Botulinum Toxin Type A Neuromuscular Blockade in the Treatment of Equinus Foot Deformity in Cerebral Palsy: A Multicenter, Open-Label Clinical Trial

Koman, L. Andrew; Brashear, Allison; Rosenfeld, Samuel; Chambers, Henry G.; Russman, Barry S.; Rang, Mercer; Root, Leon; Ferrari, Eugenio; Prous, J. Garcia de Yebenes; Smith, Beth P.; Turkel, Catherine C.; Walcott, Jennifer M.; Molloy, Patricia T.

doi:10.1542/peds.108.5.1062

Cited by 148 publications

(123 citation statements)

References 27 publications

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“…Treatment with BoNT/A was very effective in correcting the position of the feet, as shown by the reduction in the heel-ground distance and by the increased range of motion of the ankle joint, confirming the findings of previous studies [10][11][12][13][14][15] . The increased dorsiflexion of the foot caused by the greater range of motion of the ankle joint was similar both with the knee extended and with the knee flexed.…”

Section: Discussionsupporting

confidence: 88%

“…Physiological explanations for this adjustment in the feet include not only weakening of the gastrocnemii and soleus but also the increase in length of the gastrocnemii muscle-tendon unit, the shortening of the antagonist muscles or a combination of these events. Any of these effects could be the direct result of chemical denervation caused by BoNT/A, and it is unlikely that they would occur spontaneously 11 .…”

Section: Discussionmentioning

confidence: 99%

“…The effects of a single dose of BoNT/A lasted on average three to six months in other studies of children with CP. Although the duration and effect of BoNT/A reported in the literature varies, it is generally considered to be effective for at least three months 11 .…”

Section: Discussionmentioning

confidence: 99%

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Botulinum toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy

Camargo

Teive

Zonta

et al. 2009

Arq. Neuro-Psiquiatr.

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-We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75±16.26 U), or 7.45±2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.Key Words: cerebral palsy, botulinum toxin, spasticity. Toxina botulínica tipo A como tratamento para espasticidade de membros inferiores em crianças com paralisia cerebralResumo -Para avaliação da segurança e eficácia do tratamento com toxina botulínica A (TB-A) na espasticidade na paralisia cerebral (PC), foram selecionadas 20 crianças com a forma diplegia espástica. Todos os pacientes receberam injeções nos gastrocnêmios e sóleos, 15 receberam doses nos adutores da coxa. A dose total variou de 70 a 140 Us (99,75±16,26 U), 7,45±2,06 U/Kg por paciente. o tratamento com a TB-A melhorou significativamente a deambulação e o padrão de marcha. Houve também significativa alteração da distância tornozelo-solo e aumento da amplitude de movimento da articulação do tornozelo. essas mudanças estruturais dos pés se mantiveram até o final do acompanhamento. o mesmo não foi observado com parâmetros funcionais. Três pacientes apresentaram fraqueza em membros inferiores. Conclui-se que a TB-A, em uma única aplicação, é segura e eficaz. Há modificação sustentada da estrutura motora dos membros inferiores, porém mudanças funcionais são temporárias, durante o pico de ação do medicamento.PAlAvrAs-CHAve: paralisia cerebral, espasticidade, toxina botulínica.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Botulinum toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy

Camargo

Teive

Zonta

et al. 2009

Arq. Neuro-Psiquiatr.

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“…Injections of BTX-A repeated every three months have proven to be safe and effective in chronic management of focal muscle spasticity in children with equinus gait [9]. A strong correlation was found between duration of response and the dynamic component in children undergoing repeated gastrocnemius muscle injections [10].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Effect of Repeated Injections of Botulinum Toxin in Children With Cerebral Palsy – A Prospective Study

Fattal‐Valevski¹,

Hayek²,

Domenievitz³

et al. 2006

Neuropediatrics

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Purpose To prospectively evaluate long-term effects of repeated botulinum toxin A (BTX-A) injections in children with cerebral palsy (CP). Methods Repeated injections of BTX-A were offered to children with CP, according to clinical indications, for a maximum of four injections within a period of two years. Injections were administered into lower extremity muscles of 26 consecutive children (age 3.7 ± 1.2 years, 16 boys) with hemiplegic or diplegic CP. Clinical assessments before and one month following each injection included a gross motor function measure (GMFM), a modified Ashworth scale, and range-of-motion of knee extension and ankle dorsiflexion. Results Twelve children received two injections, six received three injections, five received one injection, and three received four injections. The most common reason for discontinuing treatment was the need for orthopedic surgery (n = 17). A long-term effect was demonstrated by a significant increase of the GMFM score before the first injection compared with the last injection for each patient (P \ 0.0001). There was no comparable change in the muscle tone or range-of-motion. The mean rate of GMFM change during the study was significantly higher than literature norms for CP children (13.2 vs. 5.37 per year, respectively, P \ 0.01). The increase of the GMFM score before and one-month after injection (short-term effect) was significantly higher after the first injection than after the last injection (P \ 0.05). Similar results were found for the Ashworth scale and popliteal angle. Conclusions Botulinum toxin A injections have a longterm effect on gross motor function in children with CP even though the effect on muscle tone is short-term. The effect apparently declines with repeated injections, with most children benefitting from 2 to 3 injections.

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“…1,2 Botulinum toxin A is also commonly used in conjunction with surgery or serial casting for the treatment of joint contractures. Focal, intramuscular injection of BoNT-A effectively denervates a muscle by inhibiting the release of acetylcholine at the neuromuscular junction (NMJ).…”

Section: Introductionmentioning

confidence: 99%

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

Shen

Lee

et al. 2006

Journal Orthopaedic Research

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Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the management of skeletal muscle spasticity or dynamic joint contracture. Intramuscular injection of BoNT-A causes muscle denervation, paresis, and atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and injected muscle eventually regains muscle mass and recovers muscle function. The goal of the present study was to characterize the molecular and cellular mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague-Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was injected into the right gastrocnemius muscle to serve as control. The gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7 days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after administration of toxin. In addition, the gastrocnemius muscles from 1-month-old rats with no injections were harvested to serve as uninjected control group. Muscle samples were processed and mRNA was extracted. Real-time polymerase chain reaction (PCR) and gene microarray technology were used to identify key molecules involved in NMJ stabilization and muscle functional recovery. More than 28,000 rat genes were analyzed and approximately 9000 genes are expressed in the rat gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were upregulated and 59 genes were downregulated. Key molecules involved in neuromuscular junction (NMJ) stabilization and muscle functional recovery were identified and their time course of gene expression following BoNT-A injection were characterized. This animal study demonstrates that following intramuscular injection of BoNT-A, there is a sequence of cellular events that eventually leads to NMJ stabilization, remodeling, and myogenesis and muscle functional recovery. This recovery process is divided into two stages (aneural and neural) and that the IGF-1 signaling pathway play a central role in the process. ß

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Botulinum Toxin Type A Neuromuscular Blockade in the Treatment of Equinus Foot Deformity in Cerebral Palsy: A Multicenter, Open-Label Clinical Trial

Abstract: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait.

Cited by 148 publications

References 27 publications

Botulinum toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy

Botulinum toxin type A in the treatment of lower-limb spasticity in children with cerebral palsy

Long-Term Effect of Repeated Injections of Botulinum Toxin in Children With Cerebral Palsy – A Prospective Study

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

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