Neuronox versus BOTOX for spastic equinus gait in children with cerebral palsy: a randomized, double-blinded, controlled multicentre clinical trial

Abstract

ABBREVIATIONS ITTIntention to treat PROM Passive range of motion PRS Physicians' Rating Scale AIM The aim of this study was to evaluate the efficacy and safety of a newly manufactured botulinum toxin, Neuronox, compared with BOTOX for the treatment of the spastic equinus gait in children with cerebral palsy.METHOD A total of 127 children with cerebral palsy, aged 2 to 10 years, who presented at three university hospitals with spastic equinus gait were assessed for eligibility to participate in this double-blinded, randomized, controlled trial. Of the 119 eligible participants (mean age 4.33y; SD 2.07; 76 males and 43 females; 79 with diplegia and 40 with hemiplegia), 57 were classified as Gross Motor Function Classification System level I, 29 as level II, and 33 as level III. Participants were randomly assigned to receive an injection of Neuronox (n=60) or BOTOX (n=59) to the calf muscles at a dose of 4U ⁄ kg for those with hemiplegia and 6U ⁄ kg for those with diplegia. Assessments were performed at baseline (V1) and at 4 (V2), 12 (V3), and 24 (V4) weeks after the intervention. The primary outcome measure was response rate at V3, with a positive response being defined as at least a 2-point increase in the Physicians' Rating Scale (PRS) score. The non-inferiority margin was set as )20% for the difference in the response rate. The secondary outcome measures included PRS score, passive range of motion (PROM) of the ankle and knee, and Gross Motor Function Measure 88 (GMFM-88). Any adverse events were investigated for safety implications. RESULTSThe response rate of the Neuronox group at V3 was not inferior to that of the BOTOX group (90% lower limit=)11.58%). There were significant improvements in PRS, PROM of ankle dorsiflexion, and GMFM scores at V2, V3, and V4 in both groups. The changes in PRS score were not statistically different between the two groups in serial evaluation (p=0.96). PROM of the ankle dorsiflexion increased without any significant difference between the two groups, either overall (p=0.56) or at each visit (V2, p=0.32; V3, p=0.66; V4, p=0.90). The increase in GMFM score in serial measurements were not significantly different between the two groups (p=0.16), whereas it was larger in the BOTOX group than in the Neuronox group at V2 and V4 (p=0.03 and 0.05 respectively). The frequency of adverse events was not significantly different between the two groups (p=0.97), and drug-related complications of Neuronox treatment were not addressed. INTERPRETATIONThe outcomes of Neuronox, based on PRS, proved to be as effective and safe as those of BOTOX for the treatment of spasticity in individuals with cerebral palsy.

Ambulant adults with spastic cerebral palsy: The validity of lower limb joint angle measurements from sagittal video recordings

“…However, reliability does not guarantee validity, and responsiveness includes them both [11]. Neither Scholtes et al [14], who used joint angles measured from video recordings and the Edinburgh Visual Gait Score (EVGS) [5], nor Kim et al [15], who used the Physician's Rating Scale [3], discuss the limitations of using VGA with regard to what they consider as a clinically important improvement. On the other hand a recent publication, which used VGA to evaluate the effects of selective dorsal rhizotomy on gait in persons with CP, addresses the limitations of measuring gait in only two dimensions [26].…”

“…However, other BoNT-A studies do not discuss the limitations of assessing gait with VGA [3,12,14,15]. In contrast to the categorical approach in most VGA-tools, the Salford Gait Tool (SF-GT) [9] is based on visually estimation of exact joint angles in the hip, knee and ankle at six selected events during the gait cycle, and then categorisation of them.…”

“…Most of them originate from the need for outcome measurements in clinical practice and in research and are based on categorisation of different gait strategies into ordinal scales from experts in the field of gait impairment in children with spastic CP [3][4][5][6][7][8]. Several studies, investigating the effects of botulinum toxin A (BoNT-A) on gait in children with spastic CP, have used a VGA as outcome [3,4,14,15]. Ubhi et al …”

Comparison of Treatment Effects Between Children With Spastic Cerebral Palsy Under and Over Five Years After Botulinum Toxin Type A Injection

“…Local injection of botulinum toxin type A (BTA) into spastic muscles results in reversible disruption of acetylcholine release from the muscle's nerve endings [5,6], enabling increased function over time [7]. The use of BTA as an adjunct to other interventions, including physiotherapy and casting, has been recommended for the management of children with spastic CP in order to reduce spasticity, prevent or delay orthopedic surgery and improve function and gait [6,8].…”

The Influence of Botulinum Toxin A Injections into the Calf Muscles on Genu Recurvatum in Children With Cerebral Palsy

“…In cases of a dynamic equinus, injection of botulinum toxin A (BtA) into the calf muscles is a widely accepted treatment and commonly combined with physiotherapy and/or orthotic treatment [8,10]. Although the treatment with BtA injections in adults with CP is controversial [17], in children with CP, several studies report improvement of ankle dorsiflexion in passive ROM [12,14] and as measured by gait analysis [29], lasting approximately 3 to 6 months [6,29]. The improvements are seen especially in dynamic ankle kinematics [9,29].…”