Pediatric Physical Therapy:
The Pathophysiological Basis of Weakness in Children With Cerebral Palsy
Mockford, Margaret MSc, MCSP; Caulton, Janette M. MSc, MCSP
Physiotherapy Department, Blackfriars School, North Staffordshire NHS Primary Care Trust, Newcastle-under-Lyme, Staffordshire, United Kingdom (Ms Mockford); and School of Health and Rehabilitation, Keele University, Keele, Staffordshire, United Kingdom (Ms Caulton)
Correspondence: Margaret Mockford, Physiotherapy Department, Blackfriars School, Priory Road, Newcastle-under-Lyme ST5 2TF, United Kingdom (email@example.com).
This article arises from the dissertation completed in part fulfillment of the Master of Science degree at Keele University, by Margaret Mockford.
Purpose: To examine the evidence concerning the neurologic and muscular pathophysiology that contributes to clinically observed weakness in children and young people with cerebral palsy (CP).
Method: Literature concerning the neural or muscular changes in subjects with CP was found by searching 6 databases plus supplementary searching.
Results: A final set of 51 articles was identified by 2 independent reviewers.
Summary of Key Points: Muscle weakness is due to reduced central drive, possible abnormal neural maturation, insufficient and disorganized motor recruitment, impaired voluntary control, impaired reciprocal inhibition, altered setting of muscle spindles, and reinforcement of abnormal neural circuits. Muscle tissue is altered, with selective atrophy of fast fibers and altered myosin expression, changes in fiber length and cross-sectional area, changes in the length-tension curve, reduced elasticity, and impoverished muscle tissue development.
Conclusion: Children with CP are weak because of both neurologic and muscular changes.
Cerebral palsy (CP) is defined as “a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders are often accompanied by secondary musculoskeletal problems.”1(p. 9) Children with CP are delayed in acquiring motor skills and may never attain the abilities of their peers who are typically developing.2 Those who achieve ambulation may experience deterioration during their teenage years due to many possible and interacting factors including increasing spasticity, joint contractures, knee pain, and deteriorating muscle strength.3,4 Loss of ambulation is often due to increasing fatigue and inefficiency of gait. Physiological burnout is experienced by some active adults with CP.5 This involves reduced muscle strength and cardiovascular endurance due to prolonged stress on the motor system.
Strength is defined as the ability to exert maximal voluntary force,6 and weakness is any impairment of this ability. Phelps7 identified weakness as an important element of abnormal postural movement more than 60 years ago. The presence of weakness in people with CP was questioned by Bobath8 who regarded the primary problem as one of abnormal cocontraction rather than weakness. She stated “muscles may appear weak because they cannot function optimally due to excessive resistance by spastic antagonists, or to abnormal coordination with lack of synergistic fixation, or as a result of sensory deficit.”8(p. 529) Two popular approaches to the treatment of CP in the late 20th century were neurodevelopmental therapy and conductive education. The neurodevelopmental approach to therapy that evolved from the teachings of Bobath sought to reduce spasticity and thereby facilitate normal movement. Conductive education emphasized practice of functional activities to address CP as a “learning disorder.”9 Although both these approaches were valuable, these did not specifically acknowledge, assess, or address the muscle weakness.
It is now well documented that the upper motor neuron (UMN) syndrome includes weakness, impaired selective motor control, and altered sensory feedback, as well as spasticity and exaggerated tendon jerk reflexes.10,11 Carr et al11 suggested that spasticity and exaggerated tendon jerks are relatively independent of the other features of UMN damage, questioning the assumption by Bobath8 that reducing spasticity may reveal adequate strength. Studies of children undergoing selective dorsal rhizotomy have shown that surgical reduction of spasticity does not unmask lower limb strength, although after 12 months of intensive therapy, many subjects had improved their strength measures.12,13 More recently, an objective study of 27 children with CP found that both spasticity and strength of the knee flexors and extensors are each strongly correlated with measures of function.14 The measure of spasticity in a muscle group is only moderately correlated (−0.42 to −0.61) with the strength measure of that muscle.14
The purpose of this review was to identify the evidence concerning the neurologic and muscular pathophysiology that contributes to clinically observed weakness in children and young people with CP.
Six databases (AMED, CINAHL, Cochrane, EMBASE, MEDLINE, and PEDro) were searched for literature published in English between 1985 and September 2008, using the keywords cerebral palsy, muscle strength, muscle weakness, spasticity, physiology, and pathophysiology. Reference lists of key articles were scanned for additional material. The initial date limit was set because scientific knowledge in this field has progressed so dramatically in the past 20 years, although additional references published before 1985 were considered for inclusion if they were relevant. The search had no age limits because literature from adult studies could inform this discussion, although at the same time we acknowledge that CP is a UMN lesion in an immature nervous system as opposed to an injury to a mature system in adults. The titles and abstracts of results were scanned by 2 independent reviewers applying the inclusion/exclusion criteria given in Table 1. Literature from animal studies was included where there were gaps in the human literature, particularly regarding invasive procedures such as biopsies and histology studies. Disagreements between the 2 reviewers were settled by discussion and reference to the inclusion criteria. Articles potentially meeting the inclusion criteria were read in full and agreement was reached on a final set.
The initial search produced 996 results. Of these, 124 were read in full. Forty-seven articles were selected for inclusion by both the authors, and another 4 articles15–18 were included after discussion. Finally, 51 articles were used to inform this review4,6,10–58 (Table 2). Of these, 32 were pediatric articles, 8 addressed adults, 8 addressed both adults and children, 2 gave information from animal studies, and 1 reviewed both human and animal studies. Ten articles gave evidence of weakness in subjects with CP, 14 discussed neurologic changes, and 35 discussed muscle and soft-tissue changes. Some articles addressed more than 1 of these areas. Seventy-three articles were excluded because they did not meet the inclusion criteria; many investigated the validity or reliability of outcome measures, spasticity-altering interventions such as botulinum toxin, or trial interventions in which the outcome measures were not related to strength, spasticity, or function.
The Evidence of Weakness in CP
All studies reviewed supported the finding that children with CP are weaker than their peers who are developing typically. A study of 60 subjects aged 3 to 38 years who were ambulant with mild CP were compared with 50 individuals without disabilities, and strength and spasticity of the knee and ankle flexors and extensors were measured using an isokinetic machine.19 The authors found that subjects with CP were significantly weaker; there was no significant correlation between spasticity and weakness either within a single muscle or across a joint. Weakness was found in all subjects with CP, although not all showed measurable spasticity. The study concluded weakness, and not spasticity, may be a prevailing impairment in individuals with CP. Although these investigators did not use a measure of function, they discuss why weakness may be a significant limiter of function. These subjects had mild CP, limiting the generalizability of findings to the more severely involved population. In another robust study20 of 30 children with CP who were ambulant with a wider range of ability, significant isometric weakness was found in 8 lower limb muscle groups (hip knee and ankle flexors and extensors, hip abductors and adductors). This included the unaffected leg of children with hemiplegia, when compared with 16 age-matched children who were developing typically. A study of 10 children and adults with CP found only 50% power in the calf during push-off when compared with age-matched controls.21 The latter finding is supported by Engberg et al,22 who compared isokinetic ankle strength in 27 children with CP and 12 age-matched controls and found that those with CP were significantly weaker in both dorsiflexors and plantar flexors. An isometric strength study of 12 children with spastic diplegia when compared with 12 age-matched controls clearly demonstrated a significant reduction in quadriceps maximal force in the children with CP.23 The balance of strength across a joint may be a separate construct to strength of the individual muscle groups.14 This balance or strength ratio varies at different points in the range of movement. An imbalance in the quadriceps/hamstring strength ratio due to disproportionate weakness of the quadriceps possibly contributed to the reversal of net torque direction toward the end of knee extension found in an isokinetic study of 26 children and teenagers with CP who were ambulant.24 The quadriceps/hamstring ratio seems to influence measures of gross motor and physiological function.14
Several factors affect the level of weakness found in the muscles of children with CP. First, weakness may differ between proximal and distal limb muscles. Stackhouse et al25 found that the maximum voluntary contraction (MVC) was more impaired in the plantar flexors than the quadriceps of children with mild CP compared with controls. Second, the peak torque may vary according to the velocity of limb movement. Peak torque of the knee flexors and extensors in 24 children with CP was found to decrease with increasing velocity on an isokinetic machine.26 Third, peak torque may vary according to muscle length. An isokinetic study of 44 children and young people with CP found that peak torque in the hip abductors occurred when the muscle was in a lengthened position with the leg still in adduction.27 Fourth, the type of contraction was found to consistently affect the peak torque in both children with CP and those who are typically developing, with eccentric force being greater than concentric force in the same muscle.26
The Neurologic Basis of Weakness
Central neurologic damage is the primary lesion in children with CP. A number of neurologic factors contribute to weakness in these children. Pyramidal tract damage reduces central input to the motor neurons;6 therefore, the motor neuron pool is less able to drive the agonist muscle.28 Myelination is incomplete at birth in all children.4 Maturation of the nervous system occurs as neural circuits are reinforced by repetition, which influences the processes of myelination and apoptosis.4 The child who is typically developing voluntarily repeats a normal motor activity many times over, but the child with CP may repeat abnormal movement patterns, which in turn reinforce the neural circuits producing them.
The contraction force of typical muscle is augmented either by increasing the number of active motor units or by increasing the firing rates of already active units; this occurs in an orderly recruitment pattern.29 The recruitment pattern is specific for each muscle, normally activating small motor units first21; after UMN damage, however, recruitment of motor units is insufficient, disorderly, and slower than normal.25,30 The muscle is therefore not completely activated.23,25 The study23 of quadriceps force production in 12 children with spastic diplegia compared with 12 controls demonstrated a significantly slower rate of force production, indicating inefficient recruitment of motor units.
The neural pathways of individual muscles exhibit specific balances between recruitment and firing rate modulation, but it is suggested that the pathways to spastic muscle may rely mostly on motor unit recruitment to generate torque.21 This could be due to impaired firing rate modulation, and therefore the normal match between firing rates and mechanical properties of muscle fibers is altered, causing inefficiency and fatigue.21,30 Premature recruitment of large motor units that fatigue quickly would cause early loss of force.31 The reduced ability to modulate motor responses limits selective motor control and impairs ability to generate torque.11,32
Altered neural input with a longer recruitment period results in delayed initiation of muscle action after a UMN lesion.30 The slow rate of force development in children with CP compared with those who are typically developing may be because of their reduced ability to recruit higher threshold motor units or to drive lower threshold units to increase the firing rate.23 Alterations in reciprocal inhibitory pathways may lead to abnormal cocontraction, which produces apparent agonist weakness due to prolonged spastic antagonist activity (antagonist restraint), particularly during rapid or reciprocal movements.6,28 An isokinetic study of knee flexion and extension found more than 70% of subjects with CP demonstrated excessive cocontraction even at a slow velocity.24 The extended half-relaxation time of these muscle groups indicates some impairment of reciprocal inhibition.23
The sensory and motor innervation of muscle spindles is complex and highly sensitive to the muscle microenvironment.33 The threshold of spindle sensory fibers may reset in response to chronic shortening of a spastic muscle.33 Corresponding lengthening of the opposing muscle causes abnormal resting postures and reduced drive via the spindle afferent fibers. A study of strength in children with CP found that hip abductor peak torque occurred earlier in the movement range than in a typically developing control group.27 The peak occurred when the leg was still in adduction, which showed that the abductor muscles were working most effectively in their lengthened position. These findings could be attributed to habituation of muscle spindle afferents in the chronically lengthened abductors.
In summary, the neural factors contributing to clinical weakness in this population include reduced motor drive, reinforcement of abnormal neural circuits, altered recruitment patterns, impaired reciprocal inhibition, and altered setting of muscle spindles. Normal neural maturation is associated with progressive acquisition of strength, with a faster speed of contraction and a greater isometric MVC.59 Neurophysiologic abnormalities in the child with CP persist and permanently impair the transition to adult neuromuscular properties. These abnormalities limit the ability of the growing child with CP to acquire strength in a typical way.
The Muscular Basis of Weakness
It was believed that muscle tissue remained histologically unchanged in a subject with a cerebral lesion.34 Sinkjaer et al35 raised the possibility of changes in the types of motor units seen after a UMN lesion. Recent research has led to widespread agreement that skeletal muscle is significantly altered in individuals with CP and contributes to clinically observed weakness,36 but the pattern of alteration may vary due to several factors. Muscle tissue changes may be expected to vary with ambulatory ability and according to the age of the child with CP.36 Age at acquiring cerebral damage may also affect histology: in a small muscle biopsy study of 9 children with CP,37 contractile property changes were more marked in those acquiring CP perinatally than in 1 child who acquired cerebral damage at the age of 17 months.
Changes in Fiber Type and Development
The number of muscle fibers in a motor unit and the type of myosin found in those fibers are determined largely by the size and activity of their motor neuron.60 Myosin expression is also modulated by hormones and mechanical activity.38 Most muscles exhibit a mixture of type 1 (slow) and type 2 (fast) motor units, the proportions vary according to the muscle's main function. For example, the soleus contains a high proportion of slow type 1 fibers to produce prolonged postural support; the gastrocnemius has a higher proportion of fast type 2 fibers to produce a powerful push-off in walking and running.60 An altered neural input due to cerebral damage affects this differentiation of fiber types. Muscle also undergoes maturation changes, whereby embryonic and neonatal myosin forms are replaced by adult forms. These changes occur during childhood and on into adulthood.61 They are shaped by the level of muscle activity15 and environmental cues, especially mechanical stretch.62 Altered levels of activity, and perhaps the ability to bear weight, will affect this maturation of myosin into adult forms.
Muscle spindle development and acetylcholine receptor synthesis depend on the neural activation pattern prenatally.60,63 Neural lesions occurring antenatally could alter development of fetal muscle cells,16 muscle spindles,63,64 and neurotransmission64; therefore, the child may be born with inadequately differentiated muscle tissue and possible structural abnormalities in the muscle spindles and acetylcholine receptors. The early postnatal weeks are a crucial period of muscle physiology development, with intense reshuffling of terminals and neuromuscular connections being made and broken.38,60 A study of 21 children with low birth weight and various UMN lesions showed delayed postnatal maturation of muscle fibers.39
In children with CP who are ambulant, changes in the contractile properties of muscle include selective atrophy of fast type 2A+B myosin fibers and possibly the advent of a fourth type of fiber that exhibits prolonged twitch and rapid fatigability.10 Dominance of type 1 fibers, with reduced type 2 fibers, is commensurate with muscle that produces prolonged low-force action but cannot generate rapid high-torque contractions.60 Gastrocnemius biopsies in children with CP who are ambulant revealed an increase in type 1 fibers from the normal 50% to 68% to 95%, with loss of type 2B fibers.37 A blinded biopsy study40 found increased type 1 fibers in children with CP who are ambulant and increased type 2 fibers in children who were nonambulant compared with controls of comparable age. Mature myonuclei retain the ability to express all myosin types,65 but it is not known whether the myosin profile of muscle in children with CP can alter toward normal proportions.
Changes in Muscle Fiber Length and Cross Section
Maximum torque is dependent on optimum overlap of actin and myosin filaments; therefore, muscle strength is related to the number of sarcomeres in series and the length of individual sarcomeres.36 Fiber growth occurs by addition of sarcomeres at either end, in response to excursion, loading, and bone growth.41 Sarcomeres within individual flexor carpi ulnaris fibers of teenagers and young adults with spastic CP, measured during surgery, were abnormally long compared with nonspastic controls.42 These lengthened sarcomeres were calculated to produce only 40% maximum normal force. Lengthening of sarcomeres may be due to insufficient muscle growth compared with bone growth4 or to the reduction of the pennation angle due to atrophy within the highly pennated flexor carpi ulnaris muscle. The lengthened sarcomeres could explain another mechanism of weakness in subjects with CP: in stretched sarcomeres, the reduced overlap of actin and myosin filaments, and therefore the limited number of cross-bridges that are aligned, reduces the ability to produce force.
In cross section, normal muscle tissue exhibits fibers of similar sizes, but spastic muscle shows fibers of various sizes and more rounded and “moth-eaten” fibers.43,44 These changes increase with clinical severity45 and the time since acquiring CP.37 Muscle tissue appears to be progressively changed in response to the abnormal neural inputs resulting from cerebral damage in children.
Changes in Whole Muscle Length
The medial head of the spastic gastrocnemius muscle was shown to be 10% shorter than normal in an ultrasound study of 16 preadolescent children with CP.46 This was attributed to failure of volumetric growth, with fiber atrophy and reduction of pennation angle, and possibly a shortened intramuscular aponeurosis. In addition to the shorter muscle belly, the spastic musculotendinous unit may exhibit a longer tendon than normal.34 The shorter muscle contains fewer sarcomeres; therefore, there are fewer cross bridges to produce torque. The longer tendon may contribute to biomechanical inefficiency. Spastic muscle seems to exert maximum force at a different point along the length-tension curve31; this may result in reduced functional ability because the muscle no longer works optimally at the length required for a function such as walking. A heterogeneous sample of children and young adults with CP who underwent gastrocnemius fascia lengthening showed improved torque production at push-off 12 months postoperatively.17 The authors suggest that this could have been because the lengthened spastic muscle was working in mid-range rather than end range, or the longer muscle was less susceptible to a reflex response early in the movement and so the subject was able to produce a voluntary contraction for push-off.
As the spastic muscle is shorter, the opposing muscle chronically rests in a lengthened position that causes addition of sarcomeres in series. Under these circumstances, the muscle rests at a biomechanical disadvantage and may not shorten sufficiently to produce the required functional movement. The quadriceps of 14 children with CP who were ambulant were found to be stronger when the knee was at 90 degrees than at 30 degrees of flexion.47 The hip and knee extensors should function near their shortest position during walking, yet this may be the weakest part of the muscle's range. The study of hip abductors (acting as antagonists to the shortened spastic adductors) in children with CP27 demonstrated that the abductors were strongest in a lengthened, not shortened, position. Crouch gait in children with CP could be compensatory, allowing the hip and knee extensors to work at longer, and therefore stronger, lengths.
Changes in Whole Muscle Cross-Sectional Area
Muscle force is highly correlated with physiological cross-sectional area. The pennation angle and the strength per unit of cross-sectional area increase with growth,59 and the adult cross-sectional area is probably reached soon after puberty.60 Cross-sectional area and strength per unit cross-sectional area increase through adolescence in subjects who are developing typically;59 therefore, the age of the child when muscle histology and strength studies are performed can affect results. A study comparing data from children with CP with well-matched controls found the former had reduced leg muscle cross-sectional area and an inability to produce torque commensurate with this cross-sectional area.48 Marbini et al49 identified hypotrophy in the adductors and triceps surae of children with CP, reducing the cross-sectional area and the pennation angle. Therefore, the muscle architecture and biomechanics are altered, thereby reducing efficiency.60 The medial head of the spastic gastrocnemius was found to be only two thirds of normal volume, with a reduced pennation angle within the muscle.46 Children born prematurely may never develop a full number of muscle fibers18; therefore, the cross-sectional area is less than normal, and the potential MVC is limited. A study of 38 children with CP who were more severely impaired indicated that muscle thickness is related to function,50 although the measured volume of muscle is probably not indicative of the amount of muscle voluntarily activated during functional activities.51 Although normal muscle is composed of 95% fibers, spastic muscle is only 40% fibers, with increased intramuscular fat and connective tissue.52
Changes in the Passive Properties of Muscle
Herbert53 identified that the passive mechanical properties of muscle tissue respond to altered use. Recently, Eng30 proposed that these properties may be more important than altered reflexes in limiting function. The passive viscoelastic properties of muscle are affected by the amount and type of collagen, the extent of collagen cross-linking, and the architectural organization of collagen fibrils. The viscoelastic properties affect the amount of internal resistance that a muscle has to overcome when contracting and also the passive resistance to lengthening as the opposing muscle contracts. A weakened agonist may be unable to fully elongate its spastic antagonist, allowing contractures to develop and thus perpetuating a pattern of weakness with increased passive stiffness.54 The collagen of normal muscle exhibits significant crimping, contributing to its elasticity, but this crimping is reduced in spastic muscles in people with CP.29 Additionally, bone growth may not be matched by sufficient contractile and noncontractile soft-tissue growth in children with CP4; thus, tissue becomes overstretched and viscoelasticity is reduced.
Individual spastic muscle fibers are stiffer than controls, with a greatly increased tensile strength55; therefore, more force is needed to elongate a spastic muscle fiber. As this stiffness does not correlate with any increase in electromyographic measures,48 which would indicate active resistance to lengthening, it may be that each cross bridge is inherently stiffer.44 Animal studies have indicated possible exaggerated cross-bridge binding that may be reduced immediately after movement.56 Stiffness may also be due to alteration of structures within the muscle cell that set resting length and determine cellular stiffness such as the protein titin.44 Variations in the titin isoform have already been identified between skeletal and cardiac muscle.55 Further research is needed to identify whether other isoforms exist, which could influence the physiologic function of spastic muscle. Comparing the elasticity of single fibers with that of fiber bundles indicated that the extracellular matrix in children with CP was fragile and of poor quality and reduced stiffness.36 It is not yet known whether the fragile extracellular matrix induces a compensatory stiffness in individual fibers or vice versa. These findings are contradictory to the findings of Smeulders et al,57,58 who found low passive resistance in stretched spastic muscle, questioning the existence of extra collagen within the muscle and proposing that clinical stiffness may be due to extramuscular connective tissue. They hypothesize that measured strength is affected by the position and tension of other adjacent structures to which the spastic muscle is connected.57,58 Whatever the cause, stiffness may provide stability in the presence of muscle insufficiency.29
In summary, children with CP may be weak because of muscle tissue changes including altered myosin expression and possible structural abnormalities from the perinatal period. There are also alterations in sarcomere length and fiber size, whole muscle length and cross-sectional area, and viscoelastic properties.
Clinical Relevance of the Findings
Many factors interact to affect the strength of growing children: anthropometrics, neurologic maturity, hormonal factors, muscle architecture, sex, and age.59,66 The family's lifestyle, diet, and activity levels will also influence a child's strength. In children with CP, the neural and muscle tissue changes discussed earlier are superimposed on these maturation and environmental factors. CP is a chronic disorder requiring lifelong intervention. Further research is needed to increase the understanding of the pathophysiologic basis of the impairments seen in CP to enable ongoing development of interventions that improve function and quality of life into adulthood.67
In conclusion, the weakness found in children with CP is attributable to both altered neural mechanisms and muscle tissue changes. Further research is needed to determine to what extent these changes are preventable or treatable. Because lack of strength is linked to limitations in functional activities such as walking, it would therefore seem logical that therapeutic interventions should address weakness as well as the other impairments that make up the clinical picture of CP to improve these children's levels of activity and participation.
1. Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl. 2007;109:8–14.
2. Rosenbaum PL, Walter SD, Hanna SE, et al. Prognosis for gross motor function in cerebral palsy: creation of motor development curves. JAMA. 2002;288:1357–1363.
3. Andersson C, Mattsson E. Adults with cerebral palsy: a survey describing problems, needs, and resources, with special emphasis on locomotion. Dev Med Child Neurol. 2001;43:76–82.
4. Farmer S. Key factors in the development of lower limb coordination: implications for the acquisition of walking in children with cerebral palsy. Disabil Rehabil. 2003;25:807–816.
5. Edwards S. Cerebral palsy in adult life. In: Scrutton D, Damiano D, Mayston M, eds. Management of the Motor Disorders of Children With Cerebral Palsy. 2nd ed. London: Mac Keith Press; 2004.
6. Damiano D, Dodd K, Taylor N. Should we be testing and training muscle strength in cerebral palsy? Dev Med Child Neurol. 2002;44:68–72.
7. Phelps W. Cerebral birth injuries: their orthopaedic classification and subsequent treatment. J Bone Joint Surg Am. 1932;14:773–782.
8. Bobath B. Motor development, its effect on general development, and application to the treatment of cerebral palsy. Physiotherapy. 1971;57:526–532.
9. Bairstow P, Cochrane R, Hur J. Evaluation of Conductive Education for Children with Cerebral Palsy. Final Report (Part 1). London: HMSO; 1993.
10. Bakheit A. Management of muscle spasticity. Crit Rev Phy Rehabil Med. 1996;8:235–252.
11. Carr J, Shepherd R, Ada L. Spasticity research findings and implications for intervention. Physiotherapy. 1995;81:421–429.
12. Engsberg J, Olree K, Ross S, et al. Spasticity and strength changes as a function of selective dorsal rhizotomy. J Neurosurg. 1998;88:1020–1026.
13. Buckton C, Thomas S, Harris G, et al. Objective measurement of muscle strength in children with cerebral palsy after selective dorsal rhizotomy. Arch Phys Med Rehabil. 2002;83:454–460.
14. Goh H, Thompson M, Huang W, et al. Relationships among measures of knee musculoskeletal impairments, gross motor function, and walking efficiency in children with cerebral palsy. Pediatr Phys Ther. 2006;18:253–261.
15. Moore G, Goldspink G. The effect of reduced activity on the enzymatic development of phasic and tonic muscles in the chicken. J Dev Physiol. 1985;7:381–386.
16. Blair E, Stanley F. Intrauterine growth and spastic cerebral palsy II. The association with morphology at birth. Early Hum Dev. 1992;28:91–103.
17. Rose S, DeLuca P, Davis R, et al. Kinematic and kinetic evaluation of the ankle after lengthening of the gastrocnemius fascia in children with cerebral palsy. J Pediatr Orthop. 1993;13:727–732.
18. Gondret F, Lefaucheur L, Juin H, et al. Low birth weight is associated with enlarged muscle fiber area and impaired meat tenderness of the longissimus muscle in pigs. J Anim Sci. 2006;84:93–103.
19. Ross S, Engsberg J. Relation between spasticity and strength in individuals with spastic diplegic cerebral palsy. Dev Med Child Neurol. 2002;44:148–157.
20. Wiley M, Damiano D. Lower-extremity strength profiles in spastic cerebral palsy. Dev Med Child Neurol. 1998;40:100–107.
21. Rose J, McGill K. The motor unit in cerebral palsy. Dev Med Child Neurol. 1998;40:270–277.
22. Engberg J, Ross S, Olree K, et al. Ankle spasticity and strength in children with spastic cerebral palsy. Dev Med Child Neurol. 2000;42:42–47.
23. Tammik K, Matlep M, Ereline J, et al. Quadriceps femoris muscle voluntary force and relaxation capacity in children with spastic diplegic cerebral palsy. Pediatr Exerc Sci. 2008;20:18–28.
24. Engsberg J, Olree K, Ross S, et al. Maximum active resultant knee joint torques in children with cerebral palsy. J Appl Biomech. 1998;14:52–61.
25. Stackhouse S, Binder-Macleod S, Lee S. Voluntary muscle activation, contractile properties, and fatigability in children with and without cerebral palsy. Muscle Nerve. 2005;31:594–601.
26. Damiano D, Martellotta T, Quinlivan J, et al. Deficits in eccentric versus concentric torque in children with spastic cerebral palsy. Med Sci Sports Exerc. 2001;33:117–122.
27. Engsberg J, Ross S, Hollander K, et al. Hip spasticity and strength in children with spastic diplegia cerebral palsy. J Appl Biomech. 2000;16:221–233.
28. Bohannon R. Is the measurement of muscle strength appropriate in patients with brain lesions? A special communication. Phys Ther. 1989;69:225–236.
29. Gardiner R. The pathophysiology and clinical implications of neuromuscular changes following cerebrovascular accident. Aust J Physiother. 1996;42:139–147.
30. Eng J. Strength training in individuals with stroke. Physiother Can. 2004;56:189–201.
31. Mirbagheri M, Barbeau H, Ladouceur M, et al. Intrinsic and reflex stiffness in normal and spastic, spinal cord injured subjects. Exp Brain Res. 2001;141:446–459.
32. Damiano D, Quinlivan J, Owen B, et al. Spasticity versus strength in cerebral palsy: relationships among involuntary resistance, voluntary torque, and motor function. Eur J Neurol. 2001;8 (Suppl 5):40–49.
33. Liu J, Eriksson P, Thornell L, et al. Myosin heavy chain composition of muscle spindles in human biceps brachii. J Histochem Cytochem. 2002;50:171–184.
34. Tardieu C, Huet de la Tour E, Bret M, et al. Muscle hypoextensibility in children with cerebral palsy: 1. Clinical and experimental observations. Arch Phys Med Rehabil. 1982;63:97–102.
35. Sinkjaer T, Magnussen I. Passive, intrinsic and reflex-mediated stiffness in the ankle extensors of hemiparetic patients. Brain. 1994;117:355–363.
36. Lieber R, Steinman S, Barash I, et al. Structural and functional changes in spastic skeletal muscle. Muscle Nerve. 2004;29:615–627.
37. Ito J, Araki A, Tanaka H, et al. Muscle histopathology in spastic cerebral palsy. Brain Dev. 1996;18:299–303.
38. Baldwin KM, Haddad F. Plasticity in skeletal, cardiac, and smooth muscle: effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol. 2001;90:345–357.
39. Sarnat HB. Cerebral dysgeneses and their influence on fetal muscle development. Brain Dev. 1986;8:495–499.
40. Rose J, Haskell W, Gamble J, et al. Muscle pathology and clinical measures of disability in children with cerebral palsy. J Orthop Res. 1994;12:758–768.
41. O'Dwyer NJ, Neilson PD, Nash J. Mechanisms of muscle growth related to muscle contracture in cerebral palsy. Dev Med Child Neurol. 1989;31:543–552.
42. Lieber R, Friden J. Spasticity causes a fundamental rearrangement of muscle-joint interaction. Muscle Nerve. 2002;25:265–270.
43. Romanini L, Villani C, Meloni C, et al. Histological and morphological aspects of muscle in infantile cerebral palsy. Ital J Orthop Traumatol. 1989;15:87–93.
44. Foran J, Steinman S, Barash I, et al. Structural and mechanical alterations in spastic skeletal muscle. Dev Med Child Neurol. 2005;47:713–717.
45. Booth C, Cortine-Borja M, Theologis T. Collagen accumulation in muscles of children with cerebral palsy and correlation with severity of spasticity. Dev Med Child Neurol. 2001;43:314–320.
46. Malaiya R, McNee A, Fry N, et al. The morphology of the medial gastrocnemius in typically developing children and children with spastic hemiplegic cerebral palsy. J Electromyogr Kinesiol. 2007;17:657–663.
47. Damiano D, Vaughan C, Abel M. Muscle response to heavy resistance exercise in children with spastic cerebral palsy. Dev Med Child Neurol. 1995;37:731–739.
48. Elder G, Kirk J, Stewart G, et al. Contributing factors to muscle weakness in children with cerebral palsy. Dev Med Child Neurol. 2003;45:542–550.
49. Marbini A, Ferrari A, Cioni G, et al. Immunohistochemical study of muscle biopsy in children with cerebral palsy. Brain Dev. 2002;24:63–66.
50. Ohata K, Tsuboyama T, Haruta T, et al. Relation between muscle thickness, spasticity, and activity limitations in children and adolescents with cerebral palsy. Dev Med Child Neurol. 2008;50:152–156.
51. Damiano D, Moreau N. Muscle thickness reflects activity in CP but how well does it represent strength? Dev Med Child Neurol. 2008;50:88.
52. Lieber R, Runesson E, Einarsson F, et al. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle Nerve. 2003;28:464–471.
53. Herbert R. The passive mechanical properties of muscle and their adaptation to altered patterns of use. Aust J Physiother. 1988;34:141–149.
54. Toner L, Cook K, Elder G. Improved ankle function in children with cerebral palsy after computer-assisted motor learning. Dev Med Child Neurol. 1998;40:829–835.
55. Friden J, Lieber R. Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve. 2003;26:157–164.
56. Carey J, Burghardt T. Movement dysfunction following central nervous system lesions: a problem of neurologic or muscular impairment? Phys Ther. 1993;73:538–547.
57. Smeulders M, Kreulen M, Hage J, et al. Overstretching of sarcomeres may not cause cerebral palsy muscle contracture. J Orthop Res. 2004;22:1331–1335.
58. Smeulders M, Kreulen M, Hage J, et al. Spastic muscle properties are affected by length changes of adjacent structures. Muscle Nerve. 2005;32:208–215.
59. De Ste Croix M, Deighan M, Armstrong N. Assessment and interpretation of isokinetic muscle strength during growth and maturation. Sports Med. 2003;33(10):727–743.
60. Jones D, Round J, de Haan A. Skeletal Muscle From Molecules to Movement. London: Churchill Livingstone; 2004.
61. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371–423.
62. Lieber R. Skeletal Muscle Structure, Function, and Plasticity. 2nd ed. Baltimore: Lippincott Williams and Wilkins; 2002.
63. Berry MM, Standring SM, Bannister LM. The nervous system. In: Williams PL, Bannister LH, Berry MM, et al, eds. Gray's Anatomy. 38th ed. London: Churchill Livingstone; 1995:901–1398.
64. Middleton LT. Disorders of the neuromuscular junction. In: Schapira AH, Griggs RC, eds. Muscle Diseases. Boston: Butterworth Heinemann; 1999:251–298.
65. Round J, Jones D. Skeletal muscle physiology and change. In: Isenberg DA, Maddison PJ, Woo P, et al, eds. Oxford Textbook of Rheumatology. Oxford: Oxford University Press; 2004:368–378.
66. Mayston M. Strength-training for children with cerebral palsy. Assoc Paediatr Chartered Physiother. 2003;107:14–18.
67. Fowler E, Kolobe T, Damiano D, et al. Promotion of physical fitness and prevention of secondary conditions for children with cerebral palsy: section on pediatrics research summit proceedings. Phys Ther. 2007;87:1495–1510.
cerebral palsy; muscle hypertonia; muscle weakness/pathophysiology; skeletal muscle fibers/pathophysiology
© 2010 Lippincott Williams & Wilkins, Inc.