Evaluation of the Degenerative Changes of the Distal Intervertebral Discs after Internal Fixation Surgery in Adolescent Idiopathic Scoliosis

Morteza Dehnokhalaji,Mohammad Reza Golbakhsh,Babak Siavashi,Parham Talebian,Sina Javidmehr,Mohammadreza Bozorgmanesh 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.6

Study Design: Retrospective study. Purpose: Lumbar intervertebral disc degeneration is an important cause of low back pain. Overview of Literature: Spinal fusion is often reported to have a good course for adolescent idiopathic scoliosis (AIS). However, many studies have reported that adjacent segment degeneration is accelerated after lumbar spinal fusion. Radiography is a simple method used to evaluate the orientation of the vertebral column. magnetic resonance imaging (MRI) is the method most often used to specifically evaluate intervertebral disc degeneration. The Pfirrmann classification is a well-known method used to evaluate degenerative lumbar disease. After spinal fusion, an increase in stress, excess mobility, increased intra-disc pressure, and posterior displacement of the axis of motion have been observed in the adjacent segments. Methods: we retrospectively secured and analyzed the data of 15 patients (four boys and 11 girls) with AIS who underwent a spinal fusion surgery. We studied the full-length view of the spine (anterior-posterior and lateral) from the X-ray and MRI obtained from all patients before surgery. Postoperatively, another full-length spine X-ray and lumbosacral MRI were obtained from all participants. Then, pelvic tilt, sacral slope, curve correction, and fused and free segments before and after surgery were calculated based on Xray studies. MRI images were used to estimate the degree to which intervertebral discs were degenerated using Pfirrmann grading system. Pfirrmann grade before and after surgery were compared with Wilcoxon signed rank test. While analyzing the contribution of potential risk factors for the post-spinal fusion Pfirrmann grade of disc degeneration, we used generalized linear models with robust standard error estimates to account for intraclass correlation that may have been present between discs of the same patient. Results: The mean age of the participant was 14 years, and the mean curvature before and after surgery were 67.8 and 23.8, respectively (p <0.05). During the median follow-up of 5 years, the mean degree of the disc degeneration significantly increased in all patients after surgery (p <0.05) with a Pfirrmann grade of 1 and 2.8 in the L2–L3 before and after surgery, respectively. The corresponding figures at L3–L4, L4–L5, and L5–S1 levels were 1.28 and 2.43, 1.07 and 2.35, and 1 and 2.33, respectively. The lower was the number of free discs below the fusion level, the higher was the Pfirrmann grade of degeneration (p <0.001). Conversely, the higher was the number of the discs fused together, the higher was the Pfirrmann grade. Conclusions: we observed that the disc degeneration aggravated after spinal fusion for scoliosis. While the degree of degeneration as measured by Pfirrmann grade was directly correlated by the number of fused segments, it was negatively correlated with the number of discs that remained free below the lowermost level of the fusion.

Cell clusters in intervertebral disc degeneration: an attempted repair mechanism aborted via apoptosis

Polly Lama,Jerina Tiwari,Pulkit Mutreja,Sukirti Chauhan,Ian J Harding,Trish Dolan,Michael A Adams,Christine Le Maitre 대한해부학회 2023 Anatomy & Cell Biology Vol.56 No.3

Cell clusters are a histological hallmark feature of intervertebral disc degeneration. Clusters arise from cellproliferation, are associated with replicative senescence, and remain metabolically, but their precise role in various stages of disc degeneration remain obscure. The aim of this study was therefore to investigate small, medium, and large size cell-clusters. For this purpose, human disc samples were collected from 55 subjects, aged 37-72 years, 21 patients had disc herniation, 10 had degenerated non-herniated discs, and 9 had degenerative scoliosis with spinal curvature <45°. 15 non-degenerated control discs were from cadavers. Clusters and matrix changes were investigated with histology, immunohistochemistry, and Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Data obtained were analyzed with spearman rank correlation and ANOVA. Results revealed, small and medium-sized clusters were positive for cell proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) in control and slightly degenerated human discs, while large cell clusters were typically more abundant in severely degenerated and herniated discs. Large clustersassociated with matrix fissures, proteoglycan loss, matrix metalloproteinase-1 (MMP-1), and Caspase-3. Spatial associationfindings were reconfirmed with SDS-PAGE that showed presence to these target markers based on its molecular weight. Controls, slightly degenerated discs showed smaller clusters, less proteoglycan loss, MMP-1, and Caspase-3. In conclusion, cell clusters in the early stages of degeneration could be indicative of repair, however sustained loading increases large cell clusters especially around microscopic fissures that accelerates inflammatory catabolism and alters cellular metabolism, thus attempted repair process initiated by cell clusters fails and is aborted at least in part via apoptosis.

Magnetic Resonance Imaging Comparison of Intervertebral Disc Degeneration of Normal and Disc Diseases in Dogs

Hee Chun Lee 한국임상수의학회 2023 한국임상수의학회지 Vol.40 No.1

This study compared the degree of disc degeneration of intervertebral disc between normal disc and disc disease using Magnetic Resonance images of tholacolumbar and lumbar vertebrae in dogs. The sample population consist- ed of 72 dogs and 188 intervertebral discs. These dogs were divided into four groups according to MRI criteria: normal, disc protrusion, disc extrusion, and fi- brocartilaginous embolism. The Pfirrmann classification developed by Pfirrmann for use in human medicine was used to assess the degree of disc degeneration. Statistical analysis revealed that disc diseases had a significant difference in the degree of disc degeneration compared to normal discs in the intervertebral disc. Fibrocartilaginous embolism was found to have a relatively low disc degener- ative change compared to two other disc disease groups, disc protrusion and disc extrusion. Disc degeneration in the disc extrusion group was slightly higher than that in the disc protrusion group, although the difference between the two groups was not statistically significant.

Gene Therapy Approach for Intervertebral Disc Degeneration: An Update

Yoshiki Takeoka,Takashi Yurube,Kotaro Nishida 대한척추신경외과학회 2020 Neurospine Vol.17 No.1

Intervertebral disc degeneration is the primary cause of back pain and associated with neurological disorders including radiculopathy, myelopathy, and paralysis. The currently available surgical treatments predominantly include the excision of pathological discs, resulting in the function loss, immobilization, and potential additional complications due to the altered biomechanics. Gene therapy approach involves gene transfer into cells, affects RNA and protein synthesis of the encoded genes in the recipient cells, and facilitates biological treatment. Relatively long-exerting therapeutic effects by gene therapy are potentially advantageous to treat slow progressive degenerative disc disease. In gene therapy, the delivery method and selection of target gene(s) are essential. Although gene therapy was first mediated by viral vectors, technological progress has enabled to apply nonviral vectors and polyplex micelles for the disc. While RNA interference successfully provides specific downregulation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc degeneration. Then, more recent findings of our studies have suggested autophagy, the intracellular self-digestion, and recycling system under the negative regulation by the mammalian target of rapamycin (mTOR), as a gene therapy target in the disc. Here we briefly review backgrounds and applications of gene therapy for the disc, introducing strategies of autophagy and mTOR signaling modulation through selective RNA interference.

Disc Rehydration after Dynamic Stabilization: A Report of 59 Cases

Atilla Yilmaz,Salim Senturk,Mehdi Sasani,Tunc Oktenoglu,Onur Yaman,Hakan Yildirim,Tuncer Suzer,Ali Fahir Ozer 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.3

Study Design: A retrospective study investigating decrease in the nucleus pulposus signal intensity or disc height on magnetic resonance imaging (MRI) and disc degeneration. Purpose: Although a degenerated disc cannot self-regenerate, distraction or stabilization may provide suitable conditions for rehydration and possible regeneration. This study aimed to evaluate clinical outcomes and disc regeneration via MRI in a series of patients with degenerative disc disease (DDD) who underwent lumbar stabilization with a dynamic stabilization system (DSS). Overview of Literature: A dynamic system provides rehydration during early DDD. Methods: Fifty-nine patients (mean age, 46.5 years) who undedwent stabilization with DSS for segmental instability (painful black disc) between 2004 and 2014 were retrospectively evaluated. All patients underwent MRI preoperatively and 12 months postoperatively. Intervertebral disc (IVD) degeneration grades at the implanted segment were categorized using the Pfirrmann classification system. Patients were followed for a mean of 6.4 years, and clinical outcomes were based on visual analog scale (VAS) and Oswestry disability index (ODI) scores. Results: Significant improvements in back pain VAS and ODI scores from before surgery (7 and 68%, respectively) were reported at 6 (2.85 and 27.4%, respectively) and 12 months postoperatively (1.8 and 16.3%, respectively). Postoperative IVD changes were observed in 28 patients. Improvement was observed in 20 patients (34%), whereas progressive degeneration was observed in eight patients (13.5%). Thirty-one patients (52.5%) exhibited neither improvement nor progression. Single Pfirrmann grade improvements were observed in 29% of the patients and two-grade improvements were observed in 5%. Conclusions: Our observations support the theory that physiological movement and a balanced load distribution are necessary for disc regeneration. We conclude that DSS may decelerate the degeneration process and appears to facilitate regeneration.

Vertebral Endplate Changes Correlate with Presence of Cartilaginous Endplate in the Herniated Disc Tissue: Factor Predicting Failure of Conservative Treatment

Latif Rabia,Imran Sumera,Ahmad Ijaz,Ilyas Muhammad Saad,Aziz Amer,Zehra Uruj 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.2

Study Design: Cross-sectional comparative. Purpose: To characterize the scores of disc degeneration, inflammation, and nerve density in herniated disc samples and associate findings with the presence of vertebral endplate (VEP) changes on magnetic resonance imaging (MRI). Overview of Literature: Considering the role of disc composition in spontaneous regression and persistence of pain during conservative management, it is important to identify the influencing factors. VEP changes are highly associated with disc degeneration, but their correlation with herniated disc composition has not yet been reported. Methods: Fifty-one discs were obtained from patients undergoing surgery for herniated disc. Their ages ranged from 19-65 years, and 31/51 were male. Pre-surgical T1 and T2 weighted lumbar-spine MRIs were analyzed to observe Pfirrmann grade, VEP defects, herniation type, Modic changes, and high-intensity zones (HIZ) at the affected level. Five-micron thick sections were stained with hematoxylin and eosin, Alcian blue periodic acid–Schiff stain; examined for histological degeneration scores (HDS; 0–15), inflammation (0 [absence]–3 [severe]), and presence of cartilaginous endplate (CEP). Three-micron thick sections were stained with protein-gene-product 9.5 and expression was counted/mm2. Data was analyzed, and p<0.05 was considered to indicate statistical significance. Results: VEP defects, Modic changes, and HIZ were respectively observed in 30/51, 16/51, and 6/51 of the samples. CEP was observed in 26/51 samples and in 23/51 with endplate defects. Discs with adjacent VEP defects showed increased HDS (p<0.001) and inflammation (p<0.001). Discs with adjacent Modic changes also revealed increased HDS (p=0.01). Histological sections with CEP showed increased HDS (p<0.001) and inflammation (p<0.001), and nerve density was significantly positively correlated with HDS (r=0.27, p=0.02). Conclusions: VEP changes can modulate degeneration and inflammation of herniated discs. Presence of these changes is highly predictive of the occurrence of CEP in herniated discs, which leads to slow resorption and persistent clinical symptoms.

요추 추간판 변성의 자기공명 촬영소견, 전자현미경 소견, 광학 현미경 소견과 임상증상과의 상관관계

안재성,이준규,황득수,정상윤,전택수,이충식 대한척추외과학회 2001 대한척추외과학회지 Vol.8 No.2

서 론 : 요통의 가장 흔한 원인은 추간판의 퇴행성 변화이다. 수핵은 주로 단백다당으로 구성되어있다. 연령이 증가함에 따라 수핵 내의 수분과 단백다당의 양은 점차로 감소되고 교원 섬유의 퇴행성 변화에 기인한다. 이에 저자들은 본원에서 추간판 제거술을 시행 받은 환자에서 적출 되었던 추간판을 대상으로 신생혈관, 세포 소형성, 점액다당류의 변화에 의한 조직학적 변성정도와 전자 현미경상에서의 단백다당의 변성정도와 자기공명영상에서의 변성정도간의 상관관계를 알아보고 임상증상과의 연관성을 알아보고자 본 연구를 시행하였다. 재료 및 방법 : 1998년 1월에서 1999년 12월까지 2년간 충남대학교 병원 정형외과에 입원하여 추간판 적출 술을 시행 받은 환자 중 전자 현미경 조직검사와 광학현미경 조직검사를 위한 조직절편을 얻을 수 있었던 60명을 대상으로 하였다. 평균 연령 36.6세로 남자 28예, 여자32예이었다. 자기 공명 영상 소견에 따른 추간판의 변성과 전자현미경으로 하이알유론상에서 단백다당의 변성정도에 대하여 관찰하였고 광학 현미경 상에서는 신생 혈관형성, 세포 군집 형성, 점액 다당 변화 등에 대하여 관찰하였다. 결 과 : 자기 공명 촬영상 퇴행성 변화와 전자현미경 상 퇴행정도는 환자의 임상증상과 상관 관계가 있었다. 자기 공명 촬영상 퇴행성 정도와 전자현미경상의 퇴행성 변화는 상관 관계가 있었고 광학 현미경 상의 퇴행 증상은 임상증상과 약한 연관이 있었다. 결 론 : 전자현미경하에서 하이알류론산에서의 단백다당의 소실정도를 이용한 퇴행정도는 자기공명영상에 의한 퇴행정도와 관계가 증가함에 따라 증가하는 경향을 보였고, 증상과도 연관이 있었다. 광학현미경 하에서 관찰한 세포 소, 신생혈관 형성, 점액다당류의 증가는 퇴행에 의한 변화로 생각되나 퇴행의 심한 정도와는 관계가 없는 것으로 생각되나 임상증상과는 약한 연관이 있는 것으로 생각된다. 이상의 결과로 볼 때 전자 현미경하에서의 단백다당의 소실에 의한 변성소견이 추간판의 토행성 변화와 관계가 있다고 생각되며 추간판의 퇴행 정도를 알 수 있는 하나의 방법으로 생각된다. Study Design : A retrospective study was performed in patients who had undergone any operation with removal of lumbar intervertebral disc at Chungnam National University Hospital. Objectives : To evaluate relationship among magnetic resonance image, electron microscopic findings, light microscopic findings and clinical symptoms in degenerated intervertebral disc. Summary of literature Review : Degenerative changes and disc herniations in the intervertebral disc have been shown to be accompanied by changes in the water and proteoglycan content of the tissue. Materials and Methods : Our study followed by any operation with removal of intervertebral disc was carried out on 60 patients at Chungnam National University Hospital from January 1998 to December 1999. In radiographic evaluation we used a criteria from Frymoyer. In clinical evaluation we classified clinical symptom according to scale of Kirkaldy-Willis. And we classified of electron microscopic findings into five grades according to degrees of denudation of proteoglycan from hyalunonic acid. In light microscopic findings, we classified by cell nest formation. noevascularization and amount of muccopolysaccharide. Results : In radiologic evaluation there were Ⅱ cases in grade Ⅲ, 28 cases in grade Ⅳ, and 21 cases in grade Ⅴ. There were no grade Ⅰ,Ⅱ in our study. In clinical symptom, there were 20 cases in Good, 18 cases in Fair, and 22 cases in Poor. In electron microscopic findings, there were 4 cases in grade 3, 35 cases in grade 4, and 21 cases in grade 5. There were no grade Ⅰ,Ⅱin this study. There was a relationship between magnetic resonance image and electron microscopic findings and clinical symptom (p<0.05). Conclusion : Our study of electron microscopic findings of degenerated intervertebral disc may be a help to understand of pathogenesis of disc prolapse.

Radiological Parameters of Undegenerated Cervical Vertebral Segments in a Korean Population

최성훈,이희상,조재환,정진일,이동호 대한정형외과학회 2017 Clinics in Orthopedic Surgery Vol.9 No.1

Background: Several scoring systems for cervical disc and facet joint degeneration, using radiography or computed tomography, have been developed and tested for reliability. However, definitions of disc height and facet joint space narrowing vary. To our knowledge, no study has reported quantitative data for normal radiologic values of the cervical spine in the Korean population. The purpose of this study is to determine normal cervical disc height, disc height ratio, and facet joint space values, and investigate the correlation between demographic data and these values. Methods: We performed a retrospective study of patients who underwent artificial disc replacement of the cervical spine. Disc heights and facet joint spaces were measured using cervical neutral lateral radiographs and computed tomography. The means, standard deviations, and 95% confidence intervals of the values were determined. Results: We measured 148 intervertebral discs and 352 posterior facet joints. The mean disc height measured by plain radiography and computed tomography was 5.57 ± 0.81 mm and 4.94 ± 0.94 mm, respectively. The mean facet joint space values measured by plain radiography and computed tomography were 1.94 ± 0.45 mm and 1.43 ± 0.39 mm, respectively. The disc heights and facet joint space values measured by plain radiography were greater than those measured by computed tomography. The lower limit of the 95% confidence interval of the disc height ratio calculated by plain radiography and computed tomography was greater than 0.94 at all levels except for C5–6. Patient height and disc height showed a tendency of positive correlation. Conclusions: In a Korean population, the normal cervical disc height was about 5.0 mm and the normal facet joint space was 1.4 mm. Disc height ratio can reliably identify normal cervical disc height in patients with mild degeneration. Patient height was positively correlated with disc height and facet joint space. Thus, when selecting a cervical implant, surgeons should consider patient height as well as estimated normal disc height.

A Minimally Invasive Rabbit Model of Progressive and Reproducible Disc Degeneration Confirmed by Radiology, Gene Expression, and Histology

Kwon, Young-Joon The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.53 No.6

Objective : To develop a simple, reproducible model of disc degeneration in rabbits through percutaneous annular puncture and to confirm the degree of degeneration over time. Methods : Fifteen New Zealand white rabbits (4 to 5 months old and weighing approximately 3 to 3.5 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Rabbits were sacrificed at 4, 8, or 20 weeks after puncture. For a longitudinal study to assess changes in disc height over time, serial X-rays were performed at 0, 2, 4, 8, and 20 weeks for rabbits in the 20-week group. Upon sacrifice, the whole spinal column and discs were extracted and analyzed with magnetic resonance imaging (MRI), real time reverse transcriptase-polymerase chain reaction, and histological staining. Results : The X-rays showed a slow, progressive decrease in disc height over time. Significant disc space narrowing compared to preoperative disc height was observed during the time period (p<0.001). The MRI grade, aggrecan, and matrix metalloprotease-13 mRNA expression and hematoxylin and eosin/safranin O/anti-collagen II staining were consistently indicative of degeneration, supporting the results of the X-ray data. Conclusion : Percutaneous annular puncture resulted in slow, reproducible disc degeneration that was confirmed by radiology, biochemistry, and histology. This in vivo model can be used to study and evaluate the safety and efficacy of biologic treatments for degenerative disc disease.

Detection of O-Linked-N-Acetylglucosamine Modification and Its Associated Enzymes in Human Degenerated Intervertebral Discs

Georgios Nikolaou,Aristeidis H. Zibis,Apostolos H. Fyllos,Antonios Katsioulis,Sotirios Sotiriou,Anastasios Kotrotsios,Markos Sgantzos,Aikaterini Vassiou,Dimitrios L. Arvanitis 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.6

Study Design: Human herniated discs were obtained from discectomy specimens for the immunohistochemical detection of OGlcNAc and O-GlcNAcase (OGA)/O-GlcNAc transferase (OGT). Purpose: This study aimed to quantify the extent of O-GlcNAcylation and its associated enzymes (OGT/OGA) in human degenerated intervertebral discs. Overview of Literature: The O-GlcNAcylation of nuclear, cytoplasmic, and mitochondrial proteins as well as the effects of such post-translational modifications are currently the focus of extensive research. O-GlcNAcylation is believed to contribute to the etiology of chronic illnesses by acting as a nutrient and stress sensor in the cellular environment. Mature intervertebral disc cells are chondrocyte-like cells, and O-GlcNAc has been shown to promote chondrocyte apoptosis in vitro . We believe that O-GlcNAcylation is a key regulator of disc degeneration. Methods: Fifty-six specimens were fixed for 24 hours in a 10% solution of neutral-buffered formaldehyde, dehydrated, and embedded in paraffin. Tissue slices (4-μm-thick) were used for hematoxylin-eosin staining and immunohistochemistry. Results: We found that O-GlcNAcylation of cytoplasmic proteins was less than that of nuclear proteins in both single cells and cell clusters. Cytoplasmic O-GlcNAcylation occurs subsequent to nuclear O-GlcNAcylation and is directly proportional to disc degeneration. OGT and O-GlcNAc expression levels were identical in all specimens examined. Conclusions: O-GlcNAc and OGA/OGT expression is shown to correlate for the first time with intervertebral disc cell degeneration. Increasing disc degeneration is associated with increasing O-GlcNAcylation in both nuclear and cytoplasmic proteins in human disc cells.