Age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong intra-individual correlation.

INTRODUCTION: Intervertebral disc (IVD) degeneration is characterized as a multifactorial disease, in which the hereditary background is thought to be of high importance. Accordingly, one would expect all spinal levels (lumbar/cervical/thoracal) to be affected by above-average disc degeneration in genetically predisposed individuals. The aim of this study, therefore, was to analyze the amount of degenerative changes in different spine levels in humans from different ages. MATERIALS AND METHODS: In detail, the presence, localization and abundance of histomorphological changes in the annulus fibrosus (AF) and nucleus pulposus (NP) in the cervical (C5/C6), thoracic (T2/T3) and lumbar (L2/L3) spine were investigated in complete autopsy IVD specimens (47 individuals) covering a complete age range (0-95 years). RESULTS: Results indicate that the highest degree of histo-degenerative changes were observed in the NP in all spine levels and showed an age-related expression pattern. With regard to the different spine levels, lumbar disc specimen showed significantly more degenerative changes compared to cervical and thoracic discs, whereas no statistical difference was observed between cervical and thoracic discs. In summary, highest grades of degeneration were observed in lumbar discs (especially in the NP). Intra-individual correlations between the degeneration score in the different levels showed a significant individual concordance. CONCLUSIONS: The intra-individual correlation of degenerative changes in all three examined spine regions further supports the notion that individual, i.e. genetic factors are strong predisposing factor for the development of age-related disc alterations.

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1ß treated human intervertebral disc cells.

INTRODUCTION: Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. MATERIALS AND METHODS: In order to investigate the anti-inflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1ß prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-α, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-κB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). RESULTS: Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-α at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-κB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. CONCLUSIONS: In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

Resources for preventing sickness absence due to low back pain.

BACKGROUND: After an episode of non-specific low back pain (LBP) some individuals fail to return to work. The factors leading to such LBP-related sickness absence are not yet fully understood. AIMS: To identify individual resources, over and above the already established predictors, for preventing LBP-related sickness absence in a population-based sample of workers experiencing an episode of LBP. METHODS: Cohort study with 1-year follow-up. Participants were from a working population who reported an episode of acute or subacute LBP at baseline. Four potential resources-life satisfaction, doing sports, job satisfaction and social support at work-were examined for their incremental value in predicting sickness absence over and above baseline sickness absence and fear-avoidance beliefs about work. RESULTS: In all, 279 workers participated in the study. All four resources showed an inverse relationship with regard to sickness absence. A multiple regression analysis revealed that life satisfaction as a resource protected against sickness absence, when controlling for established risk factors. Job satisfaction and social support at work minimized the influence of sickness absence at baseline and at 1-year follow-up. CONCLUSIONS: In a non-clinical working sample of individuals experiencing an acute/subacute episode of LBP, life satisfaction was a unique predictor of sickness absence after 1 year. Prevention in the occupational setting should not only address common risk factors but also occupational and individual resources that keep workers satisfied with life despite having LBP.

Cell-seeded polyurethane-fibrin structures--a possible system for intervertebral disc regeneration.

Nowadays, intervertebral disc (IVD) degeneration is one of the principal causes of low back pain involving high expense within the health care system. The long-term goal is the development of a medical treatment modality focused on a more biological regeneration of the inner nucleus pulposus (NP). Hence, interest in the endoscopic implantation of an injectable material took center stage in the recent past. We report on the development of a novel polyurethane (PU) scaffold as a mechanically stable carrier system for the reimplantation of expanded autologous IVD-derived cells (disc cells) to stimulate regenerative processes and restore the chondrocyte-like tissue within the NP. Primary human disc cells were seeded into newly developed PU spheroids which were subsequently encapsulated in fibrin hydrogel. The study aims to analyze adhesion properties, proliferation capacity and phenotypic characterization of these cells. Polymerase chain reaction was carried out to detect the expression of genes specifically expressed by native IVD cells. Biochemical analyses showed an increased DNA content, and a progressive enhancement of total collagen and glycosaminoglycans (GAG) was observed during cell culture. The results suggest the synthesis of an appropriate extracellular matrix as well as a stable mRNA expression of chondrogenic and/or NP specific markers. In conclusion, the data presented indicate an alternative medical approach to current treatment options of degenerated IVD tissue.

What comprises a good outcome in spinal surgery? A preliminary survey among spine surgeons of the SSE and European spine patients.

Standardized and validated self-administered outcome-instruments are broadly used in spinal surgery. Despite a plethora of articles on outcome research, no systematic evaluation is available on what actually comprises a good outcome in spinal surgery from the patients' and surgeons' perspective, respectively. However, this is a prerequisite for improving outcome instruments. In performing a cross-sectional survey among spine patients from different European regions and spine surgeons of the SSE, the study attempted (1) to identify the most important domains determining a good outcome from a patients' as well as a surgeon's perspective, and (2) to explore regional differences in the identified domains. For this purpose, a structured interview was performed among 30 spine surgeons of the SSE and 353 spine surgery patients (representing Northern, Central and Southern Europe) to investigate their criteria for a good outcome. A qualitative and descriptive approach was used to evaluate the data. Results revealed a high agreement on what comprises a good outcome among surgeons and patients, respectively. The main parameters determining good outcome were achieving the patients' expectations/satisfaction, pain relief, improvement of disability and social reintegration. Younger patients more often expected a complete pain relief, an improved work capacity, and better social life participation. Patients in southern Europe more often wanted to improve work capacity compared to those from central and northern European countries. No substantial differences were found when patients' and surgeons' perspective were compared. However, age and differences in national social security and health care system ("black flags") have an impact on what is considered a good outcome in spinal surgery.

Lumbar spinal stenosis: assessment of cauda equina involvement by electrophysiological recordings.

UNLABELLED: The objective of this study was to investigate the relationship between electrophysiological recordings and clinical as well as radiological findings in patients suggestive to suffer from a lumbar spinal stenosis (LSS). We hypothesise that the electrophysiological recordings, especially SSEP, indicate a lumbar nerve involvement that is complementary to the neurological examination and can provide confirmatory information in less obvious clinical cases. In a prospective cohort study, 54 patients scheduled for surgery due to LSS were enrolled in an unmasked, uncontrolled trial. All patients were assessed by neurological examination, electrophysiological recordings, and magnetic resonance imaging (MRI) of the lumbar spine. The electrophysiological recordings focused on spinal lumbar nerve involvement. RESULTS: About 88% suffered from a multisegmental LSS and 91% of patients respectively complained of chronic lower back pain and/or leg pain for more than 3 months, combined with a restriction in walking distance. The neurological examination revealed only a few patients with sensory and/or motor deficits while 87% of patients showed pathological electrophysiological recordings (abnormal tibial SSEP in 78% of patients, abnormal H-reflex in 52% of patients). CONCLUSIONS: Whereas the clinical examination, even in severe LSS, showed no specific sensory-motor deficit, the electrophysiological recordings indicated that the majority of patients had a neurogenic disorder within the lumbar spine. By the pattern of bilateral pathological tibial SSEP and pathological reflexes associated with normal peripheral nerve conduction, LSS can be separated from a demyelinating polyneuropathy and mono-radiculopathy. The applied electrophysiological recordings, especially SSEP, can confirm a neurogenic claudication due to cauda equina involvement and help to differentiate neurogenic from vascular claudication or musculo-skeletal disorders of the lower limbs. Therefore, electro-physiological recordings provide additional information to the neurological examination when the clinical relevance of a radiologically-suspected LSS needs to be confirmed.

The impact of clinical, morphological, psychosocial and work-related factors on the outcome of lumbar discectomy.

In a prospective controlled trial on 46 patients undergoing lumbar discectomy, three classes of variables (medical data including MRI-identified morphological abnormalities, general psychological factors and psychosocial aspects of work) were analyzed with regard to their predictive value for the outcome of lumbar disc surgery at 2 year follow-up. Multiple regression analyses were used to identify the best predictor variables of four different outcome measures (i.e. pain relief, reduction of disability in daily activities, return to work and surgical outcome). MRI-identified nerve root compromise and social support from the spouse were independent predictors of pain relief 2 years after surgery (R2 = 0.40, P < 0.01). Return to work 2 years after surgery was best predicted by depression and occupational mental stress (R2 = 0.36, P < 0.001). MRI-identified extent of herniation and depression were significant predictors of a good surgical outcome after lumbar discectomy (R2 = 0.61, P < 0.001). This study has demonstrated that the outcome of discectomy is critically dependent on which outcome variables are selected and that different sorts of predictor variables have a distinct influence on the various outcome variables. Obvious morphological alterations (i.e. disc extrusions, nerve root compromise) proved to be significant predictors of postoperative pain relief and improvement of disability in daily activities justifying a surgical treatment approach in these cases. The most important finding of this study was that return to work was not influenced by any clinical findings or MR-identified morphological alterations, but solely by psychological factors (i.e. depression) and psychological aspects of work (i.e. occupational mental stress).

Immunolocalization of major interstitial collagen types in human lumbar intervertebral discs of various ages.

We used complete transverse sections through 65 samples of human lumbar intervertebral discs for immunolocalization of the major interstitial collagen types I, II, III, V, VI and IX. The samples were selected from 47 patients ranging in age from 0 (fetuses) to 86 years. The results were compared with the histological findings in disc tissue degeneration and/or reparative alterations as indicated by tear and cleft formation, chondrocyte proliferation, mucous degeneration, granular matrix changes and fibrocartilage fibrillation. We observed a typical pattern for each antibody and each anatomical structure, with, however, remarkable inter- and intraindividual variability, which could be monitored only by use of the complete transverse sections. Accordingly, collagen I was seen in the normal annulus fibrosus and in the degeneratively altered nucleus pulposus, but not within the end-plate, regardless of degenerative changes. Collagens II and IX were found in the normal nucleus pulposus, the inner annulus fibrosus and the end-plate. The collagen II (and IX) staining seemed to be enhanced in areas of minor degenerative lesions, but reduced in advanced lesions and in the degenerated end-plate. Collagens III and VI were significantly increased in areas of minor to advanced degeneration in all anatomical settings, while collagen V showed only minor changes in its staining pattern. In general, histological signs of tissue degeneration coincided with significant quantitative, but also with certain qualitative, changes in the composition of the collagenous disc matrix. These observations indicate the association of degenerative and/or reparative alterations of the intervertebral disc and changes in the collagenous matrix, but document the variability in the extent of the abnormalities observed.

Tissue characterization of symptomatic and asymptomatic disc herniations by quantitative magnetic resonance imaging.

The purpose of this investigation was to determine differences in tissue composition of symptomatic and asymptomatic disc herniations as reflected in T1 and T2 relaxation times (quantitative magnetic resonance imaging). Thirty patients with sciatica severe enough to require a discectomy and 46 asymptomatic volunteers (controls) were included in this study. Both groups had a clinical examination as well as a magnetic resonance investigation of the lumbar spine. The longitudinal and transverse magnetic relaxation times (T1 and T2, respectively) were calculated from a set of 20 images obtained with five single-slice/multi-echo sequences at different repetition time values on a commercial whole-body system (1.5 T). Twenty-two symptomatic and asymptomatic disc herniations could be matched according to age, gender, disc level, and the extent of herniation (protrusion or extrusion) and were compared with regard to T1 and T2 relaxation times. Symptomatic disc herniations exhibited significantly (pT1 < 0.04 and pT2 < 0.003) shorter T1 (delta T1: -182.1 milliseconds, -15%) and T2 (delta T2: -11.0 milliseconds, -21%) relaxation times than matched asymptomatic herniations. Symptomatic disc herniations also exhibited more advanced disc degeneration as graded by Pearce's criteria (p < 0.01). These results suggest that symptomatic and morphologically matched asymptomatic disc herniations differ with regard to disc matrix composition.

Immunohistochemical analysis of type-X-collagen expression in osteoarthritis of the hip joint.

Conflicting data have been reported on the spatial distribution of type X-collagen expression in osteoarthritis, and no concise data exist on a possible correlation between type X-collagen expression and clinical and radiological alterations. Well defined clinical and radiological data were compared with histopathological and immunohistochemical findings to investigate the expression of type-X collagen in osteoarthritis of the hip joint. Femoral heads were obtained in toto from 11 patients undergoing routine hip arthroplasty for femoral neck fractures (n = 3) or osteoarthritis (n = 8) and from 13 patients (age: 12 days to 69 years) without any evidence of hip-joint pathology. Whole coronal sections from the femoral head were decalcified for routine histology and immunohistochemical analysis with use of type-specific monoclonal antibodies to type-X collagen. Our results demonstrate that type-X collagen is consistently found in osteoarthritic cartilage and is absent from normal adult cartilage (including the region of calcified cartilage). Except for the occurrence of type-X collagen in the middle zone of articular cartilage in advanced stages of osteoarthritis, there is no specific change in the staining pattern or intensity for the collagen during osteoarthritis, particularly when the staining is related to clinical and radiological parameters. Hardly more than 20% of the extracellular matrix stained for type-X collagen; therefore, we suggest that, in most cases, this type of collagen may not play a direct biomechanical role in the weakening of osteoarthritic cartilage but rather may contribute indirectly to a disturbance of the disc biomechanics by altering matrix-molecule interaction. However, expression of type-X collagen may indicate a change in chondrocyte phenotype that consistently coincides with the formation of chondrocyte clusters, one of the first alterations in osteoarthritis visible on histologic examination.

Quantitative MR imaging of lumbar intervertebral disc and vertebral bodies: methodology, reproducibility, and preliminary results.

Since relaxation times are influenced by the hydration of the tissue and the chemical environment of the water molecules, T1 and T2 measurements (quantitative MRI) could be used as an indicator for the water content and the biochemical composition of lumbar intervertebral discs. The discriminating power of quantitative MRI for tissue characterization in individuals (for clinical diagnosis) and in cohorts (e.g. for investigations on disc physiology or composition) relies on the reproducibility in relation to the expected tissue differences. We therefore investigated the reproducibility in vitro (lumbar spine phantom) and in vivo (10 volunteers). To estimate the differences between normal and pathologic tissues in vivo, 100 normal and 20 herniated intervertebral discs were examined by quantitative MRI in a first application of our method. The relaxation times were calculated from a set of 20 images obtained with five single-slice/multi-echo sequences at different TR values on a commercial whole-body system (1.5 T). We have found a satisfactory reproducibility in vitro (T1: 1.9%; T2: 6.2%), while the reproducibility was less satisfactory in vivo (T1: 16.4%; T2: 13.4%). Calculated from theses values, differences in relaxation times of various tissues must exceed 486 ms for T1 and 24 ms for T2 (tolerance limits) to allow discrimination with a 95% confidence in individuals. We observed statistically significant (p = 0.001) mean differences between normal (n = 100) and herniated (n = 20) intervertebral discs (delta T1: 196 ms; delta T2: 15 ms). Although statistical significant in cohorts, a discrimination of normal and herniated intervertebral discs is limited by quantitative MRI in individuals, since the differences are smaller than the tolerance limits necessary for a reliable clinical diagnosis. However, our results indicate that variations in the disc hydration and/or composition can be noninvasively detected by quantitative MRI in studies of cohorts with sufficient accuracy.

Therapeutic efficacy of selective nerve root blocks in the treatment of lumbar radicular leg pain.

The objective of this study was to investigate the clinical effectiveness of nerve root blocks (i.e., periradicular injection of bupivacaine and triamcinolone) for lumbar monoradiculopathy in patients with a mild neurological deficit. We have retrospectively analysed 30 patients (29-82 years) with a minor sensory/motor deficit and an unequivocal MRI finding (20 disc herniations, 10 foraminal stenoses) treated with a selective nerve root block. Based on the clinical and imaging findings, surgery (decompression of the nerve root) was justifiable in all cases. Twenty-six patients (87%) had rapid (1-4 days) and substantial regression of pain, five required a repeat injection. 60% of the patients with disc herniation or foraminal stenosis had permanent resolution of pain, so that an operation was avoided over an average of 16 months (6-23 months) follow-up. Nerve root blocks are very effective in the non-operative treatment of minor monoradiculopathy and should be recommended as the initial treatment of choice for this condition.

Quantitative magnetic resonance imaging of the lumbar spine. Potential for investigations of water content and biochemical composition.

Quantitative magnetic resonance imaging (relaxation time and proton density measurements) has gained increasing interest as a noninvasive way to study changes in water content and biochemical composition of lumbar intervertebral discs and vertebral bodies. This article reviews the current methodological problems and the feasibility of quantitative magnetic resonance imaging in the lumbar spine for investigations on water content and biological composition. This technique does not allow direct quantification of water content. Although biochemical variations may sensitively influence relaxation times and proton density under in vitro conditions, it is not feasible to obtain sufficiently reliable and specific information to monitor biochemical alterations associated with lumbar disc pathology in vivo.

Retroperitoneal endoscopically assisted minilaparotomy for anterior lumbar interbody fusion: technical feasibility and complications.

STUDY DESIGN: Description of a novel less invasive technique and prospective evaluation of associated morbidity and potential complications. OBJECTIVE: To investigate the feasibility of a novel endoscope-assisted retroperitoneal approach (REAM) for anterior lumbar interbody fusion (ALIF). SUMMARY OF BACKGROUND DATA: Minimally and less invasive approaches are currently favored to perform ALIF. However, the present endoscopic techniques have not found widespread acceptance, because they are technically demanding, and microsurgical techniques are not time effective when two separate approaches are needed for L5-S1 (transperitoneal) and L4-L5 (retroperitoneal). METHODS: The authors have developed the technique of REAM, which consists of three stages: 1) endoscopic retroperitoneal mobilization of the peritoneal sac, 2) midline minilaparotomy (4-6 cm), and 3) standard open anterior lumbar interbody fusion. Twenty patients were prospectively enrolled in this study and perioperative data (i.e., blood loss, operative time, intra- and postoperative complications) were collected to assess the feasibility of this approach. RESULTS: Six single-level and 14 two-level ALIFs from L3-L4 to L5-S1 were performed with a mean operative time of 108 minutes (range, 85-150) and an average estimated blood loss of 200 mL (range, 50-500). The follow-up (range, 12-29 months) on 20 patients showed that there were no perioperative or postoperative complications related directly to this approach. CONCLUSION: Anterior lumbar interbody fusion by REAM can be performed without additional hazard to the patient and appears to be a reasonable alternative to existing less invasive procedures.

A new magnetic resonance imaging analysis method for the measurement of disc height variations.

STUDY DESIGN: A new magnetic resonance image analysis method is proposed which is based on the definition of the borders of the vertebral bodies adjacent to the intervertebral disc and their varying relationships. The reproducibility of this method (the so-called "centroid" method) was assessed by consecutive measurements. Its potential to depict diurnal disc height variations was studied using randomized groups of volunteers. OBJECTIVE: To determine if magnetic resonance imaging can reliably measure disc height variations in the lumbar spine in vivo. SUMMARY OF BACKGROUND DATA: A review of the literature indicates that noninvasive, accurate methods to study the effect of load on intervertebral discs in vivo are needed. METHODS: The reproducibility of the centroid method was assessed in 10 healthy volunteers in 2 consecutive measurements and compared to a conventional method (mean anterior and posterior disc height). To investigate the potential for the depiction of diurnal disc height variations, 10 volunteers were randomized in a study group (1 measurement in the morning, 1 measurement in the evening) and a control group (2 consecutive measurements in the morning). RESULTS: The centroid method allows the depiction of disc height variations as small as 0.85 mm with a 95% confidence (tolerance limits), whereas a conventional method needs variations of at least 1.66 mm. In the study (diurnal) group, the disc height decreased significantly (P < 0.0001) during the day (mean, -0.9 mm), while no variation (P < 0.8) was found in the control group. CONCLUSIONS: These results indicate that the centroid method can reliably detect disc height variations in an experimental setting. The centroid method provides the potential for evaluations of the effects of various work places, work equipment, work tasks, and postures.

Treatment of severe spondylolisthesis by reduction and pedicular fixation. A 4-6-year follow-up study.

Ten consecutive patients with severe spondylolisthesis were treated with reduction and pedicular fixation (four Internal Fixator instrumentations, six Cotrel-Dubousset instrumentations). There were six Grade III spondylolisthesis and four spondyloptoses at the L5/S1 level. All patients had complete clinical and radiographic evaluation with an average follow-up of 56 months (range, 43-75 months). The percentage of slippage averaged 78.5% preoperatively and 39.6% postoperatively. The slip angle averaged 43 degrees preoperatively and 17 degrees postoperatively. Four patients with spondyloptosis were treated with combined posterolateral and interbody fusion and had solid fusion without loss of reduction. Five of six patients in whom reduction and stabilization was performed by a single posterolateral fusion demonstrated loss of reduction, nonunion, and implant failure. Four of these patients were reoperated. Ultimately all patients had resolution of pain, solid fusion, and no further slip progression. Reduction, pedicular fixation, and combined posterolateral and interbody fusion is a technically demanding procedure, which should be reserved for selected patients. Pedicular fixation systems may only allow permanent reduction and stabilization of high-grade spondylolisthesis in conjunction with a combined interbody and posterolateral fusion.

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.

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.

1995 Volvo Award in clinical sciences. 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 discectomy were compared with 46 age-, sex-, and risk factor-matched (heavy lifting, twisting and bending, vibration, and sedentary activity) asymptomatic volunteers. 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 tow 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 discriminating 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 factor-matched group of asymptomatic individuals, disc herniation had a substantially 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 fi

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.