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Herniated, spondylotic intervertebral disks differ histologically, immunohistochemically, study shows

Tuesday, September 30 2008 | Comments

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What's This? Herniated and spondylotic intervertebral disks appear to undergo different degenerative processes, according to the results of a large histological and immunohistochemical study.

Between December 1998 and February 2007, 500 cervical intervertebral disks were excised from 364 patients--248 were harvested from 198 patients (121 males; mean age at surgery, 49.9 years; age range, 25 to 78 years) who presented with cervical intervertebral disk herniation. The remaining 252 disks were obtained from 166 patients (105 males; mean age at surgery, 59.6 years; age range, 32 to 83 years) who presented with spondylosis.

All of the patients presented with clinical signs and symptoms of radiculopathy, myelopathy, or myeloradiculopathy, and none were taking corticosteroids or immunodepressants. The average duration of symptoms prior to surgery was 3.2 months (range, 0.5 to 6.0 months) for the patients with cervical intervertebral disk herniation and 5.5 months (range, 0.8 to 37.5 months) for those with spondylosis.

Plain radiographs and high-resolution magnetic resonance images were used to assess types of herniation and degrees of disk degeneration. The researchers examined en bloc samples of endplate-ligament-disk complexes histologically and immunohistochemically.

Eight cervical intervertebral disks removed during autopsies were used as positive controls (mean age at death, 73 years). Based on medical chart data, the controls were free of cervical radiculopathy and myelopathy.

The differences in the histological and immunochemical properties of the disks were readily apparent. The herniated disks showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue predominantly in the ruptured outer layer of the anulus fibrosus. According to the researchers, the vascular invasion was most significant in uncontained (extruded)-type herniated disks. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both types of disks.

Free nerve fibers, which were positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were apparent in and around the outer layer of uncontained (extruded)-type herniated disks, with enhanced expression of NGF.

Of note, the investigators found that the herniated disks showed more advanced degeneration as compared with the spondylotic disks in the outer layer of the anulus fibrosus around the granulation tissue. However, they noted that the spondylotic disks showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus, relative to the herniated disks. The spondylotic disks also had thicker bony endplates and expressed TNF-alpha and MMP-3 more diffusely, particularly in the inner layer of the anulus fibrosus.

These results led the study authors to conclude that herniated and spondylotic intervertebral disks degenerate for different reasons. It seems that the expression of TNF-alpha, MMP-3, bFGF, and VEGF is upregulated via the herniated mass in herniated intervertebral disks, whereas nutritional impairment appears to cause degeneration in spondylotic disks. Further, macrophage accumulation around newly formed blood vessels in herniated disk tissues seems to be regulated by MMP-3 and TNF-alpha expression, they noted, and both types of disks exhibit marked neoangiogenesis associated with increased bFGF and VEGF expression. The authors also remarked that nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus and in the endothelial cells of the small blood vessels.

"Future investigations should seek immunohistological evidence of free nerve endings and development of neural tissues within the disks," the authors recommended. (Kokubo Y, et al. J Neurosurg Spine 2008;9:285-295.)

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