Molecular Pathophysiology of Ossification of the Posterior Longitudinal Ligament (OPLL)

Ossification of the posterior longitudinal ligament (OPLL) can be defined as an ectopic ossification in the tissues of spinal ligament showing a hyperostotic condition. OPLL is developed mostly in the cervical spine and clinical presentations of OPLL are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility lowering the quality of life. OPLL is known to be an idiopathic and multifactorial disease, which genetic factors and non-genetic factors including diet, obesity, physical strain on the posterior longitudinal ligament, age, and diabetes mellitus, are involved into the pathogenesis. Up to now, surgical management by decompressing the spinal cord is regarded as standard treatment for OPLL, although there might be the risk of development of reprogression of ossification. The molecular pathogenesis and efficient therapeutic strategy, especially pharmacotherapy and/or preventive intervention, of OPLL has not been clearly elucidated and suggested. Therefore, in this review, we tried to give an overview to the present research results on OPLL, in order to shed light on the potential pharmacotherapy based on molecular pathophysiologic aspect of OPLL, especially on the genetic/genomic factors involved into the etiology of OPLL.

Investigation of Symptomatic Unstable Changes of Non-Fused Component in the Mixed-Type Cervical Ossification of Posterior Longitudinal Ligament Using Dynamic Magnetic Resonance Imaging: A Case Report / 대한신경손상학회지

A 43-year-old man was transferred to our hospital with recurring myelopathic symptoms after previous anterior and posterior surgical decompressions for mixed-type cervical ossification of the posterior longitudinal ligament (OPLL). Conventional magnetic resonance imaging (MRI) showed a preserved cervical curve and the achievement of successful decompression after the previous surgeries. The patient's symptoms were aggravated when he was in the extended neck posture. Dynamic MRI performed with the patient in an extended neck position revealed cord compression by OPLL from C3 to C4 with newly developed retrolisthesis of the C4–5 segment. We recommend the use of dynamic MRI to investigate motion-dependent cord compression caused by instability of the non-fused OPLL component.

Analysis of clinical efficacy of unilateral open-door cervical laminoplasty combined with foraminotomy for cervical ossification of posterior longitudinal ligament / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical efficacy of unilateral open-door laminoplasty combined with foraminotomy for cervical ossification of posterior longitudinal ligament(OPLL).</p><p><b>METHODS</b>The clinical data of 45 patients with OPLL underwent surgical treatment between September 2011 and September 2015 were retrospectively analyzed. There were 26 males and 19 females with a mean age of 53.6 years old(ranged from 28 to 71 years). Among them, 24 cases received the surgery of unilateral open-door cervical laminoplasty combined with foraminotomy(combined group), and 21 cases received a single unilateral open-door cervical laminoplasty(single group). Operation time, intraoperative blood loss, complications including C₅ nerve root palsy and axial symptoms were compared between two groups. Pre-and post-operative Japanese Orthopedic Association(JOA) score, improvement rate of neurological function, Neck Disability Index(NDI) score, and cervical Cobb angle were recorded and analyzed between the two groups.</p><p><b>RESULTS</b>All the patients were followed up for 12-24 months, with an average of (14.3±2.8) months for combined groups and (13.7±3.1) months for single group, and no significant difference was found between the two groups(>0.05). There was no significant difference in operation time and intraoperative blood loss between two groups(>0.05). Postoperative JOA scores obtained obvious improvement in all patients(<0.05). However, there was no significant difference between two groups for the improvement rate of neurological function(>0.05). At final follow-up, NDI scores of combined group and single group were 13.6±1.8 and 16.1±2.4 respectively, there was significant difference between two groups(<0.05). The incidence of C₅ nerve root palsy was lower in combined group(4.2%) than that of single group (28.6%). There was no significant difference in incidence rate of axial symptoms between two groups(>0.05). There was no significant difference in cervical Cobb angle between pre-and post-operative conditions, or between two groups(>0.05).</p><p><b>CONCLUSIONS</b>Unilateral open-door cervical laminoplasty combined with foraminotomy is an effective method to treat cervical OPLL, which could provide sufficient decompression of spinal cord and nerve root, prevent the C₅ nerve root palsy.</p>

HYPEREXTENSION TRAUMA IN PATIENTS WITH CERVICAL SPONDYLOSIS / Мэс засал

Introduction: Due to cervical spondylosispatients with cervical stenosis who hadhyperextension trauma developed spinalcord stress and contusions, tetraplegia anddisability and mortality. Cervical spondylosispatients with hyperextension traumatreatment management still not clearedout throughout the world and very fewresearch has been done in our country.We have been introduced our surgical andrehabilitation comparison research study ofcervical spondylosis trauma in 2015. Our goalis to develop treatment management forthe hyperextension trauma in patients withcervical spondylosis.1. To compare surgical treatmentresults between patients who hadhyperextension injury to the cervical spinewhich were treated at the Departmentof Spinal Surgery of the National Traumaand Orthopaedic Research Center ofMongolia.2. To study biomechanical effects after thesurgeryMaterial and methods: 42 cervicalspondylosis patients with hyperextensioninjury have been chosen retrospectively toevaluate the surgical, conservative, andrehabilitative treatments and results wereanalyzed by SPSS, EXCEL program who weretreated at the Department of Spinal Surgeryof the National Trauma and OrthopaedicResearch Center of Mongolia from 2012-September 2016. Over 20% canal stenosiscases were chosen for laminectomy andanterior discectomy and fusion surgeriesalong with conservative and rehabilitationtreatment. Up to 20% canal stenosis 10cases which is 23.8% of all patients weretreated by conservative treatment.Results: From 42 patients there was 10females and 32 males. Average ages were56±7.9. By the cause of injury 62% werecar accident, 23% motorcycle accident, 10%fall from horse riding and 5% were otherfalls respectively. All patients had neurologicdeficits according to the level of spinal cordinjury. 36 (85.7%) patients had C4-C5 andC5-C6 level injury and 15 (35.7) patients wererecovered from spinal shock after high dosesteroid treatment. According to the X-RAYall patients had cervical spondylosis signand 4 (9.5%) of them had facet fractureswith stable spine condition. After CT scanspinal cord injury located at C3-C4, C4-C5and C5-C6 levels and patients developedfacet arthrosis, ossification of ligaments andintervertebral discs. Clinical signs and CT scans were evaluated and 4 cervical spondylosispatients with hyperextension injury hadlaminectomy and 2 patient had anteriordiscectomy and fusion surgeries. Canalstenosis is decompressed after laminectomysurgery and cervical lordosis is reduced by 7degrees but after anterior discectomy andfusion surgery cervical lordosis is reducedby 3 degrees. Neurological deficit increasinglaminectomy cases had C5 palsy becauseof cord shift (2.4-4mm) which resulted bydenticulate ligament tethering.Conclusion: There were no significantstatistical (P≤.05) differences betweensurgical and rehabilitation treatmentsin cervical spondylosis patients withhyperextension injury who’s canal stenosiswere below 20% [1,2,3,4,5].In our practice itis essential to make laminectomy and anteriordiscectomy and fusion surgeries in 72 hoursafter trauma to help the patient recoverfrom the spinal shock and reabsorption ofcord contusion. For one or two level canalstenosis especially with the OPLL, artificialdisc replacement and ADF surgeries showedbetter results. In multiple level canal stenosiswith OLF and OPLL cases laminectomyand laminoplasty are choice for surgery. Incomparison to foreign study/ Biomechanicalinvestigation of spinal cord injury and diseasein cervical spine Batbayar.K Seoul.2016[2]/ our surgical treatment showed similarresults. Among cervical spondylosis patientswith hyperextension trauma cases whotreated in Spine Department of NationalTrauma and Orthopaedic Hospital, mortalityand disability is increasing and it is essentialto follow correct diagnostic and treatmentalgorithms.

Preliminary Experiences of the Combined Midline-Splitting French Door Laminoplasty with Polyether Ether Ketone (PEEK) Plate for Cervical Spondylosis and OPLL

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of cervical midline-splitting French-door laminoplasty with a polyether ether ketone (PEEK) plate. The authors retrospectively analyzed the results of patients with cervical laminoplasty miniplate (MAXPACER(R)) without bone grafts in multilevel cervical stenosis. METHODS: Fifteen patients (13 males and 2 females, mean age 50.0 years (range 35-72)) with multilevel cervical stenosis (ossification of the posterior longitudinal ligament and cervical spondylotic myelopathy) underwent a combined surgery of midline-splitting French-door laminoplasty with or without mini plate. All 15 patients were followed for at least 12 months (mean follow-up 13.3 months) after surgery, and a retrospective review of the clinical, radiological and surgical data was conducted. RESULTS: The radiographic results showed a significant increase over the postoperative period in anterior-posterior diameter (9.4+/-2.2 cm to 16.2+/-1.1 cm), open angles in cervical lamina (46.5+/-16.0degrees to 77.2+/-13.1degrees), and sectional volume of cervical central canal (100.5+/-0.7 cm2 to 146.5+/-4.9 cm2) (p<0.001). The sagittal alignment of the cervical spine was well preserved (31.7+/-10.0degrees to 31.2+/-7.6degrees, p=0.877) during the follow-up period. The clinical results were successful, and there were no significant intraoperative complications except for screw displacement in two cases. The mini plate constructs did not fail during the 12 month follow-up period, and the decompression was maintained. CONCLUSION: Despite the small cohort and short follow-up duration, the present study demonstrated that combined cervical expansive laminoplasty using the mini plate is an effective treatment for multilevel cervical stenosis.

Association Study of Fibroblast Growth Factor 2 and Fibroblast Growth Factor Receptors Gene Polymorphism in Korean Ossification of the Posterior Longitudinal Ligament Patients

OBJECTIVE: The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). METHODS: A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. RESULTS: Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). CONCLUSION: The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).

Association of Estrogen Receptor 2(ESR 2) Gene Polymorphisms with Ossification of the Posterior Longitudinal Ligament of the Spine

STUDY DESIGN: Genetic screening of the estrogen receptor 2 (ESR2) genes in patients with ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: We studied the relationships between ESR2 gene polymorphisms and OPLL to understand the pathophysiology of OPLL. SUMMARY OF LITERATURE REVIEW: The OPLL has a strong genetic component. Several familial surveys and human leukocyte antigen (HLA) haplotype studies reveal that genetic background is an important component in the occurrence of OPLL and a large number of gene analysis studies were utilized to clarify the susceptible gene for OPLL, including COL11A2, BMP-2, TNF-alpha, NPPS, leptin receptor, transforming growth factor (TGF)-beta, Retinoic X receptor, ER, IL-1, PTH, and VDR have been performed. MATERIALS AND METHOD: Genomic deoxyribonucleic acid (DNA) samples obtained from 164 patients (93 men and 71 women) with OPLL and 219 control subjects, without the disease (105 men and 114 women) were amplified by polymerase chain reaction, and polymorphism genotypes were determined by the restriction endonuclease digestion. The distribution of genotypes was compared between the patients with the disease and the control subjects. RESULTS: The polymorphism of ESR2 [rs1256049, exon6, Val328Val, p=0.018, odd ratio (OR)=2.41, 95 confidence interval (CI)=1.15-5.02 in the recessive model] only showed statistically significant association between the control and the OPLL groups. The rest SNPs of ESR2 did not show any significant differences between the control and the OPLL groups. CONCLUSIONS: Estrogen receptor 2 (ESR2) gene polymorphisms (rs 1256049) was associated with OPLL. In future studies, we will perform target SNP chip between OPLL and candidate gene.

Association of Toll-Like Receptor 5 Gene Polymorphism with Susceptibility to Ossification of the Posterior Longitudinal Ligament of the Spine in Korean Population

OBJECTIVE: Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may play a role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-kappaB). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population. METHODS: A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR). RESULTS: None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p > 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models. CONCLUSION: These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.

Post-Laminectomy Kyphosis in Patients with Cervical Ossification of the Posterior Longitudinal Ligament: Does It Cause Neurological Deterioration?

OBJECTIVE: Total laminectomy (TL) is an effective surgical technique for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) along multiple levels. However, kyphosis and probable neurological deterioration have been frequently reported after laminectomy. We analyzed the changes in the cervical curvature after TL and subsequent changes in neurological status. METHODS: We retrospectively reviewed the records of 14 patients who underwent TL for the treatment of cervical OPLL between Jan. 1998 and Dec. 2003. TL was selected according to the previously determined criteria. The curvature of the cervical spine was visualized on a lateral cervical spine X-ray and measured using Ishihara's Curvature Index (CI) before the operation and at the last follow-up examination. Perioperative neurological status was estimated using the modified Japanese Orthopedic Association score and the Improvement Rate (IR) at the same time as the images were evaluated. RESULTS: The mean age of the patients was 57 years, the male/female ratio was 10:4, and the mean follow-up period was 41 months. The mean number of OPLL was 4.9, and the mean number of operated levels was also 4.9. The CI decreased after TL (p=0.002), which was indicative of a kyphotic change. However, this kyphotic change showed no correlation with the length of the follow-up period, number of operated levels and preoperative CI. Neurological examination at the last follow-up showed an improved neurological status in all patients (p=0.001). There was no neurological deterioration in any case during the follow-up period. Moreover, there was no correlation between IR and the degree of kyphotic change. Postoperative complications, such as C5 radiculopathy and epidural bleeding, resolved spontaneously without neurological sequelae. CONCLUSION: Kyphotic change was observed in all but one patient who underwent TL for the treatment of cervical OPLL. However, we did not find any contributing factors to kyphosis or evidence of postoperative neurological deterioration.

Influence of different operations on BMP-2,BMP-7 in rat posterior longitudinal ligament / 中国矫形外科杂志

[Objective]To discuss the initiating and developing mechanism of OPLL,and the influence of different operations on happening and developing of OPLL.[Method]We subgroup healthy adult S-D rats into groups,did operation on C 3~6 level.The first group:laminectomy;the second group:laminectomy and muscle cutting;the third group:muscle cutting only;the fourth group:exposure only;contrasting group:no treatment.We got the tissue of posterior longitudinal,ligament at 1,2,4,and 8 weeks post-operation and quantify BMP-2 and BMP-7 by PCR method.[Result]BMP-2,BMP-7 increased significantly in the 1st,2nd and 3rd group compared with the contrastinggroup;BMP-2,BMP-7 of only exposure group had no significant difference compared with the contrasting group.[Conclusion]BMP-2 and BMP-7 play important roles in the early stage of OPLL,they could be the on-setting factors of OPLL.BMP-7 may play an important roles in the later ossification period.

Surgical treatment and results of ossification of posterior longitudinal ligament of cervical spine / 中国矫形外科杂志

[Objective]To discuss surgical approaches,results and complications of ossification of posterior longitudinal ligament(OPLL)of cervical spine.[Method]The clinic data of 48 patients from 2000 with cervical OPLL were reviewed and analyzed.Eighteen of them were decompressed from an anterior approach and 30 from a posterior approach.The improvement rate according to JOA scoring system were evaluated,some relevant imaging examination data including X-rays,CT and MRI were also measured,which were taken preand post-operatively.Surgical complications were also recorded.[Result]Of 48 patients,23 had cervical stenosis,the mean occupancy rate was 41.4%,and 19 had the abnormal signal in spinal cord.The mean postoperative improvement rate was 68.3% in patients treated by anterior decompression and 51.3% in those treated by posterior decompression.There were 2 patients with dural tear,5 with segmental nerve root palsy and 2 with hematoma after operation.[Conclusion]Suitable operation methods should be chosen according to the location,extent and occupancy ratio of OPLL,which is important for avoiding complications and improving surgical results.

Thoracic Myelopathy Caused by Multiple Ossified Ligamentum flavum Combined with Ossification of the Posterior Longitudinal Ligament

The authors report a case of thoracic myelopathy caused by multiple ossification of the ligamentum flavum(OLF) combined with ossification of the posterior longitudinal ligament(OPLL). A 52-year-old man had progressive motor weakness and numbness in the lower extremities. Diagnosis was made from the MR imaging that provided useful information about the multiple lesions in the lower cervical and upper thoracic area and about the degree of spinal cord compression. The surgical approach consisted of two stages: Posterior decompression for OLF(first stage) and anterior decompression for OPLL, followed by interbody fusion(second stage). The patient had satisfactory improvement after surgical intervention.

Anterior Decompression and Interbody Fusion for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine: Case Report

The authors describe a case of a 41-year-old woman who developed clumsiness and decreased sensation of both hands due to ossification of the posterior longitudinal ligament(OPLL) of the cervical spine. The central part of the vertebral body and ossified area of the posterior longitudinal ligament was removed and the defect was filled with iliac bone graft. The operative result was excellent and the brief review about OPLL was made.

Anterior Decompression and Interbody Fusion for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine: Case Report

The authors describe a case of a 41-year-old woman who developed clumsiness and decreased sensation of both hands due to ossification of the posterior longitudinal ligament(OPLL) of the cervical spine. The central part of the vertebral body and ossified area of the posterior longitudinal ligament was removed and the defect was filled with iliac bone graft. The operative result was excellent and the brief review about OPLL was made.

Ossification of Spinal Ligaments

This authors reviewed the radiographs of 20,057 patients with spinl radiculomyelopathy from April 1983 August 1990. The incidence and distribtion of the ossification of the spinal ligaments were analized as following. 1) The overall incidence of spinal ligaments ossification was 3.6% among 20,057 patients. 2) The most frequently occurs at lumbar area(67.1%), and then cervical(27.5%) thoracic(0.4%) area as in orders. 3) The OPLL was most common type(2.19%) of these spinal ligaments ossification, and then OALL(0.7%), OLF(0.24%) as in orders. 4) OPLL (1) OPLL was most frequent at lumbar area(58.6%) and then cervical(37.0%), thoracic(0.4%) area as in orders. (2) The cervical OPLL was commonly found at C5 & C6 area and morphologically, the multiple segmented type was most common then continuous type, mixed type and single segmented type in orders. (3) The multiple segmented type was more frequently found at upper cervical area, but the continuous type was more frequent at lower cervical area. 5) OALL (1) OALL was most frequent at lumbar area(86.0%) but thoracic(1.4%) and cervecal area(5.3%) were relatively low in frequency. (2) Of the lumbar OALL, the L4/5 area was most frequent site(37.8%) but the L3/4(25.3%) and L5/S1 area(24.5%) also had relatively high occurance rate. 6) OLF (1) OLF was most frequent at lumbar area(92.7%), but the incidence of OLF was relativerly rare at cervical(2.1%) and thoracic area(5.2%). (2) Of the lumbar OLF, the L4/5 area was most common site(33.1), but L5/S1 area had also high occurance rate(27.2%).

Clinical Evaluation of Cervical Ossification of the Posterior Longitudinal Ligament

The authors treated 32 patients with Ossification of the Posterior Longitudinal Ligament(OPLL). Seventeen of these patient had surgery during the past 1 year between 1987 and 1988. In this study we present a radiological and clinical analysis of these cases with a literature review. We also discuss a clinical system of grading, different types of radiological patterns, the indication of surgical treatment and the choice of operative methods. 1) The incidence of the cervical OPLL was about 5.4% in our annual study, which was based on the cervical CT and CTM. 2) The highest incidence was in patients 50-60 years of age and male: female ratio was about 3:1. 3) The highest incidence was in C5, C6 and C4 levels of cervical spine and two and three level involvement was prominent. 4) The pattern of OPLL was devided into a continuous type (21%), a multiple segmented type(48%), a mixed type(25%), a localized type(6%). 5) Absolute diameter did not always parallel the extent of spinal cord signs as did the percentage of spinal canal narrowing. 6) In cases of a clinical grading of more than III, surgery must be considered. In grade II, surgery is indicative if conservative management failed to improve the clinical symptoms. 7) For the evaluation of the cervical OPLL, the CT-Scan of CT metrizamide myelography was more useful method. 8) Cervical Corpectomy and fusion with or without bone cement were found to be advisable in Cases of cervical OPLL.

Surgical Managements of Cervical Ossification of Posterior Longitudinal Ligament

In 1960, Tskimoto first mentioned the spinal cord lesions caused by compression of posterior longitudinal ligament(OPLL), thereafter, hundreds of cases have been reported. There are, however, some controversial opinions concerning the mechanisms of the formation and development of OPLL and questions why a special ligaments, posterior longitudinal ligaments can be calcified, enlarged and compress the cord. And also, there have been many reports describing various surgical method that could manage OPLL, but the OPLL still has many problems in surgical treatment. Recently, the neurosurgical team at the St. Pauls Hospital, encountered and operated on 7 cases of OPLL at cervical area. After all dignostic tests and examinations were done, the morphological classification, combined other lesions and pathological status were verified and analyzed during treatment. The different surgical methods were taken case by case. The authors would like to share with you our experiences of the surgical methods, indications of operation the results and the progrosis of treatment in OPLL.