Chronic low back pain in relation to Modic changes, bony endplate lesions, and disc degeneration in a prospective MRI study.

PURPOSE: To clarify the significance of Modic changes, bony endplate lesions, and disc degeneration as predictors of chronic low back pain (LBP) during 1-year follow-up. METHODS: 49 patients with severe, non-specific, chronic LBP, and Modic 1 lesion (M1) were prospectively studied with MRI and questionnaire. Changes in grade of disc degeneration, severity of Modic changes, Schmorl lesions, and bony endplate irregularities were evaluated and changes assessed in LBP intensity on numeric rating scale 0-10 and severity with Oswestry disability index 0-100 (ODI). Association between change in MRI findings and symptoms was computed using generalized estimating equations analysis. RESULTS: Although pain decreased in most patients during 1-year follow-up, it increased or persisted in 36 %. Change in M1, M2, bony endplate lesions, and signal intensity (SI) and height of the disc associated with change of pain intensity, while change in M1, bony endplate lesions, and disc height associated with change of ODI. Not only persistent M1s, increasing bony endplate lesions, decreasing disc height, and M2s, but also new M2s predicted persistence of pain, while decrease of M1s and SI of the disc and increase of size of M2s predicted decrease of pain. Changes in disc bulges did not associate with pain. CONCLUSIONS: In patients with chronic non-specific LBP, persisting M1, decreasing disc height, and increasing bony endplate lesions associated with persisting pain while decrease of SI of the disc with decrease of pain. Such changing MRI findings in the same disc space have earlier been shown to progress abnormally fast. They may be signs or biomarkers of a prolonged pain causing, deforming degenerative process, and should lead to considering early intervention or specific treatments to affect that process.

Association between changes in lumbar Modic changes and low back symptoms over a two-year period.

BACKGROUND: The association of Modic changes (MC) with low back pain (LBP) is unclear. The purpose of our study was to investigate the associations between the extent of Type 1 (M1) and Type 2 (M2) MC and low back symptoms over a two-year period. METHODS: The subjects (n = 64, mean age 43.8 y; 55 [86%] women) were consecutive chronic LBP patients who had M1 or mixed M1/M2 on lumbar spine magnetic resonance imaging (MRI). Size and type of MC on sagittal lumbar MRI and clinical data regarding low back symptoms were recorded at baseline and two-year follow-up. The size (%) of each MC in relation to vertebral size was estimated from sagittal slices (midsagittal and left and right quarter), while proportions of M1 and M2 within the MC were evaluated from three separate slices covering the MC. The extent (%) of M1 and M2 was calculated as a product of the size of MC and the proportions of M1 and M2 within the MC, respectively. Changes in the extent of M1 and M2 were analysed for associations with changes in LBP intensity and the Oswestry disability index (ODI), using linear regression analysis. RESULTS: At baseline, the mean LBP intensity was 6.5 and the mean ODI was 33%. During follow-up, LBP intensity increased in 15 patients and decreased in 41, while ODI increased in 19 patients and decreased in 44. In univariate analyses, change in the extent of M1 associated significantly positively with changes in LBP intensity and ODI (beta 0.26, p = 0.036 and beta 0.30, p = 0.017; respectively), whereas the change in the extent of M2 did not associate with changes in LBP intensity and ODI (beta -0.24, p = 0.054 and beta -0.13, p = 0.306; respectively). After adjustment for age, gender, and size of MC at baseline, change in the extent of M1 remained significantly positively associated with change in ODI (beta 0.53, p = 0.003). CONCLUSION: Change in the extent of M1 associated positively with changes in low back symptoms.

Modic type I change may predict rapid progressive, deforming disc degeneration: a prospective 1-year follow-up study.

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.

Correlation of size and type of modic types 1 and 2 lesions with clinical symptoms: a descriptive study in a subgroup of patients with chronic low back pain on the basis of a university hospital patient sample.

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.

Relationship of Modic type 1 change with disc degeneration: a prospective MRI study.

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.

MRI follow-up of subchondral signal abnormalities in a selected group of chronic low back pain patients.

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.

Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus fibrosus more often in chondrocyte-like disc cells than in fibroblast-like disc cells. Control discs showed cellular immunopositivity for only TGFbeta-1 and -2 and TGFbeta receptor type II . We suggest that growth factors create a cascade in intervertebral disc tissue, where they act and participate in cellular remodelling from the normal resting stage via disc degeneration to disc herniation.

Efficacy of cold gel for soft tissue injuries: a prospective randomized double-blinded trial.

BACKGROUND: The use of cold treatment to limit edema, decrease pain, and induce effective muscle relaxation in soft tissue injuries is widespread. PURPOSE: To compare the efficacy of a novel cold gel with that of a placebo gel in patients with a soft tissue injury. STUDY DESIGN: Prospective randomized double-blinded controlled study. METHODS: Seventy-four patients with sports-related soft tissue injury were randomly assigned to active cold gel (Ice Power) or placebo gel groups. The gel was applied four times daily on the skin for 14 days. Clinical assessment was made after 7, 14, and 28 days with use of visual analog scale ratings. RESULTS: Pain scores decreased from 59 to 30 during the first week, to 14 by the second, and to 7 by the end of study in the cold gel group. In the placebo group, pain scores decreased from 58 to 45, 26, and 13, respectively (significant difference). Patient satisfaction with treatment was 71 in the cold gel group and 44 in the placebo group (significant difference). Disability decreased significantly more rapidly in the cold gel group. CONCLUSIONS: Cold gel therapy provided an effective and safe treatment for sports-related soft tissue injuries.

Complement membrane attack complexes in pathologic disc tissues.

STUDY DESIGN: Complement membrane attack complexes were located in lumbar spine disc tissues by immunohistochemistry. Their occurrence was compared in control discs obtained from organ donors (CD), discs showing a normal macroscopic anatomy, samples of intervertebral disc herniations (DH), and intervertebral discs found to be degenerated by discography, but not herniated (DD). OBJECTIVE: To look for a possible role of complement activation, specifically complement membrane attack complexes, an end product of the classic immune complex-mediated complement activation pathway, in disc pathophysiology. SUMMARY OF BACKGROUND DATA: Recent immunohistochemical and biochemical studies suggest a possible role for immune complexes, as observed by immunohistochemical location and biochemical assay of immunoglobulins M and G in intervertebral disc pathophysiology. Immune complexes may trigger complement activation and ultimately cell lysis. There are, however, currently no reports on complement activation in disc tissues, although immune (antigen-antibody) complexes have been demonstrated. Such immune complexes have been reported to occur on or near to disc cells in DH tissues. METHODS: Thin frozen sections of disc tissue from CD (n = 9 discs), DH (n = 58 discs), and DD (n = 11 discs) were cut and then immunostained with a monoclonal antibody to the complement membrane attack complex (C5b-9) using avidin-biotin complex (ABC) immunostaining. The presence or absence of complement membrane attack complex immunoreactivity was compared in the various subtypes of DH and also with preoperative duration of radicular pain. RESULTS: Complement membrane attack complexes could be observed in none of the CDs studied. In contrast, in more than one third of both the DH (21/58, 36.2%) and the DD (4/11, 36.4%), immunoreactivity to complement membrane attack complexes could be observed in disc cells. In DD discs, immunoreactivity to complement membrane attack complexes was most often present in anulus fibrosus samples (5/13, 38.5%). With respect to subtype of DH, complement membrane attack complexes were observed in 19 of 36 sequestrated discs (52.8%), 1 of 16 extrusions (6.3%), and 1 of 6 protrusions (16.7%). Complement membrane attack complexes were more often present with shorter pain duration (P= 0.03), but showed no relation to age. Disc cells often showed a heavy staining pattern for complement membrane attack complexes, suggesting an abundance of these complexes lodged in the membrane of the cells. CONCLUSIONS: The predominant presence of complement membrane attack complexes in sequestrated disc tissue could suggest a role in DH tissue-induced sciatica. Possibly immune (antigen-antibody) complexes, reported in previous studies, trigger the classic pathway of complement activation, with complement membrane attack complexes as the final product. Complement membrane attack complexes also appear to have some as yet undefined role in degenerated nonherniated disc tissue, with a predominant presence in the anulus fibrosus cells of such discs.

The diagnostic value of contrast-enhanced magnetic resonance imaging in the detection of experimentally induced anular tears in sheep.

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.

Blood clots in vessels surrounding symptomatic nerve roots in disc herniation patients: a pilot study.

Mechanical compression and biochemical influences, e.g. by various inflammatory cells and mediators, have been suggested to be involved in the pathophysiology of sciatica. In addition, it has been suggested, but so far not clearly demonstrated, that blood pooling in the venous blood vessels surrounding nerve roots may contribute to impaired nerve root function and sciatica. There is also more direct evidence from studies on an animal model that nucleus pulposus (NP) tissue may induce blood vessel thrombosis. In the present study, a specific monoclonal antibody to platelet membrane glycoprotein complex GPIIb-IIIa was used for direct visualization of blood clots in tissue samples removed from the vicinity of symptomatic nerve roots in 20 disc herniation (DH) patients. For 12 patients, the DH was primary, for 7 patients recurrent and for 1 patient the index operation was for root canal stenosis following a DH operation 3 months earlier. Blood clots immunoreactive to GPIIb-IIIa were observed in small blood vessels in 11/20 tissue samples (55%), in 5/12 patients (42%) with primary DH and in 5/7 patients (71%) with recurrent DH. The presence or absence of GPIIb-IIIa complex immunoreactivity did not show a statistically significant relationship with pain duration, DH type (primary or recurrent), gender or straight leg raising (SLR). Thus, though immunohistochemically demonstrable, the observed periradicular blood clots could not be established to have a clinical role in sciatica in this pilot study.

Oncoprotein c-Fos and c-Jun immunopositive cells and cell clusters in herniated intervertebral disc tissue.

The oncoproteins c-Fos and c-Jun create a transcriptional site early response activating protein (AP-1) mediating the regulation of gene expression in response to extracellular signalling by, for example, cytokines. These proteins are important in the signalling pathway from the cell membrane to the nucleus. Previously, oncoproteins have been located in articular synovium and in chondrocytes, participating in transcription. There is, however, no such study of intervertebral disc tissue. In disc degeneration and after herniation, cell proliferation markers have been demonstrated. In the present study we visualize the AP-1 transcriptional site factors c-Fos and c-Jun in 38 human herniated intervertebral disc tissue samples by immunohistochemical staining with monoclonal antibodies. No immunoreactivity could be observed in control disc tissue, indicating that after herniation, disc cells are entering from the resting stage to the cell cycle. Furthermore, c-Jun immunoreactivity was also observed in disc cell clusters, thus demonstrating them to be active transcriptional sites in disc tissue. c-Fos immunoreactivity was seen in 15/38 and c-Jun in 28/38 herniated discs (39% and 74% respectively). Immunopositive groups of disc cells were noted in 7/28 (25%) of the oncoprotein-immunopositive samples. We did not see any difference in immunoreactivity between female and male patients. Furthermore, we did not notice any statistical difference regarding the immunoreaction for proto-oncogenes c-Fos and c-Jun in extrusions, sequesters and protrusions. Nor did immunostaining show any significant relationship with preoperative pain duration. We concluded that, in herniated disc tissue, the oncoproteins c-Fos and c-Jun are activated in disc cells and cell clusters. In the future, learning more about this transcriptional signal pathway may result in new specific treatments for intervertebral disc pathology.