Abstract.Background. Modern intensive interventions addressing multiple challenges in children with cerebral palsy are attracting clinicians’ and researchers’ attention. One of such methods is the intensive neurophysiological rehabilitation system (INRS) — a combination of interventions focusing on different functional goals, merged into one intensive course. The purpose of the study was to assess changes in gross motor functions, muscle spasticity and passive range of motion (PROM) in children with spastic forms of cerebral palsy (CP) after the two-week of treatment course with INRS.
Materials and methods. A single-arm, single-blind pre-post study was conducted among 57 children aged 4 to 12 years with spastic CP, admitted for treatment to the tertiary care center. Patients were examined before and after the two-week course using INRS, which included multiple interventions totalling 4–5 hours of treatment daily. The Gross Motor Function Measure-66 (GMFM-66) tasks were video-recorded and evaluated independently by two investigators. The time of recordings (baseline or post-intervention) was masked. PROM in the lower extremity joints was assessed with a manual goniometer, muscle spasticity — with the Modified Ashworth scale. Results. GMFM-66 scores after INRS use increased statistically significantly from 58.8 to 60.2 points, with a mean difference of 1.4 ± 2.9 points. Substantial improvement in PROM was noted for 5 of 7 movements; the most substantial improvement was observed in hip abduction — an average of 8.0 ± 5.8° and foot dorsiflexion— 8.0 ± 6.1°. Reduction of the muscle tone was observed in all measured muscle groups. Statistically significant decrease of spasticity was noted in hip flexors, with an average reduction of 0.25 scale steps (95% confidence interval (CI) = 0.06–0.44), and hip adductors — 0.30 steps (95% CI = 0.08–0.51). Conclusions. Improvements of gross motor functions, an increase of PROM in the lower extremities and reduction of muscle spasticity have been detected after the two-week course with INRS. Intensive treatment using INRS requires further studies, including randomized controlled ones.
Keywords: cerebral palsy; rehabilitation; physical therapy; motor disorders; muscle spasticity

As a consequence of the rapid growth in CP research in the last decade, safer and more effective interventions for children with cerebral palsy have been introduced. At least 64 different interventions for cerebral palsy aimed at differ-ent dysfunctions have been presented and analyzed in the systematic review [4].Particular attention is directed towards intensive treat-ments; they are developing rapidly and are supported by a growing amount of evidence, indicating that therapies of higher intensity are more effective. A Cochrane review on constraint-induced movement therapy indicates that this intensive intervention is more effective for improving uni-manual hand functions than a low-intensity alternative [5]. A quasi-randomized trial of the intensive upper and lower extremity training providing 6.5 intensive intervention hours per day over 13 consecutive days reports significant improve-ment in gross and fine motor functions in children with bi-lateral CP [6]. A large cohort study of 442 Norwegian chil-dren based on the CP register indicates that a more frequent physical therapy is associated with increased gross motor improvement [7].So, the attention of both researchers and clinicians is fo-cused on the exploration of high-intensity and function-ori-ented treatments addressing multiple limitations in children with CP. One of such approaches is an intensive neurophysio-logical rehabilitation system (INRS) — a combination of dif-ferent interventions addressing different functional goals in one intensive course [8]. This treatment system is also known by the name of its author as the Kozyavkin method.The treatment program is tailored individually accor-ding to the patient’s condition and comprises the following components: physical therapy, occupational therapy, full body massage, spinal manipulative therapy, reflexotherapy, strength training, computer game therapy, suit therapy, vi-bration therapy, treadmill training and group session of rhythmic gymnastics. Intensive intervention includes 4–5 hours of daily treatment over two weeks.Recent retrospective analysis of medical records of children undergoing treatment with INRS indicates the improvement of gross motor function, decrease of muscle spasticity, development of fine motor skills and other posi-tive changes achieved in a relatively short period of time [9].The purpose of the study. The present exploratory study was conducted to assess changes in gross motor function in children with spastic forms of cerebral palsy after the two-week treatment with INRS in a single-blind study. A secon-dary purpose of the study was to assess the changes in muscle spasticity and passive range of motion (PROM) in the lower extremity joints.

Participants

All participants were patients of the International Clinic of Rehabilitation. To be eligible for the study, children had to be local residents, 4 to 12 years of age, with spastic bilate-ral cerebral palsy and Gross Motor Function Classification System (GMFCS) levels II–IV.Exclusion criteria were: severe epileptic syndrome, severe mental retardation and inability to understand and comply with instructions, ongoing antispastic medication intake, botox in-jections during the preceding year, and uncooperative behavior.The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The study protocol was reviewed and approved by the commission of ethics of the International Clinic of Rehabilitation (protocol number N-2014-01-20). Participants and their legal representatives re-ceived comprehensive information about the procedures and study design; written informed consent was obtained from le-gal representatives. Where appropriate, based on age and cog-nitive abilities, participants were asked to give verbal assent.Sixty-one patients have been included in the study and underwent baseline assessment. Later, 4 children have been excluded from the study due to the somatic illness develo-ping during the treatment or non-compliance with the study requirements. Hence, the data of 57 children were used.During the study, no complications or side effects have been observed by medical specialists or reported by the pa-tients/parents.Demographic characteristics of the patients are pre-sented in Table 1. The average age of the children was 7.1 years (standard deviation (SD) 2.2), among them, 58 % were males, 46 % patients had GMFCS level III and 49 %— Manual Ability Classification System (MACS) level II.

Gross motor functions

Mean values of the GMFM-66 score with standard de-viation at baseline and post-intervention assessment are summarized in Table 2.Table 2 includes data for the whole group and is also divided by GMFCS level or by age group. An increase of the mean GMFM-66 score by 1.4 ± 2.9 points from 58.8 to 60.2 after the treatment course with INRS was noted for the whole group. Paired sample t-test showed that this change was statistically significant (p < 0.05).
The most substantial improvement was noted in chil-dren with GMFCS level IV, where the score increased by 2.3 ± 2.8 points, from 46.1 to 48.4 (p < 0.05).Splitting the group by age was less informative, since the standard deviation of the GMFM-66 score for age sub-groups was considerably higher. The significant change was noted only in the 7–9-year age group.We have calculated dependence between motor im-provement and age. Fig. 1 presents a scatterplot of the change in GMFM-66 score depending on the age. Each point represents a score change in one child. Line of trend reflects very small negative correlation, Spear-man’s correlation coefficient equals –0.21, indicating that younger children experience a slightly greater motor improvement.

Passive range of motion

The data of PROM in joints are presented in Table 3. Mean values with standard deviation were calculated for baseline and post-intervention measurements for all the joints. Since all the patients had bilateral CP and both extremities were evaluated, the sample size for PROM measurements and spasticity tests included 114 observations.An increase in PROM, ranging from 2 to 8°, was ob-served in all joints. The greatest changes were observed in hip abduction and foot dorsiflexion with extended knee, where PROM increased by 8.0 ± 5.8 and 8.0 ± 6.1°, re-spectively. Also, statistically significant changes were noted in the popliteal angle and foot dorsiflexion with flexed knees. The smallest improvement was observed in knee extension.

Figure 1. Correlation between change in the GMFM-66 score and age

Table 3. Passive range of motion of lower extremity joints: baseline and post-intervention, mean (SD)

Note: * — statistically significant difference (p < 0.05) calculated using paired sample t-test.

Table 4. Muscle spasticity before and after treatment

Notes: IQR — interquartile range; 95% CI — 95% confidence interval; * — statistically significant difference (p < 0.05) calculated using Wilcoxon signed-rank test for related samples.

The primary aim of our study was to evaluate changes in gross motor functions occurring in children with CP af-ter the two-week course of intensive and multicomponent rehabilitation treatment with INRS.Advantages of intensive rehabilitation were reported by different research groups [6, 7, 15, 16]. In the pre-sent study, participants received high-intensity treatment (5 days, 20 hours per week) with a total number of treat-ment modalities used ranging between 10 and 13.The first part of the study was an assessment of gross motor functions with GMFM-66. To reduce possible bias when interpreting the results, a single-blind scoring was used. Video recordings of the patients performing GMFM-66 tasks were scored independently by two trained researchers. The dates of video recordings were removed from the file in advance, so the researchers were unaware of where the recordings had been performed before or after the treatment course.Study results demonstrated a statistically significant increase in the GMFM-66 score by a mean of 1.4 points (p < 0.05).
While answering how clinically those finding are, we should refer to the multicenter study conducted in the Shriners hospital for children [17]. By using a sys-tematic method for establishing the minimum clinically important difference on a sample of 381 children, they concluded that a change of 0.8 points in the GMFM-66 test should be interpreted as a medium-size effect and 1.3 points — as a large effect. So, the mean difference of 1.4 points on GMFM-66 in the whole group can be inter-preted as a large change. The putative mechanisms, which could have caused the medium-size to large effect on gross motor functions, could include neuroplasticity impact, motor learning, and increased strength as a result of in-tensive functional treatment [6, 16].
We observed slightly greater improvements in gross motor skills in younger children compared to older ones.A small negative correlation between the change of the GMFM-66 score and age of the child was noted (Spear-man’s correlation coefficient = –0.21). Similar results have been described by other researcher, indicating a bet-ter response to treatment in younger children with cerebral palsy [18]. These data support the idea of applying early rehabilitation programs for children with CP or at high risk of CP development [19].
The second part of the study was aimed at evaluation of the changes in muscle spasticity and passive range of motion in lower extremity joints. Statistically signifi-cant pre/post difference of PROM was observed in the hip and ankle joints (Table 3). The difference in PROM measurements is associated with statistically significant changes in spasticity, detected in the lower extremity muscle groups (Table 4). As spasticity is a factor that di-rectly affects acquisition of new motor skills, even subtle reduction of spasticity is beneficial for patients with ce-rebral palsy [20].
In this pre/post study, we decided to assess the effect of the intensive multimodal treatment on the Body struc-ture (muscle spasticity, PROM) and Activity (GMFM-66 score) domains of the ICF [3]. We found that more fre-quent rehabilitation with different components is associ-ated with improvement in the aforementioned domains. In future investigations, we will also include the participation domain for a more comprehensive understanding of how INRS affects the key aspects of the quality of life in chil-dren with CP.