Title: Human axial system: identification of connective tissues changes Objectives: The main objective of this thesis was to compile a review of techniques and methods currently used in identification of connective tissues changes. Methods: The method used in this thesis is a critical literature review - a study of research papers from available information sources accompanied by author's comments. Foreign sources are represented mostly by research papers accessible via electronic archives such as ScienceDirect, Pubmed, Springer, Wiley. Also other foreign publications were used. The theoretical part is focused on basic anatomy and physiology of the spine and states main methods of identification of connective tissues changes involved in this area. The main part describes particulars of researches dedicated to identification of functional and morphological characteristics of different spinal components. Results: In addition to classic methods of spinal research, the thesis introduces also new developing techniques and methods. Procedures used in current research are described; their advantages and limits are explained. Key words: spine, biomechanics, loading, intervertebral disc, method

Different psychosocial factors influence the experience and adaptation to pain. Previous cluster analytic studies using the Minnesota Multiphasic Personality Inventory-2nd edition described psychologically different subgroups of pain patients that had been shown valuable in determining outcome. However, these studies had limited applicability to medico-legal pain populations because they did not use newly developed scales or describe important medico-legal factors that have large effects on symptom endorsement. Using three methods of clustering, the current investigation explored the subgroups that resulted when using all the MMPI-2 and the newly developed MMPI-2-RF (Restructured Form) scales on a large and well-described population of medico-legal spine pain patients. Result demonstrated that the best solution for the current sample was the two-cluster solution when a traditional method was used. However, the best solution was the three-cluster solution when all MMPI-2 scales and a method that used all MMPI-2-RF scales were used. Thus, the three-cluster solution was considered the most adequate solution to differentiate patients in medico-legal settings. Moreover, results demonstrated that subgroup membership was not conditioned to spine related organic factors. Instead, malingering, education, ethnic background and legal status differentiated pain subgroups. Lastly, results demonstrated a dose-response relationship between perceived outcome and subgroup profile elevation. The current results are relevant for understanding the circumstances that can influence spine pain recovery and for informing decisions regarding possible interventions.

<p>Repetitive Ca2+ transients in dendritic spines induce various forms of synaptic plasticity by transmitting information encoded in their frequency and amplitude. CaMKII plays a critical role in decoding these Ca2+ signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ decoding in spines remain elusive. Here, I measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. This signal integration, at the time scale of seconds, critically depended on Thr286 phosphorylation. In the absence of Thr286 phosphorylation, only by increasing the frequency of repetitive Ca2+ elevations could high peak CaMKII activity or plasticity be induced. In addition, I measured the association between CaMKII and Ca2+/CaM during spine plasticity induction. Unlike CaMKII activity, association of Ca2+/CaM to CaMKII plateaued at the first Ca2+ elevation event. This result indicated that integration of Ca2+ signals was initiated by the binding of Ca2+/CaM and amplified by the subsequent increases in Thr286-phosphorylated form of CaMKII. Together, these findings demonstrate that CaMKII functions as a leaky integrator of repetitive Ca2+ signals during the induction of synaptic plasticity, and that Thr286 phosphorylation is critical for defining the frequencies of such integration.</p> / Dissertation

Title: Changes of trunk mobility in relation to postural stability Objectives: The main aim of this work was to quantitatively observe segmental trunk mobility in 3D space during flexion of arm and create coupled pattern phenomena of particular spine segments. Additional aim was to verify the effect of modification of the measurements on movement performance and to relate the given movement of the arm and the segmental trunk mobility to changes in the load of the lower extremities. Methods: The measurement itself was performed on 23 asymptomatic males aged 20 - 30. In 3 modifications of the motion measurement - no load, with load and with load and hold with arm forward, probands performed 5 repetitions of right arm flexion in the sagittal plane. The motion was scanned by system Qualisys markers while standing on 2 Kistler stabilometric platforms. Results: In most probands, the segmental movement of the spine was repeatable. It was possible to compare it between probands and create coupled pattern phenomena of the spine. The increased arm load and hold with arm forward caused an increase in the deflections of the particular spine segments in sagittal plane. Furthermore, the increase in load has led to demonstrably greater load changes in the lower extremities. The link between the segmental trunk...

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Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2008. / Lumbar disc replacement is a rapidly expanding surgical treatment modality for longstanding back and leg pain due to intervertebral disc degeneration. Compared to fusion surgery, it has the advantage of preserving segmental mobility, but convincing evidence of superiority over fusion surgery is missing. As part of this research project, I participated in the development of a new intervertebral disc prosthesis, with several international patents attached to the design of the prosthesis, the instrumentation and the insertion technique. The Kineflex (Centurion) lumbar disc is a mechanical, un-constrained, re-centering disc prosthesis developed in South Africa. After the development and manufacturing of the disc, prototype test racks were custom-made at the premises of the manufacturer and the disc was extensively tested for mechanical wear and fatigue. The first implantation took place in October 2002. I prospectively captured all cases performed by our centre, with documentation including demographic data, co-morbidities, clinical history, symptoms and signs. The completed consent forms were filed. The outcome was monitored, pre-operatively and in follow-up, with complete radiological documentation of all radiographs on JPEG files. Clinical outcome results were documented using two different internationally validated questionnaires as well as our own questionnaire, which expands further on work and demographic details, previous operative and conservative treatment, and satisfaction with the treatment outcome. The aim of the this project was to develop a disc prosthesis that is suitable and safe for human implantation into the lumbar spine disc space, even in severely advanced disc degeneration and to verify this in the outcome studies presented in this thesis. Existing indications and contra-indications for artificial disc replacement were critically evaluated regarding their validity for this particular implant. Results: Chapter 3 elaborates on the extensive pre-clinical mechanical wear and fatigue testing protocol to which the Centurion (Kineflex) lumbar disc prosthesis was subjected. The results of this testing protocol, together with our early clinical outcome results, formed the basis for the awarding of the European quality recognition (CE-Mark). In these extensive in vitro studies, we were able to show the durability of the Kineflex disc prosthesis in the long term. This, together with our initial clinical outcome results, formed the basis for the acceptance into a “prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the KINEFLEX Lumbar Artificial Disc versus the CHARITÉ™ Artificial Disc”. Chapter 4 is compiled from an invited submission to a new book on motion preservation surgery in the human spine, edited by leading spine surgeons in the field (James J. Yue, Rudolf Bertagnoli, Paul McAfee, and Howard An) and published by Elsevier Publishers: Chapter 42: Kineflex. In this chapter, an overview is given of the ideas behind the Kineflex disc development, as well as of the insertion instrumentation used for disc implantation. It further reports on early clinical outcome results of the first patients implanted with the device in our centre (the first 40 implantations worldwide were all performed by me). Chapter 5, our first peer reviewed international publication, reports on clinical and radiological 2-year outcome results of our first 100 patients. With the Kineflex implant, we could demonstrate equally good radiological placement accuracy in patients with severe and less severe disc degeneration of the index level, rendering the implant suitable even in severe degeneration of a spinal motion segment. Chapter 6 and Chapter 7 of this thesis consist of two further peer-reviewed publications. They both report on so-called “off-label” patient sub-groups in our disc replacement series. In Chapter 6 we present the second published series on a larger group of patients presenting with adjacent segment disease after previous lumbar fusion surgery as well as the first publication, which investigated the radiological changes in alignment parameters secondary to the disc replacement surgery in this patient group. Chapter 7 consists of the first published series on patients with “degenerative spondylolisthesis” treated with disc replacement surgery. A detailed description of the operative reduction technique is provided, which is unique to the Kineflex disc and its insertion instrumentation. In this pilot study, two-year results on a limited patient group are presented. This thesis concludes with the overall discussion in Chapter 8. It outlines the current knowledge on artificial disc replacement and places my results into perspective with recent discoveries published in the literature. It finishes with my assessment of what future research should concentrate on.

O tratamento cirúrgico das afecções que acometem a coluna cervical alta colocam em risco estruturas neurovasculares, como a artéria vertebral e a medula espinhal, durante a colocação de parafusos transarticulares em C1-C2 e parafusos de massa lateral em C1. O presente estudo visa determinar os parâmetros anatômicos do atlas (C1) em uma amostra da população brasileira, compará-los aos resultados já apresentados na literatura para outras populações e, assim, identificar e alterar as indicações dos implantes utilizados no tratamento das afecções da coluna cervical alta. Foi realizado um estudo observacional retrospectivo de um banco de dados prospectivo, incluindo 100 pacientes atendidos em um hospital terciário, entre janeiro de 2012 a dezembro de 2013. Foram utilizados cortes axiais e sagitais de tomografias computadorizadas. Os parâmetros estudados foram, no corte axial: o ponto de entrada do parafuso (DTPPE), o ângulo de segurança (ADSPA), o tamanho ideal do parafuso (TPA) e o tamanho da massa lateral entre os forames vertebral e transverso (DCVFT); no corte sagital foi medido o tamanho ideal do parafuso (TPS), o ângulo de segurança (ADSPS) e a espessura do arco posterior (EAP). Todos os parâmetros foram divididos de acordo com a idade, sexo e o lado esquerdo e direito. Resultados: O ponto de entrada dado pelo DTPPE foi 21,86 ± 1,5 mm a esquerda e 22,7 ± 1,44 mm a direita no sexo masculino; e 20 ± 1,4 mm a esquerda e 20,24 ± 1,34 mm a direita no sexo feminino. A zona de segurança (ADSPA) foi 23,68 ± 6,12º a esquerda e 24,0 ± 5,82º a direita no sexo masculino e 18,09 ± 5,46º a esquerda e 18,57 ± 5,34º a direita no sexo feminino. A espessura do arco posterior (EAP) encontrada no sexo masculino foi 8,95 ±1,75 mm a esquerda e 8,92 ± 2,22 mm a direita, no sexo feminino encontramos uma espessura menor de 7,21 ± 1,53 mm a esquerda e 7,41 ± 1,58 a direita. Por meio de uma técnica original e reprodutível de avaliação de exames de tomografia computadorizada, os parâmetros anatômicos do Atlas encontrados na amostra da população estudada em nosso estudo foram semelhantes aos apresentados previamente na literatura. No entanto, foram observadas diferenças entre os sexos. Assim, recomendamos a utilização do exame de tomografia computadorizada como método de avaliação pré-operatória quando a fixação da massa lateral pelo arco posterior do Atlas for empregada. / The surgical treatment of conditions affecting the high cervical spine puts at risk neurovascular structures, such as the vertebral artery and the spinal cord, during the placement of transarticular screws in C1-C2 and lateral mass screws in C1. The present study aims to determine the anatomical parameters of the atlas (C1) in a sample of the brazilian population, to compare them with the results already presented in the literature for other populations and thus to identify and change the indications of the implants used in the treatment of spinal affections cervical high. A retrospective observational study of a prospective database including 100 patients treated at a tertiary hospital between January 2012 and December 2013 was performed. Axial and sagittal sections of computed tomography were used. The parameters studied were, in the axial section: the screw entry point (DTPPE), the safety angle (ADSPA), the ideal screw size (TPA) and the lateral mass size between the vertebral and transverse foramina (DCVFT) ; in the sagittal cut, the ideal screw size (TPS), the safety angle (ADSPS) and the posterior arch thickness (EAP) were measured. All parameters were divided according to age, sex and left and right side. The entry point given by the DTPPE was 21.86 ± 1.5 mm on the left and 22.7 ± 1.44 mm on the right in the male; and 20 ± 1.4 mm on the left and 20.24 ± 1.34 mm on the right in the female. The safety zone (ADSPA) was 23.68 ± 6.12 ° on the left and 24.0 ± 5.82 ° on the right in the male sex and 18.09 ± 5.46 ° on the left and 18.57 ± 5.34 ° on the right in females. The posterior arch thickness (EAP) found in males was 8.95 ± 1.75 mm on the left and 8.92 ± 2.22 mm on the right, in females we found a thickness less than 7.21 ± 1.53 mm on the left and 7.41 ± 1.58 on the right. Using an original and reproducible technique for the evaluation of CT scans, the Atlas anatomical parameters found in the sample of the population studied in our study were similar to those previously reported in the literature. However, differences between the sexes were observed. Thus, we recommend the use of computed tomography (CT) examination as a preoperative evaluation method when lateral mass fixation by the posterior arch of the Atlas is used.

O sistema de fixação vertebral utilizando o parafuso pedicular é um dos métodos mais eficientes no tratamento de patologias da coluna vertebral. Quando o parafuso estiver submetido à força de arrancamento, ele gera tensões ao redor, principalmente próximo do canal medular, situação que pode ser analisada pela técnica da fotoelasticidade. O objetivo foi analisar as tensões internas geradas em modelos fotoelásticos de vértebras, utilizando diferentes medidas de parafusos do sistema de fixação vertebral, submetidos à força de arrancamento. Foi utilizado um modelo de vértebra lombar em material fotoelástico utilizando três medidas de diâmetros externos de parafusos pediculares (5, 6 e 7mm) do tipo USS1. As tensões internas ao redor do parafuso foram avaliadas em 18 pontos pré-determinados utilizando um polariscópio de transmissão plana. As regiões de maiores concentrações de tensões foram observadas entre o canal medular e as curvas do processo transverso. Nas comparações das médias das tensões cisalhantes entre os parafusos 5 e 7mm, e 6 e 7mm foram observadas diferenças estatísticas significativas, o que não ocorreu com os parafusos de 5 e 6mm onde não foram observadas diferenças estatisticamente significativas. Foi observado que as tensões internas são mais elevadas em áreas irregulares próximas do canal medular, o que sugere ser uma região crítica, em termos de esforços mecânicos. / The system of vertebrae fixation using the pedicular screw is one of the most efficient methods to treat vertebral spine pathologies. When the screw is submitted to pullout strength, it causes internal stress near the medullary canal and this situation can be analyzed using the photoelasticity technique. The objective of this study was to examine the internal stress of a photoelastic vertebrae model using different sizes of screws for the vertebral fixation submitted to pulling out. A lumbar vertebral model made of photoelastic material with three different pedicular screw sizes (5, 6 and 7mm), type USS1 was used. The internal stress around the screw were tested in 18 pre established points by a plain transmission polariscope. The areas of greater concentration of stress were placed between the medullary canal and the transverse process. Comparing the maximum average pulling out stress, statistical differences were observed between screws 5 and 7, and 6 and 7. On the other hand, when screws 5 and 6mm where compared no significant differences were found. This study identified that the internal stress are greater in irregular areas, near the medullary canal, suggesting that this may be a critical region.

A prática de atividade física, em especial a corrida de rua, vem atraindo bastante o interesse de idosos e a cada dia ganha mais adeptos com idade superior a 60 anos. Porém, o avanço da idade traz além de alterações estruturais, mudanças funcionais na coluna de idosos, o que pode influenciar o padrão de movimento do corpo durante a atividade esportiva. O objetivo deste estudo foi investigar as diferenças nos movimentos da coluna, pelve e quadril entre idosos corredores e adultos jovens corredores durante a caminhada e a corrida e paralelamente observar se os movimentos da coluna teriam relação com a absorção de impacto durante a corrida. Realizou-se uma análise cinemática dos segmentos de interesse nas duas tarefas e a força reação do solo vertical foi mensurada na corrida em dois grupos, um formado por adultos jovens corredores (n = 22) e outro por idosos corredores (n = 21). Na caminhada, a principal diferença entre os grupos foi a menor extensão de quadril e a maior anteversão pélvica nos idosos. Na corrida a amplitude de movimento torácica nos idosos se mostrou menor e a amplitude de movimento lombar positivamente correlaciona ao pico de impacto com o solo. A extensão de quadril nos idosos também foi menor na corrida, porém não apresentou correlação com a anteversão pélvica. Este trabalho mostrou diferenças entre idosos e adultos corredores como resultados de déficits articulares dos idosos e ressaltou possíveis pontos de intervenção, como a extensão de quadril, extensão torácica e movimento da coluna lombar / Practice of physical activity, especially running, has been attracting the interest of elderly people and gains more adepts older than 60 years old each day. However, aging brings structural and functional alterations on the spine, and this can influence the movement pattern of the body during sport practice. The aim of this study was to investigate the differences in spine, pelvis and hip movements between elderly runners and young adult runners during gait and running, and also to investigate the relationship between spine range of motion and impact absorption during running. Kinematic analysis of the segments of interest for both tasks was performed and the ground reaction force was measured during running for two groups, one formed by elderly runners (n=21) and the other formed by young adult runners (n=22). For gait, the main difference between the groups was the lesser hip extension and greater pelvic anterior tilt of the elderly. For running the thoracic range of motion of the elderly was lesser and the lumbar range of motion was positively correlated with the ground impact peak. The hip extension of the elderly was also lesser in running, but did not present correlation with the anterior pelvic tilt. This study showed differences between elderly and young adult runners as results of joint deficiencies of the elderly and directed treatment possibilities on the hip extension, thoracic extension and lumbar spine movement

Objetivo: Investigar a mobilidade cervical e do segmento C1/C2 com o Flexion Rotation Test (FRT) em pacientes com migrânea crônica e episódica, e analisar a influência da cronicidade, da incapacidade cervical e da alodinia cutânea nessa mobilidade. Métodos: Foram avaliadas 85 mulheres com idade de 18 a 55 anos divididas em três grupos: migrânea crônica (MC)(n=25), migrânea episódica (ME)(n=30) e controle (n=30). O FRT e a avaliação da amplitude de movimento cervical foram avaliados com o instrumento CROM® acoplado a cabeça. Foram realizadas três repetições de cada movimento, aleatorizadas previamente. A média das repetições foi utilizada para a análise dos dados. A incapacidade cervical foi avaliada pelo Neck Disability Index e a alodinia cutânea pelo Allodynia Symptom Checklist (ASC-12). Quanto a mobilidade, os grupos foram comparados utilizando o teste Manova com pós teste de Bonferroni. A razão de prevalência foi utilizada para identificar a associação entre o diagnóstico de migrânea e a cronicidade com a mobilidade do segmento C1/C2. A regressão linear simples foi usada para identificar a influência da incapacidade cervical e da alodinia cutânea no FRT. Resultados: Todos os grupos diferiram nos valores do FRT (MC = 25.79º e 26.81º; ME = 33.44º e 32.18º; controle= 41.98º e 40.18º; nos movimentos a direita e esquerda, respectivamente, p<0.05). Apenas o grupo MC diferiu na amplitude de movimento cervical (p<0.05) do grupo controle em todos os movimentos. Pacientes com migrânea apresentaram 2.85 vezes mais associação ao risco de apresentar hipomobilidade no segmento C1/C2 comparado aos controles. A incapacidade cervical influenciou em 19% a amplitude desse segmento independente do diagnóstico de migrânea, enquanto que a alodinia cutânea não apresentou influência significativa. Conclusão: Mulheres com migrânea apresentam reduzida amplitude de movimento cervical, especialmente no segmento C1/C2, e maior risco de desenvolver hipomobilidade cervical superior comparado a mulheres sem cefaleia, sendo este risco aumentado pela cronicidade da doença. Além disso, a incapacidade cervical influencia no resultado do FRT, contrariamente a alodinia cutânea / Objective: To investigate the cervical and C1/C2 mobility with the Flexion Rotation Test (FRT) in patients with chronic and episodic migraine, and analyze the influence of the chronicity, cervical disability and cutaneous allodynia in this mobility. Methods: Were analyzed 85 women with age between 18 and 55 years, divided in three groups: chronic migraine (CM)(n=25), episodic migraine (EM)(n=30) and control (n=30). The FRT and cervical range of motion has been applied with the CROM® device coupled to the head. Were conducted three repetitions of each movements, randomized previously. The mean of the repetitions was used for data analysis. Cervical disability was assessed by the Neck Disability Index and cutaneous allodynia by the Allodynia Symptom Checklist (ASC-12). As for mobility, the groups were compared using MANOVA test with post-hoc de Bonferroni. The prevalence ratio was used to identify the association between the migraine diagnostic and chronicity with C1/C2 mobility, and simple linear regression was used to identify the influence of cervical disability and cutaneous allodynia in FRT. Results: All groups differed in the FRT (CM = 25.79º and 26.81º; EM = 33.44º and 32.18º; control = 41.98° and 40.18º; right and left movements, respectively, p <0.05). Only, CM group differed in cervical range of motion (P <0.05) to the control group in all movements. Migraine patients shows 2.85 times more association with risk for C1/C2 hypomobility compared to controls. Cervical disability influenced by 19% the ranger of this segment independent the diagnosis of migraine, while the cutaneous allodynia has not a significant influence. Conclusion: Women with migraine have reduced cervical range of motion, especially in the C1/C2 segment, and higher risk of develop superior cervical hypomobility compared to women without headache, and this risk was increased by the chronicity. Also, cervical disability influence the FRT, in contrast to cutaneous allodynia