Thesis (Ph. D.)--Virginia Commonwealth University, 2010. / Prepared for: Dept. of Biomedical Engineering. Title from resource description page of electronic thesis. Include bibliographical references. Unavailable until 5/14/2015.

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2008. / Title from title page screen (viewed on February 27, 2009). Research advisor: Mark S. LeDoux, Ph.D. Document formatted into pages (viii, 102 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 81-102).

Thesis (doctoral)--Uppsala University, 1983. / Includes bibliographical references (p. 26-33).

Dystonia is a movement disorder characterized by patterned, repetitive, and sustained muscle contractions that cause ineffective and often painful movements. The overall goal of this project was to understand the physiological mechanisms of dystonia in a rodent model as a basis for developing innovative treatments for secondary dystonias. The first half of the project was focused at developing essential techniques for systematically investigating the movement disorder in these animals. For achieving this, an innovative, multi-faceted approach was pursued starting with electromyographic (EMG) analysis for animal model validation, gait analysis for dystonia quantification, and development of a novel stereotaxic apparatus for recording brain activity during awake conditions. The later half of the project was focused on understanding how brain circuitry produces abnormal motor control in dystonia. Single and multi-unit neuronal activity was collected from individual basal ganglia nuclei along with EMG recordings to characterize the abnormal patterns of firing in dystonic animals and determine how neurons within individual nuclei communicate in dystonia, respectively. The findings of the current project have lead to new insights into the pathophysiology and treatment of secondary kernicteric dystonia and other secondary dystonia in humans.

Myoclonus dystonia (MD) is a rare autosomal-dominant combined dystonia movement disorder characterised by quick, involuntary muscle jerks (myoclonus) paired with sustained muscular contraction (dystonia). Although known to be genetically heterogeneous, the most common genetic factor is mutations within SGCE, the gene encoding ε-sarcoglycan, accounting for approximately 45% of cases. Previous linkage analyses conducted on a family displaying inherited MD without SGCE mutations lead to the identification of another critical region, DYT15. Preliminary data suggested that mutations within the long non-coding RNA (lncRNA) CD108131, found within the DYT15 locus, resulted in decreased expression of both the SGCE transcript, as well as the SGCE protein. Validation of the remaining variants of interest yielded no new candidate genes. A low coverage area coinciding with the entire sequence of TMEM200C was discovered, however subsequent sequencing data revealed no potential disease-causing variants. Therefore, to further characterise the relationship between CD108131 and SGCE suggested by the preliminary data, a CRISPR-Cas9 knockout was developed in HEK293 cells using a double-cut strategy that allowed for complete excision of the CD108131 gene. Stable CD108131 knockout mutant cell lines were examined for differences in gene expression. QRT-PCR analysis was conducted and revealed a significant decrease in SGCE expression in the absence of CD108131. Additionally, expression also trended towards a decrease for ZBTB14, however ARHGAP28 and RPPH1 were not significantly altered. This data demonstrates that the lncRNA CD108131 is likely to have a regulatory effect on SGCE, and perhaps ZBTB14, transcription.

Distonia é o terceiro distúrbio do movimento mais comum. Caracteriza-se por contrações musculares sustentadas ou intermitentes que podem gerar posturas anormais. Nos últimos anos, muitos estudos tentaram relacionar a presença de sintomas não motores como parte da manifestação clínica dessa patologia; no entanto, os resultados ainda são controversos. Objetivo: Avaliar a prevalência de sintomas não motores em pacientes com distonia focal ou segmentar idiopática e seu impacto na qualidade de vida. Métodos: Foram avaliados 80 pacientes e 80 controles sem patologias neurológicas pareados para sexo, idade e anos de estudo. Os pacientes foram questionados quanto ao tempo e gravidade de doença. Dados demográficos, comorbidades e medicações em uso foram coletados de ambos os grupos. Os sintomas não motores foram avaliados por meio de escalas validadas para a população brasileira. Foram avaliados sintomas de depressão, ansiedade, fobia social, apatia, sonolência diurna, qualidade do sono, cognição e dor, assim como qualidade de vida. Resultados: 80 pacientes foram avaliados: 28 com diagnóstico de blefaroespasmo ou distonia de Meige, 28 com distonia cervical ou orocervical e 24 com distonia de membro, em sua maioria, distonia tarefa-específica da escrita (cãibra do escrivão). Os pacientes apresentaram mais sintomas de depressão, ansiedade e apatia do que os controles, assim como uma pior qualidade do sono e mais queixas de dor. Ao avaliarmos pelo tipo de distonia, os pacientes com blefaroespasmo foram os mais sintomáticos com relação a esses sintomas. Qualidade de vida foi pior nos pacientes que nos controles. Conclusões: Pacientes com distonia, principalmente com blefaroespasmo, apresentaram maior prevalência de sintomas de depressão, de ansiedade, de apatia, pior qualidade do sono e dor. Esses sintomas causaram impacto negativo na qualidade de vida desses pacientes / Dystonia is the third most common movement disorder. It´s characterized by sustained or intermittent muscle contractions causing abnormal postures. In recent years many studies have sought to relate the presence of non-motor symptoms as part of clinical manifestation of this disease, however, results are still controversial. Objective: To assess prevalence of non-motor symptoms in patients with idiopathic focal or segmental dystonia and its impact in life quality. Methods: We evaluated 80 patients and 80 healthy controls matched for sex, age and years of schooling. Questions about the time at onset and severity of illness were asked to patients. Clinical and demographic data were noted in both groups. Non-motor symptoms were assessed using validated scales for Brazilian population. We assessed symptoms of depression, anxiety, social phobia, apathy, daytime sleepiness, sleep quality, cognition and pain, as well as quality of life. Results: We evaluated 80 patients: 28 with blepharospasm or Meige syndrome, 28 with cervical or orocervical dystonia and 24 with limb dystonia, mostly with specific writing task dystonia (writer´s cramp). Patients had more symptoms of depression, anxiety and apathy than controls, as well as worse quality of sleep and more pain complaints. Analysing by type of dystonia, patients with blepharospasm were the most symptomatic group in relation to these symptoms. Quality of life was worse in dystonic patients. Conclusions: Patients with dystonia, mainly those with blepharospasm, had a higher prevalence of symptoms of depression, anxiety, apathy, worse quality of sleep and pain. These symptoms had a negative impact on these patients\' quality of life

Distonia é o terceiro distúrbio do movimento mais comum. Caracteriza-se por contrações musculares sustentadas ou intermitentes que podem gerar posturas anormais. Nos últimos anos, muitos estudos tentaram relacionar a presença de sintomas não motores como parte da manifestação clínica dessa patologia; no entanto, os resultados ainda são controversos. Objetivo: Avaliar a prevalência de sintomas não motores em pacientes com distonia focal ou segmentar idiopática e seu impacto na qualidade de vida. Métodos: Foram avaliados 80 pacientes e 80 controles sem patologias neurológicas pareados para sexo, idade e anos de estudo. Os pacientes foram questionados quanto ao tempo e gravidade de doença. Dados demográficos, comorbidades e medicações em uso foram coletados de ambos os grupos. Os sintomas não motores foram avaliados por meio de escalas validadas para a população brasileira. Foram avaliados sintomas de depressão, ansiedade, fobia social, apatia, sonolência diurna, qualidade do sono, cognição e dor, assim como qualidade de vida. Resultados: 80 pacientes foram avaliados: 28 com diagnóstico de blefaroespasmo ou distonia de Meige, 28 com distonia cervical ou orocervical e 24 com distonia de membro, em sua maioria, distonia tarefa-específica da escrita (cãibra do escrivão). Os pacientes apresentaram mais sintomas de depressão, ansiedade e apatia do que os controles, assim como uma pior qualidade do sono e mais queixas de dor. Ao avaliarmos pelo tipo de distonia, os pacientes com blefaroespasmo foram os mais sintomáticos com relação a esses sintomas. Qualidade de vida foi pior nos pacientes que nos controles. Conclusões: Pacientes com distonia, principalmente com blefaroespasmo, apresentaram maior prevalência de sintomas de depressão, de ansiedade, de apatia, pior qualidade do sono e dor. Esses sintomas causaram impacto negativo na qualidade de vida desses pacientes / Dystonia is the third most common movement disorder. It´s characterized by sustained or intermittent muscle contractions causing abnormal postures. In recent years many studies have sought to relate the presence of non-motor symptoms as part of clinical manifestation of this disease, however, results are still controversial. Objective: To assess prevalence of non-motor symptoms in patients with idiopathic focal or segmental dystonia and its impact in life quality. Methods: We evaluated 80 patients and 80 healthy controls matched for sex, age and years of schooling. Questions about the time at onset and severity of illness were asked to patients. Clinical and demographic data were noted in both groups. Non-motor symptoms were assessed using validated scales for Brazilian population. We assessed symptoms of depression, anxiety, social phobia, apathy, daytime sleepiness, sleep quality, cognition and pain, as well as quality of life. Results: We evaluated 80 patients: 28 with blepharospasm or Meige syndrome, 28 with cervical or orocervical dystonia and 24 with limb dystonia, mostly with specific writing task dystonia (writer´s cramp). Patients had more symptoms of depression, anxiety and apathy than controls, as well as worse quality of sleep and more pain complaints. Analysing by type of dystonia, patients with blepharospasm were the most symptomatic group in relation to these symptoms. Quality of life was worse in dystonic patients. Conclusions: Patients with dystonia, mainly those with blepharospasm, had a higher prevalence of symptoms of depression, anxiety, apathy, worse quality of sleep and pain. These symptoms had a negative impact on these patients\' quality of life

Dissertation (D.M.A.)--The University of North Carolina at Greensboro, 2008. / Directed by Dennis AsKew; submitted to the School of Music. Title from PDF t.p. (viewed Aug. 25, 2009). Includes bibliographical references (p. 124-146).

Orientadores: Anelyssa Cysne Frota D'Abreu, Fernando Cendes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T01:17:26Z (GMT). No. of bitstreams: 1 Pinheiro_GiordannaLuizaSelingardi_M.pdf: 1372164 bytes, checksum: e02f4b5ec43afe35e676ab843e98cda0 (MD5) Previous issue date: 2015 / Resumo: A distonia é uma síndrome caracterizada por espasmos e contrações musculares, prolongados e involuntários, causando movimentos de torção e posturas anormais, frequentemente dolorosos. A distonia craniocervical (DCC) ocorre quando há contração das musculaturas da cabeça, face e pescoço; podendo ser focal ou segmentar. Estas são as distonias mais frequentes em indivíduos adultos. O tratamento com a toxina botulínica é o mais indicado para a DCC, mas seu efeito é temporário. Disfunção ou lesão dos gânglios da base sempre foi considerado o componente central na sua fisiopatologia, porém estudos mais recentes mostram o envolvimento de diversas outras regiões cerebrais como o córtex sensorio-motor e cerebelo. O presente estudo avaliou as alterações estruturais da substância branca em 40 pacientes comparando-os a 40 controles saudáveis. Secundariamente os mesmos pacientes foram divididos em 4 grupos: blefarospasmo, blefarospasmo + oromandibular, blefarospasmo + oromandibular + cervical e cervical. Todos passaram por uma avaliação clínica detalhada, envolvendo revisão do histórico, exame neurológico e exame de ressonância magnética. As análises da técnica de imagem por tensor de difusão (DTI) foram feitas através do software Trato baseado em estatística espacial (TBSS), onde foram avaliados anisotropia fracional (FA) e difusividade média (MD). Também foram realizadas técnicas baseada em região de interesse (ROI) e tractografia nesses pacientes. Não encontramos diferenças significativas no FA e MD nas análises realizadas, sugerindo que a microestrutura da substância branca dos pacientes com DCC encontra-se preservada. Futuros estudos utilizando análises funcionais podem desvendar um acometimento funcional dos circuitos cerebrais, sem que haja necessariamente acometimento estrutural da substância branca / Abstract: Dystonia is a syndrome characterized by involuntary muscle contractions, causing twisting movements and abnormal postures, which are often painful. Craniocervical dystonia (CCD) involves the contraction of the head and neck muscles. It is the most frequent dystonia in adults, and it can be focal or segmental. Botulinum toxin is the best treatment for CCD, although the effect is temporary. Classically considered secondary to a dysfunction or lesion in the basal ganglia circuit, recent studies have shown the involvement of the sensorimotor areas and the cerebellum. In the present study, we evaluated the structural brain changes in 40 patients comparing them to 40 healthy controls. Secondarily, we divided the patients into 4 groups based on dystonia localization: blepharospasm, blepharospasm + oromandibular, blepharospasm + oromandibular + cervical and cervical. Patients and controls underwent the same MRI acquisition protocol in a 3T Philips Achieva MRI scanner. All patients were assessed by an experienced neurologist specialized in Movement Disorders. We performed DTI analyzes with Tract-Based Spatial Statistics (TBSS) and we evaluated the fractional anisotropy and the mean diffusivity. We performed two confirmatory analyses using a ROI based approach and tractography. There were no microstructural alterations neither in the primary nor the secondary analysis. We did not find microstructure changes in the white matter of subjects with craniocervical dystonia. Further studies should evaluate the presence of functional and connectivity abnormalities in these subjects / Mestrado / Fisiopatologia Médica / Mestra em Ciências

Ce travail précise le rôle du cervelet dans la physiopathologie de la dystonie. Nous étudions comment le cervelet contrôle le développement et l’étendue de la plasticité sensorimotrice, celle-ci étant anormale dans la dystonie. Nous démontrons l’implication du cervelet dans la dystonie en constatant des performances anormales à une tâche d’adaptation sensorimotrice dépendant du cervelet. (Hubsch et al., 2011) Puis chez des sujets sains, en utilisant des techniques d’induction de plasticité cérébrale nous démontrons que le cervelet module la plasticité corticale reposant sur des afférences sensorielles. Ainsi, une inhibition du cortex cérébelleux amplifie la réponse du cortex à un protocole d’induction de plasticité sensorimotrice, une excitation du cortex cérébelleux bloque la réponse du cortex à ce protocole. (Popa et al., 2013) Avec les mêmes méthodes, nous étudions le rôle du cervelet dans la modulation de la plasticité du cortex sensori-moteur chez des sujets atteints de dystonie focale. Dans la crampe de l’écrivain, le cervelet n’exerce plus ce rôle modulateur de la plasticité sensorimotrice: il n’y a ni inhibition ni renforcement du phénomène de plasticité induit par une modulation des sorties cérébelleuses. (Hubsch et al., 2013)Dans la dystonie cervicale, il persiste une modulation de la plasticité sensorimotrice par le cervelet mais cette modulation a une direction opposée par rapport aux sujets sains contrôles. Par des expériences complémentaires, nous démontrons que le contrôle cérébelleux sur la plasticité corticale sensorimotrice est adaptatif aux afférences proprioceptives de la nuque possiblement en rapport avec la construction de l’espace égocentré. / This study specifies the role of the cerebellum in the physiopathology of dystonia. We study how the cerebellum controls the development and the extent of sensorimotor plasticity, this one being abnormal in dystonia. We show the implication of the cerebellum in dystonia by noting abnormal performances with a task of sensorimotor adaptation depending on cerebellum. (Hubsch and al., 2011) Then with healthy subjects, by using techniques of cerebral plasticity’s induction we show that the cerebellum modulates cortical plasticity depending on sensory afferents. Thus, an inhibition of the cerebellar cortex amplifies the response of the cortex to a protocol of induction of sensorimotor plasticity, an excitation of the cerebellar cortex blocks the response of the cortex to this protocol. (Popa and al., 2013) With the same methods, we study the role of the cerebellum in the modulation of the plasticity of the sensorimotor cortex with dystonic subjects. In writer's cramp, the cerebellum does not exert any more this modulating role of sensorimotor plasticity: there is neither inhibition nor reinforcement of the phenomenon of plasticity induced by a modulation of the cerebellar outputs. (Hubsch and al., 2013) In the cervical dystonia, it persists a modulation of sensorimotor plasticity by the cerebellum but this modulation has a direction opposed compared to the healthy subjects. By complementary experiments, we show that cerebellar control on cortical sensorimotor plasticity is adaptive with the proprioceptive afferents of the neck possibly in keeping with the construction of egocentric space.