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      Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects ☆☆ Translated title: Tratamento focal da espasticidade com toxina botulínica A na paralisia cerebral GMFCS nível V – Avaliação de efeitos adversos

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          Abstract

          Objective

          To report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V.

          Methods

          This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox ® and five were other presentations), in which the basic aim was to look for adverse effects.

          Results

          The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month.

          Conclusion

          The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia.

          Resumo

          Objetivo

          relatar a experiência da aplicação de toxina botulínica A (TBA) em uma série de pacientes com paralisia cerebral (PC) GMFCS nível V.

          Métodos

          estudo retrospectivo de série de casos, 33 pacientes com PC GMFCS nível V que receberam 89 sessões para aplicação de TBA (84 Botox® e cinco outras apresentações), em busca basicamente de efeitos adversos.

          Resultados

          o número médio de sessões para aplicação por paciente foi três e a idade média em cada injeção foi 4 + 6 anos (1,6–13 anos). Os músculos mais frequentemente injetados foram gastrocnêmios, isquiotibiais, adutores do quadril, bíceps braquial e flexores dos dedos. A dose média total foi 193 U e a dose média por peso foi 12,5 U/k. Somente um paciente recebeu anestesia para as injeções e sedação não foi usada em qualquer caso. Não foram observados efeitos adversos locais ou sistêmicos dentro de seguimento mínimo de um mês.

          Conclusão

          a ausência de efeitos adversos em nossa série está provavelmente relacionada ao uso de doses baixas e ao não emprego de sedação ou anestesia. De acordo com nossos dados, a TBA pode ser usada de forma segura em pacientes com PC GMFCS nível V, em doses baixas e preferencialmente sem sedação ou anestesia.

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          Most cited references18

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          Botulinum toxin assessment, intervention and after-care for lower limb spasticity in children with cerebral palsy: international consensus statement.

          , M Kentish, S Love (2010)
          Botulinum neurotoxin type-A (BoNT-A) has been used in association with other interventions in the management of spasticity in children with cerebral palsy (CP) for almost two decades. This consensus statement is based on an extensive review of the literature by an invited international committee. The use of BoNT-A in the lower limbs of children with spasticity caused by CP is reported using the American Academy of Neurology Classification of Evidence for therapeutic intervention. Randomized clinical trials have been grouped into five areas of management, and the outcomes are presented as treatment recommendations. The assessment of children with CP and evaluation of outcomes following injection of BoNT-A are complex, and therefore, a range of measures and the involvement of a multidisciplinary team is recommended. The committee concludes that injection of BoNT-A in children with CP is generally safe although systemic adverse events may occur, especially in children with more physical limitations (GMFCS V). The recommended dose levels are intermediate between previous consensus statements. The committee further concludes that injection of BoNT-A is effective in the management of lower limb spasticity in children with CP, and when combined with physiotherapy and the use of orthoses, these interventions may improve gait and goal attainment.
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            Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases.

            Botulinum toxin type A (BTA) (Botox) received Food and Drug Administration (FDA) approval for therapeutic treatment of strabismus and blepharospasm in 1989, cervical dystonia in 2000, and cosmetic treatment of glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were approximately 1.1 to 1.6 million patients using cosmetic BTA. Our objective was to review adverse event (AE) reporting to the FDA after BTA administration. We reviewed all (therapeutic and cosmetic use) serious (per FDA regulations) AEs reported to the FDA for the 13.5 years since licensure of the product (December 1989-May 2003) and nonserious AEs reported from December 2001 to November 2002. AEs are reported to the FDA through the MedWatch system. We reviewed 1437 AE reports; 406 followed therapeutic use of BTA (217 serious and 189 nonserious) and 1031 followed cosmetic use (36 serious and 995 nonserious). Reported AEs occurred predominantly in female patients, with a median age of 50 years. In the year December 2001 to November 2002, when both serious and nonserious reports were evaluated, the proportion of reports classified as serious was 33-fold higher for therapeutic than for cosmetic cases. The 217 serious AEs reported in therapeutic cases involved a wide spectrum of events and included all 28 reported deaths. Among cosmetic users, no deaths were reported and, of the 36 serious AEs, 30 were included as possible complications in the FDA-approved label. The remaining 6 serious AEs did not display a pattern suggesting a common causal relationship to BTA. Among the 995 cosmetic cases reported to have nonserious AEs, most commonly noted were lack of effect (623, 63%), injection site reaction (190, 19%), and ptosis (111, 11%). Serious AEs were more likely to be reported for therapeutic than for cosmetic use, which may be related to higher doses, complicated underlying diseases, or both. Among cosmetic cases, few serious AEs were reported, and these were predominantly events that were previously recognized in clinical trials of BTA for the labeled use. This study is limited primarily by the incomplete nature of AE reporting by clinicians. Numerous departures from FDA-approved recommendations for drug dose, dilution, handling, site of injection, and storage were noted in these AE reports.
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              Systemic adverse events following botulinum toxin A therapy in children with cerebral palsy.

              We studied the incidence of incontinence and respiratory events in children with cerebral palsy who received injections of botulinum toxin A (BoNT-A). We used multivariable logistic regression to investigate relationships between (BoNT-A) dose, Gross Motor Function Classification System (GMFCS) level, and the incidence of bladder or bowel incontinence, unplanned hospital admission, emergency department consultation or prescription of antibiotics for respiratory symptoms, and diagnosis of upper respiratory tract infection. Of 1980 injection episodes in 1147 children (mean age 4y 7mo, SD 1y 10mo, range 9mo-23y), 488 (25%) were in children with unilateral involvement and 1492 (75%) in children with bilateral involvement. At the time of injection 440 (22.2%) of children were at GMFCS level I, 611 (30.9%) were at level II, 330 (16.7%) were at level III, 349 (17.6%) were at level IV, and 250 (12.6%) were at level V. The incidence of serious adverse events was low, with 19 episodes of incontinence (1% of injection episodes) and 25 unplanned hospital admissions due to respiratory symptoms (1.3%). Incontinence typically resolved spontaneously 1 to 6 weeks after injection. The incidence of adverse events was associated with GMFCS level and dose of BoNT-A. The incidence of serious adverse events was low but suggests systemic spread as well as a procedural effect. We recommend reviewing upper dose limits for children at all GMFCS levels, particularly those at levels IV and V with a history of aspiration and respiratory disease. In these children, alternatives to mask anaesthesia may be particularly important.
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                Author and article information

                Contributors
                Journal
                Rev Bras Ortop
                Rev Bras Ortop
                Revista Brasileira de Ortopedia
                Elsevier
                2255-4971
                10 May 2014
                Jul-Aug 2014
                10 May 2014
                : 49
                : 4
                : 359-363
                Affiliations
                [0005]Instituto de Neuro-Ortopedia, Caxias do Sul, RS, Brazil
                Author notes
                [* ] Corresponding author. contato@ 123456anapaulatedesco.med.br
                Article
                S2255-4971(14)00097-4
                10.1016/j.rboe.2014.04.022
                4511629
                26229827
                7ed52f72-428b-42ec-b5ae-790d7d42f755
                © 2014 Sociedade Brasileira de Ortopedia e Traumatologia. Published by Elsevier Editora Ltda.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 7 February 2013
                : 1 August 2013
                Categories
                Original Article

                cerebral palsy,muscle spasticity,botulinum toxin,paralisia cerebral,espasticidade muscular,toxinas botulínicas

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