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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
131

Estudo comparativo entre cloridrato de oxibutinina e onabotulinumtoxina em pacientes portadores de lesão medular com hiperatividade do detrusor = avaliação urodinâmica e qualidade de vida = Comparative study between oxybutynin chloride and onabotulinumtoxinA in spinal cord injured patients with detrusor overactivity urodynamic evaluation and quality of life / Comparative study between oxybutynin chloride and onabotulinumtoxinA in spinal cord injured patients with detrusor overactivity : urodynamic evaluation and quality of life

Ferreira, Rúiter Silva, 1967- 22 August 2012 (has links)
Orientador: Carlos Arturo Levi D'Ancona / Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T10:56:35Z (GMT). No. of bitstreams: 1 Ferreira_RuiterSilva_D.pdf: 2813399 bytes, checksum: a60122cb9b6dd6b69a465a84a16f289e (MD5) Previous issue date: 2012 / Resumo: Introdução: O tratamento da incontinência urinária é aspecto importante no processo de reabilitação de pacientes portadores de lesão medular (LM). Objetivos: Os objetivos desse estudo foram avaliar o impacto na qualidade de vida (QV) e nos parâmetros urodinâmicos de pacientes portadores de LM tratados com injeção intradetrusora de onabotulinumtoxina ou uso oral de oxibutinina. Pacientes e Métodos: Sessenta e oito pacientes portadores de LM e hiperatividade detrusora neurogênica foram randomizados em dois grupos. Grupo I (n=34) receberam 15 mg/dia de cloridrato de oxibutinina por via oral e grupo II (n=34) foram tratados com injeção intradetrusora de 300U de onabotulinumtoxina em 30 pontos da parede vesical com preservação do trígono. Parâmetros urodinâmicos como capacidade cistométrica máxima (CCM), pressão detrusora máxima (Pdetmax) e complacência foram avaliados juntamente com escores de QV obtidos pelo questionário Qualiveen. As avaliações foram feitas antes da randomização dos pacientes, quatro, 12 e 24 semanas após inicio do tratamento. O nível de significância adotado foi de 5%. Resultados: Sete pacientes não completaram o estudo. Dos 61 pacientes, 49 pertenciam ao sexo masculino (80,3%) com idade média de 31,84 (DP ± 8,73) anos no grupo I e 33,54 (DP ± 11,86) anos no grupo II, p=0,839. Após 24 semanas, o aumento médio da CCM no grupo I foi de 126,24 (DP ± 62,22) ml e de 289,25 (DP ± 134,52) ml no grupo II, p<0,001. A Pdetmax apresentou redução média de 21,09 (DP ± 19,95) cm H2O no grupo I e de 48,75 (DP ± 29,34) cm H2O no grupo II, p<0,001. A complacência vesical apresentou aumento médio de 6,85 (DP ± 5,13) ml/cm H2O no grupo I e de 25,82 (DP ± 24,00) ml/cm H2O no grupo II, p=0,006. O número de perdas urinárias em 24h apresentou diminuição média de 2,34 (DP ± 1,89) episódios no grupo I e de 7,55 (DP ± 3,52) episódios no grupo II, p<0,001. Os escores do impacto específico dos problemas urinários do questionário Qualiveen apresentaram redução média de 0,26 (DP ± 0,33) no grupo I e de 1,48 (DP ± 0,70) no grupo II, p<0,001. Os escores do índice de qualidade de vida apresentaram aumento médio de 0,12 (DP ± 0,26) no grupo I e de 0,63 (DP ± 0,45) no grupo II, p<0,001. Conclusão: A injeção intradetrusora de onabotulinumtoxina e a administração oral de oxibutinina promoveram melhora significativa nos parâmetros urodinâmicos e na qualidade de vida de pacientes portadores de hiperatividade detrusora devido a LM. Porém, a comparação dos dois tratamentos demonstrou que a onabotulinumtoxina apresentou resposta significativamente melhor quando comparada à oxibutinina / Abstract: Introduction: The treatment of urinary incontinence is an important issue in the rehabilitation of patients with spinal cord injury (SCI). Objectives: The goals of this study were to evaluate the impact on Quality of Life (QoL) and urodynamic parameters on patients with SCI who were treated with intradetrusor injections of onabotulinumtoxinA or oral oxybutynin. Patients and Methods: Sixty-eight patients with SCI and neurogenic detrusor overactivity were randomized into two groups. Patients in Group I (n=34) received 15 mg/day oxybutynin orally, and patients in Group II (n=34) were treated with intradetrusor injections of 300U onabotulinumtoxinA into 30 different segments of the urinary bladder wall, sparing of the trigone. Urodynamic parameters such as maximum cystometric capacity (MCC), maximum detrusor pressure (Pdetmax) and bladder compliance were evaluated, and QoL scores were obtained by applying the Qualiveen questionnaire. Evaluations were performed prior to randomisation and at 4, 12 and 24 weeks of treatment. The significance level was set at 5%. Results: Seven patients did not complete the study. Of the 61 patients, 49 (80.3%) were male. The mean age of patients was 31.84 (SD ± 8.73) years old in group I and 33.54 (SD ± 11.86) years old in group II (p=0.839). After 24 weeks, the mean increase in MCC in group I was 126.24 (SD ± 62.22) mL compared to 289.25 (SD ± 134.52) mL in group II (p<0.001). We determined a mean decrease of 21.09 (SD ± 19.95) cm H2O in Pdetmax in group I compared to 48.75 (SD ± 29.34) cm H2O in group II (p<0.001). Furthermore, the mean increase in bladder compliance was 6.85 (SD ± 5.13) mL/cm H2O in group I compared to 25.82 (SD ± 24.00) mL/cm H2O in group II (p=0.006). A mean decrease in 24-hour urine leakage of 2.34 (SD ± 1.89) episodes occurred in group I, with a mean decrease of 7.55 (SD ± 3.52) episodes in group II (p<0.001). Scores in the Qualiveen questionnaire that focused on the specific impact of urinary dysfunction were decreased by a mean of -0.26 (SD ± 0.33) in group I and -1.48 (SD ± 0.70) in group II (p<0.001). Importantly, the Qualiveen scores related to the QoL index increased by a mean of 0.12 (SD ± 0.26) in group I and 0.63 (SD ± 0.45) in group II (p<0.001). Conclusions: Both intradetrusor injections of onabotulinumtoxinA and oral administration of oxybutynin resulted in a significant improvement in urodynamic parameters and QoL in patients with detrusor overactivity due to SCI. However, a comparison of the two treatments showed a significantly improved response with onabotulinumtoxin. A compared to oxybutynin / Doutorado / Cirurgia / Doutor em Cirurgia
132

Avaliação radiográfica do balanço sagital da coluna vertebral em paraplégicos = um novo paradigma para reabilitação com estimulação elétrica funcional / Sagittal spinal alignment in paraplegics : a new paradigm for the rehabilitation under neuromuscular electrical stimulation

Medeiros, Rodrigo Castro de, 1979- 15 June 2011 (has links)
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
133

Steer by ear: clinical and neurophysiological evaluation of a novel human-machine interface

Schmalfuß, Leonie 02 March 2018 (has links)
No description available.
134

Development of a functional neuromuscular stimulation (FNS) muscle training program to prepare paraplegics for standing

Schafer, Carol Linda 21 April 2017 (has links)
Wheelchair-bound paraplegics are in an unnatural, almost all-day sitting position. This is physiologically disadvantageous as it may cause increased abdominal pressure, renal dysfunction, pressure sores, muscle atrophy and osteoporosis. Thus it would be beneficial, physiologically and psychologically, for a paraplegic to be able to stand for temporary periods of time. As a result of the muscle atrophy and functional degeneration that follows a spinal cord injury, it is essential for paraplegics to undergo a muscle restrengthening program, using Functional Neuromuscular Stimulation (FNS), before standing up under FNS control can be attempted. Six healthy spinal cord injured subjects with spinal lesions between CS and T9 (two tetraplegics and four paraplegics) exercised their quadriceps muscles at home using a portable two-channel FNS muscle stimulator. The muscles were exercised against an increasing load to maximise the training effect. Inclined standing exercise, under FNS control, was performed in the Inclistand. The subjects' general state of health and fitness were assessed, namely their responses during a maximal arm ergometry exercise test, arm muscle function, lung function, blood biochemistry and their dietary habits. Subjects have shown improvement in quadriceps muscle strength, fatigue resistance and muscle bulk to varying degrees - according to their individual circumstances. The tetraplegics responded in a different manner to that of the paraplegics. The muscle strength increased significantly by a mean (+SD) of 97,8 + 59,6% and 171,2 + 118,1% for the four paraplegics, left and right leg respectively. There was a mean improvement of 16% in fatigue resistance in the left leg (p=0,08), while the mean response of the right leg varied. Quadriceps muscle bulk increased by 4,43 + 3,4% (left) and 2,7 + 2,1% (right) (0,05&lt;p&lt;0,l). The amount of subcutaneous fat around the mid-thigh decreased significantly by 4,73 + 1,4% (left) and 3,43 + 1,1% (right leg). The group was in a state of general well-being, with the exception of one subject whose serum cholesterol concentration fell within the high risk category. This study therefore showed that the FNS was sucessful in improving the quadriceps muscle strength, bulk and fatigue response of the SCI people in our research group. The valuable experience gained from this FNS study will be used to improve the present program.
135

Physiological and molecular functions of the murine receptor protein tyrosine phosphatase sigma (RPTP[sigma])

Chagnon, Mélanie J., 1977- January 2008 (has links)
No description available.
136

Rehabilitation programme to enhance community reintegration for people living with spinal cord injuries in rural areas of Limpopo Province - South Africa

Mohamed, Ehab Elsayed January 2022 (has links)
Thesis (Ph.D. (Health Sciences)) -- University of Limpopo, 2021 / Rehabilitation programmes for PLWSCI aim to give them as much independence as possible and perfect integration at a later stage. Proper rehabilitation involves effective community integration of a person with the SCI. Rehabilitation and community integration are key to return the person with an SCI to play his/her role in the community as an effective, independent, and important person. Globally, PLWSCI are facing numerous barriers and limitations, especially in rural areas, where rehabilitation resources are limited. There is a dearth of rehabilitation centres in the Limpopo Province, which might impact negatively on the rehabilitation and community integration outcomes for PLWSCI in this region. The absence of rehabilitation centres in this province point to the need for the development of extra skills for the professionals who work in the rehabilitation team in this Province. Aim and Objectives The overall aim of this study was to develop a rehabilitation programme to enhance community reintegration for PLWSCI in rural areas of the Limpopo Province, South Africa. Methodology This study used a convergent parallel mixed method design in phase 1. A mixed methodology approach consists of a set of designs and procedures in which both quantitative and qualitative data are collected, analysed, and mixed in a single study. Quantitative data were generated and collected regarding the rehabilitation and community integration challenges of PLWSCI using the Spinal Cord Injury Community Reintegration Measure (SCICRM) tool. Qualitative data were collected through focus group discussions (FGDs). In phase 2 of the study, the Delphi study design was utilised and conducted as a forecasting method based on the results of phase 1. vi Results Quantitative results show that 37% of the respondents were fully reintegrated. Moderate reintegration was above average (54.4%), while 5.7% were minimally integrated, and 3.9% failed to reintegrate into their communities. The rehabilitation teams’ home visits were further rated as “never happened” (51%) and “rarely happened” (14.3%). Patients who received a home visit from their rehabilitation team were more likely to fully reintegrate into their community, in this case, 75%. Of those who did not receive any home visits, only 39% managed to fully reintegrate into their communities. The qualitative findings, which is based on information-rich interviews with participants, indicated an urgent need for the implementation of a rehabilitation programme to enhance a successful and better community reintegration for PLWSCI. The qualitative results also highlighted the importance of home visits and following up on the patients after they have returned to their communities. The qualitative findings were presented according to six themes that were also divided into several sub-themes. In phase 2 of this study, experts agreed that the rehabilitation programme to enhance community integration for people with SCIs in the Limpopo Province should include the identification of the rehabilitation team, distribution of powers between the team members, documentation and referral letters, mobility, assistive devices, sub-acute rehabilitation tasks, home programmes, and the outcome of the successful rehabilitation. Conclusion Rehabilitation is the bridge between the SCI and successful community integration. A comprehensive rehabilitation programme implemented by a multidisciplinary team should enhance the successful reintegration of PLWSCI.
137

Echocardiographic Assessment of the Left Ventricle in the Spinal Cord Injured Patient

Nock, Bonnie J. (Bonnie Jean) 05 1900 (has links)
Ten caucasian male quadriplegics were compared with eight sedentary caucasian male controls in regards to left ventricular dimensions and mass obtained from echocardiograrns. The interventricular septum (IVS), left ventricular posterior wall (LVPW) and left ventricular internal diameter (LVII) were within normal limits for both groups. However, the INS in the SCI were significantly thicker than controls (p <0.05). Myocardial thickness was larger in SCI subjects (p <0.05). Absolute left ventricular mass (LVM) and total left ventricular volume was not different ( p > 0.05), but SCI subjects had significantly greater LVM to lean body mass ratios. Echocardiographically, SCI patients demonstrate concentric hypertrophy. This suggests adaptive response to chronic increase in afterload pressure secondary to their daily activities and muscle spasticity.
138

Caracterização do perfil de síndromes dolorosas, psicofísica e medidas de excitabilidade cortical em doentes com neuromielite óptica controlada / Characterization of pain, psychophysics and cortical excitability profile in patients with controlled neuromyelitis optica spectrum disorders

Silva, Fernanda Valerio da 03 April 2019 (has links)
Introdução: Neuromielite óptica (NMO) é uma doença inflamatória desmielinizante do sistema nervoso central associado com auto anticorpo anti-aquaporina 4 (AQP4-Ab) em até 90% dos casos e com anticorpo anti glicoproteína de mielina oligodendrocítica (MOG-IgG) em cerca de 20% dos indivíduos negativos para AQP4-Ab. A apresentação clínica típica do NMO inclui neurite óptica grave (ON), mielite transversa longitudinalmente extensa (MTLE) e lesões do tronco encefálico conhecidas por causar náuseas,vômitos e soluços intratáveis. A dor é um dos sintomas mais frequentes e incapacitantes dessa síndrome. Sabe-se que afeta até 85% dos indivíduos, que é mais intensa e responde menos aos tratamentos usuais quando comparados aos pacientes com esclerose múltipla. O objetivo deste estudo foi caracterizar as síndromes dolorosas em indivíduos na fase crônica livre de recidiva da NMO. A doença também foi considerada um bom modelo para estudar os mecanismos de dor após lesão medular. Métodos: Trata-se de um estudo longitudinal, composto por duas avaliações. A avaliação para entrada no estudo consistiu em um exame neurológico complete padronizado, a fim de determinar as síndromes dolorosas principal e secundária de acordo com seu mecanismo e nível. Os pacientes foram convidados a preencher questionários avaliando a dor (Inventário breve de dor [BPI], Questionário de dor McGill [MPQ], inventário de sintomas de dor neuropática [NPSI]), espasmos tônicos dolorosos, sinal de Lhermitte, incapacidade (EDSS, Barthel ADL), ansiedade e depressão (escala hospitalar de ansiedade e depressão [HADS]), catastrofização (escala de pensamentos catastróficos na dor [PCTS]), disfunção urinária e fecal (questionário de bexiga hiperativa [OABV8], escore de sintomas prostáticos internacionais [IPSS]). Também foram realizados teste quantitativo sensitivo (QST) em área controle (com sensibilidade normal) e área de maior dor e medidas de excitabilidade cortical bilaterais (CE). Imagens prévias de ressonância magnética de encéfalo e medula espinhal foram revistos. Foi realizada uma consulta de acompanhamento entre 6 e 18 meses após a primeira visita, na qual a síndrome dolorosa principal foi reavaliada e os pacientes foram solicitados a preencher questionários (DN-4, BPI, MPQ, BPI, NPSI) sobre a dor. Resultados: Setenta e dois pacientes foram incluídos. Foram identificados 53 (73,6%) indivíduos com dor crônica e 19 (26,3%) sem dor. Quarenta (55,6%) pacientes apresentaram dor neuropática (NP) e 13 (18,1%) dor não neuropática (não-NP). Entre os 53 indivíduos com dor crônica, 38 (71,7%) tinham mais de uma síndrome dolorosa. Dor neuropática no nível sensitivo foi a síndrome dolorosa mais prevalente, sendo observada em 31 doentes (58,5% do total de pacientes com dor). O grupo com dor não-neuropática teve dor lombar como a síndrome mais comum, afetando 8 (61,5%) indivíduos. O grupo com dor neuropática teve um número significativamente maior de dermátomos afetados por alodínea dinâmica (0,8 ± 1,6, comparado a zero dermátomos nos outros 2 grupos, p = 0,004) e estática (0,7 ± 1,3 comparado a 0 no grupo com dor não-neuropática e 0,1 ± 0,5 dermátomos no grupo sem dor). A hiperpatia em nível foi significativamente mais prevalente no grupo com dor neuropática: 39 (97,5%) nesse grupo, contra 10 (76,9%) e 12 (68,4%) nos grupos dor não-neuropática e sem dor (p = 0,013). Os pacientes com dor neuropática apresentaram desempenho significativamente pior quando comparados aos sem dor, no PCS-12 (componente físico do SF-12), (32,5 ± 8 e 43,3 ± 11, respectivamente). O PCS-12 correlacionou-se com a intensidade da dor no BPI nos grupos dor neuropática (r = -0,387, p = 0,014) e não-neuropática (r = -0,734, p = 0,004). Dentro do grupo com dor neuropática, 16 (80%) pacientes relataram prurido na área de dor, enquanto apenas 1 (33,3%) paciente com dor não neuropática relatou o mesmo (p < 0,001). O QST apresentou maiores limiares para a detecção de estímulos quentes dentre aqueles com dor neuropática, quando comparado ao grupo com dor não-neuropática (41,3 ± 5,6 e 36,9 ± 3, respectivamente, p = 0,045). As amplitudes do potencial evocado motor a 120 e 140% foram significativamente menores nos dois grupos com dor quando comparados aos pacientes sem dor. A avaliação de acompanhamento foi realizada em 68 pacientes e 50 (73,5%) relataram dor. A dor neuropática do nível foi novamente a síndrome dolorosa mais prevalente, afetando 29 (58%) indivíduos. Três pacientes inicialmente sem dor relataram na o sintoma na segunda visita. A taxa de incidência de dor foi de 17,7 por 100 pessoas-ano. Onze pacientes que haviam relatado dor na entrada do estudo tinham uma síndrome de dor diferente na segunda avaliação (20,8% da amostra original). O grupo com dor neuropática teve uma diminuição significativa na intensidade do BPI (de 5,6 ± 1,9 para 4,8 ± 2, p = 0,039). O escore total do MPQ diminuiu significativamente em ambos os grupos com dor neuropática (de 9 ± 2,4 para 8 ± 3,1, p = 0,014) e naqueles com dor não-neuropática (9,2 ± 2,5 a 7 ± 4, p = 0,031). Conclusão: A dor é prevalente em pacientes com NMO e a dor neuropática de nível é a síndrome mais comum. A incidência de novas dores e alterações nas síndromes dolorosas não está relacionada à nova atividade inflamatória, mas ao dano estrutural permanente crônico na medula espinhal e tronco cerebral secundário à atividade autoimune prévia. A avaliação das síndromes dolorosas é importante para o tratamento correto desse sintoma e deve ser reavaliada regularmente, mesmo em pacientes sem novas recidivas clínicas / Introduction: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system. It is associated with anti-aquaporin 4 autoantibody (AQP4-Ab) in up to 90% of cases and with anti-myelin oligodendrocyte glycoprotein (MOG-IgG) in around 20% of subjects negative to AQP4-Ab. The typical clinical presentation of NMOSD includes severe optic neuritis (ON), longitudinally extensive transverse myelitis (LETM) and brainstem lesions known to cause intractable nausea, vomiting and hiccups. Pain is one of the most frequent and disabling symptoms in this syndrome. It is known to affect up to 85% of subjects with NMO which is more intense and less responsive to usual treatments when compared to multiple sclerosis patients. The aim of this study was to fully characterise all pain syndromes in individuals in the chronic relapse-free phase of NMO. The disease was also deemed a good model to study pain mechanisms in spinal cord injuries. Methods: This is a longitudinal study, comprised by 2 evaluations. The Baseline study entry visit consisted of a full standardized neurological examination, in order to determine the main and secondary pain syndrome according to its mechanism and level. Patients were requested to fill questionnaires evaluating pain (Douleur Neuropathique-4 [DN-4], brief pain inventory [BPI], Short-form McGill Pain Questionnaire [MPQ], Neuropathic pain symptoms inventory [NPSI]), painful tonic spasms, Lhermitte sign, hiccups, orthostatic intolerance, persistent nausea, pruritus, fatigue (modified fatigue scale), Uhthoff phaenomenon, quality of life (SF-12), disability (EDSS, Barthel ADL), anxiety and depression (Hospital anxiety and depression scale [HADS]), catastrophizing (PCTS), urinary and faecal dysfunction(OABV8,IPSS). Quantitative sensory test (QST) and measures of cortical excitability (CE) were performed. Previous brain and spinal cord MRIs were reviewed. A follow up visit was done between 6 and 18 months after the first visit, in which the main pain syndrome was reassessed and patients again were requested to fil pain questionnaires (DN-4, BPI, MPQ, BPI, NPSI) and report painful tonic spasms and Lhermitte sign. Results: Seventy-two patients were included. We identified 53 (73.6%) patients with chronic pain and 19 (26.3%) without any chronic pain syndrome. Forty (55.6%) patients had neuropathic pain (NP) and 13 (18.1%) had non-neuropathic pain (non-NP). Amongst those 53 subjects with chronic pain, 38 (71.7%) had more than one pain syndrome. NP at the sensory level was the most prevalent pain syndrome, being observed in 31 patients (58.5% of the total pain patients). Amid the non-NP patients, low back pain was the most common pain syndrome, affecting 8 (61.5%) subjects. NP group had a significantly higher number of dermatomes affected by allodynia to brush (0.8 ± 1.6, compared to zero dermatomes in the other 2 groups, p = 0.004) and to pressure (0.7 ± 1.3 compared to no 0 in the non-NP group and 0.1 ± 0.5 dermatomes in the no pain group). At-level hyperpathia affected a significantly proportion of patients with NP: 39 (97.5%) in this group, versus 10 (76.9%) and 12 (68.4%) in the non-NP and no pain groups (p= 0.013). Patients with NP had significantly worse performance when compared to those without pain, in the PCS-12 (physical component of the SF-12), (32.5 ± 8 and 43.3 ± 11, respectively). PCS-12 correlated with BPI intensity pain amid NP (r= -0.387, p= 0.014) and non-NP (r= -0.734, p= 0.004) groups. Within the group with neuropathic pain, 16 (80%) of patients reported itching on the pain area, whereas only 1 (33.3%) patient with non-neuropathic pain reported the same (p < 0.001). QST showed higher thresholds for warm stimuli detection within NP group, when compared to non-NP (41.3 ± 5.6 and 36.9 ± 3, respectively, p= 0.045) group. Motor evoked potential amplitudes at 120 and 140% were significantly lower in both groups with pain when compared to those without pain. The follow up assessment was done in 68 patients and 50 (73.5%) reported pain. At-level NP was the most prevalent syndrome, affecting 29 (58%) subjects. Three patients initially without pain reported it in the follow up visit. Incidence rate of pain was 17.7per 100 persons-year. Eleven patients who had reported pain upon study entry had a different pain syndrome on the second evaluation (20.8% of the original sample). NP group had a significant decrease in BPI intensity (from 5.6± 1.9 to 4.8±2, p= 0.039). MPQ total score significantly decreased in both groups with NP (from 9±2.4 to 8±3.1, p=0.014) and in those with non-NP (9.2±2.5 to 7±4, p=0.031). Conclusion: Pain is prevalent in patients with NMO and at-level NP is the most common syndrome. The incidence of new pain and changes in its syndromes is not related to new inflammatory activity but to the permanent chronic structural damage in the spinal cord and brainstem secondary to previous autoimmune activity. Assessment of pain syndromes is important for its treatment and they should be re-evaluated regularly even in patients without new clinical relapses
139

Avaliação da dor neuropática e das funções motora e somato-sensitiva após o transplante de células tronco em modelo de lesão da medula espinal em ratos / Assessment of neuropathic pain and motor and somatosensory functions after stem cell transplantation in rat spinal cord injury model

Batista, Chary Ely Martin Marquez 30 November 2018 (has links)
A dor neuropática após lesão da medula espinal é uma condição complexa que responde mal aos tratamentos convencionais. O transplante de células representa uma terapia promissora; no entanto, o tipo de célula ideal em termos de potencial neurogênico e eficácia contra a dor permanecem controversos. Assim, o objetivo do presente estudo foi avaliar a capacidade de células tronco neurais fetais (CTNf) em aliviar a dor crônica e, secundariamente, avaliar os efeitos na recuperação motora. Com este propósito, inicialmente foi realizado um piloto para definir o melhor modelo animal, no qual ratos Wistar foram submetidos à lesão medular traumática de intensidade leve ou moderada (altura do pêndulo 12,5mm e 25mm, respectivamente) utilizando o NYU Impactor. Os resultados indicaram que a lesão medular de intensidade moderada é um bom modelo para o estudo da dor neuropática central, pois, além de apresentar um déficit motor e um quadro álgico mais acentuado que os animais submetidos à lesão leve, os animais se mantiveram estáveis ao longo do estudo. Ademais, alterações sensoriais foram observadas desde os primeiros dias após a lesão e permaneceram por pelo menos oito semanas, viabilizando o objetivo do trabalho. Em vista do resultado do piloto, ratos Wistar foram submetidos à lesão medular de intensidade moderada; sete dias após a lesão medular iniciou-se a imunossupressão com ciclosporina, e dez dias após a lesão os animais receberam injeções intra-espinais de meio de cultivo (grupo sham) ou de CTNf extraídas das vesículas telencefálicas (grupo VT) ou da região ponto-bulbar ventral (grupo BV) de embriões E14 da mesma espécie. As avaliações sensitivas e motoras foram realizadas durante oito semanas. Posteriormente, as medulas espinais foram processadas para imunofluorescência e as CTNf transplantadas foram quantificadas por estereologia. Os resultados mostraram uma melhora da hiperalgesia térmica no grupo VT após a quinta semana de transplante (p < 0,001) e no grupo BV após a quarta semana (p < 0,001). Além disso, a alodínia mecânica melhorou nos grupos VT e BV na 8ª semana (VT p < 0,05 e BV p < 0,01 comparados com sham). Nenhuma recuperação motora significativa foi observada nos grupos tratados em relação ao grupo sham. A análise estereológica mostrou que ~70% das células VT e BV diferenciaram-se em neurônios NeuN+, com alta proporção de células encefalinérgicas e GABAérgicas no grupo VT (44% e 42%, respectivamente) e encefalinérgicas e serotoninérgicas no grupo BV (50% e 47%, respectivamente). Nosso estudo sugere que os precursores neuronais oriundos das VT e BV, uma vez implantados na medula espinal lesada, maturam em diferentes subtipos neuronais, principalmente GABAérgicos, serotoninérgicos e encefalinérgicos, e ambos precursores foram capazes de aliviar a dor, apesar de não haver recuperação motora significativa / Neuropathic pain after spinal cord injury (SCI) is a complex condition which responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Thus, the objective of the present study was to evaluate the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, to evaluate the effects on motor recovery. For this purpose, a pilot was initially designed to define the best animal model; accordingly, Wistar rats were submitted to traumatic spinal cord injury of mild or moderate intensity (pendulum height 12.5mm and 25mm, respectively) using the NYU Impactor. The results indicated that spinal cord injury of moderate intensity is a good model for the study of central neuropathic pain, because in addition to a motor function deficit and painful sensation more pronounced than the animals submitted to mild injury, the animals remained stable throughout the study. Additionally, sensitive deficits were observed from the first days after the injury and lasted eight weeks, enabling the objective of the work. Based on the pilot result, Wistar rats were submitted to moderate spinal cord injury; seven days after spinal cord injury, immunosuppression with cyclosporine was initiated; ten days after injury the animals received intra-spinal injections of culture medium (sham group) or fNSC extracted from the telencephalic vesicles (TV group) or from the ventral medulla (VM group) of E14 embryos of the same species. Behavioral and pain assessment were performed weekly during eight weeks. Thereafter, spinal cords were processed for immunofluorescence, and transplanted fetal cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in TV group after the fifth week of transplantation (p < 0.001) and in VM group after the fourth week (p < 0.001). Moreover, mechanical allodynia improved in both TV and VM groups at the 8th week (TV p < 0.05 and VM p < 0.01 compared to sham). No significant motor recovery was observed in TV and VM groups when compared to sham group. Stereological analyses showed that ~70% of TV and VM cells differentiated into NeuN+ neurons, with high proportion of enkephalinergic and GABAergic cells in the TV group (44% and 42%, respectively) and enkephalinergic and Serotoninergic cells in the VM group (50% and 47%, respectively). Our study suggests that neuronal precursors from the TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and both precursors were able to alleviate pain, despite no significant motor recovery
140

Avaliação da dor neuropática e das funções motora e somato-sensitiva após o transplante de células tronco em modelo de lesão da medula espinal em ratos / Assessment of neuropathic pain and motor and somatosensory functions after stem cell transplantation in rat spinal cord injury model

Chary Ely Martin Marquez Batista 30 November 2018 (has links)
A dor neuropática após lesão da medula espinal é uma condição complexa que responde mal aos tratamentos convencionais. O transplante de células representa uma terapia promissora; no entanto, o tipo de célula ideal em termos de potencial neurogênico e eficácia contra a dor permanecem controversos. Assim, o objetivo do presente estudo foi avaliar a capacidade de células tronco neurais fetais (CTNf) em aliviar a dor crônica e, secundariamente, avaliar os efeitos na recuperação motora. Com este propósito, inicialmente foi realizado um piloto para definir o melhor modelo animal, no qual ratos Wistar foram submetidos à lesão medular traumática de intensidade leve ou moderada (altura do pêndulo 12,5mm e 25mm, respectivamente) utilizando o NYU Impactor. Os resultados indicaram que a lesão medular de intensidade moderada é um bom modelo para o estudo da dor neuropática central, pois, além de apresentar um déficit motor e um quadro álgico mais acentuado que os animais submetidos à lesão leve, os animais se mantiveram estáveis ao longo do estudo. Ademais, alterações sensoriais foram observadas desde os primeiros dias após a lesão e permaneceram por pelo menos oito semanas, viabilizando o objetivo do trabalho. Em vista do resultado do piloto, ratos Wistar foram submetidos à lesão medular de intensidade moderada; sete dias após a lesão medular iniciou-se a imunossupressão com ciclosporina, e dez dias após a lesão os animais receberam injeções intra-espinais de meio de cultivo (grupo sham) ou de CTNf extraídas das vesículas telencefálicas (grupo VT) ou da região ponto-bulbar ventral (grupo BV) de embriões E14 da mesma espécie. As avaliações sensitivas e motoras foram realizadas durante oito semanas. Posteriormente, as medulas espinais foram processadas para imunofluorescência e as CTNf transplantadas foram quantificadas por estereologia. Os resultados mostraram uma melhora da hiperalgesia térmica no grupo VT após a quinta semana de transplante (p < 0,001) e no grupo BV após a quarta semana (p < 0,001). Além disso, a alodínia mecânica melhorou nos grupos VT e BV na 8ª semana (VT p < 0,05 e BV p < 0,01 comparados com sham). Nenhuma recuperação motora significativa foi observada nos grupos tratados em relação ao grupo sham. A análise estereológica mostrou que ~70% das células VT e BV diferenciaram-se em neurônios NeuN+, com alta proporção de células encefalinérgicas e GABAérgicas no grupo VT (44% e 42%, respectivamente) e encefalinérgicas e serotoninérgicas no grupo BV (50% e 47%, respectivamente). Nosso estudo sugere que os precursores neuronais oriundos das VT e BV, uma vez implantados na medula espinal lesada, maturam em diferentes subtipos neuronais, principalmente GABAérgicos, serotoninérgicos e encefalinérgicos, e ambos precursores foram capazes de aliviar a dor, apesar de não haver recuperação motora significativa / Neuropathic pain after spinal cord injury (SCI) is a complex condition which responds poorly to usual treatments. Cell transplantation represents a promising therapy; nevertheless, the ideal cell type in terms of neurogenic potential and effectiveness against pain remains largely controversial. Thus, the objective of the present study was to evaluate the ability of fetal neural stem cells (fNSC) to relieve chronic pain and, secondarily, to evaluate the effects on motor recovery. For this purpose, a pilot was initially designed to define the best animal model; accordingly, Wistar rats were submitted to traumatic spinal cord injury of mild or moderate intensity (pendulum height 12.5mm and 25mm, respectively) using the NYU Impactor. The results indicated that spinal cord injury of moderate intensity is a good model for the study of central neuropathic pain, because in addition to a motor function deficit and painful sensation more pronounced than the animals submitted to mild injury, the animals remained stable throughout the study. Additionally, sensitive deficits were observed from the first days after the injury and lasted eight weeks, enabling the objective of the work. Based on the pilot result, Wistar rats were submitted to moderate spinal cord injury; seven days after spinal cord injury, immunosuppression with cyclosporine was initiated; ten days after injury the animals received intra-spinal injections of culture medium (sham group) or fNSC extracted from the telencephalic vesicles (TV group) or from the ventral medulla (VM group) of E14 embryos of the same species. Behavioral and pain assessment were performed weekly during eight weeks. Thereafter, spinal cords were processed for immunofluorescence, and transplanted fetal cells were quantified by stereology. The results showed improvement of thermal hyperalgesia in TV group after the fifth week of transplantation (p < 0.001) and in VM group after the fourth week (p < 0.001). Moreover, mechanical allodynia improved in both TV and VM groups at the 8th week (TV p < 0.05 and VM p < 0.01 compared to sham). No significant motor recovery was observed in TV and VM groups when compared to sham group. Stereological analyses showed that ~70% of TV and VM cells differentiated into NeuN+ neurons, with high proportion of enkephalinergic and GABAergic cells in the TV group (44% and 42%, respectively) and enkephalinergic and Serotoninergic cells in the VM group (50% and 47%, respectively). Our study suggests that neuronal precursors from the TV and VM, once implanted into the injured spinal cord, maturate into different neuronal subtypes, mainly GABAergic, serotoninergic, and enkephalinergic, and both precursors were able to alleviate pain, despite no significant motor recovery

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