Distonia focal é uma desordem neurológica do movimento que pode ser altamente incapacitante afetando de maneira importante a vida, carreira professional e práticas interpretativas dos músicos. Segundo pesquisas a distonia focal pode manifestar-se em até 1% dos músicos. O objetivo principal da presente pesquisa foi investigar as estratégias de estudo utilizadas por três músicos profissionais com distonia focal (dois flautistas e um violinista). Adicionalmente se realizou um auto relato, no qual o autor (que também sofre da doença) descreve e analisa seu processo, focalizando-se nos mesmos aspectos investigados nas entrevistas. Os resultados obtidos foram confrontados com a literatura sobre o tema, a experiência pessoal do autor e com as respostas proporcionadas por um músico, neurologista e especialista em distonia focal (por meio de uma outra entrevista). A coleta de dados dos participantes foi realizada através de entrevistas semiestruturadas. Os resultados obtidos apontam que o uso das estratégias de estudo é variado e individualizado conforme: as características particulares de cada caso, gravidade da doença, instrumento interpretado, o processo pessoal com a doença, as expectativas pessoais, etc. Porém, a pesquisa destaca a importância da terapia física para desenvolver novas habilidades motoras interpretativas e também a utilização de terapia psicológica para reduzir os níveis de ansiedade no estabelecimento de uma nova relação com o instrumento. Dentre as estratégias musicais encontradas para lidar com a doença estão: adequações no repertorio de estudo, práticas musicais paralelas e modificações no instrumento. / Focal dystonia is a neurological movement disorder that can be highly incapable, affecting life, professional career and music performing. According to studies, up to 1% of musicians can be affected. The principal objective of this research was to explore the study methodologies used by three professional musicians with focal dystonia. Additionally a selfreport developed by the author (who also is affected by disease) narrates and analyze his personal process focusing on the same aspects that are investigated in the interviews. Data was collected from participants using semi-structured interviews. The results were compared with academic publications, personal experience of the author and with answers given by a musician, neurologist and specialist in focal dystonia, (collected in another interview). Part of the data is the Self- report, where the author presents its personal process with focal dystonia, based on self-observation, motor re-learning and Alexander Technique. The results obtained highlighted that the use of methodological studies diverse and personalized, according to particular characteristics of each case (the state of the disease, the instrument played by the musician, the personal process, recovery expectations, etc.). However, in general, the following aspects were founded: physical therapy, for constructing new motor patterns and psychological therapy to reduce the levels of anxiety and begin to establish a new relationship with the instrument. Among musical methodologies to face disease the following are included: adjustments in the musical repertory, parallel musical practice and instrument modifications.

Distonia focal é uma desordem neurológica do movimento que pode ser altamente incapacitante afetando de maneira importante a vida, carreira professional e práticas interpretativas dos músicos. Segundo pesquisas a distonia focal pode manifestar-se em até 1% dos músicos. O objetivo principal da presente pesquisa foi investigar as estratégias de estudo utilizadas por três músicos profissionais com distonia focal (dois flautistas e um violinista). Adicionalmente se realizou um auto relato, no qual o autor (que também sofre da doença) descreve e analisa seu processo, focalizando-se nos mesmos aspectos investigados nas entrevistas. Os resultados obtidos foram confrontados com a literatura sobre o tema, a experiência pessoal do autor e com as respostas proporcionadas por um músico, neurologista e especialista em distonia focal (por meio de uma outra entrevista). A coleta de dados dos participantes foi realizada através de entrevistas semiestruturadas. Os resultados obtidos apontam que o uso das estratégias de estudo é variado e individualizado conforme: as características particulares de cada caso, gravidade da doença, instrumento interpretado, o processo pessoal com a doença, as expectativas pessoais, etc. Porém, a pesquisa destaca a importância da terapia física para desenvolver novas habilidades motoras interpretativas e também a utilização de terapia psicológica para reduzir os níveis de ansiedade no estabelecimento de uma nova relação com o instrumento. Dentre as estratégias musicais encontradas para lidar com a doença estão: adequações no repertorio de estudo, práticas musicais paralelas e modificações no instrumento. / Focal dystonia is a neurological movement disorder that can be highly incapable, affecting life, professional career and music performing. According to studies, up to 1% of musicians can be affected. The principal objective of this research was to explore the study methodologies used by three professional musicians with focal dystonia. Additionally a selfreport developed by the author (who also is affected by disease) narrates and analyze his personal process focusing on the same aspects that are investigated in the interviews. Data was collected from participants using semi-structured interviews. The results were compared with academic publications, personal experience of the author and with answers given by a musician, neurologist and specialist in focal dystonia, (collected in another interview). Part of the data is the Self- report, where the author presents its personal process with focal dystonia, based on self-observation, motor re-learning and Alexander Technique. The results obtained highlighted that the use of methodological studies diverse and personalized, according to particular characteristics of each case (the state of the disease, the instrument played by the musician, the personal process, recovery expectations, etc.). However, in general, the following aspects were founded: physical therapy, for constructing new motor patterns and psychological therapy to reduce the levels of anxiety and begin to establish a new relationship with the instrument. Among musical methodologies to face disease the following are included: adjustments in the musical repertory, parallel musical practice and instrument modifications.

Distonia focal é uma desordem neurológica do movimento que pode ser altamente incapacitante afetando de maneira importante a vida, carreira professional e práticas interpretativas dos músicos. Segundo pesquisas a distonia focal pode manifestar-se em até 1% dos músicos. O objetivo principal da presente pesquisa foi investigar as estratégias de estudo utilizadas por três músicos profissionais com distonia focal (dois flautistas e um violinista). Adicionalmente se realizou um auto relato, no qual o autor (que também sofre da doença) descreve e analisa seu processo, focalizando-se nos mesmos aspectos investigados nas entrevistas. Os resultados obtidos foram confrontados com a literatura sobre o tema, a experiência pessoal do autor e com as respostas proporcionadas por um músico, neurologista e especialista em distonia focal (por meio de uma outra entrevista). A coleta de dados dos participantes foi realizada através de entrevistas semiestruturadas. Os resultados obtidos apontam que o uso das estratégias de estudo é variado e individualizado conforme: as características particulares de cada caso, gravidade da doença, instrumento interpretado, o processo pessoal com a doença, as expectativas pessoais, etc. Porém, a pesquisa destaca a importância da terapia física para desenvolver novas habilidades motoras interpretativas e também a utilização de terapia psicológica para reduzir os níveis de ansiedade no estabelecimento de uma nova relação com o instrumento. Dentre as estratégias musicais encontradas para lidar com a doença estão: adequações no repertorio de estudo, práticas musicais paralelas e modificações no instrumento. / Focal dystonia is a neurological movement disorder that can be highly incapable, affecting life, professional career and music performing. According to studies, up to 1% of musicians can be affected. The principal objective of this research was to explore the study methodologies used by three professional musicians with focal dystonia. Additionally a selfreport developed by the author (who also is affected by disease) narrates and analyze his personal process focusing on the same aspects that are investigated in the interviews. Data was collected from participants using semi-structured interviews. The results were compared with academic publications, personal experience of the author and with answers given by a musician, neurologist and specialist in focal dystonia, (collected in another interview). Part of the data is the Self- report, where the author presents its personal process with focal dystonia, based on self-observation, motor re-learning and Alexander Technique. The results obtained highlighted that the use of methodological studies diverse and personalized, according to particular characteristics of each case (the state of the disease, the instrument played by the musician, the personal process, recovery expectations, etc.). However, in general, the following aspects were founded: physical therapy, for constructing new motor patterns and psychological therapy to reduce the levels of anxiety and begin to establish a new relationship with the instrument. Among musical methodologies to face disease the following are included: adjustments in the musical repertory, parallel musical practice and instrument modifications.

Brass musicians are known to experience a performance problem that is sometimes called valsalva maneuver or musical stuttering. This problem is known to cause difficulty starting a first note, tension in the throat, and tightness in the chest. Unfortunately, the research literature lacks sufficient details for evidence-based interventions. Therefore, the purpose of this study is to characterize and define this performance problem as experienced by brass musicians. An online epidemiologic survey was developed and deployed to collect data from brass musicians who have experienced this problem in their own playing. The survey was designed to acquire data in order to characterize and define the phenomenon through a biopsychosocial framework. The survey was also designed to assess whether this problem aligns with Altenmuller's heuristic model of motor control disruptions. A diverse group of brass musicians (n = 252) participated and offered relevant details for characterizing and defining this problem. Analysis of characteristic data suggests this problem is not a form of musical stuttering. Considering these data through Altenmuller's model suggests that this problem is experienced as a spectrum of motor disruptions that can develop into a unique type of musician's dystonia. While additional research is warranted, the results of this study are applicable to brass musicians, brass pedagogues, music educators, and performing arts health clinicians.

Dystonia is a neurological syndrome characterized by the involuntary contraction of opposing muscles, causing twisting movements or abnormal postures (modified by Fahn, 1987). Writer's cramp is the most common form of task-specific focal dystonia. In the first study, patients with writer's cramp were evaluated for differences in cortical activation during movements likely to induce cramps (complex movements) and movements which rarely lead to dystonia (simple movements). Although complex patient movements during fMRI were never associated with dystonic cramps, they exhibited abnormally decreased cortical activity. This was not observed in simple movements and was unrelated to the character of handwriting or the presence/absence of visual feedback. Our results support the theory of dualistic sensorimotor system behavior in writer's cramp. As the somatosensory system is believed to be affected in focal dystonia, we focused on modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in the second study, in order to improve writer's cramp. In conclusion, 1 Hz rTMS of the SI cortex can improve manifestations of writer's cramp while increasing cortical activity in both hemispheres. Handwriting as well as subjective assessment improved in most...

Orientadores: Anelyssa Cysne Frota D'Abreu, Iscia Teresinha Lopes-Cendes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T05:40:31Z (GMT). No. of bitstreams: 1 Piovesana_LuizaGonzaga_M.pdf: 1656872 bytes, checksum: 2a3571bb0d9dc43e8f0405aa2c799a5e (MD5) Previous issue date: 2014 / Resumo: As distonias caracterizam-se por movimentos involuntários e torsionais, que se manifestam de diferentes formas e podem afetar quaisquer músculos voluntários. Diversas mutações genéticas foram associadas às distonias primárias, destacando-se a DYT1, DYT5 e DYT6. O gene DYT1/TOR1A foi o primeiro identificado, ao apresentar uma deleção GAG que produz uma proteína mutante que altera conexões núcleo-cito-esqueléticas e o processamento proteico. O fenótipo típico inicia-se dos três aos 26 anos, tem penetrância de 30%, sendo 60% com acometimento generalizado ou multifocal. O gene DYT6/THAP1 possui diversos polimorfismos descritos e acredita-se que seja o segundo em prevalência entre as distonias hereditárias. Possui penetrância ainda menor e fenótipo de início precoce, envolvimento crânio-cervical e de fala. A frequência, etiologia e as alterações genéticas das distonias não são conhecidas na população brasileira, que por suas características específicas, não podem ter os resultados de outras populações simplesmente transpostos para a nossa. Nosso objetivo, portanto, foi caracterizar genética e clinicamente uma amostra de pacientes brasileiros com distonia. Os indivíduos foram recrutados no Ambulatório de Distúrbios do Movimento e de Distonia. Os pacientes foram avaliados por um questionário padronizado, seguido por pesquisa das mutações DYT1 e DYT6. A avaliação clínica demonstrou que a nossa coorte apresenta padrão semelhante ao internacional, com pacientes de início jovem tendendo a apresentar quadros generalizados e com história familiar positiva e pacientes adultos mantendo quadros focais ou segmentares e esporádicos. A pesquisa de mutações identificou 1 mutação missense já descrita na literatura, envolvida na penetrância da DYT1 em indivíduos com a mutação causadora clássica da doença e que pode conferir risco quando encontrada isoladamente. Também encontramos uma deleção de 6 pares de base no fim do exon 1 do gene THAP1 que em avaliações preliminares altera o sitio de splicing e acaba por abortar a tradução da proteína por meio de um stop códon precoce. Concluímos que nossos pacientes tem apresentação clinica semelhante a literatura mundial, porém com características genotípicas diferentes, pois não encontramos em nenhum individuo as mutações mais classicamente associadas as doenças. A diferenciação das distonias em subtipos e o entendimento das vias moleculares comuns devem fazer parte de investigações futuras / Abstract: Dystonia is characterized by involuntary and torsional movements, which manifest themselves in various forms and can affect any voluntary muscle. Several genetic mutations have been associated with isolated hereditary dystonia, most notably the DYT1 and DYT6. The DYT1 is caused by a GAG deletion at the TOR1A gene, which produces a protein that alters intracellular membranes connections and protein processing. The typical phenotype starts from three to 26 years of age, it has penetrance of 30 % and 60% of the subjects will progress to a generalized or multifocal involvement. The DYT6/THAP1 gene has several polymorphisms described, believed to be the second in prevalence among the hereditary dystonias. DYT6 has an even lower penetrance. It is characteristically an early-onset, dystonia with craniocervical and speech involvement. The frequency, etiology and genetic alterations of dystonia are not known in the Brazilian population, which due to its specific characteristics may not share of the same genetic background. Our aim was to evaluate genetically and clinically a sample of Brazilian patients with dystonia. Subjects were recruited from the Outpatient Movement Disorders and Dystonia Clinics. Patients were assessed by a standardized questionnaire, followed by molecular testing for DYT1 and DYT6. Our cohort showed similar results with the literature, where young, generalized and positive family history commonly group together, as focal and segmental cases that appear in adulthood tend to stabilize. Sequencing of the DYT1 gene found a known missense mutation that contributes to low penetrance in individual with the typical DYT1 mutation but might be a risk factor when found in isolation. Sequencing of the DYT6 gene showed a novel 6bp deletion at the end of exon 1, causing alternate splicing and a premature stop codon in preliminary analysis. Subdividing phenotypes and understanding common molecular pathways through new genetic data is in the future of dystonia research / Mestrado / Fisiopatologia Médica / Mestra em Ciências

Dystonia is a neurological syndrome characterized by the involuntary contraction of opposing muscles, causing twisting movements or abnormal postures (modified by Fahn, 1987). Writer's cramp is the most common form of task-specific focal dystonia. In the first study, patients with writer's cramp were evaluated for differences in cortical activation during movements likely to induce cramps (complex movements) and movements which rarely lead to dystonia (simple movements). Although complex patient movements during fMRI were never associated with dystonic cramps, they exhibited abnormally decreased cortical activity. This was not observed in simple movements and was unrelated to the character of handwriting or the presence/absence of visual feedback. Our results support the theory of dualistic sensorimotor system behavior in writer's cramp. As the somatosensory system is believed to be affected in focal dystonia, we focused on modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in the second study, in order to improve writer's cramp. In conclusion, 1 Hz rTMS of the SI cortex can improve manifestations of writer's cramp while increasing cortical activity in both hemispheres. Handwriting as well as subjective assessment improved in most...

L’identification des muscles responsables des dystonies focales est un prérequis à l’instauration des traitements par toxine botulique et exercices correcteurs. A partir de deux dystonies apparemment dissemblables: la crampe de l’écrivain et la dystonie cervicale, nous avons montré que la réponse aux traitements est tributaire de la distribution des muscles impliqués. L’enregistrement des mouvements du segment tête-cou dans la dystonie cervicale , au moyen de capteurs inertiels 3-D, a montré qu’au mouvement volontaire de la tête, dans un plan, s’associent des mouvements non physiologiques dans les deux autres plans. Pour déterminer les actions musculaires en cause, nous avons réalisé une modélisation numérique du segment tête-cou permettant d’associer le muscle responsable aux déformations. Par ailleurs, sachant l’importance des phénomènes sensitifs dans le contrôle du mouvement, nous avons, au cours de tâches d’ajustement de la force musculaire, montré que ce contrôle de la force est perturbé dans chacune des deux dystonies focales étudiées.Nos résultats devraient avoir une implication dans les traitements symptomatiques de ces dystonies. / The identification of the muscles responsible for focal dystonia is a prerequisite to the introduction of botulinum toxin treatment and tailored exercises. From two apparently dissimilar dystonia: writer's cramp and cervical dystonia, we showed that the response to the treatments depends on the distribution of the muscles involved. Recording the movement of the head-neck segment in cervical dystonia, using 3-D inertial sensors, showed that voluntary head movement in a plane is associated with non-physiological movement in the two other planes. To determine the muscular actions involved, we performed a digital modeling of the head-neck segment which allows us to link the responsible muscle with abnormal postures.Therefore, knowing the importance of sensory phenomena in the control of movement, we have, during tasks of muscular force adjustment, demonstrated that force control is altered in both studied dystonia.Our results should have implications in the symptomatic treatment of these dystonias.

Myoclonus-Dystonia (MD) is an inherited, rare, autosomal dominant movement disorder characterized by quick, involuntary muscle jerking or twitching (myoclonus) and involuntary muscle contractions that cause twisting and pulling movements, resulting in abnormal postures (dystonia). The first MD locus was mapped to 7q21-q31 and called DYT11; this locus corresponds to the SGCE gene. Our group previously identified a second MD locus (DYT15) which maps to a 3.18 Mb region on 18p11. Two patients were chosen to undergo next-generation sequencing, which identified 2,292 shared novel variants within the critical region. Analysis of these variants revealed a 3 bp duplication in a transcript referred to as CD108131, which is believed to be a long non-coding RNA. Characterization of this transcript determined that it is 863 bp in size, it is ubiquitously expressed, with high expression in the cerebellum, and it accounts for ~3% of MD cases.

Kernicterus causes damage to the auditory system and the basal ganglia in humans. Although the Gunn rat model of kernicterus has been extensively used to characterize the auditory features, this model has not been utilized to systematically investigate the movement disorder. In the present study, spontaneously jaundiced (jj) 16 day old Gunn rat pups were treated with sulfadimethoxine to exacerbate bilirubin neurotoxicity and compared to saline treated jjs and non-jaundiced (Nj) littermates. Electromyographic (EMG) activity was recorded from antagonistic hip muscles in dystonic and in normal appearing rats. Raw EMG signals were decomposed using the Discrete Wavelet Transform based multi-resolution analysis, and signal coefficients corresponding to the dominant EMG frequency band were chosen. Gunn rats exposed to sulfadimethoxine developed a stable clinical state characterized by prolonged abnormal axial and appendicular postures. Coherence plots revealed 4-7 Hz co-activation in antagonistic muscles that was significantly more prominent in jj sulfa treated dystonic compared to normal rats. The EMG findings support the presence of dystonia in sulfadimethoxine exposed jj Gunn rats.