Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy.
Ontology highlight
ABSTRACT:
SUBMITTER: Blumetti FC
PROVIDER: S-EPMC6779591 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy.
Blumetti Francesco C FC Belloti João Carlos JC Tamaoki Marcel Js MJ Pinto José A JA
The Cochrane database of systematic reviews 20191008
<h4>Background</h4>Cerebral palsy (CP) is the most common cause of physical disabilities in children in high-income countries. Spasticity is the most common motor disturbance in CP. Botulinum toxin type A (BoNT-A) is considered the first-line treatment for focal spasticity in people with CP.<h4>Objectives</h4>To evaluate the effectiveness and safety of BoNT-A compared to other treatments used in the management of lower limb spasticity in children with CP.<h4>Search methods</h4>We searched CENTRA ...[more]
Similar Datasets
Project description:PurposeThe open-label phase 3 "Treatment with IncobotulinumtoxinA in Movement Open-Label" (TIMO) study investigated longer-term safety and efficacy of incobotulinumtoxin A in children/adolescents with cerebral palsy (CP).MethodsPatients on standard treatment, with unilateral or bilateral lower limb (LL) or combined upper limb (UL)/LL spasticity received four incobotulinumtoxinA injection cycles (16 or 20 Units/kg bodyweight total [maximum 400 or 500 Units] per cycle depending on ambulatory status/clinical pattern treated), each followed by 12-16 weeks' observation. Treatment for pes equinus was mandatory; flexed knee or adducted thigh were options for unilateral treatment and/or ULs for unilateral/bilateral treatment. The primary endpoint was safety; changes in Ashworth Scale and Gross Motor Function Measure-66 scores, and Global Impression of Change Scale scores at week 4 of each injection cycle were also evaluated.ResultsIncobotulinumtoxinA (≤500 Units for ≤98 weeks) was safe, well-tolerated, and effective across all endpoints for multipattern treatment of LL and combined LL/UL spasticity in ambulant/nonambulant children/adolescents with CP. Treatment effects increased with each injection cycle. No new/unexpected safety concerns were identified.ConclusionIncobotulinumtoxinA showed a good safety and tolerability profile, with efficacy over multiple clinical presentations. As an adjunct treatment, it offers an effective, individualized treatment option for pediatric CP-related spasticity.
| S-EPMC9028655 | biostudies-literature
Project description:PurposeInvestigate the efficacy and safety of multipattern incobotulinumtoxinA injections in children/adolescents with lower-limb cerebral palsy (CP)-related spasticity.MethodsPhase 3 double-blind study in children/adolescents (Gross Motor Function Classification System - Expanded and Revised I-V) with unilateral or bilateral spastic CP and Ashworth Scale (AS) plantar flexor (PF) scores ⩾ 2 randomized (1:1:2) to incobotulinumtoxinA (4, 12, 16 U/kg, maximum 100, 300, 400 U, respectively) for two 12- to 36-week injection cycles. Two clinical patterns were treated. Pes equinus (bilateral or unilateral) was mandatory; if unilateral, treatment included flexed knee or adducted thigh.EndpointsPrimary: AS-PF change from baseline to 4 weeks; Coprimary: investigator-rated Global Impression of Change Scale (GICS)-PF at 4 weeks; Secondary: investigator's, patient's, and parent's/caregiver's GICS, Gross Motor Function Measure-66 (GMFM-66).ResultsAmong 311 patients, AS-PF and AS scores in all treated clinical patterns improved from baseline to 4-weeks post-injection and cumulatively across injection cycles. GICS-PF and GICS scores confirmed global spasticity improvements. GMFM-66 scores indicated better motor function. No significant differences between doses were evident. Treatment was well-tolerated, with no unexpected treatment-related adverse events or neutralising antibody development.ConclusionChildren/adolescents with lower-limb spasticity experienced multipattern benefits from incobotulinumtoxinA, which was safe and well-tolerated in doses up to 16 U/kg, maximum 400 U.
| S-EPMC8673523 | biostudies-literature
Project description:ObjectivesThe therapeutic effects of botulinum neurotoxin (BoNT) are well documented in upper limb spasticity. However, several factors may influence treatment efficacy, including targeting of neuromuscular junctions (NMJs). We examined whether NMJ-targeted BoNT injections were non-inferior, in terms of efficacy, to current injection practices.DesignOpen-label prospective evaluator-blinded study.SettingConducted across 20 medical centres in Denmark, Finland, Norway and Sweden (24 September 2012 to 11 March 2015).ParticipantsAged ˃18 years with upper limb spasticity (Modified Ashworth Scale [MAS] score of 2 or 3) following stroke or traumatic brain injury, had received ≥2 consecutive BoNT-A treatment cycles (the latest of which was abobotulinumtoxinA [aboBoNT-A]) and needed BoNT-A retreatment (same modality as previous cycle). Patients requiring aboBoNT-A doses >800units were excluded. In total, 88 patients were randomised (intention-to-treat [ITT] population), most were male (n=58/88, 65.9%) and 54/88 (61.4%) completed the study (per protocol [PP] population).InterventionsRandomisation (1:1) to receive a single dose of aboBoNT-A (≤800 U) according to either current clinical practice (300 U/mL) or as an NMJ-targeted injection (100 U/mL).Primary outcome measureProportion of patients with a ≥1 level reduction from baseline in MAS score at week 4 post-injection (responders).ResultsIn the ITT population, the proportion of responders at elbow flexors was 72.7% in the current practice group and 56.8% in the NMJ-targeted group (adjusted difference -0.1673 [95% CIs: -0.3630 to 0.0284]; p=0.0986). Similar results were observed in the PP population (69.0% vs 68.0%, respectively, adjusted difference 0.0707 [-0.1948 to 0.3362]; p=0.6052).ConclusionsOwing to the limited number of participants, non-inferiority of NMJ-targeted injections could not be determined. However, there was no statistical difference between groups. Larger studies are needed confirm whether the two techniques offer comparable efficacy.Trial registration numberNCT01682148.
| S-EPMC6502046 | biostudies-literature
Project description:ObjectiveDescribe how people with lower limb spasticity present for treatment in routine clinical practice.MethodsProspective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA.ResultsThe study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. Using the Leg Activity Measure, most patients reported no or only mild difficulties in performing hygiene/positioning tasks, while 80.7% had at least mild difficulty with indoor ambulation and 90.5% had at least mild difficulty with walking outdoors. Sensory, communication and/or cognitive impairments were also common. At the first treatment cycle, 50.7% of patients set active function primary goals, including locomotion transferring or standing.ConclusionThese observations highlight the complexity of presentation that must be considered when setting treatment goals for lower limb spasticity and emphasize the types of impairment and activity (functional) limitations that treating teams may expect to encounter in their patients and should cover in their initial and follow-up assessments.
| S-EPMC10562995 | biostudies-literature
Project description:Myokymia is a rare neuromuscular disorder and limb involvement is not common in this disease. To the best of our knowledge, isolated peroneus longus muscle myokymia was not reported before in the literature; and for that reason treatment protocols were not established. Botulinum toxin type A (BoNT-A), which is used in the treatment of a variety of neurologic disorders, was also defined as a treatment option in myokymia. Herein, we will report three cases of peroneus longus muscle myokymia in children in the absence of any other neurological findings, and the successful results of treatment with local BoNT-A injections. BoNT-A is a safe and effective treatment in myokymia when administered by an experienced clinician and should always be considered when the disorder is persistent and affecting the life of the patient.
| S-EPMC9764877 | biostudies-literature
Project description:AimTo investigate whether more prominent signs of muscle fatigue occur during self-paced walking in children with cerebral palsy (CP) compared to typically developing peers.MethodIn this case-control study, 13 children with CP (four males, nine females; mean age [SD] 11y 4mo [3y 8mo]; nine in Gross Motor Function Classification System [GMFCS] level I, three in GMFCS level II, and one in GMFCS level III) and 14 typically developing peers (nine males, five females; mean age [SD] 9y 10mo [1y 10mo]) walked 5 minutes overground at a self-selected walking speed. Electromyography (EMG) median frequency and root mean square (RMS) were identified per gait cycle from EMG recordings of the tibialis anterior, gastrocnemius medialis, soleus, rectus femoris, and semitendinosus. Rate of change in those variables was analysed using mixed linear model analyses.ResultsThe decrease in EMG median frequency of gastrocnemius medialis and soleus and increase in EMG-RMS of tibialis anterior, gastrocnemius medialis, and soleus were significantly larger in the most affected leg of children with CP compared with typically developing peers.InterpretationIncreased selective muscle fatigue of the lower leg muscles was observed during self-paced walking in children with mild-to-moderate severe CP. This could contribute to and account for limited walking capacity.What this paper addsChildren with cerebral palsy (CP) show more signs of lower leg muscle fatigue than typically developing peers. No signs of muscle fatigue were observed in upper leg muscles of children with CP.
| S-EPMC7379556 | biostudies-literature
Project description:AimTo assess the efficacy and safety of repeat abobotulinumtoxinA injections in reducing upper limb spasticity in children with cerebral palsy (CP).MethodThis was a double-blind, repeat-cycle study (NCT02106351) in children with CP (2-17y). Children were randomized to receive 2U/kg (control), 8U/kg, or 16U/kg abobotulinumtoxinA injections into the target muscle group (wrist or elbow flexors) and additional muscles alongside occupational therapy via a home-exercise therapy program (HETP; minimum five 15min sessions/wk). Children received 8U/kg or 16U/kg plus HETP in cycles 2 to 4.ResultsDuring cycle 1, 210 children (126 males, 84 females; mean age [SD] 9y [4y 5mo], range 2-17y; n=70/group) had at least one upper limb abobotulinumtoxinA injection and 209 complied with the HETP. At week 6 of cycle 1, children in the 8U/kg or 16U/kg groups had significantly lower Modified Ashworth scale scores versus the 2U/kg group (primary outcome: treatment differences of -0.4 [p=0.012] and -0.7 [p<0.001] respectively). All groups improved on Physician Global Assessment and children in all groups achieved their treatment goals at least as expected. Therapeutic benefits were sustained during cycles 2 to 4; muscular weakness was the only treatment-related adverse event reported in at least one child/group (4.3% and 5.7% vs 1.4% respectively).InterpretationTreatment with 8U/kg or 16U/kg abobotulinumtoxinA significantly reduced upper limb spasticity versus the 2U/kg control dose. Therapeutic benefits of abobotulinumtoxinA plus HETP were sustained with repeat treatment cycles.What this paper addsAbobotulinumtoxinA injections significantly reduced upper limb spasticity in children with cerebral palsy. Children treated with abobotulinumtoxinA and targeted home exercises showed global improvement and goal attainment. Benefits were sustained over 1 year with repeat cycles of abobotulinumtoxinA and home exercises. AbobotulinumtoxinA injections into the upper limb were well tolerated over 1 year.
| S-EPMC8048784 | biostudies-literature
Project description:Botulinum neurotoxin type-A (BoNT) injections are commonly used as spasticity treatment in cerebral palsy (CP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised, and the BoNT effect on muscle stem cells remains not well defined. This study aims at clarifying the impact of BoNT on growing muscles (1) by analyzing the in vitro effect of BoNT on satellite cell (SC)-derived myoblasts and fibroblasts obtained from medial gastrocnemius microbiopsies collected in young BoNT-naïve children (t0) compared to age ranged typically developing children; (2) by following the effect of in vivo BoNT administration on these cells obtained from the same children with CP at 3 (t1) and 6 (t2) months post BoNT; (3) by determining the direct effect of a single and repeated in vitro BoNT treatment on neuromuscular junctions (NMJs) differentiated from hiPSCs. In vitro BoNT did not affect myogenic differentiation or collagen production. The fusion index significantly decreased in CP at t2 compared to t0. In NMJ cocultures, BoNT treatment caused axonal swelling and fragmentation. Repeated treatments impaired the autophagic-lysosomal system. Further studies are warranted to understand the long-term and collateral effects of BoNT in the muscles of children with CP.
| S-EPMC10453788 | biostudies-literature
Project description:We aimed to review and analyse the effectiveness and safety of botulinum toxin type A (BoNT-A) injections for drooling in children with cerebral palsy. We searched the EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) databases from inception to January 2020. We included randomized controlled trials and observational studies which (1) involved children with cerebral palsy, (2) used BoNT-A for control of drooling, and (3) provided quantitative evaluations of drooling before and after intervention with BoNT-A. Twenty-one trials met the inclusion criteria. Most studies showed that BoNT-A injections are safe and efficacious as a treatment for drooling in children with cerebral palsy. Four trials had sufficient data to pool the results for the meta-analysis. Both the drooling quotient (p = 0.002) and drooling Ffrequency and severity scale (p = 0.004) supported this conclusion. BoNT-A injections are a safe, reversible, effective treatment for drooling control in children with cerebral palsy that can offer effectiveness for more than 3 months with few side effects. The dosage of BoNT-A should not exceed 4 units/kg. Further studies are required to determine the optimal dosage and target glands.
| S-EPMC8700360 | biostudies-literature
Project description:Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and -3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.
| S-EPMC8876834 | biostudies-literature