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Introduction: This prospective magnetic resonance imaging (MRI) study in chronic low-back pain (CLBP) patients evaluated the natural course of degenerative lumbar spine changes in relation to Modic 1 type changes (M1) within 1 year.Materials and Methods: From 3,811 consecutive CLBP patients referred to lumbar spine MRI 54 patients with a large M1 were selected using strict exclusion criteria to exclude specific back disorders. Follow-up MRI was obtained within 11-18 months.Results: At baseline M1 was associated with an adjacent endplate lesion in 96% of the cases. In follow-up, an unstable M1 was associated both with an increase of endplate lesions, decrease of disc height and change in disc signal intensity, most found at L4/5 or L5/S1. In disc spaces without M1, progression of degenerative changes was rare.Conclusion: Endplate deformation, decreasing disc height and change of disc signal intensity appear essential features of accelerated degenerative process associated with M1. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Intensity of pain and level of disability (Oswestry Disability Index [ODI]) were compared with the relative size of Modic type 1 (M1) and Modic type 2 (M2) lesions. Clinical symptoms of patients having mixed M1-M2 lesion (n = 49) were compared with patients having a 'pure' M1 lesion (n = 13). OBJECTIVE.: To determine the relation of the sizes of M1 and M2 lesions and the type of Modic lesion (mixed M1-M2 or pure M1 lesion) with intensity of low back pain and level of perceived disability. SUMMARY OF BACKGROUND DATA.: Endplate signal abnormalities, particularly M1 changes indicating edema and inflammation, have been suggested to play an important role in the etiopathogenesis of a subgroup of patients with nonspecific chronic low back pain (CLBP). However, their association with clinical symptoms has not been studied in detail previously. METHODS.: Sixty-two CLBP patients with a large M1 lesion were selected from CLBP patients who were sent for the first time for standard lumbar spine magnetic resonance imaging at a university hospital. To exclude other causes of CLBP, as far as possible, strict exclusion criteria were used: any specific back disease, even a slight nerve root compression, a recent or major spine operation, or age older than 65 years. The relative sizes of M1 and M2 lesions were visually estimated from sagittal images for comparison with clinical symptoms. RESULTS.: The majority of patients (91.9%; 57 of 62) had an M1 lesion at a single level, 92% of the lesions being at L4-L5 or L5-S1 level. Forty-nine patients (79.0%) had a mixed M1-M2 lesion, and 13 (21.0%) had a pure M1 lesion. The mean of the pain intensity score was 6.2, and, correspondingly, the Oswestry Disability Index was 30.4. The mean relative sagittal area of the largest M1 lesion was 24.6% (SD = 16.2), and that of the M2 lesion was 10.9% (SD = 11.6). Neither the pain intensity nor the ODI scores were found to correlate with the largest relative size of the M1 lesion. The patients with 'pure' M1 lesion had statistically significantly more clinical symptoms than patients having a mixed M1-M2 lesion. CONCLUSION.: We conclude that the size of M1 lesion does not directly correlate with the clinical symptoms but that the type of Modic lesion is more important. This study supports the previous observations that when the inflammatory process turns to the mixed M1-M2 lesions, clinical symptoms decrease. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration., Materials and Methods: Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age >or=60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression)., Results: At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges., Conclusion: The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit.

Subchondral signal abnormalities have been suggested to play an important role in chronic low back pain (LBP) syndromes. Their natural course is not well known. In this study the morphology and natural course of isolated subchondral signal abnormalities in the lumbosacral spine were analyzed with MRI. Twenty-four chronic LBP patients with a subchondral hypointensity on T1-weighted image (hyperintense on T2), indicating edema, were selected from a base population of 1,015 consecutive LBP patients to a follow-up MRI study within 18-72 months. Exclusion criteria were age >60 years, nerve root compression, a more specific back disease or a recent or major spine operation. The size and location of each subchondral signal abnormality and endplate lesion and the degree of degenerative disc changes were evaluated and compared between the baseline and follow-up studies. Most subchondral hypointensities were found at the L4/L5 or L5/S1 disc space, anteriorly and in both adjacent endplates. Almost all (53/54) hypointensities were associated with an endplate lesion. Twelve of the 54 subchondral hypointensities enlarged, six remained constant and 36 decreased or disappeared while five new ones appeared. Twenty-two (41%) hypointensities changed totally to hyperintensities or to mixed lesions. If the hypointensity increased, decreased or changed into hyperintensity, a change tended to develop in the adjacent endplate. If the hypointensity was absent or unchanged, endplate lesions did not tend to progress. In the absence of disc herniation or other specific spinal disease, subchondral hypointensities indicating edema are uncommon. They seem to have a highly variable course. There appears to be a link between endplate lesions and subchondral signal abnormalities. Further study is needed to explain the contribution of these findings to low back symptoms.

Study Design: An investigation of the visualization of experimental anular tears using contrast-enhanced magnetic resonance imaging., Objectives: To investigate how different kinds of experimentally induced anular tears can be visualized on contrast-enhanced magnetic resonance imaging., Summary of Background Data: Because the outer part of the anulus is innervated, tears of this part of disc are considered one cause for lumbar back pain. Moreover, clinical and experimental studies suggest that anular injuries may lead to a progressive degeneration of the entire disc. In the human disc, vascularized anular tears associated with disc degeneration can be visualized with contrast-enhanced magnetic resonance imaging, but acute peripheral anular injuries, probably caused by sudden trauma, have not been studied with this method., Methods: Two adjacent lumbar discs in adult sheep (n = 11) were injured with a scalpel blade. The L2-L3 discs were injured superficially, whereas in the L3-L4 discs, the incision reached the nucleus pulposus (full-thickness injury). In seven animals, only a stab incision was made to the disc, and in four animals, a small fragment (5 x 2 x 3 mm) of anulus was cut and removed. The animals were killed 3 weeks (acute injury, n = 5) and 3 months (subacute injury, n = 6) after surgery. Five minutes before death, gadolinium-diethylenetriaminepentaacetic acid was injected intravenously. After death, the whole lumbar spines were excised and 1.5-T high-field magnetic resonance imaging was immediately performed. Thereafter, the disc samples were examined histologically to determine the existence of blood capillaries., Results: In all injured discs, the injured area was macroscopically visible. Histologically, blood capillaries, lamellar destruction, and granulation tissue were clearly seen in every injured anulus. Contrast-enhanced magnetic resonance imaging showed that the superficial injuries were only occasionally visible in magnetic resonance imaging (3 of 11), whereas the full-thickness injuries were visible in a majority of the discs (8 of 11). In magnetic resonance imaging, the size of the injury did not relate to the enhancement intensity. The subacute injuries, particularly the full-thickness injuries, were more often visualized than the acute ones., Conclusion: Even though macroscopically visible and histologically evident, it was not always possible to demonstrate experimental anulus injuries by contrast-enhanced magnetic resonance imaging. This experimental study shows that further research work is needed to develop more sensitive methods to detect peripheral, relatively small, but probably clinically important disc injuries.

Unlabelled: In the intervertebral disk, proteoglycans form the major part of the extracellular matrix, surrounding chondrocytelike disk cells. Keratan sulfate is a major constituent of proteoglycans., Methods: We have radioiodinated a monoclonal antibody raised against keratan sulfate. This antibody was injected into rats (n = 6), and the biodistribution was studied. A model of intervertebral disk injury was developed, and two tail disks in each animal with both acute (2 wk old) and subacute (7 wk old) injuries were studied for in vivo antibody uptake., Results: The biodistribution at 72 h was as follows: blood, 0.0018 percentage injected dose per gram of tissue (%ID/g); lung, 0.0106 %ID/g; esophagus, 0.0078 %ID/g; kidney, 0.0063 %ID/g; liver, 0.0047 %ID/g; spleen, 0.0046 %ID/g; heart, 0.0036 %ID/g; thyroid, 0.0034 %ID/g; muscle, 0.0017 %ID/g; and bone, 0.0016 %ID/g. In the subacute stage, a significant difference (P < 0.006) was found in antibody uptake between injured disks (n = 12) and adjacent healthy disks (n = 12). In vivo gamma imaging showed increased uptake in other animals having lumbar disk injuries (2, 7, and 17 d after injury). Cartilage tissue, such as the trachea, was studied separately and showed extremely high antibody uptake, 0.10 %ID/g. Rat trachea was also visualized on gamma images., Conclusion: Our data suggest that antibodies against nucleus pulposus components, such as proteoglycans, can be used for in vivo detection of intervertebral disk injury. This finding is in spite of the minimal circulation present in intervertebral disks.

Alterations involved with the intervertebral disc degeneration are partly well described, however, it is not so well known how collagen network is affected by the disease. We analyzed the rate of collagen biosynthesis (estimated by the enzymic activities of prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase) and the level of hydroxylysylpyridinoline and lysylpyridinoline crosslinks both in normal (n=7) and degenerated (n=7) human annulus fibrosus. The activity of prolyl 4-hydroxylase was significantly increased in degenerated tissue. However, no significant changes in the collagen content or in the amount of hydroxylysylpyridinoline and lysylpyridinoline collagen crosslinks were observed. On the other hand, the content of soluble proteins was significantly increased. Our results suggest that collagen biosynthesis is increased in degenerated human annulus fibrosus, obviously to compensate the impairment of collagen fibers. The faster turnover of collagen in degenerated annulus fibrosus, suggested by the increased prolyl 4-hydroxylase activity and unchanged collagen content, seems not to cause any significant changes in its mature pyridinium crosslink concentrations.

Objectives: To assess the eventual presence, tissue localization, molecular forms, amount and activity of cathepsin G in the annulus fibrosus., Methods: Normal non-autolytic disc tissue was collected from cadavers within six hours after death. Degenerate disc samples were collected from low back pain patients undergoing anterior interbody fusion due to severe, discographically verified and painful disc degeneration, and from the posterior parts of intervertebral discs from 10 patients undergoing microscopic discoidectomy because of intervertebral herniation. Avidin-biotinperxidase complex staining of cathepsin G was quantitated by morphometry. Cellular localization was analyzed using double immunofluorescence staining of cathepsin G and CD68, proline 4-hydroxylase or von Willebrand factor. Neutral salt extracts were analyzed by using synthetic cathepsin G substrate in spectrophotometry, dot-immunoblotting and Western blotting., Results: Histological and morphometric image analysis showed increased cellularity, increased numbers of cathepsin G positive cells and neovascularization in degenerated discs compared to control discs. Neutral salt extract of disc tissue, degenerated or normal, in contrast to control material from synovial capsular tissue, did not contain measurable cathepsin G activity, although immunoreactive enzyme was detected in dot-immunoblotting. Western blotting demonstrated that the discal cathepsin G had an apparent molecular weight of 27 kDa., Conclusion: Due to its properties and localization in normal and pathologically altered tissue, cathepsin G probably plays both a direct and an indirect role in extracellular matrix degradation in the annulus fibrosus. Extracted cationic cathepsin G was immunoreactive, but was functionally inhibited by serpins or, more likely, by polyanionic proteoglycans and saccharins derived from the connective tissue matrix of the annulus fibrosus.

Objective: Proteoglycans are major components of the extracellular matrix of the intervertebral disc. They are vital for the biomechanical properties of the tissue, and are subject to changes in disc degeneration. We aimed to further define these changes and their relationship to normal aging., Methods: Normal discs (age 13-53 years, n = 6) were analyzed from 5 different sites across the sagittal anterior-posterior direction. Degenerated anterior annulus fibrosus was collected from 7 patients aged 39-46 years. Extracted proteoglycans were separated using agarose and polyacrylamide gel electrophoresis and detected with toluidine blue staining and Western blotting., Results: The center of the disc showed the highest level of total proteoglycans, but lowest levels of decorin and biglycan. Western blots displayed reduced signal for both glycanated and nonglycanated biglycan and decorin after adolescence, while an increased signal of biglycan was observed in degenerated annuli. The 7D4(-) and 3B3(-) epitopes on native chondroitin sulfate chains were present in the large proteoglycans of intervertebral discs, but their signal intensity had no correlation to degeneration. Chondroitinase ABC digestion of the blots brought up 7D4(+) signal in the small proteoglycans of degenerated, but not in healthy tissue. Decrease or total loss of 2B6(+) epitope (indicating 4-sulfated stubs of chondroitin sulfate chains) were found in the large proteoglycans of all degenerated annuli., Conclusion: Human intervertebral disc degeneration involves the accumulation of decorin and biglycan relative to other uronic acid containing proteoglycans, the disappearance of 4-sulfated core region in aggrecan-like large proteoglycans, and the emergence of a core structure in the chains of small proteoglycans reacting with the 7D4 antibody; these findings indicate a fundamental alteration in matrix properties that may contribute to the pathogenesis of the disease.