Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system

BACKGROUND CONTEXTBack and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.PURPOSETo quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.STUDY DESIGNAn immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.METHODSHuman IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.RESULTSFifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).CONCLUSIONSBMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.CLINICAL SIGNIFICANCEBMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.     

Disc degeneration contributes to the denser bone in the subendplate but not in the vertebral body in patients with lumbar spinal stenosis or disc herniation

BACKGROUND CONTEXTIt is commonly believed that decreased bone quality would lead to endplate degeneration and arthritic changes in the facet joints, and thus accelerated disc degeneration (DD). However, some more detailed studies of vertebral bone structure have found that bone mineral density (BMD) in the vertebral body is increased rather than decreased in moderate or greater disc degeneration. The relationship between BMD and DD still needs further study. MRI-based vertebral bone quality scores have been shown to be effective in reflecting BMD, rendering a new way to evaluate the changes of vertebral body bone with DD using MRI alone.PURPOSETo evaluate MRI-based vertebral bone quality and Pfirrmann grades in patients with lumbar spinal stenosis or disc herniation, and to identify if DD is associated with denser bone around the endplate.STUDY DESIGN/SETTINGA single-center, retrospective cohort study.PATIENT SAMPLEA total of 130 patients with lumbar disc herniation and lumbar spinal stenosis from January 2019 to November 2020 who had a complete dual-energy X-ray absorptiometry scan and noncontrast lumbosacral spine MRI data.OUTCOME MEASURESThe vertebral bone quality score (VBQ) and sub-endplate bone quality score (EBQ) was calculated as a ratio of the signal intensity of the vertebral bodies and sub-endplate regions to the signal intensity of the cerebrospinal fluid at L3 on the mid-sagittal T1-weighted MRI images, respectively. The Pfirrmann grades of the lumbar discs were assessed as well.METHODSThe age, gender, body mass index, and T-score of the lumbar spine of the patients were collected. The degeneration grades of the lumbar discs were evaluated according to the Pfirrmann classification. VBQ and EBQ were measured through T1-weighted lumbar MRI. The VBQ and EBQ scores were compared between cranial and caudal sides. The correlation between MRI-based bone quality and DD was calculated. A linear regression model was used to examine the association between DD and adjacent EBQ and VBQ.RESULTSThis study included 569 lumbar segments from 130 inpatients. Cranial and caudal EBQ decreased with the increase of the Pfirrmann grade. The discs with Pfirrmann grade 5 had significantly lower caudal EBQ than the discs with Pfirrmann grades 2, 3, and 4. In the osteoporosis patients, the Pfirrmann grades negatively correlated both with the cranial EBQ and caudal EBQ. Pfirrmann grade greater than 4 was an independent contributor to the cranial EBQ, whereas greater than 3 was an independent contributor to the caudal EBQ.CONCLUSIONSDisc degeneration grades correlated with the EBQ but not with the VBQ. In patients with lumbar spinal stenosis or disc herniation, DD contributes to the denser bone in the sub-endplate, but not in the whole vertebral body.     

腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变Pfirrmann分级的相关性

目的 探讨腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变程度之间的关系,为腰椎椎间盘退行性疾病的诊断和治疗提供客观准确的依据。方法 回顾性分析2019年1月—2019年6月来本院就诊的61例腰椎椎间盘退行性变患者临床资料。在腰椎侧位X线片上测量腰椎椎间隙及相应上位椎体的高度,并计算椎间隙高度与上位椎体高度的比值;在腰椎矢状位MRI上评估腰椎椎间盘退行性变Pfirrmann分级;比较不同Pfirrmann分级椎间盘的椎间隙高度与上位椎体高度比值的差异,并采用Spearman相关分析研究椎间隙高度与上位椎体高度比值与相应节段椎间盘Pfirrmann分级之间的相关性。结果 除L₁/L₂节段,其余各节段椎间隙高度与上位椎体高度比值均随着Pfirrmann分级增加而逐渐减小,差异均有统计学意义（P < 0.05）。相同Pfirrmann分级的不同节段椎间盘之间椎间隙高度与上位椎体高度比值差异无统计学意义（P > 0.05）。Spearman相关分析结果显示,L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段Pfirrmann分级与椎间隙高度与上位椎体高度比值呈负相关（r =-0.568,P < 0.05）。结论 临床上测量L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段椎间隙高度与上位椎体高度比值对腰椎椎间盘退行性疾病的诊断可能具有重要意义。     

Migration patterns of herniated disc fragments: a study on 1,020 patients with extruded lumbar disc herniation

Background contextHerniated disc fragments are known to migrate in various directions within the spinal canal. To date, no comprehensive studies have been undertaken to examine the migration patterns of herniated disc material using a standard nomenclature and classification system.PurposeTo report migration patterns of extruded lumbar disc fragments.Study designA review of magnetic resonance (MR) images.Patient sampleA total of 1,020 consecutive Azeri patients with symptomatic extruded lumbar intervertebral disc herniation.Outcome measuresMigration patterns of extruded lumbar disc fragments in vertical and horizontal planes and their association with age, gender, body mass index (BMI), and the level of herniation.MethodsHigh-quality axial and sagittal MR images of the lumbar spine were used. Disc material that was displaced away from the site of extrusion, regardless of continuity, was considered “migrated.” The migration patterns observed were rostral or caudal in the vertical plane and central, paracentral, subarticular, foraminal, or extraforaminal in the horizontal plane.ResultsIn the vertical plane, rostral and caudal migrations were observed in 27.8% and 72.2% of the patients, respectively. The number of rostral migrations increased significantly with increasing age and in higher levels in the lumbar spine (p<.001 for both). Radiculopathy was significantly more frequent in caudal migrations than in rostral migrations (78.9% vs. 65.1%, p<.001). There was no significant association between gender or BMI and migration patterns in the vertical plane. In the horizontal plane, central, paracentral, subarticular, foraminal, and extraforaminal migrations were reported in 17.3%, 74.2%, 4.3%, 2.5%, and 1.8% of the patients, respectively. The youngest (median age 39 years, interquartile range [IQR] 13 years) and the oldest (median age 55 years, IQR 15 years) groups of patients (p<.001) had the most formainal and extraforaminal migrations, respectively. Radiculopathy was present in 66.5%, 76.8%, 88.6%, 96%, and 27.8% of the patients with central, paracentral, subarticular, foraminal, and extraforaminal migrations, respectively (p<.001). No significant association was found between gender, BMI, or the level of herniation and migration pattern in the horizontal plane.ConclusionsCaudal and paracentral migrations are the most common patterns of migration in patients with extruded lumbar disc herniation in the vertical and horizontal planes, respectively. Age and the level of herniation may affect the migration patterns of herniated lumbar disc material.     

The effect of disc degeneration on anterior shear translation in the lumbar spine

Many pathologies involving disc degeneration are treated with surgery and spinal implants. It is important to understand how the spine behaves mechanically as a function of disc degeneration. Shear loading is especially relevant in the natural and surgically stabilized lumbar spine. The objective of our study was to determine the effect of disc degeneration on anterior translation of the lumbar spine under shear loading. We tested 30 human cadaveric functional spinal units (L3–4 and L4–5) in anterior shear loading. First, the specimens were imaged in a 1.5 T magnetic resonance scanner. The discs were graded according to the Pfirrmann classification. The specimens were then loaded up to 250 N in anterior shear with an axial compression force of 300 N. Motion of the vertebrae was captured with an optoelectronic camera system. Inter‐ and intra‐observer reliability for disc grading was determined (Cohen's and Fleiss' Kappa), and a non‐parametric test was performed on the translation data to characterize the effect of disc degeneration on this parameter. We found fair to moderate agreement between and within observers for the disc grading. We found no significant effect of disc degeneration on anterior shear translation (Kruskal‐Wallis ANOVA). Our results indicate that disc degeneration, as classified with the Pfirrmann scale, does not predict lumbar spinal motion in shear. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:450–457, 2015.     

合并椎间盘突出的退变性腰椎滑脱椎间盘形态改变及其意义

【摘要】 目的：观察合并椎间盘突出的退变性腰椎滑脱（lumbar degenerative spondylo-listhesis,LDS）患者的椎间盘影像学特点,探讨椎间盘退变程度、椎间隙角度及高度与退变性腰椎滑脱间的关系。方法：以2009年10月～2011年11月我院和石景山医院收治的合并L4/5椎间盘突出的退变性腰椎滑脱患者37例作为观察组,另选同期单纯L4/5椎间盘突出症患者38例作为对照组,对L4/5椎间盘退变程度按照Pfirrmann法分级,CT测定L4/5椎间盘正中矢状面的椎间隙角度和椎间隙高度,对所得数据进行统计分析。结果：观察组L4/5椎间盘MRI退变程度B、C、D、E级分别为1、25、8及1例,对照组分别为2、21、13及2例,两组椎间盘退变程度间差异没有显著性（P>0.05）;CT测量L4/5椎间隙角度观察组和对照组分别为3.08°±1.87°和6.48°±2.92°,对照组椎间隙角度明显大于观察组（P<0.05）;椎间隙高度观察组和对照组分别为8.46±1.81mm和9.38±2.46mm,两组间比较差异没有显著性（P>0.05）。结论：椎间隙角度减小,可能是退变性腰椎滑脱发病的重要因素之一。     

BNIP3与LC3B在椎间盘退行性变过程中的作用

目的研究BCL2/腺病毒E1B19k Da相互作用蛋白3(BNIP3)基因及微管相关蛋白轻链3B(LC3B)基因在退变椎间盘中的表达情况,探讨其与椎间盘退行性变分级之间的相关性。方法收集2016年4月—2016年7月因腰椎椎间盘突出症于本院接受手术治疗的21例患者的退变腰椎椎间盘标本25个,依据Pfirrmann分级分成5组,分别采用实时荧光定量PCR技术和蛋白质印迹法检测BNIP3、LC3B的m RNA和蛋白表达量,用实时荧光定量PCR技术检测Bcl-2、Bax、Caspase-3的mRNA表达量,并分析BNIP3表达量、LC3B表达量、细胞自噬、细胞凋亡与Pfirrmann分级之间的关系。结果退变椎间盘组织中BNIP3、LC3B在mRNA和蛋白水平的表达均随椎间盘退行性变程度加重而减少。Bcl-2 m RNA的表达随椎间盘退行性变程度加重而减少,Bax与Casepase-3 mRNA的表达随椎间盘退行性变程度加重而增多。结论随着椎间盘退行性变程度的加重,BNIP3与LC3B的表达减少,组织内细胞凋亡水平升高,细胞自噬对组织的保护作用逐渐下降。提示BNIP3与LC3B在腰椎椎间盘退行性变过程中具有重要的调节作用,可能是细胞自噬和凋亡之间的桥梁蛋白。     

棘突间动态稳定系统治疗腰椎退行性疾病的中期疗效分析

目的:探讨Wallis和Coflex棘突间系统治疗腰椎退行性疾病的中期临床疗效以及对邻近节段退变的影响。方法:对2011年1月至2013年1月应用棘突间固定系统治疗的L_(4,5)节段腰椎退行性疾病55例患者进行回顾性分析,其中男31例,女24例;年龄25～67岁,平均43.3岁;腰椎管狭窄症21例,腰椎间盘突出症34例。根据所采用的棘突间固定系统不同将患者分为Wallis组(33例)和Coflex组(22例)。采用视觉模拟评分(visual analogue scale,VAS)对腰痛和下肢痛进行评分;根据腰椎日本骨科协会(Japanese Orthopaedic Association,JOA)评分和Oswestry功能障碍指数(Oswestry Disability Index,ODI)评价腰椎功能;通过影像学资料测量手术前后手术节段和邻近节段活动度、椎间盘高度以及上位邻近节段Pfirrmann等级的变化情况。结果:55例患者均获得随访,随访时间48～72个月,平均60.4个月。术后48个月时,两组患者腰痛VAS评分、下肢痛VAS评分、腰椎JOA评分和ODI评分较术前有明显改善(P0.01),组间比较差异无统计学意义(P0.05);两组手术节段的活动度和椎间盘高度较术前均明显减小(P0.05),而上下邻近节段的活动度和椎间盘高度无明显变化(P0.05),两组间椎间隙高度和活动度比较无统计学意义(P0.05);两组患者上位邻近节段Pfirrmann分级较术前差异不明显(P0.05)。4例腰椎间盘突出症患者手术节段在术后1～3年复发,其中Wallis组3例,Coflex组1例,平均年龄35.2岁。结论:Wallis和Coflex系统治疗腰椎退变性疾病具有相同中期疗效,可延缓邻近节段退变,但不能阻止椎间盘突出的复发。     

人工髓核假体置换术治疗腰椎间盘突出症

目的 比较人工髓核假体（PDN）置换术和传统单纯髓核摘除术治疗腰椎间盘突出症的疗效,评价人工髓核假体置换术的实用价值。方法 施行人工髓核假体置换术18例,16例为单节段腰椎问盘突出症,2例为两节段腰椎间盘突出,均采用单枚PDN置人单个椎间盘间隙。对照组单纯髓核摘除术30例,22例为单节段腰椎间盘突出,8例为两节段腰椎间盘突出。观察两组病例的临床效果。结果 PDN组术后临床症状均消失,运动功能明显好转。6例获得9～22个月的随访,9例获得3～9个月的随访,椎间隙高度较手术前平均增加10．5％,无髓核假体移位突出,术后疗效明显优于单纯髓核摘除术组,两者相比差异有显著性（P〈0．01）。结论 PDN置换术既能恢复脊柱的节段稳定性,又保持脊柱节段的活动性,适当的假体设计与材料选择也能使椎间盘与椎体后柱的负荷获得再平衡,有广泛的应用前景。     

Mature runt cow lumbar intradiscal pressures and motion segment biomechanics

Background contextThe optimal animal model for in vivo testing of spinal implants, particularly total or partial disc replacement devices, has not yet been determined. Mechanical and morphological similarities of calf and human spines have been reported; however, limitations of the calf model include open growth plates and oversized vertebrae with growth. Mature runt cows (Corrientes breed) may avoid these limitations.PurposeThis study compared vertebral morphology and biomechanical properties of human and runt cow lumbar motion segments.Study designIn vivo disc pressure measurements were obtained in six mature runt cows at L4–L5. In vitro evaluation was performed on these same segments and repeated on 12 human motion segments.MethodsDisc pressures were measured in vivo in runt cow (Corrientes breed) L45 discs using a percutaneous transducer with the animal performing various activities. These motion segments were then harvested and morphologic and biomechanical evaluations (disc pressure in compression, flexibility tests to 7.5 Nm) were performed on both cow and male human L23 and L45 segments.ResultsThe transverse lumbar disc dimensions were slightly smaller for (mixed gender) cow versus (male) humans, but were within the range of reported (mixed gender) human values. The mean±SD disc height was smaller for runt cow (7±1 mm) versus human discs (13±2 mm, p<.001). The vertebral bodies of the cow were approximately twice as tall as the human. In vitro testing revealed significantly greater disc pressure response to applied axial loading in the runt cow versus humans (1.27±0.18 vs. 0.84±0.15 kPa/N, respectively) but similar overall stiffness (2.15±0.71 vs. 1.91±0.94 kN/mm, respectively). Runt cow and human segment flexibility curves were similar with the following exceptions: runt cow stiffness was ～40% greater in torsion (p<.05), runt cow segment lateral bending motion was greater versus humans (range of motion by 30%, neutral zone by 100%; both p<.05), and flexion range of motion tended to be smaller in runt cow versus human specimens (by ～40%, p=NS). In vivo, the standing disc pressure in the runt cow was 0.80±0.24 MPa.ConclusionsAlthough no animal replicates the human motion segment, the runt cow lumbar spine had a number of biomechanical and morphological measurements within the range of human values. The closed physes and temporally stable morphology of the mature runt cow may make this model more suitable versus standard calf models for human intradiscal implant studies.     

三种手术方法治疗腰椎椎间盘突出症的影像学及临床疗效比较

目的比较单纯髓核摘除术（lumber discectomy,LD）、腰椎后外侧融合术（posterolateral lumbar fusion,PLF）和腰椎后路椎体间融合术（posterior lumbar interbody fusion,PLIF）治疗腰椎椎间盘突出较大或椎间盘突出伴有节段不稳的差异,进一步明确PLIF治疗腰椎间盘突出症的指征。方法回顾性分析2006年5月~2008年12月行手术治疗的腰椎椎间盘突出较大或椎间盘突出伴有节段不稳的患者102例。按手术方式分为3组,LD组37例,PLF组31例,PLIF组34例。比较各组手术前、后及随访时的椎间高度、椎间孔面积、腰椎生理曲度等影像学指标以及视觉模拟量表（visual analog scale,VAS）评分、Oswestry功能障碍评分等临床症状指标。同时,比较2个融合手术组的融合率。结果 PLIF组椎间高度及节段角度的恢复与维持明显优于其他组,差异有统计学意义（P〈0.05）,各组椎间孔面积手术前后均无明显变化;PLIF组融合率高于PLF组,但差异无统计学意义（P〉0.05）;PLIF组术后腰痛VAS评分低于其他组,差异有统计学意义（P〈0.05）,下肢疼痛VAS评分和Oswestry功能障碍评分差异无统计学意义（P〉0.05）,但随访发现PLIF组Oswestry功能障碍评分有逐渐优于其他组的趋势。结论与其他2种手术方式相比,PLIF治疗腰椎椎间盘突出较大或椎间盘突出伴有节段不稳时能更好的恢复腰椎的生理曲度,维持腰椎的稳定性,并能明显改善患者的腰痛症状。     

Biomechanical changes in the lumbar spine following spaceflight and factors associated with postspaceflight disc herniation

Background ContextFor chronic low back pain, the causal mechanisms between pathological features from imaging and patient symptoms are unclear. For instance, disc herniations can often be present without symptoms. There remains a need for improved knowledge of the pathophysiological mechanisms that explore spinal tissue damage and clinical manifestations of pain and disability. Spaceflight and astronaut health provides a rare opportunity to study potential low back pain mechanisms longitudinally. Spaceflight disrupts diurnal loading on the spine and several lines of evidence indicate that astronauts are at a heightened risk for low back pain and disc herniation following spaceflight.PurposeTo examine the relationship between prolonged exposure to microgravity and the elevated incidence of postflight disc herniation, we conducted a longitudinal study to track the spinal health of twelve NASA astronauts before and after approximately 6 months in space. We hypothesize that the incidence of postflight disc herniation and low back complaints associates with spaceflight-included muscle atrophy and pre-existing spinal pathology.Study DesignThis is a prospective longitudinal study.Patient SampleOur sample included a cohort of twelve astronaut crewmembers.Outcome MeasuresFrom 3T MRI, we quantified disc water content (ms), disc degeneration (Pfirrmann grade), vertebral endplate irregularities, facet arthropathy and/ fluid, high intensity zones, disc herniation, multifidus total cross-sectional area (cm²), multifidus lean muscle cross-sectional area (cm²), and muscle quality/composition (%). From quantitative fluoroscopy we quantified, maximum flexion-extension ROM (°), maximum lateral bending ROM (°), and maximum translation (%). Lastly, patient outcomes and clinical notes were used for identifying postflight symptoms associated with disc herniations from 3T MRI.MethodsAdvanced imaging data from 3T MRI were collected at three separate time points in relation to spending six months in space: (1) within a year before launch (“pre-flight”), (2) within a week after return to Earth (“post-flight”), and (3) between 1 and 2 months after return to Earth (“recovery”). Fluoroscopy of segmental kinematics was collected at preflight and postflight timepoints. We assessed the effect of spaceflight and postflight recovery on longitudinal changes in spinal structure and function, as well as differences between crew members who did and did not present a symptomatic disc herniation following spaceflight.ResultsHalf of our astronauts (n=6) experienced new symptoms associated with a new or previously asymptomatic lumbar disc protrusion or extrusion following spaceflight. We observed decreased multifidus muscle quality following spaceflight in the lower lumbar spine, with a reduced percentage of lean muscle at L4L5 (-6.2%, p=.009) and L5S1 (-7.0%, p=.006) associated with the incidence of new disc herniation. Additionally, we observed reduced lumbar segment flexion-extension ROM for L2L3 (-17.2%, p=.006) and L3L4 (-20.5%, p=.02) following spaceflight, and furthermore that reduced ROM among the upper three lumbar segments (-24.1%, p=.01) associated with the incidence of disc herniation. Existing endplate pathology was most prevalent in the upper lumbar spine and associated with reduced segmental ROM (-20.5%, p=.02).ConclusionsIn conclusion from a 10-year study investigating the effects of spaceflight on the lumbar spine and risk for disc herniation, we found the incidence of lumbar disc herniation following spaceflight associates with compromised multifidus muscle quality and spinal segment kinematics, as well as pre-existing spinal endplate irregularities. These findings suggest differential effects of spinal stiffness and muscle loss in the upper versus lower lumbar spine regions that may specifically provoke risk for symptomatic disc herniation in the lower lumbar spine following spaceflight. Results from this study provide a unique longitudinal assessment of mechanisms and possible risk factors for developing disc herniations and related low back pain. Furthermore, these findings will help inform physiologic countermeasures to maintain spinal health in astronauts during long-duration missions in space.     

The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation

BackgroundChemonucleolysis with condoliase, which degrades chondroitin sulfate, could be a new, minimally invasive therapeutic option for patients with lumbar disc herniation (LDH). The purpose of this study was to analyze prognostic factors for clinical outcomes in LDH patients subjected to chemonucleolysis with condoliase.MethodsInclusion criteria for this procedure were 1) 18–70 years of age; 2) unilateral leg pain and positive straight leg raise (SLR) (<70°) or femoral nerve stretching test; 3) subligamentous extrusion verified on magnetic resonance imaging; 4) neurological symptoms consistent with a compressed nerve root on magnetic resonance imaging (MRI) images; and 5) minimum six months of follow-up. In total, 82 patients (55 men, 27 women; mean age, 47.2 ± 15.5 years; mean follow-up, 9.1 ± 3.0 months) who underwent chemonucleolysis with condoliase for painful LDH were included. An improvement of 50% or more in the Visual analogue scale (VAS) of leg pain was classified as effective.ResultsSeventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006–26.204) was significantly associated with clinical effectiveness.ConclusionsChemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc.     

Prosthetic disc nucleus (PDN) replacement for lumbar disc herniation: preliminary report with six months' follow-up

A clinical follow-up study was performed to evaluate lumbar disc nucleus replacement clinically and functionally. The objective was to assess the clinical efficacy of the prosthetic disc nucleus (PDN) for treatment of lumbar disc herniation. The PDN was designed to treat patients suffering from disc herniation and/or degeneration. Clinical trials for PDN were first conducted in 1996, and the results showed that the PDN device was effective in most of the patients who were implanted. These studies had been carried out with patients who were implanted with a pair of the devices. The main complication was device migration. Therefore, a follow-up study based on a single PDN device implantation was designed to evaluate its clinical result. Forty-five patients with lumbar disc herniation were implanted with one PDN device from March 2002 to December 2002. Thirty (66.7%) patients came to the clinical, functional, and radiographic 6-month follow-up examinations. Independent analysis was performed by careful review of the charts, operative notes, preoperative and postoperative radiographs, magnetic resonance images, and follow-up records of all patients. After implantation, significant proportions of patients experienced pain relief. Improvements were noted in pain intensity, walking distance, lumbar mobility, neurologic weakness, Oswestry and Prolo scores, and intervertebral disc height. No difference in work status after PDN implantation could be detected. Compared with the preoperative height, the intervertebral disc had gained 19.7% (P < 0.001). Device migration, failure, and dislocation were not noticed in any patient. A few patients had minor complications such as transient low-grade fever. Clinically, a single PDN is preferred and can effectively increase the height of the intervertebral disc in patients with lumbar disc herniation. However, long-term follow-up of PDN implantation needs to be studied.     

Prediction of lumbar disc herniation resorption in symptomatic patients: a prospective,multi-imaging and clinical phenotype study

BACKGROUND CONTEXTSymptomatic lumbar disc herniations (LDH) are very common. LDH resorption may occur by a “self-healing” process, however this phenomenon remains poorly understood. By most guidelines, if LDH remains symptomatic after 3 months and conservative management fails, surgical intervention may be an option.PURPOSEThe following prospective study aimed to identify determinants that may predict early versus late LDH resorption.STUDY DESIGN/SETTINGProspective study with patients recruited at a single center.PATIENT SAMPLENinety-three consecutive patients diagnosed with acute symptomatic LDH were included in this study (n=23 early resorption and n=67 late resorption groups) with a mean age of 48.7±11.9 years.OUTCOMES MEASUREBaseline assessment of patient demographics (eg, smoking status, height, weight, etc.), herniation characteristics (eg, the initial level of herniation, the direction of herniation, prevalence of multiple herniations, etc.) and MRI phenotypes (eg, Modic changes, end plate abnormalities, disc degeneration, vertebral body dimensions, etc.) were collected for further analysis. Lumbar MRIs were performed approximately every 3 months for 1 year from time of enrollment to assess disc integrity.METHODSAll patients were managed similarly. LDH resorption was classified as early (<3 months) or late (>3 months). A prediction model of pretreatment factors was constructed.RESULTSNo significant differences were noted between groups at any time-point (p>.05). Patients in the early resorption group experienced greater percent reduction of disc herniation between MRI-0-MRI-1 (p=.043), reduction of herniation size for total study duration (p=.007), and percent resorption per day compared to the late resorption group (p<.001). Based on multivariate modeling, greater L4 posterior vertebral height (coeff:14.58), greater sacral slope (coeff:0.12), and greater herniated volume (coeff:0.013) at baseline were found to be most predictive of early resorption (p<.05).CONCLUSIONSThis is the first comprehensive imaging and clinical phenotypic prospective study, to our knowledge, that has identified distinct determinants for early LDH resorption. Early resorption can occur in 24.7% of LDH patients. We developed a prediction model for early resorption which demonstrated great overall performance according to pretreatment measures of herniation size, L4 posterior body height, and sacral slope. A risk profile is proposed which may aid clinical decision-making and managing patient expectations     

Thoracal flat back is a risk factor for lumbar disc degeneration after scoliosis surgery

Background contextLumbar segments below fused scoliotic spines are thought to be exposed to extraordinary stress. Although positive sagittal imbalance has come into focus, reports about factors influencing the outcome of these segments remain inconclusive.PurposeOur study aimed at identifying spinal risk factors for the development of lumbar degenerative disc disease (DDD) in surgically treated patients with adolescent idiopathic scoliosis (AIS).Study design/settingRetrospective comparative prognostic study (Level III) was conducted. Thirty-three patients were seen at an average follow-up of 7.5 years after either isolated selective anterior (n=18) or long combined anterior-posterior fusion (n=15) for AIS.Outcome measuresSelf-reported Scoliosis Research Society 22 questionnaire, physical examination including the detection of segmental pain and unspecific back pain, preoperative and postoperative whole-spine standing radiographs, and magnetic resonance imaging were obtained.MethodsRadiographic evaluation included the measurement of regional, coronal, and sagittal curve parameters and the assessment of spinal balance. Magnetic resonance imaging evaluation was done for preoperative and postoperative lumbar discs, according to the classification of Pfirrmann.ResultsPatients with low DDD (Pfirrmann grading <3) had a significantly higher thoracal kyphosis angle (mean 28°) than patients with advanced DDD (mean 15°). There was a trend toward a more flat-type lumbar lordosis in patients with severe DDD. Positive sagittal imbalance was associated with advanced DDD. Follow-up coronal parameters, trunk imbalance, instrumentation length, and lowest instrumented vertebra selection had no influence on DDD. Specific segmental pain could be attributed to a significantly higher coronal trunk imbalance (21 vs. 11 mm).ConclusionsThis study establishes thoracal flat back as a risk factor for lumbar DDD after spinal fusion and supports the pathogenetic role of positive sagittal imbalance in this process.     

Disproportion of end plates and the lumbar intervertebral disc herniation

Background contextIt is suggested that the shape of the vertebral end plates may play a role in the development of abnormalities in the intervertebral disc. On midsagittal magnetic resonance images of the spine in patients with lumbar intervertebral disc herniation, a notable disproportion frequently exists between the end plates of two vertebrae to which the disc is attached. There is apparently no study in the literature examining possible association of this disproportion with development of disc herniation.PurposeTo determine whether a disproportion between two neighboring vertebral end plates is associated with the presence of disc herniation at the same level.Study designCase-control study.Patient sampleTwo hundred fifty patients with primary lumbar disc herniation in the case group and 250 age- and sex-matched normal individuals in the control group.Outcome measuresOn midsagittal sections, the difference of anteroposterior diameter of upper and lower end plates neighboring a herniated (in the case group) or normal (in the control group) intervertebral disc was calculated and expressed as “difference of end plates” or “DEP.”MethodsSubjects with previous spinal surgery, spondylolisthesis, or a significant vertebral deformity were excluded. For the main outcome variable, DEP was calculated at the level with herniated intervertebral disc in the case group, and the mean value was compared with mean DEP at the same level in the controls.ResultsMean DEP was significantly higher in the case group at both L4–L5 (2.45±0.28 vs. 2.08±0.27 mm, p=.02) and L5–S1 (3.32±0.18 vs. 2.51±0.13 mm, p<.001) levels. Similar differences were only marginally insignificant at L2–L3 (1.96±0.14 mm in the cases vs. 1.33±0.15 mm in the controls, p=.07) and L3–L4 (2.17±0.11 mm in the cases vs. 1.55±0.09 mm in the controls, p=.06) levels, with no significant difference at L1–L2 level (1.81±0.10 mm in the cases vs. 1.28±0.09 mm in the controls, p=.12). Each 1 mm increase of DEP at L4–L5 and L5–S1 levels was associated with 53% and 56% elevation in disc herniation risk at the corresponding levels, respectively.ConclusionsDifference of end plate is a significant and probably independent risk factor for lumbar disc herniation.     

腰椎间盘突出症再手术原因分析

目的：分析腰椎间盘突出症再手术原因并探讨其治疗方法和疗效。方法：回顾性分析1998年1月至2006年1月手术治疗的腰椎间盘突出症175例,其中17例复发性腰椎间盘突出症需再手术治疗,17例中,男11例,女6例;年龄35-65岁,平均49岁。经原椎板间扩大开窗法切除椎间盘11例,全椎板切除减压椎间盘切除5例（同时行内固定＋后外侧植骨融合）,单侧椎板切除1例。术后对患者的疼痛、运动功能、神经根受压表现进行观察,并根据Macnab标准对疗效进行评定。结果：17例均获随访,时间15-96个月,平均51个月。所有患者的疼痛、运动功能及神经根受压表现均有不同程度改善。按Macnab评定标准：优9例,良6例,可2例。结论：腰椎间盘突出症再次手术的主要原因为同一间隙闻盘组织再突出、继发性椎管狭窄、邻近椎间盘突出等。虽然腰椎间盘突出症再手术难度大于初次手术,但只要严格掌握手术指征,术前周密计划,仍可取得满意疗效。     

Neurological examination of the peripheral nervous system to diagnose lumbar spinal disc herniation with suspected radiculopathy: a systematic review and meta-analysis

Background contextDisc herniation is a common low back pain (LBP) disorder, and several clinical test procedures are routinely employed in its diagnosis. The neurological examination that assesses sensory neuron and motor responses has historically played a role in the differential diagnosis of disc herniation, particularly when radiculopathy is suspected; however, the diagnostic ability of this examination has not been explicitly investigated.PurposeTo review the scientific literature to evaluate the diagnostic accuracy of the neurological examination to detect lumbar disc herniation with suspected radiculopathy.Study designA systematic review and meta-analysis of the literature.MethodsSix major electronic databases were searched with no date or language restrictions for relevant articles up until March 2011. All diagnostic studies investigating neurological impairments in LBP patients because of lumbar disc herniation were assessed for possible inclusion. Retrieved studies were individually evaluated and assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies tool, and where appropriate, a meta-analysis was performed.ResultsA total of 14 studies that investigated three standard neurological examination components, sensory, motor, and reflexes, met the study criteria and were included. Eight distinct meta-analyses were performed that compared the findings of the neurological examination with the reference standard results from surgery, radiology (magnetic resonance imaging, computed tomography, and myelography), and radiological findings at specific lumbar levels of disc herniation. Pooled data for sensory testing demonstrated low diagnostic sensitivity for surgically (0.40) and radiologically (0.32) confirmed disc herniation, and identification of a specific level of disc herniation (0.35), with moderate specificity achieved for all the three reference standards (0.59, 0.72, and 0.64, respectively). Motor testing for paresis demonstrated similarly low pooled diagnostic sensitivities (0.22 and 0.40) and moderate specificity values (0.79 and 0.62) for surgically and radiologically determined disc herniation, whereas motor testing for muscle atrophy resulted in a pooled sensitivity of 0.31 and the specificity was 0.76 for surgically determined disc herniation. For reflex testing, the pooled sensitivities for surgically and radiologically confirmed levels of disc herniation were 0.29 and 0.25, whereas the specificity values were 0.78 and 0.75, respectively. The pooled positive likelihood ratios for all neurological examination components ranged between 1.02 and 1.26.ConclusionsThis systematic review and meta-analysis demonstrate that neurological testing procedures have limited overall diagnostic accuracy in detecting disc herniation with suspected radiculopathy. Pooled diagnostic accuracy values of the tests were poor, whereby all tests demonstrated low sensitivity, moderate specificity, and limited diagnostic accuracy independent of the disc herniation reference standard or the specific level of herniation. The lack of a standardized classification criterion for disc herniation, the variable psychometric properties of the testing procedures, and the complex pathoetiology of lumbar disc herniation with radiculopathy are suggested as possible reasons for these findings.     

Long-term effect of physical inactivity on thoracic and lumbar disc degeneration—an MRI-based analysis of 385 individuals from the general population

BACKGROUND CONTEXTThe correlation between physical inactivity, thoracolumbar disc degeneration, and back pain remains unclear.PURPOSEThis study investigated the relationship between short- and long-term physical inactivity and degenerative changes of the thoracic and lumbar spine in a southern German cohort from the general population over a time period of 14 years.STUDY DESIGN/SETTINGThis study was designed as a cross-sectional case–control study, nested in a prospective cohort from the “Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg” (KORA) study.PATIENT SAMPLEAll participants in the population-based KORA study were assessed using a physical activity questionnaire to establish a baseline in 1999–2001 (exam 1), within an initial follow up questionnaire in 2006–2008 (exam 2), and a second follow-up questionnaire between 2013 and 2014 (exam 3). A subsample of this group (400 subjects) underwent full body MR scan performed on a 3T magnetic resonance imaging scanner current with exam 3.OUTCOME MEASUREData regarding physical inactivity over a time period of 14 years and back pain, and quantification of thoracic and lumbar disc degeneration on magnetic resonance imaging.METHODSQuantification of thoracic and lumbar disc degeneration was performed using the Pfirrmann score. Physical activity was grouped as no physical activity, irregularly for 1 hour, regularly for 1 hour, or regularly for ≥2 hours. This was used to calculate another variable “physical inactivity,” with the options of irregular activity ≤1 hour per week or regularly ≥1 hour. Physical labor, walking, and cycling activity were additionally investigated. Correlations between physical inactivity measurements and thoracic and lumbar disc degeneration were analyzed via linear regression models adjusted for age, sex, BMI, hypertension, diabetes, and back pain.RESULTSIn total, 385 individuals (mean age: 56 years, SD ± 9.19; 58.2% male) were included in this study. Mean summed Pfirrmann score was 2.41 (SD ± 4.19) in the thoracic and 1.78 (SD ± 1.81) in the lumbar spine. The level of current exercise in our cohort varied with 113 (29.4%) subjects exercising regularly ≥2 hours per week, 118 (30.7%) regularly 1 hour per week, 57 (14%) irregularly for about 1 hour per week, and 97 (25.2%) stated not to exercise at exam 3. Disc degeneration was more apparent in those with irregular activity <1 hour compared to those with regular activity of ≥1 hour and more per week (p<.01) and in those with no activity compared to those with regular activity of ≥2 (p<.001) measured using exam 3. Less physical activity over a time period of 14 years correlated with an increase of disc degeneration of the thoracic and lumbar spine after adjustment for age, sex, BMI, hypertension and diabetes mellitus (p<.05). There was no statistically significant association between physical labor, walking activity, or cycling activity with disc degeneration. Additionally, no significant correlations between degree of disc degeneration (p=.990), degree of physical inactivity (p=.158), and back pain were observed.CONCLUSIONDegree of physical inactivity as measured over a time period of 14 years demonstrated a strong correlation with disc degeneration of the thoracic and lumbar spine.