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Toxins
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Botulinum Toxin in the Management of Children with Cerebral Palsy
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Botulinum Toxin in the Management of Children with Cerebral Palsy

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 20716

Special Issue Editor

Prof. Dr. Anja Van Campenhout

E-Mail Website
Guest Editor
KU Leuven– University Hospital Leuven, 3000 Leuven, Belgium
Interests: cerebral palsy; pediatric orthopedics; spasticity management; gait analysis; pediatric rehabilitation

Special Issue Information

Dear Colleagues,

Botulinum toxin A (BTX) is an established treatment modality for children with cerebral palsy (CP) for the management of hypertonia. It has been demonstrated to be effective, especially as part of a multimodal integrated management. Goals are typically contracture prevention and comfort in non-ambulatory patients and improvement of function and motor and gait development in children GMFCS I-III. Goals should be set for each individual child, taking into account long-term management, including other spasticity treatment modalities and orthopedic procedures that might be necessary.

Nevertheless, there is still a lack of a uniform BTX treatment strategy, especially regarding guidelines such as optimal indications regarding ages and goals and  pre-and post-injection treatment. Further, outcomes have not been studied extensively on all ICF outcome domains, but mostly on body structure and function. Finally, there are concerns about the long-term effects of the toxin on the muscle morphology in the already abnormal CP muscle and concerns about possible long-term multiple repeat injections in children already demonstrating contractures and orthopedic structural abnormalities.

As a leading expert in your field, we would like you to participate in expanding the knowledge regarding the use of BTX in children with CP by submitting your research.

Prof. Dr. Anja Van Campenhout
Guest Editor

Manuscript Submission Information

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Keywords

  • cerebral palsy
  • botulinum toxin
  • spasticity management
  • muscle morphology
  • gait
  • function

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Published Papers (5 papers)

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Research

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15 pages, 1624 KiB  
Article
The Non-Affected Muscle Volume Compensates for the Partial Loss of Strength after Injection of Botulinum Toxin A
by Reinald Brunner, Enrico De Pieri, Christian Wyss, Claudia Weidensteiner, Katrin Bracht-Schweizer, Jacqueline Romkes, Meritxell Garcia, Norine Ma and Erich Rutz
Toxins 2023, 15(4), 267; https://doi.org/10.3390/toxins15040267 - 3 Apr 2023
Viewed by 2151
Abstract
Local botulinum toxin (BTX-A, Botox®) injection in overactive muscles is a standard treatment in patients with cerebral palsy. The effect is markedly reduced in children above the age of 6 to 7. One possible reason for this is the muscle volume [...] Read more.
Local botulinum toxin (BTX-A, Botox®) injection in overactive muscles is a standard treatment in patients with cerebral palsy. The effect is markedly reduced in children above the age of 6 to 7. One possible reason for this is the muscle volume affected by the drug. Nine patients (aged 11.5; 8.7–14.5 years) with cerebral palsy GMFCS I were treated with BTX-A for equinus gait at the gastrocnemii and soleus muscles. BTX-A was administered at one or two injection sites per muscle belly and with a maximum of 50 U per injection site. Physical examination, instrumented gait analysis, and musculoskeletal modelling were used to assess standard muscle parameters, kinematics, and kinetics during gait. Magnetic resonance imaging (MRI) was used to detect the affected muscle volume. All the measurements were carried out pre-, 6 weeks post-, and 12 weeks post-BTX-A. Between 9 and 15% of the muscle volume was affected by BTX-A. There was no effect on gait kinematics and kinetics after BTX-A injection, indicating that the overall kinetic demand placed on the plantar flexor muscles remained unchanged. BTX-A is an effective drug for inducing muscle weakness. However, in our patient cohort, the volume of the affected muscle section was limited, and the remaining non-affected parts were able to compensate for the weakened part of the muscle by taking over the kinetic demands associated with gait, thus not enabling a net functional effect in older children. We recommend distributing the drug over the whole muscle belly through multiple injection sites. Full article
(This article belongs to the Special Issue Botulinum Toxin in the Management of Children with Cerebral Palsy)
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21 pages, 1481 KiB  
Article
The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy
by Nicky Peeters, Eirini Papageorgiou, Britta Hanssen, Nathalie De Beukelaer, Lauraine Staut, Marc Degelaen, Christine Van den Broeck, Patrick Calders, Hilde Feys, Anja Van Campenhout and Kaat Desloovere
Toxins 2022, 14(10), 676; https://doi.org/10.3390/toxins14100676 - 29 Sep 2022
Cited by 6 | Viewed by 3047
Abstract
Children with spastic cerebral palsy (SCP) are often treated with intramuscular Botulinum Neurotoxin type-A (BoNT-A). Recent studies demonstrated BoNT-A-induced muscle atrophy and variable effects on gait pathology. This group-matched controlled study in children with SCP compared changes in muscle morphology 8–10 weeks post-BoNT-A [...] Read more.
Children with spastic cerebral palsy (SCP) are often treated with intramuscular Botulinum Neurotoxin type-A (BoNT-A). Recent studies demonstrated BoNT-A-induced muscle atrophy and variable effects on gait pathology. This group-matched controlled study in children with SCP compared changes in muscle morphology 8–10 weeks post-BoNT-A treatment (n = 25, median age 6.4 years, GMFCS level I/II/III (14/9/2)) to morphological changes of an untreated control group (n = 20, median age 7.6 years, GMFCS level I/II/III (14/5/1)). Additionally, the effects on gait and spasticity were assessed in all treated children and a subgroup (n = 14), respectively. BoNT-A treatment was applied following an established integrated approach. Gastrocnemius and semitendinosus volume and echogenicity intensity were assessed by 3D-freehand ultrasound, spasticity was quantified through electromyography during passive muscle stretches at different velocities. Ankle and knee kinematics were evaluated by 3D-gait analysis. Medial gastrocnemius (p = 0.018, −5.2%) and semitendinosus muscle volume (p = 0.030, −16.2%) reduced post-BoNT-A, but not in the untreated control group, while echogenicity intensity did not change. Spasticity reduced and ankle gait kinematics significantly improved, combined with limited effects on knee kinematics. This study demonstrated that BoNT-A reduces spasticity and partly improves pathological gait but reduces muscle volume 8–10 weeks post-injections. Close post-BoNT-A follow-up and well-considered treatment selection is advised before BoNT-A application in SCP. Full article
(This article belongs to the Special Issue Botulinum Toxin in the Management of Children with Cerebral Palsy)
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18 pages, 1083 KiB  
Article
Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy
by Nathalie De Beukelaer, Guido Weide, Ester Huyghe, Ines Vandekerckhove, Britta Hanssen, Nicky Peeters, Julie Uytterhoeven, Jorieke Deschrevel, Karen Maes, Marlies Corvelyn, Domiziana Costamagna, Ghislaine Gayan-Ramirez, Anja Van Campenhout and Kaat Desloovere
Toxins 2022, 14(2), 139; https://doi.org/10.3390/toxins14020139 - 14 Feb 2022
Cited by 18 | Viewed by 4774
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Botulinum Toxin in the Management of Children with Cerebral Palsy)
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11 pages, 1610 KiB  
Article
Effect of Botulinum Toxin Injection on the Progression of Hip Dislocation in Patients with Spastic Cerebral Palsy: A Pilot Study
by Yookyung Lee, Seungeun Lee, Joonyoung Jang, Jiwoon Lim and Ju Seok Ryu
Toxins 2021, 13(12), 872; https://doi.org/10.3390/toxins13120872 - 6 Dec 2021
Cited by 8 | Viewed by 3274
Abstract
Hip adductor spasticity is a contributing factor to hip dislocation in patients with cerebral palsy (CP). We hypothesized that botulinum toxin injected into the hip adductor muscles would reduce spasticity and help prevent hip dislocation. Twenty patients with bilateral spastic CP aged 2 [...] Read more.
Hip adductor spasticity is a contributing factor to hip dislocation in patients with cerebral palsy (CP). We hypothesized that botulinum toxin injected into the hip adductor muscles would reduce spasticity and help prevent hip dislocation. Twenty patients with bilateral spastic CP aged 2 to 10 years with gross motor function classification system level IV or V were included. Botulinum toxin was injected into the hip adductor muscles at baseline and at 6-month follow-up. Muscle tone was measured with an eight-channel surface electromyography (EMG) recorder. A hip X-ray was performed, and Reimer’s hip migration index (MI) was measured. The Wilcoxon signed-rank test was used to compare the surface EMG values of the hip muscles at baseline and follow-up. The mean root mean square surface EMG value of the hip adductor muscles was significantly reduced at 1, 2, 3, and 7 months after the first injection, up to approximately 53% of the baseline. The 1-year progression of the hip MI was −0.04%. Repeated sessions of botulinum toxin injections at the hip adductor muscles significantly reduced muscle tone and hip displacement. A botulinum toxin injection may be used as an adjunctive treatment in the prevention of hip dislocation. Full article
(This article belongs to the Special Issue Botulinum Toxin in the Management of Children with Cerebral Palsy)
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Review

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29 pages, 1110 KiB  
Review
Botulinum Toxin Intervention in Cerebral Palsy-Induced Spasticity Management: Projected and Contradictory Effects on Skeletal Muscles
by Cemre Su Kaya Keles and Filiz Ates
Toxins 2022, 14(11), 772; https://doi.org/10.3390/toxins14110772 - 8 Nov 2022
Cited by 19 | Viewed by 6451
Abstract
Spasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This [...] Read more.
Spasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This leads to functional limitations at the respective joint. Focal injection of botulinum toxin type-A (BTX-A) is effectively used to manage spasticity and improve the quality of life of the patients. By blocking acetylcholine release at the neuromuscular junction and causing temporary muscle paralysis, BTX-A aims to reduce spasticity and hereby improve joint function. However, recent studies have indicated some contradictory effects such as increased muscle stiffness or a narrower range of active force production. The potential of these toxin- and atrophy-related alterations in worsening the condition of spastic muscles that are already subjected to changes should be further investigated and quantified. By focusing on the effects of BTX-A on muscle biomechanics and overall function in children with CP, this review deals with which of these goals have been achieved and to what extent, and what can await us in the future. Full article
(This article belongs to the Special Issue Botulinum Toxin in the Management of Children with Cerebral Palsy)
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