Pfirrmann Scores Research Articles

Melatonin mitigates matrix stiffness-induced intervertebral disk degeneration by inhibiting reactive oxygen species and melatonin receptors mediated PI3K/AKT/NF-κB pathway.

Intervertebral disk degeneration (IVDD) may lead to an increase in extracellular matrix (ECM) stiffness, potentially contributing to the progression of the disease. Melatonin reportedly mitigates IVDD; however, its potential to attenuate elevated matrix stiffness-induced IVDD remains unexplored. Therefore, we aimed to investigate whether melatonin can alleviate the progression of IVDD triggered by increased matrix stiffness and elucidate its underlying mechanisms. Nucleus pulposus (NP) tissues were collected from patients, and ECM stiffness, reactive oxygen species (ROS) levels, apoptosis rates, and P65 expression in these tissues with varying Pfirrmann scores were determined. In vitro experiments were conducted to investigate the effects of melatonin on various pathophysiological mechanisms within the NP cells cultured on soft substrates with differing stiffness levels. Our findings revealed a positive correlation between ECM stiffness in human NP tissue and degree of IVDD. In addition, phosphorylation of P65 exhibited a strong association with matrix stiffness. Enhanced levels of ROS and cellular apoptosis were observed within degenerated intervertebral disks. In vitro experiments demonstrated that melatonin significantly inhibited catabolism and apoptosis induced by stiff matrices, along with elevated ROS levels. Furthermore, we observed that melatonin inhibited NP cell catabolism and apoptosis by reducing the melatonin receptors mediated activation of the PI3K/AKT and nuclear factor-kappa B (NF-κB) pathways. Also, we found that the reduction of ROS by melatonin can assist in inhibiting the activation of the NF-κB pathway. The outcomes of the in vivo experiments corroborated the results of the in vitro experiments, illustrating that melatonin treatment could alleviate the compression-induced upregulation of matrix stiffness in NP and IVDD. Collectively, melatonin can potentially alleviate high matrix stiffness-induced IVDD by reducing intracellular ROS levels and inhibiting the PI3K/AKT/NF-κB pathway.NEW & NOTEWORTHY Melatonin mitigates intervertebral disk degeneration (IVDD) induced by matrix stiffness through reactive oxygen species (ROS) reduction. Matrix stiffness is related to increased nucleus pulposus cell ROS, apoptosis, and degeneration. Melatonin inhibits PI3K/AKT/NF-κB pathways via melatonin receptors in a stiff matrix environment. In vivo, melatonin restores disk height and alleviates IVDD progression.

Impact of Preoperative Intervertebral Disc Degeneration on Patient-Reported Outcome Measures After Lumbar Fusion

The Pfirrmann scoring system classifies lumbosacral disc degeneration based on MRI signal intensity. The relationship between pre-existing disc degeneration and PROMs after one-level lumbar fusion is not well documented. The purpose of this study was to investigate the relationship between the severity of preoperative intervertebral disc degeneration and pre- and postoperative patient-reported outcome measures (PROMs) in patients undergoing one-level lumbar fusion. All adult patients underwent posterior lumbar decompression and fusion (PLDF) or transforaminal lumbar interbody fusion (TLIF) between 2014-2022 were included. Patient demographics, and comorbidities were extracted from medical records. Lumbar intervertebral discs on sagittal MRI T2-weighted images were assessed by two independent graders utilizing Pfirrmann criteria. Grades I-III were categorized as low-grade disc degeneration, while IV-V were considered high-grade. Multivariable linear regression assessed the impact of disc degeneration on PROMS. A total of 150 patients were included, of which, 69 (46%) had low grade disc degeneration, while 81 (54%) had high grade degeneration. Patients with high-grade degeneration had increased preoperative VAS-Leg scores (6.10 vs. 4.54, p=0.005) and displayed greater one-year postoperative improvements in VAS-Back scores (-2.11 vs -0.66, p=0.002). Multivariable regression demonstrated Pfirrmann scores as independent predictors for both preoperative VAS-Leg scores (p=0.004) and postoperative VAS-Back improvement (p=0.005). In patients undergoing one-level lumbar fusion, higher Pfirmann scores were associated with increased preoperative leg pain and greater one-year postoperative improvement in back pain. Further studies into the relationship of pre-operative disc degeneration and their impact on postoperative outcomes may help guide clinical decision making and patient expectations.

The relationship between paraspinal muscle atrophy and degenerative lumbar spondylolisthesis at the L4/5 level

BACKGROUND/CONTEXTDegenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. PURPOSETo examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. STUDY DESIGN/SETTINGRetrospective cross-sectional study at an academic tertiary care center. PATIENT SAMPLEPatients who underwent surgery for DLS at the L4/5 level between 2016–2018 were included. Those with multilevel DLS or insufficient imaging were excluded. OUTCOME MEASURESThe percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. METHODSDescriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity and symptom duration. RESULTSThe study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD±5.1) and average preoperative ODI was 46.4 (SD±16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MFfCSA and MFHI, and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MFfCSA was associated with a 0.9%-point increase in RS (95% CI -1.4 to - 0.4, p<.001), and each cm2/m2 decrease in MFHI was associated with an increase in slippage by 2.2%-points (95% CI -3.7 to -0.7, p=.004). Each 1%-point rise in ESFI and MFFI corresponded to 0.17%- (95% CI 0.05–0.3, p=.01) and 0.20%-point (95% CI 0.1–0.3 p<.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in PsoasfCSA and cm2/m2 in PsoasHI was associated with an increase in relative slippage by 0.3% (95% CI 0.1–0.6, p=.004) and 1.1%-points (95% CI 0.4–1.7, p=.001). While MFfCSA tended to be negatively associated with slippage, this did not reach statistical significance (p=.105). However, each 1%-point increase in MFFI and ESFI corresponded to increases of 0.15% points (95% CI 0.05–0.24, p=.002) and 0.14% points (95% CI 0.01–0.27, p=.03) in relative slippage, respectively. CONCLUSIONThis study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS.

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.

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.

Does Calcium Phosphate Cement Kyphoplasty Cause Intervertebral Disk Degeneration in Adolescents?

Balloon kyphoplasty with polymethylmethacrylate (PMMA) represents the standard procedure for the treatment of thoracic and lumbar type A compression fractures. However, an increased degeneration in adjacent intervertebral disks following PMMA kyphoplasty has been demonstrated in elderly patients. Calcium phosphate cement (CPC) appears to be superior to PMMA for the intravertebral stabilization in younger patients. It remains unkown whether CPC kyphoplasty causes degeneration of adjacent disks in adolescents. Seven adolescents with thoracolumbar spine fractures underwent kyphoplasty at a mean age of 14.5 years (range 10-18). At a mean follow-up of 3.7 years (range 1 to 4.8) postoperatively, 3.0 Tesla magnetic resonance imaging (MRI) of the spine was performed to assess intervertebral disk degeneration by quantitative T2 relaxation maps and subjective ratings using modified Pfirrmann scores. A total of 56 intervertebral disks was analyzed. Initial computed tomography (CT) examinations served as basis to assess the severity of adjacent endplate injuries in terms of articular step-offs. Initial imaging detected 18 thoracolumbar vertebral body fractures of which 9 were treated with CPC kyphoplasty. Quantitative follow-up MRI revealed signs of degeneration in 10 (17.9%) of the examined 56 intervertebral disks, 7 of them adjacent to a previously fractured vertebral body. Signs of disk degeneration were significantly higher in caudal endplates with articular step-offs larger than 5 mm compared to fractured vertebral bodies without endplate step-offs. Quantitative MRI follow-ups did not suggest CPC-related intervertebral disk degradations following thoracolumbar kyphoplasty in adolescents, but indicated disk alterations correlating to adjacent endplate fracture severity.

MRI changes of adjacent segments after transforaminal lumbar interbody fusion (TLIF) and foraminal endoscopy: A case-control study.

Background:Intervertebral foramen endoscopy has developed rapidly, but compared with transforaminal lumbar interbody fusion (TLIF), the progress of degeneration is unknown. We aim to compare the changes of intervertebral disc and intervertebral foramen in adjacent segments after TLIF and endoscopic discectomy for patients with lumbar disc herniation (LDH).Methods:From 2014 to 2017, 87 patients who were diagnosed with single-level LDH and received surgery of TLIF (group T, n = 43) or endoscopic discectomy (group F, n = 44) were retrospectively analyzed. X-ray, MRI, CT and clinical symptoms were recorded before operation and at the last follow-up (FU). The neurological function was originally evaluated by the Japanese Orthopaedic Association (JOA) scores. Radiological evaluation included the height of intervertebral space (HIS), intervertebral foramen height (FH), intervertebral foramen area (FA), lumbar lordosis (CA) and intervertebral disc degeneration Pfirrmann scores.Results:There was no significant difference in baseline characteristics, JOA improvement rate, reoperation rate and complications between the two groups. The age, average blood loss, average hospital stays and average operation time in group F were lower than those in group T. During the last FU, HIS, CA and FA decreased in both groups, and the changes in group T were more significant than those in group F (P < .05). There was no significant difference in FH changes between the two groups (P > .05).Conclusion:Both TLIF and endoscopic surgery can achieve good results in the treatment of LDH, but the risk of lumbar disc height loss and intervertebral foramina reduction in the adjacent segment after endoscopic surgery is lower.

Lumbosacral Transitional Vertebra Contributed to Lumbar Spine Degeneration: An MR Study of Clinical Patients.

We aimed to comprehensively characterize degenerative findings associated with various types of lumbosacral transitional vertebra (LSTV) on magnetic resonance images. Three hundred and fifty patients with LSTV (52.3 ± 10.9 years), including 182 Castellvi type I, 107 type II, 43 type III, and 18 type IV, and 179 controls without LSTV (50.6 ± 13.1 years), were studied. Discs, endplates, and posterior vertebral structures were assessed and compared to those of controls for the most caudal three discs on MRIs. There were no differences in degenerative findings between patients with type I LSTV and controls. For types III and IV, the transitional discs had smaller sizes, lower Pfirrmann scores, and lower rates of disc bulging (2.3% and 5.6% vs. 39.1%), osteophytes (2.3% vs. 15.1%), disc herniation (2.3% and 5.6% vs. 31.8%), and Modic changes (2.3% and 5.6% vs. 16.8%) than controls. However, the cranial discs had more severe Pfirrmann scores, disc narrowing and spinal canal narrowing, and greater rates of disc herniation (41.9% and 50.0% vs. 25.7%), endplate defects (27.9% and 33.3% vs. 14.4%) and spondylolisthesis (18.6% vs. 7.3%) than controls. Type II LSTV was associated with degenerative findings in the cranial segments but to a lesser degree, as compared with type III/IV LSTV. Thus, Castellvi type III/IV LSTV predisposed the adjacent spinal components to degeneration and protected the transitional discs. Type II LSTV had significant effects in promoting transitional and adjacent disc degeneration. Type I LSTV was not related to spinal degeneration.

Schmorl’s nodes could be associated with intervertebral disc degeneration at upper lumbar levels and end-plate disease at lower lumbar level in patients with low back pain

Schmorl’s nodes (SNs) have increasingly been recognized on vertebral end-plates using advanced imaging techniques. Even though vertebral end-plates are the closest structures to discs, their pathologies are underestimated in the etiology of low back pain (LBP). We aimed to detect the prevalence of SNs and other end-plate defects in subjects with/without LBP and to understand whether SNs were associated with LBP and spinal degeneration. Subjects were evaluated in terms of end-plate defects, intervertebral disc degeneration (IVDD), and vertebral end-plate changes (Modic changes) at all lumbar levels on lumbar spine magnetic resonance imagings (MRI). Control subjects were compared to patients with LBP. Higher Pfirrmann scores (OR: 2.696) and higher SN scores (OR: 8.076) were significantly associated with Modic changes at L4-L5 disc level. Patients with higher SN scores at L1-L2 or L2-L3 levels had approximately 7-fold increased risk of severe IVDD at the corresponding levels. The most significant factor associated with presence of SNs was body weight of the patients (OR: 1.417). The most significant factor associated with intensity of LBP was severe IVDD at L5-S1 level (OR: 3.670). Having higher total SN score had an OR of 1.230 (95% CI: 1.003–1.509; p = 0.047) for predicting LBP. Schmorl’s nodes were seen in 33.1% of patients and 11.5% of asymptomatic subjects. Body weight was the most significant factor associated with SNs. The most significant factor associated with LBP was severe IVDD at L5-S1 level.

Cervical disc degeneration is associated with a reduction in mobility: A cross-sectional study of 1211 asymptomatic healthy subjects

The aim of this study was to establish the age-related changes and gender-specific differences of cervical disc degeneration using magnetic resonance image (MRI) and to evaluate the correlation between the severity of cervical disc degeneration and mobility in asymptomatic subjects. A total of 1,211 relatively healthy volunteers (606 males and 605 females, mean age 49.5 years) without neurological symptoms underwent MRI. At least 100 males and 100 females in each decade of life between the 20 s and the 70 s were included. This study was part of a larger project and used some previously published data. Cervical disc degeneration was defined according to the modified Pfirrmann classification system. A total disc degeneration score (DDS) was calculated by the summation of individual Pfirrmann scores from C2/C3 to C7/T1. Cervical range of motion (ROM) was measured by radiograph. The total DDS increased gradually with increasing age in both genders. DDSs were lower in females than in males in all decades. A DDS of 13 or more was found in more than half the cases in the 40 s or older age groups. The total DDS was 13 or more in over 95% of the cases in the 70 s age group. The total DDS was significantly and negatively correlated with cervical ROM overall (r = − 0.46, p < 0.0001) and in both men (r = − 0.52, p < 0.0001) and women (r = − 0.40, p < 0.0001). This large-scale cross-sectional analysis of cervical spine MRI data in healthy subjects demonstrated that cervical disc degeneration progresses with age, and is correlated with a reduction in mobility.

LncRNA OIP5-AS1 accelerates intervertebral disc degeneration by targeting miR-25-3p

ABSTRACT It is obvious that epigenetic processes influence the evolution of intervertebral disc degeneration (IDD). However, its molecular mechanisms are poorly understood. Long noncoding RNAs (lncRNAs) have been validated to exert vital roles in IDD. Therefore, we tested the hypothesis that OIP5-AS1, a potential regulator of IDD, modulates IDD progression. RT-PCR was utilized to detect levels of OIP5-AS1, miR-25-3p, Collagen II and Aggrecan in IDD tissues and nucleus pulposus cells (NPCs). Immunofluorescence assay measured Collagen II expression. CCK-8, EdU, and flow cytometry estimated the levels of proliferation and apoptosis. Proteins were assessed via Western blot. The binding affinity of OIP5-AS1 with miR-25-3p was investigated by luciferase reporter assay. Enzyme-linked immunosorbent assay (ELISA) analyzed the levels of inflammatory factors. OIP5-AS1 was high expressed in IDD tissues and its expression gradually promoted with the increasing of Pfirrmann scores. The cell morphology of NPCs changed into spindle-shaped, and Collagen II expression was low. After OIP5-AS1 was silenced, cell proliferation was boosted whereas both apoptosis and extracellular matrix (ECM) degradation were restrained. In LPS-activated NPCs, OIP5-AS1 depletion also suppressed inflammation response. Further, miR-25-3p was a target of OIP5-AS1. The effects of OIP5-AS1 silence on proliferation, apoptosis, and ECM degradation were reversed upon miR-25-3p downregulation. Moreover, the inhibitory impact of OIP5-AS1 knockdown on the inflammation of LPS-treated NPCs was rescued with miR-25-3p inference. In general, lncRNA OIP5-AS1 exerted its effects in IDD by targeting miR-25-3p, implying the usage of OIP5-AS1/miR-25-3p as a novel regulatory axis for the molecular targets of IDD therapy.

Comparison of Pfirrmann classification and objective T2 signal intensity of cervical disc-cisterna magna ratio measurements in cervical intervertebral disc degeneration

ObjectiveThis study aimed to determine the relation of the intervertebral disc signal intensity to cisterna magna [1] signal intensity ratio to the morphological changes in the cervical intervertebral discs (CID) on a T2-weighted image performed on a 3.0-Tesla (3 T) magnetic resonance imaging (MRI), and its relationships to the age, disc space heights, gender, and Pfirrmann grades. Materials and MethodsOne hundred fifty patients were enrolled. Sagittal T2-weighted images were performed on 3.0-Tesla (MRI) on the cases included in the study. All intervertebral disc heights (anterior, middle, posterior), signal intensities, and cisterna magna signal intensities between C2-T1 were measured by two different researchers. Based on the resulting data, Pfirrmann scores were divided into three groups, and a cut-off value was determined between grades by using their mean and median values. ResultsWhen the data was examined, it was found that the CID-cisterna magna (CM) signal intensity ratio values were significantly statistically different in all (C2 → T1) levels according to the grades (p < 0.05); as the Pfirrmann classification goes from low to high at each intervertebral disc level (Grade 1&2 → Grade 4&5), CID-CM signal intensity ratio values statistically significantly decreased. The ROC curve obtained for each level and the area under the curve (AUC) were calculated and found to be statistically significant. ConclusionThe Pfirrmann grading system is not a reliable evaluation method for CID degeneration grading because the height of the cervical disc varies significantly according to the measurement area and level. It is thought that further research can lead to more objective classification based on widely used T2-weighted MRI intensity measurement.

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.

Lumbar spine intervertebral disc desiccation is associated with medical comorbidities linked to systemic inflammation.

Symptomatic disc degeneration is a common cause of low back pain. Recently, the prevalence of low back pain has swiftly risen leading to increased patient disability and loss of work. The increase in back pain also coincides with a rapid rise in patient medical comorbidities. However, a comprehensive study evaluating a link between patient's medical comorbidities and their influence on lumbar intervertebral disc morphology is lacking in the literature. Electronic medical records (EMR) were retrospectively reviewed to determine patient-specific medical characteristics. Magnetic resonance imaging (MRI) was evaluated for lumbar spine intervertebral disc desiccation and height loss according to the Griffith-modified Pfirrmann grading system. Bivariate and multivariable linear regression analyses assessed strength of associations between patient characteristics and lumbar spine Pfirrmann grade severity (Pfirrmann grade of the most affected lumbar spine intervertebral disc) and cumulative grades (summed Pfirrmann grades for all lumbar spine intervertebral discs). In total, 605 patients (304 diabetics and 301 non-diabetics) met inclusion criteria. Bivariate analysis identified older age, diabetes, American Society of Anesthesiologists (ASA) class, hypertension, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, and hypothyroidism as being strongly associated with an increasing cumulative Pfirrmann grades. Multivariable models similarly found an association linking increased cumulative Pfirrmann grades with diabetes, hypothyroidism, and hypertension, while additionally identifying non-white race, heart disease, and previous lumbar surgery. Chronic pain, depression, and obstructive sleep apnea (OSA) were associated with increased Pfirrmann grades at the most affected level without an increase in cumulative Pfirrmann scores. Glucose control was not associated with increasing severity or cumulative Pfirrmann scores. These findings provide specific targets for future studies to elucidate key mechanisms by which patient-specific medical characteristics contribute to the development and progression of lumbar spine disc desiccation and height loss. III (retrospective cohort).

HOXC13-AS Induced Extracellular Matrix Loss via Targeting miR-497-5p/ADAMTS5 in Intervertebral Disc.

Background/Aims: LncRNAs are a new modulator in the development of intervertebral disc degeneration. However, the functional role and mechanism of HOXC13-AS in intervertebral disc degeneration remain unclear. Methods: qRT-PCR analysis was performed to measure the relative expression levels of HOXC13-AS and miR-497-5p, and the levels of IL-1β, IL-6, and TNF-α in the medium supernatant were analyzed by ELISA. The related mechanism between HOXC13-AS and miR-497-5p was detected by luciferase assays. Results: The results revealed that TNF-α and IL-1β induced HOXC13-AS expression in NP cells. HOXC13-AS was overexpressed in IDD specimens compared to control specimens, and higher expression of HOXC13-AS was correlated with high Pfirrmann scores. Ectopic expression of HOXC13-AS promoted MMP-3 and ADAMTS4 and inhibited aggrecan and collagen II expression in NP cells. Furthermore, overexpression of HOXC13-AS increased the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Our results demonstrated that TNF-α and IL-1β induced ADAMTS5 expression and suppressed miR-497-5p expression. miR-497-5p was downregulated in IDD specimens compared to control specimens, and the lower expression of miR-497-5p was correlated with high Pfirrmann scores. The miR-497-5p level was negatively proportional to HOXC13-AS expression in IDD specimens. Luciferase analysis data indicated that ADAMTS5 was a direct target gene of miR-497-5p. HOXC13-AS induced inflammatory cytokine expression and ECM degradation by modulating miR-497-5p/ADAMTS5. Conclusion: HOXC13-AS may be a treatment target for IDD.

Mid-long-term outcome and degeneration of the remaining unfused lumbar intervertebral disc in adolescent idiopathic scoliosis patients who had posterior spinal fusion surgery.

To investigate mid-long-term effects of the lowest instrumented vertebra (LIV) selection on adolescent idiopathic scoliosis (AIS) patients who had posterior spinal fusion (PSF) surgery. Forty-eight patients were recruited. Inclusion criteria were AIS patients who have had PSF surgery more than 10 years ago. Patients were divided into G1: LIV L3 or higher and G2: LIV L4 or lower. MRI evaluation was classified using Pfirrmann grades. Pfirrmann scores were average of Pfirrmann grades for all unfused discs below LIV. SRS-22r, SF-36, Oswestry Disability Index (ODI) and Modified Cincinnati Sports Activity Scale (MCSAS) were used. There were 19 patients in G1 and 29 patients in G2. Demographic parameters showed no significant differences. We found no significant differences in Pfirrmann grades or scores between G1 and G2. There was significant correlation between age and mean Pfirrmann scores (r = 0.546, p < 0.001), Pfirrmann grade for adjacent disc + 1 below LIV (r = 0.475, p = 0.001) and adjacent disc below LIV (r = 0.365, p = 0.011). G2 had significantly lower scores for SRS-22r pain (G1: 4.3 ± 0.5, G2: 4.0 ± 0.6, p = 0.044) and the SF-36 bodily pain (G1: 88.7 ± 12.3, G2: 77.8 ± 18.7, p = 0.018) domains. There were no significant differences in ODI and MCSAS between the two groups. Patients with fusion to L4 or lower had more significant back pain. However, both groups had similar physical function, self-image, satisfaction with treatment, mental health, and functional sports activity. We did not find any significant association between lumbar discs degeneration and the selection of LIV.

Spinal Degeneration and Degenerative Disc Disease correlation identified with Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is the golden standard technique for spine disc disease diagnosis. Vertebral body endplate signal intensity on MRI is confirming lumber spine degenerative disc disease.The study aimed to record the lumbar spine degenerative relation between disc and diseaseusing magnetic resonance imaging. Our prospective and double blind investigation included 142 participants,having lumbar spine degenerativedisease confirmed by MRI. Pfirrmann score was used to record the relation between lumbar spine disc degeneration and lumbar spine degenerative disease. Modic modifications with the Pfirrmann and modified Pfirrmann scores of disc degeneration were assessed.Lumbar spine MRI was done for all participants using sagittal T1 and T2 WI. Modic was scored (0-III) The Pfirrmann scored I-V for disc degeneration. Lumbar disc degeneration was evaluated by modified Pfirrmann scoring from 1-8 according to signal intensity of the nucleus pulposus and inner annulus.Modic was recorded in 41.5%, 24.6%, 32.4% and 1.4% of participants with scores 0, I, II and III, respectively. Pfirrmann score was 13.4%, 73.9% and 12.7% of disc degeneration with scores III, IV and V, respectively, while,the modified Pfirrmann score was 2.1%, 15.5%, 38.7%, 26.8% and 16.9% of disc degeneration with scores of 4, 5, 6, 7 and 8, respectively. The modified Pfirrmann score showed notableinconsistencyin participants with Modic 0, I and II, but no difference between Modic I and II.There was significant relation between Modicand lumbar spine disc degeneration. In conclusion, there is a relation between Modic, Pfirrmann and modified Pfirrmann scores of lumbar spine disc degeneration in participants with lumbar spine degenerative disease.

Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy

BACKGROUND CONTEXT PURPOSEEvaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36-month follow-up. STUDY DESIGN/SETTINGA multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 in Australia). SUBJECT SAMPLEA total of 100 subjects with chronic low back pain associated with moderate DDD (modified Pfirrmann score of 3–6) at one level from L1 to S1 for at least 6 months and failing 3 months of conservative treatment, including physical therapy were randomized in a 3:3:2:2 ratio to receive 6 million MPCs with HA, 18 million MPCs with HA, HA vehicle control, or saline control (placebo) treatment. OUTCOME MEASURESSubjects were clinically and radiographically evaluated at 1, 3, 6, 12, 24, and 36 months postinjection. Subject-reported outcomes including adverse events, LBP on a Visual Analog Scale (VAS), Oswestry Disability Index (ODI), SF-36 and Work Productivity and Activity Index were collected. METHODSClinical and radiographic measures were collected at each visit. All randomized subjects were included in the safety assessments and analyzed based on the treatment received. Safety assessments included assessments of AEs, physical and radiographic examinations and laboratory testing. Efficacy assessments evaluated changes in VAS, ODI, and modified Pfirrmann (MP) scores between all active and control groups, respectively. Assessments included least squares mean (Mean), LS mean change from baseline (Mean Change) and responder analyses in order to assess the clinical significance of observed changes from baseline. The population for efficacy assessments was adjusted for the confounding effects of post-treatment interventions (PTIs). This study was conducted under an FDA Investigational New Drug application sponsored and funded by Mesoblast. RESULTSThere were significant differences between the control and MPC groups for improvement in VAS and ODI. The PTI-corrected VAS and ODI Means and Mean Change analyses; the proportion of subjects with VAS ≥30% and ≥50% improvement from baseline; absolute VAS score ≤20; and ODI reduction ≥10 and ≥15 points from baseline showed MPC therapy superior to controls at various time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change composite endpoints for the MPC groups was also superior compared with controls at various time points from baseline to 36 months. There were no significant differences in change in MP score from baseline across the groups. There were also no statistically significant differences in change in modified MP score at the level above or below the level treated between study arms. Both the procedure and treatment were well tolerated and there were no clinical symptoms of immune reaction to allogeneic MPCs. There was a low rate of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events, and the rates of these events in the MPC groups were not significantly different from the control groups. One TEAE of severe back pain was possibly related to study agent and one TEAE of implantation site infection was considered to be related to the study procedure. CONCLUSIONSResults provide evidence that intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.

Diabetes Mellitus-A Risk Factor for the Development of Lumbar Disc Degeneration: A Retrospective Study of an Indian Population.

Study Design:A retrospective study.Objectives:To determine the association between type-2 diabetes mellitus (T2DM) and the severity of lumbar disc degeneration disease (LDDD).Methods:We included 199 patients with low back pain (LBP) who visited our hospital from 2016 to 2018. All patients were divided into 3 groups as per inclusion criteria. Group A, patients without DM (n = 75); group B, patients with controlled DM (n = 72); and group C, patients with uncontrolled DM (n = 52). The patients were further subdivided into group B1, DM duration ≤10 years (n = 38); group B2, DM duration >10 years (n = 34); group C1 DM duration ≤10 years (n = 28); and group C2, DM duration >10 years (n = 24). Sex, age, body mass index, occupation, smoking history, alcohol use, and duration of T2DM were recorded. The severity of LDDD was evaluated using the 5-level Pfirrmann grading system. Operated patients’ disc materials were sent for histological examination.Results:Demographic data showed no difference among groups (P > 0.5), except age. Patients with DM showed more severe disc degeneration compared with patients without DM. The average Pfirrmann scores between groups A and B1 had no difference; groups B2, C1, and C2 showed higher average Pfirrmann scores than group A (P < 0.05). Groups B2 and C2 showed higher average Pfirrmann scores than groups B1 and C1 (P < 0.05). Groups C1 and C2 showed higher average Pfirrmann scores than groups B1 and B2 (P < 0.05). The severity of LDDD was significantly related to DM duration in both groups B and C (P < 0.05). DM groups showed increased disc apoptosis and matrix aggrecan fragmentation, disc glycosaminoglycan content and histological analysis were significantly different; the results are similar to Pfirrmann score results.Conclusions:DM duration >10 years and uncontrolled DM were risk factors for LDDD.