中 文 摘 要

第一部分  应用新型生长棒的初步动物实验研究

研究背景：早发性脊柱侧凸具有发病年龄早，畸形进展迅速等特点，保守治疗往往无效，外科治疗非常棘手。以生长棒为代表的非融合性脊柱内固定技术的出现，其治疗的目标就是在控制畸形进展的同时，允许脊柱和胸廓继续生长，保障心肺等重要器官的发育。但其较高并发症发生率，以及需要多次手术调整的弊端仍然使该技术的应用受到了一定限制。目前脊柱外科临床中迫切需要一种新型的生长棒技术，在矫正脊柱畸形的同时，尽量减少治疗带来的二次创伤，为临床治疗患儿的早发性脊柱侧凸提供更加理想的治疗技术。

研究目的：观察新型生长棒系统在体内有效撑开、保留脊柱生长的能力，评估其对于椎间盘退变及椎体生长潜能的影响，探讨新型生长棒的有效性和安全性。

研究方法：采用12只健康中华小型猪（10周龄；体重8～12kg）进行实验。将实验动物随机分为两组，每组各6只。新型生长棒组于T6-T7和L2-L3双侧分别植入两对椎弓根螺钉并连接新型生长棒；传统生长棒组于相同手术节段植入椎弓根螺钉并连接传统生长棒每隔4周进行一次生长棒撑开，观察12周。拍摄脊柱正侧位X线片评估生长棒的有效撑开和保留脊柱生长的能力。通过磁共振图像和计算机断层扫描评估脊柱椎间盘和小关节突的退变程度。

研究结果：传统生长棒组1只小型猪因伤口深部感染终止观察。其余所有11只动物均完成12周的观察，顺利进行了3次生长棒的撑开。新型生长棒组撑开的手术时间平均为12.1± 3.1 min，手术切口平均为1.1± 0.2 cm，均明显低于传统生长棒组（P< 0.001）。新型生长棒组一共平均撑开了40.08 mm (30.1-46.83 mm), 脊柱平均增长率为17.42% (13.77-21.67%)；而传统生长棒组一共平均撑开了43.62 mm (38.84-46.28 mm), 脊柱平均增长率为18.69% (15.97-20.03%)。两者之间的差异没有统计学意义。两组之间在椎体和椎间盘高度变化没有统计学差异(P >0.05)。脊柱CT横断面显示新型生长棒固定节段内外小关节突的关节间隙存在，未见明显退变。脊柱MRI显示新型生长棒固定节段内外的椎间盘信号正常，没有明显退变。而且，新型生长棒保留了脊柱的各向活动能力。

研究结论：新型生长棒在动物体内能够安全有效的撑开，保留了脊柱纵向生长能力。而且相比较于传统生长棒，新型生长棒撑开的手术创伤更小。同时，新型生长棒良好的保留了脊柱的各向活动度，并不会导致脊柱的僵硬度有所增加。在调节脊柱生长的过程中，对椎间盘没有明显的损伤，不会引起椎间盘发生明显退变。

第二部分 先天性脊柱侧凸合并脊髓纵裂的临床影像学研究

研究背景：脊髓纵裂是一种罕见的闭合神经管先天性发育缺陷，常与先天性脊柱侧凸伴发。由于先天性脊柱侧凸合并脊髓纵裂患者潜在的高神经损伤风险，对于脊柱外科医生来说是一种极大的技术挑战。此外，该疾病的自然史目前尚不清楚，导致患者神经系统功能损害的危险因素亦不明了，需要进一步的临床研究。

研究目的：分析先天性脊柱侧凸合并脊髓纵裂患者的影像学特点及其临床相关性研究，如果能够早期诊断具有高神经功能损害的患者，对于指导更加规范、更加个体化的治疗策略将十分有意义。

研究方法：回顾性分析2000年5月至2015年12月间我院手术治疗的266例CS合并SCM患者。共有190名女性和76名男性患者纳入研究，平均年龄14.2岁（3-39岁）。每例患者接受了全脊柱磁共振成像（MRI）和计算机断层扫描（CT）的检查，以评估脊髓纵裂的分型和位置。根据Pang的脊髓纵裂分型，所有患者被分为SCM- I型组和SCM-II型组。收集临床资料和影像学数据，探讨脊柱侧凸弯型，椎体和肋骨发育畸形和椎管内异常的发生率及相关性。进一步分析了85例SCM- I型脊髓纵裂的患者骨棘和神经系统功能之间的相关性。通过全脊柱CT和磁共振影像资料，判断骨棘的位置以及其相对于脊柱侧凸主弯顶椎的相对位置关系，同时测量骨棘的长度、厚度。此外，在横断面MRI上测量侧弯凸凹侧两个半脊髓的直径大小。

研究结果: SCM- I型组104例（39.1％），SCM-II型组162例（60.9％）。SCM最常见于下胸椎和腰椎区域。I型SCM纵隔的平均长度明显短于II型SCM（分别外2.7节和5.2节）。SCM- I型组组患者的脊柱后凸畸形发生率较高（22.1％）。单脊椎畸形仅为16.5％，多脊椎畸形为83.5％。对比发现，SCM- I型组患者的椎体畸形复杂型更多（90.4％）、累计节段更广泛（5.1节）。此外，肥厚性椎板和球茎棘突的发生率也更高（29.7％），甚至形成“火山口”样畸形。肋骨异常发生在所有患者的发生率为62.8％，其中46.1％为复杂型畸形。其他并发的椎管内异常的总发生率为42.9％，最常见的类型是脊髓空洞症（30.5％）。SCM- I型中，无神经症状组（A组）52例（占61.2％），有神经症状组（B组）33例（占38.8％）。两组之间在一般资料、主弯Cobb 角度大小和骨棘长度方面差异无统计学意义。在A组中，骨棘相对于主弯顶椎的位置为：近端13例（25％），远端28例（53.8％），中央11例（21.2％）；而B组的关系为：近端7例（21.2％），远端8例（24.2％），中央18例（54.5％）。 两组之间骨棘的位置分布差异有统计学意义（c² = 10.898，p = 0.004）。B组患者的脊柱后凸畸形比例相对较高（42.4％）。 此外，两组之间的半脊髓直径（凹/凸）比例的差异有统计学意义（分别为0.98和0.87，p = 0.045）。

研究结论：先天性脊柱侧凸合并脊髓纵裂的患者表现出更高的多脊椎畸形、肋骨畸形、椎管内异常发病率。特别是在SCM-I型的患者中，表现出更多、更复杂的椎体发育异常，甚至形成“火山口”样畸形。进一步发现先天性脊柱侧凸合并脊髓纵裂患者，其骨棘的位置与神经功能损害有着密切的相关性。当骨棘位于脊柱侧凸顶椎区，尤其合并后凸畸形时，患者出现神经功能损害的风险最大。同时，脊髓纵裂的不对称分裂也和神经功能损害的重要原因之一。认识到骨棘和脊柱侧凸之间密切的临床相关性，对于具有神经功能高风险的患者具有早期诊断的指导意义。

Abstract

Part I: A preliminary study on a new growing rod system in an immature swine model

Background: Treatment of early-onset scoliosis (EOS) in childhood is still a challenge to surgeon. Nonfusion techniques, such as growing rods, were developed to postpone or avoid the fusion procedure and maintain the development of vital organs such as heart and lung. Although growing rods have well-accepted efficacy in controlling the deformity of a growing spine, they also have a high rate of complications. Therefore, a novel system of growing rod is urgently wanted to improve surgical outcome of early-onset scoliosis, minimizing the surgical trauma and reducing surgery-related complications.

Objective: The objective of this study is to mainly investigate the efficacy and safety of new growing rod system in an immature swine model. And to evaluate its effect on the spinal disc degeneration and vertebral potential growth as well.

Methods: 12 immature swine (age：10 weeks old; weight：8-12 kg) were used in this study. They were randomly assigned to an experiment group (new growing rod system) and control group (traditional growing rod system). Dual growing rod were implanted to fix low thoracic and lumbar spine. They underwent lengthening procedure at 4-week intervals with a total of 12 weeks observation period. Radiographs, magnetic resonance image, and computed tomographic scan of the spine were obtained to evaluate the fixation, rod extension, and spine degeneration.

Results: One swine in traditional growing rod group encountered deep wound infection and thus was excluded from analysis. Of the remaining 11 swine, all animals successfully underwent 12 weeks observation with 3 times of lengthening procedure. No new growing rod complications were observed. In new growing rod group, the average operative time was 12.1 ± 3.1 min and the average length of incision was 1.1 ± 0.2 cm, which were significantly lower than that of the traditional growth group (P <0.001). New growing rod was extend by 40.08 mm (range, 30.1-46.83 mm) and spine segments within the instruments grew by 17.42% (range: 13.77-21.67%) in 12 weeks. Traditional growing rod was extend by 43.62 mm (range, 38.84-46.28 mm) and spine segments within the instruments grew by 18.69% (range: 15.97-20.03%) in 12 weeks. There was no statistical difference between two groups (P> 0.05). Besides, there was no statistically significant difference between the two groups in vertebral body and intervertebral disc height (P> 0.05). In new growing rod group, axial spinal computed tomographic scan demonstrated normal facets within the instrumented segments. Magnetic resonance imaging showed normal disc within the instrumented segments. Motion of the instrumented spinal segments was conserved.

Conclusion: The new growing rod system can be safe and effective in immature swine, reserve potential growth ability of the spine, with less surgical trauma compared with the traditional growing rod. The new growing rod system well conserved the motion ability of the instrumented spinal segments, as well as the spinal disc within the instrumented segments.

Part II：Radiological characteristics and its clinical relevance on congenital scoliosis associated with split cord malformation

Background: Split cord malformation (SCM) is a rare form of closed neural tube defect which often associated with congenital scoliosis (CS). Type I SCM is defined as two hemicords, each within a separate dural tube separated by a bony spur, while type II SCM is defined as two hemicords within a single dural tube separated by a fibrous septum. Vertebrae, ribs, and spinal cord are anatomically adjacent structures, and their close relationships are clinically important for planning better corrective surgical approach. Furthermore, the nature history of split cord malformation (SCM) is still unclear. Baseline the characteristics of bony spur and its relationship with the spinal deformity can be used to help early identify those patients with higher neurological risk and improve surgical strategy.

Objective: To identify the radiographic characteristics and its clinical relevance in surgical patients with congenital scoliosis and split cord malformation.

Methods: A total of consecutive 266 patients with CS and SCM underwent surgical treatment at our hospital between May 2000 and December 2015 was retrospectively identified. There were 190 female and 76 male patients, with a mean age of 14.2 years (3–39 yr). Each patient received examinations of an entire spine magnetic resonance imaging (MRI) and computerized tomography (CT) to evaluate the type and location of SCM. According to Pang's classification for SCM, all patients were divided into Type I group and Type II group. The demographic distribution and radiographic data were collected to investigate the characteristics of spine curve, vertebral, rib, and intraspinal anomalies.

Of them, 85 consecutive type-I SCM patients were identified to investigate the characteristics of spine curve and bony spur. There were 22 male and 63 female patients with an average age of 13.9 years at surgery. They were divided into two groups according to their neurological status (intact or deficit). The location of bony spur relative to the apex of scoliosis were evaluated by MRI and CT of whole spine. The length and thickness of bony spur was also measured. Besides, in order to quantify the asymmetric splitting of the spinal cord, the diameter of hemicords were both measured on the axial MRI scans.

Results: There were 104 patients (39.1%) in Type I group and 162 patients (60.9%) in Type II group. SCM was most commonly found in the lower thoracic and lumbar regions. The mean length of the septum in Type I SCM was significantly shorter than Type II SCM (2.7 vs. 5.2 segments). Patients in Type I group had a higher proportion of kyphotic deformity (22.1%). The vertebral deformities were simple in only 16.5% and multiple in 83.5% of 266 cases. Patients in Type I group presented higher prevalence of multiple (90.4%) and extensive (5.1 segments) malformation of vertebrae. In addition, hypertrophic lamina and bulbous spinous processes were more frequent in Type I group (29.7%), even developing into the “volcano-shape” deformities. Rib anomalies occurred in 62.8% of all patients and 46.1% of them were complex anomalies. The overall prevalence of other intraspinal anomalies was 42.9%. The most common coexisting intraspinal anomalies was syringomyelia (30.5%). Furthermore, there were 52 patients (61.2%) in Group A (intact) and 33 patients (38.8%) in Group B (deficit). No significant differences were found in the demographic distribution, curve magnitude, and length of bony spur between two groups. In Group A, the location of bony spur relative to the apex of major curve were: proximal 13 (25%), distal 28 (53.8%), centered 11 (21.2%). While, in Group B, the relationships were: proximal 7 (21.2%), distal 8 (24.2%), centered 18 (54.5%). There were statistically significant difference of the location of bony spurs between two groups (c² = 10.898, P= 0.004). In addition, patients in Group B had a higher proportion of kyphotic deformity (42.4%). Furthermore, the ratio of the diameter of hemicords (concave/ convex) were statistically different between two groups (0.98 vs. 0.87, p=0.045).

Conclusion: The current study, with the largest cohort to date, demonstrated that patients with CS and coexisting SCM presented high prevalence of multiple vertebral deformities, rib and intraspinal anomalies. Especially in those with Type I SCM, they developed into more complicated and extensive vertebral anomalies, even “volcano-shape” deformities in the posterior elements of spine. The neurological status in patients with CS and type-I SCM may have a close relationship with their bony spur’s location relative to spinal deformity. When bony spurs occur at the apex of scoliosis, it have a higher risk of developing neurological deficits, especially in cases with kyphotic deformity. Besides, the neurological deficits in these patients may also attribute to the asymmetric splitting of the spinal cord.