Pfirrmann Grade Research Articles

Risk Factors and Causes of Reoperation in Lumbar Disc Herniation Patients after Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Case Series with a Minimum 2-Year Follow-Up.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.

Relationship between lumbar disc herniation and Roussouly classification in the sagittal alignment of the spine and pelvis in young people.

The sagittal plane of spine-pelvis morphology of adult patients with lumbar disc herniation (LDH) differs from that of normal people. There is a correlation between abnormal sagittal plane morphology and adult LDH. This study aimed to investigate the relationship between LDH in young people and the Roussouly classification in the sagittal alignment of the spine and pelvis. A total of 126 patients with LDH hospitalized in our tertiary hospital between January 2020 and January 2021 who met the inclusion and exclusion criteria were retrospectively analyzed in a cross-sectional study. Participants were grouped according to the spinal level of disc herniation (L4/5 group, L5/S1 group, L3/4 group). Pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) of all cases were measured using standing lateral spinal radiographs. Facet joint angles (FJA) were measured using lumbar computed tomography (CT) horizontal radiographs, and the height of the anterior, middle, and posterior margins of the herniated disc was measured using sagittal radiographs. The classification of Pfirrmann disc degeneration was determined via magnetic resonance imaging (MRI) film of the lumbar region. Roussouly classification was performed according to sagittal plane morphology, and data were analyzed among each group. In all, 126 patients aged from 18 to 40 years, with an average age of 31.04±5.886 years were included. There were 63 cases of L4/5 disc herniation, 59 cases of L5/S1 herniation, and 4 cases of L3/4 herniation. There were 35 cases of epiphyseal separation. The Roussouly classification included 21 cases of type 1, 56 cases of type 2, 32 cases of type 3, 4 cases of type 4, and 13 cases of type 3 + anteverted pelvis (type 3-AP). The L4/5 disc herniation group had significantly more types 2 and 3 than the other groups, and the L5/S1 disc herniation group had significantly more types 1 and 2 than the other groups. There were no significant differences in the Pfirrmann grade of intervertebral disc degeneration; epiphyseal separation; the height of anterior, middle, and posterior margins of the herniated disc; the difference between left and right facet angle and bilateral facet angle; and the thoracic kyphosis (TK) value among any of the groups (P>0.05). There were significant differences in PI, PT, SS, lumbar lordosis (LL), and height of the anterior and posterior margins of the intervertebral space among all groups (P<0.05). PI values were grouped at 50°; PT, SS, and LL were significantly different (P<0.05), whereas TK values were not significantly different between the 2 groups (P>0.05). SS values were grouped at 35°, and there were significant differences in PI, TK, and LL between the 2 groups (P<0.05). According to the disc herniation segment, the patients were divided into L4/5 and L5/S1 groups. There were significant differences in PI, PT, anterior edge height, anterior to posterior edge height, left facet angle, right facet angle, and bilateral facet angle (P<0.05). LDH is common in L4/5 and L5/S1 segments. The incidence of Roussouly type 1 and 2 LDH is significantly higher than other types, and type 4 is the lowest. Small PI and small SS are more obvious in the L5/S1 segment. L5/S1 disc herniation is more common in patients with Roussouly type 1 and 2 classifications, whereas L4/5 disc herniation is more frequent in patients with Roussouly type 2 and 3 classifications.

Moderate to Severe Multifidus Fatty Atrophy is the Risk Factor for Recurrence After Microdiscectomy of Lumbar Disc Herniation.

We attempted to investigate the potential risk factors of recurrent lumbar disc herniation (rLDH) after tubular microdiscectomy. We retrospectively analyzed the data of patients who underwent tubular microdiscectomy. The clinical and radiological factors were compared between the patients with and without rLDH. This study included 350 patients with lumbar disc herniation (LDH) who underwent tubular microdiscectomy. The overall recurrence rate was 5.7% (20 of 350). The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) at the final follow-up significantly improved compared with those preoperatively. There was no significant difference in the preoperative VAS score and ODI between the rLDH and non-rLDH groups, while the leg pain VAS score and ODI of the rLDH group were significantly higher than those of the non-rLDH group at final follow-up. This suggested that rLDH patients had a worse prognosis than non-rLDH patients even after reoperation. There were no significant differences in sex, age, body mass index, diabetes, current smoking and drinking, disc height index, sagittal range of motion, facet orientation, facet tropism, Pfirrmann grade, Modic changes, interdisc kyphosis, and large LDH between the 2 groups. Univariate logistic regression analysis revealed that rLDH was associated with hypertension, multilevel microdiscectomy, and moderate-severe multifidus fatty atrophy (MFA). A multivariate logistic regression analysis indicated that MFA was the sole and strongest risk factor for rLDH after tubular microdiscectomy. Moderate-severe MFA was a risk factor for rLDH after tubular microdiscectomy, which can serve as an important reference for surgeons in formulating surgical strategies and the assessment of prognosis.

Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway.

The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.

Early disc degeneration in radiotherapy-treated childhood brain tumor survivors

BackgroundChildhood brain tumor (BT) survivors have an increased risk of treatment-related late effects, which can reduce health-related quality of life and increase morbidity. This study aimed to investigate lumbar disc degeneration in magnetic resonance imaging (MRI) in adult survivors of radiotherapy-treated childhood BT compared to age and sex-matched population controls.MethodsIn this cross-sectional comparative study, 127 survivors were identified from hospital registries. After a mean follow-up of 20.7 years (range 5–33.1), 67 survivors (mean age 28.4, range 16.2–43.5) were investigated with MRI and compared to 75 sex-matched population-based controls. Evaluated MRI phenotypes included Pfirrmann grading, , intervertebral disc protrusions, extrusions, and high-intensity-zone-lesions (HIZ). Groups were also compared for known risk factors of lumbar intervertebral disc (IVD) degeneration.ResultsChildhood BT survivors had higher Pfirrmann grades than controls at all lumbar levels (all p < 0.001). Lumbar disc protrusions at L4-5 (p = 0.02) and extrusions at L3-4 (p = 0.04), L4-5 (p = 0.004), and L5-S1 (p = 0.01) were significantly more common in the BT group compared to the control. The survivor cohort also had significantly more HIZ-lesons than the controls (n=13 and n=1, p=0.003). Age at diagnosis was associated with lower degree of IVD degeneration (p < 0.01). Blood pressure correlated with IVD degeneration (P < 0.05).ConclusionsSigns of early disc degeneration related to tumor treatment can be seen in the IVDs of survivors. Disc degeneration was more severe in children treated in adolescence.

Comparison of Ultrasound-Guided Percutaneous and Open Surgery Approaches in The Animal Model of Tumor Necrosis Factor-Alpha-Induced Disc Degeneration.

Animal models provide a deeper understanding about various complications and better demonstrate the effect of therapeutic approaches. One of the issues in the low back pain (LBP) model is the invasiveness of the procedure and it does not mimic actual disease conditions in humans. The purpose of the present study was to compare the ultrasound-guided (US-guided) percutaneous approach with the open-surgery method in the tumor necrosis factor-alpha (TNF-α)-induced disc degeneration model for the first time to showcase the advantages of this recently developed, minimally invasive method. In this experimental study, eight male rabbits were divided into two groups (open-surgery and US-guided). Relevant discs were punctured by two approaches and TNF-α was injected into them. Magnetic resonance imaging (MRI) was performed to assess the disc height index (DHI) at all stages. Also morphological changes (annulus fibrosus, nucleus pulposus) were evaluated by assessing Pfirrmann grade and histological evaluation (Hematoxylin and Eosin). The findings indicated targeted discs became degenerated after six weeks. DHI in both groups was significantly reduced (P<0.0001), however the difference was not significant between the two groups. In the open-surgery group, osteophyte formation was seen at six and eighteen weeks after the puncture. Pfirrmann grading revealed significant differences between injured and adjacent uninjured discs (P<0.0001). The US-guided method indicated significantly fewer signs of degeneration after six (P=0.0110) and eighteen (P=0.0328) weeks. Histological scoring showed significantly lower degeneration in the US-guided group (P=0.0039). The US-guided method developed a milder grade condition and such a model better mimics the chronic characteristics of LBP and the procedure is more ethically accepted. Therefore, the US-guided method could be a merit approach for future research in this domain as a safe, practical and low-cost method.

Quantitative Assessment of Intervertebral Disc Composition by MRI: Sensitivity to Diurnal Variation.

Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration.

Magnetic resonance imaging characteristics in patients with psoriatic arthritis and axial manifestations from the MAXIMISE cohort.

The current analysis of the MAXIMISE trial was conducted to investigate the presence of post-inflammatory and degenerative spinal changes and inflammatory changes in spinal processes identified in baseline MRIs and their potential for predicting differential treatment effects in a cohort of PsA patients with axial manifestations. Baseline spinal MRIs from the MAXIMISE trial were re-read to identify additional inflammatory (spinal process), post-inflammatory, and degenerative changes, and investigate the differential treatment effect of these imaging features using logistic regression modelling. In addition to bone marrow oedema assessed at primary analysis, spinal process inflammation and post-inflammatory changes evaluated by FAt Spondyloarthritis Spine Score were documented in 11.1% and 20.2% patients, respectively. At least one type of degenerative change was noted in 64% patients, with Pfirrmann grade ≥3 (51.1%) being the most common. Combining primary and re-read MRI findings, 67.1% of patients presented with inflammatory or post-inflammatory changes while 21.2% had degenerative changes alone. Although not statistically significant, post-inflammatory changes were associated with a trend for better efficacy outcomes in terms of ASAS20, ASAS40 and BASDAI50 responses; a trend for worse outcomes was observed in the presence of degenerative changes. The current analysis revealed the occurrence of additional inflammatory and post-inflammatory changes suggestive of axial PsA (axPsA) and a trend for better clinical outcomes for patients treated with secukinumab. These results elucidate the imaging characteristics and improve our current understanding of axPsA thereby supporting the interpretation of future trials. ClinicalTrials.gov, NCT02721966.

Correlations of Disc Tissue Pathological Changes With Pfirrmann Grade in Patients With Disc Herniation Treated With Microdiscectomy.

To reveal whether pathological disc changes (vascularization, inflammation, disc aging and senescence as assessed with immunohistopathological CD34, CD68, brachyury and P53 staining densities respectively) are associated with the extent of disease (Pfirrmann grade) and lumbar radicular pain in patients with lumbar disc herniation. We selectively included a homogenous group of 32 patients (16 males and 16 females) with single-level sequestered discs who had disease stages between Pfirrmann grades I to IV and excluded patients with the complete collapse of the disc space to determine histopathological correlations of the disease more precisely. Pathological assessments were performed on surgically excised disc specimens stored in a -80°C refrigerator. Preoperative and postoperative pain intensities were determined with visual analog scales (VASs). Pfirrmann disc degeneration grades were determined on routine T2-weighted magnetic resonance imaging (MRI). Stainings were especially observed with CD34 and CD68, which positively correlated with each other and Pfirrmann grading but not with VAS scores or patients' age. Weak nuclear staining with brachyury was observed in 50% of patients and did not correlate with disease features. Focal weak staining with P53 was only seen in the disc specimen of two patients. In the pathogenesis of disc disease, inflammation may trigger angiogenesis. The subsequent aberrant increase of oxygen perfusion in the disc cartilage may cause further damage, as the disc tissue is adapted to hypoxia. This vicious cycle of inflammation and angiogenesis may be a future innovative therapeutic target for chronic degenerative disc disease.

Reliability of T2-weighted signal intensity-based quantitative measurements and visual grading of lumbar disc degeneration on MRI.

Decrease in signal intensity (SI) of the nucleus pulposus (NP) on T2-weighted (T2W) images, a sign of disc degeneration (DD), is usually graded based on an observer's image interpretation. No gold standard for quantitative assessment of NP SI exists to date. To compare different quantitative methods and visual gradings of lumbar DD and to evaluate the ability of the quantitative methods to differentiate DD grades. The mean SI of 95 lumbar discs was measured from sagittal T2W images using three regions of interest (ROI): the whole disc, ellipsoid ROI on the NP, and targeted ROI on the most homogenous, brightest area of the NP. SI values were adjusted with cerebrospinal fluid (CSF) SI and compared with vertebral bone SI-adjusted values. DD was evaluated with Pfirrmann grading and visual grading of NP SI. Intra- and inter-observer agreements and relationships between measurements and visual gradings were assessed. Repeatability of all measurements was excellent. All measurements had a strong correlation with Pfirrmann grading and visual NP SI grading, and the CSF SI-adjusted values had a stronger correlation than the vertebral bone SI-adjusted values. The SI values obtained with the targeted ROI had the most significant differences between visual DD grades. Quantitative measurement of the NP SI provides a reliable method for evaluating lumbar DD. Targeted selection of the NP structures included in the measurement offers the best differentiation of DD grades. A reliable quantitative method for DD evaluation is needed for the development of machine-learning-based DD classification.

Poor muscle health and low preoperative ODI are independent predictors for slower achievement of MCID after minimally invasive decompression

Although some previous studies have analyzed predictors of non-improvement, most of these have focused on demographic and clinical variables and have not accounted for radiological predictors. In addition, while several studies have examined the degree of improvement after decompression, there is less data on the rate of improvement. To identify the risk factors and predictors (both radiological and non-radiological) for slower as well as non-achievement of minimal clinically important difference (MCID) after minimally invasive decompression. Retrospective cohort PATIENT SAMPLE: Patients who underwent minimally invasive decompression for degenerative lumbar spine conditions and had a minimum of 1-year follow-up were included. Patients with preoperative Oswestry Disability Index (ODI) <20 were excluded. MCID achievement in ODI (cut off 12.8). Patients were stratified into two groups (achieved MCID, did not achieve MCID) at two timepoints (early ≤3 months, late ≥6 months). Non-radiological (age, gender, BMI, comorbidities, anxiety, depression, number of levels operated, preoperative ODI, preoperative back pain) and radiological (MRI - Schizas grading for stenosis, dural sac cross-sectional area, Pfirrmann grading for disc degeneration, psoas cross-sectional area and Goutallier grading, facet cyst/effusion; X-ray - spondylolisthesis, lumbar lordosis, spinopelvic parameters) variables were assessed with comparative analysis to identify risk factors and with multiple regression models to identify predictors for slower achievement of MCID (MCID not achieved by ≤3 months) and non-achievement of MCID (MCID not achieved at ≥6 months). 338 patients were included. At ≤3 months, patients who did not achieve MCID had significantly lower preoperative ODI (40.1 vs. 48.1, p<0.001) and worse psoas Goutallier grading (p=0.048). At ≥6 months, patients who did not achieve MCID had significantly lower preoperative ODI (38 vs. 47.5, p<0.001), higher age (68 vs. 63 years, p=0.007), worse average L1-S1 Pfirrmann grading (3.5 vs. 3.2, p=0.035), and higher rate of pre-existing spondylolisthesis at the operated level (p=0.047). When these and other probable risk factors were put into a regression model, low preoperative ODI (p=0.002) and poor Goutallier grading (p=0.042) at the early timepoint and low preoperative ODI (p<0.001) at the late timepoint came out as independent predictors for MCID non-achievement. After minimally invasive decompression, low preoperative ODI and poor muscle health are risk factors and predictors for slower achievement of MCID. For non-achievement of MCID, low preoperative ODI, higher age, greater disc degeneration, and spondylolisthesis are risk factors and low preoperative ODI is the only independent predictor.

Assessment of quality of life, pain level and disability outcomes after lumbar discectomy

This study aimed to assess the quality of life of 113 Caucasian patients with intervertebral disc (IVD) degeneration of the lumbosacral (L/S) spine who qualified for microdiscectomy during a 12-month period after surgery. Based on magnetic resonance imaging before the surgery, the degree of radiological advancement of the degenerative changes was determined according to the Pfirrmann grading scale from 1 to 5. To assess pain intensity, the Visual Analog Scale (VAS) was used; the Satisfaction with Life Scale (SWLS) was used to evaluate quality of life; and to assess the degree of ability, the Oswestry Low Back Pain Disability Questionnaire (ODI) was employed. The level of pain, assessed using the VAS, significantly changed in the months following the surgery, with the highest values noted before surgery and the lowest a year after. In turn, the results of the SWLS questionnaire revealed a significant increase in satisfaction with life in the subsequent stages of the study. The conducted correlation analysis revealed significant dependencies in terms of quality of life in regard to pain as well as degree of disability. The level of pain and degree of disability were closely related to the degree of radiological advancement of degenerative changes according to the Pfirrmann grading scale.

DEEP LEARNING-BASED HIGH-ACCURACY QUANTITATION FOR LUMBAR INTERVERTEBRAL DISC DEGENERATION FROM MRI

Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of intervertebral disc (IVD) degeneration.A semantic segmentation network BianqueNet with self-attention mechanism skip connection module and deep feature extraction module is proposed to achieve high-precision segmentation of intervertebral disc related areas. A quantitative method is proposed to calculate the signal intensity difference (SI) in IVD, average disc height (DH), disc height index (DHI), and disc height-to-diameter ratio (DHR). According to the correlation analysis results of the degeneration characteristic parameters of IVDs, 1051 MRI images from four hospitals were collected to establish the quantitative ranges for these IVD parameters in larger population around China.The average dice coefficients of the proposed segmentation network for vertebral bodies and intervertebral discs are 97.04% and 94.76%, respectively. The designed parameters of intervertebral disc degeneration have a significant negative correlation with the Modified Pfirrmann Grade. This procedure is suitable for different MRI centers and different resolution of lumbar spine T2MRI (ICC=.874~.958). Among them, the standard of intervertebral disc signal intensity degeneration has excellent reliability according to the modified Pfirrmann Grade (macroF1=90.63%~92.02%).we developed a fully automated deep learning-based lumbar spine segmentation network, which demonstrated strong versatility and high reliability to assist residents on IVD degeneration grading by means of IVD degeneration quantitation.

Development and Validation of a Nomogram to Predict the Risk of Lumbar Disk Reherniation within 2 Years After Percutaneous Endoscopic Lumbar Discectomy.

To develop and validate a nomogram for predicting recurrent lumbar disk herniation (LDH) within 2 years after percutaneous endoscopic lumbar discectomy. Information on patients' LDH was collected from 1 medical center between January 2015 and September 2020. The LASSO (least absolute shrinkage and selection operator) method was applied to select the most significant risk factors. A multivariate logistic regression analysis was used to develop a predictive model incorporating the possible factors selected by the LASSO regression model. The discriminant, corrected, and clinically useful prediction models were evaluated using consistency index (C-index), receiver operating characteristic curve, calibration curves, and decision curve analysis. Internal validation of clinical predictive power was also assessed by bootstrap validation. A total of 690 patients with LDH were included in this study. Sixty-three patients experienced recurrence within 2 years whereas 627 experienced no recurrence. The nomogram predictors included age, body mass index, Modic change, Pfirrmann grade, and sagittal range of motion. The model had good discrimination power, with a reliable C-index of 0.868 (95% confidence interval, 0.822-0.913) and interval validation confirmed a higher C-index value of 0.846. The area under the receiver operating characteristic curve was 0.868, indicating a good predictive value. The decision curve analysis indicated that it was clinically feasible to use the predictive recurrence nomogram model. We developed and validated a new accurate and effective nomogram for predicting recurrent LDH within 2 years after percutaneous endoscopic lumbar discectomy. Age, body mass index, Modic change, Pfirrmann grade, and sagittal range of motion were significant features for predicting rLDH.

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension

BackgroundThis study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT).MethodsAccording to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin–eosin staining, and senescence-associated β-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified.ResultsIn degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration.ConclusionsICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Association between periodontitis and disc structural failure in older adults with lumbar degenerative disorders: A prospective cohort study

BackgroundBacterial microbiome as a putative trigger of inflammation might indicate the cascade of mouth-gut-disc axis for causing intervertebral disc (IVD) structural failures (such as IVD degeneration and endplate change) processed. However, direct evidence for the mouth-gut-disc axis still unclear. Therefore, it is interesting to explore periodontal inflammation related to IVD structural failures and clinical outcomes.MethodsThis prospective cohort study enrolled older adults (aged ≥ 75 years) who scheduled to undergo elective open lumbar spine surgery. Demographic, radiological, clinical, and periodontal parameters were recorded. Independent samples t-test and Pearson’s correlation analysis were calculated.ResultsA total of 141 patients with lumbar degenerative disorders (56 males and 85 females; age 79.73 ± 3.34 years) were divided into edentulous group (19 patients), No/Mild group (84 patients), and Moderate/Severe group (38 patients). The incidence rates of IVD degeneration in each lumbar segmental level based on Pfirrmann grade and endplate change in the fourth and fifth lumbar vertebrae, and Visual Analogue Scale (VAS) low back pain (LBP) and leg pain of patients at preoperative in dentate group was significantly higher compared with edentulous group, especially the comparisons between Moderate/Severe and edentulous groups. There were no significant differences in the range of motion, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope, and disc height between dentate and edentulous groups. There was a positive association between plaque index (PLI) and pain scores (VAS LBP: r = 0.215, P = 0.030 and VAS leg pain: r = 0.309, P = 0.005), but no significant difference in Oswestry disability index (ODI) score.ConclusionResults show that the severity of periodontitis is associated with higher incidence rates of IVD degeneration and endplate change and clinical outcomes in older adults with lumbar degenerative disorders. Furthermore, the discovery of these relationships unveils a novel mechanism through which the alterations in oral microbiome composition potentially promote IVD degeneration and pain.

Expression of GADD45G and CAPRIN1 in Human Nucleus Pulposus: Implications for Intervertebral Disc Degeneration.

Marked cellular changes occur in human intervertebral disc (IVD) degeneration during disc degeneration with biochemical changes. Genome-wide analysis of the DNA methylation profile has identified 220 differentially methylated loci associated with human IVD degeneration. Among these, two cell-cycle-associated genes, growth arrest and DNA damage 45 gamma (GADD45G) and cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), were focused on. The expression of GADD45G and CAPRIN1 in human IVDs remains unknown. We aimed to examine the expression of GADD45G and CAPRIN1 in human nucleus pulposus (NP) cells and evaluate those in human NP tissues in the early and advanced stages of degeneration according to Pfirrmann magnetic resonance imaging (MRI) and histological classifications. Human NP cells were cultured as monolayers after isolation from NP tissues by sequential enzyme digestion. Total RNA was isolated, and the mRNA expression of GADD45G and CAPRIN1 was quantified using real-time polymerase chain reaction. To examine the effects of pro-inflammatory cytokines on mRNA expression, human NP cells were cultured in the presence of IL-1β. Protein expression was evaluated using Western blotting and immunohistochemistry. GADD45G and CAPRIN1 expression was identified in human NP cells at both mRNA and protein levels. The percentage of cells immunopositive for GADD45G and CAPRIN1 significantly increased according to the Pfirrmann grade. A significant correlation between the histological degeneration score and the percentage of GADD45G-immunopositive cells was identified, but not with that of CAPRIN1-immunopositive cells. The expression of cell-cycle-associated proteins (GADD45G and CAPRIN1) was enhanced in human NP cells at an advanced stage of degeneration, suggesting that it may be regulated during the progression of IVD degeneration to maintain the integrity of human NP tissues by controlling cell proliferation and apoptosis under epigenetic alteration.

Prevalence of Lumbosacral Transition Vertebrae in Symptomatic Adults and the Levels of Degeneration in the Suprajacent Disc

Lumbosacral transition vertebra (LSTV) is a common occurrence and its prevalence ranges from 2.6% to 35.6%. Our aim is to study this phenomenon in the adult Singaporean population and assess the level of degeneration of the suprajacent disc in those with LSTV. Retrospectively, 545 patients (Age = 57.6 ± 18.3 years; Male = 277; Female = 268) who underwent radiographic evaluation of the lumbar spine for lower back pain or radicular symptoms were shortlisted. LSTV was found to be present in 106 patients (19.4%) with sacralization of L5 and lumbarization of S1 occurring in 96 patients (17.6%) and 10 patients (1.8%), respectively. The most common form of LSTV was Castellvi type IIA (46 patients; 43.4%). Based on Pfirrmann grading, Grade IV disc degeneration was most common in both the LSTV level (63%) and the unfused suprajacent level (77%) in those with LSTV. There was a significantly higher number of patients with grade IV and above degeneration in the suprajacent disc level among those with LSTV when compared to the last unfused (L5-S1) disc level in those without LSTV (84% vs. 65%; p = 0.0001). This suprajacent disc degeneration seen in patients with LSTV may contribute to low back pain and related problems in these patients.

Associations of myosteatosis with disc degeneration: A 3T magnetic resonance imaging study in individuals with impaired glycaemia.

Intervertebral disc degeneration (IVDD) may be linked to dysregulations of skeletal muscle glucose metabolism and fatty alterations of muscle composition (Myosteatosis). Our aim was to evaluate the different associations of magnetic resonance imaging (MRI)-based paravertebral myosteatosis with lumbar disc degeneration in individuals with impaired glucose metabolism and normoglycaemic controls. In total, 304 individuals (mean age: 56.3±9.1years, 53.6% male sex, mean body mass index [BMI]: 27.6±4.7kg/m2 ) from a population-based cohort study who underwent 3-Tesla whole-body chemical-shift-encoded (six echo times) and T2-weighted single-shot-fast-spin-echo MRI were included. Lumbar disc degeneration was assessed at motion segments L1 to L5, categorized according to the Pfirrmann score and defined as Pfirrmann grade>2 and/or disc bulging/herniation on at least one segment. Fat content of the autochthonous back muscles and the quadratus lumborum muscle was quantified as proton density fat fraction (PDFFmuscle ). Logistic regression models adjusted for age, sex, BMI and regular physical activity were calculated to evaluate the association between PDFFmuscle and outcome IVDD. The overall prevalence of IVDD was 79.6%. There was no significant difference in the prevalence or severity distribution of IVDD between participants with or without impaired glucose metabolism (77.7% vs. 80.7%, P=0.63 and P=0.71, respectively). PDFFmuscle was significantly and positively associated with an increased risk for the presence of IVDD in participants with impaired glycaemia when adjusted for age, sex and BMI (PDFFautochthonous back muscles : odds ratio [OR] 2.16, 95% confidence interval [CI] [1.09, 4.3], P=0.03; PDFFquadratus lumborum : OR 2.01, 95% CI [1.04, 3.85], P=0.04). After further adjustment for regular physical activity, the results attenuated, albeit approaching statistical significance (PDFFautochthonous back muscles : OR 1.97, 95% CI [0.97, 3.99], P=0.06; PDFFquadratus lumborum : OR 1.86, 95% CI [0.92, 3.76], P=0.09). No significant associations were shown in healthy controls (PDFFautochthonous back muscles : OR 0.62, 95% CI [0.34, 1.14], P=0.13; PDFFquadratus lumborum : OR 1.06, 95% CI [0.6, 1.89], P=0.83). Paravertebral myosteatosis is positively associated with intervertebral disc disease in individuals with impaired glucose metabolism, independent of age, sex and BMI. Regular physical activity may confound these associations. Longitudinal studies will help to better understand the pathophysiological role of skeletal muscle in those with concomitant disturbed glucose haemostasis and intervertebral disc disease, as well as possible underlying causal relationships.

Effect of Percutaneous Kyphoplasty on the progression of intervertebral disc degeneration: a retrospective cohort study

BackgroundThe effect of percutaneous kyphoplasty (PKP) or rather polymethylmethacrylate (PMMA) on adjacent intervertebral discs is still controversial. The evidence from experimental study to clinical study presents bipolar conclusions. In this study, we investigated the effect of PKP on adjacent intervertebral disc degeneration (IDD).MethodsThe experimental group included adjacent intervertebral discs of vertebrae treated with the PKP procedure, and the control group included adjacent intervertebral discs of non-traumatized vertebrae. All measurements were taken by magnetic resonance imaging or X-ray. The intervertebral disc height, the modified Pfirrmann grading system (MPGS), and its differences with Klezl Z and Patel S (ZK and SP) classifications were compared.ResultsA total of 264 intervertebral discs from 66 individuals were selected for the study. The comparison of intervertebral disc height between the two groups pre and post-operatively resulted in a p-value of > 0.05. No significant change was observed in the adjacent discs in the control groups post-operatively. Post-operatively, the mean Ridit increased significantly from 0.413 to 0.587 in the upper disc and from 0.404 to 0.595 in the lower disc in the experimental group. The comparison of MPGS differences showed that the predominant value was 0 in the Low-grade leaks group and 1 in the Medium and high-grade leaks group.ConclusionsThe PKP procedure can accelerate adjacent IDD, but it does not cause disc height changes in the early stage. The quantity of cement leaking into the disc space positively correlated with the rate of disc degeneration progression.