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      Crotoxin in humans: analysis of the effects on extraocular and facial muscles Translated title: Crotoxina em humanos: estudo da ação em músculos extraoculares e faciais

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          Abstract

          PURPOSE: Crotoxin is the main neurotoxin of South American rattlesnake Crotalus durissus terrificus. The neurotoxic action is characterized by a presynaptic blockade. The purpose of this research is to assess the ability of crotoxin to induce temporary paralysis of extraocular and facial muscles in humans. METHODS: Doses of crotoxin used ranged from 2 to 5 units (U), each unit corresponding to one LD50. We first applied 2U of crotoxin in one of the extraocular muscles of 3 amaurotic individuals to be submitted to ocular evisceration. In the second stage, we applied crotoxin in 12 extraocular muscles of 9 patients with strabismic amblyopia. In the last stage, crotoxin was used in the treatment of blepharospasm in another 3 patients. RESULTS: No patient showed any systemic side effect or change in vision or any eye structure problem after the procedure. The only local side effects observed were slight conjunctival hyperemia, which recovered spontaneously. In 2 patients there was no change in ocular deviation after 2U crotoxin application. Limitation of the muscle action was observed in 8 of the 12 applications. The change in ocular deviation after application of 2U of crotoxin (9 injections) was in average 15.7 prism diopters (PD). When the dose was 4U (2 applications) the change was in average 37.5 PD and a single application of 5U produced a change of 16 PD in ocular deviation. This effect lasted from 1 to 3 months. Two of the 3 patients with blepharospasm had the hemifacial spasm improved with crotoxin, which returned after 2 months. CONCLUSIONS: This study provides data suggesting that crotoxin may be a useful new therapeutic option for the treatment of strabismus and blepharospasm. We expect that with further studies crotoxin could be an option for many other medical areas.

          Translated abstract

          OBJETIVO: A crotoxina é a principal neurotoxina da cascavel sul-americana Crotalus durissus terrificus e sua ação neurotóxica caracteriza-se por um bloqueio pré-sináptico. O objetivo da pesquisa é avaliar a capacidade da crotoxina em induzir paralisia transitória de músculos extraoculares e faciais em seres humanos. MÉTODOS: As doses utilizadas de crotoxina foram de 2 a 5 unidades (U), sendo que cada unidade correspondia a uma DL-50. Na primeira etapa, aplicou-se 2U de crotoxina em músculos extraoculares de 3 indivíduos amauróticos, candidatos à evisceração. Na segunda etapa, realizaram-se 12 aplicações de crotoxina em músculos extraoculares de 9 indivíduos estrábicos e amblíopes. Na terceira e última etapa, utilizou-se a crotoxina para o tratamento do blefaroespasmo essencial em 3 indivíduos. RESULTADOS: Nenhum paciente demonstrou qualquer efeito sistêmico ou alteração da visão ou de qualquer estrutura ocular. O único efeito local adverso foi hiperemia conjuntival, que melhorou espontaneamente. Em 2 pacientes não houve alteração do desvio ocular após a aplicação de 2U de crotoxina. Observou-se em 8 das 12 aplicações, limitação do movimento ocular no campo de ação do músculo aplicado. A diminuição do desvio ocular com 2U crotoxina (9 aplicações) foi em média de 15,7 dioptrias prismáticas (DP); na dosagem de 4U (2 aplicações) foi em média de 37,5 DP e na única aplicação de 5U, obteve-se redução de 16 DP no desvio ocular. A alteração do alinhamento ocular manteve-se por 1 a 3 meses. Dois dos 3 pacientes portadores de blefaroespasmo apresentaram melhora dos espasmos hemifacias, os quais voltaram após 2 meses. CONCLUSÕES: Através dos resultados observados neste estudo, acreditamos que a crotoxina possa ser útil no tratamento do estrabismo e do blefaroespasmo. Novos estudos precisam ser realizados para confirmar a eficácia e a segurança da crotoxina como opção terapêutica para diversas áreas da medicina que atualmente utilizam a toxina botulínica.

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          Most cited references 40

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          Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery.

           Alan B Scott (1980)
          Sixty-seven injections of botulinum. A toxin were given to patients for correction of strabismus. No systemic complications of any kind have occurred. The maximum time of paralysis occurs four to five days following the injection, and then gradually diminishes, depending on the dose. The maximum correction of strabismus has been 40 prism diopters. The maximum follow-up following injection is six months. Injection of botulinum A toxin into extraocular muscle to weaken the muscle appears to be a practical adjunct or alternative to surgical correction.
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            ISOLATION OF NEUROTOXINS FROM THE VENOM OF BUNGARUS MULTICINCTUS AND THEIR MODES OF NEUROMUSCULAR BLOCKING ACTION.

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              Botulinum toxin injection in the management of lateral rectus paresis.

               A Scott,  S P Kraft (1985)
              Seventeen patients with lateral rectus paresis (3 bilateral) were treated by injection of botulinum toxin to the antagonist medial rectus to eliminate its unopposed action or to eliminate its contracture. This allowed maintenance of single binocular vision in most patients while waiting for the palsy to heal, especially important in two children. It allowed avoidance of surgery in some cases, and a reduction or elimination of medial rectus surgery when later intervention was needed for persistent paralysis. The release of medial rectus shortening and stiffness (contracture) after just a few days of denervation was unexpected. This implies an internal muscular mechanism of contracture, perhaps sarcomere overlap, different from the fibrotic changes found in muscles after inflammation or trauma. These results also provide a rationale for experimental denervation treatment of contracture in limb muscle disorders.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                abo
                Arquivos Brasileiros de Oftalmologia
                Arq. Bras. Oftalmol.
                Conselho Brasileiro de Oftalmologia (São Paulo, SP, Brazil )
                0004-2749
                1678-2925
                December 2012
                : 75
                : 6
                : 385-389
                Affiliations
                Belo Horizonte MG orgnameFederal University of Minas Gerais - UFMG orgdiv1School of Medicine orgdiv2Chief Professor of Ophthalmology Brazil
                Belo Horizonte MG orgnameUniversidade Federal de Minas Gerais - UFMG orgdiv1Preceptor of Strabismus Clinic Brazil
                Belo Horizonte MG orgnameHospital Foundation of Minas Gerais State - Fhemig Brazil
                Article
                S0004-27492012000600002
                10.1590/S0004-27492012000600002

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                Figures: 0, Tables: 0, Equations: 0, References: 27, Pages: 5
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