Predictors of the Effectiveness of Medical Rehabilitation of Patients with Cerebral Palsy

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LIST OF ABBREVIATIONS

VAS — Visual Analog Scale

CI — Confidence Interval

CP — Cerebral Palsy

ICF — International Classification of Functioning, Disability, and Health for Children and Youth with Cerebral Palsy

OR — Odds Ratio

GMFCS ― Global Motor Function Classification System

GMFM-88 ― Gross Motor Function Measure 88

MACS ― Manual Ability Classification System

INTRODUCTION

Cerebral palsy (CP) is one of the most common causes of disability in children. The disease is defined as a group of permanent disorders in the development of movement and posture that result from a nonprogressive damage to the developing brain of the fetus or infant [1, 2]. The prevalence of CP in the Russian Federation corresponds to the global epidemiological situation and ranges, according to different data, from 2.0 to 3.0 cases per 1,000 newborns [3, 4]. In addition to motor disorders, the clinical presentation of CP includes problems with speech, mental retardation, epilepsy, and other abnormalities that limit the vital activity of a little patient [5, 6]. Thus, the rehabilitation of children with CP should include clinical tools that allow the prediction of results [7]. Although the clinical and socioeconomic factors determining the prognosis of rehabilitation and further social adaptation of patients with CP are being actively investigated [8, 9], predictors that help forecast the effectiveness of medical rehabilitation measures have not yet been identified.

This study aimed to determine predictors of the effectiveness of medical rehabilitation in children with CP using data of anamnesis, scales, and questionnaires.

MATERIALS AND METHODS

The prospective study was performed on the base of Clinic of Privolzhsk Research Medical University (PRMU) in 2017–2019 and was approved by the Local Ethic Committee of PRMU (Protocol No. 4 of March 29, 2017).

The study included patients with different forms of CP in accordance with the International Statistical Classification of Diseases and Related Health Problems of the 10th revision (spastic diplegia, G80.1; hemiplegia, G80.2; ataxic CP, G80.4; and mixed form, G80.8). Participants received detailed information about the study and its voluntary character. Informed consent was signed by the parents of children with CP and by a doctor-researcher.

Inclusion criteria: diagnosis of CP and age 4–8 years.

Exclusion criteria: alternative diagnosis associated with disorders in the movement and maintenance of posture, concomitant disease that according to the doctor-researcher might have affected the quality of patient’s life, and a serious mental disorder (e.g., bipolar).

According to the international Global Motor Function Classification System (GMFCS), the level of motor disorders in patients with CP was 1.83 ± 0.50 points. The initial characteristics of the patients are given in Table 1.

Table 1. Initial Clinical and Demographic Data of the Patients (n = 29)

The functioning profile and life limitations of all patients were evaluated before and 12 months after the rehabilitation measures based on the complaints and anamnestic data, results of general somatic and clinical neurologic tests, and use of a short core set of the International Classification of Functioning, Disability, and Health (ICF) for children and youth with CP (Table 2). This short core set is used to evaluate the dynamics of a child’s condition from age 0 to 18 years or for epidemiological research and includes 25 categories [10].

Table 2. Short Core Set of the International Classification of Functioning, Disability, and Health for Children and Adolescents with Cerebral Palsy [10]

Note: * Personal factor (Pf) component has not been assigned the categories of the International Classification of Functioning, Disability, and Health; thus, some examples representing PFs are given

To set the determinants, various graded assessment methods were used, including specialized scales and questionnaires:

• Gross Motor Function Measure 88 (GMFM-88).
• Modified Ashworth Scale.
• Manual Ability Classification System (MACS) for children with CP.
• Visual analog scale (VAS).

To identify anatomic and structural damages to the brain, all patients underwent magnetic resonance brain tomography [3]. Parameters for the assessment of values of different codes are given in Table 3.

Table 3. Parameters for the Assessment of the Domains of the International Classification of Functioning, Disability, and Health in Patients with Cerebral Palsy

Based on the analysis of complaints and anamnestic data and on the results of physical and neuroimaging examinations of the patient, an assessment sheet was filled out where the categories of the ICF Core Sets for children and youth with CP were specified [10–12]. The assessment sheet provided a detailed description of the patient’s functional profile including relevant contextual factors.

The results of medical rehabilitation were characterized using the criterion we have proposed. According to this criterion, an improvement was considered a reduction of the level of determinant to “functions” and “activity and participation” components of ICF classification of at least 1 point in at least in three domains. The sensitivity and specificity of this criterion, according to results of a previous study, were 89% and 91%, respectively [7].

Rehabilitation measures were conducted throughout 1 year in the inpatient, outpatient, and home conditions. In a hospital setting, rehabilitation included mechanotherapy, therapeutic exercise, massage, physiotherapy, reflexology, and pharmacotherapy as needed. Courses (14 days) of inpatient rehabilitation were conducted two times a year. The outpatient rehabilitation supposed 2–3 massage courses of 10-day duration and botulinum therapy. In home conditions, rehabilitation included doing daily physical exercises recommended by the doctor. In addition, consultations were held for the patient’s parents to identify “barrier” environmental factors and modify them into “facilitating” factors, according to the ICF terminology.

Statistical processing of the results was conducted using MedCalc Statistical Software and Microsoft Office Excel (2010). The following statistical methods were used: the Shapiro–Wilk test was used to check the character of the distribution of quantitative parameters. The selected parameters were as follows: Me, median; Q1, lower quartile; Q3, upper quartile; mean, arithmetic mean; SD, standard deviation; n, volume of the analyzed group; and p, significance value of the differences. Statistical comparison of the mean values in the group was performed using parametric and nonparametric statistical methods, namely, Student paired t-test and Wilcoxon test, respectively, for related samples, and Student t-test and Mann–Whitney test, respectively, for unrelated samples. To test the hypothesis of the dependence of qualitative and order characteristics, Pearson χ2 criterion for contingency tables was used. In the case of risk of bias of the results obtained using Pearson χ2 criterion for contingency tables, Fisher’s exact test was used to test the null hypothesis by pairwise comparison of data of the analyzed groups in four-field tables, taking into account Bonferroni correction for multiple comparisons. Parameters with significant difference in the subgroups according to the single-factor analysis were introduced into the logistic regression procedure. To assess the predictive value of a predictor, the sensitivity, specificity, and predictive values of positive and negative results were calculated. To determine the threshold levels of quantitative parameters optimal for predicting a particular outcome of treatment, the receive operating characteristic curve was constructed, demonstrating the dependence of the number of true-positive cases on the number of false-negative cases of classification based on predictors. The threshold value of the quantitative predictor (e.g., result on the GMFM-88 scale) was the one for which the area under the receiver operating characteristic (ROC) curve was the largest, as such a curve corresponds to the optimal combination of sensitivity and specificity of the predictor. The critical value of the significance level was assumed to be 5% (p ≤ 0.05).

RESULTS

Within 12 months after the rehabilitation procedures, an improvement was achieved in 18 patients (62%) with CP (group 1), and 11 patients (38%) had no improvement (group 2). In group 1, there was a decrease in the intensity of pain syndrome, increased joint mobility and control of voluntary movements, and improved maintenance of body position, walking, and precise hand movements. There was also a decrease in spasticity in barriers restricting life activity and an improvement in the quality of life. An improvement in gross motor functions on the GMFM-88 scale (p<0.0001), a decrease in spasticity level on the Ashworth scale (р = 0.0005), an improvement in manual abilities on the MACS scale (р = 0.0078), and a decrease in pain syndrome on VAS (p = 0.0001) were found. In group 2, no significant change in clinical manifestations and no significant change in the parameters on the above scales were noted. The level of motor functions on the GMFCS scale remained the same in patients in both groups.

In Table 4, the number of patients in samples with different extent of severity of disorders in different ICF domains before and after rehabilitation measures is given.

Table 4. Number of Patients with Cerebral Palsy in Groups with Different Degrees of Severity of Disorders Before and After Rehabilitation Measures

Patients with improvement showed significant reduction of the determinant score (according to the criterion we have proposed [7]) in domain b134 “sleep functions” (р = 0.0020), b280 “feeling of pain” (р = 0.0001), b710 “joint mobility functions” (р = 0.0020), b735 “muscle tone functions” (р = 0.0020), b760 “control of voluntary functions” (р = 0.0001), d415 “maintenance of body position” (р = 0.0002), d440 “use of precise hand movements” (р = 0.0078), d450 “walking” (p < 0.0001), d460 “movement in different places” (p < 0.0001), d710 “basic interpersonal relations” (р = 0.0039), d760 “family relations” (р = 0.0313). In patients without improvement, no reliable changes in the determinant levels were observed in any domain.

As possible predictors of the effectiveness of rehabilitation, the results of the assessment on the Ashworth scale, MACS, VAS, and GMFM-88 were considered. Comparison of groups of patients with and without improvement showed that the groups before rehabilitation measures showed significant differences on the GMFCS scale (p = 0.0083), GMFM-88 (p = 0.001), Ashworth scale (p = 0.0001), and VAS (p = 0.0357, Table 5).

Table 5. Parameters of Questionnaires and Scales in Patients with Cerebral Palsy before Rehabilitation Depending on the Results of Subsequent Rehabilitation

Note: * Student’s t-test, ** Mann–Whitney test

Further, the levels of determinants of ICF domains characterizing pain syndrome, motor and coordination function disorders, and interpersonal relations and relations of the child were compared between the groups. Analysis of unrelated samples showed that before rehabilitation measures, patients with improvement have on average more optimal parameters in the following ICF domains: b710 “joint mobility functions” (p < 0.0001), b735 “muscle tone functions” (p < 0.0001), b760 “control of voluntary functions” (p = 0.0014), d415 “maintaining body position” (p = 0.0002), d450 “walking” (p = 0.0001), d460 “movement in different places” (p = 0.0002) and d710 “basic interpersonal relations” (p = 0.0105, Table 6).

Table 6. Level of Determinants of Domains of the International Classification of Functioning, Disability, and Health in Patients with Cerebral Palsy before Rehabilitation, Depending on the Results of Subsequent Rehabilitation

Note: * Mann–Whitney test

Among the anamnestic data, the following parameters were considered possible predictors of the effectiveness of rehabilitation: mother’s and father’s age at the time of pregnancy, sequential number of the mother’s pregnancy, term of delivery, newborn’s weight, child’s gender, Apgar scale score 1 and 5 min after birth, and child’s age at the time he was diagnosed with CP. None of the anamnestic parameters demonstrated a significant difference in the groups of patients with and without improvement and thus cannot be introduced in the binary logistic regression procedure for the determination of the predictive capacity.

The parameters of scales and ICF domains that showed significant differences in groups of patients with and without improvement were introduced in the binary logistic regression procedure to determine predictors of rehabilitation effectiveness with the highest predictive value. Initially, univariate regression analysis was conducted to evaluate the influence of each independent variable on the result. The univariate analysis showed that the more significant predictors of the effectiveness of rehabilitation are GMFM-88 score (р = 0.0127) and the level of determinant in the following ICF domains (Table 7):

• b760 “control of voluntary functions” (р = 0.0050)
• d415 “maintenance of body position” (р = 0.0040)
• d710 “basic interpersonal relations” (р = 0.0266)

Table 7. Predictors of Effectiveness of Rehabilitation in Patients with Cerebral Palsy: Results of the Univariate Logistic Regression

Note: OR, odds ratio; CI, confidence interval

Each model is recognized as adequately describing the influence of predictors on the rehabilitation outcome (improvement or its absence). This is evidenced by a high significance level of the χ2 parameter, which tests the hypothesis of a zero significance of the evaluation of the parameter for predictor (i.e., the hypothesis that the predictor influences the outcome of rehabilitation).

When performing multivariate logistic regression with various models that included several variables (GMFM-88, b760, d415, and d710), no significant predictors were identified. No model has shown that a combination of several variables can be a predictor of a positive outcome of rehabilitation. Thus, each factor can be used as a predictor of the effectiveness of rehabilitation only separately.

The sensitivity and specificity of the threshold value of all predictors of rehabilitation effectiveness were analyzed by constructing a ROC curve. The area under the ROC curve for the GMFM-88 scale was 0.937 (р < 0.001), which corresponds to a high quality of the prognosis (Figure 1). Patients with the GMFM-88 score before rehabilitation procedures > 82.1% have a positive prognosis for rehabilitation. IFC domains b760 “control of voluntary functions” (area below the ROC curve, 0.833; р < 0.001), d415 “maintenance of body position” (area under the ROC curve, 0.896; р < 0.001), and d710 “basic interpersonal relations” (area under the ROC curve, 0.760; р = 0.001) are predictors of the effectiveness of rehabilitation in patients with CP with the determinant level ≤1 (Figues 2–4).

Fig. 1. Receiver operating characteristics curve for the evaluation on the Gross Motor Function Measure 88 scale.

Fig. 2. Receiver operating characteristics curve for the evaluation by domain b760 “control of voluntary movement functions”.

Fig. 3. Receiver operating characteristics curve for the evaluation by domain d415 “maintaining body position”.

Fig. 4. Receiver operating characteristics curve for the evaluation by domain d710 “basic interpersonal relations”.

DISCUSSION

In the given work, clinical and neurologic examination results were evaluated using specialized questionnaires, scales, and ICF core set for children and adolescents with CP, which can predict the effectiveness of medical rehabilitation of children with CP. The significant predictors of the effectiveness of medical rehabilitation of children with CP were GMFM-88 score >82.1% and determinant level ≤1 in the following ICF domains: b760 “control of voluntary functions,” d415 “maintenance of body position,” and d710 “basic interpersonal relations”.

GMFM-88 is used for quantifying gross motor function [13]. This scale was proposed by Dianne Russell (CanChild Center for Childhood Disability Research, McMaster University, Institute of Applied Medical Sciences). GMFM-88 was designed to evaluate the change in the gross motor function over time in children with cortical paralysis. GMFM-88 is characterized by grouping the tasks according to the initial position when performing them: lying on hands and knees, sitting, standing, walking, running, and jumping. Complete GMFM-88 evaluation takes approximately 40 min. For most positions, there are special descriptions for each score. Thus, it is important to use the descriptions given in the manual for GMFM-88 [3].

ICF is used in both scientific research and clinical practice [7, 10]. These aspects are especially important for such a nosological form as CP, as currently numerous treatment methods for this pathology are proposed without sufficient proof of their effectiveness [11]. The efforts of parents, children, and medical personnel are directed to the selection of effective and safe therapeutic interventions [14], and ICF is the tool that helps identify the actual problems of a child with CP and determine aims and objectives of rehabilitation, plan and control treatment, and measure the achieved results [7, 14, 15]. However, certain problems impede the practical application of ICF, such as the bulkiness of this classification (it includes >1,600 categories) [12, 16]. This problem is solved by the use of the condensed classification version with a set of informative signs for a particular disease (so-called core sets or basic sets) [14]. ICF core sets are developed by a group of international experts of the World Health Organization and present a list of categories used as the international standard for the description of functions of particular nosological forms [17]. Consensus on the ICF core sets in the application to CP was achieved not so long ago, and the results of the work of the expert group were published in 2015 [10]. A short core set including 25 categories is convenient either for the evaluation of the dynamics of a child’s condition from 0 to 18 years or for epidemiological research [10, 11]. Detailed instruction on the selection and use of the core set are available in the open press [10].

GMFM-88 and the ICF basic set for children and adolescents are actively used in planning and implementation of medical rehabilitation in patients with CP [7, 10, 18]. These clinical tools are very well known to the doctors, scientists, and other specialists involved in the rehabilitation of children with CP. Knowledge of the threshold values of GMFM-88 and short ICF core set for children and adolescents with CP, which can predict the effectiveness of rehabilitation measures, plays an important role in planning medical rehabilitation and determination of rehabilitation potential of children with CP.

Despite the results obtained, the determination of the predictors of the effectiveness of medical rehabilitation of children with CP remains relevant [19]. Studies involving numerous patients and longer follow-up period are required. In the future, the identification of predictors of the effectiveness of medical rehabilitation will allow to more correctly determine the rehabilitation potential of a patient with CP and select the necessary complex of rehabilitation measures.

CONCLUSION

This study revealed the predictors of rehabilitation effectiveness and their threshold values, which can help in the development of medical rehabilitation programs for patients with CP. Higher parameters of motor and coordination functions and a higher level of interpersonal relationships of patients with CP are significant predictors of the effectiveness of rehabilitation. The results indicate the need to use the ICF and quantitative assessment of the GMFM-88 when planning rehabilitation activities for patients with CP.

ADDITIONAL INFORMATION

Funding. The research was carried out as part of the implementation of the strategic academic leadership program "Priority 2030".

Conflict of interests. The authors declares no conflicts of interests.

Contribution of the authors: G. E. Sheyko ― design of the study, acquisition and processing of the material, statistical processing, writing the text; A. N. Belova ― concept and design of the study, editing. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

Финансирование. Исследование выполнено в рамках реализации программы стратегического академического лидерства «Приоритет–2030».

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов: Шейко Г. Е. ― дизайн исследования, сбор и обработка материала, статистическая обработка, написание текста; Белова А. Н. ― концепция и дизайн исследования, редактирование. Все авторы подтверждают соответствие своего авторства международным критериям ICMJE (все авторы внесли существенный вклад в разработку концепции, проведение исследования и подготовку статьи, прочли и одобрили финальную версию перед публикацией).

About the authors

Gennadiy E. Sheyko

Email: sheikogennadii@yandex.ru
ORCID iD: 0000-0003-0402-7430
SPIN-code: 8575-1319
Scopus Author ID: 57200103738
ResearcherId: T-3280-2020

MD, Cand. Sci. (Med.), PhD, Assistant of the Department of Medical Rehabilitation

Anna N. Belova

Author for correspondence.
Email: anbelova@mail.ru
ORCID iD: 0000-0001-9719-6772
SPIN-code: 3084-3096
Scopus Author ID: 7005138294

MD, Dr. Sci. (Med.), PhD, Professor, Head of the Department of Medical Rehabilitation

References

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2. Fig. 1. Receiver operating characteristics curve for the evaluation on the Gross Motor Function Measure 88 scale.

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3. Fig. 2. Receiver operating characteristics curve for the evaluation by domain b760 “control of voluntary movement functions”.

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4. Fig. 3. Receiver operating characteristics curve for the evaluation by domain d415 “maintaining body position”.

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5. Fig. 4. Receiver operating characteristics curve for the evaluation by domain d710 “basic interpersonal relations”.

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