Gross muscle morphology and structure in spastic cerebral palsy: a systematic review

Authors


Professor Rod Barrett at School of Physiotherapy and Exercise Science, Griffith University Gold Coast Campus, Queensland 4222, Australia. E-mail: r.barrett@griffith.edu.au

Abstract

Aim  This systematic review and critical evaluation of the literature was conducted to determine how gross muscle morphology and structure are altered in individuals with spastic cerebral palsy (CP).

Method  Electronic databases were searched for articles describing studies of muscle morphological and structural properties in individuals with spastic CP. Data describing muscle fascicle length, belly length, fascicle angle, cross-sectional area, volume, and thickness were extracted and effect sizes were computed for comparisons between individuals with spastic CP and typically developed individuals, between the paretic and non-paretic side in individuals with hemiplegia for all muscles examined, and across the full spectrum of gross motor function in individuals with spastic CP.

Results  The final yield consisted of 15 articles that met the inclusion criteria. The main finding of the review was the consistent evidence for reduced muscle belly length, muscle volume, cross-sectional area, and muscle thickness in the comparisons between paretic and typically developed muscle and the paretic and non-paretic muscle across a range of muscles.

Interpretation  Given the importance of muscle morphology and structure for generating muscle force, it is likely that the observed alterations that occur secondary to the neural lesion in individuals with spastic CP contribute to muscle weakness and the attendant loss of motor function in spastic CP.

List of Abbreviation
PCSA

Physiological cross-sectional area

What this paper adds

  • • This paper summarizes the primary muscle morphological and structural changes in spastic CP identified using muscle imaging.
  • • Key methodological issues and clinical implications of findings are discussed.
  • • Recommendations for future research are also presented.

Cerebral palsy (CP) describes a group of permanent motor disorders that are attributed to disturbances that occur in the developing brain.1 Although the perinatal brain lesion is not progressive, it results in secondary muscle pathology. Spasticity, a velocity-dependent resistance to stretch, occurs in the first months of development owing to reduced inhibition of the stretch reflexes.2,3 Muscle contractures, which restrict joint range of motion, develop later in childhood and further compromise function.4 Contractures are commonly assumed by clinicians to be caused by a fixed shortening of muscles; however, this view has not been substantiated in the scientific literature.5 A consistent finding is that muscle strength is severely compromised in individuals with spastic cerebral palsy (CP)6–9 and that muscle weakness contributes to reduced functional capacity in these individuals.10–12

The mechanisms underlying the development and progression of muscle contracture and weakness and corresponding loss of motor function with age in individuals with spastic CP are complex and interrelated,8 but it is clear that a combination of neural and muscular factors are involved. Individuals with spastic CP are less able to activate their muscles maximally 13,14 and use greater amounts of antagonistic muscle activation (co-contraction) than typically developing individuals.7 In addition to neural factors, the ability of a muscle to generate force depends on its morphological and structural properties.15 Muscle force-generating capacity is directly related to the muscle’s physiological cross-sectional area (PCSA), which can be estimated as the ratio of muscle belly volume to fascicle length, and represents the number of muscle fascicles working in parallel. The angle at which the muscle fascicles attach to the aponeurosis, and the line of action of the tendon (termed fascicle and pennation angle respectively), also influence muscle force production by influencing the number of muscle fibres in parallel, and hence the PCSA, but also reduce the transmission of force to the tendon. PCSA is, therefore, often corrected by the cosine of the pennation angle.15 Muscle fascicle length, which represents the number of sarcomeres working in series, is the primary determinant of muscle excursion, with shorter muscle fascicles having a reduced range through which they can develop force and power, a reduced maximum shortening speed, and a reduced length at which they develop passive forces.15 Muscle volume is indicative of overall muscle growth, is reflective of the number of sarcomeres in series and in parallel, and is linearly related to muscle power. Muscle belly length is distinct from muscle fascicle length in pennate muscles, with reduced muscle belly length suggested to be indicative of muscle contracture.16 Tendon length and compliance can also alter the length and velocity of muscle fascicles, and, therefore, change the force-generating capacity of the muscle.17,18 Increased tendon compliance can allow the tendon to contribute more of the mechanical work required for gait;19,20 however, this may also reduce muscle control and power output.21 Another muscle morphological measure that has been reported in the recent literature on spastic CP is muscle thickness, which has been shown to be highly correlated with cross-sectional area,22 and may, therefore, be a surrogate measure of muscle strength changes that can be readily assessed in the clinical environment using ultrasound.23

Two narrative reviews have suggested that certain structural and mechanical properties may be altered in spastic skeletal muscle.5,24 These reviews provided evidence for alterations in fibre size and distribution, proliferation of extracellular material, and altered stiffness in spastic muscle cells and extracellular material, but reported no evidence for fibre length changes resulting from spasticity, based on findings from two studies.25,26 In a narrative review, Shortland12 reported some evidence for reduced muscle volume in individuals with CP compared with individuals with typically developing muscle based on some of their own previously unpublished data and those of Lampe et al.27 However, no review to date has systematically addressed the question of how gross muscle morphological and structural properties such as fascicle length, belly length, fascicle angle, and muscle cross-sectional area, volume and thickness are altered in individuals with CP. Given the recent growth in the literature on the use of imaging approaches such as magnetic resonance imaging (MRI) and ultrasound to assess muscle morphological and structural properties in individuals with spastic CP, and the potential implications of these findings for designing efficacious interventions to maximize muscle function in individuals with spastic CP, the purpose of this study was to conduct a systematic review and critical evaluation of the literature to determine how gross muscle morphology and structure are altered in individuals with spastic CP.

Method

Search strategy

Electronic research database searches for articles on muscle morphological and structural properties in spastic CP were performed by one reviewer (RB) during October 2009 using CINAHL (from 1981), Cochrane library (from 1800), Inspec (from 1969), MEDLINE (from 1950), PsycInfo (from 1806), PubMed (from 1950), and Web of Science (from 1982). Keywords were grouped and searched in the title, abstract, and keyword fields using the conjunction ‘or’. A typical search string was as follows: (cerebral palsy AND muscle*) AND (morpholog* OR architectur* OR structur* OR fascicle OR tendon OR belly OR thickness OR volume OR weakness) NOT (botul* OR baclofen).

Review process

Articles identified in each database search were downloaded into individual Endnote (version 10; Thomson Reuters, Carlsbad, CA, USA) files. Individual files were subsequently combined into a single file and duplicate records removed. The title and abstract of each record were evaluated for inclusion. In cases in which insufficient information was available in the title and abstract, the full text was inspected. Data extraction was performed by two reviewers, and any discrepancies were resolved through a third independent reviewer where required. Articles were included in the final yield if they met the criteria outlined in Table I. For simplicity and consistency with previous literature, the term non-paretic was used to define the less affected side in individuals with hemiplegia.

Table I.   Inclusion criteria
  1. GMFCS, Gross Motor Function Classification System.

Participants
Spastic cerebral palsy
 Any diagnosis
 Any level of motor function
Outcome measures
Gross muscle morphological and architectural properties (any muscle)
 Muscle fascicle length
 Muscle belly length
 Muscle fascicle angle
 Muscle cross-sectional area
 Muscle volume
 Muscle thickness
 Tendon mechanical properties (e.g. slack length and compliance)
Comparisons
 Paretic vs typically developed
 Non-paretic vs typically developed
 Paretic vs non-paretic in individuals with hemiplegia
 High vs lower motor function (e.g. by GMFCS level)
Articles
 English
 Full journal papers

Quality assessment

The methodological quality of each article was evaluated using an assessment tool developed by Galna et al.28 (Table SI, published online only). The tool consisted of 14 questions that addressed issues of internal validity, external validity, and the ability for the methods to be replicated. Questions 2 and 5 were customized to include factors with the potential to bias results that were of relevance of the present study. Each question was scored out of 1, with scores of 0 and 1 indicating relatively low and high quality respectively. Each article was independently assessed by two reviewers, and any discrepancies in scores were resolved via consensus meetings.

Data extraction and analysis

Sample sizes, participant characteristics, and details of the experimental protocol were extracted for each study. This included information concerning diagnosis (e.g. hemiplegia, diplegia), gross motor function (e.g. Gross Motor Function Classification System [GMFCS] level or Gross Motor Function Measure [GMFM] score), degree of spasticity (e.g. modified Ashworth scale), degree of contracture, previous treatment (e.g. botulinum toxin injections, orthopaedic surgery, and immobilization), and the measurement approach employed (e.g. ultrasound, MRI).

To compare results from different studies, means and standard deviations for each outcome measure were extracted and used to calculate standardized effect sizes (Cohen’s d) and their corresponding 95% confidence intervals. These data were then presented as forest plots to facilitate visual comparison of findings from different studies. Bolded error bars on the forest plots were used to indicate a statistically significant finding as reported in the original article. If the data required to calculate effect sizes were not available in the original article, the author(s) were contacted and asked to provide the required information or the data were digitized from figures in the original article.

Results

Yield

The search resulted in an initial yield of 266 unique articles, which was subsequently refined to 15 articles that met the inclusion criteria. Of the 15 articles included in the final yield, six assessed muscle fascicle length,26,29–33 four assessed muscle belly length,29,34–36 five assessed muscle fascicle angle,26,29,30,32,33 three assessed muscle cross-sectional area,7,22,32 six assessed muscle volume,7,12,27,29,34,36 and five assessed muscle thickness.22,30,32,37,38 Ten of the final 15 studies compared morphological and mechanical properties between the paretic limb in spastic CP muscle and typically developed muscle,7,12,26,29,31–36 two compared properties between the non-paretic limb in spastic CP and typically developing muscle,7,29 and five compared properties between the paretic and non-paretic side in individuals with hemiplegia.7,22,27,29,30 A further two studies compared muscle thickness across different gross motor function levels.37,38 The study by Ohata et al.37 included participants with a variety of forms of CP, but was retained in the review on the basis that the majority of participants were diagnosed with spastic CP. No study of tendon mechanical properties in individuals with spastic CP was identified.

Participant and study characteristics

With the exception of Shortland12 and Ohata et al.,38 who investigated older participants, participants in the included studies ranged in age from 4 to 15 years, and samples typically consisted of a mix of males and females. Full details of spastic CP diagnosis, gross motor function, previous treatment, and method of measurement for each included study are summarized in Table II. Two of 15 the studies reported participants’ spasticity measures (modified Ashworth scale),22,36 and 8 of 15 studies reported measures of contracture in either their Method or Results section.7,26,29–36

Table II.   Characteristics of included studies
ReferenceSampleSex (M:F)Age (y) range and/or mean (SD)Spastic CP diagnosisMotor functionPrevious treatmentMethod
Previous orthopaedic surgeryBotulinum toxin injections
  1. GMFCS, Gross Motor Function Classification System; MRI, magnetic resonance imaging; SCP, spastic cerebral palsy; TD, typically developing; U, unable to determine; Ultras., ultrasound.

Bandholm et al.229 SCP4:513 (SD 3)8 hemiplegia, 1 diplegiaGMFCS I–IIUUUltras. and MRI
Elder et al.728 SCP15:138.0 (SD 2.2)14 hemiplegiaU>9moNoMRI
14 TD5:98.6 (SD 1.7)14 diplegia
Fry et al.347 SCP6:15.5–10.4, 8.1All diplegiaIndependently ambulant, Gillette Functional Assessment Questionnaire Score=6.9 (range 5–9)NoUUltras.
10 TD4:66–12, 9.4
Fry et al.356 SCP5:15.2–12.1, 8.5All diplegiaUNoUUltras.
8 TD4:45.9–13.5, 10.6
Lampe et al.2716 SCPU16–25All hemiplegiaGMFCS I, GMFM 95–100UUMRI
Malaiya et al.2916 SCP4:124–12, 7.8All hemiplegiaAmbulantNo>6moUltras.
15 TD6:94–13, 9.5
Mohagheghi et al.3018 SCP9:98.6 (SD 3.9)All diplegiaGMFCS II=12, III=1 (5 unknown)NoNoUltras.
50 TD20:309.1 (SD 2.3)
Mohagheghi et al.318 SCP7:110.2 (SD 25.0)All hemiplegia7 participants ambulatory with equinus gait, GMFCS II=7, III=1NoNoUltras.
Moreau et al.3218 SCP9:912.0 (SD 3.2)12 diplegiaGMFCS I=4, II=2, III=9, IV=3No>3moUltras.
12 TD2:1012.3 (SD 3.9)3 triplegia
3 quadriplegia
Oberhofer et al.366 SCP
5 TD
U9.5 (SD 1.9) (Di)4 diplegiaGMFCS I–IINo>6moMRI
9.8 (SD 0.6) (hemi)
10.2 (SD 1.2) (TD)
2 hemiplegia
Ohata et al.3711 moderate CP (7 SCP)6:510.4 (SD 3.6)1 hemiplegia, 5 diplegia, 1 quadriplegiaGMFCS III=4, IV=7UUUltras.
15 severe CP (7 SCP)5:1010.6 (SD 3.1)7 quadriplegiaGMFCS V=15
Ohata et al.3825 SCP16:919–60, 37.8 (SD 10.6)10 diplegiaGMFCS III=5, IV=15, V=5UUUltras.
15 quadriplegia
Shortland1214 SCPU14–22, 17.42 hemiplegiaIndependently ambulantUUMRI
7 diplegia
Shortland et al.339 SCP5:46–15, 10.8 (SD 3.5)All diplegiaIndependently ambulantNoUUltras.
10 TD5:56–11, 8.3 (SD 1.3)
Shortland et al.267 SCP3:46–13, 10.0All diplegiaAmbulantUUUltras.
5 TD3:27–11, 7.8

Quality assessment

The findings from the methodological quality assessment are summarized in Table S. Studies scored on average above 0.7 for all criteria except for participant descriptions of spasticity (0.14) and previous treatment (0.64), explicit statements outlining inclusion and exclusion criteria (0.64), and the reliability and validity of methodology (0.28 and 0.14 respectively). The article by Shortland12 was a review and so was excluded from the quality assessment. No study was excluded from the review on the basis of the findings from the quality assessment.

Additional data

Additional data for effect size calculations of muscle belly length in the paretic and typically developing medial gastrocnemius were provided by Fry et al.34 and were estimated from digitized data from the original articles by Fry et al.,35 Lampe et al.,27 and Shortland12 Belly length effect sizes for Fry et al.35 were obtained from the adjusted means obtained using a general linear model with ankle angle as a covariate. Muscle volume estimates from Lampe et al.27 were reported in their original article as the median with 20th and 80th centiles. The numerator of the estimated effect size was calculated from the difference in median values, and the standard deviations used to compute the denominator were estimated based on the assumption of normality. Independent samples t-tests were used to test the significance of potential differences in muscle volume between the paretic muscles in individuals with spastic CP and typically developed muscles.12 Significance was accepted at p<0.05.

Muscle fascicle length

The findings for comparisons of fascicle length between the paretic side of individuals with spastic CP and their typically developing counterparts are inconsistent (Fig. 1a). Shortland et al.26 reported no differences for the medial gastrocnemius muscle independent of the ankle joint angle (resting or 30° plantarflexion) or whether the data were normalized for leg length. In a subsequent study, this research group also reported no difference in normalized fascicle length of medial gastrocnemius muscle at maximum dorsiflexion.33 Malaiya et al.29 similarly reported no difference in the normalized fascicle length of medial gastrocnemius independent of the ankle angle tested (maximum dorsiflexion and resting angle). However, the absolute fascicle length of medial gastrocnemius was significantly shorter at the resting ankle angle in those with spastic CP. In contrast, Mohagheghi et al.31 reported significantly shorter fascicle lengths for medial gastrocnemius in individuals with spastic CP when reported in absolute terms and when normalized to leg length. Absolute muscle fascicle length was reported by Moreau et al.32 to be significantly reduced in rectus femoris but not vastus lateralis.

Figure 1.

 Forest plot illustrating effect sizes and 95% confidence intervals for (a) muscle fascicle length and (b) muscle fascicle angle. Comparisons are for paretic versus typically developing muscle, non-paretic versus typically developing muscle, and paretic versus non-paretic muscle in individuals with hemiplegia. Numerical values adjacent to the error bar are percentage changes relative to the mean from the right side of the plot. Bolded error bars indicate significant group differences. TD, Typically developing; DF, dorsiflexion; Norm, normal; PF, plantarflexion.

Malaiya et al.29 found no differences in muscle fascicle length in the medial gastrocnemius between the non-paretic side in individuals with spastic CP and typically developing individuals or between the paretic and non-paretic sides in individuals with spastic CP. In contrast, Mohagheghi et al.30 reported that fascicle length was significantly reduced at all three levels of the medial gastrocnemius (proximal, mid, and distal) and at two levels (proximal and mid) of the lateral gastrocnemius on the paretic compared with the non-paretic side in individuals with spastic CP.

Fascicle angle

Comparisons of fascicle angle on the paretic side in individuals with spastic CP and in typically developing individuals have produced somewhat inconsistent findings. Although the effect sizes for these comparisons are all negative (Fig. 1b), the significant reductions in the medial gastrocnemius reported by Malaiya et al.29 and Shortland et al.26 were not evident at the resting ankle joint angle. No significant differences in fascicle angle between paretic and non-paretic sides in individuals with spastic CP or between the non-paretic side and typically developing individuals have been reported.

Muscle belly length

There is consistent evidence that medial gastrocnemius belly length is reduced on the paretic side in individuals with spastic CP compared with their typically developing counterparts in absolute and relative terms at all ankle joint angles (Fig. 2a).29,34,35 Oberhofer et al.36 reported that normalized muscle belly length was reduced in four out of six muscles assessed. With the exception of absolute length at the maximum dorsiflexion angle, Malaiya et al.29 also reported that medial gastrocnemius belly length was significantly reduced both in individuals with spastic CP compared with typically developing individuals and on the paretic compared with the non-paretic side in individuals with spastic CP.

Figure 2.

 Forest plot illustrating effect sizes and 95% confidence intervals for (a) muscle belly length and (b) muscle volume. Comparisons are for paretic versus typically developing muscle, non-paretic versus typically developing muscle, and paretic versus non-paretic muscle in individuals with hemiplegia. Numerical values adjacent to the error bar are percentage changes relative to the mean from the right side of the plot. Bolded error bars indicate significant group differences. TD, typically developing; DF, dorsiflexion; Norm, normal.

Muscle volume

There is consistent evidence that muscle volume is reduced in the paretic leg in individuals with spastic CP relative to typically developing individuals7,12,29,34,36 and in the non-paretic leg in individuals with hemiplegia (Fig. 2b).7,27,29 All effect sizes for these comparisons were negative, and volume reductions ranged from 10% to 58% across the muscle assessed. Statistical analysis was not conducted by Lampe et al.27 for individual muscles; however, muscle volumes on the paretic side were reported by these authors to be reduced to 83% for thigh muscles and to 74% for shank muscles, relative to the non-paretic side. The two studies that compared lower leg muscle volumes on the non-paretic side in individuals with spastic CP and typically developing muscles reported no significant difference.7,29

Muscle cross-sectional area and thickness

Muscle cross-sectional area and thickness tend to be reduced in paretic compared with typically developing and non-paretic muscle (Fig. 3).7,22,30,32 There is also a tendency for muscle thickness to be inversely correlated with GMFCS level, although this was not statistically significant for all muscles.37,38

Figure 3.

 Forest plot illustrating effect sizes and 95% confidence intervals for (a) muscle cross-sectional area and (b) muscle thickness. Comparisons are for paretic versus typically developing muscle and paretic versus non-paretic muscle in individuals with hemiplegia, and between different Gross Motor Function Classification System (GMFCS) levels. Numerical values adjacent to the error bar are percentage changes. Bolded error bars indicate significant group differences. TD, typically developing.

Discussion

This review identified 15 cross-sectional studies that evaluated muscle morphological and structural properties in individuals with spastic CP. A maximum of five studies were identified for each comparison of a given muscle property; comparisons were generally limited to a small number of muscles (most often the gastrocnemius), and studies were typically based on small samples of children across a wide age range. From the available evidence, it is, therefore, difficult to determine the time course of normal muscle development and how this might relate to the increasing muscle weakness and corresponding decline in motor function that occur with ageing in individuals with spastic CP. Irrespective of these limitations, this review was able to draw some preliminary conclusions concerning the consistency and relative clinical importance of the observed differences in gross muscle morphology and structure reported to date for individuals with spastic CP.

The most notable finding of the review was the consistent evidence for reduced muscle size, as indicated by reduced muscle volume, cross-sectional area, thickness, and belly length, in comparisons of paretic and typically developing muscles and of paretic and non-paretic muscles. Given that PCSA can be computed from the ratio of muscle volume to fascicle length, and that the differences in muscle volume tended to be more pronounced than the differences observed in muscle fascicle lengths, it seems reasonable to suggest that reduced muscle volume is a major determinant of reduced PCSA, and hence the force production capacity of muscle, in individuals with spastic CP. The study by Malaiya et al.29 was the only one included in the review that measured volume and fascicle lengths in the same cohort. These authors reported a 35% decrease in normalized muscle volume but just a 4% decrease in normalized fascicle length at resting joint angle between the paretic and typically developing medial gastrocnemius, which resulted in an estimated difference in PCSA of 32%. Ignoring possible differences in pennation angle, the differences in PCSA were, thus, almost completely explained by differences in muscle volume. It is also of potential functional significance that reduced fascicle length results in a greater PCSA for a given muscle volume, and may, therefore, be an adaptation that allows force production by the available muscle volume to be maximized.

The PCSA in normal muscle is primarily determined by the sum of the cross-sectional areas of all the muscle fibres within the muscle, and so a reduced PCSA in individuals with spastic CP could be explained by a reduced number of fibres and/or a decrease in the average fibre cross-sectional area.29 Unfortunately, only a limited number of muscle cells can be analysed in histological studies, and so it is difficult to know how muscle fibre number influences PCSA in individuals with spastic CP. However, there is evidence to suggest that muscle cells from patients with spasticity are severely atrophic. Spastic muscle fibres have been reported to be, on average, less than one-third the size of normal fibres of upper extremity muscles in patients with wrist flexion contractures.39,40 Indeed, a reduced fibre diameter and corresponding contraction of the aponeurosis to which the muscle fibres attach has been used to explain why gastrocnemius muscle belly length in individuals with spastic CP is typically reduced in the absence of large reductions in muscle fascicle length.26,29 A further finding that distinguishes normal muscle and spastic muscle is the total area of muscle fibre bundles accounted for by muscle fibres, which is only 40% in the latter compared with 95% in the former.40 This finding is explained by a greater proportion of extracellular matrix material in the muscle fibres of individuals with spastic CP40 and is consistent with reports of collagen accumulation and thickened endomysium in the vastus lateralis in individuals with spastic CP, findings that were also shown to be significantly correlated with clinical measures of function.41 Future studies combining histological and morphological measures will be required to identify the exact nature of the relations between muscle fibre number, size, and PCSA in individuals with spastic CP. Of particular relevance to further understanding, the mechanisms that underlie muscle adaptation in spastic CP are the unique transcriptional alterations that have been shown to influence multiple cellular processes associated with muscle function, including myogenesis.42

Although it may be intuitively expected that reduced muscle size in individuals with spastic CP would contribute together with neural factors8 to lower extremity weakness6–9 and reduced functional capacity,10–12 these relations have received scant attention in the literature to date. Only two studies included in the review compared muscle properties across levels of motor function. In these studies, Ohata et al.37,38 demonstrated that muscle thickness, a muscle morphological measure correlated with muscle cross-sectional area,22 is significantly affected by GMFCS level. A small number of studies have also assessed interventions designed to improve function in individuals with spastic CP by altering muscle properties. McNee et al.43 demonstrated that strength training over a 3-month period increased the volume of the gastrocnemius muscle and the maximum number of heel raises that could be performed. Other studies have also reported improvements in strength following resistance training in individuals with spastic CP, but with modest or no measurable changes in function.44 However, the greatest potential benefit of resistance training in individuals with spastic CP may be in sustaining muscular strength above the threshold required for performing functional activities and, thereby, maintaining mobility for a longer time.12,43 Muscle imaging studies also have the potential to contribute new understanding of the effect of pharmacological and surgical treatments on muscle morphology and structure. Concerns have been expressed that botulinum toxin injections and surgery to correct soft-tissue deformities may lead to poor long-term outcomes in individuals with spastic CP.33,45 Indeed, it has been shown that, although gastrocnemius fibre length is reduced,33 muscle volume recovers within a year of corrective surgery.34 Such intervention studies are important because of their potential to lead to more rational treatment paradigms for spastic CP.

With the exception of Moreau et al.,32 who examined rectus femoris and vastus lateralis, studies of fascicle length in individuals with spastic CP to date have been confined to the gastrocnemius muscle.26,29–31,33 The gastrocnemius muscle is an obvious candidate because of its functional significance, and also because it is superficial and has relatively short fascicles that can be tracked using a conventional ultrasound probe. The review identified some limited but inconsistent evidence for a reduction in fascicle angle and length in paretic compared with typically developing gastrocnemius muscle and a reduction in fascicle length in paretic compared with non-paretic gastrocnemius muscle in individuals with hemiplegia. The observed differences in fascicle angle depended on ankle joint angle and have not been ascribed any major functional significance.29,33 The findings for fascicle length are inconsistent because some studies reported no difference in fascicle length in the medial gastrocnemius,26,29,33 whereas others reported a reduction in fascicle length in paretic muscle in individuals with hemiplegia relative to both typically developing muscle and non-paretic muscle.30,31 Although sampling issues have been suggested as a reason for the discrepancy,31 it remains difficult to reconcile these findings at this time. In our view, a proper resolution to the issue of whether muscle fascicles are shortened in individuals with spastic CP will require measurement of muscle fascicle length while controlling for muscle tension. It is currently not feasible to measure muscle tension directly in vivo; instead, this requires attempting to solve the force-sharing problem at the joint(s) involved. Such an approach has been used to assess the passive properties of the gastrocnemius in multiple sclerosis by measuring changes in the passive ankle torque at different knee angles.46,47 Resolution of this issue is important because it could contribute to improved understanding of the mechanism of muscle contracture in individuals with spastic CP with possible implications for treatment.

To further understand the mechanical causes of contracture, it is necessary to examine the resting lengths and stiffness and compliance properties of all the constituent materials of the muscle–tendon unit and the interrelations. Progress in this area has been the subject of previous reviews5,24 and so is not elaborated here. We, instead, offer the following suggestions as potentially fruitful avenues for further investigation of the causes of contracture. These include study of the large intramuscular protein titin, tendon properties such as slack length and compliance, and myofascial force transmission. Titin is the molecular spring that spans the gap between the thick filaments and the z-lines and is an important determinant of muscle fibre extensibility.48 Although not yet investigated in individuals with spastic CP, titin stiffness can be modulated in skeletal muscle in response to changing conditions,49 and could, therefore, be expected to play a role in contracture. No study of tendon mechanical properties in individuals with spastic CP was identified in this review. However, it is notable that the Achilles tendon has been reported to become longer and more compliant in the affected than in the unaffected side in stroke patients with spasticity, which could contribute to shortened fascicle lengths for a given muscle–tendon length.50 It is also possible that myofascial connections between muscle and adjacent structures become stiffer and/or more stretched in individuals with spastic CP.51,52

It is clear from the methodological quality assessment undertaken as part of this review that a variety of confounders have the potential to bias measurement of muscle morphology and structure. There is a high degree of heterogeneity and a multitude of associated secondary impairments and co-morbidities in individuals with spastic CP.32 For example, participant characteristics such as age, sex, anthropometric characteristics, diagnosis, gross motor function, degree of spasticity, and contracture all have the potential to contribute variability to measurements of morphological and structural properties. Similarly, prior treatment including physiotherapy, immobilization (casting, bracing, splinting), orthotics, soft-tissue surgery, neurosurgery, and botulinum toxin injections may alter muscle morphology and structure. Finally, methodological issues related to how data are normalized, how joints are configured for testing, and how muscle activation and/or tension are controlled during measurements, and the level of measurement within the muscle (e.g. proximal, mid, distal portion) have the potential to influence certain specific structural measures. All of these factors warrant careful consideration when designing future studies.

Although MRI is considered to be the criterion standard for measuring muscle volume and length in vivo,53,54 ultrasound, which is more cost-effective and accessible than MRI, may be used for the same purpose.29,34 Ultrasound has also been the preferred modality for making muscle architectural measurements in the spastic CP literature to date,26,29–34 and may also be used to measure certain tendon properties.55 No study included in the present review reported validity of their ultrasound measures, and only three specifically assessed their reliability, which was generally reported to be high.30,32,38 Therefore, on average, studies scored low on this aspect of the methodological quality assessment. Sources of error in ultrasound measurement of muscle morphological and structural properties include image distortion due to tissue compression by the transducer, poor resolution of deep muscles, difficulties in discriminating muscle borders, and segmentation errors during reconstruction of muscle volumes.56 In spite of these issues, a high level of validity and reliability has been reported for in vivo measures, including cross-sectional area of vastus lateralis57 and gastrocnemius muscle belly length, and volume measured using a freehand three-dimensional reconstruction approach in individuals with normal muscle.56 Ultrasound, therefore, appears to be well suited to assessing muscle properties underlying muscle weakness and contracture in spastic CP, as well as associated changes resulting from maturity and treatment interventions in the clinical environment. Ultrasound also offers the potential to study muscle and tendon properties during dynamic tasks, thereby providing insight into how muscles generate power during functional activity.19,20 New methods to characterize muscle architecture and tendon properties using phase-contrast MRI may also be useful for future studies of muscle structure and function in individuals with spastic CP.58

Conclusion

Limited data describing morphological and structural alterations in individuals with spastic CP are currently available. However, with the exception of muscle fascicle length in the gastrocnemius muscle in individuals with spastic CP versus comparison individuals, there was a general consistency of findings across studies indicating that muscle volume, cross-sectional area, thickness, and belly length tend to be reduced in individuals with spastic CP. The findings are of clinical significance because of their theoretical relation to muscle force production capacity and corresponding potential to contribute to muscle weakness and diminished motor function in individuals with spastic CP. In future research involving the use of muscle imaging in individuals with spastic CP, it will be of benefit to (1) describe the normal trajectory of muscle morphological and structural changes that occur during development in individuals with spastic CP; (2) conduct combined morphological–structural and histological investigations to identify relations at a different level of muscle organization; (3) identify the relationship between muscle morphology and structure and muscle weakness, contracture and functional capacity in individuals with spastic CP; and (4) further assess the effect of specific interventions designed to alter muscle properties (e.g. exercise, surgery, immobilization, botulinum toxin injections) on muscle properties and associated functional outcomes in spastic CP.

Ancillary