Dissertations / Theses on the topic 'Degenerative disc disease'

Degenerative disc disease (DDD) is a medical condition whereby the intervertebral discs (IVD) of the human spine degenerates and may cause pain which significantly affects the quality of one掇 life. Its prevalence has sparked off much research in deciphering its causes and developing new treatments. Recently, attempts to treat this degenerative problem have turned to seeking answers from regenerative medicine. One approach is to deliver mesenchymal stem cells (MSCs) with or without carriers to the nucleus pulposus (NP) in degenerative disc to restore both its structural and functional properties. However, the optimal conditions and signals for inducing MSCs differentiation toward NP-like phenotype have not been identified. This work aimed to develop injectable microspheres with matrix microenvironment mimicking that of native NP tissue for MSCs delivery. Firstly, it was aimed to establish a collagen microencapsulation based 3D culture system for maintenance of the phenotype of nucleus pulposus cells (NPCs) and remodeling of the collagen matrix to one that was similar to the native NP. Secondly, it was aimed to optimize a decellularization protocol for complete removal of the encapsulated NPCs with minimal loss of remodeled extracellular matrix. Thirdly, it was aimed to investigate whether this acellular matrix produced by NPCs was inductive for MSCs discogenic differentiation. Finally, it was aimed to evaluate the efficacy of the MSC-seeded acellular matrix microspheres in a pilot rabbit disc degeneration model. It demonstrated that NPCs maintained their phenotype, survived within the collagen microspheres and produced NP-like ECM such as glycosaminoglycan (GAG) and collagen type II. GAG production of NPCs was found to positively correlate with the dosage of TGF-? within a short period, initial collagen concentration and cell seeding density. An optimized decellularization protocol with 50mM SB-10, 0.6mM SB-16 and 0.14% Triton X-200 was established to completely remove the encapsulated NPCs with partial retention of the GAG-rich matrix. The decellularized microspheres were able to be repopulated with human MSCs (hMSCs) or rabbit MSCs (rMSCs). Within the NPC-derived acellular matrix, the repopulated hMSCs were able to partially exhibit NPC phenotype with upregulated expression of a few NPC markers and NP-like ECM according to histological, biochemical, immunohistological and real-time PCR results. In the pilot in vivo evaluation study, preliminary results showed that intra-discal injection of MSCs reseeded acellular NPC-matrix microspheres maintained a better water content than the control MSC-microspheres without the NPC-derived acellular matrix. This work reconstituted in vitro a NP-like 3D matrix and provided preliminary evidence on discogenic differentiation of MSCs in such a matrix environment. This work laid down the foundation to future development of stem cell-based therapies for DDD. Further studies should focus on deciphering the soluble and insoluble composition of such a NP-like matrix environment and understanding the molecular mechanism of the cell-matrix interactions involved.
published_or_final_version
Mechanical Engineering
Doctoral
Doctor of Philosophy

Thesis (Ph.D.)--University of California, San Francisco with the University of California, Berkeley, 2009.
Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Sharmila Majumdar.

One of the primary causes of persistent lumbar back pain is degenerative disc disease (DDD). In most persons, DDD is a normal process occurring with natural age, while in others, DDD results in chronic pain. While imaging techniques can be used to detect degenerative changes, there is a low correlation between the extent of degenerative changes and the pain found upon physical evaluation, suggesting biochemical factors may be involved with the persistent pain state. The purpose of this study was to examine human cerebrospinal fluid (CSF) for changes in protein expression using high throughput proteomics technology, which would help to identify biochemical factors involved with DDD and low back pain. Differences at the protein level were observed in the CSF of persons with asymptomatic and painful degenerative disc disease. Markers of inflammation were altered in patients with degenerative disc disease. In the case of painful degenerative disc disease, our results suggest altered neuropeptide processing and nerve damage may be playing a role in the disease.
L'une des causes de la lombalgie chronique est la maladie degenerative lombaire (MDL). Chez la plupart des gens, ce processus se développe normalement au cours du vieillissement, alors que chez d'autre gens, la MDL cause de la douleur chronique. Alors que les techniques d'imageries peuvent être utilisées pour détecter la dégénérescence des disques, il y a une faible correlation entre l'étendue de la dégénérescence et la douleur ressentie à l'évaluation médicale. Il est donc possible que des facteurs biochimiques soient impliqués dans le dévellopement et la maintenance de la douleur chronique, mais qu'ils soient indétectables par imagerie. Le but de cette étude est d'analyser le liquide céphalo-rachidien (LCR) de l'humain afin de mesurer les changements d'expression de proteins et ainsi, d'identifier les facteurs biochimiques impliqués dans la MDL. Des différences au niveau des protéines ont été observées entre le CSF de personnes asymptomatiques et de personnes souffrant de la MDL avec douleur. Marqueurs inflammatoires ont été altérés chez les patients présentant la MDL. Dans le cas des patients ayant la MDL avec douleur, il est possible que le métabolisme des neuropeptides et des dommages aux terminaisons nerveuses jouent un role dans la pathologie.

Degenerative Veränderungen der Lendenwirbelsäule beginnen bereits im Alter von unter 20 Jahren und betreffen vor allem die unteren 3 Bewegungssegmente. Die degenerativen Veränderungen an der Bandscheibe gehen mit einer Kalzifizierung der Grund- und Deckplatten der Wirbelkörper einher, was zu einer Reduktion der Nährstoffversorgung der Bandscheibe und damit zu einem Untergang der matrixbildenden Zellen und konsekutiv zu einem Flüssigkeitsverlust in der Bandscheibe führt. Als Folge nimmt die Belastung der Bandscheibe weiter ab. Die aktuellen Therapieoptionen umfassen sowohl die konservative als auch die operative Therapie, wobei allerdings nur die Folgen der Degeneration behandelt werden. Ziel einer Zelltransplantation ist es, der Bandscheibe wieder matrixbildende Zellen zur Verfügung zu stellen, damit die nutritiven Veränderungen auszugleichen und eventuell reversibel zu machen. Dieser Effekt konnte im Tierversuch nachgewiesen werden, woraufhin eine klinische Studie initiiert wurde. Im Rahmen der publizierten klinischen prospektiven, randomisierten Studie konnte gezeigt werden, dass die Transplantation autologer Chondrozyten, die bei einer notwendigen operativen Therapie eines sequestrierten Bandscheibenvorfalls gewonnen wurden, einen sowohl klinisch als auch bildmorphologisch positiven Effekt auf die degenerierten Bandscheiben hat. Es kam zu einer signifikanten Reduktion der Schmerzsymptomatik und einer Steigerung der Lebensqualität in der Gruppe der transplantierten Patienten. Die Bandscheibenhöhe zeigt sich stabil über den Beobachtungszeitraum von 2 Jahren.

The intervertebral disc (IVD), situated between adjoining vertebrae, consists of the gelatinous nucleus pulposus (NP) in the centre surrounded by the tougher annulus fibrosus (AF). Its main roles are to distribute loads and to act as joints. With aging, degenerative disc disease (DDD) occurs due to an imbalance in anabolic and catabolic events in the IVD, which results in a loss of function. Lower back pain (LBP) affects 84% of people at some point in their lifetime and is strongly associated with DDD. Current LBP treatments have limited long term efficacy and are symptomatic rather than curative. Cell-based therapies are regarded to hold great potential for the treatment of DDD as it has been hypothesised that they could regenerate the damaged tissue and alleviate LBP. A number of natural and synthetic biomaterials have been investigated as NP tissue engineering scaffolds with varying results. In this study, a self assembling peptide hydrogel (SAPH) was investigated for its potential as a cell carrier and/or scaffold for NP tissue engineering. SAPHs display the advantages of natural polymer hydrogels such as biocompatibility and biodegradability whilst combining the advantages of synthetic materials such as controlled structural and mechanical propertiesCharacterisation determined that the SAPH nanofibrous architecture had features that were of similar scale to extracellular matrix (ECM) components of the human NP. The mechanical properties of the SAPH could be optimised to closely match the native tissue. The system could shear thin and self-heal making the system ideally suited to delivery via minimally invasive procedure. The three dimensional (3D) culture of bovine NP cells (bNPCs) in the SAPH demonstrated that the NP phenotype could be restored after de-differentiation during monolayer culture. Gene expression results demonstrated that ‘traditional’ and ‘novel’ NP markers were highly expressed throughout in vitro culture. Cell viability was high, cell population remained stable and bNPCs adopted the characteristic rounded morphology of native NPCs. Finally, type II collagen and aggrecan, the main ECM components of the NP, were deposited with increasing production over culture period. Growth differentiation factor 6 (GDF-6) has been identified as the most promising current growth factor for inducing discogenic differentiation from human bone marrow mesenchymal stem cell (h-BMMSCs). After samples were stimulated with GDF-6, gene expression results confirmed that a NP-like phenotype could be induced with high expression of ‘traditional’ and ‘novel’ NP markers. Cell viability was high, cell population remained stable and NP associated ECM components were deposited with cells displaying a rounded morphology. Interestingly, when h-BMMSCs were cultured without GDF-6, it was strongly suggested that spontaneous discogenic differentiation occurred after culture in the SAPHs as ‘traditional’ and ‘novel’ NP markers were highly expressed, morphology was comparable to native NPCs and type II collagen and aggrecan were deposited extracellularly. If these findings were accurate then this is the first study to demonstrate that a NP-like phenotype could be induced from MSCs without use of an exogenous growth factor or a discogenic bioactive motif. Despite exciting and novel results, further work is required to confirm the potential of SAPHs for NP tissue engineering scaffolds.

La dégénérescence discale lombaire (DDL) est caractérisée par un vieillissement prématuré du disque intervertébral (DIV) et une déshydratation progressive du nucleus pulposus (NP) entrainant in fine des lombalgies. L'objectif général de ce travail est d'établir des données précliniques afin de régénérer le DIV en cas de DDL modérée. Dans un premier chapitre, nous avons déterminé une association de facteur de croissance et un mode de culture visant à obtenir une prédifférentiation nucléopulpogénique de cellules stromales mésenchymateuses (CSMs) humaines issues de la moelle osseuse. Nos résultats montrent que la culture tridimensionnelle des CSMs en billes d'alginate en présence de TGF-β3, GDF-5 et BMP-7 les oriente vers un phénotype cartilagineux. Dans un deuxième chapitre, nous avons élaboré un modèle porcin de DDL induite par cryolésion et nous l'avons comparé aux techniques de référence. L'évaluation de l'importance de la DDL a été effectuée par scanner, IRM et histologiquement. Un score histologique de DDL porcine a été décrit et validé. La cryolésion a permis d'obtenir une DDL plus importante que les autres techniques. Dans un troisième chapitre, nous avons injecté les CSMs préorientées dans les DIV lésés. L'analyse IRM a montré une amélioration de l'intensité du signal et de la surface du NP après injection des cellules. L'analyse immunohistologique a montré une survie des CSMs dans les DIV porcins à 2 mois. Dans un quatrième chapitre, nous avons comparé les taux de fusion et de complication pour la RhBMP-2 et la greffe spongieuse autologue dans les arthrodèses lombaires par voie antérieure dans une même cohorte de patients. La RhBMP-2 était associée à un taux de fusion inférieur et un taux de complications radiologiques supérieur à l'autogreffe spongieuse
Degenerative disc disease (DDD) is characterized by premature aging of the intervertebral disc (IVD) and gradual dehydration of the nucleus pulposus (NP), ultimately causing back pain. The general objective of this work is to establish preclinical data to regenerate the IVD in moderate DDD. In the first chapter, we have identified a growth factor association and a culture method to achieve nucleopulpogenic prédifférentiation of mesenchymal stromal cells (MSCs) derived from human bone marrow. Our results show that the three-dimensional culture of MSCs in alginate beads in the presence of TGF-β3, GDF-5 and BMP-7 directs them to a cartilaginous phenotype. In the second chapter, we developed a porcine model of DDD, induced by cryoinjury, and compared it to reference techniques. Assessing the importance of DDD was performed by CT, MRI and histologically. A histological score of porcine DDD has been described and validated. Cryoinjury yielded a higher DDD that other techniques. In a third chapter, we injected preoriented MSCs in cryo-injured IVDs. MRI analysis showed an improvement in the signal intensity and the surface of the NP after the injection. The immunohistological analysis showed a survival of the MSCs in the porcine IVD 2 months after injection. In a fourth chapter, we compared the rate of fusion and complication for rhBMP-2 and autologous cancellous graft in the anterior lumbar interbody fusion, in the same cohort of patients. RhBMP-2 was associated with a lower fusion rate and a higher rate of radiological complications than the cancellous autograft

Orientador: João Batista de Miranda
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-21T06:02:57Z (GMT). No. of bitstreams: 1 Pasqualini_Wagner_D.pdf: 1157517 bytes, checksum: f927ba791a4b318be74e60bad2138135 (MD5) Previous issue date: 2012
Resumo: Modelo de Estudo: Estudo diagnóstico Transversal de caso controle. Objetivos: comparar pacientes com estenose do canal lombar com indicação de cirurgia e um grupo controle, assintomáticos para esta doença, levando em consideração imagens de ressonância magnética (RM) e o questionário de Oswestry. Material e Método: Vinte e três pacientes com estenose do canal lombar foram comparados com um grupo controle de 17 indivíduos. Todos foram submetidos a RM e responderam ao questionário de Oswestry. Medidas qualitativas foram descritas segundo os grupos com uso de frequências absolutas e relativas e, verificada a existência de associação dessas medidas com uso do teste exato de Fisher. Medidas quantitativas foram descritas e comparadas entre os grupos com uso do teste Mann-Whitney. O teste de Spearman foi utilizado para avaliar a correlação entre os grupos. Resultados: Lombalgia foi a queixa mais frequente nos dois grupos. O índice de Oswestry mostrou média de percentual de invalidez de 45,69% no Grupo Estenose e 11,60% no Grupo Controle. A RM mostrou que a área de secção transversa do saco dural, o diâmetro do canal e a avaliação dos forames e recesso lateral estavam alterados em ambos os grupos. Conclusões: Não houve relação entre o grau de estenose do canal lombar mensurado em exame de RM com o índice de Oswestry em ambos os grupos
Abstract: Study design: Transversal Case-control, diagnostic study. Objectives: To verify the relationship between the degree of lumbar spinal canal stenosis (LCS), as seen in magnetic resonance imaging (MRI), and the severity of disability as seen in the Oswestry Index, in patients with LCS compared to controls without a diagnosed LCS. Methods: Twenty-three patients with a previous diagnosis of LCS were compared with a control group of 17 volunteers. All participants underwent MRI and answered the Oswestry questionnaire. Qualitative data were described according to the groups with the use of absolute and relative frequencies, and the association of these measures was checked by using the Fisher exact test. Quantitative measures were described and compared between groups using the Mann-Whitney test. Spearman's test was used as well. Results: Low back pain was the most frequent complaint in both groups. The Oswestry index showed average percentage of disability of 45.69% in patients with stenosis and 11.60% in the control group. MRI revealed that the dural sac cross-sectional area (DCSA), the diameter of the canal and the evaluation of lateral recesses and foramina were equally changed in both groups. Conclusions: There was no correlation between the degree of lumbar canal stenosis measured on MRI with the Oswestry Disability Index in both groups
Doutorado
Cirurgia
Doutor em Cirurgia

Abstract Musculoskeletal diseases, such as osteoarthritis (OA), lumbar disc degeneration (LDD) and osteoporosis (OP), are common complex disorders affected by both environmental and genetic factors. OA and LDD are degenerative diseases affecting joints and spine and Modic changes (MC) are a specific phenotype of LDD. OP is a disorder causing bone fragility. There are families with a history of early onset cartilage degradation, disc disorders and bone fragility as well as rare, more severe disorders with these traits as part of the phenotype. The aim of this study was to identify predisposing genetic factors in Finnish families with three different musculoskeletal phenotypes and to investigate the use of whole exome sequencing (WES) as a tool. Six families were studied here, three diagnosed with hip and knee OA, two with MC and one with primary OP. Using WES together with in silico and in vitro analyses we identified new candidate genes. In the two OA families we identified family specific variants, c.-127G>T in the 5’UTR of FIP1L1 and p.Arg210Gly in OLIG3. We observed expression of these genes in human bone and cartilage. Both FIP1L1 and OLIG3 participate in the regulation of transcription. Family specific variants were also found in both families with MC: p.Gln1611fs in HSPG2 and p.Glu553Lys in MAML1. HSPG2 encodes for an important structural protein in the disc and MAML1 is a transcription factor. The family with primary OP had previously been reported to carry a heterozygous COL1A2 deletion leading to nonsense-mediated mRNA decay. In the WES we identified an additional change that may contribute to the phenotype: p.Arg428* in ZNF528. We showed experimentally that the variant leads to expression of a truncated form of ZNF528 in the nucleus. ZNF528 binding sites are located near genes associated with bone phenotypes. We identified twelve potential target genes for ZNF528 that were differentially expressed in patients’ cells compared to controls. Altogether, we identified five new candidate genes for the studied phenotypes demonstrating that WES can be used as a tool in studying complex musculoskeletal phenotypes in families. One of the identified candidate genes, HSPG2, encodes a structural protein, whereas, OLIG3, FIP1L1, MAML1 and ZNF528, participate in the regulation of transcription supporting the importance of regulatory mechanisms in the pathogenesis of musculoskeletal diseases
Tiivistelmä Tuki- ja liikuntaelinsairaudet, kuten nivelrikko, välilevyrappeuma ja osteoporoosi, ovat yleisiä, monitekijäisiä sairauksia. Nivelrikko ja välilevynrappeuma ovat eteneviä nivelten ja selkärangan sairauksia. Modic muutokset ovat välilevyn ja nikaman välisten päätelevyjen muutoksia. Osteoporoosi on luuta haurastuttava sairaus. Varhaisessa iässä ilmenevää ruston haurastumista, välilevyn sairauksia tai luun haurautta tavataan myös suvuittain esiintyvinä sairauksina tai vakavien harvinaisten sairauksien oireina. Tutkimuksen tarkoitus oli tunnistaa altistavia geneettisiä tekijöitä kolmelle tuki- ja liikuntaelimistön sairaudelle suomalaisissa perheissä käyttäen eksomisekvensointi-menetelmää. Aineisto koostui kuudesta perheestä: kolmessa oli diagnosoitu lonkan ja polven nivelrikko, kahdessa selän välilevyjen Modic muutoksia ja yhdessä primaarinen vaikea selän osteoporoosi. Tunnistimme uusia ehdokasgeenejä käyttäen eksomisekvensointi-menetelmää sekä in silico ja in vitro analyysejä. Kahdessa nivelrikkoperheessä tunnistimme perhekohtaiset variantit kahdessa geenissä: c.-127G>T variantin FIP1L1 geenin säätelyalueella ja p.Arg210Gly variantin OLIG3 geenissä. Osoitimme, että nämä traskription säätelyyn osallistuvat geenit ilmenevät ihmisen luu- ja rustokudoksessa. Perhekohtaiset variantit havaittiin myös perheissä, joilla oli todettu Modic muutoksia: p.Gln1611fs HSPG2 -geenissä ja p.Glu553Lys MAML1 -geenissä. HSPG2 koodaa välilevylle tärkeää rakenneproteiinia ja MAML1 on transkriptiota säätelevä tekijä. Primaarista osteoporoosia sairastavalla perheellä oli aiemmin havaittu heterotsygootti, geenituotteen hajottamiseen johtava deleetio, COL1A2 -geenissä. Eksomisekvensoinnlla havaitsimme mahdollisesti taudin ilmiasuun lisäksi vaikuttavan muutoksen ZNF528 -geenissä. Osoitimme kokeellisesti, että havaittu variantti johtaa lyhentyneen proteiinin tuottoon solussa. ZNF528 on transkriptiotekijä, jolle tunnistimme kaksitoista mahdollista kohdegeeniä ja havaitsimme että niiden tuotto oli muuttunut potilaiden soluissa kontrollisoluihin verrattuna. Tunnistimme viisi uutta ehdokasgeeniä kolmessa eri sairaudessa eksomisekvensointi-menetelmän avulla. Yksi tunnistetuista geeneistä, HSPG2, koodaa rakenneproteiinia, ja muut osallistuvat transkription säätelyyn. Tämä tukee käsitystä säätelytekijöiden tärkeydestä TULE sairauksien synnyssä

Background: An association between cartilaginous endplate (CEP) defects and intervertebral disc (IVD) degeneration has been previously suggested in animal and cadaveric studies. CEP defects may also be involved in Schmorl’s nodes (SN). There have been no previous reports in the literature that describe the use of ultrashort time-to-echo (UTE) MRI to assess the CEP in humans in vivo. In chapter 5 of this thesis, a retrospective study of paediatric spines and the neurocentral synchondrosis (NCS) was singled out to report the incidence of NCS and to raise the hypothesis of NCS as a precursor of SN. Purpose: To assess the feasibility of detecting CEP defects in live humans using UTE MRI, and to assess their relationship with IVD degeneration and SN. Subjects and Methods: A total number of 22 subjects underwent T2-weighted (T2W) and UTE MRI to assess for the presence and severity of IVD degeneration, the presence of SN and for the presence of CEP defects. SN and IVD degeneration were confirmed by assessing T2W images and IVD degeneration was graded according to the Schneiderman classification. CEP defects were defined as discontinuity of high signal over 4 consecutive images and were independently assessed by two raters. Results: Analyses of CEP defects between IVD degeneration and SN were performed separately. For the study of CEP defects and IVD degeneration, subjects with SN were excluded. 37 out of 108 (34.3%) CEPs had defects, which mainly occurred at T12/L1, L1/L2 and L4/L5 (p=0.008). Inter-rater reliability was substantial (Kappa statistic= 0.67, p<0.001). Multivariate logistic regression revealed that lower BMI (p=0.009) and younger (p=0.034) individuals had a decreased likelihood of having CEP defects. A statistically significant association was found to exist between the presence of cartilaginous endplate defects and intervertebral disc degeneration (p=0.036). Degenerated discs with CEP defects were found in L4/5 and L5/S1, while degenerated discs with no CEP defects were found throughout the whole lumbar region. Mean degeneration scores of L4/5 and L5/S1 levels with CEP defects were higher than that of L4/5 and L5/S1 levels without. For the study of CEP defects and SN, with all 22 subjects assessed, 125 out of 264 (47.3%) CEPs had defects. 40 SN were found, and among those, 35 SN had CEP defects (87.5%). 125 CEPs had the presence of CEP defects; among them, a large number of CEP defects did not have SN underneath (92 out of 125, 73.2%). Conclusion: The studies demonstrate the feasibility of using UTE MRI in live humans to assess the integrity of the CEP. Longitudinal studies may reveal the diagnosis of CEP defects to be clinically beneficial for assessment of IVD degeneration and SN.
published_or_final_version
Diagnostic Radiology
Master
Master of Philosophy

Resumo Este trabalho encontra-se dividido em três capítulos distintos. No primeiro, é caracterizada a doença degenerativa lombar, demorando-se o autor na descrição pormenorizada das alterações anatómicas, biomecânicas, e bioquímicas inerentes à sua ocorrência. Segue-se a descrição da evolução das diferentes formas de terapêutica, enumerando as que de forma clássica mais frequentemente são utilizadas (cirúrgicas e não cirúrgicas). No segundo capítulo, são referidos os mais recentes avanços tecnológicos nesta área, mencionando, nas suas vertentes biomecânicas, clínicas e terapêuticas, as particularidades das estabilizações dinâmicas interespinhosas e pediculares, bem como da artroplastia de disco. Após esta longa introdução, inicia-se o terceiro capítulo no qual se apresenta um estudo prospectivo da avaliação clínica, funcional, imagiológica e da variação da densidade mineral óssea vertebral em 20 doentes com patologia degenerativa, tratados com sistemas de estabilização dinâmica semi-rígida interespinhosa, e seguidos durante dois anos. Do estudo realizado conclui-se que os sistemas referidos são eficazes clínica e funcionalmente no tratamento de doentes com doença degenerativa lombar. Mais ainda, estes instrumentais proporcionam um aumento da altura do disco confirmado na incidência radiográfica de perfil no nível instrumentado. Constatámos ainda que a densidade mineral óssea vertebral dos doentes intervencionados, avaliada com sistema DXA, não demonstra diferenças com significância estatística ao longo do tempo, omparativamente à determinada em idêntica população mas sem qualquer patologia lombar. Acresce que se obteve uma correlação entre a funcionalidade física e a BMD radial, com significância estatística crescente nas duas medições realizadas. Abstract This study is divided in three different chapters. In the first one the author describes the anatomical, biomechanical and biochemical changes that go along with degenerative lumbar spine disease. The therapeutically possibilities are mentioned, mainly with the classic fusion and decompression as well as the non surgical options. Then, in the second chapter, the author describes, from the biomechanical, clinical and therapeutically point of view, the new techniques of dynamic stabilization, interspinous and pedicular systems, as well as disc replacement. After this introduction, in the third chapter a prospective clinical, functional, imagiologic and vertebral bone mineral density variation study is presented. Twenty patients with degenerative lumbar spine disease are selected, and operated with a semi rigid interspinous system device, and followed for a two year period. The author concludes that the interspinous semi rigid systems were clinically and functionally effective in lumbar degenerative patients. It was also founded that the disc height at the implant segment level increased after surgery. Bone density was assessed with a DXA system device. As far as vertebral bone density is concerned, the author found no differences what so ever inside the group during the study, or to an identical control group without any lumbar pathology. The correlation study between the BMD and physical function showed that there was only significant statistically data in radial BMD measurement, and this happened with growing correlation from year 2006 to 2007.

[EN] The World Health Organization estimates that in 2010 there were 285 million people visually impaired in the world. It is calculated that the 80\% of these cases are preventable or treatable. In addition, aging population and chronic disease increase are two factors that predict a higher number of blindness cases in the future. Hypertension, diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the most common pathologies in the current society that provoke retinal damage and can be directly related to blindness and vision loss. The early diagnosis of these diseases allows, through appropriate treatment, to reduce costs generated when they are in advanced states and may become chronic. This fact justifies screening campaigns. However, a screening campaign requires a heavy workload for trained experts in the analysis of anomalous patterns of each disease, which in addition to the increase of population at risk, makes these campaigns economically unfeasible. Therefore, the need of automatic screening system developments is highlighted. The final goal of this thesis is the implementation of novel methods that allow the analysis and processing of fundus images to implement an automatic screening of four of the most important diseases that affect world population. In particular, the main objective of the thesis is to build up algorithms for the characterization of the retinal structures and the retina background in order to assist in the discrimination between a ``normal" and pathological retina. Mathematical morphology along with other operators are used for the detection of the retinal vessels and the optic disk. The proposed methods work properly on databases with a large degree of variability. Not only have the main structures been segmented, but significant features have also been extracted from them to be used in a computer aided diagnosis software for hypertensive risk determination. The texture of the retina background is also analyzed in this work by means of local binary patterns with the aim of identifying DR and AMD and avoiding the need of segmentation of the characteristic retinal lesions of each disease. The results are promising above all for AMD diagnosis.
[ES] La Organización Mundial de la Salud estima que en 2010 había 285 millones de personas con alguna discapacidad visual en el mundo. Se calcula que el 80\% de estos casos son evitables o tratables. Además, el envejecimiento de la población y el aumento de las enfermedades crónicas son dos factores que hacen prever un número todavía mayor de casos de ceguera en el futuro. La hipertensión, la retinopatía diabética (RD), la degeneración macular asociada a la edad (DMAE) y el glaucoma son las enfermedades más comunes que provocan daños en la retina y, por tanto, están directamente relacionadas con la ceguera y con la pérdida de visión. El diagnóstico de estas enfermedades en estadios tempranos permite, mediante el tratamiento adecuado, reducir los costes que generan en estados ya avanzados y que en la mayoría de los casos acaban convirtiéndose en crónicas, lo que justifica la realización de campañas de cribado. Sin embargo, una campaña de cribado exige una gran carga de trabajo de personal experto entrenado en el análisis de los patrones anómalos propios de cada enfermedad, lo que sumado al aumento de la población de riesgo, hace que estas campañas sean inviables económicamente. Por lo tanto, se evidencia la necesidad del desarrollo de sistemas de cribado automáticos. El objetivo final del presente trabajo es la implementación de métodos novedosos de análisis de imágenes de fondo de ojo para usarlos en un sistema de cribado de cuatro de las enfermedades más importantes que afectan a la población actual. En concreto, el objetivo principal de la tesis es el desarrollo de algoritmos para la caracterización de las estructuras y del fondo retiniano, los cuales servirán de ayuda para discriminar una retina ``normal" de otra patológica. Para la detección de los vasos retinianos y del disco óptico, se ha usado morfología matemática además de otros operadores. Se ha demostrado que los métodos propuestos para este fin funcionan adecuadamente en bases de datos con un alto grado de variabilidad. No sólo se han segmentado las principales estructuras retinianas, sino que, además, se han extraído sus características más significativas para determinar el riesgo hipertensivo. En este trabajo, también se han analizado las texturas presentes en el fondo de la retina por medio de la teoría de los patrones binarios locales con el objetivo de identificar la RD y la DMAE a la vez que se evita la necesidad de la segmentación de las lesiones específicas de cada enfermedad. Los resultados son prometedores, sobre todo, para la detección de la DMAE.
[CAT] L'Organització Mundial de la Salut estima que en 2010 havia 285 milions de persones amb alguna discapacitat visual en el món. Es calcula que el 80\% d'aquests casos són evitables o tractables. A més, l'envelliment de la població i l'augment de les malalties cròniques són dos factors que fan preveure un número encara major de casos de ceguera en el futur. La hipertensió, la retinopatia diabètica (RD), la degeneració macular associada a l'edat (DMAE) i el glaucoma són les malalties més comuns que provoquen danys en la retina i, per tant, estan directament relacionades amb la ceguera i amb la pèrdua de visió. El diagnòstic d'aquestes malalties en estadis primerencs permet, per mitjà del tractament adequat, reduir els costos que generen en estats ja avançats i que en la majoria dels casos acaben convertint-se en cròniques, la qual cosa justifica la realització de campanyes de garbellament. No obstant això, una campanya de garbellament exigix una gran càrrega de treball de personal expert entrenat en l'anàlisi dels patrons anòmals propis de cada malaltia, que si es suma a l'augment de la població de risc, fa que aquestes campanyes siguen inviables econòmicament. Per tant, s'evidencia la necessitat del desenrotllament de sistemes de garbellament automàtics. L'objectiu final del present treball és la implementació de mètodes nous d'anàlisi d'imatges de fons d'ull per a usar-los en un sistema de garbellament de quatre de les malalties més importants que afecten la població actual. En concret, l'objectiu principal de la tesi és el desenvolupament d'algoritmes per a la caracterització de les estructures i del fons retinià, els quals serviran d'ajuda per a discriminar una retina ``normal" d'una altra patològica. Per a la detecció dels vasos retinians i del disc òptic, s'ha usat morfologia matemàtica a més d'altres operadors. S'ha demostrat que els mètodes proposats per a aquest fi funcionen adequadament en bases de dades amb un alt grau de variabilitat. No sols s'han segmentat les principals estructures retinianes, sinó que, a més, s'han extret les seues característiques més significatives per a determinar el risc hipertensiu. En aquest treball, també s'han analitzat les textures presents en el fons de la retina per mitjà de la teoria dels patrons binaris locals amb l'objectiu d'identificar la RD i la DMAE al mateix temps que s'evita la necessitat de la segmentació de les lesions específiques de cada malaltia. Els resultats són prometedors, sobretot, per a la detecció de la DMAE.
Morales Martínez, S. (2015). Fundus characterization for automatic disease screening through retinal image processing [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/53933
TESIS

The chorda tympani nerve, also known as the taste nerve, runs uncovered through the middle ear cavity, a localization that exposes the nerve to pathological processes and surgical trauma in the middle ear. People operated on for otosclerosis tend to complain more about postoperative taste disturbances than those operated on for chronic otitis media. It has been suggested that this difference may be explained by gradual deterioration of chorda tympani nerve function caused by chronic otitis media infection and that further impairment caused by surgery is less noticeable in these patients. This thesis aimed to evaluate the function of the chorda tympani nerve, the effects of middle ear disease on taste and complications resulting from ear surgery for chronic otitis media or otosclerosis. This information will help to improve the ear surgeon’s ability to predict the prognosis of iatrogenic taste disturbances in patients with middle ear disease and after ear surgery. Taste was assessed using electrogustometry and the filter paper disc method before and after surgery for chronic otitis media or otosclerosis. Patients also completed questionnaires about symptoms and quality of life. The status of the chorda tympani nerve upon surgical opening of the ear and grading of the trauma to the nerve during the surgery were recorded. The ultrastructure of the chorda tympani nerve from healthy ears and from ears with chronic otitis media was examined. Electrogustometry and the filter paper disc method were evaluated. The results of electrogustometry and the filter paper disc method were highly reproducible, although their correlation was moderate. Patients with chronic otitis media, patients with a more traumatized nerve, female patients and younger patients were more likely to report postoperative taste disturbances. Most of the patients recovered their taste after 1 year. The quality of life study showed only minor changes after surgery. Electron microscopic observations of nerves from ears with chronic otitis media showed signs of structural degeneration, although signs of regeneration, such as sprouting were also observed. This results may explain the recovery of taste postoperatively and indicate that the nerve should be carefully handled during surgery.

Introduction: A computer-based classification system is proposed for the characterization of cervical intervertebral disc degeneration from saggital magnetic resonance images. Materials and methods: Cervical intervertebral discs from saggital magnetic resonance images where assessed by an experienced orthopaedist as normal or degenerated (narrowed) employing Matsumoto’s classification scheme. The digital images where enhanced and the intervertebral discs which comprised the regions of interest were segmented. First and second order statistics textural features extracted from thirty-four discs (16 normal and 16 degenerated) were used in order to design and test the classification system. In addition textural features were calculated employing Laws TEM images. The existence of statistically significant differences between the textural features values that were generated from normal and degenerated discs was verified employing the Student’s paired t-test. A subset with the most discriminating features (p<0.01) was selected and the Exhaustive Search and Leave-One-Out methods were used to find the best features combination and validate the classification accuracy of the system. The proposed system used the Least Squares Minimum Distance Classifier in combination with four textural features with comprised the best features combination in order to classify the discs as normal or degenerated. Results: The overall classification accuracy was 93.8% misdiagnosing 2 discs. In addition the system’s sensitivity in detecting a narrow disc was 93.8% and its specificity was also 93.8%. Conclusion: Further investigation and the use of a larger sample for validation could make the proposed system a trustworthy and useful tool to the physicians for the evaluation of degenerative disc disease in the cervical spine.
Σκοπός: Η στένωση των μεσοσπονδύλιων δίσκων της αυχενικής μοίρας, ως κύρια έκφραση εκφυλιστικής νόσου, είναι μια από τις σημαντικότερες αιτίες πρόκλησης πόνου στην περιοχή του αυχένα. Στην κλινική πράξη η αξιολόγηση της στένωσης γίνεται μέσω μέτρησης του μεσοσπονδύλιου διαστήματος, σε διάφορες απεικονίσεις της αυχενικής μοίρας του ασθενούς. Στην παρούσα εργασία προτείνεται μια υπολογιστική μέθοδος ανάλυσης εικόνας, για την αυτοματοποιημένη εκτίμηση της στένωσης από εικόνες μαγνητικής τομογραφίας. Υλικό και Μέθοδος: Μελετήθηκαν 34 μεσοσπονδύλιοι δίσκοι από οβελιαίες τομές μαγνητικής τομογραφίας της αυχενικής μοίρας, οι οποίες ελήφθησαν με χρήση Τ2 ακολουθίας. Η στένωση των μεσοσπονδύλιων δίσκων αξιολογήθηκε από έμπειρο ορθοπαιδικό βάσει της κλίμακας Matsumoto. Οι δίσκοι χωρίστηκαν σε δύο κατηγορίες: (α) 16 φυσιολογικοί και (β) 16 δίσκοι που παρουσίαζαν στένωση. Με χρήση διαδραστικού περιβάλλοντος επεξεργασίας εικάνας καθορίστηκε το περίγραμμα των μεσοσπονδύλιων δίσκων οι οποίοι αποτελούν τις προς ανάλυση περιοχές ενδιαφέροντος (Π.Ε.). Σε κάθε Π.Ε. εφαρμόστηκαν αλγόριθμοι εξαγωγής χαρακτηριστικών υφής. Συγκεκριμένα υπολογίστικαν χαρακτηριστικά υφής από στατιστικά πρώτης και δεύτερης τάξης καθώς και χαρακτηριστικά από τα μέτρα ενέργειας υφλης κατλα Laws. Τα παραπάνω χαρακτηριστικά, ποσοτικοποιούν διαγνωστικές πληροφορίες της έντασης του σήματος της Π.Ε. και συσχετίζονται με τη βιοχημική σύσταση των απεικονιζόμενων δομών. Τα εξαχθέντα χαρακτηριστικά υφής αξιοποιήθηκαν για τη σχεδίαση του ταξινομητή ελάχιστης απόστασης ελαχίστων τετραγώνων, ο οποίος χρησιμοποιήθηκε για το διαχωρισμό μεταξύ φυσιολογικών δίσκων και δίσκων που παρουσίαζαν στένωση (εκφυλισμένων). Αποτελέσματα: Η ακρίβεια της ταξινόμησης φυσιολογικών και εκφυλισμένων μεσοσπονδύλιων δίσκων ανήλθε σε 93.8%. Η ευαισθησία καθώς και η ειδικότητα της μεθόδου, σε ότι αφορά την ανίχνευση εκφυλισμένων δίσκων, είναι επίσης 93.8%. Συμπέρασμα: Με δεδομένο το μικρό μέγεθος του δείγματος που χρησιμοποιήθηκε για το σχεδιασμό της μεθόδου, απαιτούνται περετέρω εργασίες πιστοποίησης της ακρίβειας ταξινόμησης, προκειμένου η μέθοδος αυτή να αξιοποιηθεί από ακτινολόγους και ορθοπαιδικους, ως βοηθητικό διαγνωστικό εργαλείο.

碩士
國立臺灣科技大學
機械工程系
101
Fusion has been the gold standard treatment for treating the disc degeneration. Many clinical studies have showed that adjacent segment degeneration was observed in patients over time. In order to overcome problems with fusion devices, dynamic stabilization systems are being used to treat disc degeneration related problems. Recently it’s began to combine fusion and non-fusion techniques in the treatment of multi-segmental Degenerative disc disease (DDD). It is hybrid dynamic stabilization designed to promote a balance of stability and adjacent segment degeneration. However, no report investigated whole spine motion and the segment adjacent to the hybrid dynamic stabilization. The purpose of this study was to investigate how different treatment methods influence the biomechanics of adjacent segment and which one is the best treatment of hybrid dynamic stabilization. A 3-D nonlinear finite element model of the T11-S1 lumbar spine was used to evaluate biomechanics of various device including rigid rod, semi-rigid rod, Dynesys and hybrid stabilization systems inserted at level L4/L5 in comparison with intact spine. Mild disc degeneration was simulated at L4-L5 level. The loading cases of flexion, extension, lateral bending and axial rotation were simulated. Intersegmetal rotation, disc stresses and screw stresses were calculated at implant level and at the adjacent level. Compared to an intact spine, a dynamic implant reduced inter-segmental rotation at implant level, decreased disc stresses and at implant level. With a rigid implant, these effects are more pronounced. Screw stresses were generally higher in a rigid fixator than in a dynamic implant. The rigid implant had more effect than dynamic implant at the adjacent level. With the hybrid stabilization systems, our results indicated that where the dynamic implant placed superior to the rigid fixator inserted at degenerative disc level was the better treatment.

abstract: Intervertebral Disc Degeneration (IVDD) is a complex phenomenon characterizing the desiccation and structural compromise of the primary joint in the human spine. The intervertebral disc (IVD) serves to connect vertebral bodies, cushion shock, and allow for flexion and extension of the vertebral column. Often presenting in the 4th or 5th decades of life as low back pain, this disease was originally believed to be the result of natural “wear and tear” coupled with repetitive mechanical insult, and as such most studies focus on patients between 40 and 50 years of age. Research over the past two decades, however, has demonstrated that environmental factors have only a modest effect on disc degeneration, with genetic influences playing a much more substantial role. Extensive research has focused on this process, though definitive risk factors and a clear pathophysiology have proven elusive. The aim of this study was to assemble a cohort of patients exhibiting definitive signs of degeneration who were well below the average age of presentation, with minimal or no exposure to suspected environmental risk factors and to conduct a targeted genome analysis in an attempt to elucidate a common genetic component. Through whole genome sequencing and analysis, the results corroborated findings in a previous study, as well as demonstrated a potential connection and influence between mutations found in IVD structural or functional genes, and the provocation of IVDD. Though the sample size was limited in scale and age, these findings suggest that further IVDD research into the association of variants in collagen, aggrecan and the insulin-like growth factor receptor genes of young patients with an early presentation of disc degeneration and minimal exposure to suspected risk factors is merited.
Dissertation/Thesis
Masters Thesis Biology 2016

碩士
國立臺灣科技大學
應用科技研究所
105
Fusion has been the gold standard treatment for treating lumbar degenerative disc disease. Many clinical studies have demonstrated that adjacent segment degeneration was observed in patients over time. Various instrumentations of stabilization systems have been investigated using numerical approaches. However, numerical models developed in the past were simplified to reduce computational time or compare a few different stabilization systems. The aim of this study was to evaluate and to compare the biomechanical performance of different spinal fixation systems as pedicle screw and rod system, translaminar facet screw system, transfacet pedicle screw system, and Coflex system using a more realistic numerical model. Three-dimensional nonlinear finite element models of the T10-S1 multilevel spine with various posterior instrumentations were developed. The intersegmental rotation, the maximum disc stress, and the maximum implant stress were calculated. The results indicated that pedicle screw and rod system had the greatest stability but also a greater risk of adjacent segment failure. The biomechanical performance of Coflex system was closer to that of the intact spine model compared with pedicle screw and rod system, translaminar facet screw system, and transfacet pedicle screw system. The results of this study could help surgeons understand the biomechanical characteristics of different posterior instrumentations for the treatment of lumbar degenerative disc diseases

碩士
國立陽明大學
醫學工程研究所
100
The low intensity plus ultrasound (LIPUS) is forms of physical stimulations, ultrasound have been found to be effective non-invasive treatments for bone healing and tissue repair in clinical. Despite the efficacy exhibited in clinical application, molecular evidence of ultrasound therapeutic effects and biochemical mechanisms on intervertebral disc remain limited. The therapeutic effects of ultrasound could be explained by a propagation of acoustic waves that transfers mechanical energy into tissues. The mechanical forces could serve as extracellular information, which may induce certain intracellular signaling pathway and regulate cell growth, function and differentiation. In this study, the aim is elucidate the effects of physical stimulations on annulus fibrosus cells (AF) mechanotransduction and regulation of extracellular matrix metabolisn in vitro. First, we investigate the effects of ultrasound on cultured AF cell and the molecular and biochemical mechanisms by which ultrasound promote AF cell proliferation and regulate extracellular matrix metabolism. Next, we investigate mechanotransduction pathways of AF cell, and crosstalk mechanisms between transforming growth factor-β (TGF-β) and ultrasound stimulation during mechanotransduction. In this study, the best parameters of ultrasound was treat by 0.5W/cm2 for 5 min for 5 days. The result shows that the cell viability and total GAGs contents has significantly enhanced after treatment, and, the transforming growth factor beta1 (TGF-β1) also activited . Therefore, the synthesis of collagen type I content was increased, otherwise, matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13) decreased. Furthermore, ultrasound induces Extracellular signal-regulated kinases (ERK) pathway, which doesn’t relate on cell viability. This study revealed that ultrasound stimulation regulates extracellular matrix metabolism through the crosstalk between TGF-β and ultrasound-induced mitogen-activated protein kinases (MAPKs) signaling pathways. Physical stimulus induced the synthesis and release of transformation growth factor-β1, which plays an important role in the synthesis of extracellular matrix catabolism, and the present experimental results show that ultrasound stimulation can indeed enhance the repair of the annulus fibrosus cells.

碩士
國立成功大學
土木工程學系
103
There are two methods for the treatment of cervical degenerative disc disease; fusion surgery and non-fusion surgery. In fusion surgery, operating segment motion of intervertebral disc is restricted. It leads to adjacent segment increasing motion, thereby accelerating degeneration of adjacent segment. Therefore, non-fusion surgery is increasingly important. However, studies have pointed out that the degeneration of adjacent segments may be related to pre-existing degeneration before fusion surgery. Therefore, this study will investigate the reason of whether the adjacent segments cause degeneration, the adjacent segments with pre-existing degeneration before fusion surgery. And also explore the biomechanics of operating and adjacent segment on different methods of surgical treatment. In this study, we use finite element method by ABAQUS, which is finite element analysis software, to analyze cervical degenerative disc disease. And reducing Young's modulus of the annulus fibrosus to simulate degeneration. Operating segment is set in the fifth and sixth cervical disc (C56) which occurs problem frequently and implanted cage or total disc replacement (TDR).Then degenerative segment is set in 4th and 5th cervical disc. Finally, the research said that the treatment of using TDR is better than cage. For one thing, TDR can provide operating segment certain motion; for another, it can reduce the burden on the adjacent segment, but need to concern about the influence of facet joint on operating segment. The more serious degree of degeneration of the degenerative segment, the larger impact of postoperative. It will accelerate adjacent segment degeneration and increase the opportunity of the second surgery. Especially the cage insertion is more obvious.

碩士
高雄醫學大學
醫學研究所-臨床醫學組
102
Objectives: Over the past decade, spinal arthrodesis with or without instrumentation has become a common technique for multilevel lumbar degenerative disc disease. However, evidence is growing that fusion may in fact have undesirable long-term effects on the remainder of the spine, particularly on the immediately adjacent motion segments. The severity of degeneration and instability in multilevel lumbar degenerative disc disease varies widely. Thus, a concept of dynamic or non-fusion stabilization or hybrid technique (segment-by-segment stabilization using dynamic stabilization and fusion) of the lumbar spine is emerged. The objective of this study was to evaluate the clinical outcome and kinematic changes in bridged and adjacent segments of patients with multilevel lumbar degenerative disc disease treated using this segment-by-segment application of the interspinous device for segmental dynamic stabilization( Coflex™ ) in upper segment level as a non-fusion device and in lower segment level with a posterior lumbar interbody fusion. Methods: This study analyzed 46 patients who had received posterior lumbar interbody fusion with posterior dynamic stabilization fixation for spondylolisthesis with adjacent level stenosis between Oct, 2010 and Dec, 2011. All patients were followed up for at least 2 years. Clinical characteristics were then retrospectively reviewed. The visual analog scale (VAS) was used to score both lower-limb pain and back pain. Patient functioning was evaluated using the Oswestry Disability Index (ODI). Results: The sample included 32 females and 14 males with a mean age of 63.4 ± 10.9 years . Mean follow-up time was 30.6 months (range 25–38 months). Preoperative Oswestry disability index (ODI), back- and leg-pain scores (VAS) were compared to postoperative status. Fusion success and system failure were assessed by an independent reviewer who analyzed AP and lateral X-rays. Back pain improved from 7.24±1.23 to 2.24±1.78 (p< 0.00003), leg pain from 7.03±1.64 to 2.58±1.5 (p< 0.0006), and ODI from 53.68±14.34% to 24.37±13.2% (p< 0.00005). Analyses of adjacent segment motion after surgery showed significant increases inneutral lordotic curves (p<0.001). Whereas the adjacent segment tended to show flextion hypermobility but limited extension, ROM measured in the bridged segment before and after surgery did not significantly change. Conclusion: A hybrid dynamic interspinous stabilization(Coflex™ ) with interbody fusion system for treating multilevel degenerative lumbar disc disease improves clinical outcomes, enables successful interbody fusion, and maintains range of motion (ROM) in the bridged segment. It limits the hypermobility in the adjacent segment, especially from neutral to extension. Further in vivo and in vitro experiments to if this system could prevent adjacent segment degeneration are needed.

Degenerative Veränderungen der Lendenwirbelsäule beginnen bereits im Alter von unter 20 Jahren und betreffen vor allem die unteren 3 Bewegungssegmente. Die degenerativen Veränderungen an der Bandscheibe gehen mit einer Kalzifizierung der Grund- und Deckplatten der Wirbelkörper einher, was zu einer Reduktion der Nährstoffversorgung der Bandscheibe und damit zu einem Untergang der matrixbildenden Zellen und konsekutiv zu einem Flüssigkeitsverlust in der Bandscheibe führt. Als Folge nimmt die Belastung der Bandscheibe weiter ab. Die aktuellen Therapieoptionen umfassen sowohl die konservative als auch die operative Therapie, wobei allerdings nur die Folgen der Degeneration behandelt werden. Ziel einer Zelltransplantation ist es, der Bandscheibe wieder matrixbildende Zellen zur Verfügung zu stellen, damit die nutritiven Veränderungen auszugleichen und eventuell reversibel zu machen. Dieser Effekt konnte im Tierversuch nachgewiesen werden, woraufhin eine klinische Studie initiiert wurde. Im Rahmen der publizierten klinischen prospektiven, randomisierten Studie konnte gezeigt werden, dass die Transplantation autologer Chondrozyten, die bei einer notwendigen operativen Therapie eines sequestrierten Bandscheibenvorfalls gewonnen wurden, einen sowohl klinisch als auch bildmorphologisch positiven Effekt auf die degenerierten Bandscheiben hat. Es kam zu einer signifikanten Reduktion der Schmerzsymptomatik und einer Steigerung der Lebensqualität in der Gruppe der transplantierten Patienten. Die Bandscheibenhöhe zeigt sich stabil über den Beobachtungszeitraum von 2 Jahren.

Posterior lumbar spinal dynamic stabilisation devices are intended to relieve the pain of spinal segments while prolonging the lifespan of adjacent intervertebral discs. This study focuses on the design of such a device, one that has the correct stiffness to stabilise the spinal segment by the correct amount. An initial literature survey covers contemporary topics related to the lumbar spine. Included topics are lumbar anatomy and kinematics, pathology of degenerative disc disease and treatment thereof, other spinal disorders such as spondylolisthesis and spinal stenosis, as well as the complications associated with lumbar dynamic stabilisation. The influence of factors such as fatigue and wear, as well as the properties of appropriate biomaterials are considered when determining the basis of the device design and development. Stabilising the spinal segment begins with correct material selection and design. Various designs and biomaterials are evaluated for their stiffness values and other user requirements. The simplest design, a U-shaped spring composed of carbon fibre-reinforced poly-ether-ether-ketone (CFR-PEEK) and anchored by polyaxial titanium pedicle screws, satisfies the most critical user requirements. Acceptable stiffness is achieved, fatigue life of the material is excellent and the device is very imaging-friendly. Due to financial constraints, however, a simpler concept that is cheaper and easier to rapid prototype was chosen. This concept involves a construct primarily manufactured from the titanium alloy Ti6Al4V extra-low interstitial (ELI) and cobalt-chrome-molybdenum (CCM) alloys. The first rapid prototype was manufactured using an additive manufacturing process (3D-printing). The development of the device was performed in three main stages: design, verification and validation. The main goal of the design was to achieve an acceptable stiffness to limit the spinal segmental range of motion (ROM) by a determined amount. The device stiffness was verified through simple calculations. The first prototype’s stiffness was validated in force-displacement tests. Further validation, beyond the scope of this study, will include fatigue tests to validate the fatigue life of the production-ready device.
MIng (Mechanical Engineering), North-West University, Potchefstroom Campus, 2014

碩士
國立成功大學
土木工程學系
102
Human’s intervertebral disc will degenerate as time goes by. The nucleus pulposus in disc will be crushed and protrudes through the annulus fibrosus and pressure to the Ligament. This disease which called” Degenerative Disc Disease，DDD”.Traditional intervertebral disc surgery is using cage or anterior plate.But generally considere that spinal fusion surgery will cause the degeneration of adjacent segment. So in recent years,the invention of artificial disc attempt to prevent the degeneration of adjacent segment.This research discuss multisegmental cervical degenerative disease treated by artificial disc,cage,and plate.Trying to find case that can reduce the influence of adjacent segment.This research use finite element method to simulate human,and using finite analysis software ABAQUS. All in all,we found that artificial disc in C56 will reduce the influence of adjacent segment,and plate prefer to place at C34. Detailed description in chapter 4.

Bibliography: leaves 102-116.
116, [43] leaves, [51] leaves of plates : ill. (some col.) ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Analyses the characteristics and relative incidence of annular defects in the human lumbar spine and investigates their role in the pathogenesis of invertebral disc degeneration.
Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1992

博士
國立臺灣大學
職業醫學與工業衛生研究所
103
Background and Objective: Lumbar disc degeneration (LDD) has been related to heavy physical loading. However, the quantification of the exposure has been controversial and the dose-response relationship with the LDD has not been established. It is also unclear whether a specific threshold value exists in each lifting load, the accumulation above which best predicts lumbar disc protrusion, or on the other hand, all lifting load should be accumulated. In a clinical setting, the radiographic diagnosis of disc condition typically requires magnetic resonance imaging (MRI), which is less readily available than plain radiograph is in most primary care facilities. If the relationship between reduced disc height and disc bulging or protrusion was existed, useful insight can be obtained to guide further direction of patient evaluation. The purposes of this study are to investigate the dose-response relationship between lifetime cumulative lifting load and LDD; to determine the optimal threshold value of lumbar compression load in each lifting, which allowed for best prediction for disc protrusion while lifetime cumulative load was calculated; and to determine the association between disc morphology and disc bulging or protrusion. Method: This is a cross-sectional study. Every participant received assessments with a questionnaire, MRI of the lumbar spine and lumbar disc compression load. MRI assessments included disc dehydration, annulus tear, disc height narrowing, bulging, protrusion, extrusion, sequestration, degenerative and spondylolytic spondylolisthesis, foramina narrowing, and nerve root compression on each lumbar disc level. The compression load was predicted by a biomechanical software system. We sum up all lifting exposure to the calculation for examining the association between lifetime cumulative lifting load and LDD; and sum up only lifting load greater than proposed thresholds for determining the optimal threshold value of lumbar compression load in each lifting .For accumulation above different thresholds, predictive capabilities for disc protrusion were compared using four statistical values, (1) Area under the curve of a receiver operating characteristic curve, (2) R2, (3) Akaike information criterion, and (4) Bayesian information criterion. The intervertebral disc height and disc depth were measured. Logistic regression analysis was applied to identify the association between anthropometric factors, disc morphology factors, and disc bulging/protrusion. Model 1 was constructed using anthropometric variables to investigate the capacity for predicting disc bulging/protrusion. Model 2 was constructed using anthropometric variables and disc morphology variables. The ability of the models to discriminate between participants with and without disc bulging/protrusion was evaluated using a receiver operating characteristic curve. Result: A total of 553 participants were recruited in this study and categorized into tertiles by cumulative lifting load, i.e., <4.0 × 105, 4.0 × 105–8.9 × 106, and >= 8.9 × 106 Newton× hours. The risk of LDD increased with cumulative lifting load. The best dose-response relations was found at the L5–S1 disc level, in which high cumulative lifting load was associated with elevated odds ratios of 2.5 (95% CI 1.5–4.1) for dehydration, and 4.1(95% CI 1.9–10.1)for disc height narrowing comparing to low lifting load. Participants exposed to intermediate lifting load had increased odds ratios of 2.1(95% CI 1.3–3.3) for bulging comparing to low lifting load. The tests for trend were significant. For men, 3000 Newton for each lifting task was the optimal threshold value for predicting L4-S1 disc protrusion, whereas for women, 2800 Newton was optimal. Total of 452 MRI scans were analyzed for the morphology study. Age, body weight, body height, disc height, and disc depth were significantly associated with disc bulging/protrusion. The area-under-the-curve (AUC) statistics of Model 2 were significantly better than Model 1 at the L3-L4 (p<.05) and L4-L5 level (p<.05) but not at the L5-S1 level. Conclusions: The results suggest a dose-response relationship between cumulative lifting load and LDD. Cumulative lifting load predicted L4-S1 disc protrusion best when the threshold value was set at 3000 Newton for men, and 2800 Newton for women. The results showed an association between disc morphology and disc bulging/protrusion at the L3-L4, L4-L5, and L5-S1 level. We also developed a model by using anthropometric factors and disc morphology to predict disc bulging/protrusion.

碩士
國立陽明大學
解剖學及細胞生物學研究所
103
In the past, the study of Lumbar Disc Degeneration Disease (DDD) are always use the patient with DDD vertebrae compared with normal people, but this kind of clinical researches already have very amount of results and data in now existing medical knowledge, and these studies have been frequently cited as the basis for the diagnosis and determine the extent of DDD. The other issue is the relationship between DDD and disc prolapse（DP）.

T1rho弛豫是旋轉坐標系中的自旋晶格弛豫，它決定橫向磁化向量在存有自旋鎖定射頻脈衝情況下的衰減，自旋鎖定脈衝與橫向磁化向量同向。T1rho磁共振成像對於低頻運動過程敏感，故可研究水與其周大分子物質環境間的交互作用，有鑒別組織內早期生化改變的潛力。
衰老與慢性高血壓是常見腦退行性疾病的兩個主要危險因素。但是正常腦衰老過程及慢性高血壓兩個因素與腦組織T1rho是否有相關性，尚缺乏研究。序貫性測量SD老鼠自5至15月齡、WKY（血壓正常）和SHR（患有自發性高血壓）老鼠自6至12月齡的雙側丘腦、海馬、和皮質的腦組織T1rho值。發現三組老鼠的丘腦、海馬及皮質的T1rho均隨年齡增長而增高；且SHR的顯著高於WKY老鼠。
T1rho值與椎間盤退變等級的相關性已有報導。但相比T2值，T1rho在評價椎間盤退變方面是否優於或如何優於T2值尚缺乏研究。將椎間盤髓核及纖維環的T1rho和T2值與5級和8級椎間盤退變等級系統做比較；發現髓核的T1rho及T2與椎間盤退變等級的相關性均呈二次函數降低，且無顯著差別(P=0.40)。纖維環的T1rho及T2與椎間盤退變等級的相關性呈線性函數降低，T2降低的斜率明顯比T1rho降低的斜率要平坦(P<0.001)。故T1rho值比T2值更加適合評價纖維環退變，而兩者在評價髓核時相似。
肝纖維化是幾乎所有慢性肝病的常見特徵，包括大分子物質在細胞外基質的沉積。選用四氯化碳CCl4腹腔注射6周來製造肝纖維化模型。肝臟T1rho在注射後的第二天輕度上升，然後持續上升，直到注射六周後T1rho達最高值，此後T1rho隨CCl4注射停止而降低。顯示T1rho磁共振成像對於監測慢性注射CCl4誘導的肝纖維化及肝損傷有價值。當沒有明顯肝纖維化時，肝T1rho輕微受水腫及急性炎症的影響。
為將肝臟T1rho磁共振成像轉化到臨床使用，我們研究了其可行性，以及正常志願者肝臟T1rho值分佈範圍。發現採用六個自旋鎖定時間來測量健康志願者肝T1rho，結果有較高的可重複性和一致性，肝T1rho平均值為42.5ms，分佈範圍為38.8到46.5ms。採用三個自鎖鎖定時間點掃描，可以減少一半掃描時間，且可以得到可信的肝T1rho值，但採用兩個自旋鎖定時間點則不行。
T1rho relaxation is spin-lattice relaxation in the rotating frame. It determines the decay of the transverse magnetization in the presence of a spin-lock radiofrequency pulse, which applied along the transverse magnetization. T1rho MRI is sensitive to low frequency motional processes, so it can be used to investigate the interaction between water molecules and their macromolecular environment. T1rho imaging is suggested to have the potential to identify early biochemical changes in tissues.
Aging and chronic hypertension are two major risk factors for common neurodegenerative disease. However, whether normal brain aging and chronic spontaneous hypertensive are associated with brain T1rho values changes were not reported. We longitudinally measured the T1rho value in rat brain of Sprague-Dawley (SD) rats from 5-month to 15-month, and spontaneous hypertensive rats (SHR) with Wistar Kyoto (WKY) rats from 6-month to 12-month. The T1rho values in three brain regions of thalamus, hippocampus, and cortices increased with aging process, and were significantly higher in SHR than WKY rats.
For intervertebral disc, the correlation between T1rho and degenerative grade has been reported. However, whether and how T1rho specifically offer better evaluation of disc degeneration compared with T2 was not studied previously. T1rho and T2 value of nucleus pulposus (NP) and annulus fibrosus (AF) was compared with reference to the five-level and eight-level semi-quantitative disc degeneration grading systems. For NP, T1rho and T2 decreased quadratically with disc degeneration grades and had no significant trend difference (P=0.40). In NP, T1rho and T2 decrease in a similar pattern following disc degeneration. For AF, T1rho and T2 decreased linearly and the slopes of T2 were significantly flatter than those of T1rho (P<0.001). Therefore, the T1rho is better suited for evaluating AF in degenerated disc than T2.
Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves macromolecules accumulated within the extracellular matrix. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl4 twice weekly for up to 6 weeks. Then CCl4 was withdrawn for recovery. The liver T1rho values increased slightly on day 2, then increased further and were highest at week 6 post CCl4 insults, and decreased upon the withdrawal of the CCl4 insult. This study demonstrated that T1rho MRI is a valuable imaging biomarker for liver injury and fibrosis induced by CCl4. Liver T1rho value was only mildly affected by edema and acute inflammation when there was no apparent fibrosis.
To translate liver T1rho MRI to clinical application, the technical feasibility of T1rho MRI in human liver was explored and the normal range of T1rho values in healthy volunteers was determined. We found it is feasible to obtain consistent liver T1rho measurement for healthy human liver with six spin-lock time (SLT) points of 1, 10, 20, 30, 40, and 50ms; the mean liver T1rho value of the healthy subjects was 42.5ms, with a range of 38.8-46.5ms. Adopting 3-SLT points of 1, 20, and 50ms for T1rho measurement could provide reliable measurement and reduce the scanning time, while 2-SLT points of 1 and 50ms do not provide reliable measurement.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Zhao, Feng.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 119-143).
Abstracts also in Chinese.
ABSTRACT --- p.i
ACKNOWLEDGEMENTS --- p.vi
LIST OF FIGURES --- p.viii
LIST OF TABLES --- p.xvi
LIST OF ABBREVIATIONS --- p.xvii
CONTENTS --- p.xxi
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- Conventional Magnetic Resonance Imaging --- p.1
Chapter 1.1.1 --- Basic Principle of Conventional Magnetic Resonance Imaging --- p.1
Chapter 1.1.2 --- T1 Relaxation --- p.2
Chapter 1.1.3 --- T2 Relaxation --- p.3
Chapter 1.2 --- T1rho Magnetic Resonance Imaging --- p.3
Chapter 1.2.1 --- T1rho Relaxation --- p.3
Chapter 1.2.2 --- Principle of T1rho Magnetic Resonance Imaging --- p.4
Chapter 1.2.3 --- Radiofrequency Pulse for T1rho Magnetic Resonance Imaging --- p.5
Chapter 1.2.4 --- T1rho-weighted Contrast Imaging and Application --- p.10
Chapter 1.2.5 --- Quantitative T1rho Mapping and Application --- p.11
Chapter 1.2.6 --- T1rho Dispersion and Application --- p.13
Chapter 1.3 --- Thesis Overview --- p.14
Chapter Chapter 2 --- T1rho MRI in brain aging of animal model --- p.19
Chapter 2.1 --- Introduction --- p.19
Chapter 2.2 --- Materials and Methods --- p.20
Chapter 2.2.1 --- Animal Model of Brain Aging --- p.20
Chapter 2.2.2 --- T1rho Data Acquisition --- p.21
Chapter 2.2.3 --- T1rho Data Processing --- p.23
Chapter 2.2.4 --- T1rho Measurement and Statistical Analysis --- p.24
Chapter 2.3 --- Results --- p.27
Chapter 2.4 --- Discussion --- p.38
Chapter 2.5 --- Summary --- p.42
Chapter Chapter 3 --- T1rho MRI in lumbar disc degeneration of human subjects --- p.43
Chapter 3.1 --- Introduction --- p.43
Chapter 3.2 --- Methods --- p.45
Chapter 3.2.1 --- Subjects --- p.45
Chapter 3.2.2 --- MR Image Acquisition --- p.46
Chapter 3.2.2.1 --- T2-weighted MRI --- p.46
Chapter 3.2.2.2 --- T2 Mapping Imaging --- p.47
Chapter 3.2.2.3 --- T1rho MRI --- p.47
Chapter 3.2.3 --- Data Processing --- p.49
Chapter 3.2.4 --- Data Measurement and Statistical Analysis --- p.49
Chapter 3.3 --- Results --- p.52
Chapter 3.3.1 --- Range of T1rho/T2 Values for Discs --- p.52
Chapter 3.3.2 --- The Relationship between NP T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.52
Chapter 3.3.3 --- The Relationship between NP T1rho/T2 Values and 5-level Degeneration Grading of Discs --- p.55
Chapter 3.3.4 --- The Relationship between AF T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.58
Chapter 3.3.5 --- The Relationship between AF T1rho/T2 Values and 8-level Degeneration Grading of Discs --- p.61
Chapter 3.4 --- Discussion --- p.64
Chapter 3.5 --- Summary --- p.69
Chapter Chapter 4 --- T1rho MRI in rat liver fibrosis model induced by CCl4 insult --- p.71
Chapter 4.1 --- Introduction --- p.71
Chapter 4.2 --- Materials and Methods --- p.73
Chapter 4.2.1 --- Animal Preparation --- p.73
Chapter 4.2.2 --- MR Image Acquisition --- p.74
Chapter 4.2.2.1 --- T2-weighted MRI --- p.75
Chapter 4.2.2.2 --- T1rho MRI --- p.75
Chapter 4.2.3 --- Data Processing --- p.76
Chapter 4.2.4 --- Data Measurement and Statistical Analysis --- p.78
Chapter 4.2.5 --- Histology Analysis --- p.79
Chapter 4.3 --- Results --- p.80
Chapter 4.3.1 --- T1rho Measurement Reproducibility --- p.80
Chapter 4.3.2 --- Rat Liver T1rho Values at Different Time Phase --- p.81
Chapter 4.3.3 --- Relative Rat Liver Signal Intensity on T2WI at Different Time Phase --- p.83
Chapter 4.3.4 --- Histology Results --- p.84
Chapter 4.4 --- Discussion --- p.86
Chapter 4.5 --- Summary --- p.91
Chapter Chapter 5 --- T1rho MRI in liver of healthy human subjects --- p.93
Chapter 5.1 --- Introduction --- p.93
Chapter 5.2 --- Methods --- p.95
Chapter 5.2.1 --- Subjects --- p.95
Chapter 5.2.2 --- MR Image Acquisition --- p.96
Chapter 5.2.2.1 --- T2-weighted MRI --- p.96
Chapter 5.2.2.2 --- T1rho MRI --- p.97
Chapter 5.2.3 --- T1rho Data Processing --- p.99
Chapter 5.2.4 --- T1rho Measurement --- p.100
Chapter 5.3 --- Results --- p.102
Chapter 5.3.1 --- T1rho Measurement Reproducibility --- p.105
Chapter 5.3.2 --- T1rho Value Agreement of the Fasting Status with Post Meal Status --- p.105
Chapter 5.3.3 --- T1rho Value Agreement for T1rho Maps Constructed by Different Spin-lock Time Points --- p.106
Chapter 5.3.4 --- T1rho Value Range of Healthy Human Subjects --- p.108
Chapter 5.4 --- Discussion --- p.108
Chapter 5.5 --- Summary --- p.113
Chapter Chapter 6 --- General discussion and further work --- p.115
References: --- p.119
LIST OF PUBLICATIONS --- p.138

碩士
國立臺灣科技大學
機械工程系
104
Fusion has been the main treatment for degenerative disc disease (DDD). However, many clinical studies have showed that adjacent segment degeneration was observed after fusion surgery. To solve these problems, dynamic stabilizations were used to treat disc degeneration. In recent years, some researchers proposed to combine rigid and dynamic stabilization in the treatment of degenerative disc disease. Hybrid dynamic stabilization is designed to achieve the original stability and reduce adjacent segment degeneration. However, previous research did not specify what kind of hybrid dynamic stabilization is a better choice. The purpose of my study was to investigate which hybrid dynamic stabilization is the best combination to treat DDD. A three-dimensional finite element model of the T10-S1 lumbar spine was used to evaluate biomechanics of various device including double hybrid stabilization and triple hybrid stabilization in comparison with intact spine. I remove degenerative disc at L3-L4 level or L4-L5 level and insert into the cage. The loading cases of flexion, extension, lateral bending and axial rotation were simulated. Intersegmental rotation, the von Mises stress of adjacent disc and the von Mises stress of posterior device were calculated and discussed at the index level and at the adjacent levels. The results to double hybrid dynamic stabilization showed that the degenerative segments and the upper adjacent segments using dynamic stabilization can have a greater inter-segmental rotation. Posterior device with Dynesys has the lowest stress at the index level and the upper adjacent level. The von Mises stress of adjacent intervertebral disc has same trend to the inter-segmental rotation. The results to triple hybrid dynamic stabilization showed that the degenerative segments and the adjacent segments using dynamic stabilization can have a greater inter-segmental rotation. Posterior device using rigid stabilization at the index level and using Dynesys stabilization at the adjacent level has the lowest stress. The adjacent intervertebral disc stress is closed to the intact spine with Dynesys at the index and adjacent levels. Using the dynamic stabilization on double and triple hybrid posterior device can reduce the load on the adjacent segments. Finally, my research could help surgeons to understand the biomechanical performances of hybrid posterior stabilization.

Orientação : João Filipe Requicha
Esta Dissertação de Mestrado é subordinada ao papel da neurorreabilitação funcional na doença degenerativa do disco intervertebral. Esta doença é uma das causas mais comuns de disfunção neurológica em cães. A neurorreabilitação funcional baseia-se nas propriedades da medula espinhal, tais como a neuroplasticidade, neuromodulação e memorização. Os seus protocolos são implementados após uma abordagem de diagnóstico correta por parte do neurologista ou neurocirurgião veterinário. O presente estudo tem como objetivo avaliar a importância da neurorreabilitação funcional na recuperação da capacidade ambulatória e funcional de cães com doença degenerativa do disco intervertebral toracolombar. No presente trabalho foram incluídos 98 cães com diagnóstico de doença degenerativa do disco intervertebral toracolombar que foram sujeitos a um protocolo de neurorreabilitação funcional no Centro de Reabilitação Animal da Arrábida (Azeitão, Portugal), aonde permaneceram em regime de internamento. Este protocolo incluiu técnicas de eletromioestimulação, treino locomotor terrestre e aquático e modalidades complementares, no sentido de promover a estimulação das vias motoras descendentes, assim como os geradores de padrão central, de modo a que a libertação de correntes despolarizantes permitisse uma locomoção equilibrada e coordenada. A amostra foi composta por 46 machos e 52 fêmeas, com idades compreendidas entre os 2 e 16 anos de idades, peso vivo médio de 14 Kg e de diferentes raças. Em relação à doença do disco, 58 animais apresentavam hérnias de Hansen tipo I e 40 de Hansen tipo II. O presente estudo demonstrou que, para existir locomoção voluntária funcional, é imprescindível a presença de sensibilidade à dor profunda, embora, tal não seja limitante, pois a mesma esteve presente em 75,5% dos cães e, ainda assim, foi atingindo um sucesso clínico de 80,7%, incluindo-se aqui animais que alcançaram a locomoção fictícia funcional. Demonstrou-se também que, independentemente do tipo de hérnia, são necessários, em média, 2 meses para se alcançar o estado ambulatório e funcional. O sucesso clínico nestes casos é uma conjugação multifatorial da extensão da lesão, velocidade da hérnia, utilização de glucocorticoides, estado de perfusão sanguíneo e oxigenação da medula, presença de sensibilidade à dor profunda e aplicação da neurorreabilitação funcional.
This Master Thesis is regarding the functional neurorehabilitation role in the intervertebral disc disease. This is a common disease causing neurologic dysfunction in dogs. In functional neurorehabilitation it’s needed to understand spinal cord properties like neuroplasticity, neuromodulation and memorization. Functional neurorehabilitation protocols must be applied after a correct diagnose by the veterinary neurologist or neurosurgeon’s decision about resolution. The study aimed to evaluate the functional neurorehabilitation on the recovery of ambulatory and functional capacity in dogs with thoracolombar intervertebral disc disease. In the present study were included 98 dogs with thoracolombar intervertebral disc disease diagnostic, which were subjected to a functional neurorehabilitation protocol on Centro de Reabilitação Animal da Arrábida (Azeitão, Portugal), where they remained. This protocol included electromyostimulation techniques, terrestrial and aquatic locomotor training and complementary modalities, in an effort to promote descendent motor pathways stimulation and central pattern generators, so that persistent inward currents allow a coordinated and balanced locomotion. The sample was composed by 46 males and 52 females, with ages between 2 and 16 years, average weight of 14 kg and from several breeds. Regarding the disc disease, 58 had type I Hansen hernia and 40 had type II Hansen hernia. The present study shown that to exist functional voluntary locomotion it is necessary the presence of deep pain perception, although, this is not limiting, as this one was present in 75.5% of the dogs and, even so, there was reached an 80.7% of clinical success, which were included animals that achieve fictitious functional locomotion. It was also proved that it’s necessary in average two months to achieve a functional ambulatory state independently of the type of hernia. This is also an important and concrete information to the owners. It is is important to refer the clinical success in this cases it is a multifactorial conjugation between lesion extension, lesion velocity, glucocorticoids usage, medullary blood perfusion and oxygenation, deep pain perception and functional neurorehabilitation application.