Objective - To investigate the effects of injected protease solution on the mechanical advancement of disc degeneration, and to establish test protocol for future pre-clinical validation of spinal arthroplasty devices. The hypothesis that injection of a protease into a cadaveric lumbar disc will mimic advanced degeneration mechanics was the subject of this study. Summary of Background Information - Spinal disc degeneration is a universal condition that progresses in adults due to aging, disease, or injury. Stages of disc degeneration have been categorized in cadaver specimens, with each degeneration level exhibiting characteristic changes in flexibility parameters. Spinal disc tissue can be compromised through introduction of proteolytic enzymes into the collagenous fibers of the annulus fibrosus. Methods - 18 motion segments from 8 human lumbar spines were subjected to flexibility testing. Each specimen was either injected with 0.600 mL of trypsin solution in the annulus fibrosus, 0.600 mL of phosphate-buffed saline, or a fluid-less needle-stick. Motion testing followed with rotations applied in all three major spinal motions. Test sections were transected mid-disc after testing to characterize initial degeneration severity, and acquired motion data was analyzed to show flexibility traits over time. Results - Trypsin, saline, and control injections all caused changes in motion from pre-injection baselines. Saline injections were slightly more effective at mimicking the mechanics of higher grades of degeneration with more fidelity than trypsin injections. All motion parameters were altered by the study treatments, with hysteresis and neutral zone parameters experiencing changes similar to that seen in natural degeneration with greater fidelity. Lateral Bending motion showed the greatest magnitude response to injections, with Flexion-Extension tests showing the smallest change. Discussion - Unexpectedly, fluid-less control injections caused changes to hysteresis and neutral zone parameters, suggesting an alteration to viscoelastic properties due to simple needle puncture. Fluid injections (Trypsin and Saline) caused an immediate transient post-injection change to biomechanics that dissipated over time, except in Axial Rotation. Saline injections provided the highest fidelity in mimicking the motion of more advanced stages of degeneration.

No description available.

Introdução: A degeneração do disco intervertebral tem alta prevalência e é sabidamente associada à dor lombar. O objetivo deste trabalho foi correlacionar os valores de relaxometria T2 dos discos intervertebrais lombares com os parâmetros espinopélvicos em pacientes com dor lombar crônica. Materiais e métodos: Entre março a setembro de 2015, 91 pacientes consecutivos (56 mulheres, média de idade 53,5 anos, DP 11,6 anos, 23-76 anos e 35 homens, média de idade 53,6 anos, DP 11,9 anos, 19-73 anos) com dor lombar crônica foram incluidos neste estudo prospectivo. O Comitê de Ética Local aprovou o estudo e o consentimento foi obtido de cada paciente. Todos os indivíduos foram avaliados pelo índice de incapacidade Oswestry e escala visual analógica e não possuiam outras doenças da coluna vertebral, exceto degeneração discal. Os parâmetros espinopélvicos incidência pélvica (IP) versão pélvica (VP), inclinação sacral (IS), eixo vertical sagital (EVS), versão global (VG), ângulo espinopélvico (ASP), ângulo espinossacral (ASS), ângulo T1 pélvico (ATP), lordose lombar (LL), cifose torácica (CT), diferença entre a incidência pélvica e a lordose lombar (IP-LL) e a falta de lordose lombar (FLL) foram mensurados a partir de radiografias panorâmicas da coluna e pelve com o paciente na posição supina utilizando o software Surgimap®. O grupo de estudo foi categorizado de acordo com a classificação de Roussouly. Os mapas de relaxometria T2 foram adquiridos em aparelho de ressonância magnética de 1.5 Tesla para extrair os tempos de relaxação T2 e a segmentação manual completa dos discos lombares intervertebrais de cada paciente foi realizada no software Display®. Para verificar a reprodutibilidade desta avaliação, a concordância inter-observador para a segmentação manual dos discos intervertebrais lombares e mensuração dos parâmetros espinopélvicos foi avaliada. A significância estatística foi aceita quando p <0,05. Resultados: Os valores de relaxação T2 se correlacionaram significativamente com os parâmetros VP, VG, ASP, ATP, IP-LL e FLL em pacientes com dor lombarcrônica. Não encontramos correlação significativa entre os valores de relaxação T2 e os parâmetros IS, IP, ASS, EVS, LL, CT e questionários clínicos. A divisão por subtipos de Roussouly não se correlacionou com a degeneração discal avaliado pelo tempo de relaxação T2. A mensuração dos parâmetros espinopélvicos e a segmentação manual dos discos intervertebrais lombares mostraram uma alta reprodutibilidade interobservador. Conclusões: Indivíduos com maiores VP, VG, ATP, IP-LL e FLL apresentaram valores mais baixos de relaxação T2 nos discos intervertebrais. Para o nosso conhecimento, esse é o primeiro estudo a correlacionar os parâmetros espinopélvicos com a degeneração discal avaliada por meio da relaxometria T2. / Purpose: Intervertebral disc degeneration has a high prevalence and is known to be associated with low back pain.The purpose of this study was to correlate quantitative T2 relaxation measurements of lumbar intervertebral discs (IVD) with spinopelvic parameters and clinical symptoms in patients with chronic low back pain. Methods: From March to September 2015, 455 intervertebral discs from 91 consecutive patients (56 women, mean age 53.5 years, SD 11,7 years, 23-76 years and 35 men, mean age 53,6 years, SD 11.9 years, 19-73 years) with chronic low back pain were included in this prospective study. The study was approved by the local ethics committee, and written consent was obtained from all patients. All subjects were assessed by Oswestry Disability Index and Visual Analog Score questionnaires and were confirmed to have no other spine diseases except disc degeneration. Spinopelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), sagittal vertical axis (SVA), global tilt (GT), spinopelvic angle (SPA), spinosacral angle (SSA), T1-pelvic angle (TPA), lumbar lordosis (LL), thoracic kyphosis (TK), PI-LL (pelvic incidence minus lumbar lordosis) and lack of lumbar lordosis (LLL) were measured from standing spine and pelvis lateral radiographs using the software Surgimap®. The study group was categorized according to the Roussouly classification. Saggital T2 maps were acquired in a 1.5T MRI scanner to extract the IVD relaxation times and the complete manual segmentation of the IVD of each patient in all levels was performed using the software Display®. To assess the reproducibility of this evaluation, the interobserver agreement fot the manual segmentation of the lumbar intervertebral discs and measurement of the spinopelvic parameters was performed. Statistical significance was accepted when p <0.05. Results: Lumbar intervertebral discs T2 relaxation times correlated significantly with PT, GT, SPA, TPA, PI-LL and LLL in patients with chronic low back pain. We found no significant correlation between T2 values and SS, PI, ASS, SVA, LL, TK andclinical questionnaires. Roussouly subtypes and clinical questionnaires did not correlate with T2 relaxation times. Conclusions: Individuals with higher PT, GT, TPA, PI-LL and LLL showed decreased intervertebral disc T2 relaxation values. To our knowledge, this is the first study to correlate spinopelvic parameters with disc degeneration evaluated by T2 relaxometry.

The main purpose of this study was to determine whether playing soccer at high intensity training for a long period causes degeneration of the lumbar spine or not. This degeneration may occur without any symptoms or low back pain. Results of the present study were discussed in the framework of lumbar disc degeneration, trunk strength, lumbar and hip bone mineral density, trunk flexibility, activity MET scores for active and veteran soccer groups. There have been four subject groups in this study (15 active soccer players, 15 sedentary participants, 14 veteran soccer players, 13 sedentary participants). The BMD was measured in anterior-posterior view with a second-generation dual energy X-ray absorptiometry (DEXA) device. Isokinetic trunk strength data were recorded with the Biodex System Dynamometer (Biobex Medical Inc, Shirly, NY) at the 60&ordm / /sec and 120&ordm / /sec. Plain lateral radiographs were taken. The presence of degenerative changes of each lumbar vertebra was determined by using the Kellgren and Lowrence Score. A modified Schober test was used to measure lumbar flexion. Findings of the study demonstrated that veteran soccer players displayed greater lumbar disc degeneration than other groups. Moreover, v active soccer group had more BMD than other groups, but the veteran group&amp / #8217 / s BMD results were not different while comparing the control participants. Isokinetic test findings of the current study, trunk extension strength at 60/sec was significantly higher in active 1st group players than 2nd group participants, but there were no significant differences between the 1st group and 2nd group in terms of trunk flexion strength and agonist/antagonist ratio at 60/sec. In conclusion, Findings of the study support the main hypothesis that playing soccer at high intensity training at a long period of time may cause lumbar spine degeneration. Degeneration may occur without low back symptoms. Moreover, results supported the idea that Soccer can be accepted an impact loading sport that are to keep or accelerate bone mineral density. At last, having abnormal trunk extension strength while playing actively may cause lumbar disc degeneration on the spine at later years. A similar study should be carried out with a larger number of subjects, and longitudinal studies should be designed to examine the factors that effect the degeneration on the lumbar spine.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Intervertebral disc disease (IVD) is a common pathology in clinical neurology of dogs, representing 45.8% of neurological cases treated at Veterinary Hospital of the Universidade Federal de Santa Maria. The most affected segments are the thoracolumbar (T3-L3) and cranial cervical (C1-C5) of the spinal cord. The clinical sign occurs due a combination of the compressive effect of the disc material and the injury of impact on spinal cord, probably due to an extrusion. A clinical sign varies according to the affected segment of the spinal cord and the severity of the injury. It could be presented only by spinal hyperesthesia, whereas more severe injuries can lead to tetra / paraplegia with no nociception (deep pain) caudal to the lesion. Clinical management for IVD is generally indicated for dogs with hyperesthesia with or without minimal neurological deficits and consists of absolute rest in cage between four to six weeks. Surgery is the treatment of choice for dogs with severe neurological deficits (not ambulatory tetraparesis, tetraplegia, paraplegia with or without nociception in less than 48 hours) in dogs with unsuccessful of clinical management, or dog that have recurrence of disease. In contrast to the numerous studies evaluating the efficacy of surgical treatment in dogs with thoracolumbar and cervical IVD, studies demonstrating the effectiveness of conservative treatment are rare. The aim of this study was to identify dogs with presumptive diagnosis of thoracolumbar and cervical IVD who underwent clinical management and evaluate the response to therapy; and to analyze the effect of age, gender, duration of clinical signs, neurological degree and therapy, as prognostic factors in clinical outcome of the patient. Five hundred six neurological records were used to identify affected dogs (n = 379 thoracolumbar; n = 127 cervical), and was selected those patients with presumptive diagnosis of IVD submitted to clinical management as a first option. The outcome was satisfactory in 73.3% of cases of thoracolumbar IVD, and 92.7% of cases of cervical IVD, demonstrating that clinical management (cage rest, anti-inflammatory and analgesic opioid administration) is effective, especially in milder disease. Conservative treatment has a substantial rate of recurrence and neurological signs may be more severe than the first clinical presentation. The gender, age and duration of clinical signs has no prognostic effect on clinical outcomes of patients IVD of thoracolumbar and cervical, in the sample of the study. / A doença do disco intervertebral (DDIV) é uma afecção frequente na clínica neurológica de cães, representando 45,8% dos casos neurológicos atendidos pelo Serviço de Neurologia do Hospital Veterinário Universitário da Universidade Federal de Santa Maria. Os locais mais acometidos pela doença são os segmentos toracolombar (T3-L3) e cervical cranial (C1-C5) da medula espinhal. A manifestação clínica ocorre devido a uma combinação do efeito compressivo do material de disco e da lesão de impacto na medula espinhal, decorrente principalmente da extrusão do disco e varia de acordo com o segmento da medula espinhal afetado e da severidade da lesão. Pode ser evidenciada apenas por hiperestesia espinhal, enquanto as lesões mais graves podem levar a tetra/paraplegia com ausência da nocicepção (dor profunda) caudal a lesão. O tratamento clínico para DDIV geralmente é indicado para cães com hiperpatia associada ou não a mínimas deficiências neurológicas e consiste em repouso absoluto em gaiola entre quatro a seis semanas. Já a cirurgia é o tratamento de eleição para cães com deficiências neurológicas graves (tetraparesia não ambulatória, tetraplegia, paraplegia com ou sem nocicepção em menos de 48 horas), em cães refratários ao tratamento clínico, ou que apresentem recidiva da doença. Em contraste com os inúmeros estudos avaliando a eficácia do tratamento cirúrgico em cães com DDIV toracolombar e cervical, estudos demonstrando a eficácia do tratamento conservativo são escassos na literatura. Diante desses fatores, o objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar e cervical que foram submetidos ao tratamento clínico e avaliar a resposta à terapia instituída; além de avaliar a relação da idade, do gênero, da duração dos sinais clínicos e do tratamento de acordo com o grau neurológico como fatores prognósticos na evolução clínica desses pacientes. Foram analisados 506 registros neurológicos (n=379 toracolombar; n=127 cervical), e selecionados aqueles pacientes com diagnóstico presuntivo de DDIV submetidos ao tratamento clínico como primeira opção. A evolução clínica foi satisfatória em 73,3% dos casos de DDIV toracolombar, e 92,7% dos casos de DDIV cervical, demonstrando que o tratamento clínico com repouso absoluto, administração de anti-inflamatórios e analgésicos opióides é efetivo, principalmente em graus mais leves da doença. O tratamento conservativo apresenta um índice considerável de recidiva, cujos sinais neurológicos poderão ser mais graves do que a primeira apresentação clínica. O gênero, a idade e a duração dos sinais clínicos não apresentam efeito prognóstico na evolução clínica dos pacientes de DDIV toracolombar e cervical, na amostra estudada.

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

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

Abstract Low back pain (LBP) causes enormous costs to society. Certain magnetic resonance imaging (MRI) findings, including disc degeneration and disc herniation, have been associated with LBP in epidemiologic studies. Even though LBP should be considered a biopsychosocial condition, there is a need to define the possible existence of specific pathological conditions beyond LBP. One of these possible conditions is Modic change (MC). Modic changes are subchondral and vertebral bone marrow changes revealed by MRI. Although their association with LBP has been previously studied, some results remain contradictory, and we need to explore MC more thoroughly and to determine whether they are a feature of intervertebral disc degeneration or whether they exist in isolation. Moreover, it is unknown whether heritability is a contributing factor to MC. This study explored the heritability and morphology of MC and their association with severe, prolonged and disabling LBP. The data consisted of two general population samples, TwinsUK from the United Kingdom (mainly female), and the Hong Kong Disc Degeneration Cohort (HKDDC) from Hong Kong, China. The TwinsUK sample included a longitudinal ten-year follow-up, whereas the HKDDC sample was cross-sectional. The heritability of MC was found to be 30%. Modic changes were associated with other MRI findings such as disc degeneration, disc displacement and Schmorl’s nodes. A greater size of MC increased these associations. Type 1 MC were more strongly associated with disc displacement and disc degeneration than Modic type 2 change. Modic changes appeared to be independently associated with disabling LBP; severe, prolonged LBP; and back-related disability. Posterior MC and MC in the whole antero-posterior (AP) length of the vertebral body were more strongly associated with severe, prolonged LBP than other MC. A greater number and size of MC increased this association. In terms of disc degeneration, MC were independently associated with loss of disc height and disc signal intensity. Incident MC were independently associated with loss of disc height and disc bulge in a ten-year follow-up. Modic changes are heritable, and are associated with severe and disabling LBP. The location, size and number of MC affect the association of MC with other MRI findings, LBP and back-related disability. / Tiivistelmä Alaselkäkivusta aiheutuu valtavat kustannukset yhteiskunnalle. Tietyt magneettikuvauslöydökset, kuten välilevyrappeuma ja välilevytyrä, on yhdistetty alaselkäkipuun epidemiologisissa tutkimuksissa. Alaselkäkipua arvioidaan yleensä biopsykososiaalisen mallin avulla, koska sen syytekijät tunnetaan huonosti. Lannerangan Modic-muutoksia pidetään yhtenä mahdollisena alaselkäkivun syytekijänä. Modic-muutokset ovat rustonalaisia, nikaman luuytimen muutoksia, jotka näkyvät magneettikuvantamisella. Tulokset Modic-muutosten ja alaselkäkivun yhteydestä ovat kuitenkin ristiriitaisia. Modic-muutosten sijainnin, koon ja muodon vaikutus alaselkäkipuun tunnetaan edelleen puutteellisesti. Lisäksi niiden perinnöllisyys on epäselvä. Tässä tutkimuksessa tarkasteltiin Modic-muutosten perinnöllisyyttä ja tarkempaa morfologiaa, kuten sijaintia ja kokoa lannerangassa, sekä selvitettiin niiden yhteyttä haittaavaan ja voimakkaaseen alaselkäkipuun. Tutkimus perustui kahteen väestöperäiseen aineistoon: TwinsUK-kaksosaineistoon (pääosin naisia) Yhdistyneistä kuningaskunnista ja Hong Kong Disc Degeneration -kohorttiin Hongkongista, Kiinasta. TwinsUK-aineisto sisälsi seurantatietoja 10 vuoden ajalta, ja Hongkongin aineisto oli kerätty yhdestä aikapisteestä. Modic-muutosten perinnöllisen osuuden todettiin olevan 30 %. Modic-muutokset olivat yhteydessä muihin magneettikuvauslöydöksiin kuten välilevyrappeumaan, välilevypullistumaan ja Schmorlin keräsiin. Tyypin 1 Modic-muutokset olivat voimakkaammin yhteydessä välilevypullistumiin ja -rappeumaan kuin tyypin 2 muutokset. Modic-muutokset olivat yhteydessä toimintakykyä alentavaan ja voimakkaaseen, pitkittyneeseen alaselkäkipuun. Koko nikaman läpimitan käsittävät ja nikaman takaosassa sijaitsevat muutokset olivat voimakkaammin yhteydessä alaselkäkipuun. Muutosten suurempi koko ja yhteislukumäärä lannerangassa voimistivat sen yhteyttä alaselkäkipuun. Modic-muutokset olivat yhteydessä välilevyn madaltumiseen ja signaali-intensiteetin laskuun. Kymmenen vuoden seuranta-aikana ilmaantuneet Modic-muutokset olivat yhteydessä välilevyn madaltumiseen ja välilevypullistumaan. Modic-muutokset ovat perinnöllisiä ja ne ovat yhteydessä voimakkaaseen sekä toimintakykyä heikentävään alaselkäkipuun. Muutosten tyypin lisäksi niiden sijainti, koko ja lukumäärä tulee huomioida alaselkäkipua arvioitaessa.

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

No description available.