Submitted by BIANCA ANDRIOLO MONTEIRO null (bia_andriolo@hotmail.com) on 2017-09-04T17:12:55Z No. of bitstreams: 1 tese_impressão pós.pdf: 1200489 bytes, checksum: d6d576511877e132bd55c9b142323dcf (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-09-06T12:51:59Z (GMT) No. of bitstreams: 1 monteiro_ba_dr_bot.pdf: 1200489 bytes, checksum: d6d576511877e132bd55c9b142323dcf (MD5) / Made available in DSpace on 2017-09-06T12:51:59Z (GMT). No. of bitstreams: 1 monteiro_ba_dr_bot.pdf: 1200489 bytes, checksum: d6d576511877e132bd55c9b142323dcf (MD5) Previous issue date: 2017-08-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O trauma raquimedular, a discopatia e a cinomose são distúrbios que se caracterizam por sinais neurológicos, os quais muitas vezes são de difícil tratamento. Nesse contexto, a terapia celular busca minimizar os sinais e as sequelas neurológicas adquiridas pelas afecções, com objetivo de melhorar a qualidade de vida dos pacientes. Desta forma, o objetivo deste trabalho foi avaliar o resultado do tratamento com células tronco mesenquimais de tecido adiposo nas afecções de trauma rquimedular, sequela de cinomose e discopatia de cães atendidos no serviço de Acupuntura e Dor Crônica da FMVZ-UNESP. Foram utilizados 62 animais, sendo 14 com trauma raquimedular, 17 com discopatias e 31 com sequela de cinomose, todos submetidos ao exame neurológico prévio seguido de terapia celular. A comparação entre os graus antes e após o tratamento com CTMs alogênicas de tecido adiposo para cada tipo de lesão foi realizada utilizando o teste de Mann-Whitney para medidas repetidas. Foi observada diferença entre as medianas referentes ao grau de gravidade das enfermidades tratadas. Nos casos de sequela de cinomose 43.3% (13/30) dos animais tratados apresentaram diminuição dos sinais neurológicos com melhora da graduação da doença. Nos animais com trauma raquimedulares a melhora foi observada em 50% (7/14), e 66.7% dos animais (12/18) que apresentavam discopatias tiveram uma melhora de quadro clínico. Concluiu-se que as aplicações de células tronco mesenquimais em animais com distúrbios neurológicos da lesão da medula espinhal, doença do disco intervertebral e sequelas de cinomorfose diminuíram o grau de lesão das demais afecções. / Spinal cord injury, intervertebral disc disease and distemper are disorders characterized by neurological signs, which are often difficult to treat. In this context, cell therapy seeks to minimize the signs and the neurological sequelae acquired by injuries, aiming to improve the patients' quality of life. Thus, the aim of this study was to evaluate the results of treatment with mesenchymal stem cells of adipose tissue in conditions of spinal cord injury, distemper sequelae and intervertebral disc disease of dogs treated at the Acupuncture and Chronic Pain Service of FMVZ-UNESP. Sixty-two animals were used, 14 of them with spinal cord injury, 18 with intervertebral disc disease and 30 with distempersequelae, all submitted to previous neurological examination followed by cell therapy. A comparison between grades before and after treatment with allogenic adipose tissue MSCs for each type of injury was performed using the Mann-Whitney test for repeated measurements. A difference was observed between to the injury degree of the diseases treated. In the case of distemper, 43.3% (13/30) of the treated animals showed decreased neurological signs with a reduction in the injury degree. In animals with spinal cord injury was observed decrease in 50% (7/14) of injury degree, and 66.7% of the intervertebral disc disease animals (12/18) had a reduced injury degree. It can be concluded that mesenchymal stem cells in animals with nervous system injuries, it covers a medical clinic of second-hand products with neurological disorders of spindle trauma, discopathy and sequelae of distemper. It was concluded that the MSCs applications in animals with neurological disorders of spinal cord injury, intervertebral disc disease and distemper sequelae decreased the injury degree of the diseases treated.

Orientador: Stelio Pacca Loureiro Luna / Banca: Juliany Gomes Quitzan / Banca: Renata Navarro Cassu / Resumo: A dor crônica é a causa mais frequente de sofrimento e redução da qualidade de vida em cães. Deve-se avaliá-la e tratá-la de forma multidimensional, na qual se inclui a acupuntura (AP). Objetivou-se caracterizar o perfil dos pacientes atendidos e averiguar a eficácia da AP e terapias associadas, na dor crônica e qualidade de vida de 181 cães com doenças neurológicas e osteomusculares. As enfermidades neurológicas prevaleceram, sobretudo as discopatias toracolombares e os trauma raquimedulares agudos. O sucesso no tratamento das lesões medulares foi de 69,5%. A AP manual e a eletroacupuntura foi a associação mais frequente e os analgésicos foram a terapia adicional mais utilizada. Na segunda parte do estudo comparou-se a AP isolada (GAL) ou associada a outras modalidades analgésicas (GAA) por meio de avaliação dos escores iniciais e após 24 semanas de tratamento pelo teste de Wilcoxon e a evolução do sucesso pelas curvas de Kaplan-Meier, com significância de p<0,05. Observou-se 95%, 100%, 95% e 89% de sucesso para o índice de dor crônica de Helsinque (IDCH), escala de qualidade de vida (EAV) e escalas analógicas visuais para dor e locomoção, respectivamente. Para os dois tipos de doenças (em conjunto e isoladas) ambos os grupos de tratamento apresentaram sucesso em todas as avaliações. Para IDCH e EAV locomoção, os cães com doenças osteomusculares apresentaram resultados mais favoráveis do que aqueles portadores de doenças neurológicas (p=0,0027; p=0,045). Conclui-se que o uso isolado de AP ou associado à terapias analgésicas reduziu a dor e melhorou a qualidade de vida em cães com doenças neurológicas e osteomusculares / Abstract: Chronic pain is the most frequent cause of suffering and decreased in quality of life in dogs. It should be evaluated and treated in a multidimensional way, which includes acupuncture (AP). The aim of this study was to analyize the patients profile and investigate the efficacy of AP and associated therapies in chronic pain and quality of life of 181 dogs with neurological and/or musculoskeletal diseases. Neurological diseases were prevalent, especially thoracolumbar intervertebral disk disease and acute spinal cord injury. Treatment was successful in 69.5%. of spinal cord injuries. Association between AP manual and electroacupuncture was the most frequent technique and analgesics were the most used additional therapy. The second part of the study compared the AP (ALG) independently or associated with other analgesic therapies (AAG) through evaluation of initial scores and after 24 weeks of treatment using the Wilcoxon test and the evolution of success by the Kaplan Meier curves, with significant differences when p<0.05. There was 95%, 100%, 95% e 89% success for Helsinki chronic pain index (HCPI), quality of life scale and visual analog scales (VAS) for pain and mobility, respectively. For the two types of diseases both groups showed success in all evaluations. The AP results with or without analgesic therapy for HCPI and VAS were better in musculoskeletal patients than in those with neurologic disease / Mestre

Lesões agudas da medula espinhal são de ocorrência comum em certas raças condrodistróficas como a Dachshund. Nessa raça, um desenvolvimento anormal do disco intervertebral causa uma precoce desidratação e mineralização do núcleo pulposo. Como conseqüência da degeneração discal, esses cães são propensos à extrusão discal aguda que resulta em lesão da medula espinhal contusiva e compressiva. A cirurgia descompressiva é o método de tratamento para cães com disfunção neurológica secundária à compressão da medula espinhal e o prognóstico para recuperação funcional é determinado principalmente pela severidade da lesão na medula espinhal. A perda da sensação de dor profunda em cães com doença do disco intervertebral indica lesão grave da medula espinhal e costuma ser considerada como um mau prognóstico. Existem poucos estudos com um número significativo de casos documentando a recuperação após cirurgia descompressiva em cães com ausência de percepção de dor profunda. A cirurgia raramente é recomendada se a percepção de dor profunda está ausente por mais de 48 horas, mas não foi comprovado um período de tempo mais preciso para tal recomendação. Este trabalho teve como objetivo avaliar a recuperação funcional dos membros pélvicos de cães da raça Dachshund paraplégicos com ausência de percepção de dor profunda por um período inferior e superior a 48 horas, devido à extrusão discal, submetidos à cirurgia descompressiva. Trinta cães paraplégicos foram distribuídos em dois grupos, sendo o primeiro formado por animais com ausência da sensação de dor profunda nos membros pélvicos por um período inferior a 48 horas e o segundo por um período superior a 48 horas. Em todos os pacientes foram realizados exame mielográfico e cirurgia descompressiva (hemilaminectomia). Posteriormente, esses animais foram submetidos a exame neurológico e avaliados quanto ao grau de locomoção e percepção de dor profunda. Apenas foram considerados recuperados os animais que demonstraram grau 3, 4 ou 5 de locomoção (paresia leve, ataxia ou exame neurológico normal). Os resultados comprovaram que pacientes com ausência de dor profunda devido à extrusão do disco intervertebral devem ser considerados candidatos à cirurgia descompressiva. O argumento de um prognóstico ruim, como afirmado em alguns estudos prévios, não se justifica baseado na duração da ausência de dor profunda antes do procedimento cirúrgico. O retorno da percepção de dor profunda dentro de 4 semanas pode ser associado com prognóstico favorável para retorno da locomoção (grau 3, 4 ou 5). A nova escala estabelecida dos graus de locomoção foi útil na avaliação da recuperação funcional de cães paraplégicos. / Acute lesions of spinal cord are a common occurrence in certain chondrodystrophic breeds such as Dachshund. In this race, an abnormal development of the intervertebral disc causes an early dehydration and mineralization of the pulposus core. As a result of disc degeneration, these dogs are prone to acute disc extrusion, resulting in a compressive and contusive spinal cord injury. Surgical decompression is the treatment method for dogs with neurological dysfunction secondary to spinal cord compression and the prognosis for functional recovery is mainly determined by the severity of spinal cord injury. The loss of deep pain perception in dogs with IVDD indicates severe injury of the spinal cord and is often considered as a bad prognosis. There are few studies with a good number of cases documenting the recovery after decompressive surgery in dogs with no deep pain perception (DPP). Surgery is rarely recommended if DPP is absent for more than 48 hours, but an exact period of time for such a recommendation has not been clearly established. This study aims to evaluate the functional recovery of pelvic limbs of paraplegic Dachshund breed dogs paraplegic with no deep pain perception for a period inferior and superior to 48 hours due to disc extrusion and submitted to surgical decompression. Thirty dogs were divided into two groups; the first consists of paraplegic dogs with no sense of deep pain in the pelvic limbs for less than 48 hours and the second, formed by dogs more than 48 hours. All patients underwent to myelographic examination and surgical decompression (hemilaminectomy). Thereafter, these animals were submitted to neurological examination and evaluated about their degree of movement and deep pain perception. Only were considered as recovered animals that reached locomotion grade 3, 4 or 5. The results showed that patients with absence of deep pain due to intervertebral disc extrusion should be considered candidates for decompressive surgery. The argument of a poor prognosis, as stated in some previous studies, was not justified based on duration of deep pain absence before surgery. The return of deep pain perception within 4 weeks may be associated with favorable prognosis for return of locomotion (grade 3, 4 or 5). The established grade of movement degrees was useful in evaluating the functional recovery of paraplegic dogs.

Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul.

Abstract Magnetic resonance imaging (MRI) provides methods to study the microstructure and functional properties of tissues that can be utilized to acquire information about the degenerative processes in the spine. The purpose of the current study was to evaluate the value of diffusion-weighted MRI and quantification of delayed gadolinium enhancement in assessing intervertebral disc degeneration. An experimental degeneration model was used to evaluate the sensitivity of diffusion-weighted MRI and T2 relaxation time measurements in detecting early degenerative changes in the disc. In six pigs, an annular disc lesion was induced surgically, after which the discs were repeatedly MR imaged for up to eight weeks. T2 relaxation time of the lesioned discs decreased postoperatively, whereas apparent diffusion coefficient (ADC) initially increased, but at eight weeks decreased when compared to the control discs. The value of ADC in degeneration of human discs was evaluated by imaging 228 voluntary middle-aged men. ADC values of the three lowest lumbar intervertebral discs were measured and disc degeneration was visually graded. The reduction in ADC between visually normal and moderately degenerated discs was 4%, whereas severely degenerated discs showed 5% higher ADC values than normal discs. T2 signal intensity of the discs was significantly correlated with the ADC values. Because of a considerable overlap between ADC values of normal and degenerated discs the clinical relevance of the ADC measurements of lumbar intervertebral discs remains questionable. A method to quantify delayed enhancement of the nucleus pulposus after intravenous gadolinium contrast agent injection was developed to evaluate the diffusion of small solutes into the disc. Twenty male volunteers were imaged in order to correlate the measured change in the T1 relaxation rate with visually evaluated degenerative changes. The percentual change of T1 relaxation rate for individual discs was up to 126%, and a positive trend was observed between the delayed enhancement and the disc degeneration grades. In order to study the factors that determine the intensity of delayed enhancement, T1 relaxation rate measurements were further correlated with lumbar artery stenosis, bone marrow changes adjacent to endplates, endplate defects, and ADC of the disc. Lumbar artery stenosis and ADC values of the discs were not correlated with enhancement, while disc space narrowing and the presence of degenerative endplate changes had a strong correlation, suggesting an important role for the endplate in maintaining the integrity of the disc.

Abstract The purpose of this study was to evaluate the role of diminished arterial blood flow in painful disc degeneration. Diffusion in intervertebral discs of 37 asymptomatic adults measured by magnetic resonance imaging (MRI) and their lumbar arterial blood supply measured by magnetic resonance angiography (MRA) correlated significantly. End plate degeneration in intervertebral discs evaluated with MRI was analysed with reference to disc distress evaluated with computed tomography (CT) discography, and a significant correlation between end plate degeneration and disc degeneration was found among 36 low back pain patients. Intradiscal pain caused by discography did not correlate with end plate degeneration. There were significantly more atheromatous plaques in the abdominal aorta among 29 chronic low back pain patients compared to 52 asymptomatic people, especially in the age group under 50 years. Occlusion of lumbar arteries in MRA correlated significantly with disc degeneration in MRI among 113 sciatica patients. Furthermore, the disc degeneration and the occlusion of lumbar arteries were severe among 41 sciatica patients and 41 asymptomatic people. During a three-year follow-up, the occlusion of lumbar arteries in MRA correlated significantly with physical and mental ability measured by a self-efficacy questionnaire at every assessment point (1,2,3 years). Furthermore, the intensity of back pain at 1 year and leg pain at 2 years correlated with the occlusion of lumbar arteries. Re-stenosis of lumbar arteries within 3 years correlated significantly with medical consultations for low back pain, prolonged low back pain and prolonged sciatica during one year before the baseline assessment.

Abstract Low back pain (LBP) is the leading cause of years lived with disabilities worldwide. Intervertebral disc (IVD) degeneration is a strong contributing factor to LBP. Recent studies have shown that genetic determinants contribute markedly to IVD degeneration but knowledge about the actual genes involved as well as their roles is still limited. The aim of this thesis work was to study genetic factors that may predispose to IVD degeneration. Using both family and case-control association study designs, variants in five genes showed association with IVD degeneration on magnetic resonance imaging (MRI) in a population-based sample and among patients with sciatica due to lumbar disc herniation (LDH). We performed a candidate gene association study of the known variants implicated in IVD degeneration in a Finnish cohort of 538 young individuals with a moderate degree of lumbar IVD degeneration on MRI. We were able to confirm the associations of variants in the IL6, SKT, and CILP genes, which provides further evidence for true associations. Based on our earlier linkage study in Finnish sciatica families, we performed a candidate gene analysis and identified IL17F as a potential candidate gene. To the best of our knowledge this is the first study to observe an association between this gene and discogenic sciatica. Both IL-6 and IL-17 are pro-inflammatory cytokines with elevated expression levels in herniated tissues, which suggest a role in IVD degeneration. Study of the role of genes coding for inflammatory mediators is of interest as it may contribute to the understanding of the overall inflammatory response of the disc. In addition, we reported on the involvement of SKT in the etiology of lumbar disc herniation (LDH) both in Japanese and Finnish case-control samples. Experimental studies in mice have shown that Skt homozygous mutants exhibit disc abnormalities resulting in a kinky tale phenotype. We hypothesized that the human homolog SKT could have long-term importance in the onset of IVD degeneration by making the discs more vulnerable. Finally, through linkage studies and in the subsequent association analyses, the role of CHST3 as a novel risk factor for IVD degeneration was identified. CHST3 encodes an enzyme that catalyzes the sulfation of chondroitin, and mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. In our study, we identified this gene using genome –wide linkage based on data from a Southern Chinese family and speculated that mild CHST3 reduction caused by the reported susceptibility SNP could result in disc degeneration in adults in conjunction with other risk factors. This thesis provides new information about the genetic background of IVD degeneration and new insights into the etiology of the disease. The specific roles of these genes in the IVD function and pathogenesis of sciatica are not clear however, and need to be elucidated. / Tiivistelmä Alaselkäkipu on yksi yleisimmistä sairauksista ja johtava syy työkyvyttömyyteen. Välilevyrappeuma myötävaikuttaa merkittävästi alaselän kipuun. Vaikka aiemmat tutkimukset ovat osoittaneet, että perintötekijöillä on vahva osuus välilevyrappeumaan, altistavat geenit ja niiden rooli tunnetaan huonosti. Tämän tutkimuksen tavoitteena oli arvioida tiettyjen perintötekijöiden osuutta välilevyrappeumassa ja tunnistaa taudille altistava geeni perheaineistossa aiemmin havaitulta kromosomialueelta. Aineistoina tutkimuksessa olivat perheaineistot sekä laajat potilas-kontrolliaineistot suomalaisesta ja aasialaisista väestöistä. Tutkimuksessa osoitimme, että perimän vaihtelut viidessä tutkitussa geenissä altistivat erilaisille välilevyrappeuman taudin muodoille. Tutkimus, jossa analysoimme aiemmin tunnistettuja alttiusgeenejä, vahvisti IL6, SKT ja CILP geenien vaihteluiden osuuden taudin alttiustekijöinä. Tutkimusaineistona oli pohjoissuomalainen syntymäkohortti, jossa välilevyrappeuma oli määritetty magneettikuvauksella (MRI). Suomalaisessa perheaineistossa tehdyn kokogenomin laajuisen kartoituksen pohjalta analysoimme IL17F geenin mahdollisena uutena alttiusgeeninä oireiselle välilevytaudille. Kahdesta geenin variantista koostuva haplotyyppi assosioitui tautiin merkitsevästi. Lisäksi osoitimme, että SKT-geenin tietty muutos altistaa välilevyn pullistumille sekä japanilaisessa että suomalaisessa potilasaineistossa. Hiirikokeissa on havainnoitu, että SKT-geenin homotsygootti mutaatio johtaa välilevy-poikkeamaan, joka edelleen aiheuttaa hiiren poikkeavan häntäilmiasun-. Hypoteesimme oli, että ihmisen SKT -geeni voi myötävaikuttaa välilevypullistuman kehittymiseen altistamalla välilevyt rappeumalle. Edelleen, laajassa usean populaation aineiston käsittävässä tutkimuksessa osoitimme CHST3-geenin muutoksen altistavan välilevyrappeumalle. Peittyvästi periytyvät muutokset tässä geenissä aiheuttavat perinnöllisiä harvinaisia luusairauksia. Tämä väitöstutkimus tarjoaa uutta tietoa välilevyrappeuman geneettisestä taustasta ja auttaa taudin syiden tutkintaa. Geenien rooli välilevyn toiminnassa ja muutosten vaikutus taudin kulkuun vaativat kuitenkin vielä lisätutkimuksia.

Title: Physical activity of patients after surgical treatment of the lumbar spine. Aim: Main aim of the diploma thesis is to investigate which physiotherapeutic intervention for patients after spinal surgery is the most effective one and offer optimal activity immediately after the surgery and in a long term phase. Investigate questions: 1. Which physiotherapeutic intervention is the most effective one? 2. Which type of physical activity is the most optimal one? Methods: A systematic review on the topic. Results: The review answers the questions about physiotherapy after lumbar surgery in acute and long term phase after surgery and shows current trends and unique approaches in this study area. Keywords: Lumbar spine, intervertebral disc herniation, microdiscectomy, physiotherapy, physical activity.

M.Tech. / aim of this unblinded randomized control study was to compare Chiropractic Adjustive Therapy (CAT) to Interferential Current Therapy (IFC) as treatment for Painful Minor Intervertebral Dysfunction (PMID) in the lumbar spine. The effects of CAT and IFC on lumbar spine range of motion (ROM) and pain relief from PMID were also examined. The participants of the trials were treated at the Chiropractic Day Clinic at the University of Johannesburg. Thirty participants presenting with Low Back Pain (LBP) and PMID on segmental intervertebral examination were used for this study and divided into two groups of fifteen. Group A participants were treated with CAT applied to the painful intervertebral segment. Group B participants were treated with IFC over the painful intervertebral segment. The objective data for this research was recorded by the readings obtained from the application of transverse pressure by a Pressure Algometer to the lateral aspect of a painful spinous process. Further objective readings were taken using a Digital Inclinometer to measure the participants Range of Motion (ROM). Subjective data was obtained by an Oswestry Pain and Disability Index (ODI). The subjective and the objective data were both recorded at the first, fourth and seventh visit which took place over a three week period. The results of the study showed that Group A had a statistically significant decrease in Pressure Algometer Readings and ODI scores. Group A also showed a statistically significant improvement in ROM readings for Left Lateral Flexion, Left Rotation and Right Rotation. Group B did not show any statistical significance in either the subjective or objective data. Importantly, an Inter-group comparison for the Pressure Algometer Readings also revealed an increasing statistically significant difference between Group A and Group B from the first to the fourth and seventh visit. The pain elicited by transverse pressure to a spinous process is core to the diagnosis of PMID, which can result in many pain syndromes of vertebral origin (Maigne, 2006). This research provides evidence that CAT is more beneficial than IFC for the treatment of PMID in the lumbar spine over a short and longer period of time.

The degenerative and traumatic injuries of a spine are very frequent. In those cases it is necessary to stabilize the corresponding spine segment using a spine implant. The spinal implants are rigid or flexible, the latter known as dynamic ones in medical practice. In this thesis, the problems of the physiological spinal segment and the segment with implant were solved using the computational modelling (finite element method). Computational model consists of 4 lumbar vertebrae L2 – L5, intervertebral discs, joints and spinal implants. The spinal segment was loaded by the force 400N and 200N, than by force 200N together with bending moments 2,5Nm and 5Nm depending of the motion. The displacement of the whole system, contact pressure of cartilages, equivalent strain in cancellous bone and equivalent stress in the implant were analyzed. The deformation of the physiological model and the model with the implant are comparable, but the bone tissue of the model with the implant is dramatically more loaded in vicinity of the screws.