6 Grading Scales for Disc Degeneration and Regeneration: Clinical and Experimental
Peter Grunert
Abstract
Several grading scales have been developed to quantify disc degeneration and regeneration. They are either based on macroscopic anatomy, histology or X-ray and magnetic resonance imaging (MRI). Macroscopic changes are evaluated ex vivo on mid-sagittal sections of explanted spinal segments. The most common grading system was developed by Thompson et al. It takes nucleus pulposus morphology, annulus fibrosus and end plate intactness as well as osteophyte formation into account. The Thompson grade is commonly used to validate degenerative changes assessed by novel imaging techniques or biochemical markers. Various histology based classifications have been developed for the human and animal spine. Boos et al established a grading scale for the human spine which takes matrix staining properties, cell quantity and as well as endplate morphology into account. Histological animal spine classifications are often used for in vivo disc regeneration experiments. Han et al developed a grading system in the rat spine which based on cell composition and morphology as well as staining properties of the extracellular matrix. X-Ray and MRI techniques allow for in vivo assessment of disc degeneration which makes it the most relevant assessment for clinical outcome studies. Pfirrmann developed an MR imaging grading system predominantly based on nucleus pulposus T2 signal intensity as well as loss of disc height. Recently quantitative MRI techniques have been introduced which allow for indirect assessments of the biochemical tissue composition of intervertebral discs. This facilitates to detect early degenerative changes in vivo.
Keywords: degeneration, grading system, histology, intervertebral disc, regeneration, MR imaging
6.1 Introduction
Grading scales for intervertebral disc (IVD) degeneration are important to evaluate degenerative processes and success of regenerative efforts. Scales allow researchers to present and compare study outcomes more objectively given that results on disc health are presented with a numeric value in contrast to nonquantitative assessments, which most commonly rely on an objective morphological description of disc pathology.
There are three different diagnostic assessments for which grading scales have been established to quantify degenerative changes of IVDs: (1) macroscopic anatomy, (2) histology, and (3) radiology.
6.2 Macroscopic Anatomy
Macroscopic anatomy is studied on gross sections of IVDs either by a mid-sagittal cut through a spinal segment or an axial cut through the middle of the disc. It allows ex vivo evaluation of native unstained tissue.
6.2.1 Grading Scales
Nachemson was the first to establish a grading scale for mid-axial (transverse) IVD sections in 1960.1 This four-scale grading system takes into account nucleus pulposus (NP) morphology (gelatinous or fibrotic), the intactness of the annulus fibrosus (AF), and whether both structures maintain a visible border. The disadvantage of a mid-axial cut is that it does not allow for evaluation of changes in end plate cartilage and the vertebral body. In 1990, Thompson et al developed a grading system for mid-sagittal sections that included those structures and therefore allowed for a more complete evaluation of spinal segments.2 It is the most commonly used macroscopic scale and became the standard system for quantifying degenerative changes in humans and animals.3,4 The Thompson system involves five scales that are graded according to the progression of NP, AF, end plate, and vertebral body alterations. Nuclear changes involve formation of fibrous tissue and clefts throughout the NP; annular changes include disruption of the lamellar tissue and loss of demarcation to the nucleus. End plate alterations range from focal defects to diffuse sclerotic changes. Vertebral bodies are evaluated for osteophyte formation (▶ Table 6.1). The excess of these degenerative alterations have been shown to correlate with specimen age.2
6.2.2 Experimental Value
The Thompson grade has proven to be of high experimental value and is therefore broadly used for research purposes.4 It has demonstrated a low intra- and interobserver variability2,4 resulting in reproducible and comparable scores. It has shown a correlation to cellular and biochemical degenerative parameters as evidenced by Iatridis et al, who demonstrated an inverse correlation of decreasing proteoglycan and water content.5 The same was found for the proteolytic enzyme aggrecanase.6 Antoniou et al demonstrated a positive correlation to the amount of denatured type II collagen.7 Additionally, the amount of senescent cells (without ability to proliferate) in the AF of degenerated discs has also shown a positive correlation.8
The Thompson grade also reflects degenerative changes on magnetic resonance imaging (MRI) in humans as well as in animals.3,9 Loss of NP T2 signal intensity as well as loss of disc height has been shown to correlates to increasing Thompson grades.3
6.2.3 Clinical Value
In contrast to its experimental value, the Thompson grade is of low clinical relevance given that it is based on gross sections from human cadavers. However, it is often used to validate clinical diagnostic tests such as MRI or X-ray imaging.10
6.3 Histology
Histology is used to study IVD tissue samples microscopically most commonly using mid-sagittal cuts through the segment. Histology analysis is used for ex vivo and in vivo11 evaluation of stained tissue in humans and animals. Compared with macroscopic anatomy it allows for evaluation of changes of cell density and composition as well as evaluation of matrix components via different staining methods. Besides hematoxylin and eosin (H&E), various stains are used for specific IVD structures. Alcian blue and Safranin-O are used to stain for proteoglycans12 and picrosirius red for collagen.13 Recently, a combination of both has been proposed.14
6.3.1 Grading Scales
Boos et al first introduced a histological grading system for human spinal segments using H&E and alcian blue stains.15 Degenerative changes were subdivided into changes of the IVD, cartilage end plate, and end plate bone. The disc is graded based on chondrocyte cell decay and density, mucus degeneration (accumulation of eosinophilic tissue), tear or cleft formation, and granular changes (basophilic tissue on alcian blue stains). End plate changes are graded according to intactness of cartilage tissue and bony sclerosis (▶ Table 6.2). These histological alterations showed a significant positive correlation with specimen age.15 Due to its complex design and large number of grading parameters, the Boos classification often had to be modified for research purposes.16,17 Another disadvantage is that the IVD is evaluated as a whole and not by its NP and AF component individually.
Table 6.2 Histology grading by Boos et al15 of intervertebral disc degeneration. Grading is based on sagittal paraffin sections stained with H&E, Masson-Goldner, and alcian blue-PAS.
Intervertebral disc | End plate |
Cells (chondrocyte proliferation) 0 = No proliferation 1 = Increased cell density 2 = Connection of two chondrocytes 3 = Small size clones (i.e., several chondrocytes group together, i.e., 2–7 cells) 4 = Moderate-size clones (i.e., > 8 cells) 5 = Huge clones (i.e., 15 cells) 6 = Scar/tissue defects | Cells 0 = Normal cellularity 1 = Localized cell proliferation 2 = Diffuse cell proliferation 3 = Extensive cell proliferation 4 = Scar/tissue defects |
Mucous degeneration 0 = Absent 1 = Rarely present 2 = Present in intermediate amounts 3 = Abundantly present 4 = Scar/tissue defects | Cartilage disorganization 0 = Well-structured hyaline cartilage 1 = Cartilage irregularities (obliterated vessels?) 2 = Disorganized matrix with thinning 3 = Complete cartilage disorganization with defects 4 = Scar/tissue defects |
Cell death 0 = Absent 1 = Rarely present 2 = Present in intermediate amounts 3 = Abundantly present 4 = Scar/tissue defects | Cartilage cracks 0 = Absent 1 = Rarely present 2 = Present in intermediate amounts 3 = Abundantly present 4 = Scar/tissue defects |
Tear and cleft formation 0 = Absent 1 = Rarely present 2 = Present in intermediate amounts 3 = Abundantly present 4 = Scar/tissue defects | Microfracture 0 = Absent 1 = Present 2 = Scar/tissue defects |
Granular changes 0 = Absent 1 = Rarely present 2 = Present in intermediate amounts 3 = Abundantly present 4 = Scar/tissue defects | New bone formation 0 = Absent 1 = Present 2 = Scar/tissue defects Bony sclerosis 0 = Absent 1 = Present 2 = Scar/tissue defects |
| Abbreviations: H&E, hematoxylin and eosin; PAS, periodic acid-Schiff. | |
Rutges et al designed a simpler grading system that evaluates the AF and NP separately.18 This classification system is similar to the macroscopic Thompson grading. The AF is described as organized or ruptured with a sharp or not distinguishable border to the NP. Nuclear alterations are classified with NP chondrocyte cellularity (cluster or no cluster formation) and nuclear matrix organization and staining with Safranin-O and alcian blue (▶ Table 6.3).
Table 6.3 Histology scoring items and grades according to Rutges18 classification.
