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PurposeTo probe the pathophysiological basis of Modic change (MC) by multimodal imaging rather than by MRI alone.MethodsNineteen radiological signs found in mild infections and traumatic endplate fractures were identified by MRI and CT, and by elimination, three signs unique to infection and trauma were distilled. By ranking the Z score, radiological ‘Endplate Infection Probability Score’ (EIPS) was developed. The score’s ability to differentiate infection and traumatic endplate changes (EPC) was validated in a fresh set of 15 patients each, with documented infection and trauma. The EIPS, ESR, CRP, and Numeric Pain Rating Scale (NRS) were then compared between 115 patients with and 80 patients without MC.ResultsThe EIPS had a confidence of 66.4%, 83% and, 100% for scores of 4, 5 and, 6, respectively, for end plate changes suggesting infection. The mean EIPS was 4.85 ± 1.94 in patients with Modic changes compared to − 0.66 ± 0.49 in patients without Modic changes (p < 0.001). Seventy-eight (67.64%) patients with MC had a score of 6, indicating high infection possibility. There was a difference in the NRS (p < 0.01), ESR (p = 0.05), CRP (p < 0.01), and type of pain (p < 0.01) between patients with and without MC.ConclusionMultimodal imaging showed many radiological signs not easily seen in MRI alone and thus missed in Modic classification. There were distinct radiological differences between EPCs of trauma and infection which allowed the development of an EIPS. The scores showed that 67.64% of our study patients with Modic changes had EPCs resembling infection rather than trauma suggesting the possibility of an infective aetiology and allowing us to propose an alternate theory of ‘Primary Endplatitis’.

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22–79), and 11 degenerated NP’s was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP’s. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in ‘collagen biosynthesis’ pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of ‘tissue development’. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in ‘negative regulation of cell death’. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

BackgroundTo document the role of sub-clinical infections in disc disorders and investigate the existence of microbiome in intervertebral discs (IVD).MethodsGenomic DNA from 24 lumbar IVDs [8—MRI normal discs (ND) from brain dead yet alive organ donors, 8—disc herniation (DH), 8—disc degeneration (DD)] was subjected to 16SrRNA sequencing for profiling the diversity of human disc microbiome in health and disease. The disc microbiome was further compared to established human gut and skin microbiomes.ResultsAll healthy MRI normal discs from brain dead yet alive organ donors also had a rich bacterial presence. A total of 424 different species (355-ND, 346-DD, and 322-DH) were detected, with 42.75% OTUs being classified at kingdom level, 44% at the phylum level, 22.62% at genus level, and 5.5% at species level. Varying biodiversity and abundance between healthy and diseased discs were documented with protective bacteria being abundant in normal discs, and putative pathogens abundant in DD and DH. Propionibacterium acnes had a similar but lower abundance to other pathogens in all three groups ND (3.07%), DD (3.88%), DH (1.56%). Fifty-eight bacteria were common between gut and IVD microbiomes, 29 between skin and IVD microbiomes, and six common to gut/skin/IVD.ConclusionOur study challenges the hitherto concept of sterility in healthy IVD and documented a microbiome even in MRI normal healthy discs. The varying abundance of bacteria between ND, DD, and DH documents ‘dysbiosis’ as a possible etiology of DD. Many known pathogens were identified in greater abundance than Propionibacterium acnes, and there was evidence for the presence of the gut/skin/spine microbiome axis.

Study Design Observational comparative study. Objective To study the role of magnetic resonance spectroscopy (MRS) and T2 relaxometry (T2r) as imaging biomarkers for identifying early lumbar disc degeneration. Methods We evaluated 236 discs in normal volunteers and 215 discs in low back pain (LBP) patients by MRS and T2r to document the molecular spectra of various metabolites as well as disc hydration and collagen content, respectively. All volunteer discs were Pfirrmann grade 1 (PF1), whereas patients with LBP had PF 1 (n = 156) and PF 2 (n = 59). The study population was compared in three age groups: A (20-30 years), B (30-40 years), and C (40-50 years). Results T2r, an indicator of collagen and hydration, was higher in volunteers (121.8 ± 31.1), compared to PF 1 patients (110.68 ± 23.96) and PF 2 patients (90.15 ± 25.81) (P = 0.001). Proteoglycan assessed by MRS was more stable for volunteers (3.39 ± 1.69) and PF 1 patients (3.6 ± 1.69) but reduced in PF 2 patients (2.86 ± 1.47), showing that structural molecules did not alter within the PF 1. However, lactate and other metabolites showed a difference even within PF1 between volunteers and LBP patients. We were able to identify a unique subset of PF 1 that had a normal value of proteoglycan and T2r but altered metabolite distribution, which may represent early disc degeneration (DD). Conclusion MRS and T2r can be used as imaging biomarkers for early DD by identifying altered metabolic activity with an intact matrix.

Study design Observational cohort study. Objective To assess the association of Modic changes and DEBC classification in patients with cervical degenerative disc disease. Methods The study includes 2 groups, neck pain patients presenting to the out-patient services (neck pain group) (n = 301) and polytrauma patients without cervical spine injury or a history of neck pain, who underwent whole spine MRI (control group) (n = 200). Degenerative changes in the MRI were classified according to the Modic changes (MC) and DEBC classification. Modifiers including End-Plate (EP) erosion and herniation (H+) presence were documented. Results 3612 EPs of 301 patients with neck pain and 2400 EPs of 200 controls were assessed. The incidence of MC and DEBC in the neck pain group was 20.93% and in the control group, it was 12%, (P < 0.05). In the neck pain group with DEBC changes, the distribution was Type A-6.51%; Type B-20.71%; Type C-71.6%; and Type D - 1.18%, while in the controls the distribution was Type A-10.29%, Type B-29.41%, Type C-54.41%, and Type D - 5.88%, The co-occurrence of H+ with DEBC in cases and controls was 13.95% vs 5.5% (P < 0.005). The odds ratio for the need for surgery was highest (OR: 6.8) when H+ and DEBC change co-occurred. Conclusion Our study highlights that patients with DEBC changes and disc herniation were more likely to experience neck pain and require surgical intervention, indicating the reliability and clinical significance of the DEBC classification in degenerative cervical spine patients.

Study design: Prospective comparative cohort study. Objectives: The study aims to elucidate the relationship between Modic endplate changes and clinical outcomes after a lumbar microdiscectomy. Methods: Consecutive patients undergoing microdiscectomy for lumbar disc herniation (LDH) were prospectively studied. Pre-operative clinical and radiological parameters were recorded. The pain was assessed by Numeric pain rating scale (NPRS), and functional assessment by Oswestry Disability Index (ODI). Minimal clinically important difference (MCID) in outcome was calculated for both the groups. Complications related to surgery were studied. Follow-up was done at 6 weeks, 3 months, 6 months and 1 year. Mac Nab criteria were used to assess patient satisfaction at 1 year. Results: Out of 309 patients, 86 had Modic changes, and 223 had no Modic changes. Both groups had similar back pain (p-value: 0.07) and functional scores (p-value: 0.85) pre-operatively. Postoperatively patients with Modic changes had poorer back pain and ODI scores in the third month, sixth month and 1 year (p-value: 0.001). However, MCID between the groups were not significant (p-value: 0.18 for back pain and 0.58 for ODI scores). Mac Nab criteria at 1 year were worse in Modic patients (p-value: 0.001). No difference was noted among Modic types in the pre-operative and postoperative pain and functional outcomes. Four patients in Modic group (4.7%) and one patient in the non-Modic group (0.5%) developed postoperative discitis (p-value: 0.009). Conclusions: Preoperative Modic changes in lumbar disc herniation is associated with less favorable back pain, functional scores and patient satisfaction in patients undergoing microdiscectomy.

Purpose Recently, there has been significant focus on extracellular matrix proteolysis due to its importance in the pathological progression of intervertebral disc degeneration (IVDD). The present study investigates the circulating levels of extracellular matrix proteins in the plasma of IVDD and determines their potential relevance as biomarkers in disc degeneration. Methods Global proteomic analysis was performed in the plasma samples of 10 healthy volunteers (HV) and 10 diseased subjects (DS) after depletion of highly abundant proteins such as albumin and IgG. Results We identified 144 and 135 matrix-associated proteins in plasma samples from healthy volunteers (HV) and patients with disc degeneration (DS), respectively. Among these, 49 of the matrix-associated proteins were identical to the proteins found in intervertebral disc (IVD) tissues retrieved from the in-house library. Applying stringent parameters, we selected 28 proteins, with 26 present in DS and 21 in HV. 19 proteins were found common between the groups, two of which—aggrecan (ACAN) and fibulin 1 (FBLN1) - showed statistically significant differences. Specifically, ACAN was up-regulated and FBLN1 was down-regulated in the DS-plasma. In particular, DS-plasma exhibited specific expression of collagen type 2a1 (COL2A1), native to the nucleus pulposus. Conclusion The distinct presence of collagen type 2a1 and the elevated expression of aggrecan in IVDD plasma may serve as the basis for the development of a potential biomarker for monitoring the progression of disc degeneration.

Case-control study. Sarcopenia is an age associated condition characterized by decrease in muscle mass, strength, and physical performance. We aimed to investigate whether sarcopenia increased the risk of vertebral fragility fractures among the elderly. Initial reports on sarcopenia suggest its contribution to the development of vertebral fragility fractures. However, recent studies showed contradictory findings. Fifty-one consecutive patients with vertebral fragility fractures and matched controls without fractures were evaluated for sarcopenia, T-score, body mass index, and presence of preexisting vertebral fractures. Sarcopenia was diagnosed as total psoas cross-sectional area (TPA) 2 standard deviations below normative value from normal young adults and decreased handgrip strength (26 kg for men and 18 kg for women). Univariate and multivariate analyses were performed using the fresh fracture occurrence as the dependent variable. Sarcopenia was confirmed in 29.4% and 7.8% of cases and controls (p=0.005), respectively; 56.8% and 13.7% of cases and controls had previous vertebral fractures. Sarcopenia prevalence was greater among those with previous fractures (38% vs. 7.6%; odds ratio, 7.76; p<0.001). TPA was lower among the cases (1,278 mm2 vs. 1,569 mm2 , p=0.001) and those with previous fractures (1,168 mm2 vs. 1,563 mm2 , p<0.001). Handgrip strength was greater among those without previous fractures (19.6 kg vs. 16.3 kg, p=0.05). In multivariate analysis, sarcopenia was not identified as a significant predictor of fresh fractures whereas previous fractures and lower T-score were found to be significant. Sarcopenia is not an independent risk factor for fresh vertebral fragility fractures in the elderly.

Study Design: Prospective case series. Purpose: This study aimed to investigate the impact of education, financial income, occupation, and patient counseling on the timing of enrolment in a spinal cord injury (SCI) rehabilitation program. Overview of Literature: A rehabilitation program following SCI is essential to improve functional outcomes. Socioeconomic factors can affect the timing of enrolment to a rehabilitation program. Literature on the effects of socioeconomic factors among patients with SCI in the Indian scenario is limited. Methods: A prospective, consecutive analysis of patients with SCI was performed with 1-year follow-up. Assessment of the timing of enrolment to a rehabilitation program was performed using the modified Kuppuswamy socioeconomic scores (MKSS). Patients admitted to the SCI unit (group A), underwent intensive individual, group, and family counseling sessions to encourage early enrolment into a rehabilitation program. Patients presenting directly for rehabilitation (group B) were analyzed for comparison. Results: A total of 153 patients were recruited. Group A was composed of 122 patients who started the rehabilitation program after a mean of 28 days, compared with a mean of 149 days for 31 patients in group B. In group A, 104 patients (85%; mean MKSS, 14.02) and 18 patients (15%; mean MKSS, 15.61) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. In group B, 12 patients (39%; mean MKSS, 13.69) and 19 patients (61%; mean MKSS, 12.10) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. The total MKSS and scores for education, income, and occupation did not show a significant difference between the two both groups (p>0.05). Conclusions: Early patient counseling in the acute care unit helps in the early enrolment of patients with poor socioeconomic demographic profile to a rehabilitation program.

Purpose We utilized the Fast Low Angle Shot (FLASH) sequence to document the sequential changes in cartilaginous (CEP) and bony end plate (BEP) to study the influence on disc degeneration (DD). Methods Routine MRI and FLASH sequences were used in 500 lumbar discs in 100 each of healthy volunteers (HV), low back pain patients treated conservatively (CG) and surgically (SG) to document CEP and BEP status, Pfirrmann Grade (PG) and various MRI parameters. Results The three groups were identical demographically but had a significantly different number of healthy discs ( p  < 0.01) and changes in CEP and BEP ( p  < 0.01), with patients having a higher severity of end plate changes and DD, even in asymptomatic discs. CEP abnormalities always appeared first, followed by a sequence of BEP defects of different severity, allowing the development of an ‘Integrated Total End Plate Score’ (I-TEPS). There was a good correlation between I-TEPS and PG, with a steep escalation of DD after a score of 7. A score of ≥  7 was also associated with higher surgical incidence in patients with both degenerated and herniated discs. The most significant influencing factors for surgery was a combination of I-TEPS  ≥  7 with herniation (OR7.7;p-0.00), smoking (OR4.63;p-0.02), and an I-TEPS  ≥  7 (OR3.37;p-0.04). Conclusion CEP changes identified by FLASH preceded BEP defects and DD. I-TEPS was superior to TEPS in identifying a subgroup of discs that had CEP abnormalities without BEP. An I-TEPS  ≥  7 had a significant correlation to the severity of DD, influenced variations in herniation and also surgical incidence.