Efeito Agudo da Terapia do Espelho na Reabilitação do Membro Superior de Indivíduos com Hemiparesia após Acidente Vascular Cerebral

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1 UNIVERSIDADE FEDERAL DE CIÊNCIAS DA SAÚDE DE PORTO ALEGRE UFCSPA CURSO DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA REABILITAÇÃO Ariane Bôlla Freire Efeito Agudo da Terapia do Espelho na Reabilitação do Membro Superior de Indivíduos com Hemiparesia após Acidente Vascular Cerebral Porto Alegre

2 Ariane Bôlla Freire Efeito Agudo da Terapia do Espelho na Reabilitação do Membro Superior de Indivíduos com Hemiparesia após Acidente Vascular Cerebral. Dissertação submetida ao Programa de Pós-Graduação em Ciências da Reabilitação da Fundação Universidade Federal de Ciências da Saúde de Porto Alegre como requisito para a obtenção do grau de Mestre. Orientadora: Dra. Caren Luciane Bernardi Porto Alegre

3 DEDICATÓRIA Dedico este trabalho à minha família, meu alicerce em todos os momentos da vida. À eles, toda a minha motivação por evoluir e batalhar sempre. 3

4 AGRADECIMENTOS Agradeço primeiramente a Deus e aos meus mentores espirituais, por se fazerem sempre presentes em minha vida, oferecendo todo o suporte, energia e força necessária para a conclusão desta etapa. A minha família, por todo o apoio e entendimento que foram essenciais para que essa conquista fosse concretizada. A Santa Teresinha das Rosas, que mesmo antes do resultado sair já havia me deixado um recado, de que eu mudaria sim para Porto Alegre e seria aprovada na seleção que eu tanto almejava. À minha amiga e orientadora, Caren Bernardi. Serei eternamente grata por ter aberto as portas e o coração para mim, com certeza tu fizestes essa trajetória ser mais leve, feliz e honesta. A começar pelas reuniões que tu enfatizavas que deveriam ser breves e acabavam levando um turno inteiro, incluindo café, almoço e café novamente; discutíamos o projeto sim, e um pouco da vida toda. Hoje, levo daqui uma amiga muito especial e com certeza estarás sempre no meu coração. A professora Ana Lúcia Cervi, a quem eu tenho grande admiração pelo conhecimento científico e didático, mas sobretudo pelos ensinamentos e sangue no olho quando falámos da fisioterapia neurológica, esse sangue no olho também carrego. Tu foste minha guia e também inspiração dentro da neuro, mostrou o caminho e antes mesmo de eu ter conhecimento, contatou quem seria minha futura orientadora. A todos os professores de graduação e pós-graduação que passaram pela minha vida e transmitiram sua inspiração e amor pela fisioterapia neurológica e neurociências, que me instigam a buscar sempre mais. Ao programa de pós-graduação em Ciências da Reabilitação da Universidade Federal de Ciências da Saúde de Porto Alegre, pela oportunidade de realização do mestrado. A minha querida parceira e hoje, finalmente, bolsista de iniciação científica Chen Chai Ling, por sua dedicação e incontáveis horas de coletas, tabulação de dados e tudo mais que fosse necessário ser feito. 4

5 A querida doutoranda Elren Passos, que tentava sempre me acalmar dizendo que tudo daria certo. Sem a tua ajuda e positividade durante todo o processo, seria muito mais difícil. Aos amigos que sempre incentivaram e torceram pelo meu sucesso, entenderam minha ausência, e mesmo longe fizeram-se sempre presentes. A todos os colegas que me auxiliaram na fase de construção desse projeto. A CAPES pelo auxílio financeiro nesses dois anos de formação, o que facilitou muito minha mudança para Porto Alegre e me deu maior segurança para que eu conseguisse finalizar essa etapa. 5

6 RESUMO O Acidente vascular cerebral (AVC) caracteriza-se pela má perfusão encefálica decorrente de um evento isquêmico ou hemorrágico, sendo uma das principais causas de morte e incapacidade no mundo. Dentre as possíveis complicações incapacitantes causadas pelo AVC, a principal delas é a paresia no membro superior (MS) contralateral à lesão, pois está diretamente relacionada à capacidade funcional. A Terapia do Espelho (TE) tem sido utilizada na recuperação motora do MS de indivíduos após AVC e seus efeitos podem estar relacionados à ativação de neurônios espelho e alterações do córtex motor primário. Ainda não há evidências sobre os efeitos agudos da TE sobre o controle motor do MS parético de pacientes após AVC durante a realização de uma tarefa funcional. Dessa maneira, o objetivo desta pesquisa foi investigar o efeito agudo da TE sobre as estratégias de controle motor do MS parético de indivíduos após AVC crônico, durante tarefa de alcance. O estudo caracterizase como um ensaio clínico cruzado randomizado (cross-over), no qual foram avaliados indivíduos após AVC, com idade entre 30 e 80 anos. Os pacientes que primeiramente participaram do grupo intervenção realizaram uma única sessão de TE com duração de 30 minutos, enquanto no grupo controle foi realizada uma única sessão composta pelos mesmos exercícios, porém sem o espelho. Após um mês de washout, os pacientes trocaram de grupo de intervenção. Trinta e três pacientes concluíram o estudo e foram avaliados, antes e após as intervenções, quanto ao controle motor, destreza manual e espasticidade do MS. Entre as variáveis cinemáticas, somente o tempo do ciclo do movimento apresentou significância estatística em ambos os grupos após as intervenções (ES=0.53; p<0.006). A destreza manual (ES=0.03; p< 0.016), espasticidade de flexores de cotovelo (ES=0.29; p<0.000), punho (ES=0.54; p<0.001) e adutor horizontal de ombro (ES=0.68; p<0.011) também apresentaram melhora significativa após ambas as intervenções. Apenas a espasticidade de flexores de punho demonstrou diferença entre as intervenções (p<0.046), sugerindo que a magnitude da redução da espasticidade observada após a TE foi maior que a observada após a intervenção controle. Esses resultados demonstram uma melhora efetiva no tempo de ciclo de movimento durante a tarefa, destreza manual e a espasticidade do MS parético após ambas as intervenções, no entanto, as comparações entre grupos não revelaram diferenças significativas, exceto para espasticidade dos flexores do punho. Sendo assim, este estudo indica que a TE isolada não foi mais eficaz que o treinamento direto de ambos os membros superiores dos pacientes após AVC crônico. Palavras-Chave: Acidente vascular cerebral, terapia do espelho, extremidade superior, análise cinemática. 6

7 ABSTRACT Stroke is characterized by poor brain perfusion resulting from an ischemic or hemorrhagic event, being one of the leading causes of death and disability in the world. Among the possible incapacitating complications caused by stroke, the main one is paresis in the upper extremity (UE) contralateral to the injury, because it is directly related to functional capacity. Mirror Therapy (MT) is a new modality in the motor recovery of the UE of individuals after stroke, and its effects may be related to the activation of mirror neurons and alterations of the primary motor cortex. There is still no evidence on the acute effects of MT on the motor control of paretic UE in post-stroke patients during the performance of a functional task. Thus, the aim of this study was to investigate the acute effect of MT on motor control of paretic UE of individuals after chronic stroke, during a task of reaching. This study is a randomized cross-over trial, where subjects after stroke were evaluated, with ages between 30 and 80 years. Patients who first participated in the intervention group performed a single session of MT with duration of 30 minutes, whereas in the control group a single session composed of the same exercises, was conducted, but without the mirror. After a month of washout, the patients switched groups. Thirty-three patients completed the study and were evaluated, before and after the interventions, regarding kinematic outcomes, manual dexterity, and UE spasticity. Among the kinematic variables, only the movement cycle time presented statistical significance in both groups after interventions (ES=0.53; p<0.006). The manual dexterity (ES=0.03; p<0.016), spasticity of elbow flexors (ES=0.29; p<0.000), wrist flexors (ES=0.54; p<0.001) and horizontal shoulder adductor (ES=0.68; p<0.011) also improved after both interventions. Only the spasticity of wrist flexors demonstrated a significant difference between the interventions (p<0.046), suggesting that the magnitude of the spasticity reduction observed after MT was higher than that observed after the control intervention. These results demonstrate an effective improvement in movement cycle time during the task, manual dexterity and spasticity of paretic UE after both interventions, however, comparisons between groups did not reveal significant differences except for spasticity of the wrist flexors. Thus, this study indicates that isolated MT was no more effective than direct training of both UE of patients after chronic stroke. Keywords: Stroke, mirror therapy, upper extremity, kinematic analysis. 7

8 LISTA DE FIGURAS Figura 1. The participants flow diagram Figura 2. Mirror Therapy Figura 3. Kinematic analysis of the reach task Figura 4. Box and Block Test

9 LISTA DE TABELAS Tabela 1. Baseline patient s characteristics Tabela 2. Statistical analysis pre and post evaluations of interventions for Mirror Therapy Intervention versus Control Intervention

10 LISTA DE ABREVIATURAS E SIGLAS AJ AS AVC AVD S BBT CAPES CEP CG FMA IC MAS MCT MMV MS MT RM-EFE RM-SAA RM-SFE SNC SPSS TE UE UFCSPA Average Jerk Adjusting Sway Acidente Vascular Cerebral Atividades de Vida Diária Box and Block Test Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Comitê de Ética e Pesquisa Control Group Fugl-Meyer Assessment Scale Index of Curvature Modified Ashworth Scale Movement Cycle Time Mean Movement Velocity Membro Superior Mirror Therapy Range of Motion Elbow Flexion/Extension Range of Motion Shoulder Abduction/Adduction Range of Motion Shoulder Flexion/Extension Sistema Nervoso Central Statistical Package for Social Sciences Terapia do Espelho Upper Extremity Universidade Federal de Ciências da Saúde de Porto Alegre 10

11 SUMÁRIO 1 INTRODUÇÃO REVISÃO DE LITERATURA Acidente Vascular Cerebral Análise Cinemática do membro superior Destreza manual Espasticidade do membro superior Terapia do Espelho REFERÊNCIAS BIBLIOGRÁFICAS DA REVISÃO ARTIGO CONCLUSÃO GERAL ANEXOS ANEXO A Normas de formatação do periódico Clinical Rehabilitation ANEXO B Parecer do CEP

12 1 INTRODUÇÃO As doenças cerebrovasculares estão em segundo lugar dentre as doenças que mais resultam em óbitos no mundo, perdendo a posição apenas para as doenças cardiovasculares, segundo o Ministério da Saúde (2013). O Acidente vascular cerebral (AVC) caracteriza-se como uma doença do sistema nervoso central (SNC) causada pela perda parcial da função cerebral (1) que pode levar a distúrbios motores, cognitivos e sensoriais (2). Dessa forma, o AVC é uma das patologias mais frequentes e incapacitantes no Brasil e no mundo (3), caracterizando-se como a principal causa de limitações nas atividades de vida diária (AVD s) dos pacientes e, podendo causar dependência de cuidados de longa-duração (4). Embora as disfunções sensoriais e cognitivas contribuam em grande proporção para a deficiência global, o comprometimento motor é, muitas vezes, o déficit mais marcante (5). Aproximadamente 85% dos indivíduos após o AVC apresentam paresia do membro superior (MS), o que resulta em comprometimentos sensório-motores (6), restrição das atividades funcionais (7), podendo levar a déficits de controle motor (8, 9), disfunção motora (10) e na execução de AVD s (11). Sendo assim, sabendo-se que a função do MS é fundamental para o desempenho adequado das AVD s, a reabilitação do membro acometido deve ser enfatizada durante os programas de reabilitação (12). Cada vez mais buscam-se estratégias focadas na neuroplasticidade que promovam a recuperação funcional e o bem estar biopsicossocial dos indivíduos que sofreram AVC (13). Diante disso, uma das terapias sugeridas por Altschuler et al. (1999) (14) é a Terapia do Espelho (TE), a qual consiste em um estímulo sensório-motor baseado na teoria da plasticidade cerebral e reorganização funcional cortical. A TE foi introduzida por Ramachandran, em 1996, para tratar a dor do membro fantasma após amputação (15) e, a partir disso, vem sendo aplicada para o tratamento de pacientes após AVC, lesões do sistema nervoso periférico, distrofia simpático reflexa e desordens de coordenação (16). A TE é aplicada por meio de um espelho que é posicionado entre os MSs do indivíduo de modo sagital. Com a intenção de promover uma ilusão 12

13 visual e sinestésica, o indivíduo realiza movimentos com o membro saudável que são refletidos pelo espelho e interpretados como se fossem realizados pelo membro afetado/parético (15, 17). Autores demonstram que essa estimulação visual e ilusiva relaciona-se à reorganização cortical funcional e pode, terapeuticamente, ser usada para melhorar o desempenho motor e a percepção do MS afetado (18, 19). Os mecanismos exatos pelos quais a TE promove seu efeito ainda não são bem claros, porém sabe-se que o movimento assistido através do espelho influencia na comunicação cerebral inter-hemisférica, e outras áreas são ativadas além das áreas motoras (5, 18). Estudos demonstram que a presença do espelho altera o padrão de ativação inicialmente assimétrico em pacientes após AVC para um padrão mais simétrico (20), gerando mudança no equilíbrio de ativação no córtex motor primário em direção ao hemisfério afetado após a TE (21). Diversos estudos envolvendo ressonância magnética funcional e eletroencefalograma têm demonstrado os mecanismos através dos quais a TE exerce seus efeitos sobre o SNC (22, 23). Além disso, outras pesquisas mostram o efeito da TE sobre os mecanismos de controle motor do MS, através das variáveis cinemáticas, durante a execução de uma tarefa funcional (24). De acordo com Wagner et al. (2007) (25), a ação de alcançar um objeto é um elemento fundamental para muitas AVD s e tem sido utilizada, frequentemente, como a tarefa representada por medidas cinemáticas em diversos estudos (26, 27). A análise cinemática do movimento permite avaliar os aspectos do controle do motor e pode ser utilizada para detectar as características espaciais e temporais dos movimentos do MS (28), importantes para a compreensão dos mecanismos de aprendizagem motora, além de detectar os efeitos do tratamento no controle motor em pacientes após AVC (29). As informações cinemáticas, incluindo: tempo, suavidade de movimento, linearidade, assimetria de movimento, velocidade do movimento e coordenação multiarticular, podem auxiliar a entender se há aumento nas habilidades motoras de pacientes após AVC (28) e refletem a possível reestruturação cerebral induzida pela TE (30). Autores propõem que a ilusão visual durante a TE gera um feedback positivo para o córtex motor e pode remodelar os mecanismos corticais de 13

14 sensação e movimento, capaz de melhorar a função do MS (23, 31). Entretanto, como essas alterações corticais influenciam no controle motor ainda não está bem elucidado na literatura. Vários estudos têm mostrado efeitos positivos da TE em indivíduos após AVC, porém, a maioria destes utiliza a terapia associada a outras técnicas como terapia de contensão induzida, estimulação elétrica funcional, estimulação transcraniana, reabilitação convencional, dentre outras (32-36). Desta forma, ainda não é possível afirmar que essa melhoria decorre puramente da TE, já que a maioria dos estudos associam-na à outras técnicas (5). Além disso, salienta-se que apenas um estudo investigou o efeito agudo de uma sessão de TE, tendo evidenciado um aumento na conectividade efetiva entre o córtex motor primário e o córtex somatossensorial no hemisfério lesionado (37). Estes fatores realçam a falta de evidências que verifiquem os efeitos de uma única sessão de TE, sem associação com outras terapias, sobre as estratégias de controle motor do MS de pacientes após AVC. Dessa maneira, o objetivo desta pesquisa foi investigar o efeito agudo da TE sobre o controle motor, destreza manual e espasticidade do MS parético de indivíduos com paresia crônica após AVC, durante tarefa de alcance. 2 REVISÃO DE LITERATURA 2.1 Acidente Vascular Cerebral O AVC é um quadro clínico neurológico agudo causada pela interrupção do suprimento sanguíneo cerebral. A maior parte dos casos de AVC é de origem isquêmica (80%), resultando da obstrução do fluxo sanguíneo, enquanto 20% são devido à hemorragia intracerebral primária. Essa doença é uma das maiores causas de incapacidade crônica e morte no Brasil e em países industrializados ocidentais (4, 38). De acordo com o Ministério da Saúde (2013), as doenças cerebrovasculares estão em segundo lugar dentre as doenças que mais acometem vítimas com óbitos no mundo, perdendo a posição apenas para as doenças cardiovasculares. 14

15 Na presença do déficit energético gerado pelo evento isquêmico ou hemorrágico, os neurônios são incapazes de manter os seus gradientes iônicos transmembrana, resultando em um desbalanço hidroeletrolítico que dispara cascatas de morte celular por necrose e apoptose o que, consequentemente, leva a sinais e sintomas neurológicos focais (39). Déficits motores, incluindo hemiparesia, incoordenação motora e espasticidade, são os sintomas mais comuns após o AVC (40). Dentre os distúrbios sensório-motores, o paciente com AVC pode apresentar hemiplegia ou hemiparesia, que caracterizam-se, respectivamente, por uma paralisia completa ou parcial dos músculos de um lado do corpo, contralateral à lesão encefálica. A fase inicial da patologia caracteriza-se pela presença de hipotonia muscular (flacidez) associada à hiporreflexia ou arreflexia (41). A evolução do quadro de flacidez para a fase de espasticidade ocorre de modo lento e insidioso, sem tempo determinado e com variações de uma pessoa para outra (42). O MS parético do indivíduo com sequela de AVC limita suas atividades motoras, desde a mais simples tarefa, como levar um copo até a boca, até a mais complexa tarefa, como abotoar uma camisa. Essas restrições são consequências dos prejuízos relacionados à alteração do tônus, força muscular, amplitude de movimento e habilidades motoras específicas para o membro referido, como alcançar, pegar e manipular objetos (43). Pacientes após AVC demonstram déficits no controle motor final do movimento, no recrutamento articular e coordenação articular. O déficit no controle motor final do movimento é caracterizado por menor amplitude de movimento, tempo de movimento prolongado e trajetórias de movimento segmentadas (9, 44). Em um estudo anterior, autores descobriram que as variáveis que descrevem o tempo de movimento, suavidade, velocidade do movimento, movimento compensatório do tronco e do braço, apresentaram diferença significativa entre indivíduos saudáveis e pacientes após AVC, bem como entre pacientes com comprometimento leve e moderado (8). É de suma importância enfatizar a reabilitação da função do MS desses pacientes. As bases neurais para a recuperação após AVC relacionam-se ao conceito de plasticidade neuronal, que é a habilidade das células do SNC de modificar sua estrutura e função em resposta a uma variedade de estímulos 15

16 externos (experiência) (45). As propriedades plásticas/restauradoras do encéfalo são determinadas pelo balanço entre mecanismos celulares intrínsecos e moléculas regulatórias extrínsecas, as quais são reguladas por processos atividade dependentes e diferentes tipos de interação com o ambiente externo (46). 2.2 Análise Cinemática do membro superior A incorporação da avaliação cinemática na avaliação clínica é necessária para entender o impacto de uma deficiência ou prever efeitos de tratamentos, que vão desde as estratégias de controle motor até a funcionalidade (8). A análise cinemática fornece uma avaliação valiosa e objetiva do desempenho motor durante tarefas funcionais (8), capturando estratégias de controle motor, que dificilmente podem ser detectadas por escalas clínicas (47), e permitindo a compreensão da melhora do desempenho motor. Dessa forma, as medidas cinemáticas, juntamente com avaliações clínicas, podem esclarecer as estratégias de controle motor subjacentes às melhorias motoras de pacientes após AVC (28). A avaliação cinemática tem sido amplamente aplicada para discriminar as diferenças nas estratégias de movimento entre pessoas com AVC e adultos saudáveis (48), para avaliar os efeitos de intervenções terapêuticas (49, 50) bem como a recuperação do MS após o AVC (25). Descrições de padrões motores utilizados para execução de tarefas podem ajudar a quantificar os níveis de prejuízo em indivíduos após AVC, visto que esses pacientes apresentam déficits no controle motor, caracterizado por amplitude de movimento pequena, tempos de movimento prolongados e trajetórias de movimento segmentadas (44). As variáveis cinemáticas do movimento fornecem medidas detalhadas em dois níveis: de desempenho motor e qualidade de movimento. Ambos os níveis de descrição do movimento estão sendo cada vez mais utilizados como desfechos em estudos envolvendo a reeducação do movimento do MS em indivíduos após AVC (49, 51). O alcance, um elemento fundamental de muitas AVD s, é comumente escolhido como tarefa representada para medidas cinemáticas (25). Alcançar um alvo envolve controle motor final e coordenação articular do MS, isto é, 16

17 comandos centrais planejam uma trajetória linear, eficiente e suave e, em seguida, coordenam os movimentos das articulações do MS para atingir o alvo (52). As variáveis cinemáticas, incluindo as trajetórias de movimento, recrutamento articular e coordenação articular, são frequentemente utilizadas para caracterizar o déficit, a recuperação e os efeitos do tratamento nas estratégias de controle motor durante o alcance (29). Estudos sobre os efeitos da TE na recuperação do MS de pacientes após o AVC mostram melhora na amplitude de movimento, na velocidade e precisão dos movimentos, aumento da força muscular, melhora na função motora e recuperação funcional em pacientes com AVC crônico (21). Em estudo prévio, Alt Murphy et al. (2011) (8) relatam que variáveis que descrevem tempo de movimento, suavidade e velocidade, demonstraram diferenças significativas entre indivíduos saudáveis e pacientes pós-avc. Ainda, a suavidade do movimento parece ser um parâmetro importante para discriminar a qualidade do movimento entre pacientes com AVC e indivíduos saudáveis (6). Estudo que investigou os efeitos do protocolo de observação de ação baseado em TE, em pacientes com AVC crônico, revelou uma diminuição significativamente maior no tempo de movimento no grupo experimental em comparação com o grupo controle (36). As descobertas através de análises cinemáticas também mostraram que o tempo de reação mais curto (maior eficiência no pré-planejamento motor), movimento mais linear do MS e uma melhor coordenação ombro-cotovelo ocorreram após tratamento intensivo de 4 semanas de TE (53), indicando que a TE promove a normalização do movimento (54). Embora existam estudos que demonstrem os efeitos crônicos da TE em associação com outras técnicas de tratamento sobre as variáveis cinemáticas do MS de pacientes após AVC durante a execução de uma tarefa funcional (24), ainda não existem estudos que relatem o efeito agudo da TE sobre essas variáveis. Sendo assim, mais pesquisas envolvendo a TE são necessárias para conhecer seus efeitos agudos e isolados sobre o controle motor e a funcionalidade do MS de indivíduos após AVC, durante uma tarefa funcional. 2.3 Destreza manual 17

18 O AVC é a primeira causa de déficit manual adquirido em adultos e aproximadamente 50% dos sobreviventes de AVC apresentam prejuízos na função do MS e na destreza manual, o que afeta negativamente as AVD s e a independência (55, 56). A destreza manual é definida como a habilidade de realizar movimentos precisos e coordenados de mãos e dedos, como o controle fino de agarrar e manipular objetos pequenos. A maioria dos componentes de destreza manual foi estudada em indivíduos com AVC, e deficiências na destreza manual estão correlacionadas com a menor independência dos movimentos dos dedos, tempo prolongado de movimento, déficit no movimento sequencial de dedos e diminuição da precisão no controle de força (57). O Box and Block Test (BBT) consiste em um teste muito utilizado em vários estudos para avaliação da destreza manual grossa (33, 34, 36, 58). A confiabilidade deste teste foi relatada como excelente (correlação intraclasse coeficiente 0.89 a 0.97) (59). Diversos estudos com pacientes após AVC, que associaram a TE com outras modalidades terapêuticas, demonstraram melhora na destreza manual desses pacientes (32-36, 60, 61). 2.4 Espasticidade do membro superior Dentre os distúrbios sensório-motores, o paciente com AVC pode apresentar alteração do tônus muscular. A fase inicial após o acidente caracteriza-se pela presença de hipotonia muscular (41), que evolui para a fase de espasticidade, sem tempo determinado e com variações individuais (42). A espasticidade é caracterizada por aumento na resistência passiva ao alongamento velocidade-dependente e postula-se que após o AVC, esteja relacionada à incapacidade por limitar a amplitude dos movimentos do músculo agonista (62). Essas restrições são consequências dos prejuízos relacionados à alteração do tônus, força muscular, amplitude de movimento e habilidades motoras específicas para o membro referido, como alcançar, pegar e manipular objetos (43). Assim, a hipertonia de músculos flexores de cotovelo, por exemplo, tornaria impossíveis movimentos coordenados dos músculos extensores de cotovelo durante atividades de alcance (62). 18

19 A Escala Modificada de Ashworth consiste no padrão outro de avaliação de tônus muscular, possuindo boa confiabilidade inter e intra-avaliadores (63). Ela consiste em uma escala de 6 pontos que avalia a resistência ao movimento passivo, nos quais escores mais altos correspondem a espasticidade ou aumento do tônus, enquanto escores mais baixos indicam tônus muscular normal (64). Estudos utilizando a TE associada a outras técnicas (estimulação elétrica funcional, reabilitação convencional) apresentaram melhorias significativamente maiores nas funções motoras e espasticidade do MS distal do que proximal, comparada aos grupos controle (32, 65, 66). 2.5 Terapia do Espelho A TE é uma das técnicas de reabilitação potencialmente benéficas para a recuperação sensório-motora do MS de pacientes após AVC e é baseada na teoria da plasticidade cerebral e reorganização funcional cortical (12, 21, 67, 68). A TE foi primeiramente introduzida por Ramachandran, em 1996, para tratar a dor no membro fantasma após a amputação (15), e este estudo tornou-se a base para futuras pesquisas sobre a neuroplasticidade do SNC. Desde então, a TE vem sendo aplicada para o tratamento do AVC, lesões do sistema nervoso periférico, distrofia simpático reflexa e desordens de coordenação motora (7, 12, 65). Somente no final da década de 1990, Altschuler et al. (1999) (14) introduziram a TE na reabilitação de pacientes hemiparéticos após AVC, apresentando melhorias na amplitude de movimento, velocidade, destreza, força muscular e recuperação funcional do braço parético (69). A partir de então, a TE tem sido utilizada para melhorar a função do MS, principalmente em indivíduos após AVC crônico (7). A maioria das pesquisas mostram a eficácia da TE na melhora da função do MS (68), entretanto, se essa melhora é devido a TE ou apenas a sua associação com outras abordagens terapêuticas, ainda não é claro, já que a maioria dos estudos associam a TE com outras modalidades terapêuticas (5). A TE é aplicada por meio de um espelho que é posicionado entre os MSs do indivíduo de modo sagital. Com a intenção de reeducar o cérebro e 19

20 promover uma ilusão visual e sinestésica, o indivíduo realiza uma série de movimentos com o membro saudável que são refletidos pelo espelho e interpretados como se fossem realizados pelo membro afetado (15). Assim, criase uma ilusão convincente de que os movimentos do braço afetado atrás do espelho parecem ser feitos de forma tão eficaz quanto o braço não afetado (70). Esta ilusão visual pode ser utilizada para melhorar o desempenho motor e a percepção do membro afetado (19, 68). Sugere-se que os efeitos da TE podem estar relacionados à ativação de neurônios espelho, os quais são ativados quando um indivíduo observa outro realizando movimentos, e durante a prática mental de tarefas motoras (17), (19). Neurônios espelho são células nervosas com propriedades visual-motoras, que foram descobertas na área F5 do cérebro do macaco (71, 72). Esse tipo específico de neurônios, também presente no cérebro humano, são ativados quando uma ação está em andamento ou quando a ação é observada, sendo realizada por outros (73). Embora pesquisas clínicas indiquem a eficácia da TE, as alterações neurais subjacentes associadas à ela ainda são pouco compreendidas. Pesquisas sugerem que o feedback do espelho modifica o funcionamento do córtex motor primário do hemisfério que controla o braço atrás do espelho (hemisfério lesionado) (74). Após a TE, há um declínio na ativação do hemisfério contralesional e movimentos de equilíbrio de ativação em direção ao hemisfério lesionado (5). Assim, a TE induz uma reorganização das áreas pré-motoras bilaterais para estabelecer comunicação funcional com o córtex motor primário contralateral; há uma comunicação calosa aumentada do hemisfério lesionado para o sadio, equilibrando a inibição inter-hemisférica; o cerebelo também pode demonstrar ativação para melhorar o controle motor e a aprendizagem motora (18). Uma interconexão funcional, essencial para o movimento do membro parético, também é estabelecida entre o córtex somatossensorial e motor ipsilesional após sessão única de TE (37). Além disso, é observada uma excitabilidade aumentada das vias corticoespinhais correspondentes ao lado do corpo afetado, há uma ativação da área motora primária, córtex somatossensorial primário, área motora suplementar e área pré-motora do hemisfério lesionado em resposta aos movimentos realizados na TE (18). 20

21 Em um estudo de magnetoencefalografia, a presença do espelho mudou o padrão de ativação inicialmente assimétrico em pacientes com AVC para um padrão mais simétrico, indicando que a assimetria de ativação entre os hemisférios cerebrais pode ser normalizada pela TE (20). Além das áreas motoras, a TE também estimula áreas como o córtex pré-frontal dorsolateral relacionado à cognição, aumenta a atividade no córtex precuneus e cingulado posterior, áreas associadas à consciência corporal e atenção espacial (67). A maioria dos estudos sobre TE relatam o seu efeito (associado a outras modalidades terapêuticas) através de movimentos simétricos bilaterais, estimulando os pacientes verbalmente para que movam ambos os braços, da maneira que for possível (7, 14, 21, 61, 65, 68). Já, outros autores testaram diferentes condições de treinamento (unilateral ou bilateral, com ou sem espelho) a fim de investigar os efeitos de curto prazo durante a tarefa de alcance e não observaram diferenças em relação ao tempo de movimento entre as condições bimanuais com ou sem espelho (24). De outra maneira, Rodrigues et al. (2016) (75) observou melhora significativa na comparação do desempenho pré e pós-treinamento apenas para tarefas bilaterais. O valor agregado da TE é que o espelho substitui o feedback sobre o movimento do lado afetado por um feedback visual que cria a ilusão de que o lado parético se move com um padrão de movimento normal. No entanto, a partir do número relativamente pequeno de estudos e a falta de comparação direta, devido aos diferentes tipos de treinamento da TE, a forma de treinamento ideal ainda não está clara (24). 3 REFERÊNCIAS BIBLIOGRÁFICAS DA REVISÃO 1. Prange GB, Jannink MJ, Groothuis-Oudshoorn CG, Hermens HJ, Ijzerman MJ. Systematic review of the effect of robot-aided therapy on recovery of the hemiparetic arm after stroke. J Rehabil Res Dev. 2006;43(2): Rostami HR, Arefi A, Tabatabaei S. Effect of mirror therapy on hand function in patients with hand orthopaedic injuries: a randomized controlled trial. Disabil Rehabil. 2013;35(19): Mendis S. Stroke disability and rehabilitation of stroke: World Health Organization perspective. Int J Stroke. 2013;8(1):

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28 4 ARTIGO ACUTE EFFECT OF MIRROR THERAPY ON MOTOR CONTROL, MANUAL DEXTERITY AND SPASTICITY OF PARETIC UPPER EXTREMITY AFTER CHRONIC STROKE (Este artigo será submetido ao periódico Clinical Rehabilitation) Ariane Bôlla Freire 1, Elren Passos Monteiro 2, Chen Chai Ling 3, Rochelle Rocha Costa 4, Caren Luciane Bernardi 5 1 Rehabilitation Sciences Graduate Program, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil 2,4 Health Sciences Graduate Program, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil. 3 Undergraduate in Physiotherapy course, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil 4 School of Physical Education, Universidade Federal do Rio Grande do Sul, Brazil 5 Departmentof Physiotherapy, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Brazil. Correspondent Author: Ariane Bôlla Freire, PT, MSc Programa de Pós-Graduação em Ciências da Reabilitação Universidade Federal de Ciências da Saúde de Porto Alegre UFCSPA 245 Sarmento Leite Street - Porto Alegre, RS, Brazil - Zip code: Phone: aribfreire@hotmail.com 28

29 ABSTRACT Objective: To investigate the acute effect of mirror therapy (MT) on motor control, manual dexterity and spasticity of the paretic upper extremity (UE) of individuals with chronic hemiparesis after stroke, during reaching task. Design: Randomized cross-over single-blinded trial. Subjects: Thirty-three patients post chronic stroke completed the study. Intervention: Patients who first participated in the MT intervention performed a single session of MT, whereas in the control intervention a single session composed of the same exercises was performed, but without the mirror. After a month washout, the patients switched groups. Main measure: The primary outcome measure was motor control. The secondary outcome measure was manual dexterity and UE spasticity. Results: Among the kinematic outcomes, only the movement cycle time (MCT) presented statistical significance in both groups after interventions (ES=0.53; p<0.006). The manual dexterity (ES=0.03; p<0.016), spasticity of elbow flexors (ES=0.29; p<0.000), wrist flexors (ES=0.54; p<0.001) and horizontal shoulder adductor (ES=0.68; p<0.011) also improved after both interventions. Only the spasticity of wrist flexors demonstrated a difference between the interventions (p<0.046), suggesting that the magnitude of the spasticity reduction observed after MT was higher than that observed after the control intervention. Conclusions: These results demonstrate an effective improvement in MCT, manual dexterity and spasticity of paretic UE after both interventions, however, comparisons between groups did not reveal significant differences except for spasticity of the wrist flexors. Thus, this study indicates that isolated MT was no more effective than training of both UE in post chronic stroke subjects. Key words: Stroke, mirror therapy, upper extremity, kinematic analysis 29

30 INTRODUCTION Stroke is a leading global cause of incapacity (1).Although complex motor, sensory and cognitive dysfunctions contribute in various proportions to the global disability, motor impairment is often the most striking deficit (1). Up to approximately 85% of stroke survivors experience paresis of the upper extremity (UE) after the stroke (2). Patients with hemiparesis generally demonstrate abnormal motor patterns in terms of muscle tone, coordination, disrupted joint recruitment and deficits in endpoint control, which is characterized by smaller movement amplitude, prolonged movement times and segmented movement trajectories, considerably reducing motor function of the affected limb (3). An accurate and precise measurement of UE performance is essential for rehabilitation (4). Kinematic measures can better clarify the motor control strategies underlying the motor improvements of stroke patients (5), including movement trajectories (endpoint control), joint recruitment and inner joint coordination, variables frequently used to characterize the deficit, recovery and treatment effects of motor control strategies during reaching (6). Reaching has often been chosen as the represented task for kinematic measures in previous studies (7). Developing and providing effective therapeutic techniques to the improvement of UE motor control and recovery is crucial (7). Mirror Therapy (MT) was first described by Ramachandran et al. (1995) (8) in patients with phantom pain after limb amputation. In 1999, it was introduced by Altschuler et al. (9) in the rehabilitation of hemiparetic stroke survivors, showing improvements in their range of motion, speed and dexterity of the paretic arm (10). MT uses visual feedback to induce recovery of motor functions in the UE. Movements of the non-paretic arm are reflected in a mirror and create a compelling illusion in which movements of the impaired arm, behind the mirror, appear to be made as efficiently as the unimpaired arm (11). Most of the available reviews show that MT may improve UE function (12), However, whether it can do so alone or just in association with other therapeutic approaches is not clear, as most of the study paradigms associate MT with 30

31 another type of therapy (1). In this way, it is evident the lack of studies that verify the single effect of MT in motor control of the paretic UE of subjects after stroke. Besides that, only one study using functional magnetic resonance imaging (fmri) assessed the effect of a single session of MT (13), and demonstrated that the effective connectivity between the primary motor cortex and the somatosensory cortex in the lesioned hemisphere increases under a singlesession of MT. The chronic effect of MT associated with other therapies is already well documented in the literature, however, there is no one study about the acute effect of MT on motor control strategies and clinics characteristics of the paretic UE of patients post-stroke. Therefore, the purpose of this study was to investigate the acute effect of MT on the motor control, manual dexterity and spasticity of the paretic UE of participants with chronic hemiparesis after stroke, during a task of reaching. It is hypothesized that the MT offers better results than the control intervention without the use of the mirror, in the kinematic outcomes, manual dexterity and spasticity of the paretic UE of patients post-stroke. METHODS This study is a randomized crossover trial, single-blinded (evaluator), in which participants, after signature of the informed consent term, had the order of the acute interventions randomly assigned into two groups: Mirror therapy (MT) and control group (CG) (Figure 1). To the randomization of the interventions, it was used the tool available in This research was conducted in the Motion Analysis and Neurorehabilitation Laboratory at Federal University of Health Sciences of Porto Alegre (UFCSPA), upon approval of the Ethics and Research Committee (CEP) ( ). Participants The patients were recruited from the vascular ambulatory of Santa Clara Hospital (Santa Casa de Misericórdia) in Porto Alegre, RS, Brazil. After the initial contact by telephone (from August 2016 to February 2017), the 31

32 patients were invited to participate in the study, by appointment for an evaluation. The eligibility of the subjects were: 1) to have a diagnosis of unilateral, ischemic or hemorrhagic, stroke for at least 6 months and at most 4years; 2) age between 30 and 80 years; 3) cognitive ability to follow the instructions of the study (Mini-Mental score 18 for schooling and 13 for illiterate) (14) ;4) mild or moderate motor sensory impairment (Fugl-Meyer Assessment Scale - mild: points, moderate: points) (3) ; 5) spasticity 2 in the flexor elbow and wrist muscles, and horizontal shoulder adductor (Modified Ashworth Scale); 6) muscle strength 3 in the flexor muscles of the shoulder, elbow and wrist, and elbow and wrist extensors (Kendall assessement). Patients with visual impairment; history of severe depression or severe psychiatric disorder; other neurological or musculoskeletal disorders in the UE; visuospatial heminegligence; or pain file 4 on the compromised UE (Visual Analog Pain Scale), were excluded from the study. Sample Size The sample consisted of individuals with a diagnosis of stroke, of both genders, and who participated in the study on a voluntary basis. For the sample size calculation, the smoothness of the movement during the kinematic analysis of a reach task was the main outcome. The calculations were performed based on a previous study that used a similar methodology (15), through the tool: Considering the difference between the means of movement smoothness during the reach test, from pre (5.4 ± 2.3) and post (3.8 ± 2.0) treatment, adopting a bi-caudal normal distribution, standard deviation of ± 2.3, level of significance of 5% and power of the test of 80%, the number of individuals (n) calculated was 32 patients. Estimating sample loss of 10%, we used a n of 36 patients. Intervention 32

33 Mirror Therapy During the intervention, patients were placed seated next to a table with a mirror (50cm x 50cm) placed vertically. The healthy UE was positioned in front of the mirror and the paretic UE behind it, enabling the patient to observe the movements of the healthy limb through the mirror, interpreting that image as the affected limb (Figure 2). The MT protocol was composed of active bimanual exercises of range of motion and functional exercises (1,16,17). Three sets of 15 repetitions were performed for each exercise with a 20 seconds interval between each series, for 30 minutes. The exercises were: 1) Elbow flexion/extension; 2) Wrist flexion/extension in neutral position; 3) Fingers flexion/extension in neutral position; 4) Forearm pronation/supination; 5) Roll the ball with hands; 6) Squeezing the sponge; 7) Drag a towel in anteroposterior direction; 8) Opponence of fingers; 9) Climb the mirror with the fingers (similar to walking the spider). The therapist verbally encouraged the patient to move both UE, as much as possible. Control Intervention In the control intervention, patients performed the same bimanual activities proposed by the MT protocol, but without the reflector side of the mirror. The mirror was in the same position as the MT intervention. However, the subject had access to the non-reflective side of the mirror, directly visualizing the movement of his healthy arm. Both interventions performed a single session of MT or control composed of 30 minutes of exercises (1,18). The therapist was properly trained to the procedures and performed all the interventions. The participants who were first assigned to the MTintervention, after 4- weeks washout period (19), performed the same procedures, but in the control intervention. Likewise, patients who were first allocated to control intervention, after 4-weeks of washout, performed the same procedures, however in MT intervention. 33

34 Outcomes Measures Primary outcome measures: Motor control of paretic UE Kinematic analysis of the patient UE was performed during the functional reaching test, through the Rab Protocol, through BTS SMART-Clinic Software, Milan Italy, using motion analysis system BTS SMART DX Motion Capture System 400, that consists of six infrared cameras with a sampling frequency of 100Hz. The BTS program performed the reconstruction and processing of the position of the markers in the three-dimensional volume. This protocol allows the UE kinematics study while performing functional tasks (20). The test - Rab Pointing - consists of moving both UE alternately, with the aim of touching the index finger in a target positioned in front of the patient, along the central sagittal plane, at the level of the shoulders. To standardize the task, the distance from the target, starting from the acromion, was fixed at 80% of the length of the UE. The participants remained seated in an adjustable height chair, aiming at the standardization of the positioning of the ankles, knees, and hips at angles of 90º (21). The trunk was supported on the chair back, the UE was resting on the table, with an elbow flexion of 90 and forearms pronated (4). Each subject performed five replicates tested at each UE to become familiar with the task, and then, there were three collections of three replicates each (4, 7). A static collection lasting 5 seconds was performed, where the patient remained in the resting position, with arms resting on the table. Before the test start, the target marker was removed, and then, after hearing a beep, the patient started the Pointing task. The orientation of the task consisted in moving, alternately, one UE at a time to touch the target that was placed in front of the subject previously. This test requires the placement of 16 body markers: nasofrontal region, bilateral zygomatic processes, suprasternal region, right and left acromion, right and left olecranon, styloid processes of radius and ulna, third metacarpal head, and fingernail nail. In addition, one marker was positioned on the target and 3 additional markers were placed on the plane where the target was located (20) (Figure 3). 34

35 Reaching and touching a target on the table requires refined motor control through highly coordinated joint movements of the UE joints (22). The kinematic outcomes analyzed in this study to describe the motor control strategies of the paretic UE of patients during the task included: (a) Movement Cycle Time (MCT), representing the time to perform the cycle of movement in seconds, which includes the going and return phase of the arm to the table; (b) Index of Curvature (IC), representative of the movement straightness during the going phase, an IC equal to 1 indicates a perfectly rectilinear motion; (c) Average Jerk (AJ), measure of the movement smoothness, this index decreases with increased smoothness; (d) Mean Movement Velocity (MMV),fingernail marker mean velocity during the going phase, an increased MMV indicates an improves task performance; (e) Adjusting Sway (AS), measure of the adjustments made to reach the target, decreases as the movement precision increases; (f) Range of motion of shoulder (flexion/extension, abduction/adduction) and elbow (flexion/extension). Secondary outcome measures: Manual dexterity and Spasticity Box and Block Test (BBT) was used to assess the gross manual dexterity (Figure 4), likewise several previous studies (23-26). The test consists in moving, one by one, the largest possible number of blocks from one box compartment to the other, first with the uncommitted UE and then with the paretic UE. The recorded score is equivalent to the number of blocks moved from one side of the box to the other in 60 seconds (27). The BBT has a reliability considered as excellent (intraclass correlation coefficient 0.89 to 0.97) (28). The Modified Ashworth Scale (MAS) was used to assess spasticity, evaluating the resistance to passive movement (29). The patients stayed in a sitting position to the assessment of the muscle tone of the elbow flexors, wrist flexors and horizontal shoulder adductor of the paretic UE, with three mobilizations for each muscle group. Higher scores correspond to spasticity or increase in tone, while lower scores indicate normal muscle tone. This scale has good inter- and intra-rater reliability (30). 35

36 The evaluations were performed before and immediately after the 30 minutes of exercise (through MT or control), by a third investigator, who was not aware of the distribution of the patients in the groups (blind)and trained in the use of assessment tools. Due to the nature of the therapy, it was not possible to blind the patients or the therapist. Statistical Analysis The sample characterization data are expressed as mean and 95% confidence interval (continuous variable) and absolute frequency (categorical variables). To compare the outcomes of the different experimental sessions and at the different moments (pre and post session), the Generalized Estimating Equations with post hoc LSD (Least Significant Difference) methods were used. Furthermore, the effect size (Cohen's d) was calculated from mean values between MT and control interventions and classified as small (between 0.2 and 0.5), moderate (between 0.5 and 0.8), or large (0.8 or more) (31). For all analysis the significance level was set at α = 0.05 and statistical software SPSS (Statistical Package for Social Sciences for Mac, version 22.0, IBM, USA) was used. RESULTS Thirty-nine patients were randomized, however, six patients were excluded because they reported pain in the paretic UE during physical assessments. Then, thirty-three patients with hemiparesis post-stroke fulfilled eligibility criteria and completed the study. Table 1 provides demographic and clinical characteristics of participants. The analysis of the effect of the interventions on the kinematic outcomes, manual dexterity and spasticity, as well as the p values of the group factor, time factor and group*time interaction, obtained through the statistical analysis, are described in Table 2. Among the kinematic outcomes analyzed in this study, it was possible to observe that only MCT showed statistically significant improvement regarding the time factor, evidencing that both groups presented movement cycle time 36

37 significantly decreased post-intervention. MT intervention presented 0.33 seconds of decreased, while control intervention presented 0.14 seconds of decreased (p < 0.006). For the other kinematic outcomes (IC, AJ, MMV, AS and range the motion) no significant main effects (group and time) or significant interaction were found. With regard to manual dexterity (BBT), this study demonstrated a significant effect on the time factor, suggesting that both groups improved significantly after the interventions (p < 0.016), with no difference between the groups. MT intervention presents 1.79 more blocks, while control intervention presented 1.73 more blocks. The variables related to UE spasticity (MAS) presented a significant time factor, evidencing that both groups showed improvement after the interventions. The results demonstrate that there was reduction of spasticity of the elbow flexor muscles (MT intervention decreased 0.5 points, while control intervention decreased 0.23 points; p < 0.000), wrist flexors (MT intervention decreased 0.6 points, while control intervention decreased 0.27 points p<0,000) and horizontal shoulder adductor (MT intervention decreased 0.29 points, while control intervention decreased 0.09 points; p<0,011) in the post-intervention periods. In addition, for the spasticity variable of the wrist flexors, there was a significant time*group interaction (p<0,046), demonstrating that although both interventions have provided reductions in this outcome, the magnitude of reduction observed after MT intervention was greater than that observed after the control intervention. The analysis of the effect size, comparing both interventions, showed a moderate magnitude of effect between interventions for MCT (0.53; 95%CI 0.04 to 1.02), MAS-horizontal shoulder adductor (0.68; 95%CI 0.18 to 1.17) and MAS-wrist flexor (0.54; 95%CI 0.05 to 1.03). For all other variables, the effect size was small, namely, IC (0.00; 95%CI to 0.48), AJ (0.48; 95%CI to 0.97), MMV (0.29; 95%CI to 0.78), AS (0.24; 95%CI to 0.72), RM- SFE (0.17; 95%CI to 0.65), RM-SAA (0.23; 95%CI to 0.71), RM- EFE (0.16; 95%CI to 0.64), BBT (0.03; 95%CI to 0.51), MAS-elbow (0.29; 95%CI to 0.78). DISCUSSION 37

38 In this trial, we aimed to explore the acute effect of MT on kinematics variables, manual dexterity and spasticity of patients with chronic hemiparesis post-stroke. Our findings demonstrate that both groups showed significant improvements after interventions, refuting our hypothesis that MT would promote better outcomes than the control intervention. However, intergroup comparisons did not reveal significant differences, except for spasticity of wrist flexors. MT is widely used as a treatment for stroke patients and promotes functional recovery of paretic UE, encouraging movement on the affected side (32). After a single-session of MT, the effective connectivity between the primary motor cortex (M1) and the somatosensory cortex in the lesioned hemisphere increase (13). Some studies indicate that MT seems to activate the damaged brain area (8, 10), improves the inter-hemispheric communication (1, 33), and the activity in the cortex areas associated with awareness of the self and spatial attention (10). As in this study, research shows the effect of MT on the motor control mechanisms of UE, through kinematic variables, during the reaching task (6, 34).Among the kinematic outcomes, in this study, only the MCT showed a significant improvement, that is, both groups performed the task in a shorter time after interventions, without a significant difference between groups. Other research that investigated the effects of MT-based action observation protocol on motor learning in patients post-stroke, also reveals a significantly larger decrease in movement time in MT intervention than in the control intervention (35). However, these results do not seem to be a single consequence of MT, since the study used other therapeutic modalities associated with MT. The majority of studies on MT, as well as the present study, have reported the effect of visual feedback for bilateral symmetrical movements and similar instructions were given in order to encourage bimanual training (9, 16, 18, 26). This situation provides a direct motor training paradigm, related to the known effects of bimanual training programs (36).However, while from a motor learning perspective it may be most effective to instruct patients to move both UE as much as possible, it could be argued that the strength of the mirror illusion decreases as a result of paretic side movement, as it causes an incongruence 38

39 between task performance and visual feedback (34). This condition may explain our findings, which both groups showed a decrease in MCT with no significant differences between groups. Besides, movement of the paretic arm seems to increase proprioceptive feedback of this arm, which then may partly disrupt the visual illusion, suggesting that movement of the paretic arm is not beneficial (34). Otherwise, another explanation for our findings (no significant difference between groups) was given by Rodrigues et al. (2016) (37), which reveals that bilateral training with a focus on the paretic UE directly produces better results than the same training with the use of a mirror. According to the authors, probably the suppression of visual errors committed by the paretic UE reduces or eliminates the correction of movement in different phases of UE reaching (37). Besides that, the experience of correcting errors is important in motor learning and can facilitate the improvement of skills. Corroborating with our study, which demonstrates improvement in MCT for both groups after interventions, a significant improvement on comparing pre and post training performance also was noted only for bilateral tasks (37). Other authors have tested different training conditions (i.e., unilateral or bilateral, with or without a mirror) in short-term effect training for a pointing task, and they did not observe differences in relation to the movement time between bimanual conditions with or without a mirror (34), as in the present study. In disagreement with several other studies that use bimanual tasks (16, 18, 23), Selles et al. (2014) (34) shows that, with or without a mirror, bilateral training was less effective than unilateral training in relation to improving the movement time.another possible reason why the bimanual training effects were relatively small might be that these conditions were more tiresome for the affected arm of the patients (34).Thus, seems that MT alone is not more effective than directly training of the paretic UE, which was confirmed by our study, and it would indicate the added value of using MT in severely affected patients without any residual motor function in paretic arm or when the UE is easily fatiguing (34). In the secondary outcome of this study, manual dexterity presented a significant improvement in both groups after the intervention, without significant differences among groups. Poor manual dexterity impacts activities of daily livingstrongly, and these impairments are correlated with a lower independence of finger movements, slowed timing or deficient finger sequencing and 39

40 decreased of accuracy in force control (38). Corroborating with our findings, another study that associated functional electrical stimulation with MT, reveal that both groups showed an increase in BBT data after intervention, but also, no significant intergroup differences were observed (23). Researches show that MT combined with other therapies was effective to improve hand dexterity when compared with sham MT or another type of intervention. These studies usually associate MT with many kinds of therapies, as electromyography-triggered neuromuscular stimulation, functional electrical stimulation, transcranial direct current stimulation, conventional physical therapy (23-26, 35).Otherwise, agreeing with our results, a recent study reports that MT alone is more effective in the short term for recovery UE function and manual dexterity than conventional rehabilitation or associated with conventional rehabilitation (39). Concerning spasticity results, we observed in both groups a significant improvement in the three muscle groups assessed after the intervention, which corroborates with Lin et al. (2014) (26), which associate MT with somatosensory stimulation, that also found no differences between groups in MAS scale. Moreover, in the present study, a significant difference among groups was found only in the wrist flexors, demonstrating a significant reduction of spasticity in this muscles in the MT intervention compared to CI and suggesting that MT alone was effective in reducing wrist flexors spasticity. These results corroborate with the findings of Dohle et al. (2009) (18),who concluded that MT associated with conventional rehabilitation is more effective at recovering of the distal than proximal UE. Other studies, that associated MT with different types of therapies (functional electrical stimulation, conventional physical therapy), indicate that MT groups presented significantly greater improvements in motor functions and spasticity of elbow, wrist, and hand than the control groups (1, 23). Differently, Yavuzer et al. (2008) (16) reported in your study, which associate MT with conventional rehabilitation, that spasticity of wrist flexor muscles did not differ between the groups. Muscle tone is related to movement control, thus a reduction of spasticity in hand might promote grip release and improve manual dexterity (26).It should be noted by our results and other authors that constant practice of sequentially simple motor tasks may lead to motor improvements.the protocol of exercises 40

41 performed in this study was based on other protocols already described in the literature, which consists of range of motion movements (1,16,17). You et al. (2011) (40) related that these programs are limited to improve UE motor function. However, our results demonstrate that simple exercises can promote improvement in movement cycle time, manual dexterity, and spasticity of paretic UE of subjects after chronic stroke. These results show an effective improvement in movement cycle time during task, manual dexterity and spasticity of paretic UE post chronic stroke after both interventions, although it did not show differences between groups. MT has a strong neural explanation to be utilized in the motor rehabilitation of stroke, but the present study indicates that a single MT session is not more efficient than a single session of sham MT training of the both UE. Besides that, our results suggest the potential efficacy of simple exercises to improve motor function of paretic UE post chronic stroke. As limitation of this study, as already mentioned earlier, possibly was that fatigue of the involved arm because the bimanual exercises, which demand greater effort of patient and may have influenced the results. Future studies with a larger sample and unimanual exercises group is required for a definitive study to evaluate which method of MT training is most effective for these patients. It would be interesting as well, to direct toward hemiplegic patients, without motor function in the affected arm, to clarify if a single session of MT, through unimanual exercises, can promote mirror neuron activation sufficient to promote an immediate improvement in motor function of this patients. Also, it is suggested studies with chronic effects of isolated MT, comparing bimanual and unimanual exercises, on motor control and functionality of paretic UE of subjects after chronic stroke. Clinical Message Thirty minutes of exercises was effective toimprovement movement cycle time during task, manual dexterity and spasticity of paretic UE of individuals post chronic stroke. A single MT session is not more efficient than a single session of sham MT training of the both UE in these subjects. 41

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45 33. Arya KN. Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke. Neurol India. 2016;64(1): Selles RW, Michielsen ME, Bussmann JB, Stam HJ, Hurkmans HL, Heijnen I, et al. Effects of a mirror-induced visual illusion on a reaching task in stroke patients: implications for mirror therapy training. Neurorehabil Neural Repair. 2014;28(7): Harmsen WJ, Bussmann JB, Selles RW, Hurkmans HL, Ribbers GM. A Mirror Therapy-Based Action Observation Protocol to Improve Motor Learning After Stroke. Neurorehabil Neural Repair. 2015;29(6): Stoykov ME, Corcos DM. A review of bilateral training for upper extremity hemiparesis. Occup Ther Int. 2009;16(3-4): Rodrigues LC, Farias NC, Gomes RP, Michaelsen SM. Feasibility and effectiveness of adding object-related bilateral symmetrical training to mirror therapy in chronic stroke: A randomized controlled pilot study. Physiother Theory Pract. 2016;32(2): Térémetz M, Colle F, Hamdoun S, Maier MA, Lindberg PG. A novel method for the quantification of key components of manual dexterity after stroke. J Neuroeng Rehabil. 2015;12: Pérez-Cruzado D, Merchán-Baeza JA, González-Sánchez M, Cuesta- Vargas AI. Systematic review of mirror therapy compared with conventional rehabilitation in upper extremity function in stroke survivors. Aust Occup Ther J. 2017;64(2): You SJ HK, Kim HJ, et al. An effect of mirror therapy on upper extremity function and activities of daily living in patients with poststroke hemiplegia. J Korean Soc Occup Ther2011. p

46 TABELAS Table 1 Baseline patient s characteristics. Characteristics Mean IC 95% or n (n = 33) Age (years) to Weight (kg) to Stature (m) to 1.66 Gender (male/female) 20/13 Time since stroke (months) to Affected side (right/left) 18/15 Type of stroke (hemorrhagic/ischemic) 6/27 Mini-Mental to FMA (mild/moderate) 6/27 Abbreviations: FMA, Fugl-Meyer Assesment. Values are presented as mean or number, 95% confidence interval. 46

47 Table 2 Statistical analysis pre and post evaluations of interventions for Mirror Therapy Intervention versus Control Intervention. Outcomes (Mean - IC 95%) MT group (n = 33) Control group (n = 33) Group Time Group*Time Pre Post Pre Post P p p Kinematics outcomes MCT (s) 1.97 (1.53 to 2.41) 1.64 (1.34 to 1.93) 2.48 (1.94 to 3.03) 2.34 (1.78 to 2.91) * IC 0.99 (0.93 to 1.05) 0.99 (0.88 to 1.11) 0.98 (0.93 to 1.04) 0.99 (0.92 to 1.07) AJ (m/s^3) 5.84 (4.78 to 6.90) 6.15 (5.04 to 7.26) 4.5 (3.77 to 5.72) 4.74 (3.91 to 5.58) MMV (m/s) 0.44 (0.38 to 0.50) 0.46 (0.39 to 0.53) 0.41 (0.35 to 0.46) 0.40 (0.34 to 0.46) AS (m/m) (12.57 to 21.17) (12.23 to 21.32) (13.90 to 21.63) (15.23 to 25.00) RM - SFE (37.78 to 43.85) (32.47 to 43.53) (36.06 to 43.23) (35.43 to 45.84) (degree) RM - SAA (8.20 to 11.91) 9.57 (7.46 to 11.68) (10.36 to 13.94) (8.62 to 13.61) (degree) RM - EFE (17.57 to 22.58) (14.77 to 22.60) (17.33 to 23.10) (16.65 to 24.40) (degree) BBT (23.47 to 31.96) (24.64 to 34.36) (22.97 to 31.66) (24.28 to 33.82) * MAS - elbow 0.75 (0.38 to 1.11) 0.25 (-0.00 to 0.50) 0.73 (0.40 to 1.07) 0.50 (0.19 to 0.80) * flexor MAS - wrist 0.60 (0.32 to 0.89) 0.00 (0.00 to 0.00) 0.55 (0.23 to 0.87) 0.28 (0.03 to 0.54) * 0.046* flexor MAS - horizontal shoulder adductor 0.42 (0.10 to 0.75) 0.71 (-0.6 to 0.20) 0.60 (0.29 to 0.92) 0.51 (0.23 to 0.82) * Abbreviations: MCT, Movement Cycle Time; IC, Index of Curvature; AJ, Average Jerk; MMV, Mean Movement Velocity; AS, Adjusting Sway; RM-SFE, Range of Motion Shoulder Flexion/Extension; RM-SAA, Range of Motion Shoulder Abduction/Adduction; RM-EFE, Range of Motion Elbow Flexion/Extension; BBT, Box and Block Test; MAS, Modified Ashworth Scale. Values are presented as mean, 95% confidence interval. *p< 0,05. 47

48 FIGURAS Enrollment Assessed for eligibility (n = 416) Sequence protocol randomization (n = 39) Excluded (n = 377) Not meeting inclusion criteria. Excluded (n = 6) Reported pain on paretic UE during the tests. Allocation Pre-test Post-test Allocated to Mirror Therapy Intervention (n = 15) Received intervention through MT for 30 min. Allocated to Control Intervention (n = 18) Performed the same MT exercises, but without the mirror, for 30 min. Pre-test Post-test Allocated to Control Intervention (n = 18) Performed the same MT exercises, but without the mirror for 30 min. Allocated to Mirror Therapy Intervention (n = 15) Received intervention through MT for 30 min. One-month washout Analysis Analyzed for acute effect (n = 33) Analyzed for acute effect (n = 33) Figure 1. The participants flow diagram. 48

49 Figure 2. Mirror Therapy. 49

50 (A) Figure 3. Kinematic analysis of the reach task. Body markers and target positioning (A); Image of the analysis system (B). (B) 50

51 Figure 4. Box and Block Test. 51

52 5 CONCLUSÃO GERAL A TE possui uma forte base neural para ser utilizada na reabilitação motora de pacientes após AVC, entretanto o presente estudo indica que uma única sessão de TE não foi mais eficaz do que uma única sessão de treinamento direto (sem o espelho) de ambos os membros superiores. Os resultados deste trabalho demonstram uma melhora efetiva no tempo de ciclo de movimento durante a tarefa, na destreza manual e na espasticidade do MS parético de pacientes após AVC crônico, após as intervenções, embora não tenha mostrado diferenças significativas entre os grupos. Esses achados têm implicações importantes para a prática clínica, pois sugerem que a TE pode ser efetiva em situações específicas, como por exemplo, no paciente hemiplégico que ainda não é capaz de mover o braço afetado. Além disso, nossos resultados sugerem a eficácia de exercícios simples para melhorar a função motora do MS parético após AVC. Sugere-se para pesquisas futuras, estudos com efeitos agudos e crônicos da TE de forma isolada, comparando exercícios bimanuais e unimanuais, sobre os aspectos do controle motor e funcionalidade do MS parético desses indivíduos. Também sugerimos que estudos futuros possam investigar o efeito agudo da TE no alívio da dor e na melhora da sensibilidade e propriocepção do MS parético nessa população. Ainda, salienta-se direcionar estudos para pacientes hemiplégicos, sem função motora no braço afetado, a fim de esclarecer se uma única sessão de TE, através de exercícios unimanuais, é capaz de promover ativação de neurônios espelho suficiente que produza uma melhora no controle motor e na função motora desses pacientes. 52

53 6 ANEXOS ANEXO A Normas de formatação do periódico Clinical Rehabilitation 1.1 Aims & Scope Before submitting your manuscript to Clinical Rehabilitation, please ensure you have read the Aims & Scope. 1.2 Article Types The journal publishes original papers, systematic reviews, Rehabilitation in Practice articles correspondence relating to published papers and short reports. Other article types should be discussed with the editor before submission Summary of manuscript structure: A title page with names and contact details for all authors A structured abstract of no more than 250 words (the website checks this) The text (usually Introduction, Methods, Results, Discussion) Clinical Messages (2-4 bullet points, 50 words or less) Acknowledgements, author contributions, competing interests and funding support References (Vancouver style) Tables, each starting on a new page Figures, each starting on a new page Please note that short reports follow a different format: The main text of a short report will usually be between 1000 and 1500 words in length. A short report should have sufficient key references to cover all important points, but no more and usually there will be a maximum of 15 references. Tables and figures can be very efficient and effective ways of presenting data. A short report will usually have no more than three tables and figures (in total) and most will be restricted to two. 1.3 Writing your paper The SAGE Author Gateway has some general advice and on how to get published, plus links to further resources Make your article discoverable When writing up your paper, think about how you can make it discoverable. The title, keywords and abstract are key to ensuring readers find your article through search engines such as Google. For information and guidance on how best to title your article, 53

54 write your abstract and select your keywords, have a look at this page on the Gateway: How to Help Readers Find Your Article Online 2. Editorial policies 2.1 Peer review policy The journal's policy is to obtain at least two independent reviews of each article. It operates a double-blind reviewing policy in which the reviewer s name is always concealed from the submitting author; authors may choose to reveal their name but the journal otherwise leaves the article anonymous. Referees will be encouraged to provide substantive, constructive reviews that provide suggestions for improving the work and distinguish between mandatory and non-mandatory recommendations. All manuscripts accepted for publication are subject to editing for presentation, style and grammar. Any major redrafting is agreed with the author but the Editor's decision on the text is final. Clinical Rehabilitation is committed to delivering high quality, fast peer-review for your paper, and as such has partnered with Publons. Publons is a third party service that seeks to track, verify and give credit for peer review. Reviewers for Clinical Rehabilitation can opt in to Publons in order to claim their reviews or have them automatically verified and added to their reviewer profile. Reviewers claiming credit for their review will be associated with the relevant journal, but the article name, reviewer s decision and the content of their review is not published on the site. For more information visit the Publons website 2.2 Authorship Papers should only be submitted for consideration once consent is given by all contributing authors. Those submitting papers should carefully check that all those whose work contributed to the paper are acknowledged as contributing authors. The list of authors should include all those who can legitimately claim authorship. This is all those who: Made a substantial contribution to the concept or design of the work; or acquisition, analysis or interpretation of data; Drafted the article or revised it critically for important intellectual content; Approved the version to be published; Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content. Authors should meet the conditions of all of the points above. When a large, multicentre group has conducted the work, the group should identify the individuals who accept direct responsibility for the manuscript. These individuals should fully meet the criteria for authorship. 54

55 Acquisition of funding, collection of data, or general supervision of the research group alone does not constitute authorship, although all contributors who do not meet the criteria for authorship should be listed in the Acknowledgments section. Please refer to the International Committee of Medical Journal Editors (ICMJE) authorship guidelines for more information on authorship 2.3 Acknowledgements All contributors who do not meet the criteria for authorship should be listed in an Acknowledgements section. Examples of those who might be acknowledged include a person who provided purely technical help, or a department chair who provided only general support. Any acknowledgements should appear first at the end of your article prior to your Declaration of Conflicting Interests (if applicable), any notes and your References 2.4 Funding Clinical Rehabilitation requires all authors to acknowledge their funding in a consistent fashion under a separate heading. Please visit the Funding Acknowledgements page on the SAGE Journal Author Gateway to confirm the format of the acknowledgment text in the event of funding, or state that: This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors. 2.5 Declaration of conflicting interests It is the policy of Clinical Rehabilitation to require a declaration of conflicting interests from all authors enabling a statement to be carried within the paginated pages of all published articles. Please ensure that a Declaration of Conflicting Interests statement is included at the end of your manuscript, after any acknowledgements and prior to the references, under a heading Conflict of Interest Statement. If no conflict exists, please state that The Author(s) declare(s) that there is no conflict of interest. For guidance on conflict of interest statements, please see the ICMJE recommendations here. When making a declaration, the disclosure information must be specific and include any financial relationship that all authors of the article have with any sponsoring organization and the for-profit interests that the organisation represents, and with any for-profit product discussed or implied in the text of the article. Any commercial or financial involvements that might represent an appearance of a conflict of interest need to be additionally disclosed in the covering letter accompanying your article to assist the Editor in evaluating whether sufficient disclosure has been made within the Conflict of Interest statement provided in the article 55

56 2.6 Research ethics and patient consent Medical research involving human subjects must be conducted according to the World Medical Association Declaration of Helsinki Submitted manuscripts should conform to the ICMJE Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals, and all papers reporting animal and/or human studies must state in the methods section that the relevant Ethics Committee or Institutional Review Board provided (or waived) approval. Please ensure that you have provided the full name and institution of the review committee, in addition to the approval number. Information on informed consent to report individual cases or case series should be included in the manuscript text. A statement is required regarding whether written informed consent for patient information and images to be published was provided by the patient(s) or a legally authorized representative. Please also refer to the ICMJE Recommendations for the Protection of Research Participants 2.7 Reporting guidelines The relevant EQUATOR Network reporting guidelines should be followed depending on the type of study. For example, all randomized controlled trials submitted for publication should include a completed CONSORT flow chart as a cited figure and the completed CONSORT checklist should be uploaded with your submission as a supplementary file. Systematic reviews and meta-analyses should include the completed PRISMA flow chart as a cited figure and the completed PRISMA checklist should be uploaded with your submission as a supplementary file. The EQUATOR wizard can help you identify the appropriate guideline. Clinical Rehabilitation expects all clinical trials to be registered with a recognised registry, and the name of the registry and the registration number to be given in the paper, usually in the first paragraph in the methods section. Other resources can be found at NLM s Research Reporting Guidelines and Initiatives 3. Publishing Policies 3.1 Publication ethics SAGE is committed to upholding the integrity of the academic record. We encourage authors to refer to the Committee on Publication Ethics International Standards for Authors and view the Publication Ethics page on the SAGE Author Gateway Plagiarism Clinical Rehabilitation and SAGE take issues of copyright infringement, plagiarism or other breaches of best practice in publication very seriously. We seek to 56

57 protect the rights of our authors and we always investigate claims of plagiarism or misuse of published articles. Equally, we seek to protect the reputation of the journal against malpractice. Submitted articles may be checked with duplication-checking software. Where an article, for example, is found to have plagiarised other work or included third-party copyright material without permission or with insufficient acknowledgement, or where the authorship of the article is contested, we reserve the right to take action including, but not limited to: publishing an erratum or corrigendum (correction); retracting the article; taking up the matter with the head of department or dean of the author's institution and/or relevant academic bodies or societies; or taking appropriate legal action Prior publication If material has been previously published it is not generally acceptable for publication in a SAGE journal. However, there are certain circumstances where previously published material can be considered for publication. Please refer to the guidance on the SAGE Author Gateway or if in doubt, contact the Editor at the address given below. 3.2 Contributor's publishing agreement Before publication, SAGE requires the author as the rights holder to sign a Journal Contributor s Publishing Agreement. SAGE s Journal Contributor s Publishing Agreement is an exclusive licence agreement which means that the author retains copyright in the work but grants SAGE the sole and exclusive right and licence to publish for the full legal term of copyright. Exceptions may exist where an assignment of copyright is required or preferred by a proprietor other than SAGE. In this case copyright in the work will be assigned from the author to the society. For more information please visit the SAGE Author Gateway. 3.3 Open access and author archiving Clinical Rehabilitation offers optional open access publishing via the SAGE Choice programme. For more information please visit the SAGE Choice website. For information on funding body compliance, and depositing your article in repositories, please visit SAGE Publishing Policies on our Journal Author Gateway. 4. Preparing your manuscript for submission 4.1 Formatting The preferred format for your manuscript is Word. LaTeX files are also accepted. Word and (La)Tex templates are available on the Manuscript Submission Guidelines page of our Author Gateway. 4.2 Artwork, figures and other graphics 57

58 For guidance on the preparation of illustrations, pictures and graphs in electronic format, please visit SAGE s Manuscript Submission Guidelines. Figures supplied in colour will appear in colour online regardless of whether or not these illustrations are reproduced in colour in the printed version. For specifically requested colour reproduction in print, you will receive information regarding the costs from SAGE after receipt of your accepted article. 4.3 Supplementary material This journal is able to host additional materials online (e.g. datasets, podcasts, videos, images etc) alongside the full-text of the article. For more information please refer to our guidelines on submitting supplementary files. 4.4 Reference style Clinical Rehabilitation adheres to the SAGE Vancouver reference style. View the SAGE Vancouver guidelines to ensure your manuscript conforms to this reference style. If you use EndNote to manage references, you can download the SAGE Vancouver EndNote output file. 5. Submitting your manuscript Clinical Rehabilitation is hosted on SAGE Track, a web based online submission and peer review system powered by ScholarOne Manuscripts. Visit Clinical Rehabilitation to login and submit your article online. IMPORTANT: Please check whether you already have an account in the system before trying to create a new one. If you have reviewed or authored for the journal in the past year it is likely that you will have had an account created. For further guidance on submitting your manuscript online please visit ScholarOne Online Help. 5.1 ORCID As part of our commitment to ensuring an ethical, transparent and fair peer review process SAGE is a supporting member of ORCID, the Open Researcher and Contributor ID. ORCID provides a persistent digital identifier that distinguishes researchers from every other researcher and, through integration in key research workflows such as manuscript and grant submission, supports automated linkages between researchers and their professional activities ensuring that their work is recognised. We encourage all authors to add their ORCIDs to their SAGE Track accounts and include their ORCIDs as part of the submission process. If you don t already have one you can create one here 5.2 Information required for completing your submission You will be asked to provide contact details and academic affiliations for all coauthors via the submission system and identify who is to be the corresponding author. 58

59 These details must match what appears on your manuscript. At this stage please ensure you have included all the required statements and declarations and uploaded any additional supplementary files (including reporting guidelines where relevant). 6. On acceptance and publication 6.1 SAGE Production Your SAGE Production Editor will keep you informed as to your article s progress throughout the production process. Proofs will be sent by PDF to the corresponding author and should be returned promptly. Authors are reminded to check their proofs carefully to confirm that all author information, including names, affiliations, sequence and contact details are correct, and that Funding and Conflict of Interest statements, if any, are accurate. Please note that if there are any changes to the author list at this stage all authors will be required to complete and sign a form authorising the change. 6.2 Online First publication Online First allows final articles (completed and approved articles awaiting assignment to a future issue) to be published online prior to their inclusion in a journal issue, which significantly reduces the lead time between submission and publication. Visit the SAGE Journals help page for more details, including how to cite Online First articles. 6.3 Access to your published article SAGE provides authors with online access to their final article. 6.4 Promoting your article Publication is not the end of the process! You can help disseminate your paper and ensure it is as widely read and cited as possible. The SAGE Author Gateway has numerous resources to help you promote your work. Visit the Promote Your Article page on the Gateway for tips and advice. In addition, SAGE is partnered with Kudos, a free service that allows authors to explain, enrich, share, and measure the impact of their article. Find out how to maximise your article s impact with Kudos. 7. Further information 7.1 Important Instructions to Authors from the Editor Further specific advice on editorial aspects of the journal and of writing for the journal are also available. 59

60 ANEXO B Parecer do CEP 60

61 61

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