 162

    Nordmark, E., Hägglund, G., Lauge-Pedersen, H., Wagner, P. & Westbom, L. Development of lower limb range of motion from early childhood to adolescence in cerebral palsy: a population-based study. BMC Med. 7, 65 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  163. 163

    Singh, D. & Silverskiold, N. Nils Silfverskiöld and gastrocnemius contracture. Foot Ankle Surg. 19, 135–138 (2013).

    Article  PubMed  Google Scholar 

  164. 164

    Silfverskiold, N. Reduction of the uncrossed two-joints muscles of the leg to one-joint muscles in spastic conditions. Acta Chir. Scand. 56, 315–328 (1924).

    Google Scholar 

  165. 165

    Firth, G. B. et al. Lengthening of the gastrocnemius–soleus complex: an anatomical and biomechanical study in human cadavers. J. Bone Joint Surg. Am. 95, 1489–1496 (2013).

    Article  PubMed  Google Scholar 

  166. 166

    Metaxiotis, D., Wolf, S. & Doederlein, L. Conversion of biarticular to monoarticular muscles as a component of multilevel surgery in spastic diplegia. J. Bone Joint Surg. Br. 86, 102–109 (2004).

    Article  CAS  PubMed  Google Scholar 

  167. 167

    Ma, F. Y. P. et al. Lengthening and transfer of hamstrings for a flexion deformity of the knee in children with bilateral cerebral palsy: technique and preliminary results. J. Bone Joint Surg. Br. 88, 248–254 (2006).

    Article  CAS  PubMed  Google Scholar 

  168. 168

    Cosgrove, A. P., Corry, I. S. & Graham, H. K. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev. Med. Child Neurol. 36, 386–396 (1994).

    Article  CAS  PubMed  Google Scholar 

  169. 169

    Fortuna, R., Vaz, M. A., Youssef, A. R., Longino, D. & Herzog, W. Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox). J. Biomech. 44, 39–44 (2011).

    Article  PubMed  Google Scholar 

  170. 170

    Minamoto, V. B., Suzuki, K. P., Bremner, S. N., Lieber, R. L. & Ward, S. R. Dramatic changes in muscle contractile and structural properties after two botulinum toxin injections. Muscle Nerve 52, 649–657 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. 171

    Park, C., Park, K. & Kim, J. Growth effects of botulinum toxin type A injected unilaterally into the masseter muscle of developing rats. J. Zhejiang Univ. Sci. B 16, 46–51 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. 172

    Simpson, D. M. Assessment: botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 70, 1691–1698 (2008).

    Article  CAS  PubMed  Google Scholar 

  173. 173

    Thomason, P. et al. Single-event multilevel surgery in children with spastic diplegia: a pilot randomized controlled trial. J. Bone Joint Surg. Am. 93, 451–460 (2011).

    Article  PubMed  Google Scholar 

  174. 174

    Dreher, T. et al. Long-term results after gastrocnemius-soleus intramuscular aponeurotic recession as a part of multilevel surgery in spastic diplegic cerebral palsy. J. Bone Joint Surg. Am. 94, 627–637 (2012).

    Article  PubMed  Google Scholar 

  175. 175

    McGinley, J. L. et al. Single-event multilevel surgery for children with cerebral palsy: a systematic review. Dev. Med. Child Neurol. 54, 117–128 (2012).

    Article  PubMed  Google Scholar 

  176. 176

    Shore, B. J., White, N. & Graham, H. K. Surgical correction of equinus deformity in children with cerebral palsy: a systematic review. J. Child. Orthop. 4, 277–290 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  177. 177

    Gage, J. R. & Novacheck, T. F. An update on the treatment of gait problems in cerebral palsy. J. Pediatr. Orthop. B 10, 265–274 (2001).

    CAS  PubMed  Google Scholar 

  178. 178

    Robin, J. et al. Proximal femoral geometry in cerebral palsy: a population-based cross-sectional study. J. Bone Joint Surg. Br. 90, 1372–1379 (2008).

    Article  CAS  PubMed  Google Scholar 

  179. 179

    Bobroff, E. D., Chambers, H. G., Sartoris, D. J., Wyatt, M. P. & Sutherland, D. H. Femoral anteversion and neck-shaft angle in children with cerebral palsy. Clin. Orthop. Relat. Res. 364, 194–204 (1999).

    Article  Google Scholar 

  180. 180

    Shefelbine, S. J. & Carter, D. R. Mechanobiological predictions of femoral anteversion in cerebral palsy. Ann. Biomed. Eng. 32, 297–305 (2004).

    Article  PubMed  Google Scholar 

  181. 181

    Rethlefsen, S. A., Healy, B. S., Wren, T. A. L., Skaggs, D. L. & Kay, R. M. Causes of intoeing gait in children with cerebral palsy. J. Bone Joint Surg. Am. 88, 2175–2180 (2006).

    PubMed  Google Scholar 

  182. 182

    Selber, P. et al. Supramalleolar derotation osteotomy of the tibia, with T plate fixation. Technique and results in patients with neuromuscular disease. J. Bone Joint Surg. Br. 86, 1170–1175 (2004).

    Article  CAS  PubMed  Google Scholar 

  183. 183

    Stefko, R. M. et al. Kinematic and kinetic analysis of distal derotational osteotomy of the leg in children with cerebral palsy. J. Pediatr. Orthop. 18, 81–87 (1998).

    CAS  PubMed  Google Scholar 

  184. 184

    Lee, S. H., Chung, C. Y., Park, M. S., Choi, I. H. & Cho, T.-J. Tibial torsion in cerebral palsy: validity and reliability of measurement. Clin. Orthop. Relat. Res. 467, 2098–2104 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  185. 185

    Chung, C. Y. et al. Validity and reliability of measuring femoral anteversion and neck-shaft angle in patients with cerebral palsy. J. Bone Joint Surg. Am. 92, 1195–1205 (2010).

    Article  PubMed  Google Scholar 

  186. 186

    Pons, C., Rémy-Néris, O., Médée, B. & Brochard, S. Validity and reliability of radiological methods to assess proximal hip geometry in children with cerebral palsy: a systematic review. Dev. Med. Child Neurol. 55, 1089–1102 (2013).

    Article  PubMed  Google Scholar 

  187. 187

    Terjesen, T., Anda, S. & Rønningen, H. Ultrasound examination for measurement of femoral anteversion in children. Skeletal Radiol. 22, 33–36 (1993).

    Article  CAS  PubMed  Google Scholar 

  188. 188

    Dubousset, J. et al. EOS: a new imaging system with low dose radiaton in standing position for spine and bone and joint disorders. J. Musculoskelet. Res. 13, 1–12 (2010).

    Article  Google Scholar 

  189. 189

    Buck, F. M., Guggenberger, R., Koch, P. P. & Pfirrmann, C. W. A. Femoral and tibial torsion measurements with 3D models based on low-dose biplanar radiographs in comparison with standard CT measurements. AJR Am. J. Roentgenol. 199, W607–W612 (2012).

    Article  PubMed  Google Scholar 

  190. 190

    Thomason, P., Selber, P. & Graham, H. K. Single event multilevel surgery in children with bilateral spastic cerebral palsy: a 5 year prospective cohort study. Gait Posture 37, 23–28 (2013).

    Article  PubMed  Google Scholar 

  191. 191

    Rutz, E., Donath, S., Tirosh, O., Graham, H. K. & Baker, R. Explaining the variability improvements in gait quality as a result of single event multi-level surgery in cerebral palsy. Gait Posture 38, 455–460 (2013).

    Article  PubMed  Google Scholar 

  192. 192

    Soo, B. et al. Hip displacement in cerebral palsy. J. Bone Joint Surg. Am. 88, 121–129 (2006).

    PubMed  Google Scholar 

  193. 193

    Hägglund, G. et al. Prevention of dislocation of the hip in children with cerebral palsy. The first ten years of a population-based prevention programme. J. Bone Joint Surg. Br. 87, 95–101 (2005).

    Article  PubMed  Google Scholar 

  194. 194

    Persson-Bunke, M., Hägglund, G., Lauge-Pedersen, H., Wagner, P. & Westbom, L. Scoliosis in a total population of children with cerebral palsy. Spine (Phila Pa 1976) 37, E708–E713 (2012).

    Article  Google Scholar 

  195. 195

    Miller, F., Slomczykowski, M., Cope, R. & Lipton, G. E. Computer modeling of the pathomechanics of spastic hip dislocation in children. J. Pediatr. Orthop. 19, 486–492 (1999).

    Article  CAS  PubMed  Google Scholar 

  196. 196

    Graham, H. K. et al. Does botulinum toxin A combined with bracing prevent hip displacement in children with cerebral palsy and ‘hips at risk’? A randomized, controlled trial. J. Bone Joint Surg. Am. 90, 23–33 (2008).

    Article  PubMed  Google Scholar 

  197. 197

    Shore, B. J. et al. Adductor surgery to prevent hip displacement in children with cerebral palsy: the predictive role of the Gross Motor Function Classification System. J. Bone Joint Surg. Am. 94, 326–334 (2012).

    Article  PubMed  Google Scholar 

  198. 198

    Flynn, J. M. & Miller, F. Management of hip disorders in patients with cerebral palsy. J. Am. Acad. Orthop. Surg. 10, 198–209 (2002).

    Article  PubMed  Google Scholar 

  199. 199

    Willoughby, K., Ang, S. G., Thomason, P. & Graham, H. K. The impact of botulinum toxin A and abduction bracing on long-term hip development in children with cerebral palsy. Dev. Med. Child Neurol. 54, 743–747 (2012).

    Article  PubMed  Google Scholar 

  200. 200

    Wynter, M. et al. The consensus statement on hip surveillance for children with cerebral palsy: Australian standards of care. J. Pediatr. Rehabil. Med. 4, 183–195 (2011).

    CAS  PubMed  Google Scholar 

  201. 201

    Dobson, F., Boyd, R. N., Parrott, J., Nattrass, G. R. & Graham, H. K. Hip surveillance in children with cerebral palsy. Impact on the surgical management of spastic hip disease. J. Bone Joint Surg. Br. 84, 720–726 (2002).

    Article  CAS  PubMed  Google Scholar 

  202. 202

    Narayanan, U. G. et al. Initial development and validation of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Dev. Med. Child Neurol. 48, 804–812 (2006).

    Article  PubMed  Google Scholar 

  203. 203

    Graham, H. K. & Narayanan, U. G. Salvage hip surgery in severe cerebral palsy: some answers, more questions? Bone Joint J. 96-B, 567–568 (2014).

    Article  Google Scholar 

  204. 204

    Gough, M. Continuous postural management and the prevention of deformity in children with cerebral palsy: an appraisal. Dev. Med. Child Neurol. 51, 105–110 (2009).

    Article  PubMed  Google Scholar 

  205. 205

    Terjesen, T., Lange, J. E. & Steen, H. Treatment of scoliosis with spinal bracing in quadriplegic cerebral palsy. Dev. Med. Child Neurol. 42, 448–454 (2000).

    Article  CAS  PubMed  Google Scholar 

  206. 206

    Nuzzo, R. M., Walsh, S., Boucherit, T. & Massood, S. Counterparalysis for treatment of paralytic scoliosis with botulinum toxin type A. Am. J. Orthop. (Belle Mead. NJ) 26, 201–207 (1997).

    CAS  Google Scholar 

  207. 207

    Tsirikos, A. I., Lipton, G., Chang, W.-N., Dabney, K. W. & Miller, F. Surgical correction of scoliosis in pediatric patients with cerebral palsy using the unit rod instrumentation. Spine (Phila Pa 1976) 33, 1133–1140 (2008).

    Article  Google Scholar 

  208. 208

    Raphael, B. S., Dines, J. S., Akerman, M. & Root, L. Long-term followup of total hip arthroplasty in patients with cerebral palsy. Clin. Orthop. Relat. Res. 468, 1845–1854 (2010).

    Article  PubMed  Google Scholar 

  209. 209

    Becher, J. G. Pediatric rehabilitation in children with cerebral palsy: general management, classification of motor disorders. J. Prosthet. Orthot. 14, 143–152 (2002).

    Article  Google Scholar 

  210. 210

    Kerkum, Y. L. et al. Optimising ankle foot orthoses for children with cerebral palsy walking with excessive knee flexion to improve their mobility and participation; protocol of the AFO-CP study. BMC Pediatr. 13, 17 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  211. 211

    Myrden, A., Schudlo, L., Weyand, S., Zeyl, T. & Chau, T. Trends in communicative access solutions for children with cerebral palsy. J. Child Neurol. 29, 1108–1118 (2014).

    Article  PubMed  Google Scholar 

  212. 212

    Guerette, P., Furumasu, J. & Tefft, D. The positive effects of early powered mobility on children's psychosocial and play skills. Assist. Technol. 25, 39–48 (2013).

    Article  PubMed  Google Scholar 

  213. 213

    Ragonesi, C. B. & Galloway, J. C. Short-term, early intensive power mobility training: case report of an infant at risk for cerebral palsy. Pediatr. Phys. Ther. 24, 141–148 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  214. 214

    Tefft, D., Guerette, P. & Furumasu, J. The impact of early powered mobility on parental stress, negative emotions, and family social interactions. Phys. Occup. Ther. Pediatr. 31, 4–15 (2011).

    Article  PubMed  Google Scholar 

  215. 215

    Sawers, A. & Ting, L. H. Perspectives on human–human sensorimotor interactions for the design of rehabilitation robots. J. Neuroeng. Rehabil. 11, 142 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  216. 216

    Meyer-Heim, A. et al. Feasibility of robotic-assisted locomotor training in children with central gait impairment. Dev. Med. Child Neurol. 49, 900–906 (2007).

    Article  CAS  PubMed  Google Scholar 

  217. 217

    Borggraefe, I. et al. Robotic-assisted treadmill therapy improves walking and standing performance in children and adolescents with cerebral palsy. Eur. J. Paediatr. Neurol. 14, 496–502 (2010). This is the first large report of outcomes with robotic gait training from multiple sites. This article defines outcomes and parameters of treatment.

    Article  PubMed  Google Scholar 

  218. 218

    Cioi, D. et al. Ankle control and strength training for children with cerebral palsy using the Rutgers Ankle CP: a case study. IEEE Int. Conf. Rehabil. Robot. 2011, 5975432 (2011).

    PubMed  Google Scholar 

  219. 219

    Zhang, M., Davies, T. C. & Xie, S. Effectiveness of robot-assisted therapy on ankle rehabilitation — a systematic review. J. Neuroeng. Rehabil. 10, 30 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. 220

    Wu, Y.-N., Hwang, M., Ren, Y., Gaebler-Spira, D. & Zhang, L.-Q. Combined passive stretching and active movement rehabilitation of lower-limb impairments in children with cerebral palsy using a portable robot. Neurorehabil. Neural Repair 25, 378–385 (2011).

    Article  PubMed  Google Scholar 

  221. 221

    Levac, D., Espy, D., Fox, E., Pradhan, S. & Deutsch, J. E. ‘Kinect-ing’ with clinicians: a knowledge translation resource to support decision making about video game use in rehabilitation. Phys. Ther. 95, 426–440 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  222. 222

    Labruyère, R., Gerber, C. N., Birrer-Brütsch, K., Meyer-Heim, A. & van Hedel, H. J. A. Requirements for and impact of a serious game for neuro-pediatric robot-assisted gait training. Res. Dev. Disabil. 34, 3906–3915 (2013).

    Article  PubMed  Google Scholar 

  223. 223

    Barton, G. J., Hawken, M. B., Foster, R. J., Holmes, G. & Butler, P. B. The effects of virtual reality game training on trunk to pelvis coupling in a child with cerebral palsy. J. Neuroeng. Rehabil. 10, 15 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  224. 224

    Mao, Y., Chen, P., Li, L. & Huang, D. Virtual reality training improves balance function. Neural Regen. Res. 9, 1628–1634 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  225. 225

    Monge Pereira, E. et al. Use of virtual reality systems as proprioception method in cerebral palsy: clinical practice guideline. Neurologia 29, 550–559 (2014).

    Article  CAS  PubMed  Google Scholar 

  226. 226

    Weiss, P. L. T., Tirosh, E. & Fehlings, D. Role of virtual reality for cerebral palsy management. J. Child Neurol. 29, 1119–1124 (2014).

    Article  PubMed  Google Scholar 

  227. 227

    Snider, L. & Majnemer, A. Virtual reality: we are virtually there. Phys. Occup. Ther. Pediatr. 30, 1–3 (2010). This is a systematic review of current virtual reality technologies and the evidence to support the intervention.

    Article  PubMed  Google Scholar 

  228. 228

    Tatla, S. K. et al. Evidence for outcomes of motivational rehabilitation interventions for children and adolescents with cerebral palsy: an American Academy for Cerebral Palsy and Developmental Medicine systematic review. Dev. Med. Child Neurol. 55, 593–601 (2013).

    Article  PubMed  Google Scholar 

  229. 229

    Zafeiriou, D. I., Kontopoulos, E. E. & Tsikoulas, I. Characteristics and prognosis of epilepsy in children with cerebral palsy. J. Child Neurol. 14, 289–294 (1999).

    Article  CAS  PubMed  Google Scholar 

  230. 230

    Wanigasinghe, J. et al. Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke. Dev. Med. Child Neurol. 52, 1021–1027 (2010).

    Article  PubMed  Google Scholar 

  231. 231

    Hundozi-Hysenaj, H. & Boshnjaku-Dallku, I. Epilepsy in children with cerebral palsy. J. Pediatr. Neurol. 6, 43–46 (2008).

    Article  Google Scholar 

  232. 232

    Sullivan, P. B. et al. Impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy. Dev. Med. Child Neurol. 46, 796–800 (2004).

    Article  PubMed  Google Scholar 

  233. 233

    Holmes, L. Jr et al. Pediatric cerebral palsy life expectancy: has survival improved over time? Pediat. Therapeut. 3, 146 (2013).

    Google Scholar 

  234. 234

    Fehlings, D. et al. Informing evidence-based clinical practice guidelines for children with cerebral palsy at risk of osteoporosis: a systematic review. Dev. Med. Child Neurol. 54, 106–116 (2012).

    Article  PubMed  Google Scholar 

  235. 235

    Walshe, M., Smith, M. & Pennington, L. Interventions for drooling in children with cerebral palsy. Cochrane Database Syst. Rev. 11, CD008624 (2012).

    PubMed  Google Scholar 

  236. 236

    [No authors listed.] The World Health Organization Quality of Life assessment (WHOQOL): position paper from the World Health Organization. Soc. Sci. Med. 41, 1403–1409 (1995).

  237. 237

    World Health Organization. International Classification of Functioning, Disability and Health (WHO, 2001).

  238. 238

    Dickinson, H. O. et al. Self-reported quality of life of 8-12-year-old children with cerebral palsy: a cross-sectional European study. Lancet 369, 2171–2178 (2007). This paper identified for the first time in a large quantitative study of a representative sample of children with cerebral palsy that their QOL was similar to that of their peers in the general population. The importance of cerebral palsy-associated pain in lowering QOL was also identified.

    Article  PubMed  Google Scholar 

  239. 239

    Colver, A. et al. Self-reported quality of life of adolescents with cerebral palsy: a cross-sectional and longitudinal analysis. Lancet 385, 705–716 (2014).

    Article  PubMed  Google Scholar 

  240. 240

    Majnemer, A. et al. Participation and enjoyment of leisure activities in school-aged children with cerebral palsy. Dev. Med. Child Neurol. 50, 751–758 (2008).

    Article  PubMed  Google Scholar 

  241. 241

    Orlin, M. N. et al. Participation in home, extracurricular, and community activities among children and young people with cerebral palsy. Dev. Med. Child Neurol. 52, 160–166 (2010).

    Article  PubMed  Google Scholar 

  242. 242

    Arnaud, C. et al. Parent-reported quality of life of children with cerebral palsy in Europe. Pediatrics 121, 54–64 (2008).

    Article  PubMed  Google Scholar 

  243. 243

    White-Koning, M. et al. Determinants of child–parent agreement in quality-of-life reports: a European study of children with cerebral palsy. Pediatrics 120, e804–e814 (2007).

    Article  PubMed  Google Scholar 

  244. 244

    Shikako-Thomas, K. et al. Quality of life from the perspective of adolescents with cerebral palsy: ‘I just think I'm a normal kid, I just happen to have a disability’. Qual. Life Res. 18, 825–832 (2009).

    Article  PubMed  Google Scholar 

  245. 245

    Parkinson, K. N., Gibson, L., Dickinson, H. O. & Colver, A. F. Pain in children with cerebral palsy: a cross-sectional multicentre European study. Acta Paediatr. 99, 446–451 (2010).

    Article  CAS  PubMed  Google Scholar 

  246. 246

    Opheim, A., Jahnsen, R., Olsson, E. & Stanghelle, J. K. Walking function, pain, and fatigue in adults with cerebral palsy: a 7-year follow-up study. Dev. Med. Child Neurol. 51, 381–388 (2009).

    Article  PubMed  Google Scholar 

  247. 247

    Parkinson, K. N., Dickinson, H. O., Arnaud, C., Lyons, A. & Colver, A. Pain in young people aged 13 to 17 years with cerebral palsy: cross-sectional, multicentre European study. Arch. Dis. Child. 98, 434–440 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  248. 248

    Katalinic, O. M., Harvey, L. A. & Herbert, R. D. Effectiveness of stretch for the treatment and prevention of contractures in people with neurological conditions: a systematic review. Phys. Ther. 91, 11–24 (2011).

    Article  PubMed  Google Scholar 

  249. 249

    Palermo, T. M. Evidence-based interventions in pediatric psychology: progress over the decades. J. Pediatr. Psychol. 39, 753–762 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  250. 250

    Roebroeck, M. E., Jahnsen, R., Carona, C., Kent, R. M. & Chamberlain, M. A. Adult outcomes and lifespan issues for people with childhood-onset physical disability. Dev. Med. Child Neurol. 51, 670–678 (2009).

    Article  PubMed  Google Scholar 

  251. 251

    Michelsen, S. I., Uldall, P., Kejs, A. M. T. & Madsen, M. Education and employment prospects in cerebral palsy. Dev. Med. Child Neurol. 47, 511–517 (2005). This paper, and its companion paper (reference 252), used the unique facility in Denmark to link health, social and educational records from birth to death to demonstrate the disadvantage experienced in adulthood by those with cerebral palsy.

    Article  PubMed  Google Scholar 

  252. 252

    Michelsen, S. I., Uldall, P., Hansen, T. & Madsen, M. Social integration of adults with cerebral palsy. Dev. Med. Child Neurol. 48, 643–649 (2006).

    Article  PubMed  Google Scholar 

  253. 253

    Van Der Slot, W. M. A. et al. Chronic pain, fatigue, and depressive symptoms in adults with spastic bilateral cerebral palsy. Dev. Med. Child Neurol. 54, 836–842 (2012).

    Article  PubMed  Google Scholar 

  254. 254

    Blackman, J. A. & Conaway, M. R. Adolescents with cerebral palsy: transitioning to adult health care services. Clin. Pediatr. (Phila) 53, 356–363 (2014).

    Article  Google Scholar 

  255. 255

    Delgado, M. R. et al. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child. Neurology 74, 336–343 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. 256

    Butler, C. & Campbell, S. Evidence of the effects of intrathecal baclofen for spastic and dystonic cerebral palsy. AACPDM Treatment Outcomes Committee Review Panel. Dev. Med. Child Neurol. 42, 634–645 (2000).

    Article  CAS  PubMed  Google Scholar 

  257. 257

    Sullivan, P. B. et al. Gastrostomy tube feeding in children with cerebral palsy: a prospective, longitudinal study. Dev. Med. Child Neurol. 47, 77–85 (2005).

    Article  PubMed  Google Scholar 

  258. 258

    Graham, H. K. Cerebral palsy prevention and cure: vision or mirage? A personal view. J. Paediatr. Child Health 50, 89–90 (2014).

    Article  PubMed  Google Scholar 

  259. 259

    Herskind, A., Greisen, G. & Nielsen, J. B. Early identification and intervention in cerebral palsy. Dev. Med. Child Neurol. 57, 29–36 (2015).

    Article  PubMed  Google Scholar 

  260. 260

    Fager, S., Bardach, L., Russell, S. & Higginbotham, J. Access to augmentative and alternative communication: new technologies and clinical decision-making. J. Pediatr. Rehabil. Med. 5, 53–61 (2012).

    PubMed  Google Scholar 

  261. 261

    Dalous, J. et al. Use of human umbilical cord blood mononuclear cells to prevent perinatal brain injury: a preclinical study. Stem Cells Dev. 22, 169–179 (2013).

    Article  CAS  PubMed  Google Scholar 

  262. 262

    Gonzales-Portillo, G. S., Reyes, S., Aguirre, D., Pabon, M. M. & Borlongan, C. V. Stem cell therapy for neonatal hypoxic–ischemic encephalopathy. Front. Neurol. 5, 147 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  263. 263

    Xiao, J., Nan, Z., Motooka, Y. & Low, W. C. Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev. 14, 722–733 (2005).

    Article  CAS  PubMed  Google Scholar 

  264. 264

    Willing, A. E. et al. Intravenous versus intrastriatal cord blood administration in a rodent model of stroke. J. Neurosci. Res. 73, 296–307 (2003).

    Article  CAS  PubMed  Google Scholar 

  265. 265

    Bae, S.-H. et al. Long-lasting paracrine effects of human cord blood cells on damaged neocortex in an animal model of cerebral palsy. Cell Transplant. 21, 2497–2515 (2012).

    Article  PubMed  Google Scholar 

  266. 266

    Borlongan, C. V., Hadman, M., Sanberg, C. D. & Sanberg, P. R. Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke. Stroke. 35, 2385–2389 (2004).

    Article  PubMed  Google Scholar 

  267. 267

    Bennet, L. et al. Cell therapy for neonatal hypoxia–ischemia and cerebral palsy. Ann. Neurol. 71, 589–600 (2012).

    Article  PubMed  Google Scholar 

  268. 268

    Carroll, J. E. & Mays, R. W. Update on stem cell therapy for cerebral palsy. Expert Opin. Biol. Ther. 11, 463–471 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  269. 269

    Ruff, C. A., Faulkner, S. D. & Fehlings, M. G. The potential for stem cell therapies to have an impact on cerebral palsy: opportunities and limitations. Dev. Med. Child Neurol. 55, 689–697 (2013).

    PubMed  Google Scholar 

  270. 270

    Chen, A. & Clowry, G. J. Could autologous cord blood stem cell transplantation treat cerebral palsy? Transl. Neurosci. 2, 207–2018 (2011).

    Article  CAS  Google Scholar 

  271. 271

    Dean, J. M. et al. Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization. Sci. Transl. Med. 5, 168ra7 (2013).

    Article  CAS  PubMed  Google Scholar 

  272. 272

    Wang, X.-L. et al. Umbilical cord blood cells regulate endogenous neural stem cell proliferation via hedgehog signaling in hypoxic ischemic neonatal rats. Brain Res. 1518, 26–35 (2013).

    Article  CAS  PubMed  Google Scholar 

  273. 273

    Andres, R. H. et al. Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain. Brain 134, 1777–1789 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  274. 274

    Lee, Y.-H. et al. Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy. J. Transl. Med. 10, 58 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  275. 275

    Min, K. et al. Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial. Stem Cells 31, 581–591 (2013).

    Article  CAS  PubMed  Google Scholar 

  276. 276

    Sharma, A. et al. Positron emission tomography-computer tomography scan used as a monitoring tool following cellular therapy in cerebral palsy and mental retardation — a case report. Case Rep. Neurol. Med. 2013, 141983 (2013).

    PubMed  PubMed Central  Google Scholar 

  277. 277

    Sun, J. et al. Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders. Transfusion 50, 1980–1987 (2010).

    Article  PubMed  Google Scholar 

  278. 278

    US National Library of Medicine. A randomized study of autologous umbilical cord blood reinfusion in children with cerebral palsy. ClinicalTrials.gov[online], (2015).

  279. 279

    US National Library of Medicine. Safety and effectiveness of cord blood stem cell infusion for the treatment of cerebral palsy in children. ClinicalTrials.gov[online], (2014).

  280. 280

    US National Library of Medicine. Safety and effectiveness of banked cord blood or bone morrow stem cells in children with cerebral palsy (CP). (ACT for CP). ClinicalTrials.gov[online], (2015).

  281. 281

    Kang, M. et al. Involvement of immune responses in the efficacy of cord blood cell therapy for cerebral palsy. Stem Cells Dev. 24, 2259–2268 (2015).

    Article  CAS  PubMed  Google Scholar 

  282. 282

    US National Library of Medicine. Efficacy of stem cell transplantation compared to rehabilitation treatment of patients with cerebral paralysis (CP). ClinicalTrials.gov[online], (2013).

  283. 283

    Patoine, B. NerveCenter: media focus on ‘miracle cure’ for cerebral palsy pits science versus hype. Ann. Neurol. 66, A9–A11 (2009).

    PubMed  Google Scholar 

  284. 284

    Palisano, R. et al. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev. Med. Child Neurol. 39, 214–223 (1997).

    Article  CAS  PubMed  Google Scholar 

  285. 285

    Palisano, R. J., Rosenbaum, P., Bartlett, D. & Livingston, M. H. Content validity of the expanded and revised Gross Motor Function Classification System. Dev. Med. Child Neurol. 50, 744–750 (2008).

    Article  PubMed  Google Scholar 

  286. 286

    Reid, S. M. et al. Temporal trends in cerebral palsy by impairment severity and birth gestation. Dev. Med. Child Neurol. 57 (Suppl. 3), 21 (2015).

    Google Scholar 

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Contributions

Introduction (P.R.); Epidemiology (N.P.); Mechanisms/pathophysiology (B.D., R.L.L. and J.-P.L.); Diagnosis, screening and prevention (D.S.R., P.R. and H.K.G.); Management (J.-P.L., D.L.D., H.K.G., J.G.B. and D.G.-S.); Quality of life (A.C.); Outlook (D.S.R. and K.E.C.); Overview of Primer (P.R. and H.K.G.).

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Correspondence to H. Kerr Graham.

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Competing interests

H.K.G. has received unrestricted educational grants from pharmaceutical companies including Allergan. Current research support is from the Hugh Williamson Foundation and the National Health and Medical Research Council of Australia, Cerebral Palsy Centre of Research Excellence (CRE). J.-P.L. has held grants from the Guy's and St. Thomas Charity New Services and Innovation Grant G060708; the Dystonia Society UK Grants 01/2011 and 07/2013 and Action Medical Research GN2097, has acted as a consultant for Medtronic Ltd and benefited from unrestricted educational grants by Medtronic Ltd. B.D. and P.R. are senior members of the editorial board of Mac Keith Press, the publisher of the 2014 book “Cerebral Palsy: Science and Clinical Practice” (Mac Keith Press: London) and have contributed to several chapters, for which they are likely to receive modest royalties. All other authors declare no competing interests.

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Graham, H., Rosenbaum, P., Paneth, N. et al. Cerebral palsy. Nat Rev Dis Primers 2, 15082 (2016). https://doi.org/10.1038/nrdp.2015.82

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