Severity Of Disc Degeneration Research Articles

288 Impact of Disc Degeneration on Clinical Outcomes After Fusion for Grade 1 Spondylolisthesis: A 5-year QOD Study

INTRODUCTION: Disc degeneration with loss of disc height can be an indication to fuse patients with lumbar spondylosis. However, its relevance for spondylolisthesis is unknown. METHODS: The Quality Outcomes Database was queried for adult patients who underwent fusion for single-level degenerative grade 1 lumbar spondylolisthesis. Pfirrmann grade at the level to be fused was assessed on preoperative sagittal T2-weighted MRI. VAS-back pain (BP-VAS), VAS-leg pain (LP-VAS), and ODI were collected preoperatively and at 3, 12, 24, 36, and 60 months postoperatively. RESULTS: The query returned 395 patients. Mean age (95% CI) was 60 (58.9-61.1) years; 39.5% were male. None had a Pfirrmann grade 1 disc. One (0.3%) had a grade 2 disc, 53 (13.4%) had a grade 3 disc, 245 (62%) had a grade 4 disc, and 96 (24.3%) had a grade 5 disc. Posterior-only approach was performed in 92.6%; interbody graft was placed in 92.7%. Mean BP-VAS (95% CI) at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were 7.1 (6.8-7.3) (n = 343), 3.1 (2.8-3.3) (n = 353), 2.9 (2.6-3.2) (n = 305), 3.2 (2.8-3.5) (n = 283), 3.5 (2.9-4.1) (n = 107), and 3.7 (3.3-4.0) (n = 324). Mean LP-VAS (95% CI) were 6.7 (6.4-7.0) (n = 392), 2.3 (2.0-2.6) (n = 353), 2.2 (1.9-2.6) (n = 306), 2.6 (2.2-2.9) (n = 284), 2.8 (2.2-3.4) (n = 107), and 2.8 (2.4-3.1) (n = 322). Mean ODI (95% CI) were 49.4 (47.8-51.1) (n = 392), 27.4 (25.3-29.5) (n = 347), 22.9 (20.6-25.2) (n = 313), 22.4 (20.1-24.8) (n = 291), 22.4 (18.3-26.4) (n = 97), and 25.9 (23.7-28.2) (n = 325). Utilizing linear regression, Pfirrmann grade was not associated with improvements in VAS-BP, VAS-LP, or ODI at any time point in unadjusted and adjusted analyses (p > 0.05). CONCLUSIONS: Patients who undergo fusion for single-level grade 1 spondylolisthesis are likely to experience significant and sustained improvements in pain and function regardless of severity of disc degeneration.

Диабетическая дорсопатия: от теории к практике

ABSRTACT INTRODUCTION. Currently, in the scientific literature, the problem of the relationship between pain in the lower back and diabetes mellitus is given great attention, and therefore the term diabetic dorsopathy has appeared. CONCLUSION. The treatment strategy for a patient with back pain depends on the age of presentation, the severity of disc degeneration associated with nerve compression, the stability of the functional spine, and the overall balance of the spinal column (ie, sagittal balance). Therapy for diabetic dorsopathy is based on the general principles of treating nonspecific back pain. The drugs of choice for acute back pain are non-steroidal anti-inflammatory drugs, when choosing which you need to take into account their pharmacodynamics and pharmacokinetics. Artoxan (tenoxicam) according to these parameters demonstrates proper efficiency and safety. In a patient with a polyneuropathic component of back pain and diabetic polyneuropathy, it is advisable to include the drug Cocarnit in complex therapy. The quadro-effect of Cocarnit components is able to influence different points of formation of complications of diabetes and significantly improve the quality of life of such patients, restoring neurometabolic processes, reducing pain, the drug increases patient adherence to therapy. KEYWORDS: comorbidity, pain, diabetes, diabetic dorsopathy

Obesity increases the odds of intervertebral disc herniation and spinal stenosis; an MRI study of 1634 low back pain patients.

The objective of this study was to examine the relationships between BMI and intervertebral disc degeneration (DD), disc herniation (DH) and spinal stenosis (SS) using a large, prospectively recruited and heterogeneous patient population. Patients were recruited through the European Genodisc Study. An experienced radiologist scored MRI images for DD, DH and SS. Multivariate linear and logistic regression analyses were used to model the relationship between these variables and BMI with adjustment for patient and MRI confounders. We analysed 1684 patients with a mean age of 51years and BMI of 27.2kg/m2.
The mean DD score was 2.6 (out of 5) with greater DD severity with increasing age (R2 = 0.44). In the fully adjusted model, a 10-year increase in age and a 5kg/m2 increase in BMI were associated, respectively, with a 0.31-unit [95% CI 0.29,0.34] and 0.04-unit [CI 0.01,0.07] increase in degeneration. Age (OR 1.23 [CI 1.06,1.43]) and BMI (OR 2.60 [CI 2.28,2.96]) were positively associated with SS. For DH, age was a negative predictor (OR 0.70 [CI 0.64,0.76]) but for BMI (OR 1.19 [CI 1.07,1.33]), the association was positive. BMI was the strongest predictor of all three features in the upper lumbar spine. While an increase in BMI was associated with only a slight increase in DD, it was a stronger predictor for DH and SS, particularly in the upper lumbar discs, suggesting weight loss could be a useful strategy for helping prevent disorders associated with these pathologies.

Male spondyloarthritis patients and those with longer disease duration have less severe disc degeneration: propensity score-matched comparison.

Using whole spine sagittal T2 MRI, we aimed to compare the severity and prevalence of disc degeneration (DD) in axial SpA patients vs the general population and to determine any association between spinal inflammation, structural changes, mobility and DD among SpA patients. Two prospectively collected cohorts of SpA patients (n = 411) and the general population (n = 2007) were recruited. Eventually, 967 participants from the populational cohort and 304 participants from the SpA cohort were analysed. Two hundred and nineteen matched pairs were generated by propensity score matching. Imaging parameters, including Pfirrmann grading, disc herniation, high-intensity zone, Schmorl's node, Modic change and anterior marrow change were studied and compared from C2/3 to L5/S1. DD was defined as Pfirrmann grade 4 or 5. Demographic factors, including age, sex and BMI, were collected. Multivariable linear regression was used to determine the association between spinal inflammation [Spondyloarthritis Research Consortium of Canada (SPARCC) spine MRI index], structural changes [modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS)] and mobility (BASMI) with lumbar Pfirrmann score. SpA patients had lower prevalence of DD (P < 0.001). The disease stage-stratified regression model showed that SPARCC spinal MRI index was associated with higher lumbar Pfirrmann scores in early disease (β = 0.196, P = 0.044), whereas mSASSS was associated with lower lumbar Pfirrmann scores in later disease (β = -0.138, P = 0.038). Males had higher mSASSS (P < 0.001) and lower odds of whole spine DD (odds ratio = 0.622, P = 0.028). SpA patients had lower DD severity than the general population. Males had higher mSASSSs, and increased mSASSS at later disease was associated with less severe DD.

Relation of lumbar intervertebral disc height and severity of disc degeneration based on Pfirrmann scores

BackgroundDisc height (DH) change is considered one of the most critical factors in assessing intervertebral disc degeneration (IVD). Pfirrmann et al. developed a scoring system for disc degeneration evaluation based on changes in DH in magnetic resonance imaging (MRI). While the relationship between DH measurements and Pfirrmann scores for disc degeneration has been explored, the validity of different DH measuring techniques or their connection with disc degeneration is yet uncertain. The present study investigates intra-rater and inter-rater agreement and reliability of different DH measurement methods on MRI and evaluates the relationship between different DH measurement methods and Pfirrmann scores of IVD degeneration, as well as between different Pfirrmann scores and clinical outcomes. MethodsAdult patients with MRI scans of the lumbar spine were recruited. Eight DH measuring techniques were tested for intra-rater and inter-rater agreement and reliability. Bland and Altman's Limits of Agreement (LOA) was used to evaluate intra-rater and inter-rater agreements. Intra-rater and inter-rater reliability were evaluated using intra-class correlations (ICC) with 95 % confidence intervals (95 % CI). The association between DH and Pfirrmann scores was examined using one-way ANOVA. ResultsExcellent intra-rater reliability was reported for 332 participants on DH (ranging from 0.912 (0.901, 0.923) to 0.973 (0.964, 0.981) and from 0.902 (0.892, 0.915) to 0.975 (0.962, 0.985) by two independent raters). All measuring methods had high intra-rater agreement, except for methods 4 and 5. All methods had good-to-excellent of inter-rater reliability on DH (ICCs ranging from 0.812 (0.795, 0.828) to 0.995 (0.994, 0.995)) except for the posterior disc material length of method 5 (ICC 0.740 (0.718, 0.761)). Methods 1 to 6 for evaluating DH in patients with spondylolisthesis had poor inter-rater reliability. The IVD levels with grades IV and V in Pfirrmann scores had significantly lower DH than the IVD levels with grades I to III in Pfirrmann scores. IVD levels with grades IV and V in Pfirrmann scores had significantly higher VAS and ODI than IVD levels with grades I in Pfirrmann scores. ConclusionA good-to-excellent intra-rater and inter-rater reliability was achieved on most DH measuring methods on MRI following a standardized and structured protocol. However, small anatomical structures and different tissue borders could influence measurements. Additionally, DH can differentiate between grade IV and V Pfirrmann scores, and severe IVD degeneration (IV and V Pfirrmann) is linked to clinical outcomes.

Development of normalized quantitative measures of lumbar disc degeneration.

Lumbar disc degeneration (DD) is widely regarded as a likely contributor to low back pain (LBP), but the association between DD and LBP is relatively weak. No known studies have normalized quantitative measures of DD severity relative to multiple variables such as age, height, and disc level. This study developed normalized quantitative measures (z-scores) of disc signal intensity (DSI) and disc height (DH) to rate relative severity of DD. Raw (unnormalized) quantitative measures of DSI and DH alongside potential normalization variables were acquired from MRI scans and clinical data of 76 patients. The associations between the raw quantitative measures and potential normalization variables were investigated to develop the normalized quantitative measures (z-scores) of DSI and DH. Construct validity was assessed by comparing the normalized measures to an experienced radiologist's subjective measures of relative severity of DSI and DH loss. CSF signal intensity, age, and disc level were significantly associated with raw DSI (R 2 = 0.06, 0.25, and 0.09, respectively). Lumbar height and disc level were significantly associated with raw DH (R 2 = 0.13 and 0.31). Normalizing DSI and DH by these variables resulted in stronger relationships (R 2 = 0.39 and 0.37) than raw DSI and DH (R 2 = 0.24 and 0.31) with the radiologist's subjective measures. Normalized DSI and DH were both normally distributed (p = 0.32 and 0.12). Construct validity and the distributions suggested that normalized quantitative measures of DSI and DH are better than existing measures of DSI and DH at rating relative DD severity. Determining whether normalized quantitative measures are more predictive of clinical outcomes is important future research.

Association between fatty infiltration in the cervical multifidus and treatment response following cervical interlaminar epidural steroid injection.

Recent attention has been directed towards fatty infiltration in the cervical extensor muscles for predicting clinical outcomes in several cervical disorders. This study aimed to investigate the potential association between fatty infiltration in the cervical multifidus and treatment response following cervical interlaminar epidural steroid injection (CIESI) in patients with cervical radicular pain. The data of patients with cervical radicular pain who received CIESIs between March 2021 and June 2022 were reviewed. A responder was defined as a patient with a numerical rating scale decrease of ≥ 50% from the baseline to three months after the procedure. The presence of fatty infiltration in the cervical multifidus was assessed, along with patient characteristics, and cervical spine disease severity. To assess cervical sarcopenia, fatty infiltration in the bilateral multifidus muscles was evaluated at the C5-C6 level using the Goutallier classification. Among 275 included patients, 113 (41.1%) and 162 (58.9%) were classified as non-responders and responders, respectively. The age, severity of disc degeneration, and grade of cervical multifidus fatty degeneration were significantly lower in responders. Multivariate logistic regression analysis revealed that pre-procedural symptoms (radicular pain with neck pain, odd ratio [OR] = 0.527, P = 0.024) and high-grade cervical multifidus fatty degeneration (Goutallier grade 2.5-4, OR = 0.320, P = 0.005) were significantly associated with an unsuccessful response to CIESI. These results suggest high-grade cervical multifidus fatty infiltration is an independent predictor of poor response to CIESI in patients with cervical radicular pain.

Correlation between inflammatory cytokine expression in paraspinal tissues and severity of disc degeneration in individuals with lumbar disc herniation

PurposePrevious animal studies have discovered dysregulation of the local inflammatory state as a novel mechanism to explain structural changes in paraspinal muscles in association with disc degeneration. This study aimed to determine whether the expression of inflammatory genes in the multifidus muscle (MM) differs between individuals with disc degeneration and non-degeneration, which may cause changes in the cross-sectional area (CSA) of paraspinal muscles and clinical outcomes.MethodsMuscles were procured from 60 individuals undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation (LDH). Total and functional CSAs and fatty degeneration of paraspinal muscles on ipsilateral and unilateral sides were measured. Gene expression was quantified using qPCR assays. Paired t-test and Pearson’s correlation analysis were used to compare the mean difference and associations, respectively.ResultsThere were significant differences in total CSAs of paraspinal muscles and functional CSA and fatty degeneration of MM between ipsilateral and unilateral sides. Participants in the disc degeneration group displayed higher fat infiltration in MM. The expression of TNF was moderately correlated with total CSAs of paraspinal muscles and functional CSA and fatty degeneration of MM. The expression of IL-1β was strongly correlated with the total and functional CSA of MM. The expression of TGF-β1 was moderately correlated with the functional CSA of MM. The expression of TNF, IL-1β, and TGF-β1 was moderate to strongly correlated with clinical outcomes.ConclusionThe results show that there were differences in the characteristics of paraspinal muscles between the ipsilateral and unilateral sides, which were affected by disc degeneration and the degree of fat infiltration. High-fat filtration and reduction of CSA of MM are associated with inflammatory dysfunction. There was evidence of a dysregulated inflammatory profile in MM in individuals with poor clinical outcomes.

Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence.

Lumbar stenosis due to wild-type transthyretin amyloid-induced thickening of the ligamentum flavum: a separate etiology from degeneration of intervertebral discs?

Wild-type transthyretin amyloid (ATTRwt) is deposited in the ligamentum flavum (LF) of a subset of patients with spinal stenosis who undergo decompressive surgery, although its role in the pathophysiology of spinal stenosis is unknown. It has been theorized that degeneration of intervertebral discs causes increased mechanical stress and inflammatory/degenerative cascades and ultimately leads to LF fibrosis. If ATTRwt deposits contribute to LF thickening and spinal stenosis through a different pathway, then patients with ATTRwt may have less severe disc degeneration than those without it. In this study, the authors compared the severity of disc degeneration between patients with lumbar stenosis with and without amyloid in their LF to test whether ATTRwt is a unique contributor to LF thickening and spinal stenosis. Of 324 consecutive patients between 2018 and 2019 who underwent decompression surgery for spinal stenosis and had LF samples sent for pathological analysis, 31 harboring ATTRwt were compared with 88 controls. Patient medical records were retrospectively reviewed for demographic and surgical information. Disc degeneration was assessed on preoperative T2-weighted MR images with the modified Pfirrmann grading system at every lumbar disc level. Baseline characteristics were similar between the groups, except for a statistically significant increase in age in the ATTRwt group. The crude unadjusted comparisons between the groups trended toward a less severe disc degeneration in the ATTRwt group, although this difference was not statistically significant. A multivariable linear mixed-effects model was created to adjust for the effects of age and to isolate the influence of ATTRwt, the presence of an operation at the level, and the specific disc level (between L1 and S1). This model revealed that ATTRwt, the presence of an operation, and the specific level each had significant effects on modified Pfirrmann scores. Less severe disc degeneration was noted in patients with degenerative spinal stenosis harboring ATTRwt compared with those without amyloid. This finding suggests that ATTRwt deposition may play a separate role in LF thickening from that played by disc degeneration. Future studies should aim to elucidate this potentially novel pathophysiological pathway, which may uncover an exciting potential for the development of amyloid-targeted therapies that may help slow the development of spinal stenosis.

Albumin-to-Alkaline Phosphatase Ratio as a Prognostic Biomarker for Spinal Fusion in Lumbar Degenerative Diseases Patients Undergoing Lumbar Spinal Fusion.

Objective: To determine if preoperative albumin-alkaline phosphatase ratio (AAPR) is predictive of clinical outcomes in patients with degenerative lumbar diseases undergoing lumbar fusion. Method: 326 patients undergoing posterior lumbar decompression and fusion were retrospectively analyzed. The cumulative grade was calculated by summing the Pfirrmann grades of all lumbar discs. Grouping was based on the 50th percentile of cumulative grade. The relationship between AAPR, intervertebral disc degeneration (IDD) severity, and fusion rate was explored using correlation analyses and logistic regression models. Meanwhile, the ROC curve evaluated the discrimination ability of AAPR in predicting severe degeneration and non-fusion. Results: High AAPR levels were significantly negatively correlated with severe degeneration and non-fusion rate. A multivariate binary logistic analysis revealed that high preoperative AAPR was an independent predictor of severe degeneration and postoperative non-fusion (OR: 0.114; 95% CI: 0.027–0.482; p = 0.003; OR: 0.003; 95% CI: 0.0003–0.022; p < 0.001). The models showed excellent discrimination and calibration. The areas under the curve (AUC) of severe degeneration and non-fusion identified by AAPR were 0.635 and 0.643. Conclusion: The AAPR can help predict the severity of disc degeneration and the likelihood of non-fusion.

MRI Assessment of the Early Disc Degeneration Two Levels above Fused Lumbar Spine Segment: A Comparison after Unilateral and Bilateral Transforaminal Lumbar Interbody Fusion (TLIF) Procedure.

Background: Adjacent segment degeneration (ASD) has become a great concern as a late complication in patients following fusion spine surgery with a potential need for revision surgery. Segments above the fused spine have higher mobility and they are especially prone to accelerated disc degeneration. The purpose of our study is to investigate early disc degenerative changes two levels above a surgically fused lumbar spine segment and to compare MRI analyses after unilateral and bilateral TLIF procedures. Methods: A total of 117 patients were included in this cross-sectional retrospective single center study (after bilateral TLIF surgery: n = 91, and after unilateral TLIF: n = 26). In both groups, the average patient age was similar: 62.84 years (SD = 12.53) in the unilateral TLIF group and 60.67 years (SD = 11.89) in the bilateral TLIF group. On average, MRI was performed 2.5 years after surgery (SD = 2.09). The modified eight-level Pfirrmann grading system was used for the assessment of disc degeneration severity. Descriptive statistics and the Mann–Whitney test were used to show differences in the Pfirrmann grades regarding the after-surgery period and the patient age. The Wilcoxon signed-rank test results were used to display differences in the Pfirrmann grades before and after surgery. Results: The comparison of mean values, regardless of the type of surgery, shows that this mean value is on average higher in the first segment adjacent to the fused spine segment. The assessment of the intervertebral disc structure in BIL TLIF is higher in both the first and the second segment. Early disc degeneration progression is subtle yet detectable (UNI TLIF 9.28% vs. BIL TLIF 16.74%). The assessment of the intervertebral disc structure is on average lower in patients aged less than 50 years at time of surgery compared with patients aged more than 50 years in UNI TLIF, and higher in the BIL TLIF group, for both the first and the second segment. Conclusion: Patients who had undergone unilateral TLIF fusion surgery have a lower rate of early disc degenerative changes. Considering a significantly higher rate of progressive disc degenerative changes in the elderly with bilateral fusion surgery, extra caution is required in the selection of appropriate surgical technique.

The contributions of cartilage endplate composition and vertebral bone marrow fat to intervertebral disc degeneration in patients with chronic low back pain

PurposeThe composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration.MethodsMRI data from 60 patients with cLBP were included in this prospective observational study (28 female, 32 male; age = 40.0 ± 11.9 years, 19–65 [mean ± SD, min–max]). Ultra-short echo-time MRI was used to calculate CEP T2* relaxation times (reflecting biochemical composition), water-fat MRI was used to calculate vertebral BMFF, and T1ρ MRI was used to calculate T1ρ relaxation times in the nucleus pulposus (NP T1ρ, reflecting proteoglycan content and degenerative grade). Univariate linear regression was used to assess the independent effects of CEP T2* and vertebral BMFF on NP T1ρ. Mixed effects multivariable linear regression accounting for age, sex, and BMI was used to assess the combined relationship between variables.ResultsCEP T2* and vertebral BMFF were independently associated with NP T1ρ (p = 0.003 and 0.0001, respectively). After adjusting for age, sex, and BMI, NP T1ρ remained significantly associated with CEP T2* (p = 0.0001) but not vertebral BMFF (p = 0.43).ConclusionPoor CEP composition plays a significant role in disc degeneration severity and can affect disc health both with and without deficits in vertebral perfusion.

Characteristics and Short-Term Surgical Outcomes of Patients with Recurrent Lumbar Disc Herniation after Percutaneous Laser Disc Decompression.

Background and Objectives: Although percutaneous laser disc decompression (PLDD) is one of the common treatment methods for patients with lumbar disc herniation (LDH), the recurrence of LDH after PLDD is estimated at 4–5%. This study compares the preoperative clinical data and clinical outcomes of patients who underwent primary microendoscopic discectomy (MED) or MED following PLDD. Materials and Methods: We retrospectively analyzed 2678 patients who underwent MED for LDH. The PLDD group included patients with previous PLDD history at the same level of LDH, and a matched control group was created using propensity score matching for age, sex, and body mass index. Preoperative data, preoperative radiographic findings, and surgical data of the groups were compared. To compare postoperative changes in clinical scores between the groups, a mixed-effect model was used. Results: As a result, 42 patients (1.6%) had previously undergone PLDD, and a control group with 42 patients were created. The disc degeneration severity was not significantly different between the groups. However, Modic changes were more frequent in the PLDD group than in the matched control group (p = 0.028). There were no significant differences in dural adhesion rate or surgery-related complications including dural injury, length of stay, and recurrence rate of LDH after surgery. In addition, the improvement of clinical scores did not significantly differ between the two groups (p = 0.112, 0.913, respectively). Conclusions: We concluded that patients with recurrent LDH after PLDD have advanced endplate degeneration, which may reflect endplate injury from a previous PLDD. However, a previous history of PLDD does not have a negative impact on the clinical result of MED.

Is There Any Association between the Severity of Disc Degeneration and Low Back Pain?

Objective  To access the possibility that higher degrees of disc degeneration lead to higher levels of pain and dysfunction. Methods  Magnetic resonance imaging (MRI) scans of 85 patients with low back pain lasting for more than 12 weeks were evaluated, and the degree of disc degeneration was quantified according to the Pfirrmann grading system. The Pfirrmann degree in each disc space from L1-L2 to L5-S1, the maximum degree of Pfirrmann (Pfirrmann-max) between the lumbar discs, and the sum of Pfirrmann (Pfirrmann-sum) degrees were correlated (through the Spearman test) with the Oswestry Disability Index (ODI) and the Visual Analogical Scale (VAS) for pain. Results  In total, 87% of the patients had moderate to severe lumbar disc degeneration measured by Pfirrmann-max, and the most degenerated discs were L4-L5 and L5-S1. There was a week to moderate correlation regarding the Pfirrmann-max (r = 0,330; p  = 0.002) and the Pfirrmann-sum (r = 0,266; p  = 0,037) and the ODI, and the Pfirrmann scores in L1-L2 were correlated with the ODI and the VAS. Conclusion  Patients with chronic idiopathic low back pain frequently have moderate to severe lumbar disc degeneration, which has a negative impact on the quality of life of the patients. Low degrees of degeneration in L1-L2 might be related with higher degrees of pain and of functional disability.

The association of lumbar intervertebral disc degeneration and lumbar spinal stenosis on magnetic resonance imaging with body mass index in overweight and obese adults in Indian population

Aims: To investigate the association of being overweight or obese with the presence, extent, and severity of lumbar disc degeneration and lumbar spinal stenosis on magnetic resonance imaging (MRI) in adults in the Indian population.Study Design: Level 4, Cross-sectional studyPlace and duration of study: Department of Orthopaedics, SVP Hospital, Ahmedabad between February 2019 and October 2019. Methodology: A population-based cross-sectional study of 500 Indian volunteers was conducted. Subjects underwent radiographic and clinical assessment, and weight and height were measured. T2-weighted MRIs of the lumbar spine were obtained. The presence, extent, and severity of disc degeneration and additional radiographic and clinical parameters were assessed. Asian-modified body mass index (BMI) (kg/m2) categories were used.Results: The study included 305 men and 195 women (mean age 50.59 years). Disc degeneration was noted in 450 (90%) subjects. BMI was significantly higher in subjects with disc degeneration (mean 29.18 kg/m2) than in subjects without degeneration (mean 23.66 kg/m2). A significant increase in the number of degenerated levels, global severity of disc degeneration, and end-stage disc degeneration with lumbar spinal stenosis was noted with elevated BMI, in particular in overweight and obese subjects. End-stage disc degeneration with disc space narrowing was significantly more pronounced in obese subject.Conclusion: Our findings, to systematically assess lumbar disc degeneration and lumbar spinal stenosis on MRI, indicated a significant association between the presence, extent, and global severity of disc degeneration and lumbar spinal stenosis with BMI (>23 kg/m2) in overweight and obese adults.

IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model

BACKGROUND CONTEXTLumbar intervertebral disc herniation (LDH) is a common disease that causes low back pain, radiating leg pain, and sensory impairment. Preclinical studies rely heavily upon standardized animal models of human diseases to predict clinical treatment efficacy and to identify and investigate potential adverse events in human subjects. The current method for making the LDH model involves harvesting the nucleus pulposus (NP) from autologous coccygeal discs and applying to the lumbar nerve roots just proximal to the corresponding dorsal root ganglion. However, this surgical method generates a model that exhibits very different characteristics of disc herniation than that observed in human. PURPOSETo produce a rat LDH model that better resembles disc herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1β). STUDY DESIGNExperimental rat LDH model. METHODSWe exposed the L5–6 disc dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disc with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1β) was injected simultaneously to heighten the pathological processes of disc degeneration, including inflammatory responses, matrix destruction, and herniation of the NP. We performed histological staining to assess morphological changes, immunohistochemistry to analyze inflammation- and pain-related expression within and around the puncture site of the L5–6 disc, and real-time polymerase chain reaction to examine expression of markers for degenerative processes. In addition, we performed locomotor tests on the rats. RESULTSWe found that the IL-1β groups showed that the border between the annulus fibrosis and nucleus pulposus was severely interrupted compared to that of the control (puncture only) group. And, the injection of IL-1β leads to accelerated disc degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1β in the exposed disc. CONCLUSIONSThe method proposed here can be used as an index to control the severity of disc degeneration and inflammation through the injected IL-1β concentration concurrent with surgically induced herniation. CLINICAL SIGNIFICANCEOur proposed model may facilitate research in drug development to evaluate the efficacy of potential therapeutic agents for disc herniation and neuropathic pain and may also be used for nonclinical studies to more accurately assess the effectiveness of various treatment strategies according to the severity of disc degeneration.

Radiographic cervical spine degenerative findings: a study on a large population from age 18 to 97\xa0years

PurposeThe aims of this study were (1) to determine the prevalence of radiographic cervical disc degeneration in a large population of patients aged from 18 to 97 years; (2) to investigate individually the prevalence and distribution of height loss, osteophyte formation, endplate sclerosis and spondylolisthesis; and (3) to describe the patterns of cervical disc degeneration.MethodsA retrospective study was performed. Standard lateral cervical spine radiographs in standing, neutral position of 1581 consecutive patients (723 males, 858 females) with an average age of 41.2 ± 18.2 years were evaluated. Cervical disc degeneration was graded from C2/C3 to C6/C7 based on a validated quantitative grading system. The prevalence and distribution of radiographic findings were evaluated and associations with age were investigated.Results53.9% of individuals had radiographic disc degeneration and the most affected level was C5/C6. The presence and severity of disc degeneration were found to be significantly associated with age both in male and female subjects. The most frequent and severe occurrences of height loss, osteophyte formation, and endplate sclerosis were at C5/C6, whereas spondylolisthesis was most observed at C4/C5. Age was significantly correlated with radiographic degenerative findings. Contiguous levels degeneration pattern was more likely found than skipped level degeneration. The number of degenerated levels was also associated with age.ConclusionsThe presence and severity of radiographic disc degeneration increased with aging in the cervical spine. Older age was associated with greater number of degenerated disc levels. Furthermore, the correlations between age and the degree of degenerative findings were stronger at C5/C6 and C6/C7 than at other cervical spinal levels.

225. Severity of cervical disc degeneration and health-related quality of life outcomes following anterior cervical discectomy and fusion

BACKGROUND CONTEXT Cervical disc degeneration is a common radiographic finding among patients with cervical spine pathology. While not all patients with radiographic evidence of disc degeneration are symptomatic, there has been little literature exploring the relationship between severity of cervical disc degeneration and postoperative health-related quality of life (HRQOL) outcomes in patients following anterior cervical discectomy and fusion (ACDF). PURPOSE The purpose of this study was to explore the relationship between the severity of cervical disc degeneration and postoperative HRQOL outcomes in patients’ status post one- to three-level ACDFs. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE A cohort of patients status post ACDF with available preoperative/postoperative cervical radiographic imaging was obtained using Standardized Query Language (SQL) of a hospital database from a single-center, high-volume academic hospital from January 2013 to December 2018. OUTCOME MEASURES The primary outcomes of interest were HRQOL outcomes: Short Form-12 Physical/Mental Component Scores (SF-12 PCS/MCS), neck disability index (NDI), and visual analog scale arm/neck scores (VAS Arm/Neck). METHODS Patient demographics and case characteristics were obtained via SQL query and electronic medical record (EMR) chart reviews. HRQOL outcomes were obtained via SQL query with at least 1-year follow-up. Cervical disc degeneration was graded using a previously established scoring system incorporating: middle intervertebral disc height loss, anterior osteophyte length, and endplate sclerosis. Patients were then categorized into mild, moderate, or severe degeneration groups. Statistical analysis was performed with regression to examine the relationship between severity of disc degeneration and patient/clinical outcomes. RESULTS Of the 211 patients in the final cohort, 27 had mild degeneration, 100 moderate degeneration and 84 severe degeneration. Univariate analysis showed a significantly higher age in patients with severe disc degeneration compared to mild and moderate (58.4 vs 55.5 vs 52.5; p: 0.034). among HRQOL outcomes, patients with severe disc degeneration reported significant improvement in SF-12 PCS (9.4 vs 3.6 vs 4.9; p: 0.024) and VAS neck scores (-4.6 vs -2.6 vs -3.8; p: 0.036). This was further supported with multiple linear regression analysis, showing significant improvement in SF-12 PCS (β: 3.59; p: 0.005) and VAS neck (β: -1.13; p: 0.005) scores in the severe degeneration group when compared with the mild and moderate disc degeneration groups. Patients among all three groups showed significant improvement in SF-12 PCS, NDI, VAS neck, and VAS arm scores after surgical intervention. CONCLUSIONS Overall, our data validates that patients suffering from preoperative severe disc degeneration report the greatest improvement in symptoms and functional status when compared to patients with mild and moderate disease. Cervical disc degeneration has been meticulously studied at a basic science level, however clinical data regarding its effect on patient clinical outcomes has been lacking. Our study provides evidence that the preoperative degree of cervical disc degeneration has a significant effect on postoperative patient-reported outcomes, and discussion of these findings can help physicians and patients make informed decisions during the preoperative period. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

88. Cell stiffness decreases with severity of disc degeneration and inflammatory stimulation

BACKGROUND CONTEXT Disc degeneration (DD) is associated with elevated levels of proinflammatory cytokines, such as TNFα; pro-inflammatory stimulation of cells within the disc promotes catabolic breakdown of disc matrix and a positive feedback of further loss of tissue integrity and inflammation. Previously we have shown that pro-inflammatory stimulation of bovine NP cells leads to significant changes in cellular biomechanical properties, specifically increased hydraulic permeability and decreased elastic modulus, in a mechanism dependent on actomyosin contractility. These findings suggest that IVD cells exposed to inflammatory milieu during the degenerative cascade may undergo changes in biophysical properties, leading to perpetuation of mechanobiological dysfunction. However, the extent to which the biomechanical properties of single IVD cells are disrupted in human DD has yet to be investigated. Here we measure the elastic modulus of single cells isolated from patients with varying degrees of DD and with or without inflammatory stimulation. We hypothesize that increasing levels of DD will be associated with decreased cell elastic modulus, that inflammatory stimulation will further perpetuate alterations in cell biomechanics. We also investigated the protective effects of increasing actomyosin contractility in human DD cells using the RhoA activator, CN03. PURPOSE Increasing DD will be associated with decreased cell elasticity and the protective effects of RhoA activator, CN03. STUDY DESIGN/SETTING Prospective. PATIENT SAMPLE Seven patients from 2018-2019 that had consented to an IRB approved study and was scheduled to undergo lumbar spine surgery. Disc tissue was collected during the surgery. OUTCOME MEASURES Assessing cell elastic modulus using Asylum MFP-3D Bio Infinity Atomic Force Microscope (AFM) with a spherical polystyrene tip probe. Single force indentation curves were obtained for each cell and were fitted to a Hertz model of elasticity METHODS Subjects (n=7) were consented and enrolled into our IRB approved study. Adult subjects were recruited from those undergoing surgery for in the lumbar spine and disc tissue was collected during surgery. In order to assess the integrity of the disc from which tissue was isolated, the severity of degeneration was scored on MRI using Pfirrmann grade. The breakdown of patients according to Pfirrmann grade were: grade II (N=1), grade III (N=3), grade IV (N=3). Cell Isolation: cells were isolated from human IVD tissue using a “crawl out” method in which the tissue was cultured in high FBS (20%) media for up to two weeks allowing cells to migrate out of the tissue. This approach protects cell integrity from the effects of digestive enzymes. AFM Analysis: Cells (n=40-50 per donor) were tested using an Asylum MFP-3D Bio Infinity Atomic Force Microscope (AFM) with a spherical polystyrene tip probe (3µm radius). Single force indentation curves were obtained for each cell and were fitted to a Hertz model of elasticity to determine elastic modulus (E). Treatment groups: Cells from a single patient (Grade IV) were split among 4 treatment groups (1) untreated, (2) 10ng/ml TNFα, (3) CN03 or (4) TNF+CN03. After 24 hours, cells (n=20-30 cell per treatment group) were tested using AFM as described above. Statistics: Data was analyzed with ANOVA and Fisher LSD post-hoc test (STATISTICA, TIBCO Software, Palo Alto), with p RESULTS Cell elastic modulus decreased with increasing severity of degeneration. Cell modulus from Pfirrmann grades of III or IV were significantly lower than cells from grade II samples (p CONCLUSIONS The goal of this study was to measure the effect of increasing disc degeneration severity on single cell biomechanics. Our findings show that increasing degeneration severity results in lower cell modulus. Interestingly, we have previously shown similar effects on cell biomechanics with in vitro stimulation of bovine nucleus pulposus cells with TNFα. We postulate that increased levels of inflammatory stimulation during the degenerative cascade may be contributing to altered cellular biophysical properties in vivo. Indeed, when human NP cells from a Grade IV patient were stimulated with TNFα, we saw further loss of cell modulus. However, TNFα stimulation had a larger effect on cell elastic modulus in grade IV cells as compared to the effects on Grade II cells, indicating that inflammatory disruption of cell biomechanics is more pronounced in advanced disc degeneration. To examine the potential for modulating cell responses using actomyosin contractility, we found that the RhoA activator, CN03, counteracted the effects of TNFα on cells modulus, protecting against TNFα induced changes in biomechanical properties of NP cells. Ongoing studies seek to further expand the data set illustrated here as well as evaluate the roll or cytoskeletal induced changes on elastic modulus in these conditions. To our knowledge, this is the first report that evaluates single cell biophysical properties of human IVD cells from patient samples with a focus on determining the relationship of elastic modulus with degeneration severity and the role of TNFα in degenerative changes. These findings advance the understanding of how IVD cells change with degeneration, and are consistent with the hypothesis that elevated pro-inflammatory activity in vivo may contribute to altered mechanobiology of disc cells. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.