Prevalence and related clinical factors of thoracic ossification of the ligamentum flavum—a computed tomography-based cross-sectional study

Background Text

Thoracic ossification of the ligamentum flavum (TOLF) is an uncommon pathology, but it may sometimes grow and cause serious neurologic manifestations. Little has been demonstrated yet about the epidemiology and etiology of TOLF.

Prevalence,Distribution, and Significance of Incidental Thoracic Ossification of the Ligamentum Flavum in Korean Patients with Back or Leg Pain : MR-Based Cross Sectional Study

Objective

Thoracic ossification of the ligamentum flavum (OLF) is a relatively rare disease. Because of ambiguous clinical symptom, it is difficult for early diagnosis of OLF and subsequent treatment can be delayed or missed. Therefore, the purpose of this study is to comprehensively assess the prevalence and distribution of thoracic OLF by magnetic resonance imaging (MRI) and coexisting spinal disease in Korean patients with back pain or leg pain.

Methods

The sample included 2134 Korean patients who underwent MRI evaluation for back pain. The prevalence and distribution of thoracic OLF were assessed using lumbar MRI with whole spine sagittal images. Additionally, we examined the presence of coexisting lumbar and cervical diseases. The presence of thoracic OLF as well as clinical parameters such as age, sex, and surgery were retrospectively reviewed.

Results

The prevalence of thoracic OLF in total patients was 16.9% (360/2134). The prevalence tended to increase with aging and was higher in women than in men. The lower thoracic segment of T10-11 was the most frequently affected segment. Of the 360 patients with OLF, 31.9% had coexisting herniated thoracic discs at the same level. Approximately 74% of the patients with OLF had coexisting lumbar and cervical disease. Nine (2.5%) of 360 OLF patients underwent surgery for thoracic lesion.

Conclusion

The prevalenceof thoracic OLF was relatively higher than those of previous reports. And coexisting lumbar and cervical disease were very frequent. Therefore, we should check coexisting spinal diseases and the exact diagnostic localization of ossification besides lumbar disease.     

弥漫性特发性骨质增生症骨化相关特异性miRNAs分析

 目的 三维黏附培养下获得并分析弥漫性特发性骨质增生症(diffuse idiopathic skeletal hyperostosis,DISH)骨化相关特异性miRNAs。方法 2012年1月至2014年1月通过手术分别获取4份DISH患者骨化黄韧带组织块与4份创伤患者正常黄韧带组织块,采用胶原酶消化法分离组织块中成纤维细胞,在人完全脱细胞羊膜(human acellular amniotic membrane,HAAM)上培养,收获前进行细胞免疫荧光鉴定;提取细胞总RNA并检测其质量,通过YM-100 (Millipore) 微离心过滤柱得到片段< 300 nt的小RNA,采用μParaflo? miRNA微阵列基因表达实验和分析技术分析miRNAs表达谱,对结果中部分差异miRNAs进行qRT-PCR验证;采用PicTar 2005、miRanda v5、TargetScan 5.1软件预测靶基因;使用Gene Ontology进行靶基因功能注释,基于KEGG Pathway数据库分析靶基因所参与的骨化相关信号传导通路;使用TRANSFAC 7.0 public转录因子数据库及Patser预测程序预测转录因子结合位点。结果 成纤维细胞在HAAM上生长时形态保持良好,呈簇状分布,复层生长并建立起细胞间联系; 免疫荧光鉴定发现DISH组细胞骨钙素和Ⅰ、Ⅱ、Ⅲ型胶原呈阳性,正常组细胞Ⅰ和Ⅲ型胶原呈阳性;共获得15种信号比值>1.5倍差异表达的miRNAs,12种上调、3种下调,qRT-PCR验证结果与微阵列芯片检测结果一致;共预测出 67个靶基因,影响细胞分化、黏附及矿物质沉积等活动,参与MAPK、Wnt、TGF-β、Focal adhesion等多个骨化相关信号途径,预测出10种差异性miRNAs的转录因子。结论 HAAM可实现成纤维细胞在体外三维黏附下生长,部分miRNAs的异常表达可能参与DISH发病。     

Semi-Circumferential Decompression: Microsurgical Total en-bloc Ligamentum Flavectomy to Treat Lumbar Spinal Stenosis with Grade I Degenerative Spondylolisthesis

Background

To describe and assess clinical outcomes of the semi-circumferential decompression technique for microsurgical en-bloc total ligamentum flavectomy with preservation of the facet joint to treat the patients who have a lumbar spinal stenosis with degenerative spondylolisthesis.

Methods

We retrospectively analyzed the clinical and radiologic outcomes of 19 patients who have a spinal stenosis with Meyerding grade I degenerative spondylolisthesis. They were treated using the "semi-circumferential decompression" method. We evaluated improvements in back and radiating pain using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). We also evaluated occurrence of spinal instability on radiological exam using percentage slip and slip angle.

Results

The mean VAS score for back pain decreased significantly from 6.3 to 4.3, although some patients had residual back pain. The mean VAS for radiating pain decreased significantly from 8.3 to 2.5. The ODI score improved significantly from 25.3 preoperatively to 10.8 postoperatively. No significant change in percentage slip was observed (10% preoperatively vs. 12.2% at the last follow-up). The dynamic percentage slip (gap in percentage slip between flexion and extension X-ray exams) did not change significantly (5.2% vs. 5.8%). Slip angle and dynamic slip angle did not change (3.2° and 8.2° vs. 3.6° and 9.2°, respectively).

Conclusions

The results suggested that semi-circumferential decompression is a clinically recommendable procedure that can improve pain. This procedure does not cause spinal instability when treating patients who have a spinal stenosis with degenerative spondylolisthesis.     

扩大全椎板切除减压术治疗黄韧带骨化型胸椎管狭窄症

目的探讨后路扩大全椎板切除减压并内固定术治疗黄韧带骨化型胸椎管狭窄症（ossification of ligamentum fLavum-thoracic spinal stenosis,OLF-TSS）的手术方法及治疗效果。方法2004年4月至2010年2月,采用后路扩大全椎板切除减压并内固定术治疗OLF-TSS患者12例,男7例,女5例;年龄40～69岁,平均53岁;病程为40天～3年,平均10.4个月;病变节段为1～3个,平均1.75个。其中1例合并胸椎间盘突出。根据JOA评分标准,术前评分为2～10分,平均（6.75±2.73）分。结果 7例患者获得随访,随访时间为2～8个月,平均4.7个月。术中1例发生硬膜破裂,经修补愈合良好。术后3例出现神经功能下降,术前与术后2周的JOA评分比较,差异无统计学意义（P〉0.05）,术前与末次随访的JOA评分比较,差异有统计学意义（P〈0.05）。无一例出现其他并发症。结论后路扩大全椎板切除减压并内固定术治疗OLF-TSS安全而有效。     

The Increased Expression of Matrix Metalloproteinases Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum in Patients with Lumbar Spinal Stenosis

Background

One of the characteristics of spinal stenosis is elastin degradation and fibrosis of the extracellular matrix of the ligamentum flavum. However, there have been no investigations to determine which biochemical factors cause these histologic changes. So we performed the current study to investigate the hypothesis that matrix metalloproteinases (MMPs), which possess the ability to cause extracellular matrix remodeling, may play a role as a mediator for this malady in the ligamentum flavum.

Methods

The ligamentum flavum specimens were surgically obtained from thirty patients with spinal stenosis, as well as from 30 control patients with a disc herniation. The extents of ligamentum flavum elastin degradation and fibrosis were graded (grade 0-4) with performing hematoxylin-eosin staining and Masson''s trichrome staining, respectively. The localization of MMP-2 (gelatinase), MMP-3 (stromelysin) and MMP-13 (collagenase) within the ligamentum flavum tissue was determined by immunohistochemistry. The expressions of the active forms of MMP-2, MMP-3 and MMP-13 were determined by western blot analysis, and the blots were quantified using an imaging densitometer. The histologic and biochemical results were compared between the two conditions.

Results

Elastin degradation and fibrosis of the ligamentum flavum were significantly more severe in the spinal stenosis samples than that in the disc herniation samples (3.14 ± 0.50 vs. 0.55 ± 0.60, p < 0.001; 3.10 ± 0.57 vs. 0.76 ± 0.52, p < 0.001, respectively). The expressions of the active form of MMPs were identified in all the ligamentum flavums of the spinal stenosis and disc herniation patients. The expressions of active MMP-2 and MMP-13 were significantly higher in the spinal stenosis samples than that in the disc herniation samples (both p < 0.05). The expression of active MMP-3 was slightly higher in the spinal stenosis samples than that in the disc herniation samples, but the difference was not statistically significant (p = 0.131). MMP-2, -3, and -13 were positively stained on the ligamentum flavum fibroblasts.

Conclusions

The current results suggest that the increased expression of active MMPs by the ligamentum flavum fibroblasts might be related to the elastin degradation and fibrosis of the ligamentum flavum in the patients who suffer with lumbar spinal stenosis.     

动力失衡性大鼠颈椎黄韧带早期退变模型的建立

目的通过切除颈椎后方肌肉的方法制作动力失衡性大鼠颈椎黄韧带退变动物模型。方法将120只健康雄性Wistar大鼠随机分为三组:对照组、肌肉剥离组、肌肉切除组。造模术后不同时间点分别进行大体观察、斜板实验及CR片观察。结果造模后1月,颈后肌肉缺损区肌肉完全再生,椎间隙变窄、骨赘形成、关节突硬化出现较早,术后2个月大鼠颈椎的退变尚不至于造成后肢运动功能的改变。结论切除颈后方肌肉可造成颈椎动力失衡性大鼠黄韧带的退变,为颈椎病的研究提供了重要的动物模型。     

保留黄韧带预防椎间盘术后硬膜外粘连的实验研究

目的 观察保留黄韧带预防硬膜外粘连的效果,为临床保留黄韧带预防椎间盘术后硬膜外粘连提供实验依据.方法 选取45只健康成年新两兰大白兔,雌雄不分,体重2～2.5 kg,随机分为A、B、C 3组,每组15只.在A组每只新四兰大白兔上完全切除黄韧带,在B组保留一半黄韧带,在C组完全保留黄韧带.术后于2、4、8周对硬膜外纤维性瘢痕粘连的情况进行大体观察及组织学观察,并对其进行相应评分,对病理切片进行计算机图像分析,所得数据进行统计学处理.结果 大体观察术后2、4、8周,各组差异均有统计学意义(F值分别为4.660、8.591、31.858,均P<0.05)、组织学观察,术后2、4、8周,各组差异均有统计学意义(F值分别为5.190、9.561、34.658,均P<0.05);计算机图像分析,术后各时间点,组间差异均有统计学意义(F值分别为30.783、47.350、25.544,均P<0.01);各组随时间的推移,硬膜外粘连长度与硬膜囊的周径比值逐渐增加.结论 完全保留黄韧带,能有效防止硬脊膜外来自后方的瘢痕组织向椎管内侵入,起到空间屏障作用,明显地减少了瘢痕组织形成的量,减轻了来自后方的纤维瘢痕组织侵入椎管所造成的硬脊膜周围纤维性粘连.     

左归丸对免疫性卵巢早衰小鼠性激素的影响

目的测定8种清热解毒类藏药异叶青兰、甘青乌头、獐芽菜、乌奴龙胆、五脉绿绒蒿、铁棒锤、蒺藜、兔耳草体外抑菌活性。方法用琼脂扩散法和微量稀释法研究8种清热解毒类藏药体外抑菌活性,以抑菌圈和最小抑菌浓度(MIC)为评价指标。结果藏药水提取物和醇提取物对所选菌种都具有一定的抑制作用,形成抑菌圈直径范围为8~22 cm,MIC范围为1.56~50.00 mg.mL-1。其中异叶青兰和甘青乌头抑菌活性最强,五脉绿绒蒿基本没有抑菌作用。结论8种藏药水提取物,抑菌活性异叶青兰>甘青乌头>獐芽菜>兔耳草>铁棒锤>蒺藜>乌奴龙胆>五脉绿绒蒿;而对于醇提取物,异叶青兰>甘青乌头>铁棒锤>兔耳草>蒺藜>獐芽菜>乌奴龙胆>五脉绿绒蒿。