Pacientes com doença de Parkinson (DP) apresentam diversos sintomas não motores, dentre eles, alterações cognitivas. Déficits de função executiva podem ser observados desde os estágios iniciais da DP e impactam na independência funcional e na qualidade de vida. A função executiva é essencial para a realização de atividades de vida diária, que requerem integração cognitivo-motora. A realização de atividades cotidianas depende não só do sistema motor, mas também da interpretação e do processamento sensorial/ perceptual e da seleção e do planejamento da melhor estratégia motora. Sendo assim, um grande número de atividades de vida diária pode ser afetado por déficits na função executiva em pacientes com DP. Nessas tarefas, os componentes cognitivos e motores competem por recursos atencionais, o que pode prejudicar o desempenho em um ou em ambos os componentes. Entretanto, os estudos são muito direcionados para a análise de tarefas-duplas que envolvam equilíbrio em ortostatismo e marcha, mas contemplam pouco outras tarefas motoras. Os objetivos desse estudo foram (1) comparar o desempenho de pacientes com DP com o de um grupo controle nos testes de função executiva (Trail Making Test) e de fluência verbal (fluência semântica e fonêmica e diadococinesia oral /pataka/) e (2) investigar possíveis correlações entre função executiva e fluência verbal. O estudo foi realizado de maneira transversal, em uma única sessão, em uma avaliação de cerca de 50 minutos. Quarenta pacientes com DP (idade entre 50 e 79 anos, Hoehn & Yahr entre 2 e 3) e quarenta controles (com idade e escolaridade semelhantes) foram avaliados com o Trail Making Test, a fluência verbal semântica e fonêmica e o teste de diadococinesia oral. Na parte A do TMT, os participantes conectaram círculos numerados de 1 a 25, em sequência. Na parte B, os participantes conectaram círculos alternando números e letras (1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13). No teste de fluência verbal fonêmica, foi solicitado que os participantes dissessem palavras começando com a letra F. No teste de fluência verbal semântica, os participantes disseram o maior número de animais possível, em 60 segundos. No teste de diadococinesia oral, os participantes repetiram a sequência /pataka/ o mais rápido possível. Os grupos foram comparados por meio de análises de variância e as relações entre as variáveis foram investigadas pelo teste de correlação de Pearson. A análise de variância mostrou diferenças significativas entre grupos (F1,78=10,55; p=0,002) e entre partes do Trail Making Test (F1,78=154,02; p < 0,001). A parte B apresentou tempos maiores que a parte A (p < 0,001). Pacientes com DP disseram menos palavras nos testes de fluência verbal, em comparação aos controles (p < 0,001). Pacientes com DP repetiram a sequência /pataka/ menos vezes que os controles (p=0,019). Houve forte correlação entre o teste de fluência verbal fonêmica e a parte B do Trail Making Test (valor de r=-0,874 e p=0,001) e entre a diadococinesia oral e as partes A e B do Trail Making Test (valor de r=-0,824 e p=0,001). A correlação entre a parte B do Trail Making Test, que é uma medida de função executiva e reflete a habilidade de integração cognitivo-motora e as tarefas de fluência verbal, evidencia a importância do controle motor para as tarefas de fala. A tarefa da fala fornece não somente sobrecarga cognitiva, mas também motora para pacientes com DP. Esse conhecimento é importante para a prática clínica, uma vez que é necessário detectar a natureza do acometimento e da tarefa para usá-las de maneira adequada em programas de reabilitação / Patients with Parkinson´s disease (PD) can present several non-motor symptoms, including cognitive deficits. Executive function deficits can be observed since the early stages of PD and impact on functional independence and quality of life. The executive function is essential to the activities of daily living, which require cognitive-motor integration. The performance of activities of daily living depends not only on the motor system, but also on the sensory/ perceptual interpretation and processing and the selection and planning of the best motor strategy. Therefore, many activities of daily living can be affected by deficits in the executive function in patients with PD. In such tasks, cognitive and motor components compete for attentional resources, which may impair the performance of one or both tasks. However, most studies focus on to the analysis of dual-tasks involving orthostatic balance and gait, but they do not approach other motor tasks. The objectives of this study were (1) to compare the performance of patients with PD with a control group in executive function (Trail Making Test) and verbal fluency tests (semantic and phonemic and oral diadochokinesis /pataka/) and (2) to investigate possible correlations between executive function and verbal fluency. This was a cross-sectional study and the tests were performed individually in a 50-minute single session. Forty people with PD (aged 50 - 79 years, Hoehn & Yahr 2 - 3) and forty controls (with similar age and education) were evaluated with Trail Making Test (TMT, executive function), phonemic/semantic verbal fluency and oral diadochokinesis (/pataka/) tests. In part A of Trail Making Test, participants connected circles with the numbers 1-25, in sequence. In part B, participants connected circles in a sequence with alternated numbers and letters (1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13). In the phonemic verbal fluency test, participants were instructed to say words beginning with the letter F. In the semantic verbal fluency test, participants were instructed to say out loud as many animals as they could remember, in 60 seconds. In the oral diadochokinesis test, participants were asked to say the /pataka/ sequence as fast as they could. Groups were compared by analyses of variance and the relationships between the variables were investigated by Pearson correlation tests. Analysis of variance showed significant differences between groups (F1,78=10.55; p=0.002) and between Trail Making Test parts (F1,78=154.02; p < 0.001). Part B showed longer times than part A (p < 0.001). People with PD said fewer words in both fluency tests, compared to controls (p < 0.001). People with PD repeated the sequence /pataka/ less times than controls (p=0.019). There was a strong correlation between the phonemic verbal fluency test and the part B of Trail Making Test (r=-0.874 and p=0.001) and between the oral diadochokinesis test and both parts of the Trail Making Test (r=-0.824 e p=0.001). The correlation between the part B of Trail Making Test, which is an executive function measure and reflects the cognitive-motor integration ability, and the verbal fluency tests, evidences the importance of motor control for speech tasks. Speech tasks not only provide cognitive overload, but also motor overload in patients with PD. This knowledge is important in clinical practice, in which therapists must detect the nature of the disability and the task to use this information properly in rehabilitation programs

Deep brain stimulation (DBS) surgery, a type of microelectrode-guided surgery, is an effective treatment for the movement disorders patients that can no longer be treated by medications. New rigid and non-rigid image registration methods were developed for the movement disorders patients that underwent DBS surgery. These new methods help study and analyze the brain shift during the DBS surgery and perform atlas-based segmentation of the deep brain structures for the DBS surgery planning and navigation. A diploë based rigid registration method for the intra-operative brain shift analysis during the DBS surgery was developed. The proposed method for the brain shift analysis ensures rigid registration based on diploë only, which can be treated as a rigid structure as opposed to the brain tissues. The results show that the brain shift during the DBS surgery is comparable to the size of the DBS targets and should not be neglected. This brain shift may further lengthen and complicate the DBS surgery contrary to the common belief that brain shift during the DBS surgery is not considerable. We also developed an integrated electrophysiological and anatomical atlas with eleven deep brain structures segmented by an expert, and electrophysiological data of four implant locations obtained from post-op MRI data of twenty patients that underwent DBS surgery. This atlas MR image is then non-rigidly registered with the pre-operative patient MR image, which provides initial DBS target location along with the segmented deep brain structures that can be used for guidance during the microelectrode mapping of the stereotactic procedure. The atlas based approach predicts the target automatically as opposed to the manual selection currently used. The results showed that 85% of the times, this automatic selection of the target location was closer to the target when compared to currently used technique.

Humans perform complex sensorimotor tasks, such as walking on uneven terrain, in a seemingly effortless manner. However, even simple voluntary tasks, like lifting the arm to shake hands, require intricate adjustments to maintain balance. With experience, humans learn to produce the appropriate patterns of muscle activity necessary to maintain balance during everyday activities, as well as highly specialized motor tasks. Here, I investigated the neural feedback mechanisms controlling the formation of the muscle activity used during balance tasks. I hypothesized that humans use feedback from on-going balance perturbations to establish their muscular responses. Specifically, I investigated center-of-mass (CoM) kinematics as a control signal for the formation of these muscle activation patterns. Using an inverted pendulum model under delayed feedback control, I both reconstructed the temporal EMG patterns measured during experimental perturbations and predicted the optimal EMG patterns for responding to the same perturbations. By modulating four feedback parameters, this feedback law accounted for 91% of the variability in all experimentally-recorded EMG patterns - regardless of the mechanical action of the muscle or the response strategy chosen by the subject. To investigate the changes in postural control during motor learning, I used this feedback model to characterize responses while naïve subjects adapted to repetitive unidirectional and reversing perturbations. By adjusting feedback gains related to CoM velocity and displacement, subjects adapted their muscle activity to improve control over the CoM for both perturbation types. Though subjects were unable to use anticipatory strategies to reduce muscle onset latency or to mute inappropriate responses to reversing perturbations, more subtle feedforward adjustments to feedback-mediated postural responses were evident. With experience, subjects adapted their postural responses toward the optimal solution. The results of this work, when combined with on-going studies of muscle synergies, will provide a powerful tool for investigating the consequences that result from the changes in spatiotemporal muscle activity associated with aging, neurological dysfunction, musculoskeletal injury, and specialized training programs. This quantitative knowledge is critical to the development of diagnostic tools for balance and movement disorders, as well as for the design of effective interventional therapies, bipedal robots, and neural prostheses.

Thesis (MSc (Genetics))—University of Stellenbosch, 2007. / No obvious explanations exist for the development of abnormal involuntary movements (AIM), but several hypotheses have been proposed for tardive dyskinesia (TD) development. Since TD seems to have a genetic basis, several genetic variants have been investigated in TD development in various populations. Few studies have focused on African populations. This study focused on genetic variants (previously investigated in other populations) and the development and severity of AIM and TD in a Xhosa schizophrenia population. Genotype and allele frequencies determined were compared to those described in the literature for other populations. Following a report of an association between Ala-9Val and schizophrenia in a Turkish population, this study subsequently investigated this association in the Xhosa population. MnSOD Ala-9Val was genotyped using HEX-SSCP analysis and the DRD3 Ser9Gly variant was genotyped using restriction enzyme digestion by MscI. Genotyping was followed by statistical comparisons of the various groups, as well as association analyses between the variant and schizophrenia (only for MnSOD), AIM, or TD development and severity. The groups included a Xhosa schizophrenia group, a subgroup of the Xhosa schizophrenia group that had AIM (AIM+) and did not have AIM (AIM-), a subgroup of the AIM+ group that had TD (TD+), and a healthy Xhosa control group. A possible interaction between Ala-9Val and Ser9Gly in the development of AIM and TD was also investigated. Lastly, it was attempted to genotype CYP2D6*4, CYP2D6*10 and CYP2D6*17 using various PCR methods followed by restriction enzyme analysis. MnSOD Ala-9Val genotype and allele frequencies were similar to those of the Turkish population, but differed to those of the Asian populations. No association between Ala-9Val and the development and severity of schizophrenia was found. However, a relationship between genotype and AIM or TD development was observed, as well as an association between TD severity and Ala- 9Val genotype. DRD3 Ser9Gly genotype and allele frequencies were similar to those of the African American population, but differed from other populations. No significant association between Ser9Gly and the development and severity of AIM or TD was detected, nor was an interactive effect between Ala-9Val and Ser9Gly in AIM or TD development observed. The genotyping of CYP2D6 proved difficult and these variants could therefore not be analysed. The CYP2D6*4 genotype and allele frequencies that could be determined from some samples, were similar to the frequencies described previously for African populations. While we did not find an association between Ser9Gly in TD or AIM development and severity, nor an interaction between Ala-9Val and Ser9Gly, we did observe a relationship between Ala-9Val and AIM or TD development and TD severity. The effect of this variant is probably small and other variants, specifically those in genes involved in free radical removal should be investigated in combination with Ala-9Val. With regard to CYP2D6 it is suggested that high-throughput genotyping methods (e.g. microarray technology) should be used in the future. This will enable simultaneous genotyping of several variants and can be used in various populations. This study is the first of its kind by focusing on the unique South African Xhosa population and TD or AIM development.

A espasticidade é uma desordem comum em pessoas que apresentam lesão no neurônio motor superior. O acometimento pode ocorrer em diferentes níveis. A Escala Modificada de Ashworth (EMA) é o instrumento de avaliação mais utilizado para medir os níveis de acometimento, entretanto apresenta subjetividade. Já a mecanomiografia (MMG) trata-se de uma técnica objetiva, que quantifica as vibrações musculares durante os eventos de contração e alongamento e, por isso, pode dimensionar com precisão o nível de espasticidade. Diante disso, objetivou-se investigar a correlação entre os níveis de espasticidade determinados pela EMA com os sinais mecanomiográficos em músculos espásticos e não espásticos. Avaliaram-se 34 membros de 22 voluntários, de ambos os sexos, com idade média de 39,91±13,77 anos. O protocolo experimental consistiu na realização de avaliação pela EMA dos grupos musculares flexores e extensores de joelho e/ou cotovelo, onde um grupo era o agonista e o outro antagonista. Simultaneamente, captavam-se os sinais de MMG. Utilizou-se um equipamento de MMG customizado para registrar e gravar os sinais, configurados em um programa da plataforma LabView®. No programa computacional MatLab®, processaram-se os sinais da MMG no domínio temporal (mediana da energia) e espectral (mediana da frequência) dos eixos de movimento X (transversal), Y (longitudinal) e Z (perpendicular). Para delimitação da banda passante, empregou-se um filtro Butterworth de 3a ordem atuando na faixa de 5 a 50 Hz. Aplicaram-se testes estatísticos como coeficiente de correlação de Spearman, teste de Kruskall-Wallis e teste de correlação linear. Como resultados, no domínio temporal, o teste de Kruskal- Wallis mostrou diferenças na mediana da energia (MMG ME) entre cada grupo de EMA. O teste de correlação linear mostrou alta correlação entre a EMA e a MMGME, tanto no grupo muscular agonista quanto no antagonista. Assim, no domínio do tempo, a maior correlação linear ocorreu entre a EMA e a MMGME do eixo Z do grupo muscular agonista (R2 = 0,9557) e a menor correlação no eixo X, do antagonista (R 2 = 0,8862). O teste de correlação de Spearman também confirmou alta correlação em todos os eixos, nesta análise. O processamento no domínio espectral mostrou que houve aumento na mediana da frequência (MMGMF) nos maiores graus de EMA. Porém, os coeficientes de correlação linear determinados foram moderados e baixos. O maior coeficiente de correlação linear entre a EMA e a MMGMF ocorreu no eixo Z, do grupo muscular agonista (R2 = 0,4883) e o menor valor no eixo Y, do grupo antagonista (R 2 = 0,1657). No teste de Spearman, a maior correlação ocorreu entre o eixo Y do grupo agonista (0,6951; p < 0,001) e o menor valor no eixo X do grupo antagonista (0,3592; p < 0,001). Por meio dos dados obtidos, concluiu-se que entre a MMGME e a EMA houve correlação significativamente elevada em ambos os grupos musculares. Entre a MMGMF e a EMA também houve correlação significativa, porém moderada no grupo agonista, e fraca no grupo antagonista. Desta forma, dentre os descritores estudados, a MMGME mostrou ser a mais adequada para correlacionar-se com o grau de espasticidade definido pela EMA. / Spasticity is a common disorder in people who have upper motor neuron injury. The involvement may occur at different levels. The Modified Ashworth Scale (MAS) is the most used method to measure involvement levels. But it corresponds to a subjective evaluation. Mechanomyography (MMG) is an objective technique that quantifies the muscle vibration during the contraction and stretching events. So, it may assess the level of spasticity accurately. This study aimed to investigate the correlation between spasticity levels determined by MAS with MMG signal in spastic and not spastic muscles. In the experimental protocol, we evaluated 34 members of 22 volunteers, of both genders, with a mean age of 39.91 ± 13.77 years. We evaluated the levels of spasticity by MAS in flexor and extensor muscle groups of the knee and/or elbow, where one muscle group was the agonist and one antagonist. Simultaneously the assessment by the MAS, caught up the MMG signals. We used a custom MMG equipment to register and record the signals, configured in LabView platform. Using the MatLab computer program, it was processed the MMG signals in the time domain (median energy) and spectral domain (median frequency) for the three motion axes: X (transversal), Y (longitudinal) and Z (perpendicular). For bandwidth delimitation, we used a 3rd order Butterworth filter, acting in the range of 5-50 Hz. Statistical tests as Spearman's correlation coefficient, Kruskal-Wallis test and linear correlation test were applied. As results in the time domain, the Kruskal-Wallis test showed differences in median energy (MMGME) between MAS groups. The linear correlation test showed high linear correlation between MAS and MMGME for the agonist muscle as well as for the antagonist group. The largest linear correlation occurred between the MAS and MMG ME for the Z axis of the agonist muscle group (R2 = 0.9557) and the lowest correlation occurred in the X axis, for the antagonist muscle group (R2 = 0.8862). The Spearman correlation test also confirmed high correlation for all axes in the time domain analysis. In the spectral domain, the analysis showed an increase in the median frequency (MMGMF) in MAS’ greater levels. The highest correlation coefficient between MAS and MMGMF signal occurred in the Z axis for the agonist muscle group (R2 = 0.4883), and the lowest value occurred on the Y axis for the antagonist group (R2 = 0.1657). By means of the Spearman correlation test, the highest correlation occurred between the Y axis of the agonist group (0.6951; p <0.001) and the lowest value on the X axis of the antagonist group (0.3592; p <0.001). We conclude that there was a significantly high correlation between the MMGME and MAS in both muscle groups. Also between MMG and MAS occurred a significant correlation, however moderate for the agonist group, and low for the antagonist group. So, the MMGME proved to be more an appropriate descriptor to correlate with the degree of spasticity defined by the MAS.

A espasticidade é uma desordem comum em pessoas que apresentam lesão no neurônio motor superior. O acometimento pode ocorrer em diferentes níveis. A Escala Modificada de Ashworth (EMA) é o instrumento de avaliação mais utilizado para medir os níveis de acometimento, entretanto apresenta subjetividade. Já a mecanomiografia (MMG) trata-se de uma técnica objetiva, que quantifica as vibrações musculares durante os eventos de contração e alongamento e, por isso, pode dimensionar com precisão o nível de espasticidade. Diante disso, objetivou-se investigar a correlação entre os níveis de espasticidade determinados pela EMA com os sinais mecanomiográficos em músculos espásticos e não espásticos. Avaliaram-se 34 membros de 22 voluntários, de ambos os sexos, com idade média de 39,91±13,77 anos. O protocolo experimental consistiu na realização de avaliação pela EMA dos grupos musculares flexores e extensores de joelho e/ou cotovelo, onde um grupo era o agonista e o outro antagonista. Simultaneamente, captavam-se os sinais de MMG. Utilizou-se um equipamento de MMG customizado para registrar e gravar os sinais, configurados em um programa da plataforma LabView®. No programa computacional MatLab®, processaram-se os sinais da MMG no domínio temporal (mediana da energia) e espectral (mediana da frequência) dos eixos de movimento X (transversal), Y (longitudinal) e Z (perpendicular). Para delimitação da banda passante, empregou-se um filtro Butterworth de 3a ordem atuando na faixa de 5 a 50 Hz. Aplicaram-se testes estatísticos como coeficiente de correlação de Spearman, teste de Kruskall-Wallis e teste de correlação linear. Como resultados, no domínio temporal, o teste de Kruskal- Wallis mostrou diferenças na mediana da energia (MMG ME) entre cada grupo de EMA. O teste de correlação linear mostrou alta correlação entre a EMA e a MMGME, tanto no grupo muscular agonista quanto no antagonista. Assim, no domínio do tempo, a maior correlação linear ocorreu entre a EMA e a MMGME do eixo Z do grupo muscular agonista (R2 = 0,9557) e a menor correlação no eixo X, do antagonista (R 2 = 0,8862). O teste de correlação de Spearman também confirmou alta correlação em todos os eixos, nesta análise. O processamento no domínio espectral mostrou que houve aumento na mediana da frequência (MMGMF) nos maiores graus de EMA. Porém, os coeficientes de correlação linear determinados foram moderados e baixos. O maior coeficiente de correlação linear entre a EMA e a MMGMF ocorreu no eixo Z, do grupo muscular agonista (R2 = 0,4883) e o menor valor no eixo Y, do grupo antagonista (R 2 = 0,1657). No teste de Spearman, a maior correlação ocorreu entre o eixo Y do grupo agonista (0,6951; p < 0,001) e o menor valor no eixo X do grupo antagonista (0,3592; p < 0,001). Por meio dos dados obtidos, concluiu-se que entre a MMGME e a EMA houve correlação significativamente elevada em ambos os grupos musculares. Entre a MMGMF e a EMA também houve correlação significativa, porém moderada no grupo agonista, e fraca no grupo antagonista. Desta forma, dentre os descritores estudados, a MMGME mostrou ser a mais adequada para correlacionar-se com o grau de espasticidade definido pela EMA. / Spasticity is a common disorder in people who have upper motor neuron injury. The involvement may occur at different levels. The Modified Ashworth Scale (MAS) is the most used method to measure involvement levels. But it corresponds to a subjective evaluation. Mechanomyography (MMG) is an objective technique that quantifies the muscle vibration during the contraction and stretching events. So, it may assess the level of spasticity accurately. This study aimed to investigate the correlation between spasticity levels determined by MAS with MMG signal in spastic and not spastic muscles. In the experimental protocol, we evaluated 34 members of 22 volunteers, of both genders, with a mean age of 39.91 ± 13.77 years. We evaluated the levels of spasticity by MAS in flexor and extensor muscle groups of the knee and/or elbow, where one muscle group was the agonist and one antagonist. Simultaneously the assessment by the MAS, caught up the MMG signals. We used a custom MMG equipment to register and record the signals, configured in LabView platform. Using the MatLab computer program, it was processed the MMG signals in the time domain (median energy) and spectral domain (median frequency) for the three motion axes: X (transversal), Y (longitudinal) and Z (perpendicular). For bandwidth delimitation, we used a 3rd order Butterworth filter, acting in the range of 5-50 Hz. Statistical tests as Spearman's correlation coefficient, Kruskal-Wallis test and linear correlation test were applied. As results in the time domain, the Kruskal-Wallis test showed differences in median energy (MMGME) between MAS groups. The linear correlation test showed high linear correlation between MAS and MMGME for the agonist muscle as well as for the antagonist group. The largest linear correlation occurred between the MAS and MMG ME for the Z axis of the agonist muscle group (R2 = 0.9557) and the lowest correlation occurred in the X axis, for the antagonist muscle group (R2 = 0.8862). The Spearman correlation test also confirmed high correlation for all axes in the time domain analysis. In the spectral domain, the analysis showed an increase in the median frequency (MMGMF) in MAS’ greater levels. The highest correlation coefficient between MAS and MMGMF signal occurred in the Z axis for the agonist muscle group (R2 = 0.4883), and the lowest value occurred on the Y axis for the antagonist group (R2 = 0.1657). By means of the Spearman correlation test, the highest correlation occurred between the Y axis of the agonist group (0.6951; p <0.001) and the lowest value on the X axis of the antagonist group (0.3592; p <0.001). We conclude that there was a significantly high correlation between the MMGME and MAS in both muscle groups. Also between MMG and MAS occurred a significant correlation, however moderate for the agonist group, and low for the antagonist group. So, the MMGME proved to be more an appropriate descriptor to correlate with the degree of spasticity defined by the MAS.

L'évolution des connaissances dans le domaine de la neurochirurgie fonctionnelle, la neuroradiologie et les études de traçage neuronal par virus neurotropes ont permis d'étudier les circuits sous-tendant l'expression clinique de plusieurs syndromes neurologiques. La stimulation cérébrale profonde (SCP) du globus pallidus interne (GPi) est une thérapie validée dans les syndromes dystono-dyskinétiques (SDD) isolés. L'extension des indications vers des SDD secondaires ou hérédo-dégénératifs nous confronte à la nécessité d'améliorer notre compréhension des mécanismes de réorganisation fonctionnelle du circuit moteur et de l'intégrité résiduelle des connexions anatomiques. L'efficacité de la SCP dans les SDD complexes est déterminée par la préservation relative de la voie pyramidale, les interactions du circuit cortico-striato-pallido-thalamique et cérébello-thalamo-cortical et la réorganisation du réseau moteur au niveau cortical. Ce travail de thèse a essayé d’évaluer différentes composantes du réseau moteur in vivo chez l’homme à travers de l’étude de trois pathologies du mouvement associées à un SDD complexe. L’application de la SCP à la maladie de Huntington (MH) est un modèle d'étude du réseau moteur dans le contexte d’un SDD associé à une dégénérescence des neurones striato-pallidaux. Nous avons fait une étude prospective pour évaluer l'efficacité à long terme de la SCP du GPi sur les symptômes moteurs de la MH. Sept patients ayant une chorée sévère réfractaire au traitement pharmacologique ont été inclus dans l'étude. Nous avons observé une réduction significative de la chorée chez tous les patients avec un effet maintenu dans le temps (suivi médian de 3 ans). La bradykinésie et la dystonie ont montré une tendance (non significative) à une aggravation progressive. L'analyse anatomo-fonctionnelle du réseau moteur résiduel sous-tendant un SDD secondaire (dû à une lésion cérébrale acquise) a été abordée par deux techniques de neuroimagerie avancée. La réorganisation du circuit moteur dans le cadre d’une hémidystonie a été évaluée par IRM fonctionnelle. Les objectifs principaux ont été: 1) l’évaluation des régions activées par l'exécution d’une tâche motrice chez un groupe de patients hémidystoniques par rapport à un groupe de sujets témoins; 2) l’identification des profils d'activation selon le phénotype clinique (hypo/hyperkinétique) ou radiologique (lésion localisée en amont ou en aval du GPi) (des critères qui orientent l’éligibilité pour la SCP pallidale). Les études individuelles des patients ont montré des profils d'activation hétérogènes avec une activation bilatérale possible malgré le caractère unilatéral des lésions. En comparaison avec les sujets témoins, les patients ont présenté une réduction de l'activation au niveau thalamique, pallidal et temporal médial du côté ipsilatéral à la lésion. Les patients atteints d'une hémidystonie hypokinétique ont montré un profil d'activation bi-hémisphérique, désorganisé, ce qui pourrait expliquer le manque de réponse à la SCP observée dans cette présentation clinique. L'imagerie du tenseur de diffusion (DTI) a été appliquée à l'étude de la distribution topographique et la gravité des lésions de la substance blanche d'un groupe de patients atteints d'un SDD secondaire à une encéphalopathie anoxique néonatale par rapport à un groupe témoin. L'étude TBSS (tract based spatial statistics) a identifié la présence d'anomalies diffuses de la microstructure de la substance blanche (diminution de la fraction d’anisotropie (FA)) chez les patients. La technique de tractographie probabiliste a été utilisée pour reconstruire les faisceaux corticospinaux (CS) et thalamocorticaux (TC) (les voies efférentes du circuit moteur) et pour obtenir des paramètres quantitatifs DTI moyens pour chaque faisceau. La FA moyenne des faisceaux TC est diminuée chez les patients. Nous avons étudié la corrélation entre les paramètres cliniques et neurophysiologiques et les paramètres DTI du groupe de patients. / Advances in the field of functional neurosurgery, neuroradiology and virus neuronal tracing studies have enabled to deepen our knowledge of the circuits underlying the clinical expression of several neurologic syndromes. Globus pallidus internus (GPi) deep brain stimulation (DBS) is a validated technique for the treatment of isolated (primary) dystonia-dyskinesia syndromes (DDS). Broadening indications for DBS therapy to complex DDS (secondary and heredodegenerative disorders) require further understanding of motor circuit functional reorganization mechanisms and residual anatomic connections integrity. The efficacy of neuromodulation in these complex dystonia syndromes is determined by the relative preservation of pyramidal pathway, the interactions between cortico-striato-pallido-thalamic and cerebello-thalamo-cortical circuits and motor network reorganization at the cortical level. This thesis has tried to evaluate the different components of human motor network in vivo through the study of three different movement disorders associated with complex dystonia. The application of DBS to Huntington’s disease (HD) is a model for the study of the motor network in the context of this heredodegenerative DDS associated with striatal neuron degeneration in the cortico-striato-pallido-thalamic loop. We have conducted a prospective study to evaluate long-term motor outcome of GPi DBS in HD. Seven patients with severe chorea refractory to medical treatment were included in the study. Significant and sustained reduction of chorea was observed for all patients until last follow-up visit (median follow-up was 3 years). Bradykinesia and dystonia showed a non-significant trend towards progressive worsening. Anatomic and functional assessment of the motor circuit following brain injury (secondary DDS) has been approached by two different advanced neuroimaging techniques. We have studied motor circuit reorganization underlying hemidystonia in functional magnetic resonance imaging (fMRI). The main objectives of this study were: 1) to evaluate activation regions associated with motor task execution in a group of hemidystonic patients compared with another group of healthy control subjects; 2) to identify activation patterns related to clinical (hypo or hyperkinetic) or radiological (prepallidal or postpallidal) phenotypes (following clinical criteria relevant for DBS therapy eligibility). Activation patterns associated with motor-task execution were heterogeneous in single-subject studies. Despite the unilateral distribution of lesions leading to dystonia, bilateral activation was found in several subjects. Compared with healthy control group, hemidystonic patients showed reduced brain activation in ipsilesional thalamus, globus pallidus and medial temporal areas. Hypokinetic hemidystonic subgroup showed widespread bilateral overactivity involving both hemispheres. Poor clinical outcome associated with this clinical presentation could be explained by DBS therapy inability to modulate a highly disorganized network. Diffusion tensor imaging (DTI) has been applied to the study of the topographic distribution and severity of white matter lesions in a group of patients with a DDS secondary to neonatal anoxic encephalopathy in comparison with a healthy control group. TBSS (tract based spatial statistics) found widespread areas of abnormal white matter microstructure (decreased fractional anisotropy (FA)) in the corpus callosum, corona radiata and posterior limb of the internal capsule in the group of patients. After running probabilistic tractography to reconstruct corticospinal and thalamocortical tracts (motor circuit output pathways), mean quantitative tract-derived DTI parameters were calculated for each single tract. This study found decreased mean FA in thalamocortical tracts in the group of patients as compared to healthy controls. Clinical scores and neurophysiological measures were also analyzed and correlated with DTI parameters.

Orientador: Alberto Cliquet Júnior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T12:33:02Z (GMT). No. of bitstreams: 1 Medeiros_RodrigoCastrode_M.pdf: 1107012 bytes, checksum: 8c4a2b98916bf061db40e20d0c7d01a6 (MD5) Previous issue date: 2011 / Resumo: Nas últimas décadas, a reabilitação nos lesado-medulares vem evoluindo através do uso da estimulação elétrica funcional (EEF). Apesar dos inegáveis ganhos cardiovasculares, psicológicos e na densidade mineral óssea advindos desta técnica, o ortostatismo e a deambulação destes pacientes sob estímulo elétrico ainda dependem do suporte fornecido pelos membros superiores. A literatura pertinente aos estudos biomecânicos sobre EEF para ortostatismo em paraplégicos está baseada em teoremas matemáticos fundamentados na física mecânica referente aos braços de alavanca musculoesqueléticos. Contudo, percebe-se uma falha conceitual nestes teoremas a medida que desconsideram os princípios de regulação do reflexo postural observados nos indivíduos sem alterações neurológicas. Nos indivíduos saudáveis, o princípio da conservação de energia exige que, na posição ortostática, a cabeça e tronco estejam alinhados sobre a pelve e centrados em relação aos pés. Para obtenção de uma postura adequada, o organismo utiliza primariamente o reflexo postural espinopélvico, através do qual as curvaturas sagitais da coluna são adaptadas à posição da pelve e dos quadris. O objetivo deste estudo é descrever os aspectos radiográficos do perfil sagital obtidos em pacientes paraplégicos em postura bipedal através da estimulação elétrica funcional dos quadríceps complementados com apoio bimanual. Dez pacientes paraplégicos que participam do ambulatório de reabilitação foram selecionados. Após serem submetidos a radiografias panorâmicas em perfil, foram analisados as médias e os desvios-padrão dos vários parâmetros geométricos descritos na literatura referentes ao equilíbrio sagital em indivíduos saudáveis. Os valores obtidos para cifose torácica e lordose lombar foram semelhantes a dos pacientes saudáveis descritos na literatura. Os parâmetros pélvicos revelaram inversão do tilt pélvico, aumento do slop sacral e diminuição do ângulo sacrofemoral. Nos parâmetros espinopélvicos, foram observados aumentos nas distâncias horizontais entre as vértebras e a bacia e/ou quadris. Estes aspectos traduzem a presença de uma importante anteversão da bacia associada à flexão dos quadris com consequente translação anterior da linha de prumo da coluna expressada através de um intenso desequilíbrio sagital anterior. Para quem deseja optimizara postura bipedal dos paraplégicos sob EEF, este estudo inédito lança uma nova e importante visão sobre a compreensão das alterações ergonômicas presentes no balanço sagital. Tal fato possivelmente servirá de base para o desenvolvimento de novas configurações de EEF / Abstract: In recent decades, the rehabilitation of injured spinal cord-has been evolving through the use of functional electrical stimulation (FES). Despite the undeniable gains cardiovascular, psychological and bone mineral density resulting from this technique, the standing and ambulation of these patients still depend on electrical stimulation of the support provided by the upper limbs. The literature pertaining to the biomechanical studies on FES for standing in paraplegics is based on mathematical theorems based on the physical mechanics related to musculoskeletal lever arms. However, we find a conceptual flaw in these theorems as they disregard the principles of regulation of postural reflex observed in subjects without neurological damage. In healthy subjects, the principle of conservation of energy requires that, in standing position, head and torso are aligned in the pelvis and centered over the feet. To obtain a proper posture, the body uses primarily espinopélvico postural reflex, whereby the sagittal curvatures of the spine are adapted to the position of the pelvis and hips. The aim of this study is to describe the radiographic features of the sagittal profile obtained in bipedal posture in paraplegic patients by functional electrical stimulation of the quadriceps supplemented with bimanual support. Ten paraplegic patients participating in outpatient rehabilitation were selected. After being subjected to panoramic radiography in profile, we analyzed the means and standard deviations of various geometrical parameters described in the literature for the sagittal balance in healthy subjects. The values obtained for thoracic kyphosis and lumbar lordosis were similar to healthy patients in the literature. The parameters revealed pelvic tilt reversal of pelvic, sacral and increase the slop angle reduction sacrofemoral. The spinopelic parameters increases were observed in the horizontal distances in relation to vertebrae and pelvis and/or hips. These aspects reflect the presence of a significant anteversion of the pelvis associated with hip flexion with subsequent anterior translation of the plumb line of the column expressed through an intense anterior sagittal imbalance. For those who want to optimize the bipedal posture of paraplegic patients under FES, this new study sheds new and important insight into the understanding of these ergonomic changes in sagittal balance. This fact possibly serve as the basis for the development of new configurations of FES / Mestrado / Fisiopatologia Cirúrgica / Mestre em Cirurgia

Pacientes com doença de Parkinson (DP) apresentam diversos sintomas não motores, dentre eles, alterações cognitivas. Déficits de função executiva podem ser observados desde os estágios iniciais da DP e impactam na independência funcional e na qualidade de vida. A função executiva é essencial para a realização de atividades de vida diária, que requerem integração cognitivo-motora. A realização de atividades cotidianas depende não só do sistema motor, mas também da interpretação e do processamento sensorial/ perceptual e da seleção e do planejamento da melhor estratégia motora. Sendo assim, um grande número de atividades de vida diária pode ser afetado por déficits na função executiva em pacientes com DP. Nessas tarefas, os componentes cognitivos e motores competem por recursos atencionais, o que pode prejudicar o desempenho em um ou em ambos os componentes. Entretanto, os estudos são muito direcionados para a análise de tarefas-duplas que envolvam equilíbrio em ortostatismo e marcha, mas contemplam pouco outras tarefas motoras. Os objetivos desse estudo foram (1) comparar o desempenho de pacientes com DP com o de um grupo controle nos testes de função executiva (Trail Making Test) e de fluência verbal (fluência semântica e fonêmica e diadococinesia oral /pataka/) e (2) investigar possíveis correlações entre função executiva e fluência verbal. O estudo foi realizado de maneira transversal, em uma única sessão, em uma avaliação de cerca de 50 minutos. Quarenta pacientes com DP (idade entre 50 e 79 anos, Hoehn & Yahr entre 2 e 3) e quarenta controles (com idade e escolaridade semelhantes) foram avaliados com o Trail Making Test, a fluência verbal semântica e fonêmica e o teste de diadococinesia oral. Na parte A do TMT, os participantes conectaram círculos numerados de 1 a 25, em sequência. Na parte B, os participantes conectaram círculos alternando números e letras (1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13). No teste de fluência verbal fonêmica, foi solicitado que os participantes dissessem palavras começando com a letra F. No teste de fluência verbal semântica, os participantes disseram o maior número de animais possível, em 60 segundos. No teste de diadococinesia oral, os participantes repetiram a sequência /pataka/ o mais rápido possível. Os grupos foram comparados por meio de análises de variância e as relações entre as variáveis foram investigadas pelo teste de correlação de Pearson. A análise de variância mostrou diferenças significativas entre grupos (F1,78=10,55; p=0,002) e entre partes do Trail Making Test (F1,78=154,02; p < 0,001). A parte B apresentou tempos maiores que a parte A (p < 0,001). Pacientes com DP disseram menos palavras nos testes de fluência verbal, em comparação aos controles (p < 0,001). Pacientes com DP repetiram a sequência /pataka/ menos vezes que os controles (p=0,019). Houve forte correlação entre o teste de fluência verbal fonêmica e a parte B do Trail Making Test (valor de r=-0,874 e p=0,001) e entre a diadococinesia oral e as partes A e B do Trail Making Test (valor de r=-0,824 e p=0,001). A correlação entre a parte B do Trail Making Test, que é uma medida de função executiva e reflete a habilidade de integração cognitivo-motora e as tarefas de fluência verbal, evidencia a importância do controle motor para as tarefas de fala. A tarefa da fala fornece não somente sobrecarga cognitiva, mas também motora para pacientes com DP. Esse conhecimento é importante para a prática clínica, uma vez que é necessário detectar a natureza do acometimento e da tarefa para usá-las de maneira adequada em programas de reabilitação / Patients with Parkinson´s disease (PD) can present several non-motor symptoms, including cognitive deficits. Executive function deficits can be observed since the early stages of PD and impact on functional independence and quality of life. The executive function is essential to the activities of daily living, which require cognitive-motor integration. The performance of activities of daily living depends not only on the motor system, but also on the sensory/ perceptual interpretation and processing and the selection and planning of the best motor strategy. Therefore, many activities of daily living can be affected by deficits in the executive function in patients with PD. In such tasks, cognitive and motor components compete for attentional resources, which may impair the performance of one or both tasks. However, most studies focus on to the analysis of dual-tasks involving orthostatic balance and gait, but they do not approach other motor tasks. The objectives of this study were (1) to compare the performance of patients with PD with a control group in executive function (Trail Making Test) and verbal fluency tests (semantic and phonemic and oral diadochokinesis /pataka/) and (2) to investigate possible correlations between executive function and verbal fluency. This was a cross-sectional study and the tests were performed individually in a 50-minute single session. Forty people with PD (aged 50 - 79 years, Hoehn & Yahr 2 - 3) and forty controls (with similar age and education) were evaluated with Trail Making Test (TMT, executive function), phonemic/semantic verbal fluency and oral diadochokinesis (/pataka/) tests. In part A of Trail Making Test, participants connected circles with the numbers 1-25, in sequence. In part B, participants connected circles in a sequence with alternated numbers and letters (1-A-2-B-3-C-4-D-5-E-6-F-7-G-8-H-9-I-10-J-11-K-12-L-13). In the phonemic verbal fluency test, participants were instructed to say words beginning with the letter F. In the semantic verbal fluency test, participants were instructed to say out loud as many animals as they could remember, in 60 seconds. In the oral diadochokinesis test, participants were asked to say the /pataka/ sequence as fast as they could. Groups were compared by analyses of variance and the relationships between the variables were investigated by Pearson correlation tests. Analysis of variance showed significant differences between groups (F1,78=10.55; p=0.002) and between Trail Making Test parts (F1,78=154.02; p < 0.001). Part B showed longer times than part A (p < 0.001). People with PD said fewer words in both fluency tests, compared to controls (p < 0.001). People with PD repeated the sequence /pataka/ less times than controls (p=0.019). There was a strong correlation between the phonemic verbal fluency test and the part B of Trail Making Test (r=-0.874 and p=0.001) and between the oral diadochokinesis test and both parts of the Trail Making Test (r=-0.824 e p=0.001). The correlation between the part B of Trail Making Test, which is an executive function measure and reflects the cognitive-motor integration ability, and the verbal fluency tests, evidences the importance of motor control for speech tasks. Speech tasks not only provide cognitive overload, but also motor overload in patients with PD. This knowledge is important in clinical practice, in which therapists must detect the nature of the disability and the task to use this information properly in rehabilitation programs

Pathophysiologische und therapeutische Bedeutung der a1- und a2-Untereinheiten des GABAA-Rezeptors für Dystonien: Untersuchungen im dtsz Hamstermodell