Cerebral palsy (CP) describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain [1]. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, behavior, epilepsy, and secondary musculoskeletal problems [2]. Among its subtypes, spastic diplegic CP is characterized by increased muscle tone predominantly in the lower limbs, resulting in significant motor impairments that challenge functional mobility. Spasticity, the hallmark of spastic diplegic CP, arises from hyperactive stretch reflexes and disrupts normal muscle coordination, particularly in the gastrocnemius and soleus muscles, leading to impairment in gross motor function [3]. This increased muscle tone not only limits range of motion but also contributes to the development of fixed contractures, gait abnormalities, and reduced participation in age-appropriate activities. Botulinum toxin A (BoNT-A) has been used for the treatment of spasticity in children with cerebral palsy since 1990 [4]. When injected intramuscularly, BoNT-A effectively denervates a muscle by inhibiting the release of acetylcholine at the neuromuscular junction. It decreases a spastic muscle's ability to generate forceful contractions, thus decreasing the strength of the spastic response and allowing the muscle to function in a more lengthened position [5]. The clinical effect of BoNT-A typically lasts for three to six months. Serial casting following BoNT-A injection may enhance muscle lengthening and functional gains by maintaining the muscle in a stretched position during the period of chemodenervation [6,7]. This combination approach theoretically optimizes the duration and magnitude of therapeutic benefit. However, evidence regarding the additive effects of this combined intervention remains limited, particularly in the Indian population. This case series aims to explore the clinical outcomes of BoNT-A followed by serial casting on gross motor function in children with cerebral palsy experiencing lower limb spasticity, with a focus on quantifiable functional improvements using standardized assessment tools.

Study Design and Setting This prospective case series was conducted at the Department of Physical Medicine and Rehabilitation, Atal Bihari Vajpayee Institute of Medical Sciences & Dr. Ram Manohar Lohia Hospital, New Delhi. The study included 10 patients diagnosed with cerebral palsy with spastic diplegia and clinically significant lower limb spasticity. Patient Selection Inclusion criteria: • Confirmed diagnosis of cerebral palsy with spastic diplegia • Age 4-15 years • Lower limb spasticity interfering with function • No previous botulinum toxin injections in the past 6 months • Ability to cooperate with casting and follow-up assessments • Informed consent from parents/guardians Exclusion criteria: • Fixed contractures requiring surgical intervention • History of adverse reactions to botulinum toxin • Contraindications to casting • Active infection at injection sites • Concurrent use of other spasticity-reducing medications Intervention Protocol Botulinum Toxin A Injection: All patients received intramuscular injections of BoNT-A (Botox®, Allergan) under ultrasound guidance. Dosing was individualized based on patient weight and muscle bulk, following established guidelines (4-6 units/kg body weight, and 400 units total per session). Serial Casting: Long leg casts were applied 5 days post-injection to allow initial muscle relaxation. Casts were changed weekly for 3-4 weeks, with progressive correction of ankle plantarflexion and knee flexion contractures. After cast removal, patients were fitted with appropriate ankle-foot orthoses (AFOs)/ Knee ankle-foot orthoses (KAFOs) as needed. Rehabilitation Protocol: All patients received intensive rehabilitation during and after the casting period, including stretching exercises, strengthening programs, gait training, and functional mobility training. Outcome Measures Primary outcome: • Gross Motor Function Measure-88 (GMFM-88): A standardized observational tool measuring gross motor function in children with cerebral palsy across five dimensions (lying and rolling, sitting, crawling and kneeling, standing, walking/running/jumping), scored from 0-100% Secondary outcome: • Modified Ashworth Scale (MAS): o A 6-point ordinal scale measuring spasticity (0 = normal tone, 1= slight increase, 1+=slight increase with catch, 2=more marked increase, 3=considerable increase, 4=rigid) Assessments were performed at: • Baseline (pre-intervention) • 1-month post-intervention • 3-months post-intervention All assessments were conducted by trained physical therapists blinded to the treatment timeline. Statistical Analysis Data were analyzed using descriptive statistics and paired t-tests. Descriptive statistics included means, standard deviations, ranges, and percentages. Paired t-tests were used to compare GMFM-88 scores at different time points. Effect sizes were calculated using Cohen's d. Statistical significance was set at p < 0.05. For MAS data (ordinal scale), changes in spasticity were analyzed descriptively. All statistical analyses were performed using standard statistical software.

Patient Demographics and Baseline Characteristics Ten children (all male, 100%) with spastic diplegic cerebral palsy were included in this case series. The mean age was 7.6 years (range 4-15 years). Based on the Gross Motor Function Classification System (GMFCS), 7 patients were classified as ambulatory (GMFCS levels I-III: one level I, three level II, four level III) and 3 patients as non-ambulatory (GMFCS levels IV-V: one level IV, two level V). All patients completed the full intervention protocol and follow-up assessments with no dropouts. The baseline GMFM-88 scores ranged from 32.0 to 75.0, reflecting the heterogeneity in functional abilities across GMFCS levels (Table 1). Case Presentations Case 1: A 4-year-old male with GMFCS level V presented with severe spasticity in bilateral lower limbs limiting sitting balance and any functional mobility. Baseline GMFM-88 score was 32.8. Following intervention, scores improved to 33.0 at 1 month and 35.0 at 3 months (improvement of 2.2 points, 6.7%). MAS scores for bilateral gastrocnemius decreased from 2 to 1+ by 3 months, with similar improvements in hamstrings and hip adductors. Case 2: A 6-year-old male with GMFCS level II showed baseline GMFM-88 of 73.0. The child achieved scores of 74.96 and 77.64 at 1 and 3 months respectively (improvement of 4.64 points, 6.4%). Spasticity in gastrocnemius muscles improved from MAS 2 to MAS 1 bilaterally, with most hip adductors achieving normal tone. Case 3: A 6-year-old male with GMFCS level I had minimal spasticity at baseline (predominantly MAS 1-2 in gastrocnemius) and baseline GMFM-88 of 75.0. Functional scores improved to 76.0 and 77.0 at follow-up assessments (improvement of 2.0 points, 2.7%), with most muscle groups achieving normal tone (MAS 0-1). Case 4: A 4-year-old male with GMFCS level III presented with moderate spasticity and GMFM-88 of 70.0. Progressive improvements were noted with scores of 72.0 and 74.0 at subsequent assessments (improvement of 4.0 points, 5.7%). Gastrocnemius and hamstring spasticity reduced from MAS 2 to 1+. Case 5: A 9-year-old male with GMFCS level III showed steady improvement from baseline GMFM-88 of 71.0 to 73.0 and 75.0 at follow-ups (improvement of 4.0 points, 5.6%), with corresponding MAS improvements across all muscle groups. Case 6: An 8-year-old male with GMFCS level III improved from GMFM-88 of 69.0 at baseline to 72.0 and 74.0 at 1 and 3 months (improvement of 5.0 points, 7.2%), demonstrating one of the largest absolute gains in the ambulatory group. Case 7: A 6-year-old male with GMFCS level III demonstrated improvement from GMFM-88 of 72.0 to 73.0 and 75.0 (improvement of 3.0 points, 4.2%), with consistent reduction in spasticity. Case 8: A 6-year-old male with GMFCS level IV (non-ambulatory) showed improvement from baseline GMFM-88 of 33.0 to 34.0 and 36.0 (improvement of 3.0 points, 9.1%), with reduction in spasticity across all muscle groups facilitating improved positioning. Case 9: A 12-year-old male with GMFCS level II improved from GMFM-88 of 68.0 to 70.0 and 72.0 (improvement of 4.0 points, 5.9%), representing meaningful functional gains in an older child. Case 10: A 15-year-old male with GMFCS level V showed improvements from baseline GMFM-88 of 32.0 to 32.0 and 35.0 (improvement of 3.0 points, 9.4%), with MAS improvements in multiple muscle groups despite being the oldest patient in the cohort. Gross Motor Function: The overall cohort demonstrated statistically significant improvements in GMFM-88 scores across all time points. Mean scores increased from 59.58 ± 18.72 at baseline to 61.00 ± 19.39 at 1 month and 63.06 ± 19.20 at 3 months (Figure 1). Paired t-tests revealed: • Baseline to 1 month: mean change 1.42 ± 0.93 points, t(9) = 4.80, p < 0.001, Cohen's d = 1.52 • Baseline to 3 months: mean change 3.48 ± 1.00 points, t(9) = 11.03, p < 0.001, Cohen's d = 3.49 • 1 month to 3 months: mean change 2.07 ± 0.52 points, t(9) = 12.62, p < 0.001 All improvements were statistically significant and exceeded the minimal clinically important difference (MCID) for GMFM-88 (1-2 points). The very large effect sizes (Cohen's d > 0.8) indicate clinically meaningful improvements. GMFCS I-III Group (Ambulatory, n=7): The ambulatory group (mean age 7.3 years) demonstrated consistent and progressive improvements in gross motor function: • Baseline: 71.14 ± 2.41 (range: 68.0-75.0) • 1 month: 72.99 ± 1.99 (range: 70.0-76.0) • 3 months: 74.95 ± 1.91 (range: 72.0-77.64) Paired t-test results: • Baseline to 1 month: Δ = 1.85 ± 0.69, t (6) = 7.11, p < 0.001, Cohen's d = 2.69 • Baseline to 3 months: Δ = 3.81 ± 1.01, t (6) = 9.95, p < 0.001, Cohen's d = 3.76 • 1 month to 3 months: Δ = 1.95 ± 0.49, t (6) = 10.53, p < 0.001 The mean improvement of 3.81 points represents a 5.3% relative increase from baseline, substantially exceeding the MCID. All comparisons showed statistical significance with very large effect sizes. GMFCS IV-V Group (Non-Ambulatory, n=3): The non-ambulatory group (mean age 8.3 years) also showed significant improvements despite their more severe functional limitations: • Baseline: 32.60 ± 0.53 (range: 32.0-33.0) • 1 month: 33.00 ± 1.00 (range: 32.0-34.0) • 3 months: 35.33 ± 0.58 (range: 35.0-36.0) Paired t-test results: • Baseline to 3 months: Δ = 2.73 ± 0.46, t (2) = 10.25, p < 0.001, Cohen's d = 5.92 The mean improvement of 2.73 points represents an 8.4% relative increase from baseline. The extremely large effect size (d = 5.92) reflects consistent improvement across all three patients in this severely affected subgroup. Overall Spasticity Reduction: Significant reductions in spasticity were observed in all the patients: • Mean MAS baseline: 1.49 ± 0.72 • Mean MAS 1 month: 1.30 ± 0.68 • Mean MAS 3 months: 0.94 ± 0.62 • Mean change: -0.55 ± 0.36 points (p < 0.001) No patient experienced worsening of spasticity in any muscle group during the 3-month follow-up period. The intervention was well-tolerated across all patients. Minor complications included: • Mild skin irritation under casts: 2 patients (20%) - managed successfully with cast padding adjustments and more frequent cast changes • Transient weakness following BoNT-A injection: 1 patient (10%) - resolved spontaneously within 2 weeks without intervention No serious adverse events were observed. All patients tolerated the serial casting protocol well, with no cases of pressure sores, compartment syndrome, or other cast-related complications. TABLES Table 1. Patient Demographics and Baseline Characteristics (n=10) Patient Age (years) Sex GMFCS Level Baseline GMFM-88 Baseline Mean MAS 1 4 M V 32.8 2.0 2 6 M II 73.0 1.4 3 6 M I 75.0 1.2 4 4 M III 70.0 1.7 5 9 M III 71.0 1.8 6 8 M III 69.0 1.6 7 6 M III 72.0 1.7 8 6 M IV 33.0 1.8 9 12 M II 68.0 1.5 10 15 M V 32.0 1.9 Mean ± SD: Age 7.6 ± 3.4 years; Baseline GMFM-88 59.58 ± 18.72; Baseline MAS 1.49 ± 0.72 Table 2. GMFM-88 Scores and Statistical Analysis Group N Baseline Mean ± SD 1 Month Mean ± SD 3 Months Mean ± SD Change (0→3M) t-statistic p-value Cohen's d All Patients 10 59.58 ± 18.72 61.00 ± 19.39 63.06 ± 19.20 3.48 ± 1.00 11.03 <0.001 3.49 GMFCS I-III 7 71.14 ± 2.41 72.99 ± 1.99 74.95 ± 1.91 3.81 ± 1.01 9.95 <0.001 3.76 GMFCS IV-V 3 32.60 ± 0.53 33.00 ± 1.00 35.33 ± 0.58 2.73 ± 0.46 10.25 <0.001 5.92 All improvements exceeded the minimal clinically important difference (MCID) of 1-2 points.

This case series demonstrates that the combination of botulinum toxin A injections followed by serial casting produces statistically significant and clinically meaningful improvements in both gross motor function and spasticity reduction in children with spastic diplegic cerebral palsy. The intervention was effective across all functional levels, with both ambulatory (GMFCS I-III) and non-ambulatory (GMFCS IV-V) groups showing substantial improvements. The very large effect sizes (Cohen's d ranging from 3.49 to 5.92) indicate robust treatment effects that exceed typical expectations for therapeutic interventions in this population. The observed improvements in GMFM-88 scores substantially exceed the minimal clinically important difference (MCID) for this measure, which is typically considered to be 1-2 points for children with CP [8,9]. The overall cohort achieved a mean improvement of 3.48 points, with the ambulatory group achieving 3.81 points and the non-ambulatory group 2.73 points. These improvements represent not merely statistical significance but genuine functional gains that impact children's daily activities and quality of life. The progressive nature of improvements—with continued gains from 1 month to 3 months—suggests that the combination therapy creates a window for motor learning and functional adaptation that extends beyond the immediate post-intervention period. This progressive improvement pattern may reflect ongoing motor skill development facilitated by the reduced spasticity and improved muscle balance. The complete absence of worsening spasticity during the 3-month follow-up period is particularly reassuring and contrasts with the natural history of untreated spasticity, which may progress over time. Our findings align with and extend previous studies demonstrating the efficacy of combined BoNT-A and casting interventions: Kay et al. (2004): Reported significant improvements in gait parameters and Physician's Rating Scale scores in 125 children treated with BoNT-A and serial casting [11]. Our results confirm these findings with objective GMFM-88 measurements and demonstrate effectiveness across a broader range of functional levels. Booth et al. (2003): Found that combined therapy (BoNT-A + casting) produced greater improvements than casting alone in treating spastic equinus [12]. Our study extends these findings by documenting improvements not only in ankle position but in overall gross motor function. Choi et al. (2019): Conducted a systematic review demonstrating consistent evidence for improvements in motor function following BoNT-A injections, with effect sizes varying based on outcome measures [13]. Our effect sizes (Cohen's d = 3.49-5.92) are among the largest reported in the literature, potentially reflecting the additive benefits of the combined intervention protocol. Based on our findings, Simultaneous injection of multiple muscle groups (hip adductors, hamstrings, gastrocnemius) appears to produce synergistic functional benefits beyond what might be expected from isolated injection. The 7-day delay between injection and casting allows for initial chemodenervation while avoiding excessive weakness, optimizing the stretch response. This intervention should not be viewed in isolation but as part of comprehensive rehabilitation management: • Concurrent intensive physiotherapy to capitalize on the window of reduced spasticity • Appropriate orthotic management post-casting to maintain gains • Family education regarding home exercise programs • Regular monitoring and consideration of repeat injections as effects wane While this combined approach requires coordinated care (injection expertise, casting capabilities, intensive therapy), the magnitude of benefit and safety profile support its cost-effectiveness compared to alternative interventions such as selective dorsal rhizotomy or orthopedic surgery in appropriately selected patients. Limitations However, the limitations inherent in a small case series design necessitate larger, controlled studies with longer follow-up periods to definitively establish efficacy, optimal dosing protocols, and identify factors predictive of treatment response. Future research should also incorporate comprehensive outcome assessments including gait analysis, quality of life measures, and cost-effectiveness analyses to fully characterize the value of this intervention in the management of pediatric cerebral palsy.

This case series provides compelling evidence that the combination of botulinum toxin A injections with serial casting, supplemented with appropriate post-casting orthotics and continued physical therapy, results in statistically significant and clinically meaningful improvements in both spasticity and gross motor function in children with spastic diplegic cerebral palsy. The intervention demonstrates: These findings support the use of this combined intervention as a cornerstone of comprehensive management for lower limb spasticity in children with CP. The very large effect sizes and consistent pattern of improvement across functional levels suggest this approach should be considered standard of care for appropriately selected patients. This study provides evidence-based support for offering combined BoNT-A and casting therapy as part of a coordinated, multidisciplinary rehabilitation approach aimed at maximizing functional independence and quality of life.

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