【作者】 李雄；

【导师】 李康华； 胡建中；

【作者基本信息】 中南大学 ， 外科学， 2007， 博士

【摘要】 颈椎病是骨科的常见病、多发病，发病年龄日益年轻化，对其研究意义重大。颈椎间盘退变是颈椎病发生和发展的核心病理基础，对颈椎间盘的研究有望从根本上预防、早期诊断和治疗颈椎病。对经严格保守治疗无效的脊髓型和神经根型颈椎病患者，前路颈椎间盘切除、椎间植骨融合术已成为经典术式。然而，临床和实验研究发现由于该术式牺牲了病变节段的颈椎活动，导致邻近节段的负荷增加而退变加速，并且融合的节段越多，邻近节段的退变越明显，症状的迁延复发率也越高。如何恢复和重建退变后颈椎问盘的功能是目前骨科研究的难点，也是热点之一。人工颈椎间盘置换是近年来发展起来的一项骨科新技术，为颈椎病的治疗提供了新的途径，其目的是替代病变的椎间盘并企图恢复手术节段椎间盘功能，从而减少相邻节段继发性退变。由于颈椎病的高发节段为C_4／5、C_5/6和C_6/7，达总数的80.7％；并且往往以C_5/6一个椎间盘突出为主，伴随周围一到两个椎间盘突出。人工颈椎间盘置换，特别是临床多见的C_4/5、C_5／6双节段颈椎间盘病变行人工颈椎间盘置换能否恢复颈椎的正常力学性能要求?临床疗效如何?尚有待进一步研究。有关C_4／5、C_5／6双节段人工颈椎间盘置换颈椎的生物力学报道不多，尚未见对比分析双节段颈椎间盘摘除、前路椎间融合内固定和椎间盘置换对相邻下位节段(C_6/7)椎间隙影响的实验和临床研究。本课题从以下三个方面进行研究：（1）对新鲜尸体颈椎标本的椎体、椎间隙高度进行实体、X线和SCT测量，探寻诊断颈椎间盘退变的敏感指标。（2）对比分析C_4／5、C_5/6双节段椎间盘摘除、前路椎间融合内固定和椎间盘置换新鲜尸体颈椎标本模型在不同载荷下邻近下位椎间隙内的压力。（3）随访双节段人工颈椎间盘置换和前路椎间融合内固定病例的临床疗效，探讨两种术式对邻近下位(C_6/7)椎间隙的影响。旨在为双节段颈人工椎间盘置换提供理论依据。第一章正常成人下颈椎椎体和椎间隙高度的实体、X线和SCT测量及意义目的：观测正常成人下颈椎椎体和椎间隙的高度，了解国人的颈椎形态，为治疗颈椎间盘退行性疾病提供形态学基础，探寻能够诊断颈椎间盘退变的敏感影像学指标。方法：采用正常成人新鲜尸体颈椎标本9具，先后行颈椎X线摄片、SCT扫描和矢状面剖开，测量椎体、椎间隙的高度，计算椎间隙／椎体高度的比值。运用SPSS13.0统计软件包进行统计分析。结果：1．X线测量的椎体高度值大于实体和SCT测量值，椎间隙高度、椎间隙／椎体高度比值低于实体和SCT测量值，差异有显著性（P＜0.05）；SCT与实体测量值差异均无显著性（P＞0.05）。2．X线、SCT和实体测量均显示下颈椎椎体的高度中部最低，前部和后部高度接近；椎间隙的高度中部最高，前部次之，后部最低。3．SCT与实体测量的椎间隙／椎体高度比值在前部自C₃到C₇依次为：0.336±0.027（0.333±0.029）、0.448±0.053（0.447±0.054）、0.511±0.054（0.508±0.048）、0.456±0.043（0.453±0.042）、0.372±0.032（0.369±0.030）；中部自C₃到C₇依次为：0.454±0.038（0.449±0.036）、0.611±0.091（0.614±0.086）、0.789±0.137（0.791±0.135）、0.680±0.086（0.685±0.077）、0.542±0.078（0.536±0.071）；后部自C₃到C₇依次为：0.249±0.015（0.245±0.016）、0.261±0.021（0.261±0.023）、0.277±0.021（0.280±0.026）、0.263±0.023（0.259±0.027）、0.248±0.015（0.247±0.012）。SCT与实体测量的C_5／6椎间隙与C₅椎体高度比值0.789±0.137（0.791±0.135）较其它节段、其它部位均大，差异有显著性（P＜0.05）。结论：1．SCT扫描较X线摄片更能真实地反映下颈椎椎体和椎间隙的实际高度。2．颈椎椎体的高度中部最低，前部和后部高度接近；椎间隙高度中部最高，前部次之，后部最低。3．SCT扫描测量的C_5／6椎间隙／C₅椎体中部高度比值最大，可能是反映颈椎间盘退变的敏感指标之一。第二章C_4/5、C_5/6双节段颈人工椎间盘置换后下位椎间隙内压力变化的生物力学实验研究目的：测量C_4/5、C_5/6双节段颈椎间盘摘除、人工椎间盘置换和前路椎间融合内固定对邻近下位C_6/7椎间隙内压力的影响，为临床运用人工颈椎间盘进行C_4/5、C_5/6双节段置换提供理论依据。方法：采用11具新鲜成人尸体颈椎标本，先后建立C_4/5、C_5/6双节段椎间盘完整、摘除、人工颈椎间盘置换、前路椎间融合内固定四组模型。将特制圆片状微型阻电式压力传感器置入C_6/7椎间隙内，分别进行轴向、侧弯、前屈和后伸分级加载，测量邻近下位节段(C_6/7)椎间隙内的压力。运用SPSS13.0统计软件包进行对比分析。结果：1．轴向、侧弯、前屈和后伸分级加载时，四组标本模型C_6/7椎间隙内的压力均随载荷的增大而增大。2．C_4/5、C_5/6椎间盘完整组和置换组在前屈工况时C_6/7椎间隙内的压力最大，其余依次是侧弯、轴向和后伸工况，差异有显著性（P＜0.05）。3．C_4/5、C_5/6双节段椎间盘摘除组在侧弯工况时椎间隙内的压力最大，其余依次是后伸、前屈和轴向工况，差异有显著性（P＜0.05）4．融合组在轴向工况时C_6/7椎间隙内的压力最大，侧弯工况时最小，前屈和后伸工况时差别不大，差异均显著性（P＜0.05）。5．C_4/5、C_5/6双节段椎间盘摘除组在轴向、前屈工况时椎间隙内的压力低于完整组和置换组，在侧弯和后伸工况时高于完整组和置换组，差异均有显著性（P＜0.05）。6．前路椎间融合内固定组在四种工况时下位椎间隙的压力较完整、摘除和置换组均增高，差异有显著性（P＜0.05）。7．C_4/5、C_5/6双节段人工椎间盘置换组与椎间盘完整组相比，四种工况时下位节段椎间隙内的压力均相近，差异无显著性（P＞0.05）。结论：1．特制圆片状微型阻电式压力传感器是测量离体颈椎标本椎间隙压力的良好实验工具。2．双节段颈椎间盘摘除和椎间融合内固定后下位椎间隙的压力分布较正常情况均发生了改变。3．双节段颈椎间盘摘除后下位椎间隙内的压力在侧弯和后伸时高于正常，轴向和前曲低于正常，压力分布的紊乱可能会导致或加剧颈椎退变。4．双节段椎间融合内固定后下位椎间隙内的压力均明显高于正常，这可能是导致或加剧下位椎间隙退变的原因之一。5．双节段人工颈椎间盘置换后下位椎间隙内的压力及分布均近似于正常，提示双节段人工颈椎间盘置换可以有效维持颈椎的正常生物力学性能。第三章C_4/5、C_5/6双节段人工颈椎间盘置换、椎间融合对邻近下位节段影响的临床应用研究目的：观察C_4/5、C_5/6双节段人工颈椎间盘置换和前路融合内固定术的临床疗效，探讨不同术式对邻近下位节段退变的影响，为进行C_4/5、C_5/6双节段人工颈椎间盘置换提供临床依据。方法：收集1998年1月～2006年2月因C_4/5、C_5/6双节段颈椎退变而接受手术的病例35例，按照手术方式及随访时间长短分为三组：（1）人工颈椎间盘置换组5例，随访12个月～22个月，平均14.66个月；（2）前路植骨融合内固定短期随访组（融合组一）15例，随访12个月～30个月，平均15.75个月；（3）前路植骨融合内固定中长期随访组（融合组二）15例，随访5年～8年，平均6.75年。记录术前和术后随访6个月、12个月、2年和5年时的JOA分值、Odom评级，X线观察邻近下位节段椎体／椎间隙高度比值、椎间活动度、曲度和椎间盘退变情况。运用SPSS13.0统计软件比较分析以上各组、各时段的各项指标。结果：1．三组病例术后各随访时段的JOA评分、Odom评级较术前均有提高，差异有统计学意义（P＜0.05）。2．人工椎间盘置换组较融合组一，术后6个月、12个月的JOA评分、Odom评级、邻近下位节段椎体／椎间隙高度比值、椎间活动度、曲度和椎间盘退变均相近，差异无显著性（P＞0.05）。3．融合组二术后5年较术后6个月、12个月、2年，及较融合组一术后6个月、12个月，JOA评分、Odom评级改善率降低，邻近下位节段活动度增加、曲度减少，椎体／椎间隙高度比值下降、椎间盘退变增多，差异均有显著性（P＜0.05）。结论：1．C_4/5、C_5/6双节段颈人工椎间盘置换和前路植骨融合内固定的近期手术疗效均良好，能有效维持下位节段椎间隙的高度、活动度和曲度，未见椎间盘退变，是治疗颈椎退行性疾病的有效方法之一。2．双节段前路植骨融合内固定术的中远期疗效下降，邻近下位节段椎间隙的高度下降，活动度增加、曲度减少，椎间盘出现退变。3．C_4/5、C_5/6双节段人工颈椎间盘置换的远期疗效尚有待进一步观察。更多还原

【Abstract】 Cervical syndrome is a common and frequent disease in orthopedics,the age of onset it is younger and younger, it is significantly to study on it.Intervertebral disc degeneration is the core pathology basis to theoccurrence and development of cervical syndrome, therefor, researcheson disc can prevent, diagnose early and cure cervical syndrome possiblyand fundamentally. To those patients who had been treated withconservative therapy strictly and had no effect, anterior surgeries to thedisc, decompression/excision of discectomy with interbody fusion was aclassic method to cervical spondylotic myelopathy and radiculopathy.Unfortunatly, the traditional anterior surgery managements lost themotions of fusion segment, leaded to adjacent segment stress focused,instability and accelerat to its degeneration. The more segments had beenfusioned, the degeneration of adjacent segment were more significant,and the recurrence rate of syndrome were higher.How to recover and reconstruct the function of degenerated disc is ahard and hot focuse in orthopedics researches. Based on the idea ofcervical arthroplasty, cervical artificial disc replacement （CADR） is a newtechnique and developed quickly in the past few years. It can recover theoperated disc’s founction, decrease its degeneration and approved a newmethod to treat cervical syndrome. Because the higher occurrent place ofCDDD is C_4/5, C_5/6 and C_6/7 segment, it can possess 80.7% of all patientsand always appear with C_5/6 disc herniation compared with one or twoadjacent discs herniation. But whether CADR, especially in the treatmentto the higher occurrence in clinical practice of C_4/5 and C_5/6 doublesegments CDDD, can reconstruct the normal biomechanical performationof cervical spine and fulfill the function of the disc, decrease the sideeffect on adjacent segments? The effect of its clinical therapy is excellent or poor? Unfortunatly, all of those had few been reported in the past years.There is no basic and clinical researches on compare analyze to the stressof inferior intervertebral space after C_4/5 and C_5/6 double segmentsdiscectomy, fusion and CADR.In our study, measured the anterior, media and posterior heights ofsagittal plane of vertebral body and intervertebral disc by X ray, SCT andfresh cadaver practice measurement firstly, in order to explore a sensitiveindication to diagnosis cervical syndrome. Then, builted C_4/5 and C_5/6double segments intervertebral disc complete, discectomy, CADR andfusion model, analyzed the inferior intervertebral space (C_6/7) stresschange during the biomechanical test with different load. Finally,followed-up the clinical cured effect of 5 patients of C_4/5 and C_5/6 doublesegments CADR and 30 cases of fusion, approach the two surgerytreatment to the effects of adjacent inferior intervertebral space. In a word,approve experiment and clinical evidence to choice which operation totreat C_4/5 and C_5/6 double segments CDDD.ChapterⅠX ray, SCT and entity measurement and itssignificance to the heightsof inferior cervical spinal vertebral body and spaceObjectives In order to measure the heights of inferior cervicalspinal vertebral body and space in normal Chinese adult, and comprehendthe morphous of Chinese cervical spine, approve morphous evidence totreat CDDD and approach a new sensitive radiographic indication todiagnosis cervical syndrome.Methods 9 fresh cervical specimens from young adultcadavers（C₃～C₇） were measured by X ray, SCT and fresh cadaver entitymeasurement. In sagittal plane of vertebral body and space, measured andanalysised its anterior, media and posterior heights and calculate the rate of space and body. All datas were analyzed with SPSS.Results 1. The measurement of X ray to the sagittal heights ofvertebral body is higher than SCT and entity method, while the space ofcervical spine and the rate of space and body are lower then them, thedifference is significant（P＜0.05）. The datas between SCT and entity haveno significance changes（P＞0.05）. 2. The heights of media vertebral bodyis the lowest than anterior and posterior, while, the anterior and posteriorhas no difference. The heights of space in media is the highest, andanterior is the second, posterior is the third. 3. The rate of anterior spaceand body heights in SCT and entity measurement show that from C₃ to C₇are 0.336±0.027（0.333±0.029）, 0.448±0.053（0.447±0.054）, 0.511±0.054（0.508±0.048）, 0.456±0.043（0.453±0.042）, 0.372±0.032（0.369±0.030）.The rate of media space and body heights in SCT and entity measurementshow that from C₃ to C₇ are 0.454±0.038（0.449±0.036）, 0.611±0.091（0.614±0.086）, 0.789±0.137（0.791±0.135）, 0.680±0.086 （0.685±0.077）、0.542±0.078（0.536±0.071）. The rate of posterior space and body heightsin SCT and entity measurement show that from C₃ to C₇are0.249±0.015（0.245±0.016）, 0.261±0.021 （0.261±0.023）, 0.277±0.021（0.280±0.026）, 0.263±0.023（0.259±0.027）, 0.248±0.015（0.247±0.012）.The ratio of media C_5/6 space/C₅ body in SCT and entity is 0.789±0.137（0.791±0.135）, is the highest in all segment and location（P＜0.05）.Conclusions 1. SCT can measure the vertebral body and spacemore really than computed X ray. 2. In normal cervical spine, the heightsof media vertebral body is the lowest, anterior and posterior is similar.The heights of space in media is the highest, anterior is the second,posterior is the third. 3. The rate of C_5/6 space/C₅ body in SCT is maybea sensitive indication to reflect CDDD. ChapterⅡA biomechanical study on the stress of inferiorintervertebral space after C_4/5and C_5/6 double segments CADRObjectives To observe the biomechanical effect and compare thestress changes of C_6/7 intervertebral space pre- and post C_4/5 and C_5/6double segments discectomy, CADR and intervertebral fusion, provide abasic theory evidence to application of the C_4/5 and C_5/6 double segmentsCADR.Methods Eleven healthy adult fresh-frozen cadavers cervical spinesegments were utilized in this research. Builted the models of C_4/5 andC_5/6 double segment disc complete spine, discectomy, the Bryan Discprosthesis implantation, inter body fusion. The stress changes of theinferior (C_6/7) intervertebral space was tested by modified cyclo-shapedminiature transducer, the load including axial, flexion, extension, andlateral bending were applied in each group. The data was analyzed bySPSS for windows 13.0.Results 1. Under axial, flexion, extension and lateral bendingloading, the stress in inferior intervertebral space were increased with theloads.2. In C_4/5 and C_5/6 double segment disc intact and CADR samples,the stress in flexion condition was the highest, while lateral bending wasthe second, axial was the third and extension was the lowest （P＜0.05）. 3.In double discectomy samples, the stress in lateral bending was thehighest, while extension was the second, flexion was the third and axialwas the lowest. 4. In inter body fusion samples, the stress in axialcondition was the highest, lateral bending was the lowest, while it wassimilar in flexion and extension conditions. All difference was significant（P＜0.05）. 5. The stress of discectomy group was lower than disc intactand CADR groups in axial and flexion conditions, while it was higherthan them in lateral bending and extension conditions. 6. In anterior inter body fusion group, the stress in the inferior space was increased whencompared to disc intact, discectomy and CADR groups （P＜0.05）. 7. Thestress had no difference in C_4/5 and C_5/6 double segment disc intact andCADR samples in those four conditions （P＞0.05）.Conclusions 1. The specially modified cyclo-shaped pressuretransducer is a excellent tool in this biomechanical study, and canmeasure the stress change of intervertebral space fidelity and correctly. 2.C_4/5, C_5/6 double segments discectomy and intervertebral fusion havechanged the stress distribution in inferior intervertebral space, whencompared to the disc intact samples. 3. Double segments discectomycompared to disc complete group, had lower stress in the inferior spacewhen loaded lateral bending and extension conditions, and had higherstress in the space when loaded axial and flexion conditions, the stressdistribution confused, which will leads to cervical spine degenerated oraccelerated it. 4. In the double inter body fusion groups, the stressincreased significantly, and it is also one of the reasons lead to cervicalspine degenerate or accelerate it. 5. C_4/5 and C_5/6 double segments CADRcan remain the stress and its distribution in inferior space similar to discintact condition, indicate that double segments CADR can retain thenormal biomechanical performs in cervical spine perfectly.ChapterⅢThe clinical research of the effect of adjacentinferior segment after C_4/5 and C_5/6 double segments CADRObjectives To investigate the clinical outcome of the patient whoaccepted the C_4/5 and C_5/6 double segments Bryan artificial discreplacement and cervical inter body fusion, so can approve evidence forclinical application of double segments replacement. Methods From January 1998 to February 2006, 35 patients withcervical C_4/5 and C_5/6 double segments disc degenerative disease wereenrolled in this study. According to different operations and the length offollow-up, those patients were divided into 3groups. In group one, fivecases were treated with double segments CADR, which were followed-up12 months to 22 months, average 14.66 months. In group two or fusiongroupⅠ, 15 patient who had been treated with anterior inter body bonegraft fusion and inter fixation, had been followed-up 12 months to 30months, average 15.75 months. In group three or fusion groupⅡ, 15patient who had been treated with anterior bone graft fusion and interfixation, had been followed-up 5 years to 8 years, average 6.75 years.Record those JOA score, Odom scale, the ratio of vertebral body andspace height in X ray film, the range of flexion-extension, curvature ofadjacent inferior segment, calculated the ratio of disc degeneration, inpro- and post operation 6 months, 12 months, 2 years and 5 years. Thedata was analyzed by SPSS for windows 13.0.Results 1. In the follow-up of each groups, the score of JOA, scaleof Odom, were higher than pre-operation, the difference was significant（P＜0.05）. 2. Compared CADR group and fusion groupⅠ, the JOA score,Odom scale, the rate of vertebral body and space height in X ray film, therange of flexion-extension, curvature of adjacent inferior segment,calculated the ratio of disc degeneration, in pro- and post operation 6months, 12 months, they were similar, the difference has no significant（P＜0.05）. 3. In group three or fusion groupⅡ, when compared the 5 yearseffect to post operation, 6 months, 12 months and 2 years, the JOA scoreand Odom scale reduced, the range of flexion-extension rised, curvatureof adjacent inferior segment and rate of vertebral body and space heightin X ray film decreased, the ratio of disc degeneration increased. All ofthem showed significant difference （P＜0.05）. Conclusions 1. his study has shown that the C_4/5 and C_5/6 doublesegments CADR and intervertebral fusion are good choice to CDDD, thetherapy effect is excellent and the morphous and function of the adjacentinferior intervertebral space can be maintained well in the near future.2.The therapy effect of interbody fusion decreased in long time follow-up,it can leads to the heights of adjacent inferior disc decrease, range ofmotion increase, curvature of the space reduce and accelerated spacedegenerate. 3. The effect of C_4/5 and C_5/6 double segments CADR in longtime fellow-up should been studied forward.更多还原