Norbert Boos

Magnetic resonance classification of lumbar intervertebral disc degeneration.

Study Design. A reliability study was conducted. Objectives. To develop a classification system for lumbar disc degeneration based on routine magnetic resonance imaging, to investigate the applicability of a simple algorithm, and to assess the reliability of this classification system. Summary of Background Data. A standardized nomenclature in the assessment of disc abnormalities is a prerequisite for a comparison of data from different investigations. The reliability of the assessment has a crucial influence on the validity of the data. Grading systems of disc degeneration based on state of the art magnetic resonance imaging and corresponding reproducibility studies currently are sparse. Methods. A grading system for lumbar disc degeneration was developed on the basis of the literature. An algorithm to assess the grading was developed and optimized by reviewing lumbar magnetic resonance examinations. The reliability of the algorithm in depicting intervertebral disc alterations was tested on the magnetic resonance images of 300 lumbar intervertebral discs in 60 patients (33 men and 27 women) with a mean age of 40 years (range, 10–83 years). All scans were analyzed independently by three observers. Intra- and interobserver reliabilities were assessed by calculating kappa statistics. Results. There were 14 Grade I, 82 Grade II, 72 Grade III, 68 Grade IV, and 64 Grade V discs. The kappa coefficients for intra- and interobserver agreement were substantial to excellent: intraobserver (kappa range, 0.84–0.90) and interobserver (kappa range, 0.69–0.81). Complete agreement was obtained, on the average, in 83.8% of all the discs. A difference of one grade occurred in 15.9% and a difference of two or more grades in 1.3% of all the cases. Conclusion. Disc degeneration can be graded reliably on routine T2-weighted magnetic resonance images using the grading system and algorithm presented in this investigation.

Classification of age-related changes in lumbar intervertebral discs. 2002 Volvo Award in basic science

Study Design. A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. Objectives. To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. Summary of the Background Data. No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). Methods. A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. Results. A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (&kgr; values, 0.49–0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age (P < 0.0001) and macroscopic grade of degeneration (P < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. Conclusions. Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.

The diagnostic accuracy of magnetic resonance imaging, work perception, and psychosocial factors in identifying symptomatic disc herniations

Study Design This was a prospective study of patients (study group) with symptomatic disc herniations and asymptomatic volunteers (control group) matched for age, sex, and work-related risk factors. Objective To determine the prevalence of disc herniation in a matched group of asymptomatic volunteers and to access the diagnostic accuracy of magnetic resonance imaging, work perception, and psychosocial factors in identifying symptomatic disc herniations. Summary of Background Data Disc herniations have been reported to occur in 20–36% of asymptomatic volunteers. A valid comparison of asymptomatic individuals and patients with disc herniations has not been performed. Methods Forty-six patients with low back pain and sciatica severe enough to require a disceclomy were compared with 46 age-, sex-, and risk factor-matched (heavy lifting, twisting and bending, vibration, and sedentary activity) asymptomatic voluteers. Both groups had a complete clinical and magnetic resonance imaging examination and completed a questionnaire to assess differences in the psychosocial and work perception profiles. The prevalence and the severity of morphologic alterations (disc herniation, disc degeneration, and neural compromise) was analyzed by two independent radiologists in a blinded fashion. Differences between both groups regarding MRI findings, work perception (occupational mental stress, intensity of concentration, job satisfaction, and job-related resignation) and psychosocial factors (anxiety, depression, self-control, social support, and marital status) were compared using multivariate techniques. Stepwise discriminate analysis was used to identify the best discriminating variables within the magnetic resonance image, work perception, and psychosocial categories in terms of the diagnostic accuracy to predict group membership (study [pain] or control [no pain] group). Results Matched controls had significantly more risk factors than a group of normal individuals. The present study has presented evidence that an age-, gender-, and occupational risk factors-matched group of asymptomatic patients shows a high incidence rate of disc herniations (76%). Although significantly less than the symptomatic group incidence of 96%, this represents a much higher prevalence rate than generally expected and reported in other studies of unmatched asymptomatic volunteers. Patients had more severe disc herniations (disc extrusions) than asymptomatic volunteers (35% vs. 13%). There was no significant differences regarding disc degeneration between both groups (96% vs. 85%). The only substantial morphologic difference between both groups was the presence of a neural compromise (83% vs. 22%), which was highly significant (P < 0.0001). There were significant differences between both groups regarding work perception (occupational mental stress, intensity of concentration, job satisfaction, and resignation; P<0.027) and psychosocial factors (anxiety, depression, self-control, marital status; P<0.0001). The best single predictor of a group membership was the extent of neural compromise. A combination of this factor with occupational mental stress, depression, and marital status was the best predictive model. With this model, the false-negative rate (potential overtreatment of disc morphology) was reduced by more than half compared with morphologic factors (nerve root compression) alone (22% vs. 11%). Conclusions. In an age-, sex-, and risk factormatched group of asymptomatic individuals, disc herniation had a substatially higher prevalence (76%) than previously reported in an unmatched group. Individuals with minor disc herniations (i.e., protrusion, contained discs) are at a very high risk that their magnetic resonance images are not a causal explanation of pain because a high rate of asymptomatic subjects (63%) had comparable morphologic findings. The only highly significant difference between the study group and control group regarding morphologic findings was the criteria of a nerve root compromise. Work perception and psychosocial factors were helpful in discriminating between symptomatic and asymptomatic disc herniations.

1997 volvo award winner in basic science studies: Immunohistologic markers for age-related changes of human lumbar intervertebral discs

Study Design. The authors performed a correlative macroscopic, histologic, and immunohistochemical investigation on human lumbar intervertebral discs using complete motion segment slices, including all age groups and stages of degeneration. Objectives. To identify markers for age‐related changes of human lumbar intervertebral discs. In particular, to investigate changes in the distribution pattern of collagen Types I, II, III, IV, V, VI, IX, and X. In addition, to study posttranslational protein modification by the immunolocalization of N‐(carboxylmethyl)lysine (CML), which is regarded as a biomarker for oxidative stress. Summary of Background Data. Data on a correlation of age‐related changes in disc morphology and disc matrix composition is sparse. So far, no comprehensive analysis considered a correlation of macroscopic, histologic, and biochemical age‐related alterations using complete sections of intervertebral discs (i.e., including nucleus pulposus, anulus fibrosus, endplates, and vertebral bodies). In addition, there is need for specific markers for these disc changes to allow for a better correlation with disc function. Methods. After photodocumentation of the macroscopic appearance, 229 sagittal lumbar motion segments obtained from 47 individuals (fetal to 86 years) during routine autopsy were processed for histologic and immunohistochemical analysis. All slices were investigated for histologic alterations of disc degeneration. A randomly selected subset of these specimens (n = 45) was used for a correlative analysis of interstitial collagens and molecular modifications of matrix proteins. Results. The presence of CML‐modification of extracellular matrix proteins, mainly collagen, was observed first in the nucleus pulposus of a 13‐year‐old individual and increased significantly with age. In elderly people, both the nucleus pulposus and the anulus fibrosus showed extensive CML deposition. This CML deposition was accentuated in areas of macroscopic and histologic disc degeneration. After the occurrence of CML in the nucleus pulposus, we found a change in the collagen type pattern. An initial increase in nuclear collagen Types II, III, and VI staining was followed by a loss of collagen Type II, the occurrence of collagen Type I, and the persistence of high collagen Type III and VI levels, which were finally decreased again. The nuclear chondrocytes revealed significant changes in their immediate pericellular matrix, indicating phenotypic changes. Thus, exclusively in the nucleus pulposus of adolescents and young adults a significant proportion of cells positively stained for the basement membrane collagen Type IV. Collagen Type X was expressed by nuclear chondrocytes at a higher age and was associated with advanced degenerative disc alterations. Conclusions. The authors present the first study in which age‐related changes are correlated on a macroscopic, histologic, and molecular level using complete sections of lumbar motion segments. They reconfirm the notion that disc degeneration starts as early as in the second decade of life. Therefore, only early prevention of disc damage may inhibit disc degeneration and its sequelae. Phenotypic alterations of nuclear chondrocytes as monitored by collagen Type IV in young adults with minor lesions and collagen Type X in advanced lesions indicate distinct cellular reactions, possibly as a reaction to enhanced oxidative stress. The degree of this oxidative stress is reflected by the CML‐staining pattern which, in turn, indicates that the disc undergoes an accumulative stress, possibly leading to altered properties of the collagen fibrils and, thereby, tissue destruction. The deposition of CML proved to be the best marker for ongoing age‐related changes in the intervertebral disc.

2002 SSE Award Competition in Basic Science: Expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption

Abstract. During the process of degeneration, the intervertebral disc (IVD) shows a progressive and significant reduction in height due to tissue resorption. Intradiscal clefts and tears are major hallmarks of disc degeneration. Matrix-degrading enzymes such as matrix metalloproteinases (MMPs) are assumed to play a pivotal role in disc tissue degradation and resorption. The objective of this study was therefore to investigate the potential role of MMPs in extracellular matrix degradation leading to disc degeneration. This study was conducted on 30 formalin-fixed and EDTA-decalcified complete cross-sections of lumbar IVDs from cadavers of individuals aged between 0 and 86 years. Tissue sections were used for the immunolocalization of MMPs-1, -2, -3 and -9. The number of labeled cells was assessed by morphometric analyses, and was statistically correlated with the formation of clefts and tears, cellular proliferation, granular matrix changes and mucous degeneration. Furthermore, 30 disc specimens obtained during spinal surgery were used for in situ hybridization of MMP-2 and -3-mRNA. In addition, the enzymatic gelatinolytic activity was determined by in situ zymography in autopsy material. Immunohistochemistry showed the intradiscal expression of all four MMPs, which was confirmed by in situ hybridization, providing clear evidence for the synthesis of the enzymes within nucleus pulposus and annulus fibrosus cells. Gelatinolytic enzymatic activity was verified by in situ zymography. IVDs from infants and young adolescents remained almost completely unlabeled for all MMPs tested, while more MMPs-1 and -3 were seen in disc cells of younger adults than in those of a more advanced age; MMP-2 remained unchanged over the adult age periods, and MMP-9 was expressed in only relatively few cells. This pattern significantly correlated with the occurrence of clefts and tears. This correlation was strongest for MMP-1 (P<0.0001), MMP-2 (P<0.0017) and MMP-3 (P<0.0005) in the nucleus, and MMP-1 (P<0.0001) and MMP-2 (P<0.038) in the annulus. In parallel, the proliferation of disc cells and matrix degeneration (granular changes and mucous degeneration) were related to MMP expression. Likewise, enzymatic activity was seen in association with cleft formation. Our data suggest that major MMPs play an important role in the degradation of the IVD. This is evidenced by the high correlation of MMP expression with the formation of clefts and tears. These findings implicate a leading function for MMPs in IVD degeneration resulting in the loss of normal disc function, eventually leading to low-back pain.

Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls.

Study Design. Immunohistochemical study of tumor necrosis factor &agr; expression in autopsy and surgical specimens of human lumbar intervertebral discs. Objectives. To investigate the occurrence and localization of tumor necrosis factor &agr; in intervertebral disc tissue and to correlate its expression with age and the degree of disc degeneration. Summary of Background Data. The source and origin of discogenic pain are as yet unknown. Recently identified changes of the cellular phenotype during senescence and disc pathology with partly phagocytic properties suggest an ‘inflammatory’ phenotype. Tumor necrosis factor &agr; is one of the most potent proinflammatory cytokines possibly modulating cellular phenotypes. It may also promote pain induction. Very little is known about the occurrence and localization of tumor necrosis factor &agr; in intervertebral disc tissue of defined age and degree of histologic tissue degeneration. Methods. The study population comprised 20 cross-sections of the complete motion segment of human lumbar vertebrae (age range 0–86 years) obtained at autopsy and 28 surgical disc specimens of individuals undergoing lumbar surgical interventions for various reasons. The temporospatial distribution of tumor necrosis factor &agr;-positive cells using a polyclonal antibody was correlated with a histologic degeneration score. Results. Tumor necrosis factor &agr; is expressed substantially in (nonsymptomatic) autopsy material in fetal/infantile and older adult nucleus pulposus, whereas it is sparsely expressed in adolescent and young adult nucleus pulposus. In the anulus fibrosus, tumor necrosis factor &agr; is not found in young adults (<25 years), but then significantly increases in extent. In contrast, symptomatic nucleus pulposus and anulus fibrosus (surgical material) contain substantially more tumor necrosis factor &agr;-positive cells. A significant positive correlation of tumor necrosis factor &agr; expression and disc degeneration (histologic degeneration score) was found for the anulus fibrosus in both sample groups. In the surgical material, an additional significant positive correlation was identified for nuclear tumor necrosis factor &agr;, disc degeneration, and age. Conclusions. Tumor necrosis factor &agr; is substantially expressed in disc material of symptomatic patients (surgical specimens) in comparison to samples taken at autopsy. The expression of tumor necrosis factor &agr; in early fetal/infantile nucleus pulposus may indicate ‘physiologic’ tissue disarrangement with closure of the blood vessel canals. The expression of tumor necrosis factor &agr; in adult discs, in contrast, is statistically associated with disc degeneration. Its occurrence in adults of more advanced age suggests that tumor necrosis factor &agr; is not involved in the initiation of disc degeneration, but may be associated with further promotion of degenerative disarrangement and pain induction.

MR imaging and CT in osteoarthritis of the lumbar facet joints

Abstract Objective. To test the agreement between MR imaging and CT in the assessment of osteoarthritis of the lumbar facet joints, and thus to provide data about the need for an additional CT scan in the presence of an MR examination. Design and patients. Using a four-point scale, two musculoskeletal radiologists independently graded the severity of osteoarthritis of 308 lumbar facet joints on axial T2-weighted and on sagittal T1- and T2-weighted turbo-spin-echo images and separately on the corresponding axial CT scans. Kappa statistics and percentage agreement were calculated. Results. The weighted kappa coefficients for MR imaging versus CT were 0.61 and 0.49 for readers 1 and 2, respectively. The weighted kappa coefficients for interobserver agreement were 0.41 for MR imaging and 0.60 for CT, respectively. There was agreement within one grade between MR and CT images in 95% of cases for reader 1, and in 97% of cases for reader 2. Conclusion. With regard to osteoarthritis of the lumbar facet joints there is moderate to good agreement between MR imaging and CT. When differences of one grade are disregarded agreement is even excellent. Therefore, in the presence of an MR examination CT is not required for the assessment of facet joint degeneration.

Pedicle screw fixation in spinal disorders: a European view.

Continuing controversy over the use of pedicular fixation in the United States is promoted by the lack of governmental approval for the marketing of these devices due to safety and efficacy concerns. These implants have meanwhile become an invaluable part of spinal instrumentation in Europe. With regard to the North American view, there is a lack of comprehensive reviews that consider the historical evolution of pedicle screw systems, the rationales for their application, and the clinical outcome from a European perspective. This literature review suggests that pedicular fixation is a relatively safe procedure and is not associated with a significantly higher complication risk than non-pedicular instrumentation. Pedicle screw fixation provides short, rigid segmental stabilization that allows preservation of motion segments and stabilization of the spine in the absence of intact posterior elements, which is not possible with non-pedicular instrumentation. Fusion rates and clinical outcome in the treatment of thoracolumbar fractures appear to be superior to that achieved using other forms of treatment. For the correction of spinal deformity (i.e., scoliosis, kyphosis, spondylolisthesis, tumor), pedicular fixation provides the theoretical benefit of rigid segmental fixation and of facilitated deformity correction by a posterior approach, but the clinical relevance so far remains unknown. In low-back pain disorders, a literature analysis of 5,600 cases of lumbar fusion with different techniques reveals a trend that pedicle screw fixation enhances the fusion rate but not clinical outcome. The most striking finding in the literature is the large range in the radiological and clinical results. For every single fusion technique poor and excellent results have been described. This review argues that European spine surgeons should begin to back up the evident benefits of pedicle screw systems for specific spinal disorders by controlled prospective clinical trials. This may prevent forthcoming medical licensing authorities from restricting the use of pedicle screw devices and dictating the practice of spinal surgery in Europe in the near future.

Young Investigator Award 2001 Winner : Risk Factors for Lumbar Disc Degeneration : A 5-Year Prospective MRI Study in Asymptomatic Individuals

Study Design. A longitudinal magnetic resonance imaging investigation of lumbar disc degeneration in asymptomatic individuals was conducted. Objective. To investigate risk factors for the development or deterioration of lumbar disc degeneration. Summary of Background Data. Numerous studies have explored the significance of certain risk factors for the development or progression of disc degeneration, but no comprehensive longitudinal magnetic resonance imaging–based study has been reported that simultaneously considers clinical, morphologic, physical, psychosocial, and occupational risk factors. Methods. In the 5-year follow-up evaluation of 41 asymptomatic individuals, the risk factors for the development of lumbar disc degeneration and its progression were investigated. All 41 individuals had a magnetic resonance imaging scan at baseline and at the minimum 5-year follow-up assessment using the same scanner and protocol. The magnetic resonance images were analyzed independently by two radiologists with regard to disc degeneration. Various predictor variables were assessed both at baseline and follow-up, with special emphasis on physical job characteristics, sports activities, and magnetic resonance image–based morphologic findings. Results. Of the 41 individuals, 17 (41%) exhibited a deterioration of the disc status. In 10 individuals, the progression of disc degeneration was one grade or more. Only a weak correlation existed between progressive disc degeneration and low back pain development during a 5-year follow-up period. Multiple logistic regression analysis demonstrated that the extent of disc herniation (odds ratio [OR], 12.63; confidence interval [CI], 1.24–128.49), the lack of sports activities (OR, 2.71; CI, 1.04–7.07), and night shift work (OR, 23.01; CI, 1.26–421.31) were significant predictors for disc degeneration during follow-up evaluation when control was used for the number of degenerated discs at baseline, gender, age, and body mass index. Conclusions. The results indicate that the extent of disc herniation, the lack of sports activities, and night shift work are significant risk factors for the development of lumbar disc degeneration and its progression.

Natural History of Individuals With Asymptomatic Disc Abnormalities in Magnetic Resonance Imaging : Predictors of Low Back Pain-Related Medical Consultation and Work Incapacity

Study Design. Prospective study on individuals with asymptomatic lumbar disc abnormalities detected in magnetic resonance imaging. Objectives. To determine the natural history of asymptomatic disc abnormalities in magnetic resonance imaging and to identify predictors of future low back pain–related medical consultation and work incapacity. Summary of Background Data. The natural history of individuals with asymptomatic disc herniations has not been well established, but the high rate of lumbar disc alterations recently detected in asymptomatic individuals by magnetic resonance imaging demands reconsideration of a pathomorphology-based explanation of low back pain and sciatica. Methods. Forty-six asymptomatic individuals who had a high rate of disc herniations (73%) were observed for an average of 5 years (range, 54–72 months). Four classes of variables (medical data including magnetic resonance imaging–identified disc abnormalities, general psychological factors, physical job characteristics, and psychosocial aspects of work) were assessed at baseline and follow-up. Results. Disc herniations and neural compromise did not significantly worsen at follow-up, whereas disc degeneration progressed in 17 individuals (41.5%). Minor episodes of low back pain occurred in 19 individuals (41.3%), 6 of whom had to seek medical treatment and 5 of whom had to stop work temporarily. The requirement for low back pain–related medical consultation was predicted with high accuracy by listlessness, job satisfaction, and working in shifts (P < 0.001). Work incapacity was best predicted by physical job characteristics, job disaffection, and working in shifts (P < 0.01). Conclusion. Physical job characteristics and psychological aspects of work were more powerful than magnetic resonance imaging–identified disc abnormalities in predicting the need for low back pain–related medical consultation and the resultant work incapacity. However,the conclusions are still preliminary, and replication of the findings in larger and more representative study samples is needed.