Submitted by Gustavo José Luvizutto null (gluvizutto@fmb.unesp.br) on 2016-06-17T14:29:20Z No. of bitstreams: 1 Tese_Doutorado_Gustavo_Final.pdf: 2479589 bytes, checksum: 29a51ed15da908051b8667068b430e40 (MD5) / Rejected by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo a orientação abaixo: O arquivo submetido não contém o certificado de aprovação. A versão submetida por você é considerada a versão final da dissertação/tese, portanto não poderá ocorrer qualquer alteração em seu conteúdo após a aprovação. Corrija esta informação e realize uma nova submissão contendo o arquivo correto. Agradecemos a compreensão. on 2016-06-22T14:48:29Z (GMT) / Submitted by Gustavo José Luvizutto null (gluvizutto@fmb.unesp.br) on 2016-06-23T11:32:49Z No. of bitstreams: 1 Tese_Doutorado_Gustavo_Final.pdf: 2479589 bytes, checksum: 29a51ed15da908051b8667068b430e40 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-06-23T19:56:57Z (GMT) No. of bitstreams: 1 luvizutto_gj_dr_bot.pdf: 2479589 bytes, checksum: 29a51ed15da908051b8667068b430e40 (MD5) / Made available in DSpace on 2016-06-23T19:56:57Z (GMT). No. of bitstreams: 1 luvizutto_gj_dr_bot.pdf: 2479589 bytes, checksum: 29a51ed15da908051b8667068b430e40 (MD5) Previous issue date: 2016-06-16 / Não recebi financiamento / Introdução: A negligência espacial unilateral (NEU) é caracterizada pela incapacidade de reportar ou responder pessoas ou objetos do lado contralateral à lesão cerebral, e ocorre principalmente após Acidente Vascular Cerebral (AVC) do lobo parietal direito, sendo associada à pior desfecho funcional à longo prazo. Objetivo: Os objetivos desta tese foram: normatizar os principais testes diagnósticos de NEU e verificar a relação com fatores sócio-demográficos na população brasileira; avaliar as variáveis bioquímicas que interferem na NEU na fase aguda do AVC; e revisar sistematicamente os principais tratamentos farmacológicos na NEU em pacientes após AVC. Método: Para o primeiro objetivo foi realizado estudo transversal em 150 indivíduos sem alterações neurológicas, sendo aplicados: teste face-mão (TFM), testes de cancelamento de linhas (TCL), cancelamento de estrelas (TCE) e bisseção de linhas (TBL). Os resultados dos testes foram relacionados com o perfil sócio demográfico da população, sendo estipulado pontos de cortes para a normalidade; para o objetivo 2 foi realizado estudo observacional em 40 indivíduos com diagnostico de NEU após AVC. Foram aplicados os TCL, TCE e TBL, sendo relacionado com o nível de hemoglobina na fase aguda do AVC corrigido para potenciais confundidores; para o objetivo 3 foi realizado revisão sistemática de literatura por meio de ensaios clínicos randomizados e quasi-randomizados para determinar o melhor tratamento farmacológico. Resultados: os resultados do objetivo 1 estão apresentados nos artigos 1 e 2; o objetivo 2 no artigo 3; e o objetivo 3 no artigo 4. Conclusão: Com base nos resultados obtidos dos artigos 1 e 2, o TFM apresenta taxa de normalidade entre 8 a 10 estímulos sensoriais, com prevalência de extinção associada com o grau de escolaridade e aumento da idade; no TCL o ponto de corte para considerar NEU é acima de 0 e no TCE acima de 2, ambos associados à idade. No TBL o ponto médio de corte para considerar NEU foi de 6,6 mm, associado com pior escolaridade. No artigo 3 foi observado que quanto menor o valor de hemoglobina na fase aguda do AVC, pior o desempenho nos testes de NEU; No artigo 4 foi observado que a efetividade e segurança dos tratamentos farmacológicos para NEU após AVC permanecem incertos, necessitando de ensaios clínicos randomizados adicionais para avaliar o efeito deste tratamento. / Background: Unilateral spatial neglect (USN) is characterized by the inability to report or respond to people or objects presented on the side contralateral to the lesioned side of the brain and has been associated with poor functional outcomes. Objective: The objectives of this thesis were: to standardize the USN tests and verify the relationship with socio-demographic data in the Brazilian population; evaluate the biochemical variables that influence in USN tests after acute stroke; and systematically review the pharmacological interventions to treat USN after stroke. Method: For the first aim, we performed a cross-sectional study of 150 individuals without neurological changes by applying: face-hand test (FHT), line cancellation test (LCT), star cancellation test (SCT) and line bisection test (LBT). The test results were related to the sociodemographic data, with cutoff points being stipulated to define USN; the second aim was achieved by conducting an observational study of 40 individuals with USN after acute stroke. The tests applied – LCT, SCT and LBT – were correlated with the hemoglobin level in the acute phase of stroke corrected by confounders; the third aim was analyzed by a systematic review of randomized controlled trials and quasi-randomized clinical trials to determine the efficacy of pharmacological intervention. Results: The first aim is presented in Articles 1 and 2, the second aim in Article 3 and the third in Article 4. Conclusion: Based on the results of Articles 1 and 2, the FHT shows normal rate between 8-10 sensory stimuli, with an extinction prevalence associated with the education level and increasing age; The LCT cutoff point to define is USN above 0 and SCT above 2, and both were associated with age. The LBT cutoff point to indicate NEU was 6.6 mm, associated with poorer education level. Article 3 reveals the relationship between a lower hemoglobin level in acute phase of stroke with worse performance on USN tests; Article 4 reports that the effectiveness and safety of pharmacological treatments for USN after stroke remain uncertain, requiring additional randomized clinical trials to evaluate the effect of treatment.

Orientador: Luiz Antônio de Lima Resende / Resumo: Introdução: A negligência espacial unilateral (NEU) é caracterizada pela incapacidade de reportar ou responder pessoas ou objetos do lado contralateral à lesão cerebral, e ocorre principalmente após Acidente Vascular Cerebral (AVC) do lobo parietal direito, sendo associada à pior desfecho funcional à longo prazo. Objetivo: Os objetivos desta tese foram: normatizar os principais testes diagnósticos de NEU e verificar a relação com fatores sócio-demográficos na população brasileira; avaliar as variáveis bioquímicas que interferem na NEU na fase aguda do AVC; e revisar sistematicamente os principais tratamentos farmacológicos na NEU em pacientes após AVC. Método: Para o primeiro objetivo foi realizado estudo transversal em 150 indivíduos sem alterações neurológicas, sendo aplicados: teste face-mão (TFM), testes de cancelamento de linhas (TCL), cancelamento de estrelas (TCE) e bisseção de linhas (TBL). Os resultados dos testes foram relacionados com o perfil sócio demográfico da população, sendo estipulado pontos de cortes para a normalidade; para o objetivo 2 foi realizado estudo observacional em 40 indivíduos com diagnostico de NEU após AVC. Foram aplicados os TCL, TCE e TBL, sendo relacionado com o nível de hemoglobina na fase aguda do AVC corrigido para potenciais confundidores; para o objetivo 3 foi realizado revisão sistemática de literatura por meio de ensaios clínicos randomizados e quasi-randomizados para determinar o melhor tratamento farmacológico. Resultados: os resul... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

L'objectif de cette thèse était d'étudier la modalité auditive dans le syndrome de négligence spatiale unilatérale (NSU) que ce soit dans l'évaluation ou dans la prise en charge. Notre première hypothèse défendue était que, bien que la NSU touche aussi la modalité auditive, des différences dues aux spécificités de chaque modalité existent entre les symptômes auditifs et visuels de ce syndrome neuropsychologique. En conséquence, notre seconde hypothèse était que les spécificités propres à la modalité auditive pourraient permettre de pallier les déficits attentionnels rencontrés en modalité visuelle et, donc, faire de cette modalité un support efficace pour la rééducation. Concernant l'évaluation des symptômes auditifs, les mécanismes d'orientation de l'attention en modalité auditive ainsi que la latéralisation de sons ont été explorés chez des patients atteints de NSU. Ces études ont souligné des difficultés dans les deux domaines dans la NSU. Concernant la réhabilitation, la place de l'audition, et plus particulièrement de la musique, dans les rééducations proposées aux patients atteints de NSU a été explorée. Enfin, un programme de rééducation basé sur la pratique musicale a été créé et testé auprès d'une patiente atteinte de NSU chronique. Celui-ci a montré des bénéfices à long-terme sur les signes visuels de la NSU mais également dans la vie quotidienne. Les résultats de ces études vont dans le sens des hypothèses et soulignent l'importance de prendre en compte la modalité auditive dans la pratique clinique que ce soit lors de l'évaluation du syndrome de NSU ou lors de sa réhabilitation. / The aim of this thesis was to focus on hearing in the evaluation and the rehabilitation of unilateral spatial neglect (USN) syndrome. USN not only affects the visual, but also the auditory modality. The first hypothesis of this thesis was that, due to the specificities of each modality, differences exist between the auditory and visual symptoms of USN. Consequently, the second hypothesis was that the specificities of the auditory modality could permit to compensate the attentional deficits that occur in the visual modality and, thus, make this modality an efficient tool for the rehabilitation. Concerning the evaluation of the auditory symptoms, orienting attention mechanisms in the auditory modality as well as sound lateralisation were explored with patients with USN. These studies showed patients with USN to have difficulties in both. Concerning the rehabilitation, the place of hearing, and in particular of music, in the re-educations in patients with USN was explored. Finally, a program based on music practice was developed and tested with a patient with a chronic USN. This patient showed long-term benefits on USN visual signs and also on daily activities. The results of these studies are consistent with the hypotheses and underline the importance of considering hearing in clinical practice either for the USN evaluation or for its rehabilitation.

La négligence spatiale unilatérale (NSU) est une affection neurologique fréquemment observée après une lésion de l'hémisphère cérébral droit. Les patients ne vont plus être en mesure de prendre en compte les stimuli présentés dans l'hémi-espace gauche. La NSU participe à l'aggravation du handicap des patients, par la réduction des possibilités en rééducation motrice et cognitive à la phase aigue d'un accident vasculaire comme sur le long terme. L'identification des facteurs prédictifs de sa chronicité pourrait permettre une meilleure prise en charge clinique de ces patients. Nous avons étudié les altérations des connexions anatomiques observées en IRM de diffusion sous-tendant la persistance de la NSU. Nos résultats démontrent qu'en plus d'un dysfonctionnement fronto-pariétal hémisphérique droit, la persistance de ce syndrome serait associée à une déconnexion interhémisphérique. L'hémisphère gauche isolé ne serait pas en mesure de compenser les déficits des patients. La récupération devrait s'effectuer par une amélioration dans les capacités d'échange des informations entre les deux hémisphères, notamment dans les régions postérieures pariétales et occipitales. Nous nous sommes intéressés à tester cette hypothèse par le biais d'une méthode de rééducation, l'adaptation prismatique (AP). Il s'agit d'une thérapie dont les effets sur la sémiologie des patients sont remarquables. Nos résultats suggèrent que l'amélioration de la NSU pourrait s'observer par le recrutement du réseau fronto-ponto-cérébelleux. Les régions frontales gauches seraient un relais anatomique entre le cervelet droit et le réseau fronto-pariétal gauche / Unilateral spatial neglect is a frequent neurological condition after right hemisphere damage. Patients behave as if objects on their left did not exist anymore. The presence of neglect has negative prognostic value for functional recovery in the acute and chronic phases after a stroke. Finding predictors of persistent neglect would permit to adapt rehabilitation procedures. We used diffusion MRI to define the state of anatomical connections in neglect and their predictor value for neglect persistence. Our results revealed that, together with right intra-hemispheric fronto-parietal disconnections, persistence of neglect is associated with inter-hemispheric disconnection. We concluded that an isolated left hemisphere may fail to compensate neglect because it cannot take into account left-sided objects. Recovery of neglect would instead occur thanks to the sharing of visual information between the two hemispheres, notably in posterior parietal and occipital cortices. We tested this hypothesis by using prism adaptation (PA) therapy. PA is a non-invasive and convenient technique to rehabilitate neglect. We showed that patients with damaged fronto-ponto-cerebellar pathways did not benefit from PA. This finding strongly suggests that PA can ameliorate signs of neglect by improving inter-hemispheric communication through enhanced activity of these connections. Left frontal areas may constitute the anatomical link between the right cerebellum and the left fronto-parietal network. Thus, connectional anatomy can help predict both neglect recovery and the quality of its response to rehabilitation therapies

Unilateral spatial neglect (USN) is a common disorder after stroke. An application especially developed for stroke rehabilitation, the RehAtt Mixed Reality (MR) intends to train cognitive and motor functions that are affected by USN, by the means of interactive 3D games played in mixed reality, through smart glasses. The present study targets one specific cognitive function, namely spatial attention, and compares individual performances in one of the games (scenarios) to performances in a widely used test for detection of deficits in spatial attention – the Posner test. The hypothesis is that user reaction times in the RehAtt MR scenario correlates with user reaction times in the Posner test. Another test, including a questionnaire, to validate the usability of the RehAtt MR is also conducted. The sample for the usability test and questionnaire includes a total of 74 participants (47 women, 27 men, M = 39.6 years of age), of which 29 individuals (13 women, 16 men, M = 35 years of age) carried out the experimental part of the study. The results suggest that there is a significant correlation, r(27) = .411, p = .027, between reaction times in the Posner test and the scenario in the RehAtt MR, and that the product usability shows high quality. It is concluded that the results support that the scenario explored in the RehAtt MR trains spatial attention, although further research is needed for full validation. / Unilateraltspatialt neglekt (USN) är en vanlig funktionsnedsättning efter stroke. En applikation som utvecklats speciellt för strokerehabilitering - RehAtt Mixed Reality (MR) - har som mål att träna kognitiva och motoriska funktioner som är påverkade av USN, med hjälp av 3D-spel som spelas i mixed reality, genom smarta glasögon. Den aktuella studien siktar in sig på en specifik kognitiv funktion – spatial uppmärksamhet – och jämför individuella prestationer i ett av spelen i RehAtt MR med prestationer i ett vanligt, ofta använt test för att upptäcka nedsättningar i spatial uppmärksamhet – Posner-testet. Hypotesen är att användares reaktionstider i spelet i RehAtt MR korrelerar med användares reaktionstider i Posner-testet. Ett annat test, inklusive en enkät, görs också, för att validera användbarheten i RehAtt MR. 74 deltagare (47 kvinnor, 27 män, M = 39.6 år) finns med i användbarhetstestet och enkäten, av vilka 29 individer (13 kvinnor, 16 män, M = 35 år) medverkade i den experimentella delen av studien. Resultaten indikerar att det är en signifikant korrelation, r(27) = .411, p = .027, mellan reaktionstiderna i Posner-testet och spelet i RehAtt MR, och att användbarheten hos produktenvisar hög kvalitet. Slutsatsen är att vad som hittats i den aktuella studien stödjer idéen att spelet i RehAtt MR tränar spatial uppmärksamhet, även om vidare studier krävs för en full validering.