Effectiveness of Integrating Botulinum Toxin Type A with Rehabilitative Strategies for Managing Spastic Diplegia in Children: Scope Review

Danilo Donati ^1,2, Giacomo Farì ³, Federica Giorgi ⁴, Vincenza Amoruso ⁵, Valentina Boetto ⁶, Riccardo Marvulli ⁷, Laura Dell’Anna ³, Andrea Bernetti ³, Roberto Tedeschi ^8,*

1. Physical Therapy and Rehabilitation Unit, Policlinico di Modena, 41125 Modena

2. Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy

3. Department of Biological and Environmental Science and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy

4. IRCCS Institute of Neurological Sciences, UOC Child Rehabilitation Medicine, Bologna, Italy

5. UOC Neuroriabilitazione ad Alta Intensità, Fondazione Policlinico Universitario A.Gemelli IRCCS, 00168 Rome, Italy

6. Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

7. Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy

8. Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy

* Correspondence: Roberto Tedeschi

Academic Editor: Luc Jasmin

Special Issue: The New Frontiers of Neurological Rehabilitation: Sport, New Technologies and Advancements in Traditional Therapies

Received: May 31, 2024 | Accepted: October 06, 2024 | Published: October 10, 2024

OBM Neurobiology 2024, Volume 8, Issue 4, doi:10.21926/obm.neurobiol.2404248

Recommended citation: Donati D, Farì G, Giorgi F, Amoruso V, Boetto V, Marvulli R, Dell’Anna L, Bernetti A, Tedeschi R. Effectiveness of Integrating Botulinum Toxin Type A with Rehabilitative Strategies for Managing Spastic Diplegia in Children: Scope Review. OBM Neurobiology 2024; 8(4): 248; doi:10.21926/obm.neurobiol.2404248.

© 2024 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

1. Introduction

Cerebral palsy (CP) is a complex neurological condition affecting approximately 2-3.5 per thousand live births in Western countries. One of the most common clinical variants of CP is spastic diplegia, which primarily manifests as spasticity in the lower limbs, with less severe involvement of the upper limbs [1,2]. Managing spasticity is critical, as this condition significantly impairs mobility and overall quality of life in affected patients [3,4,5,6]. The literature widely recognizes botulinum toxin type A (BONT-A) as one of the most effective treatments for focal spasticity. BONT-A works by temporarily weakening targeted muscles, reducing spasticity, and improving functional outcomes such as gait. However, despite its efficacy in reducing muscle tone, there remains a lack of clarity regarding the optimal rehabilitative strategies to be employed following BONT-A injection [7,8,9]. This gap in knowledge poses a significant challenge for clinicians seeking to maximize the therapeutic benefits of BONT-A treatment. Several studies have explored various post-injection rehabilitation approaches, yet no consensus exists on the most effective methods [4,10,11,12,13]. This uncertainty can lead to inconsistent treatment protocols and potentially suboptimal patient outcomes. The need for a comprehensive synthesis of existing evidence is evident to guide clinical practice and improve patient care [14,15,16,17,18,19]. To address this gap, the present literature review aims to examine and synthesize the scientific evidence regarding rehabilitative strategies following BONT-A injections in children with spastic diplegia. The research involved systematic searches of relevant biomedical databases, using specific keywords to identify pertinent studies. The primary objective of this review is to identify and evaluate the rehabilitative interventions that have proven effective in enhancing outcomes such as spasticity reduction and gait improvement in children with spastic diplegia treated with BONT-A. By critically analyzing the selected studies, this review seeks to provide evidence-based recommendations that can inform clinical practice, ultimately aiming to enhance the quality of life for pediatric patients with this condition. Moreover, the findings may highlight areas where further research is needed, contributing to the ongoing development of best practices in the management of spastic diplegia [14,20].

2. Methods

The present scoping review was conducted following the JBI methodology [21] for scoping reviews. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) [22] Checklist for reporting was used.

2.1 Review Question

We formulated the following research question: "What are the most effective rehabilitative strategies to enhance outcomes such as spasticity reduction and gait improvement in children with spastic diplegia following treatment with botulinum toxin type A (BONT-A)?".

2.2 Eligibility Criteria

Studies were considered for inclusion based on the following criteria related to Population, Concept, and Context (PCC):

2.2.1 Population

Children aged 0-18 years diagnosed with cerebral palsy, specifically those with spastic diplegia who, have undergone treatment with botulinum toxin type A (BONT-A).

2.2.2 Concept

Rehabilitative strategies employed post-BONT-A treatment aimed at improving outcomes such as spasticity reduction and gait enhancement. This includes various physiotherapeutic and adjunctive interventions designed to maximize the benefits of BONT-A.

2.2.3 Context

Clinical settings where children with spastic diplegia receive post-BONT-A rehabilitative care. Studies included must be randomized controlled trials (RCTs), available in English, and accessible through online biomedical databases.

2.3 Exclusion Criteria

Studies that did not align with the defined Population, Concept, and Context (PCC) criteria were excluded from the review. This exclusion applied to research that either did not focus on the specified age group or condition, lacked relevant rehabilitative interventions post-BoNT-A treatment, or failed to assess outcomes in clinical rehabilitation settings.

2.4 Search Strategy

A preliminary search of MEDLINE was carried out using the PubMed platform to locate relevant articles. The search terms and indexing used in the initial articles helped shape a broader search strategy, which was then applied to other databases such as Cochrane Central, Scopus, and PEDro. Additionally, grey literature sources (including Google Scholar and consultations with field experts) and the reference lists of key studies were reviewed. The comprehensive search, conducted on March 23, 2024, did not impose any restrictions on the publication date.

("Diplegic children" AND "Cerebral palsy" AND "Botulinum toxin type A" AND "Spasticity reduction" AND "Rehabilitative strategies" AND "Physical therapy" AND "Functional outcomes" AND "Gait improvement" AND "Randomized controlled trials").

2.5 Study Selection

The process used for study selection in the scoping review followed a systematic and structured method. Initially, search results were compiled and refined using Zotero, eliminating duplicates. The screening process was conducted in two phases: first, by reviewing titles and abstracts and then by assessing the full texts. Two authors independently performed both stages, with any disagreements resolved through consultation with a third reviewer. This procedure adhered strictly to the PRISMA 2020 guidelines to ensure accuracy and transparency. The aim was to identify articles highly relevant to the research question, providing a thorough and systematic review process.

2.6 Data Extraction and Data Synthesis

For this scoping review, data extraction was performed using a customized form based on the JBI tool, designed to capture essential information such as authorship, country and year of publication, study design, patient demographics, interventions, outcomes, procedures, and other key details. Descriptive analyses were then carried out, with numerical data used to illustrate the distribution of studies. The entire review process was carefully documented to ensure transparency, and the extracted data were organized into tables, facilitating easy comparison and interpretation of the core findings across different studies.

3. Results

As presented in the PRISMA 2020 flow diagram (Figure 1), from 60 records identified by the initial literature searches, 45 were excluded, and five articles were included (Table 1). The quality of the studies was assessed using the al PEDro scale (Table 2).

Figure 1 Preferred reporting items for systematic reviews and meta-analyses 2020 (PRISMA) flow diagram.

Table 1 Main characteristics of included studies.

Table 2 PEDro Scale.

The studies included in this review provide compelling evidence of the effectiveness of combining botulinum toxin type A (BONT-A) with various rehabilitative interventions in children with spastic diplegia. The study by Elnaggar et al. [11] demonstrated that integrating reciprocal electrical stimulation (RES) with BONT-A significantly improved the dynamic limits of postural stability and ankle kinematics compared to either treatment alone. Specifically, the group receiving both RES and BONT-A showed substantial enhancements in anterior-posterior (AP-LOS), mediolateral (ML-LOS), and overall limits of stability (O-LOS), as well as in ankle dorsiflexion during the stance phase and swing phase. These improvements suggest that a multimodal approach can better address the neuromuscular limitations contributing to gait abnormalities in children with spastic diplegia.

Dursun et al. [4] investigated the effects of intermittent serial casting combined with standard BONT-A treatment on spastic equinus foot in children with cerebral palsy. The study found that the casting group experienced significant reductions in spasticity as measured by the Modified Ashworth Scale (MAS) and the Tardieu Scale, as well as notable improvements in passive range of motion (PROM). Additionally, the casting group showed significant enhancements in gait function, as evidenced by higher scores on the Observational Gait Scale (OGS) and the Physician Global Assessment (PGA), both at weeks 4 and 12 post-treatment. These findings underscore the added value of serial casting in prolonging and enhancing the therapeutic effects of BONT-A.

Williams et al. [12] explored the impact of combining muscle-strengthening exercises with BONT-A injections on muscle morphology and strength in children with cerebral palsy. Both the PRE and POST BONT-A groups exhibited significant gains in muscle strength, particularly in knee flexors and extensors, and improvements in muscle volume as assessed by MRI. However, the timing of the muscle strengthening relative to the BONT-A injections appeared to influence the outcomes. The PRE BONT-A group showed more pronounced long-term improvements, suggesting that reducing spasticity before initiating a strength training program might optimize muscle performance and functional gains. The Goal Attainment Scaling (GAS) scores indicated significant functional improvements for both groups, highlighting the practical benefits of this combined approach.

In the study by Yigitoglu et al. [13], adding electrical stimulation to BONT-A treatment did not yield statistically significant differences in spasticity reduction, gait function, or muscle spasms compared to BONT-A treatment alone. Both groups showed similar improvements in these areas, indicating that while electrical stimulation may support BONT-A therapy, it might not provide substantial additional benefits in this context. The study did, however, report significant gains in standing and walking abilities as measured by the Gross Motor Function Measure (GMFM-88), reflecting the overall effectiveness of BONT-A in improving functional outcomes.

Lastly, Bottos et al. [10] conducted a study comparing the effects of BONT-A with and without inhibitory casting in children with spastic diplegia and dynamic equinus foot. The casting group demonstrated significant reductions in spasticity and improvements in gait parameters, including walking speed and step length, at the four-month follow-up. These children also performed better standing and walking on the Gross Motor Function Measure (GMFM) compared to those who only received BONT-A. Despite the lack of significant changes in the kinetic and kinematic parameters of the ankle, the study confirmed the added benefits of combining inhibitory casting with BONT-A to enhance functional mobility and reduce muscle spasticity.

Overall, these studies collectively highlight the importance of a comprehensive, multimodal approach in managing spastic diplegia in children. Combining BONT-A with additional rehabilitative strategies such as serial casting, muscle strengthening, and electrical stimulation can significantly improve spasticity, muscle strength, range of motion, and gait function. These findings support integrating rehabilitation plans tailored to the individual needs of pediatric patients with cerebral palsy, aiming to maximize therapeutic outcomes and enhance their quality of life.

4. Discussion

The present review aimed to identify and synthesize the most effective rehabilitative strategies following botulinum toxin type A (BONT-A) injections in children with spastic diplegia, focusing on outcomes such as spasticity reduction and gait improvement. The collective findings from the included studies underscore the significant benefits of integrating BONT-A with various rehabilitative interventions, providing valuable insights for clinical practice [10,13]. The reviewed studies demonstrated that BONT-A injections, when combined with tailored rehabilitative strategies, consistently significantly reduce spasticity and improve gait function across different age groups and therapeutic settings [11,12]. Intensive physical therapy [23,24], serial casting [25], electrical stimulation [26], combined physiotherapy and occupational therapy, and robotic-assisted gait training [27] all showed marked benefits when used in conjunction with BONT-A. An essential aspect of successful rehabilitation protocols in cerebral palsy treatment is promoting motor learning. Utilizing interventions such as electrical stimulation or orthoses without ensuring that motor learning is integrated may limit the effectiveness of these treatments. Motor learning facilitates the long-term retention of motor skills, ensuring that improvements in spasticity and mobility persist. Future rehabilitation protocols should incorporate motor learning principles, emphasizing task-specific, repetitive, and engaging activities that promote neuromuscular adaptation alongside traditional interventions like BONT-A injections and physical therapy [13,28,29]. These interventions significantly enhanced spasticity reduction and gait improvements compared to traditional or placebo-controlled therapies. The consistent improvements observed in spasticity and gait function highlight the importance of an integrated treatment approach [20,30]. Clinicians should consider combining BONT-A with comprehensive rehabilitative strategies tailored to each child's specific needs. Personalized rehabilitation plans that account for individual capabilities and therapeutic goals are crucial for achieving the most significant functional improvements. The findings suggest that early intervention with BONT-A and rehabilitative therapies can be particularly effective. Additional studies have emerged that further support the integration of rehabilitative strategies following Botulinum Toxin A treatment. For example, Lannin et al. [31] demonstrated the importance of early intensive therapy combined with BONT-A in improving motor function in children with cerebral palsy. Similarly, Güç et al. [32] highlighted the benefits of combining electrical stimulation with BONT-A, showing improved outcomes in spasticity reduction and functional mobility. These studies underscore the evolving understanding of how to maximize outcomes post-BONT-A treatment. Early treatment may prevent the progression of spasticity and the development of secondary complications, leading to better long-term outcomes. This emphasizes the need for timely and proactive management of spastic diplegia in children. Interdisciplinary collaboration among physiotherapists, occupational therapists, pediatric neurologists, and other healthcare professionals is essential for effective management. A coordinated approach ensures that all aspects of the child's care are addressed comprehensively, optimizing therapeutic outcomes and enhancing the quality of life for pediatric patients with cerebral palsy. Despite the robust findings, several limitations must be acknowledged [10,11,12,33]. The studies included in this review varied significantly in their rehabilitative approaches, making direct comparisons challenging. This heterogeneity limits the ability to draw definitive conclusions about the superiority of specific interventions. Additionally, some studies had relatively small sample sizes and limited age ranges, which may affect the generalizability of the findings to broader populations. The duration of follow-up varied among studies, with some not extending beyond six months. Longer follow-up periods are necessary to assess the sustained impact of these interventions on spasticity and gait function. Furthermore, the studies employed different outcome measures to evaluate spasticity and gait, complicating cross-study comparisons. Standardized outcome measures would enhance the comparability and reliability of results. The findings of this review have significant implications for clinical practice. The integration of BONT-A with various rehabilitative strategies should be considered a standard approach in managing children with spastic diplegia [10,13]. The consistent evidence supporting improved outcomes through such integrative methods emphasizes the necessity of personalized and early interventions. Tailored rehabilitation plans that address the unique needs of each child can maximize therapeutic benefits, ultimately leading to better functional outcomes and quality of life. Future research should focus on addressing the limitations identified in this review. Larger, multicenter randomized controlled trials (RCTs) with standardized outcome measures and longer follow-up periods are needed to validate the findings and assess the long-term sustainability of treatment benefits. Additionally, studies exploring the cost-effectiveness of different rehabilitative strategies will provide valuable insights into healthcare policy and resource allocation. The potential for improved clinical outcomes through integrating BONT-A with rehabilitative therapies is significant [34,35,36]. As such, healthcare providers should be encouraged to adopt these combined approaches and collaborate across disciplines to ensure comprehensive care. By doing so, the full spectrum of therapeutic benefits can be realized, significantly enhancing the quality of life for children with spastic diplegia. The integration of BONT-A with various rehabilitative strategies significantly enhances spasticity reduction and gait function in children with spastic diplegia. Recent evidence suggests that Omega-3 fatty acids may be important in modulating inflammation and neuropathic pain associated with spasticity. Omega-3 supplementation could help reduce pro-inflammatory cytokine levels, potentially improving functional outcomes in children with spastic diplegia [37]. Another emerging treatment is rhizotomy, a neurosurgical procedure that selectively disrupts nerve roots responsible for spasticity, providing long-term improvements in muscle tone in severe cases. Additionally, pharmacological treatments such as baclofen, diazepam, and tizanidine, used to reduce muscle tone, can be combined with botulinum toxin and rehabilitation to optimize spasticity management [38,39]. However, further research is needed to confirm the long-term benefits of these therapeutic options in combination with post-BONT-A rehabilitative therapy [40,41].

These findings support implementing comprehensive, personalized rehabilitation plans in clinical practice to optimize therapeutic outcomes and improve the quality of life for pediatric patients with cerebral palsy. The evidence underscores the need for interdisciplinary collaboration and early intervention to maximize the benefits of these combined therapeutic approaches. The consistent results across studies highlight the critical role of tailored rehabilitation in achieving substantial improvements in both spasticity and gait functionality, making it an essential component of effective cerebral palsy management.

5. Conclusions

This review demonstrates that integrating botulinum toxin type A (BONT-A) with tailored rehabilitative strategies significantly reduces spasticity and improves gait in children with spastic diplegia. Personalized rehabilitation plans, including intensive physical therapy, serial casting, electrical stimulation, and robotic-assisted gait training, are essential for optimizing outcomes. Early intervention and interdisciplinary collaboration are crucial for maximizing therapeutic benefits. Future research should focus on more extensive trials with standardized measures to validate these approaches further. The findings support comprehensive care strategies to enhance the quality of life for pediatric patients with cerebral palsy.

Author Contributions

Danilo Donati, Roberto Tedeschi: Conceptualization, Methodology, Software, Data curation, Writing-Original draft preparation. Federica Giorgi, Riccardo Marvulli, Laura Dell’Anna: Supervision. Vincenza Amoruso, Valentina Boetto, Andrea Bernetti, Giacomo Farì: Visualization, Investigation, Writing-Reviewing and Editing.

Competing Interests

The authors have declared that no competing interests exist.