Cerebral palsy (CP) is one of the most common neurodevelopmental disorders in children and is characterized by permanent motor impairment resulting from nonprogressive injury to the developing brain. Epidemiological studies indicate that the prevalence of CP among children aged 1 to 6 years is approximately 2.46% in China and ranges from 0.14% to 0.32% globally [1]. Spastic CP, the predominant subtype, accounts for nearly 70% of cases [2,3]. It is characterized by hypertonia and hyperreflexia, often leading to abnormal posture and gait patterns, including limb spasticity, flexor dominance, trunk flexion, knee flexion, and scissor gait. These motor impairments frequently persist throughout childhood and may evolve with growth and development, substantially affecting functional independence and quality of life.

The pathophysiology of spastic CP is complex and multifactorial, involving cortical and subcortical injury, impaired neurodevelopment, and secondary musculoskeletal abnormalities [4]. A widely recognized mechanism is the disruption of supraspinal regulation of spinal stretch reflexes following central nervous system injury, resulting in exaggerated reflex excitability and increased muscle tone [5,6]. Current rehabilitation strategies are typically multimodal and include physical therapy, occupational therapy, pharmacological management, orthopedic surgery, and complementary approaches, such as traditional Chinese medicine. Despite these interventions, functional recovery remains challenging, particularly in children with moderate-to-severe motor impairments. Consequently, there is growing interest in innovative rehabilitation approaches capable of promoting neuroplasticity and improving motor outcomes.

Among these emerging interventions, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a noninvasive neuromodulation technique. By delivering pulsed magnetic stimulation to targeted cortical regions, rTMS can modulate neuronal excitability and facilitate neuroplastic reorganization [7]. Previous studies have demonstrated its therapeutic potential in various neurological and neuropsychiatric disorders, including stroke, anxiety, depression, and, increasingly, CP [8-12]. Mechanistically, rTMS is believed to regulate synaptic plasticity, restore interhemispheric balance, and enhance corticospinal tract function, particularly when applied to the primary motor cortex. Importantly, rTMS is generally well tolerated in pediatric populations and allows relatively precise cortical targeting. A recent meta-analysis of 16 randomized controlled trials reported that rTMS was associated with improvements in gross motor function (Gross Motor Function Measure [GMFM]; standardized mean difference [SMD] 0.47-0.63) and gait velocity (SMD 1.28) in children with CP [13]. Nevertheless, the optimal stimulation protocols and their integration with rehabilitation training remain insufficiently established.

Parallel to developments in neuromodulation, rehabilitation robotics has emerged as a promising technology in pediatric neurorehabilitation. Robotic systems can incorporate real-time monitoring, adaptive algorithms, and task-oriented training environments to deliver intensive, repetitive, and individualized motor rehabilitation [14,15]. Compared with conventional therapy, robot-assisted interventions offer improved movement reproducibility, precise control of training parameters, and enhanced feedback mechanisms that may facilitate motor learning. In this study, we used a pediatric gait rehabilitation robot (BFR-K-A200; Chengdu Buffalo Robotics Technology Company), which combines an exoskeleton with a wheeled walker to assist in standing, walking, and lower-limb coordination. This device provides active and passive joint assistance and may improve gait efficiency and training adaptability compared with conventional exoskeleton-based systems.

Although both robotic gait training and rTMS have demonstrated potential benefits individually, evidence regarding their combined application in pediatric spastic CP remains limited. Given their complementary therapeutic mechanisms—robot-assisted training targeting peripheral motor execution and gait relearning, and rTMS targeting central neuromodulation and cortical plasticity—their integration may produce synergistic rehabilitation effects. Therefore, this prospective observational study aims to evaluate the clinical outcomes associated with robot-assisted gait training combined with rTMS in children with spastic CP. Treatment effects will be assessed using 3D gait analysis, neuromuscular electromyography, the GMFM-88, and the Modified Ashworth Scale (MAS), with the goal of generating evidence to inform multimodal and evidence-based rehabilitation strategies for this population.

The primary objective of this study is to evaluate the clinical outcomes associated with a pediatric gait rehabilitation robot combined with rTMS in adolescents with spastic CP, compared with conventional rehabilitation therapy.

The primary hypothesis is that participants receiving robot-assisted gait training combined with rTMS may show greater improvements in gross motor function, gait performance, and muscle tone than those receiving conventional rehabilitation after 8 weeks of intervention. However, due to the observational design, causal inference is not possible. Specifically, changes in GMFM-88 scores from baseline to week 8 will serve as the primary end point. Secondary hypotheses are that the intervention group will exhibit superior improvements in 3D gait parameters, electromyography outcomes, and MAS scores at weeks 4 and 8.

Given the observational nature of the study, any observed between-group differences will be interpreted as associations rather than causal effects.

This study is designed as a prospective observational controlled study to evaluate the clinical outcomes associated with robotic gait training combined with rTMS in adolescents with spastic CP. An observational design was selected primarily because treatment allocation is influenced by family preference and clinical decision-making in real-world rehabilitation settings. In addition, the highly visible and technology-intensive nature of robotic rehabilitation limits the feasibility of participant and therapist blinding. Nevertheless, to minimize assessment bias, outcome evaluations will be conducted by independent rehabilitation physicians who are not involved in treatment delivery and are blinded to group allocation whenever feasible.

Eligible participants will be allocated to either an intervention group (robot-assisted gait training combined with rTMS) or a comparison group (conventional rehabilitation therapy) according to guardian preference after receiving standardized study information from a neutral research coordinator who is not involved in treatment administration or outcome assessment. Allocation decisions will be prospectively documented, and no randomization will be performed. Both groups will receive 5 treatment sessions per week over an 8-week intervention period. Clinical evaluations will be performed at baseline, week 4, and week 8 by trained rehabilitation physicians using standardized assessment procedures. The study flowchart is presented in Figure 1, and the schedule of enrollment, intervention, and assessment is summarized in Figure 2. This protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines and will be reported following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement for observational studies [16,17]. Participant recruitment is scheduled to commence in January 2025, with data collection anticipated to be completed by December 2027.

A total of 108 adolescents with spastic CP will be recruited from the outpatient clinic of the Department of Rehabilitation Medicine, China National Nuclear Corporation 416 Hospital. The department is a tertiary rehabilitation center providing integrated clinical, teaching, and research services with extensive experience in pediatric neurodevelopmental disorder rehabilitation.

A structured summary of all eligibility criteria is presented in Textbox 1. Inclusion criteria define the target population, while exclusion criteria identify conditions that may confound outcome interpretation or pose safety risks.

Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this study because of the technical and methodological complexity of the intervention protocol.

Participants may be withdrawn from the study under the following circumstances:

All withdrawals and reasons for discontinuation will be prospectively documented.

Participants in both groups will receive structured rehabilitation interventions over an 8-week period, consisting of 5 sessions per week.

Sample size estimation was based on the primary outcome (change in GMFM-88 score at week 8). On the basis of a recent meta-analysis of noninvasive brain stimulation (including rTMS) in children with CP, which reported effect sizes ranging from 0.47 to 0.63 for GMFM outcomes [13], a moderate between-group effect size (Cohen d=0.60) was assumed for the primary outcome.

Using G*Power (version 3.1.9.7), with a 2-sided α level of .05 and 80% statistical power, the estimated minimum sample size was 46 participants per group. Allowing for an anticipated attrition rate of 15%, the final recruitment target was set at 54 participants per group, yielding a total sample size of 108.

Statistical analyses will be conducted using SPSS (version 26.0; IBM Corp). A 2-sided α level of .05 will be adopted.

Continuous variables will be summarized as means and SDs or medians and IQRs, depending on data distribution assessed using the Shapiro-Wilk test. Categorical variables will be summarized using frequencies and percentages.

This study will be conducted in accordance with the Declaration of Helsinki and has received approval from the ethics committee of China National Nuclear Corporation 416 Hospital (YJ-2025-020-01).

Written informed consent will be obtained from all participants and/or their legal guardians before enrollment. Participants and guardians will be informed of the study procedures, potential risks, and benefits, and their right to withdraw from the study at any time without consequences to future medical care. Participant confidentiality will be protected through coded identification and secure data storage. Study findings will be disseminated through peer-reviewed scientific journals and academic conferences.

This study aims to evaluate the clinical outcomes associated with pediatric gait rehabilitation robot-assisted training combined with rTMS in adolescents with spastic CP, compared with conventional rehabilitation therapy. Although both robotic gait training and rTMS have demonstrated potential benefits individually, evidence regarding their combined application in pediatric CP rehabilitation remains limited. Existing studies have suggested that robotic rehabilitation may improve gait biomechanics and motor learning through repetitive task-oriented training, while rTMS may facilitate cortical reorganization and enhance corticospinal excitability [21-23]. However, pediatric-specific protocols and multimodal intervention strategies remain insufficiently established.

The proposed intervention integrates peripheral motor training with central neuromodulation, providing a theoretically synergistic rehabilitation framework. Objective assessments, including 3D gait analysis, electromyography, GMFM-88, and MAS, are incorporated to provide a multidimensional evaluation of gait function, motor performance, and muscle tone.

This study is designed as a prospective observational controlled study rather than a randomized controlled trial. Consequently, any between-group differences observed should be interpreted as associations rather than causal effects.

To reduce bias associated with nonrandom allocation, multivariable adjustment and propensity score–based methods will be used. Nevertheless, residual confounding due to unmeasured factors cannot be excluded.

Should the intervention group demonstrate superior outcomes, such findings would support the preliminary clinical value of the combined intervention and provide justification for future randomized controlled trials. Conversely, null findings would not necessarily exclude potential benefit but may suggest limited additional effectiveness within the current observational framework.

Several strengths of this protocol should be acknowledged. First, the intervention combines robot-assisted gait rehabilitation with rTMS, targeting both peripheral motor execution and central neuroplastic modulation. Second, outcome assessment incorporates objective and multidimensional measures, including gait analysis and electrophysiological evaluation. Third, standardized intervention procedures and predefined statistical adjustment strategies have been incorporated to improve methodological rigor.

However, several limitations should also be recognized. First, the open-label nature of robotic rehabilitation limits participant and therapist blinding and may introduce performance bias. Although assessor blinding will be implemented whenever feasible, subjective assessments may still be influenced.

Second, the follow-up period is limited to 8 weeks. Given the chronic and developmental nature of CP, short-term outcomes may not fully capture sustained functional improvement. Future studies should incorporate longer-term follow-up assessments (eg, 6 or 12 months) to evaluate the durability of any observed improvements.

Third, participant heterogeneity, including differences in age, severity of motor impairment, and cognitive function, may influence treatment responsiveness.

Fourth, the age range of 13 to 18 years was selected primarily for device compatibility and developmental consistency. Consequently, findings may not be generalizable to younger children with CP.

Fifth, this study is conducted at a single tertiary rehabilitation center, which may limit generalizability. Multicenter studies are needed to validate the findings across diverse populations and clinical settings.

Finally, as an observational study, residual confounding and confounding by indication remain possible despite statistical adjustment. Furthermore, differences in intervention structure and treatment frequency between groups may partially influence observed outcomes.

Previous studies investigating rTMS or robotic rehabilitation in CP have primarily evaluated these modalities independently, with limited evidence regarding integrated intervention models. Additionally, stimulation parameters, training intensity, and intervention duration remain heterogeneous across studies, limiting comparability and standardization.

This study may contribute preliminary evidence regarding combined neuromodulation and robotic rehabilitation strategies and help inform future protocol optimization. Future research should prioritize multicenter randomized controlled trials, longer-term follow-up, and mechanistic investigations using neuroimaging and neurophysiological techniques. Integration with emerging technologies, such as virtual reality and biofeedback systems, may further enhance individualized rehabilitation approaches.

This protocol describes a prospective observational study evaluating the clinical outcomes associated with robot-assisted pediatric gait rehabilitation training combined with rTMS in adolescents with spastic CP.

By integrating objective outcome assessment with multimodal rehabilitation intervention, this study is expected to provide preliminary evidence regarding the feasibility and potential clinical value of combining neuromodulation and robot-assisted therapy in pediatric rehabilitation.

Given the nonrandomized design, findings should be interpreted cautiously and viewed as hypothesis-generating rather than confirmatory. Future randomized and multicenter studies will be necessary to establish causality and optimize intervention strategies.