Cerebral palsy (CP) is one of the most common developmental disorders in childhood, affecting the entire life cycle. CP children require treatment and management plans according to the developmental tasks they face, throughout their whole life cycle. Spasticity of CP interrupts longitudinal muscle growth, decreases muscle volume, and eventually shortens spastic muscles [1]. Children with bilateral spastic CP frequently have spasticity in the upper extremities. Spasticity and increased muscle tone with associated reactions cause limitation of activity and restrict participation in various activities [2]. All these problems become prominent in school age children, who need more independence in several domains, such as in activities involved in learning and applying knowledge, general tasks, mobility, and self-care.

It was noted that treatment of spasticity is important in the management of CP [3]. Botulinum type A toxin (BoNT-A) injection is a major method of treatment for managing spasticity of the upper extremities. The ultimate aim of the BoNT-A injection in children with CP is to enhance motor learning and achieve a greater functional gain through the reduction of tone in the injected muscles [4]. Studies on the effects of BoNT-A injection on spastic upper limb of CP children used various evaluation tools and reported varying results accordingly [3,5-8].

The purpose of this study was to prospectively investigate the long-term effects of BoNT-A injection on the upper limb function and performance of activities in school age children with spastic bilateral CP, who have limitations in school and home activities, due to spasticity of the upper extremities.

Since botulinum toxin was firstly introduced as a treatment for cerebral palsy in 1993, it has become popular throughout the world as a method of therapy for this disorder [11]. A number of studies reported the effect of BoNT-A injections in cerebral palsy children [3]. Many previous articles reporting the effects of BoNT-A on upper limb function focused on subjects with better gross motor functional level than the subjects in this study, and with a follow-up period of less than 6 months [3,4,12,13]. Only a few studies performed long-term follow-up of more than one year [14]. The literature review for BoNT-A injection on the upper limbs of cerebral palsy patients could not find consistent results about the effect of BoNT-A injections, and found confounding factors [3]. In addition, an optimal age for dynamic motor development when most potential motor skills can be obtained was suggested by some researchers. In this review, preschool children, the age from four to six, was reported to be most suitable for BoNT-A injections if the child had the motivation to use the affected parts in performing activities of daily living (ADL). Another systemic review reported that a combination of BoNT-A and occupational therapy is more effective than occupational therapy alone in reducing impairment, improving the activity level outcomes and attaining goal achievement [15]. The reviewers recommended that BoNT-A should not be used in isolation, but should be combined with a well-organized program of occupational therapy. Recently, a published systemic review and meta-analysis of the therapeutic management of upper limb dysfunction in children with congenital hemiplegia investigated the therapeutic effects of non-surgical intervention in a survey of twelve studies and seven systemic reviews [16]. No one treatment approach seems to be superior over the other; however, injections of BoNT-A provide a supplementary benefit in a variety of upper-limb training approaches, such as constraint-induced movement therapy, hand-arm bimanual intensive training, and neurodevelopment therapy. The analyzed studies in this article showed a wide age range of subjects, from 0 to 19 years old. Those previously published articles regarding the effects of BoNT-A on upper limbs dealt with mostly younger children. No study that investigated solely school aged children has been published and no study focusing on subjects with bilateral spastic cerebral palsy has been reported on.

This study on the effect and duration of BoNT-A for treating the spasticity of the upper limbs restricted subjects to only those with bilateral spastic cerebral palsy and older school age children because the hemiplegic group and preschool age children have been previously investigated in many articles [3,17]. The mean age of our subjects in this study was 11.4 years, and ages ranged from 8.7 to 15.6 years old. This study indicates that school age children and teenagers could also benefit from BoNT-A injections, with improvement in the domains of upper limb functioning and performance of tasks as well as actions. In addition, it was encouraging that the effects of injection lasted throughout the one-year follow-up.

Many current articles about school age children and teenagers with CP reported that gross motor development regressed in these people. The study in 2009 about the natural history of gross motor development in CP noted that children with CP, who were categorized into GMFCS III, IV, and V, have a peak of function around 6-8 years of age and prominent regression of motor function follows after that time [18]. Also gross motor skills can get worse due to muscle contracture when children with bilateral spastic CP enter school, because they usually experience rapid growth during this time, and besides, they usually sit on a chair for long periods of time once they enter school [19]. In this study, thirteen out of fifteen subjects belonged to GMFCS IV and V, which they attained at the age of gross motor regression.

Students with limited movement skills might experience serious deterioration in their quality of life, and as a result, the performance capability of their upper limbs in doing ADLs is very important in determining their quality of life. Therefore, helping these children to develop skills in ADLs (getting dressed, self-toileting, and feeding), and in recreational activities and educational activities is extremely important in school age children and adolescents [20].

It was pointed out that fine motor functions, including upper-limb speed, dexterity and visual-motor control, were the most important factors associated with health-related quality-of-life (QOL) in ambulatory subjects with cerebral palsy [21]. Considering all these aspects, when school age children with bilateral spastic CP experience deterioration of ambulation and function, due to progressed deformity of the lower limbs, their upper limb function for ADLs performance is significant for QOLs assessment. Thus, the effectiveness of BoNT-A treatment that was seen, including advancement of upper limb function in the school age children, is presumed to be meaningful. However, BoNT-A injections for spasticity have not generally been used as a therapy for CP in school age children. Since school age children and teenagers have a strong desire and requirement for adequate upper limb functioning, as this can influence their QOL, it is reasonable to attempt to improve upper limb functioning and prevent fixed contractures in school age children with more aggressive management, such as the use of BoNT-A injections.

In this study, the subjects actively participated in the rehabilitation treatment. First of all, during an interview for COPM, the subjects selected the activities they wanted to perform as part of the treatment evaluation, and they were expected to perform the task, to set performance goals and find their limitations while pursuing the ADL. The subjects chose the items of dressing, eating using tools without spilling, using a computer mouse, fast writing in tiny letters, bimanual activities in the restroom and pushing wheelchairs, measuring the importance score of these items, with a mean score of 8.3 out of 10. Along these lines, the school age children showed they had a strong desire for executing ADLs; therefore, improvement in upper limb functioning and in the performance of skills involved in the ADLs is imperative.

The change of spasticity and improvement in performance in this study showed different patterns during the one-year follow-up after the BoNT-A injection. The degree of spasticity, which was evaluated by a Modified Ashworth Scale and Modified Tardieu Scale, was the lowest at two weeks after the injection, and spasticity gradually increased from 3 months after the injection. Meanwhile, performance of activities, which was evaluated by QUEST and COPM, improved the most at 3 months, and not two weeks after the injection. The explanation for this could be that the reduced spasticity enabled patients to experience and practice good mobility, inducing a learning effect in these subjects, which was manifested as enhanced performance at the 3 months follow-up, although the spasticity had already started to return. The statistically significant changes of QUEST and COPM compared to the baseline were maintained until 12 months, although the improvement diminished at 9 months after the injection. The motor age of TVMS-R, however, showed a gradual improvement at nine and 12 months. This tendency reflects the characteristics of this test tool. QUEST evaluates both quantitative and qualitative aspects of the upper limbs, but is more focused on the performance components of tasks, such as dissociated movement, excepting grasp, rather than the task performance itself. TVMS-R, however, directly evaluates the motor skills that could be considered as a performance area of school age children. When the spasticity was significantly reduced after BoNT-A injection, the performance components of QUEST, such as dissociated movement or weight bearing, might have improved with the ability of the children to produce more smooth movements, but these improvements were evaluated as reduced from 9 months when the spasticity returned. COPM evaluates the performance area, which is scored by the subjects (or guardians) themselves. The performance score and satisfaction score in COPM were reduced again after 9 months, and the reduction of the performance score from the peak point was less than the reduction in the satisfaction score. It is possible that patients, who had already experienced reduced spasticity after the injection, might have felt more dissatisfied by the time the spasticity returned, even though their actual performance had not decreased much. Although muscle spasticity began to return after 3 months, children who had experienced a better performance pattern when the spasticity declined, gained gradual performance enhancement by repeatedly practicing their writing, which is a repetitive task in school, leading to a better outcome on TVMS-R at a later time. The results suggest that the reduced spasticity attained with BoNT treatment combined with continuous upper limb use in performing ADLs and school activity, might lead to continuously improved actual performance. A raw score of performance skills was converted into a motor age of TVMS-R. The motor age of TVMS-R was not adjusted for chronological age, and the learning effects of repetitive tests were not clearly manifested. The mean chronological age was 11.4 years old and the motor age was 53.33 months on average before injection. At 12 months after the injection, motor age progressed to 64.67 months. The progression was expected from the effects of the treatment because the motor age was considerably delayed before treatment, and the advancement was remarkable during the one year of the study; thus, the advancement cannot be due to chronological aging.

The results showed that despite the different patterns of improvement as shown by the assessment tools, there was decreased spasticity below the elbow joint, and the functional progression showed statistical significance compared to the baseline until 12 months later, in spite of the functional progression dwindling after the return of spasticity.

Previously, the optimal age expected for maximal effectiveness of BoNT-A treatment was younger than the age of the present subjects or was preschool age. Moreover, this study concludes that school age children and teenagers will benefit from the injections and show satisfaction with the treatment because they have a strong desire and requirement for improved upper limb functioning. Furthermore, the frequent use of their upper limbs in performing ADLs and school activities brings about repetitious training of their muscles and enhanced learning. Therefore, more active treatment with BoNT-A is considered to contribute to the improvement of QOLs in ADLs, school and social activities by advancing upper limb function in school age children.

This study has several limitations: small sample size, lack of controls, and exclusion of the measurement of spasticity in the adductor pollicis. Another limitation is that the effect of occupational therapy was not eliminated by a control study. More randomized control studies on the effects of repeated BoNT injections on the degree of functional improvement and various combined intensive rehabilitation therapies are necessary.

In conclusion, botulinum toxin treatment in school age children remained effective after 12 months, causing persistent upper limb performance enhancement, despite a slight return of spasticity. For older school age subjects with bilateral spastic CP, with poor gross motor function, whose upper limb function is crucial for functional requirement and satisfaction, more active treatment of upper limb spasticity is recommended.