Samuel Tin Yan Cheung,Prudence Wing Hang Cheung,Jason Pui Yin Cheung
Why Are Some Intervertebral Discs More Prone to Degeneration? Insights Into Isolated Thoracic “Dysgeneration”
disc herniation,dysgeneration,high-intensity zones,intervertebral disc,low back pain,Pfirrmann,Schmorl’s nodes,Schneidermann,thoracic disc degeneration,SF-36
Study Design. Prospective observational study. Objective. To determine the prevalence of isolated thoracic degeneration on magnetic resonance imaging (MRI), demographic factors and imaging features, as well as the patient-reported quality of life outcomes associated with this condition. Summary of Background Data. Thoracic intervertebral discs are least susceptible to disc degeneration (DD) and may represent a manifestation of “dysgeneration.” These discs may never be hydrated from the beginning and seem hypointense on MRI. Patients and Methods. A population-based MRI study of 2007 volunteers was conducted. Each disc from C2/3 to L5/S1 was measured by Pfirrmann and Schneiderman grading. Disc herniation, Schmorl node (SN), high-intensity zones (HIZ), and Modic changes were studied. DD was defined by Pfirrmann 4 or 5. patient-reported quality of life scores, including a 36-item short-form questionnaire and visual analog scale for low back pain, were recorded. Subjects were divided into “isolated thoracic degeneration” (only thoracic segment) and “tandem thoracic degeneration” (thoracic with other segments). The association between imaging findings and isolated thoracic degeneration was determined using multivariate logistic regression. Results. The mean age of the subjects was 50.0 ± 0.5 and 61.4% were females (n = 1232). Isolated thoracic degeneration was identified in 2.3% of the cohort. Factors associated with isolated thoracic degeneration included lower age, C6/7 HIZ, T8/9 HIZ, and T8/9 SN. Factors associated with tandem thoracic degeneration included L4/5 posterior bulging. The thoracic and lumbar tandem degeneration group demonstrated higher bodily pain, despite a lower visual analog scale, and a higher physical component score of the 36-item short form. Conclusions. Isolated thoracic degeneration demonstrated an earlier age of onset, mostly involving the mid-thoracic region (T5/6–T8/9), and in association with findings such as SN. Subjects with tandem thoracolumbar degeneration had less severe lumbar DD and low back pain as compared with those with isolated lumbar degeneration. This paints the picture of “dysgeneration” occurring in the thoracic and lumbar spine. Level of Evidence. 1.
Why Are Some Intervertebral Discs More Prone to Degeneration? Insights Into Isolated Thoracic “Dysgeneration”

Prospective observational study.

To determine the prevalence of isolated thoracic degeneration on magnetic resonance imaging (MRI), demographic factors and imaging features, as well as the patient-reported quality of life outcomes associated with this condition.

Thoracic intervertebral discs are least susceptible to disc degeneration (DD) and may represent a manifestation of “dysgeneration.” These discs may never be hydrated from the beginning and seem hypointense on MRI.

A population-based MRI study of 2007 volunteers was conducted. Each disc from C2/3 to L5/S1 was measured by Pfirrmann and Schneiderman grading. Disc herniation, Schmorl node (SN), high-intensity zones (HIZ), and Modic changes were studied. DD was defined by Pfirrmann 4 or 5. patient-reported quality of life scores, including a 36-item short-form questionnaire and visual analog scale for low back pain, were recorded. Subjects were divided into “isolated thoracic degeneration” (only thoracic segment) and “tandem thoracic degeneration” (thoracic with other segments). The association between imaging findings and isolated thoracic degeneration was determined using multivariate logistic regression.

The mean age of the subjects was 50.0 ± 0.5 and 61.4% were females (n = 1232). Isolated thoracic degeneration was identified in 2.3% of the cohort. Factors associated with isolated thoracic degeneration included lower age, C6/7 HIZ, T8/9 HIZ, and T8/9 SN. Factors associated with tandem thoracic degeneration included L4/5 posterior bulging. The thoracic and lumbar tandem degeneration group demonstrated higher bodily pain, despite a lower visual analog scale, and a higher physical component score of the 36-item short form.

Isolated thoracic degeneration demonstrated an earlier age of onset, mostly involving the mid-thoracic region (T5/6–T8/9), and in association with findings such as SN. Subjects with tandem thoracolumbar degeneration had less severe lumbar DD and low back pain as compared with those with isolated lumbar degeneration. This paints the picture of “dysgeneration” occurring in the thoracic and lumbar spine.

1.

Thoracic disc degeneration (DD) manifesting with pain is uncommon due to the stiff ribcage and coronal orientation of the facet joint.1 The prevalence of thoracic disc herniation was found to be only 6.5%,2 however when present, it may lead to spinal cord compromise.3,4 Thoracic DD may result from a number of factors. Previous studies found that T6/7 at the apex of spinal curvature was associated with decreases in magnetic resonance imaging (MRI) signal intensity,5,6 suggesting a role of compressive stress at the mid-thoracic region. There is a paucity of literature focusing on thoracic DD alone.6,7 Whether DD occurs in isolation or in tandem within the thoracic spine is unknown. The relationship between thoracic DD and cervical and lumbar DD is also unclear. The location of Schmorl nodes (SN) in the thoracolumbar spine has been shown to be independent of age in adulthood, pointing toward a potential developmental etiology.8 These findings have a resemblance to the theory of “dysgeneration,”9 where some discs, which seem hypointense earlier on MRI may have never been hydrated since the beginning, as opposed to “degeneration,” which is a pathologic process that involves water loss in the intervertebral discs (IVDs). Furthermore, previous work evaluating the linkage between SN and low back pain (LBP) has shown that only the combination of a hypointense disc and endplate signal change, with or without SN, is significantly associated with LBP.10 This is in line with the phenomenon that the early onset of hypointense discs does not necessarily produce back pain, and subjects with back pain may not have degenerative findings on imaging.9 The prevalence, pattern, and determinants of isolated thoracic degeneration have yet to be elucidated and remain difficult to predict.11 We hypothesize that isolated thoracic degeneration is associated with findings like SN, which may predispose subjects to earlier onset thoracic DD. Thus, we asked, (1) What is the prevalence of isolated thoracic degeneration on MRI? (2) What are the demographic factors and degeneration-related imaging phenotypes that are associated with isolated thoracic degeneration? (3) Is upper or lower thoracic DD associated with tandem degeneration in the cervical and lumbar spine? (4) Is isolated thoracic degeneration associated with better patient-reported quality of life (PRQoL) outcome scores than tandem thoracic degeneration?

A total of 2062 Southern Chinese volunteers were openly recruited through newspaper advertisements, posters, and emails regardless of social and economic status. None had previous spinal surgery, spinal tumors, or marked spinal deformities. The selection was not based on the presence or absence of clinical symptoms. Among these subjects, 55 were excluded due to poor image quality, leaving 2007 subjects for imaging analysis. The mean age of the subjects was 50.0 ± 0.5 years and 61.4% were females (n = 1232). A subanalysis of the PRQoL outcomes included 713 subjects out of the 2007 subjects who voluntarily filled in the PRQoL questionnaires on the day of imaging (Figure 1). Ethics approval had been obtained from the local Institutional Review Board with written informed consent obtained from recruited subjects.

3T high-definition MRI machines were used and all patients were placed in the supine position for scanning. The following protocol was used: for T2-weighted sagittal scans; field of view of 28 cm×28 cm, slice thickness of 5 mm, slice spacing of 1 mm, and imaging matrix of 448×336. The repetition time was 3320 ms, whereas the echo time was 85 ms.

Information related to age, sex, weight, height, history of low back injury, and smoking, was collected. Body mass index (BMI; kg/m2) categories modified for Asian populations based on World Health Organization guidelines were used.12 Individuals with a BMI of >27.5 kg/m² were classified as obese. Individuals with any event of a blow or traumatic episode that resulted in back pain were regarded as having a history of low back injury. Smoking status was categorized as a current or previous cigarette smoker, and the duration of smoking (yr) was also considered.

Disc and endplate measurements included any disc herniation,13 Pfirrmann grading,14 Schneiderman grading,15 SN,16 high-intensity zones (HIZ) lesions,17 and Modic changes (MC).18 All parameters were studied per level from C2/3 to L5/S1. Disc herniation score had 5 categories: 0 = no disc herniation; 1 = posterior disc bulging (disc is displaced beyond a virtual line connecting the posterior edges of 2 adjacent vertebrae); 2 = disc protrusion (distance between the edges of the disc material beyond the disc space is less than the distance between the edges of the base in the same plane); 3 = disc extrusion (distance between the edge of the protruded disc into the spinal canal is greater than the distance between edges of the base of the disc); 4 = disc sequestration.18 Pfirrmann and Schneiderman gradings were used for scoring DD. For Pfirrmann grading: 1 = homogeneous bright white disc; 2 = inhomogeneous white disc with or without horizontal bands; 3 = inhomogeneous grey disc; 4 = inhomogeneous grey to black disc; 5 = inhomogeneous black disc. Schneiderman grading: 1 = slight decrease in signal intensity in the nucleus pulposus; 2 = generalized hypointense nucleus; 3 = generalized hypointense nucleus with disc space narrowing. Disc hypointensity seen in Pfirrmann grades 4 and 5 was considered as DD.6,7,19 A particular spinal segment (cervical, thoracic, or lumbar) was considered to be degenerated if any disc within the segment has degenerated. A subanalysis of subjects with thoracic DD divided participants into 2 groups, subjects with “isolated thoracic degeneration”—those with any level(s) of DD found exclusively in the thoracic spine, versus “tandem thoracic degeneration”—those with thoracic degeneration and concurrent degeneration in the cervical and/or lumbar segment.6 SN was described as herniation of the nucleus pulposus into the adjacent vertebrae.16 HIZ was characterized by a high-intensity area of the annulus fibrosus either posteriorly or anteriorly.17 MC were signal intensity changes in the vertebral body adjacent to the endplates.18 We also noted the anterior location of MC if it occurs in the anterior region of the endplate in isolation.20 PRQoL scores including Oswestry Disability Index (ODI), 36-item short-form questionnaire, Roland-Morris Questionnaire, and visual analog scale (VAS) for LBP were recorded.

Descriptive statistics on patient demographics and frequency statistics on imaging phenotypes were obtained. Kolmogorov-Smirnov test was used for normality testing, where all continuous variables investigated were significantly different from the normal distribution (P < 0.001), hence they were analyzed using the Mann-Whitney U test (Supplemental File 1, Supplemental Digital Content 1, http://links.lww.com/BRS/C41), to determine any differences between the two groups. Categorical variables were analyzed with Pearson χ2 to determine any differences in occurrence between the two groups (Supplemental File 2, Supplemental Digital Content 2, http://links.lww.com/BRS/C42). Univariate logistic regression was used to detect associations between the demographics, imaging characteristics, and clinical implications with the outcome of isolated thoracic degeneration (Supplemental File 3, Supplemental Digital Content 3, http://links.lww.com/BRS/C43). The variables, which were statistically significant in univariate logistic regression (except Pfirrmann and Schneiderman grading, since a pattern of DD was the case-defining criterion) were included in the multivariable stepwise regression, with age and sex-adjusted, as we consider this an exploratory approach. Odds ratios (OR) with a 95% CI were reported. Variance inflation factor was used for the assessment of multicollinearity between the variables in the last step of multivariate logistic regression, which ranged from 1.004 to 1.032 and was satisfactory. Thoracic discs were divided into 3 regions (upper thoracic: T1/2–T4/5; mid-thoracic: T5/6–T8/9; lower thoracic: T9/10–T12/L1). The association between upper thoracic and cervical DD, and lower thoracic with lumbar DD, was analyzed using univariate logistic regression. PRQoL scores between groups of subjects were analyzed using the Mann-Whitney U test to determine any additional effect of thoracic degeneration on the quality of life in this population. Cronbach α was utilized to assess intraobserver and interobserver reliabilities for the imaging parameters. An α value of 0.90 to 1.00 was noted to have excellent reliability and an α value of 0.80 to 0.89 was noted to have good reliability.21 All images were read and graded by 2 readers. Twenty subjects were randomly drawn out of the study population by a third person (a statistician) and first tested for interobserver agreement. The same 20 images were read again after 4 weeks of the first reading but in a randomized order. Intraobserver reliability was noted to be good to excellent (α = 0.84-0.93) whereas interobserver reliability was noted to be good to excellent (α = 0.89-1.00) between 2 independent observers. Any deviations were discussed among the readers and the final agreed measurement was used for analysis. Statistical tests were carried out by SPSS 27.0 software (SPSS Inc.) and a P value of <0.05 was treated as significant.

Baseline demographics of both isolated thoracic degeneration and tandem thoracic degeneration groups are shown in Table 1. The mean age of the isolated thoracic group was lower than that of a tandem thoracic group (49.4 vs 53.5 yr, P = 0.003), where there was no significant difference between weight, height, BMI, smoking duration, and sex between the two groups. The prevalence of DD stratified by age (decade) and sex in the cervical, thoracic, and lumbar segments and the whole spine is shown in Table 2. The presence of thoracic DD was not associated with LBP (P = 0.827) and bodily pain (BP) (P = 0.402) but was associated with cervical DD (P < 0.001) and lumbar DD (P < 0.001). The number of thoracic degenerative discs was associated with less BP (r = −0.092, P = 0.014), whereas the association between overall thoracic Pfirrmann score and BP was not significant (r = −0.069, P = 0.066). The prevalence of thoracic degeneration in the 2007 subjects was 58.5% (n = 1174, 455 males and 719 females). Out of the subjects with thoracic degeneration, 4% had isolated degeneration and 96% had tandem degeneration. Overall, those with tandem degeneration involving all 3 segments had the highest prevalence (74.8%). The prevalence of each pattern of degeneration is shown with a Venn diagram (Figure 2). Associations between isolated thoracic degeneration and lower age (OR = 0.93; 95% CI: 0.90–0.97; P < 0.001), C6/7 HIZ (OR = 3.30; 95% CI: 1.12–9.74; P = 0.031), T8/9 HIZ (OR = 60.02; 95% CI: 11.15–323.16; P < 0.001), T8/9 SN (OR = 3.93; 95% CI: 1.41–10.93; P = 0.009), and L4/5 posterior bulging (OR = 0.23; 95% CI: 0.01–-0.56; P = 0.001) were observed after multivariate logistic regression (Table 3). The presence of T8/9 SN had a male predominance (OR = 3.57, P < 0.001) but no association with age or BMI. The presence of T8/9 HIZ was also significantly associated with age (OR = 1.18, P < 0.001) but not with sex or BMI (Table 4). Of note, the isolated thoracic group showed the highest prevalence of SN in some cervical disc levels, namely C3/4, C4/5, and C6/7, as well as in the mid-thoracic region (T5/6, T7/8, and T8/9; Figure 3A). The highest prevalence of HIZ was found in the mid-thoracic and lower thoracic regions (Figure 3B). The presence of upper thoracic degeneration was associated with cervical and thoracic tandem degeneration (OR = 3.014, P = 0.001). The prevalence of upper thoracic (T1/2–T4/5) DD was higher in cervical and thoracic tandem degeneration than in isolated thoracic degeneration. No significant association was observed between lower thoracic degeneration and thoracic or lumbar tandem degeneration (OR = 2.245, P = 0.064; Figure 4). Although there were no significant differences in PRQoL scores between subjects presenting with isolated thoracic as compared with tandem thoracic degeneration, tandem thoracic degeneration had distinctive manifestations of back pain as compared with other patterns of regional spine degeneration (Table 5). The thoracic and lumbar tandem degeneration group had higher BP (P = 0.012), despite a lower VAS score (LBP) on the day of imaging (P = 0.021), and higher physical component summary (PCS; P = 0.016) when compared with isolated lumbar degeneration. In addition, the thoracic and lumbar tandem degeneration group had higher physical function scores (P = 0.029). The cervical and thoracic tandem degeneration group had lower physical function than the isolated cervical degeneration group (P = 0.04). Degeneration in all 3 regions had higher ODI (P = 0.005), lower social function (P = 0.004), and lower PCS (P = 0.022).

The concept of dysgeneration suggests a possible mechanism for earlier loss of disc signal intensity without discogenic pain. Thoracic IVDs are less susceptible to painful DD,6 and isolated thoracic degeneration may well be a manifestation of dysgeneration. The prevalence of isolated thoracic degeneration in our cohort was 2.3%. Factors associated with isolated thoracic degeneration included younger age and mid-thoracic (T8/9) disc maldevelopment in the form of SN. Isolated thoracic SN is associated with DD, and these often present with cervical SN in the absence of DD. Upper thoracic DD is also similarly associated with cervical DD. Subjects with tandem degeneration involving the thoracic and lumbar region have less pain when compared with isolated lumbar degeneration. The prevalence of degeneration was lowest (58.5%) in the thoracic region, compared with 74.9% in the cervical spine and 68.9% in the lumbar region. This is aligned with the findings of Matsumoto et al,22 whereas our findings stratified by biological sex are comparable to those of Teraguchi et al.6 Overall, the low prevalence of thoracic DD supports the concept of ribcage protection and lack of thoracic motion with coronally orientated facets reducing the risk of degenerative changes.1,23 The isolated thoracic degeneration group had a lower mean age and was associated with SN (Figure 5) as compared with the tandem group, suggesting maldevelopment as a possible etiology for this condition. Specifically, we observed T8/9 SN with DD, especially in the isolated thoracic degeneration group. The significance of the T8/9 level can be explained by the difference in compressive load acting on IVDs. A previous study on compressive stress24 noted that T8/9 were the 2 vertebral bodies under the highest compressive stress in the entire spine. It is also the level, at which anterior and posterior loads are balanced, and coupled with the fact that vertebral endplate cortical thickness is the thinnest in the central portion,25 it is understandable why SNs are more likely to be found here. Therefore, we propose that despite the developmental origin of SNs, variations in compressive loads across the thoracic spine and varying sagittal plane alignment26 could play a role in the location of SN and subsequent predisposition for earlier degenerative issues. As for why SN and HIZ in the mid-thoracic region are associated with isolated thoracic degeneration, 2 proposed pathways of DD namely “annulus-driven degeneration” and “endplate-driven degeneration”27 should be considered. These are represented by HIZ and SN on MRI, respectively. HIZs are conventionally observed to be manifestations of early DD,28–31 and are more prevalent in older patients.32,33 The contradictory finding is that a higher prevalence of T8/9 HIZ manifests in the isolated thoracic degeneration group despite the group having a lower mean age, a lower prevalence of DD within thoracic disc levels, and lower overall thoracic Pfirrmann scores (P < 0.001–0.012) than the tandem thoracic degeneration group (8.5% vs 0.4%, P < 0.001). This suggests that the presence of HIZ in the isolated thoracic degeneration group is not derived from aging and DD alone.34 Therefore, the role of SN in the formation of HIZ should be considered. As shown by Adams et al,35 endplate structural defects reduce the pressure in the nucleus of adjacent discs and transfer the stress to the posterior annulus. It has also been shown in the lumbar spine that repetitive loading during bending and compression can cause the nucleus to herniate into the annulus.35,36 Based on our findings, mid-thoracic HIZ is unlikely a singular cause for isolated thoracic DD. The etiology of upper, mid, and lower thoracic DD is likely different. Upper thoracic DD was associated with cervical DD but lacked HIZ and SN characteristics. Isolated thoracic DD is mostly related to the mid-thoracic region, in which SN was also highly prevalent. This again suggests SN as an indicator of maldevelopment and a potential precursor for this pattern of DD. In our cohort, the presence of DD was associated with higher VAS on the day of imaging (P < 0.001), higher VAS at the severest timepoint (P = 0.001), higher ODI (P < 0.001), and higher Roland-Morris Questionnaire (P < 0.002). Therefore, our findings support the proposition of lumbar DD being associated with LBP, in contrast to thoracic DD being independent of LBP and BP. Interestingly, the severity of lumbar degeneration was lower in the thoracic and lumbar tandem degeneration group than that of the isolated lumbar group exemplified by a lower overall lumbar Pfirrmann score (P < 0.001). This supports the finding of lower VAS scores and higher PCS scores in the thoracic and lumbar tandem degeneration group. The less “degenerated” lumbar spine in these tandem groups suggests the potential scenario of thoracic dysgeneration followed by contiguous lumbar DD,37,38 which should be verified in future longitudinal work. In addition, higher BP scores in tandem thoracic and lumbar degeneration than isolated lumbar degeneration group confirms our hypothesis that thoracic degeneration concurrent with degeneration in other segments presents differently than lumbar DD alone. There are some limitations inherent to our cross-sectional design—the most obvious of which is that causation cannot be derived from the data. We also cannot rule out the possibility that those with tandem thoracic degeneration involving the cervical and/or the lumbar segment started out with isolated thoracic degeneration only, and progressed to involve the cervical and lumbar segments as well, as a manifestation of age-related DD.7 This leads to an underestimation of the prevalence of isolated thoracic degeneration as may be seen with a 4% prevalence. The design and approach of this work remain exploratory and findings should be seen as hypothesis-generating.

We maintain that the presence of SN in the mid-thoracic region predisposes individuals to the development of earlier isolated DD. Furthermore, the incidence of isolated thoracic DD may be dependent on accumulated compression and loading with age, as exemplified by the highest compressive load at T8/9 in the mid-thoracic region. This is unique to the mid-thoracic region as upper thoracic DD seems more similar to cervical DD. Imaging of the thoracic spine in addition to the imaging of the cervical or lumbar spine in isolation could prove useful in estimating a subject’s PRQoL as those with tandem thoracic degeneration may experience worse back pain as compared with those with isolated cervical or lumbar degeneration.

Subjects with isolated thoracic degeneration are younger than tandem thoracic degeneration. Isolated thoracic degeneration mostly involves the mid-thoracic region (T5/6–T8/9), where the prevalence of DD and SN is the highest. Thoracic degeneration in addition to lumbar degeneration (compared with isolated lumbar degeneration) presents with higher BP but lower VAS for LBP and a lower overall lumbar Pfirrmann score on the day of imaging.

