1142 - Single Event Multi Level Chemoneurolysis with AbobotulinumtoxinA Improves Walking Efficiency and Increases Energy Expenditure in Children with Cerebral Palsy

Objectives: This study aimed to investigate the impact of spasticity management through single event multi-level chemoneurolysis (SEMLC) using abobotulinumtoxinA (Dysport®) on the walking efficiency and energy expenditure of children with cerebral palsy (CP).

Design: We conducted an open-label before-and-after trial at a tertiary academic medical center, enrolling twelve children aged 6-17 years with spastic diplegic CP of GMFCS levels I-III. All participants received SEMLC and regular rehabilitation therapy, with assessments at baseline, 1-month, and 3-month post-SEMLC.

Main Outcome Measure(s): The primary outcomes were energy expenditure assessed by oxygen consumption (VO2) during the 6-minute walk test (6MWT), and walking efficiency measured by 6MWT and gait parameters, including cadence, step length, gait velocity, and stride length. Secondary measures included spasticity evaluated by Modified Ashworth Scales (MAS) and range of motion (ROM) of lower limbs, with consideration of minimal clinically important differences (MCID) applied if possible.



Results: Eleven patients (GMFCS I, n=2; GMFCS II, n=8; GMFCS III, n=1) were included in the analysis. The mean abobotulinumtoxinA dosage was 18.9 units/kg, with a mean of 7.9 muscles injected per subject. VO2 significantly increased at 1-month (p=0.048) and 3-month (p=0.074) post-SEMLC. Moreover, 6MWT and gait velocity exhibited improvements surpassing MCID at 1-month and 3-month post-SEMLC. Most MAS scores significantly improved at 1-month, with hip adductors maintaining the effect at 3-month post-SEMLC. Change of ROM is not observed.

Conclusions: SEMLC with abobotulinumtoxinA was associated with increased oxygen consumption, improved gait parameters, and reduced spasticity, likely due to enhanced gait velocity. Further research is necessary to investigate the long-term effects and potential range of motion improvements.

Keywords: Cerebral palsy, AbobotulinumtoxinA, Spasticity management, Walking efficiency, Energy expenditure



Scientific Paper Best Paper Award Abstract:

Introduction:
Spasticity is a common movement disorder in children with cerebral palsy (CP), often resulting in increased energy expenditure during walking. The use of botulinum toxin-A (BoNT-A) injections has emerged as a primary therapeutic approach for managing lower limb spasticity in children with CP, with the aim of improving gait, range of motion (ROM), and overall quality of life. AbobotulinumtoxinA (Dysport®) received approval in 2016 for the treatment of pediatric patients with upper or lower limb spasticity in the United States. Single-event AbobotulinumtoxinA injections have shown significant efficacy in reducing muscle tone, spasticity grade, and functional outcomes, with benefits lasting for 16-22 weeks and persisting through repeated injections.

Objective:
This study aimed to investigate the impact of spasticity management through single-event multi-level chemoneurolysis (SEMLC) using abobotulinumtoxinA (Dysport®) on walking efficiency and energy expenditure in children with cerebral palsy.

Methods:
Design: We conducted a single-center, open-label, before-and-after trial, registered under NCT03469999, with ethical approval (IRB AAAR1322). Participants were assessed at baseline, 1-month, and 3-month intervals following SEMLC.

Setting: The study was conducted at a tertiary academic medical center in the United States.

Participants: We enrolled 12 children aged 6-17 years with spastic diplegic CP of Gross Motor Function Classification System (GMFCS) levels I-III. Recruitment took place during their standard office visits, spanning from December 12, 2018, to January 29, 2020.

Interventions: All 12 participants underwent SEMLC, combined with regular rehabilitation therapy. AbobotulinumtoxinA dosage was determined based on muscle involvement, spasticity severity, and body weight. It followed recommended guidelines (10-15 units/kg per limb, max 1000 units/session). Muscle-specific dosage considered muscle size, spasticity, and body weight. Injections, guided by ultrasound for precision, took 10-20 minutes, depending on targeted muscles. Muscles treated included hamstrings, gastrocnemius, hip adductor longus, gracilis, iliopsoas, tensor fascia lata (TFL), and tibialis posterior. All subjects received injections in both hamstrings and gastrocnemius muscles.

Main Outcome Measures: Assessments at each visit included three-dimensional gait analysis, oxygen consumption (VO2) measured during the 6-minute walk test (6MWT), and physical examinations. The primary outcomes were energy expenditure (VO2) during 6MWT and walking efficiency measured by 6MWT and gait parameters, encompassing cadence, step length, gait velocity, and stride length. Secondary measures encompassed spasticity as evaluated by Modified Ashworth Scales (MAS) and lower limb range of motion (ROM). Minimal clinically important differences (MCID) were considered in all measurements, except step length and lower limb ROM, which were compared using t-tests.

Results and

Discussion:
One subject was excluded due to a lack of follow-up following SEMLC, attributed to the pandemic in March 2020. Demographic characteristics such as sex, age, weight, and height of the 11 subjects were distributed across GMFCS Levels I (n=2), II (n=7) and III (n=2). The age range was 7-17 years old, with a mean of 11.5±3.4 years. There were 5 males and 6 females. Dysport dosage (units) ranged from 500 to 1000 units, with a mean of 741.82±212.69 units. Weight (kg) ranged from 24.6 to 63.63, with a mean of 45.40±12.59 kg, height (cm) was 151.60 +/-17.55 cm, and BMI had a mean of 19.70 +/- 4.41. The mean abobotulinumtoxinA dosage per subject was 760 units, ranging from 500 to 1000 units, and the mean dosage per kilogram of body weight was 18.9 units/kg (ranging from 11 to 30 units/kg). In total, 87 muscles were injected in 11 subjects, with a mean of 7.9 muscles per subject (ranging from 4 to 12 muscles).

In our study, we observed significant and clinically meaningful changes in oxygen consumption at both 1-month (p=0.048) and 3-month (p=0.074) post-SEMLC. Additionally, there may be a clinically meaningful difference in the 6-minute walk test (6MWT) at 1 month post-SEMLC, and a clinically meaningful difference was evident at 3-month post-SEMLC when compared to the 6MWT results prior to SEMLC, even though the statistical significance was not achieved (Table1). For secondary outcomes, we noted a significant decrease in spasticity, as measured b y the MAS, in all evaluated lower limb muscle at 1 month post-SEMLC, though this effect did not persist until 3 months post-SEMLC, except in the case of hip adductors (Table 2). Change in ROM were generally not observed.

The rise in energy consumption in our study may indicate improved aerobic fitness, as it was evidenced by enhanced endurance and gait efficiency, which would in turn increase fitness reduce the risk of lifestyle-related diseases.

Conclusions/Significance:
This study underscores the efficacy of SEMLC utilizing abobotulinumtoxinA injections in enhancing gait parameters in children with cerebral palsy. Clinically meaningful improvements were observed in gait velocity, stride length, step length, and cadence post-treatment. Additionally, the concomitant rise in VO2 consumption post-SEMLC may indicate improved aerobic fitness in these children. Although an improvement in spasticity was observed shortly after injection, the long-term effects remain uncertain, and no evidence of ROM improvement was found. Further investigations are imperative to elucidate the implications of these findings.

Keywords:
Cerebral palsy, AbobotulinumtoxinA, Spasticity management, Walking efficiency, Energy expenditure, Oxygen consumption, Botulinum toxin A, Dysport, Pediatric rehabilitation.

Table 1. Measurements of energy expenditure, 6MWT and walking efficacy at pre-, 1-month post-, and 3-month post-SEMLC

	Pre-SEMLC	1-month post-SEMLC	3-month post-SEMLC	P value
				Pre- vs 1-month post-SEMLC	Pre- vs 3-month post-SEMLC
6 MWT (m)	193±90	205±68	219±65	0.3064	0.1091
VO2 (ml/kg/min)	14.82±2.8	16.75±4.49	28.77± 27.18	0.0477	0.0739
Gait analysis
Cadence (steps/min)	101.85±19.00	104.61±11.18	100.09±19.12	0.2362	0.3154
Gait Velocity (cm/s)	84.86±23.70	92.84±17.89	87.11±28.45	0.0955	0.2903
Step Length (cm)	46.4± 12.5	49.0±14.1	50.4±10.9	0.2034	0.1294
Stride Length (%)	95.4± 6.6	101.2± 6.4	101.4± 6.7	0.1483	0.1461

VO2: oxygen consumption; 6MWT: 6-minute walk test; SEMLC: single event multi-level

Table 2. Degree of spasticity measured with MAS at pre-, 1-month post-, and 3-month post-SEMLC

	Degree of Spasticity in MAS				P value
	Pre-SEMLC	1-month post-SEMLC	3-month post-SEMLC		Pre- vs 1-month post-SEMLC	Pre- vs 3-month post-SEMLC
Hip adductor
Right	1.71±0.49	1.29±0.49	1.17±0.75		0.0391	0.0125
Left	1.71±0.49	1.14±0.38	1.17±0.75		0.015	0.0125
Hamstring
Right	2.11±0.60	1.44±0.53	1.89±0.60		0.0023	0.0845
Left	1.89±0.60	1.78±0.67	1.78±0.83		0.7029	0.6356
Gastrocnemius
Right	2.33±0.50	1.89±0.33	2.38±0.5		0.0176	1
Left	2.11±1.05	1.89±0.60	2.63±0.92		0.1733	0.2582

MAS: Modified Ashworth Scales; SEMLC: single event multi-level chemoneurolysis.