Regional difference in the appearance of apoptotic cell death in the ligamentum flavum of the human cervical spine

Ossification or calcification of the ligamentum flavum (LF) is relatively common in the middle and lower cervical, thoracic, and lumbar spine but extremely rare in the upper cervical region. This clinical fact suggests that there exist local factors promoting or preventing ossification or calcification of LF. However, little is known about the differences in the ultrastructure and cellular alterations of the LF between the different spinal levels, even in the cervical spine. With electron microscopy, we examined samples of LF collected surgically from the upper and lower cervical spine regions; we then studied the apoptotic appearance of ligament cells using a preferential labeling method. We found direct evidence of apoptosis of ligament cells in the LF. Apoptosis was more apparent in the upper region samples than in the lower region samples. The spaces around the normal fibroblasts were filled with thick collagen fibrils, but the collagen fibrils disappeared around the apoptotic bodies and thin fibrils were formed. The difference of the level of apoptosis may correlate to the ultrastructual difference of LF, and our data will benefit further investigations seeking to clarify the mechanism of various pathological conditions in the human LF.     

Gender-specific haplotype association of collagen α2 (XI) gene in ossification of the posterior longitudinal ligament of the spine

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen α2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11A2 haplotype with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males, with a prevalence ratio of 2 : 1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males. Received: September 5, 2000 / Accepted: October 2, 2000     

Bone mineral density in patients with ossification of the posterior longitudinal ligament in the cervical spine

Bone mineral density (BMD) has not been clearly determined in patients with ossification of the posterior longitudinal ligament (OPLL) in the cervical spine. BMD in patients with OPLL was measured in the third vertebral body in the lateral projection and in the distal part of the radius in the anteroposterior projection using dual-energy X-ray absorptiometry (DXA). Patients with OPLL had significantly higher BMD than healthy controls in both the lumbar spine and radius. Observing BMD by gender and age group, high BMD was recognized especially in female patients over 60 years of age. Significantly increased BMD was observed in patients with ankylosing spinal hyperostosis (ASH) in addition to OPLL. These findings suggest that patients with OPLL may tend to develop systemic hyperostosis, leading to the pathological ectopic ossification observed in OPLL. Received: July 7, 1998 / Accepted: March 17, 1999     

Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation     

Three-dimensional evaluation of volume change in ossification of the posterior longitudinal ligament of the cervical spine using computed tomography

Background

Two-dimensional imaging is not adequate for evaluating ossification of the posterior longitudinal ligament (OPLL). This study was designed to evaluate the accuracy of a novel computed tomography (CT)-based three-dimensional (3D) analysis method that we had devised to measure volume changes in OPLL.

Subjects and methods

Twenty OPLL patients (12 male and 8 female; mean age 63.6 years) who were being followed conservatively were examined twice with an interval of at least 1 year between the two scans. The mean interval was 22 (range 12–45) months. A 3D model was created with DICOM data from CT images, using the MIMICS^® software to calculate the volume. The mean ossification volume was determined from two measurements. Since ossification size varies widely, evaluation of change in volume is generally affected by the original size. Therefore, the change in ossification volume between the first and second CT examinations was calculated as the annual rate of progression.

Results

The type of OPLL was classified as continuous in 3 patients, segmented in 3, and mixed in 14. The mean ossification volume was 1,831.68 mm³ at the first examination and 1,928.31 mm³ at the second, showing a significant mean increase in ossification volume. The mean annual rate of lesion increase was 3.33 % (range 0.08–7.79 %).

Conclusion

The 3D method used allowed detailed OPLL classification and quantification of change in the ossified volume. Thus, this method appears to be very useful for quantitative evaluation of OPLL with only minimal measurement error.     

Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients

A case–control study was conducted to examine the association between two single nucleotide polymorphisms (SNPs) in exon 2 of the bone morphogenetic protein-2 gene (BMP-2) and ossification of the posterior longitudinal ligament (OPLL), and to investigate whether SNPs of the Ser37Ala (T/G) and the Ser87Ser (A/G) in the BMP-2 gene are associated with genetic susceptibility to OPLL and its severity in Chinese subjects. The Ser87Ser (A/G) SNP has been implicated in bone mineral density (BMD) and increases the risk of OA in women. The Ser37Ala (T/G) SNP is associated with BMD and the rate of bone loss in osteoporosis and osteoporosis fractures. A total of 57 OPLL patients and 135 non-OPLL controls were studied. Radiographs of the cervical spine were analyzed to determine the presence and the severity of OPLL. The association of two SNPs with the occurrence and the extent of OPLL were statistically evaluated. There was a significant association between the Ser37Ala (T/G) polymorphism and the occurrence of OPLL in the cervical spine. However, no significant association was found between the Ser37Ala (T/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. There was a significant association between the Ser87Ser (A/G) polymorphism and the more number of ossified cervical vertebrae in OPLL patients. However, there was no statistical difference between the Ser87Ser (A/G) SNP and the occurrence of OPLL in the cervical spine. In addition, the Ser87Ser (A/G) polymorphism in male patients and in female patients showed no statistical difference between cases and controls. The present results demonstrate that BMP-2 Gene is not only a factor associated with the occurrence of OPLL, but also a factor related to more extensive OPLL. The “G” allele in the Ser37Ala (T/G) polymorphism is associated with the occurrence of OPLL, but not more extensive OPLL in the cervical spine. The “G” allele in the Ser87Ser (A/G) polymorphism promotes the extent of OPLL, whereas the “A” allele in the Ser87Ser (A/G) polymorphism restricts ectopic ossification in the cervical spine at least in Chinese subjects.     

延伸至上颈椎的颈椎后纵韧带骨化的治疗策略

目的探讨延伸至上颈椎的颈椎后纵韧带骨化的治疗策略。方法从我院2010年5月至2017年3月收治的460例颈椎后纵韧带骨化症患者中筛选出骨化的后纵韧带向上延伸至颈2/3椎间盘平面以上、资料完整且获得随访的39例患者。其中9例行颈3-7单开门椎管扩大成形术(第种手术方式),3例行颈3-7单开门+颈2椎板下缘潜行减压椎管扩大术(第种手术方式),22例行颈3-7单开门+颈2半椎板切除、椎管潜行减压术(第种手术方式),5例颈2-7或2-6单开门椎管扩大成形术(第种手术方式)。所有患者术前、术后、随访时常规颈椎正侧位片、屈伸功能位片、CT三维重建、MRI检查。测量术前和随访时颈椎活动度、颈椎曲度、JOA评分及缓解率、颈2平面矢状径椎管占位率,在MRI T2加权像上评价颈2/3椎间盘平面和颈2椎体平面脊髓前后脑脊液信号是否存在。结果 39例中后纵韧带骨化范围累及颈2/3椎间盘平面13例,累及颈2椎体后缘26例。术前全部患者颈脊髓前方脑脊液信号消失范围3-6个节段、后方消失范围1-6个节段。术后有8例前方脑脊液信号消失范围0-4个节段、后方消失范围0-5个节段。术前与术后脊髓前方和后方脑脊液信号消失范围的比较差异均有显著性意义(P=0.000,P=0.000)。采用第种手术方式的9例患者中有4例术后仍有脊髓前和/或后脑脊液信号的消失,采用第种手术方式的30例患者中仅有4例术后仍存在脊髓前和/或后脑脊液信号的消失,术后两类手术方式之间前后脑脊液信号消失范围差异均有统计学意义(P=0.038;P=0.042)。随访6~36个月,JOA术前(3~13)分,平均(6.85±3.35)分,JOA末次随访(4~17)分,JOA改善率0.07~1.00;两类手术方式之间的术前、末次随访JOA评分、JOA缓解率差异均无统计学意义(P>0.05)。结论颈椎后纵韧带骨化累及颈2/3椎间盘平面以上时减压范围应到颈2椎平面,颈2半椎板切除+潜行减压和颈2椎板成形术是较好的手术方式,减压后脊髓前后脑脊液信号恢复良好。     

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.     

Ossification of the posterior cervical longitudinal ligament

Summary Forty patients with cervical myelopathy due to OPLL (Ossification of the Posterior Longitudinal Ligament) of the cervical spine were studied. According to Abe's or Yamamoto's classification, 12 of them had a 50% decrease in the cross-sectional area of the spinal canal. Subtotal vertebrectomy was carried out in 8 of these patients and the remaining 4 patients received posterior decompression. We concluded that anterior decompression, if possible, is the treatment of choice and posterior decompression is recommended only for the longitudinal type involving more than 3 segments.