Relationship between clinical outcome measurements and muscle thickness in cerebral palsy

Abstract

BACKGROUND:

The World Health Organization (WHO) uses the International Classification of Functioning, Disability, and Health (ICF) model to provide physical therapy diagnoses and interventions. However, the relationship between clinical assessment and imaging remains unclear.

OBJECTIVE:

This study aimed to determine the relationships between body function/structure, activity, and participation outcomes following neurorehabilitation in children with cerebral palsy (CP).

METHODS:

Nineteen children (9 girls mean age 8.8 $\pm$ 1.8 years) with CP participated in this study. Clinical motor function tests included the quality of upper extremity skills test (QUEST), Wolf motor function test (WMFT), Functional Independence Measure for Children (WeeFIM), and the Jebsen-Taylor Hand Function Test (JTHFT). Ultrasound imaging was used to measure muscle thickness, which characterizes the body structure, and activity domain variables.

RESULTS:

The correlations between body structure domain (muscle thickness), activity domain (QUEST, WMFT, WeeFIM) and participants variable (JTHFT) were significant, ranging from $r=-$ 0.484 to 0.893, $P<$ 0.05.

CONCLUSIONS:

These novel findings suggest that muscle thickness ultrasound imaging is closely associated with WMFT, WeeFIM, and QUEST variables. This finding provides important clinical insights when using broad clinical assessment and imaging in children with CP.

1. Introduction

The World health organization (WHO) has developed the international classification of functioning, disability, and health (ICF), which is an important conceptual diagnostic measurement and interventional framework for medical doctors and allied health professions [1, 2]. The ICF provides a theoretical basis for developing standardized clinical outcome measurements for the domains of body structure and function, activity, and participation. Recently, the ICF model has been applied to clinical measurements to evaluate the intervention-associated changes in children with cerebral palsy (CP) [1, 3]. The clinical outcome measurements entailed impairment in the body structure (i.e., muscle atrophy, spasticity) and function (muscle imbalance), limitation in activity (reaching, grasping), and restriction in participation (stacking checkers and card turning) domains [3].

CP is a common neuromuscular dysfunction in children that often affects the impairment of body structure (i.e., muscle weakness, muscle contracture) and function (altered motor recruitment, muscle imbalance, spasticity), limitation in activity (reaching, grasping, core instability, and loss of balance), and restriction in participation (inability to participate in age-appropriate play, community-based school competitions) domains [4, 5, 6, 7, 8, 9]. Despite the importance of comprehensive measurement accounting for the three ICF domains, limited studies have attempted to utilize this ICF model. Østensjø and colleagues (2004) examined how body structure/function (spasticity, range of motion deficits, and selective motor control problems) impairments are associated with each other, gross motor function in the gross motor function measure (GMFM), and everyday activities in the pediatric evaluation of disability inventory (PEDI) in children with CP [10].

However, a lack of understanding of outcome variable relationships among ICF domains can make it difficult to use the ICF framework to select the appropriate assessment tool and intervention. For example, on identification of atrophy of the triceps brachialis and extensor carpi radialis muscle atrophy (body structure domain), the extent to which the reaching and grasping abilities (activity) are affected and what might happen to the children’s abilities to participate in age-appropriate games (participation) requiring reaching and grasping function at a school or community are not yet understood. This study aimed to determine the relationships between muscle thickness, activity, and participation outcomes following neurorehabilitation in children with CP. We hypothesized that muscle thickness would positively correlate with the body structure, body activity and participation domain variables in the ICF model for CP.

2. Methods

2.1 Participants

Nineteen children with CP (10 boys, mean age, 8.8 $\pm$ 1.8 years) were recruited from rehabilitation hospitals or community-based pediatric rehabilitation centers. This study conforms to the ethical standards of the Declaration of Helsinki. All the participants were notified of the purpose and experimental procedure of the study, and informed consent was obtained before participation (No. JHIRB-2020-01). The inclusion criteria included (1) children with hemiparetic or quadriplegic CP, (2) age ranging from 6 to 11 years, and (3) ability to follow instructions. The exclusion criteria included (1) history of musculoskeletal impairments, any surgical procedure within the last 6 months, or any medication influencing the experimental test. Table 1 presents the participants’ demographic characteristics.

Table 1

Clinical demographic characteristics of the participants

Variable	Characteristics
Sex (male/female)	10/9
Age (years)	8.8 $\pm$ 1.8
Cerebral palsy type
Hemiplegia	10
Quadriplegia	9
Height (cm)	125.4 $\pm$ 12.1
Weight (kg)	24.2 $\pm$ 7.1

2.2 Procedure

The participants’ parents or caregivers completed a demographic and pre-health questionnaire concerning age, current medication, medical history, and other health issues. A trained physiotherapist at the children’s rehabilitation center consistently performed the tests. All the tests were conducted by the same investigator to improve the internal validity of the measurements.

2.3 ICF body structure domain-based ultrasound muscle thickness

Ultrasound imaging measurements were used to determine the muscle thickness and selective motor control as the structure domain variable measures in the more affected upper limb. Ultrasound sonography (Medison Co. Ltd., Seoul, South Korea) was performed with an 8-MHz linear array transducer to assess the muscle thickness of the triceps brachialis and extensor carpi radialis during maximal voluntary isometric contractions (MVIC) [11]. For extensor carpi radialis imaging, the child was placed in the supine position with the head and neck in a neutral position. The shoulder was abducted to 30 ${}^{\circ }$ and internally rotated with full elbow extension and forearm pronation. The head of the radius was palpated and marked as the reference point. Exploratory scanning was first performed by moving the transducer to align transversally and moved 2 cm distally from the tip of the radial head until the sharpest cross-sectional area of the entire extensor carpi radialis was captured [12]. The cross-sectional area image was acquired during the resting and maximal isometric contraction conditions as the child exerted resistance to wrist extension and radial deviation movement against the therapist. For triceps brachialis scanning, the child was placed in the prone position with the head positioned on the testing side and the elbow flexed and abducted to 90 ${}^{\circ }$ hanging over the side of the bed. First, the olecranon process was identified, and the probe was moved in a transverse and cephalic manner 10 cm from that point to capture the largest cross-sectional area of the entire triceps brachialis [12]. The cross-sectional area image was acquired during the resting and maximal isometric contraction conditions as the child exerted resistance to the therapist’s elbow extension movement. Although the cross-sectional areas of the bilateral triceps brachialis and extensor carpi radialis were acquired, only the cross-sectional area data recorded from the more affected side were used for further analysis. The MVIC of each muscle was consistently measured and monitored using a dynamometer to avoid any testing variability associated with the three repeated measurements.

2.4 ICF activity domain-based clinical motor function tests

The clinical motor and activity function tests included the quality of upper extremity skills test (QUEST) and Functional Independence Measure for Children (WeeFIM). QUEST is a criterion-referenced measurement tool for motor behaviors of the upper extremity. It examines the quality of upper extremity fine motor behaviors in four domains: dissociated movement (19 items with one level), grasp (six items), weight bearing, and protective extension [13]. The response criteria included “yes (2 points),” “no (1 point),” or “not tested (1 point).” The range of the initial grading scores was 50–100 and was standardized to range from zero (or below zero in the grasp section) to 100 using the formula while factoring for the not-tested items. The total test score was computed as the sum of all the domain scores divided by the number of tested domains.

The Wolf motor function test (WMFT) quantifies upper extremity motor ability through timed and functional tasks [14]. The WMFT consisted of 21 items. The first 6 items involve timed functional tasks, items 7 and 14 are measures of strength, and the remaining 9 items consist of analyzing movement quality when completing various tasks [15]. The examiner should test the less affected upper extremity followed by the most affected side. The following items should be performed as quickly as possible, truncated at 120 seconds. The reliability of the WMFT was $r=$ 0.95 [16].

The WeeFIM is a criterion measure designed to assess the performance in functional skills [17]. The six WeeFIM subscales, comprising self-care, sphincter control, transfers, locomotion, communication, and social cognition, were scored on a 7-point scale. The WeeFIM instrument consists of six subsets with a total of 18 measurement items. The subsets were categorized as self-care (six items), sphincter control (two items), transfers (three items), locomotion (two items), communication (two items), and social cognition (three items). Each measurement item of the subsets is scored on a scale of 1–7, where 1 indicates total assistance and 7 indicates complete independence. The score ranges from 18 (total dependence) to 126 (independence) [18].

2.5 ICF participation domain-based clinical motor function tests

The Jebsen-Taylor Hand Function Test (JTHFT) is a referenced measure and designed to examine the hand function associated with activities of daily living tasks and amount of time spent to complete each test item [19]. It contains seven timed subtests: writing, card turning, picking up small items, simulated feeding, stacking checkers, and picking up light and heavy cans [20]. Time data were objectively measured using a stopwatch. The score ranges from 0 (total dependence) to 105 (independence) [20]. The validity of the JTHFT was $r=$ 0.60 to 0.99 and validity was $r=-$ 0.64 to $-$ 0.69 [21].

2.6 Statistical analysis

Statistical data are expressed as mean and standard deviation. We used the G-Power software (G-Power version 3.1.5) to assess the sample size based on our previous pilot study which yielded 19 participants, computing from the effect size (Eta squared, ${\eta }^2=$ 0.6) and power ( $1-\beta =$ 0.8) for muscle thickness. The statistical tests included the parametric Pearson correlation coefficient in determining multiple relationships between the body structure/function domain, the body activity domain, and participants’ domain variables. SPSS for Windows (version 26.0; IBM Corp., Armonk, NY, USA) was used, with the significance level set at $\alpha =$ 0.05.

3. Results

3.1 Relationship between muscle thickness and activity

Pearson’s correlation analysis showed a moderate relationship ( $r=$ 0.667, $P<$ 0.05) between triceps brachii muscle thickness and WeeFIM, supporting that body structure was associated with the activity domain. The other variables were not correlated (Table 2).

Table 2

Relationship among body structure, activity, and participation

		JTHFT AS		JTHFT LS		QUEST		WeeFIM		WMFT AS (average)		WMFT LS (average)		WMFT AS (second)		WMFT LS (second)
Participation	JTHFT AS	–		0	.341	$-$ 0	.315	$-$ 0	.485 ${}^{*}$	$-$ 0	.638 ${}^{**}$	$-$ 0	.378	0	.893 ${}^{**}$	0	.542 ${}^{*}$
	JTHFT LS	0	.341	–		$-$ 0	.024	$-$ 0	.098	$-$ 0	.311	$-$ 0	.702 ${}^{**}$	0	.359	0	.776 ${}^{**}$
Activity	QUEST	$-$ 0	.315	$-$ 0	.024	–		0	.820 ${}^{**}$	0	.182	$-$ 0	.125	$-$ 0	.118	0	.015
	WeeFIM	$-$ 0	.485 ${}^{*}$	$-$ 0	.098	0	.820 ${}^{**}$	–		0	.151	$-$ 0	.031	$-$ 0	.258	$-$ 0	.104
	WMFT AS
(average)	$-$ 0	.638 ${}^{**}$	$-$ 0	.311	0	.182	0	.151	–		0	.736 ${}^{**}$	$-$ 0	.822 ${}^{**}$	$-$ 0	.662 ${}^{**}$
	WMFT LS
(average)	$-$ 0	.378	$-$ 0	.702 ${}^{**}$	$-$ 0	.125	$-$ 0	.031	0	.736 ${}^{**}$	–		$-$ 0	.597 ${}^{**}$	$-$ 0	.866 ${}^{**}$
	WMFT AS
(second)	0	.893 ${}^{**}$	0	.359	$-$ 0	.118	$-$ 0	.258	$-$ 0	.822 ${}^{**}$	$-$ 0	.597 ${}^{**}$	–		0	.711 ${}^{**}$
	WMFT LS
(second)	0	.542 ${}^{*}$	0	.776 ${}^{**}$	0	.015	$-$ 0	.104	$-$ 0	.662 ${}^{**}$	$-$ 0	.866 ${}^{**}$	0	.711 ${}^{**}$	–
Body structure	US TB AS Rest	$-$ 0	.484 ${}^{*}$	$-$ 0	.364	$-$ 0	.024	0	.299	0	.017	0	.082	$-$ 0	.291	$-$ 0	.282
	US TB AS Max	$-$ 0	.591 ${}^{**}$	$-$ 0	.316	$-$ 0	.182	0	.095	0	.016	0	.058	$-$ 0	.409	$-$ 0	.274
	US ECR AS Rest	$-$ 0	.017	$-$ 0	.145	$-$ 0	.066	$-$ 0	.158	$-$ 0	.168	$-$ 0	.102	0	.108	0	.145
	US ECR AS Max	$-$ 0	.490 ${}^{*}$	$-$ 0	.112	0	.264	0	.218	0	.091	$-$ 0	.055	$-$ 0	.317	0	.013
	US TB LS Rest	$-$ 0	.308	$-$ 0	.254	0	.312	0	.667 ${}^{**}$	$-$ 0	.168	$-$ 0	.084	$-$ 0	.051	$-$ 0	.150
	US TB LS Max	$-$ 0	.379	$-$ 0	.223	0	.062	0	.284	$-$ 0	.206	$-$ 0	.147	$-$ 0	.104	$-$ 0	.117
	US ECR LS Rest	$-$ 0	.094	$-$ 0	.328	0	.011	0	.169	$-$ 0	.150	0	.082	$-$ 0	.076	$-$ 0	.198
	US ECR LS Max	$-$ 0	.180	$-$ 0	.418	$-$ 0	.111	0	.178	$-$ 0	.177	0	.156	$-$ 0	.204	$-$ 0	.368

JTHFT, Jebsen-Taylor hand function test; QUEST, Quality of upper extremity skills test; WMFT, Wolf motor function test; AS, Affected side; LS, Less-affected side; US, Ultrasound, TB; Triceps brachii, ECR, Extensor carpi radials, ${}^{**}P<$ 0.05.

3.2 Relationship between muscle thickness and participation variables

Pearson’s correlation analysis showed moderate correlations between the JTHFT and ultrasound triceps brachii-affected side rest ( $r=-$ 0.484, $P<$ 0.05), between the JTHFT-affected side and ultrasound triceps brachii-affected side max ( $r=-$ 0.591, $P<$ 0.01), and between the JTHFT-affected side and ultrasound extensor carpi radialis-affected side max ( $r=-$ 0.490, $P<$ 0.05). However, the other variables were not correlated (Table 2).

3.3 Relationship between activity and participation variables

Spearman’s rank order analysis revealed a strong relationship between the WMFT side (sec) and JTHFT-affected side ( $r=$ 0.893, $P<$ 0.01). A strong relationship was observed between WMFT-affected side (ave) and JTHFT-affected side ( $r=-$ 0.638, $P<$ 0.01). A moderate relationship was noted between QUEST and WeeFIM, which was weak on the JTHFT-affected side ( $r=-$ 0.338, $P<$ 0.01) (Table 2).

4. Discussion

The present study assessed the relationship between ultrasound imaging and clinical outcome measures using the ICF classification model. Most importantly, our results demonstrated the multidimensional ability to include control of what the outcome variables in treatment at different levels of body function and structure, activities, and participation domain variables in children with CP. As a hypothesis, the Pearson correlation coefficient or Spearman’s rank-order analysis indicated an interactive relationship between muscle thickness structure domain, activity domain, and participation variables.

Impaired voluntary motor control occurs when abnormal synergies disturb isolated functional hand movements, resulting in an impaired handgrip, grasping, and reaching [22, 23]. Elder and colleagues (2003) reported on the muscle cross-sectional area, muscle volume, and specific tension of flexion and extension using magnetic resonance imaging (MRI) in 14 patients with CP [24]. They demonstrated muscle weakness from decreased muscle cross-sectional areas and an inability to produce torque levels commensurate with the muscle cross-sectional areas. Muscle morphology may be related to muscle strength and activity [24]. Our study demonstrated that ultrasound is another useful device for muscle imaging and measurement of muscle thickness in individuals with CP.

The current finding revealed a very strong relationship between WMFT affected side and JTHFT affected side ( $r=$ 0.893, $P<$ 0.01). A previous study reported that Pearson’s correlation also showed statistically significant results, associating the JTHFT with the WMFT while demonstrating good validity of the test for the dominant hand. Previously demonstrated correlations with the WMFT were positive mainly for the items related to the arm and hand, which was expected as the WMFT assesses the arm and hand [25].

Despite moderate-to-strong pairwise relationships for several body structures and activity/participation measures at baseline, the strength of change score relationships were typically no more than fair. Similarly, while activity and participation baseline relationships were strong, this was not evident in the corresponding change-score relationships.

Wright et al. also reported a mild correlation ( $r<$ 0.40) between the measures of body functions and structures (spasticity and time walk), activity (gross motor function measure and pediatric evaluation of disability inventory), and participation (pediatric outcome data collection instrument) [26]. The possible rationale for such improvement is that CP causes impairments in various body systems, including the nervous, respiratory, cardiovascular, and musculoskeletal systems [27]. The primary limiting factor in children with CP is the absence of coordination of muscular activity, characterized by reduced motor unit recruitment and firing rates as well as the co-contraction of agonistic and antagonistic muscles around the joint movement. An increased motor neuron excitability in spastic hypertonia results from changes in muscle mechanical properties and impaired inhibitory modulation of reflex activity, which increases the responsiveness of muscle receptors to passive stretching [28, 29].

Most studies on ultrasound have focused on a single muscle in CP [30, 31, 32]. Our findings emphasize the importance of measuring multidimensional assessments in children with CP. Not all the items were associated with the hypothesized underlying dimensions. Despite a moderate-to-strong relationship between body function/structure and participation and activity and participation, the relationship between body function/structure and activity was no greater than moderate, except for the Wolf-affected side and triceps brachii less-affected side rest. The strengths of our study include the control data provided by the upper extremities and the use of the JTHFT as a validated measure of hand motor function in children with CP.

However, the main limitation of this study was a lack of standardized treatment before the assessment and the use of a single time point for the assessment of JTHFT. In addition, the JTHFT test measures the time required to complete tasks during the forced unilateral use of the hand. Children with CP use their more affected hand as the other hand. Further investigation should include an assessment of changes in the motor and sensory functions after surgical and nonsurgical interventions. Additionally, the lack of a follow-up evaluation can have important effects on the sustainable relationship in patients with CP.

5. Conclusion

The present study demonstrated relationships between body structure and activity (triceps brachii muscle thickness and WeeFIM), muscle thickness and participation variables (JTHFT and ultrasound triceps brachii affected side), and activity and participation variables (WMFT affected side [sec] and JTHFT-affected side). The results showed strong relationships between WMFT affected side (sec) and JTHFT affected side and between WMFT affected side (ave) and JTHFT affected side. However, the structure domains and participation variables (JTHFT-affected side and ultrasound extensor carpi radialis-affected side max) were not associated with each other. Our findings provide essential insights for the development of a comprehensive clinical and imaging assessment tool that will successfully address the clinically based model.

Author contributions

CONCEPTION: Chanhee Park.

PERFORMANCE OF WORK: Wonjun Oh and Chanhee Park.

INTERPRETATION OR ANALYSIS OF DATA: Wonjun Oh and Chanhee Park.

PREPARATION OF THE MANUSCRIPT: Wonjun Oh and Chanhee Park.

REVISION FOR IMPORTANT INTELLECTUAL CONTENT: Wonjun Oh and Chanhee Park.

SUPERVISION: Chanhee Park.

Ethical considerations

This study conforms to the ethical standards of the Declaration of Helsinki. All the participants were notified of the purpose and experimental procedure of the study, and informed consent was obtained before participation (No. JHIRB-2020-01).

Funding

The authors report no funding.