颅骨修补对患者神经及认知功能的影响
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摘要
背景和目的
颅骨缺损大都继发于开放性颅脑损伤、手术颅内减压及肿瘤切除、先天畸形和进行性骨骼疾病等所致的病变颅骨切除术后，是颅脑术后较常见的后遗症。由于脑组织失去了正常颅骨的屏障作用而易受伤，且颅骨缺损能引起各种症状和影响外观。通常颅骨缺损除了直径小于3cm，以及颞肌下和枕下的颅骨缺损由于有肥厚的肌肉及筋膜覆盖并在缺损区形成的坚韧纤维性愈合层起到对脑的保护作用外，其余的多有临床症状，常需积极进行颅骨缺损修复。颅骨缺损直径大于3cm，可能会引起如头昏、头痛、忧郁、易激怒、自制力差和焦躁不安等躯体、心理各方面的症状；大面积的颅骨缺损会造成病人头颅严重畸形并影响颅内压的生理性平衡，大气压的长期直接作用于缺损区的局部脑组织可导致该部脑组织萎缩，加重脑损伤症状；小儿的颅骨缺损，随着发育缺损变大、边缘外翻，突出的脑组织呈进行性萎缩及囊变。颅骨成形术可以避免脑的再次损伤，外观上达到整形效果，还能增加大脑血流量，改善脑组织的能量代谢促进脑组织的功能恢复，治疗脑膨出，改善颅骨缺损患者神经、认知及精神方面的症状。目前尚没有理想的技术和材料使颅骨缺损从形态、结构和功能上完整地得到修复，组织工程特别是骨组织工程的出现和发展，给理想向现实的转变带来了希望。
在临床工作中发现，对颅骨缺损患者进行修补不仅有整形及保护颅内容物的作用，而且对患者的神经及认知功能的改善也有帮助。虽然国内也有颅骨修补前后患者神经功能和轻中度认知能力的改善的报道。但对颅骨缺损患者神经及认知功能改善的原因尚缺乏具体分析，本研究对我院自2005年7月-2007年1月行颅骨修补患者进行前瞻性研究，观测颅骨修补患者手术前后神经、认知及颅内血流速率的变化，探讨患者手术前后神经及认知功能的变化及其原因。
方法
共计32例。其中男27例，女5例，年龄13-65岁，平均31岁。其中2例为自体缺损颅骨修补，其余30例为钛网修补，皮瓣切口应尽量利用原手术切口，另行切口时，需考虑到原手术切口疤痕对皮瓣血运的影响，以防术后血运差而延缓切口愈合；剥离皮肌瓣时，应避免头皮过薄出现血供不足而坏死，同时也尽量不要损伤硬脑膜，以减少术后切口脑脊液外漏的发生。钛网的多孔状结构便于引流皮下及硬膜外的积液，组织长入后有铆合固定作用，加快组织愈合。骨缺损周边无需修整，骨衣不必切开，将大于缺损处的金属钛网覆盖在缺损处，四周螺钉固定。钛网植入位置应在原位，即硬膜外颞肌下，不可将颞肌置于钛网下，以避免颞肌反复运动产生牵拉痛，要充分暴露骨缺损区，将金属钛网塑形后与缺损区吻合后牢固固定。若颅骨缺损较大，需用丝线将缺损中央的硬脑膜悬吊固定在金属钛网上，以减少死腔，防止术后血肿或积液的发生，若有皮下积液时需穿刺抽吸并加压包扎。分别于术前2d和术后10d左右对患者的神经功能和认知功能进行评价，神经功能评价用NIHSS(美国国立卫生研究院卒中量表)，认知功能采用MMSE(简明智能量表)。颅内血流分别于术前2d和术后10d左右行经颅多普勒超声(TCD)检测。
结果
1．其中30例用钛网进行颅骨修补的患者只有一例术后发生皮下积液、一例术后发生癫痫。其中部分采用电脑塑形，术后患者修补效果满意，并发症少。两例用自体颅骨瓣进行颅骨修补，均采用医用乙醇保存，术后无骨瓣下陷等明显并发症。
2．颅骨修补后，患者的认知功能与术前相比有明显改善(P＜0.05)
3．颅骨修补后，患者的神经功能与术前相比有明显改善(P＜0.05)
4．颅骨修补患者手术前患侧血流速率与健侧相比明显降低，两侧血流速率不对称(P＜0.05)，修补后患者颅骨缺损侧血流有明显提高(P＜0.05)，术前两侧血流不对称性得到改善。
结论
1．颅骨修补可以明显改善患者的认知功能。
2．颅骨修补可以明显改善患者的神经功能。
3．颅骨修补可以提高患者缺损侧的血流速率，这在一定程度上可以解释颅骨修补对患者神经及认知功能的改善。
Objective
Most of the skull defect caused by the open head injury, surgical decompression and intracranial tumor resection, congenital malformations, continual bone disorders and other disease , is the more common side effect of the brain surgery. The brain can be easily injured because of the losing of normal skull barrier, and skull defect can cause a variety of symptoms and effects of appearance. Generally if the skull defects smaller than 3 cm in diameter and the temporal and occipital muscle under the skull defect due to muscle and anadesma cover the skull defects in the formation of fibrous more tenacity played with skull-brain protection have no clinical symptoms, the rest often have clinical symptoms which need reconstruction. The defect which more than 3 cm in diameter, probably cause dizziness, headaches, depression, irritability, poor discipline and restlessness physical, psychological aspects of the symptoms; Large areas of the skull defect will cause serious cranium malformation and damage the physiological balance of intracranial pressure, atmospheric pressure of the long-term directly affect the brain tissue of the defect area can lead to the telatrophy of the brain, increasing symptoms of brain damage; The skull defects in children with developmental defect in turn, marginalized valgus, a prominent brain atrophy was conducted and cystic degeneration .Cranioplasty can avoid the recurrence of brain injury, can achieve the plastic effect ,also increase the brain blood flow, can improve the brain energy metabolism and promote the resumption of brain tissue, treat the enencephalocele skull defects patients with neurological cognition and mental syndrome. At present, there is no ideal technology and materials so that the skull defect from the shape, structure and function to be completely restored, engineering tissue especially the bone engineering tissue's emergence and development bring hope for ideals to the reality.
At present, due to various reasons the skull defect repair is the main purpose for the protection of plastic and cranial contents needs. In clinical found that cranioplasty also can affect the neurological and cognitive function of the patients. Although in domestic there are some reports of the improvement of the effect of cranioplasty to neurological and moderate cognitive patients. But there are not analysis of the reason for the improvement of neurological and cognitive of the skull defect patients. This test summed up the clinical data of the cranioplasty patients of our hospital since July 2005 to January 2007 .Observing cranioplasty patient's neurolocal, cognitive and intracranial blood flow velocity changes before and after surgery, discuss the changes of neurological and cognitive function and analysis its reason.
Methods
There are 32 patients .27 of them are men ,the rest are women, the ages 13-65,average 31 years old. Two cases of autologous reconstruction skull defects, 30 cases of titanium mesh ,the skin flap should make full use of the original incision, if take a seperately incision, taking into account the influence of the original incision scar on the flap revascularization, prevent poor revascularization delayed wound healing; when decoherence skin Flap, should avoid emerging too thin scalp lead necrosis because of poor blood, also advised not to injury dura, in order to reduce the recurrence of cerebrospinal fluid leakage . The porous titanium mesh structure to facilitate drainage subcutaneous fluid and the epidural, after the organization grew into a riveting stationary, accelerate tissue healing. The peripheral of the bone defect need not repair, bone clothing need not open ,covering the metal titanium mesh to the defect, screw around. Titanium mesh implant in situ, that is, epidural temporalis muscle, the temporalis muscle will not be placed under the titanium mesh, to avoid the repeatedly movement of temporalis muscle cause pulling pain, fully exposed bone defects, the metal titanium mesh should be firmly fixed if it cover the skull defect. The large skull defect required a central thread fix the dura to metal titanium mesh to reduce dead space. Prevent postoperative hematoma and fluid, if needed subcutaneous hydrops should be punctured and compression bandaging. On the 2nd day before surgery and 10 days after surgery for patients with neurological and cognitive function evaluation, the evaluation of neurological function with NIHSS (National Institutes of Health Stroke Scale). Cognitive function using MMSE (mini-mental state examination). On the 2d pre-operative and 10d post-operative days via transcranial Doppler ultrasound (TCD) to detection intracranial blood flow.
Results
1. Thirty patients with titanium mesh for the cranioplasty with only one occurred subcutaneous fluid after surgery, and one patient had epilepsy. Some titanium mesh molding with computer, and the patient satisfacty with the repair effects, have fewer complications. 2 patients use autologous bone flap for cranioplasty, the skull flaps are preserved through medical alcohol, there was no skull flap subsidence and other significant complications.
2. After cranioplasty, cognitive function of the patients showed a significant improvement compare with preoperative evaluation (P<0.05)
3. After cranioplasty, neurological function of the patients showed a significant improvement compare with preoperative evaluation (P<0.05)
4. Before Cranioplasty ,the blood flow of the injuried side lower than the uninjuried side ,the blood flow of the two side not at the same level(P<0.05).After cranioplasty , the blood flow of the injuried side have a significant increase(P<0.05), the blood flow of the two side are at the same level with.
Conclusion
1. Cranioplasty can significantly improve the cognitive function of the patients.
2. Cranioplasty can significantly improve the neurological function of the patients.
3. Canioplasty can increase the brain blood flow of the injuried side, this can partly explain the improvement of cranioplasty to neurological and cognitive function of the patients.
颅骨缺损大都继发于开放性颅脑损伤、手术颅内减压及肿瘤切除、先天畸形和进行性骨骼疾病等所致的病变颅骨切除术后，是颅脑术后较常见的后遗症。由于脑组织失去了正常颅骨的屏障作用而易受伤，且颅骨缺损能引起各种症状和影响外观。通常颅骨缺损除了直径小于3cm，以及颞肌下和枕下的颅骨缺损由于有肥厚的肌肉及筋膜覆盖并在缺损区形成的坚韧纤维性愈合层起到对脑的保护作用外，其余的多有临床症状，常需积极进行颅骨缺损修复。颅骨缺损直径大于3cm，可能会引起如头昏、头痛、忧郁、易激怒、自制力差和焦躁不安等躯体、心理各方面的症状；大面积的颅骨缺损会造成病人头颅严重畸形并影响颅内压的生理性平衡，大气压的长期直接作用于缺损区的局部脑组织可导致该部脑组织萎缩，加重脑损伤症状；小儿的颅骨缺损，随着发育缺损变大、边缘外翻，突出的脑组织呈进行性萎缩及囊变。颅骨成形术可以避免脑的再次损伤，外观上达到整形效果，还能增加大脑血流量，改善脑组织的能量代谢促进脑组织的功能恢复，治疗脑膨出，改善颅骨缺损患者神经、认知及精神方面的症状。目前尚没有理想的技术和材料使颅骨缺损从形态、结构和功能上完整地得到修复，组织工程特别是骨组织工程的出现和发展，给理想向现实的转变带来了希望。
在临床工作中发现，对颅骨缺损患者进行修补不仅有整形及保护颅内容物的作用，而且对患者的神经及认知功能的改善也有帮助。虽然国内也有颅骨修补前后患者神经功能和轻中度认知能力的改善的报道。但对颅骨缺损患者神经及认知功能改善的原因尚缺乏具体分析，本研究对我院自2005年7月-2007年1月行颅骨修补患者进行前瞻性研究，观测颅骨修补患者手术前后神经、认知及颅内血流速率的变化，探讨患者手术前后神经及认知功能的变化及其原因。
方法
共计32例。其中男27例，女5例，年龄13-65岁，平均31岁。其中2例为自体缺损颅骨修补，其余30例为钛网修补，皮瓣切口应尽量利用原手术切口，另行切口时，需考虑到原手术切口疤痕对皮瓣血运的影响，以防术后血运差而延缓切口愈合；剥离皮肌瓣时，应避免头皮过薄出现血供不足而坏死，同时也尽量不要损伤硬脑膜，以减少术后切口脑脊液外漏的发生。钛网的多孔状结构便于引流皮下及硬膜外的积液，组织长入后有铆合固定作用，加快组织愈合。骨缺损周边无需修整，骨衣不必切开，将大于缺损处的金属钛网覆盖在缺损处，四周螺钉固定。钛网植入位置应在原位，即硬膜外颞肌下，不可将颞肌置于钛网下，以避免颞肌反复运动产生牵拉痛，要充分暴露骨缺损区，将金属钛网塑形后与缺损区吻合后牢固固定。若颅骨缺损较大，需用丝线将缺损中央的硬脑膜悬吊固定在金属钛网上，以减少死腔，防止术后血肿或积液的发生，若有皮下积液时需穿刺抽吸并加压包扎。分别于术前2d和术后10d左右对患者的神经功能和认知功能进行评价，神经功能评价用NIHSS(美国国立卫生研究院卒中量表)，认知功能采用MMSE(简明智能量表)。颅内血流分别于术前2d和术后10d左右行经颅多普勒超声(TCD)检测。
结果
1．其中30例用钛网进行颅骨修补的患者只有一例术后发生皮下积液、一例术后发生癫痫。其中部分采用电脑塑形，术后患者修补效果满意，并发症少。两例用自体颅骨瓣进行颅骨修补，均采用医用乙醇保存，术后无骨瓣下陷等明显并发症。
2．颅骨修补后，患者的认知功能与术前相比有明显改善(P＜0.05)
3．颅骨修补后，患者的神经功能与术前相比有明显改善(P＜0.05)
4．颅骨修补患者手术前患侧血流速率与健侧相比明显降低，两侧血流速率不对称(P＜0.05)，修补后患者颅骨缺损侧血流有明显提高(P＜0.05)，术前两侧血流不对称性得到改善。
结论
1．颅骨修补可以明显改善患者的认知功能。
2．颅骨修补可以明显改善患者的神经功能。
3．颅骨修补可以提高患者缺损侧的血流速率，这在一定程度上可以解释颅骨修补对患者神经及认知功能的改善。
Objective
Most of the skull defect caused by the open head injury, surgical decompression and intracranial tumor resection, congenital malformations, continual bone disorders and other disease , is the more common side effect of the brain surgery. The brain can be easily injured because of the losing of normal skull barrier, and skull defect can cause a variety of symptoms and effects of appearance. Generally if the skull defects smaller than 3 cm in diameter and the temporal and occipital muscle under the skull defect due to muscle and anadesma cover the skull defects in the formation of fibrous more tenacity played with skull-brain protection have no clinical symptoms, the rest often have clinical symptoms which need reconstruction. The defect which more than 3 cm in diameter, probably cause dizziness, headaches, depression, irritability, poor discipline and restlessness physical, psychological aspects of the symptoms; Large areas of the skull defect will cause serious cranium malformation and damage the physiological balance of intracranial pressure, atmospheric pressure of the long-term directly affect the brain tissue of the defect area can lead to the telatrophy of the brain, increasing symptoms of brain damage; The skull defects in children with developmental defect in turn, marginalized valgus, a prominent brain atrophy was conducted and cystic degeneration .Cranioplasty can avoid the recurrence of brain injury, can achieve the plastic effect ,also increase the brain blood flow, can improve the brain energy metabolism and promote the resumption of brain tissue, treat the enencephalocele skull defects patients with neurological cognition and mental syndrome. At present, there is no ideal technology and materials so that the skull defect from the shape, structure and function to be completely restored, engineering tissue especially the bone engineering tissue's emergence and development bring hope for ideals to the reality.
At present, due to various reasons the skull defect repair is the main purpose for the protection of plastic and cranial contents needs. In clinical found that cranioplasty also can affect the neurological and cognitive function of the patients. Although in domestic there are some reports of the improvement of the effect of cranioplasty to neurological and moderate cognitive patients. But there are not analysis of the reason for the improvement of neurological and cognitive of the skull defect patients. This test summed up the clinical data of the cranioplasty patients of our hospital since July 2005 to January 2007 .Observing cranioplasty patient's neurolocal, cognitive and intracranial blood flow velocity changes before and after surgery, discuss the changes of neurological and cognitive function and analysis its reason.
Methods
There are 32 patients .27 of them are men ,the rest are women, the ages 13-65,average 31 years old. Two cases of autologous reconstruction skull defects, 30 cases of titanium mesh ,the skin flap should make full use of the original incision, if take a seperately incision, taking into account the influence of the original incision scar on the flap revascularization, prevent poor revascularization delayed wound healing; when decoherence skin Flap, should avoid emerging too thin scalp lead necrosis because of poor blood, also advised not to injury dura, in order to reduce the recurrence of cerebrospinal fluid leakage . The porous titanium mesh structure to facilitate drainage subcutaneous fluid and the epidural, after the organization grew into a riveting stationary, accelerate tissue healing. The peripheral of the bone defect need not repair, bone clothing need not open ,covering the metal titanium mesh to the defect, screw around. Titanium mesh implant in situ, that is, epidural temporalis muscle, the temporalis muscle will not be placed under the titanium mesh, to avoid the repeatedly movement of temporalis muscle cause pulling pain, fully exposed bone defects, the metal titanium mesh should be firmly fixed if it cover the skull defect. The large skull defect required a central thread fix the dura to metal titanium mesh to reduce dead space. Prevent postoperative hematoma and fluid, if needed subcutaneous hydrops should be punctured and compression bandaging. On the 2nd day before surgery and 10 days after surgery for patients with neurological and cognitive function evaluation, the evaluation of neurological function with NIHSS (National Institutes of Health Stroke Scale). Cognitive function using MMSE (mini-mental state examination). On the 2d pre-operative and 10d post-operative days via transcranial Doppler ultrasound (TCD) to detection intracranial blood flow.
Results
1. Thirty patients with titanium mesh for the cranioplasty with only one occurred subcutaneous fluid after surgery, and one patient had epilepsy. Some titanium mesh molding with computer, and the patient satisfacty with the repair effects, have fewer complications. 2 patients use autologous bone flap for cranioplasty, the skull flaps are preserved through medical alcohol, there was no skull flap subsidence and other significant complications.
2. After cranioplasty, cognitive function of the patients showed a significant improvement compare with preoperative evaluation (P<0.05)
3. After cranioplasty, neurological function of the patients showed a significant improvement compare with preoperative evaluation (P<0.05)
4. Before Cranioplasty ,the blood flow of the injuried side lower than the uninjuried side ,the blood flow of the two side not at the same level(P<0.05).After cranioplasty , the blood flow of the injuried side have a significant increase(P<0.05), the blood flow of the two side are at the same level with.
Conclusion
1. Cranioplasty can significantly improve the cognitive function of the patients.
2. Cranioplasty can significantly improve the neurological function of the patients.
3. Canioplasty can increase the brain blood flow of the injuried side, this can partly explain the improvement of cranioplasty to neurological and cognitive function of the patients.
引文
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17 侯立军，卢亦成，于明琨，袁国良等．颅骨重建对创伤性颅骨缺损患者神经功能的影响．中华创伤杂志，2004，20(12)：772-773．
18 Gottlob I, Simonsz-Toth B, Heilbronner R. midbrain syndrome with eye movement disorder: dramatic improvement after cranioplasty. J Strabismus, 2002 Dec;10(4):271-277
19 郑少钦，杨应明．颅骨缺损修复研究进展[J]．中国临床神经外科杂志，2001,6(4)：255-256．
20 Fallahi B, Foroutan M, Motavalli S, et al. Computer-aided manufacturing of implants for the repair of large cranial defects: an improvement of the stereolithography technique. Neurol Res, 1999 Apr;21(3):281-286.
21 Segal D H, Oppenheim J S, Muyovic J A. Neurological recovery After cranioplasty[J]. Neurosurgery, 1994,34:729.
22 Stula D. Intracranial pressure measurementin large skull defects. Ncurochirurgia(Stuttg), 1985, 28:164—169.
23 Dujiovny M, Fernandez p, Alperin N, et al. Post-cranioplasty cerebrospinal fluid hydrodynamic changes: magnetic resonanse imaging quantitative analysis. Neurol Res, 1997.19:311-316.
24 Winkler P A, Stummer W, Linke R, et al. Influence of cranioplasty on postural blood flow regulaion, cerebrovascualar reserve capacty, and cerebral glucose metabolism[J]. J Neurosurgery, 2000,93:5-61.
25 孙双华．外伤后颅骨修补时机的临床观察[J]．中国误诊学杂志，2003，3：879．
26 赵雅度，赵元立，赵继宗等．颅脑创伤患者的后期康复．现代神经疾病杂志，2001，1(1)：20-21
1 Sanan A, Haines SJ. Repairing holes in the head:a history of cranioplasty[J]. Neurosurgery, 1997,40(3):588-603.
2 Gladstone HB, McDermott MW, Cooke DD. Implants for cranioplasty. Otolaryngol Clin North Am, 1995 Apr;28(2):381-400.
3 李文字，宁学权，高英等．颅骨骨膜缘下植入钛网锁边缝合．中华神经志，2003，19(5)：396
4 Guil L, Zuo F, Zhang ZY, et al. Individual prefabricated titanium implant for the reconstruction of the skull bone defect. Zhonghua Zheng Xing Wai Ke Za Zhi. 2004 Mar; 20(2):98-100
5 Lara WC, Schweitzer J, Lewis RP, et al. Technical considerations in the use of polymethylmethacrylate in cranioplasty. J Long Term Eff Med Implants. 1998;8(1):43-53.
6 杨涵铭，杨德泰，鲁守龙等．硅橡胶涤纶丝网颅骨成形处修补颅骨缺损48例报告．中华神经外科杂志，1986．2(2)：123．
7 黄纯真，甘雨．颅骨缺损修补材料的研究．中国临床神经外科杂志，2003，8(2)：157．
8 刘宝梅，李建．硅橡胶颅骨修补手术配合的体会．职业与健康，2002，18(12)：162-163．
9 Frodel JL, Lee S. The use of high-density polyethylene implants In facial Deformities. Arch Otolaryngol Head Neck Surg, 1998,124(11):1219.
10 吴承远，刘玉光．临床神经外科学．人民卫生出版社，2001．217-218．
11 杨尊清．自体骨修补颅骨缺损84例报告．医师进修杂志，1995，18(5)：17．
12 魏建功，黎建明，张日华等．自体颅骨帽状腱膜下保存及回植．中华神经外科杂志，2003，19(2)：152．
13 顾国山，徐启武，毛颖等．颅骨缺损修补新方法-自体颅骨辦牵拉复位应用报告．中国神经精神病杂志，1997，23(3)：148．
14 黄河清，谭英华，陈泉康等．推移颅骨辦减压后牵引复位22例报告．中国神经精神杂志，1997，23,(3)：166．
15 张弘，刘芷明，朱侠等．自体颅骨低温冷藏的研究与应用．中华神经外科杂志，1994，10(4)：205．
16 罗文杰，李军等．低温保存自体颅骨及颅骨钻孔行颅骨修补临床疗效．基层医学论坛．2006，20(8)：703-704．
17 谭国伟，方耀春，姜月明等．自体颅骨瓣离体保存后再植的临床应用．中国临床神经外科杂志，2003，8(5)：371．
18 Hiroji M, Tomio O, Hideo T. A new technique for cranioplasty with L-shaped titanium plates and combination ceraxnic implants composed Of hydroxyapatite and tricalcium phosphate(Ceratite)[J]. Neurosurgery, 2000,46(2):414-418.
19 李鲲，杨述华．可注射磷酸钙骨水泥临床应用新进展[J]．国外医学骨科学分册，2003，24(3)：184-186．
20 孙明林，胡蕴玉．磷酸钙骨水泥的研究和应用进展[J]．中华骨科杂志，2002，22(1)：49-52．
21 李静，曹谊林，崔磊．骨组织工程学研究进展及展望[J]．国外医学骨科学分册，2001，22(1)：5-9．
22 雷德林，羊书勇，杨维东，等．藻酸钙／骨髓基质成骨细胞复合物修复兔颅骨缺损实验研究[J]．中华神经外科疾病研究杂志，2003，2(1)：33-35
23 Yamamoto Y, Mendel E, Raffel C. Acrylic cranioplasty with alginate molding:Technical note[J]. Neurosurgery, 1997,41(1):305-307.
24 孙明林，胡蕴玉．骨形态发生蛋白在矫形外科的应用研究[J]．中华创伤杂志，2001，17(11)：695-697．
25 郑少钦，杨应明．颅骨缺损修复研究进展[J]．中国临床神经外科杂志，2001，6(4)：255-256．
26 Helm GA, Alden TD, Sheehan JP, et al. Bone morphogenetic proteins and bone morphogenetic protein gene therapy in neurologicalsurgery:A review[J]. Neurosurgery, 2000,46(5):1213-1222.
27 汪宇，闫景龙，张滨等．复合骨形态发生蛋白载体材料的研究现状[J]．实用骨科杂志，2003，9(2)：139-142．
28 李静，曹谊林，崔磊．骨组织工程学研究进展及展望[J]．国外医学骨科学分 册，2001，22(1)：5-9．
29 Kubo S, Takimoto H, Kato A, et al. Endoscopic cranioplasty with Calcium phosphate cement for pterional bone defect after frontotemporal craniotomy: technical note[J]. Neurosurgery, 2002,51(4):1094-1096.
30 孙崇然，刘恩重．颅骨缺损的组织工程学修复研究进展[J]．国外医学神经病学神经外科学分册，2004，31(2)：183-186．
31 张磊．复合异种骨的相关研究和进展[J]．国外医学生物医学工程分册，2004，27(4)：242-245．
32 Charles A, Vacanti MP, joseph P, et al. The science of tissue engineering[J]. Orthop Chin North AM, 2000,31(3):512.
33 Crane GM, Ishaug SL, Mikos AG, et al. Bone tissue engineering [J]. J Nat Med, 1995,1(12):1322
34 Rickard dj, kassem M, hefferan TE, et al. Isolation and Characterization of Osteoblast Precursor Cells from Human Bone Marrow[J]. J bone miner Res, 1996,11(3):312
35 Gafni Y, Turgeman G, Libergal M, et al. Stem cells as vehicales for orthopedic gene therapy[J]. Gene Ther, 2004,11(4):417
36 Patricia A, Min zhu, Peter A, et al. Hunan Adipose Tissue is a Source of Multipotent Stem Cells[J]. Mol Bio of the Cell, 2002,13:4279
37 Dragoo J, Samimi B, zhu M, et al. Tissue-engineered cartilage and bone using stem cell from human infrapatellar fat pads[J]. J Bone Joint Surg Br, 2003,85(5):740
38 Schmitt J, Hwang K, Winn S, et al. Bone morphogenetic proteins:an update on basic biology and clinical relevance [J]. J Orthop Res, 1999.17:269
39 Higuchi T, Kinosshita A, Takahashi K, et al. Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects[J]. J Periodontol, 1999,70:1026
40 SMS Bidic, J W Calvert, K Marra, et al. Rabbit calvarial wound healing by means of seeded caprotite scaffolds[J]. Journal of Dental Research, 2003,82(2):131
41 Paul H, Krebsbach MH, Mankani KS, et al. Repair of craniotomy defects using bone marrow stromal cells [J]. Transplantation, 1998,66:1272
42 Arnold S, Daniel A, Grande D, et al. Tissue engineered bone repire of calvarial defects using cutured periosteal cells [J]. Pla& Rec S, 1998,101(3):567.
43 Shang Qinxin, Wang zhuo. Tissue-engineered bone repir of sheep cranial defects with autologous bone marrow stromal cells [J]. J Craniofa S, 2001,12(6):586.
44 Chang SC, Chuang H, Chen YR, et al. Craninal repair using BMP-2 gene engineered bone marrow stromal cells[J]. Journal of Dental Research, 2003,82(2):131
45 Hairong peng, Hsain-chung shen, Arvydas usas, et al. The role of cell tYpe in bone healing mediated by ex vivo gene therapy[J]. Langenbecks Arch Surg, 2003,388:347
46 李永谦，孙昭胜，李勇等．颅骨缺损再生10例．中华创伤杂志，2005，21(3)：219-220
47 Schmoceke IHG, Weber FE, SchenseJC, et al. Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell in growth matrices[J], biotechnol bioeng, 2005,89(3):253-262
48 pang EK, im SU, Kim CS,etal Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model[J].J periodontal.2004,75(10): 1364-1370
49 段国升，朱诚．神经外科手术学[M]．人民军医出版社，2004，110-112．
50 段国升，朱诚．手术学全集．神经外科卷[M]．人民军医出版社，1994，108
51 马廉亭．实用神经外科手册[M]．人民军医出版社，1996。353
52 王忠诚．神经外科学[M]．湖北科学技术出版社，1998．378
53 高立达．急性颅脑损伤大骨辦减压问题[C]．西南地区颅脑损伤学术交流会论文摘要汇编，1991．90
54 卓大宏．康复医学[M]．四川科学技术出版社，1988．67．
55 冯爱平，陈宏刚，唐运涛．提早修补巨大颅骨缺损的临床研究．西藏医药杂志，2005，26(3)：17．
56 Kuo JR, Wang CC, Chio CC, et al. Neurological improvement after cranioplasty -analysis by transcranial doppler ultrasonography[J].J Chin Neurosci,2004,11(5):486-489
57 孟兵，陈立华，秦天森．颅骨修补术27例临床体会[J]．湖南医学，1999，16：442．
58 杨炳湖，荆国志，杨魁元．颅骨缺损修补208例临床分析[J]．实用医学杂志，2002，18：114．
59 韩振亚，孙华北，陈召廷．负压引流在硅橡胶颅骨修补中的应用[J]．江苏医药杂志2001，27：845．
60 林时松．颅骨缺损修补术并发症分析[J]．现代诊断治疗，1994，5：365．
61 anecka IP. Reconstructive technologies in skull base surgery, role of titanium mesh and polyethylene[J]. Arch Otolaryngol Head neck Surg, 2000,126:396.
62 Richaud J, Boetto S, Guell A, et al. Effectsof cranioplasty on neurological function andcerebral blood flow. Neurochirurgie, 1985, 31: 183—188.
63 Stula D. Intracranial pressure measurement in large skull defects. Ncurochirurgia(Stuttg), 1985,28:164—169
64 Dujiovny M, Fernandez p, Alperin N, et al. Post-cranioplasty cerebrospinal fluid hydrodynamic changes: magnetic resonanse imaging quantitative analysis. Neurol Res, 1997,19:311—316.
65 赵雅度，赵元立，赵继宗等．颅脑创伤患者的后期康复．现代神经疾病杂志，2001，1(1)：20-21
66 刘波，梁冶矢，栾文忠等．脑震荡患者恢复期心理状况调查．现代神经疾病杂志2002，2(2)：90-91
2 Sanan A, Haines SJ. Repairing holes in the head:a history of cranioplasty[J]. Neurosurgery, 1997,40(3):588-603.
3 Gladstone HB, McDermott MW, Cooke DD. Implants for cranioplasty. Otolaryngol Clin North Am, 1995 Apr;28(2):381-400.
4 Boden Scott D, Martain George J, Morone M, et al. The Use of Coralline Hydroxyapatite With Bone Marrow, Autogenous Bone Graft, or Osteoinductive Bone Protein Extract for Posterolateral Lumbar Spine Fusion[J]. J Spine, 1999,24(4):320.
5 Sawin PD, Traynelis VC, Menezes AH, et al. A Comparative analysis of fusion rates and donor-site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions[J]. J Neurosurg, 1998,88(2):255.
6 Hollinger J, Jefrey O, Winn Sheley R, et al. Tissue Engineering of Bone in the Craniofacial Complex[J]. Annals of the New York Academy of Sciences, 1999,875:379.
7 Hollinger J, Jeffrey O, et al. Tissue Engineering of Bone in the Craniofacial Complex[J]. Annals of the New York Academy of Sciences, 1999,875:379.
8 Charles A, Vacanti MP, Joseph P, et al. The science of tissue engineering[J]. Orthop Chin North AM, 2000,31(3):512.
9 段国升，朱诚．手术学全集．神经外科卷[M]．人民军医出版社，1994．108．
10 马廉亭．实用神经外科手册[M]．人民军医出版社，1996．353．
11 王忠诚．神经外科学[M]．湖北科学技术出版社，1998．378．
12 Yoshida, Furuse, Masahiro, et al. Suguru Dynamics of cerebral blood flow and metabolism in patients with cranioplasty as evaluated by sup 133 Xe CT and sup 31 P magnetic resonance spectroscopy. Journal of Neurology, Neurosurgery & Psychiatry. 61(2):166-171, August 1996.
13 高立达．急性颅脑损伤大骨辦减压问题[C]．西南地区颅脑损伤学术交流会论文摘要汇编，1991．90．
14 冯爱平，陈宏刚，唐运涛．提早修补巨大颅骨缺损的临床研究．西藏医药杂志，2005，26(3)：17
15 Kuo JR, Wang CC, Chio CC, et al. Neurological improvement after cranioplastyanalysis by transcranial doppler ultrasonography[J]. J Chin Neurosci, 2004,11(5):486-489
16 陈伟焯，燕铁斌．颅骨修补对轻中度颅脑损伤的认知及日常生活的影响 中国康复理论与实践，2005，11(11)：953．
17 侯立军，卢亦成，于明琨，袁国良等．颅骨重建对创伤性颅骨缺损患者神经功能的影响．中华创伤杂志，2004，20(12)：772-773．
18 Gottlob I, Simonsz-Toth B, Heilbronner R. midbrain syndrome with eye movement disorder: dramatic improvement after cranioplasty. J Strabismus, 2002 Dec;10(4):271-277
19 郑少钦，杨应明．颅骨缺损修复研究进展[J]．中国临床神经外科杂志，2001,6(4)：255-256．
20 Fallahi B, Foroutan M, Motavalli S, et al. Computer-aided manufacturing of implants for the repair of large cranial defects: an improvement of the stereolithography technique. Neurol Res, 1999 Apr;21(3):281-286.
21 Segal D H, Oppenheim J S, Muyovic J A. Neurological recovery After cranioplasty[J]. Neurosurgery, 1994,34:729.
22 Stula D. Intracranial pressure measurementin large skull defects. Ncurochirurgia(Stuttg), 1985, 28:164—169.
23 Dujiovny M, Fernandez p, Alperin N, et al. Post-cranioplasty cerebrospinal fluid hydrodynamic changes: magnetic resonanse imaging quantitative analysis. Neurol Res, 1997.19:311-316.
24 Winkler P A, Stummer W, Linke R, et al. Influence of cranioplasty on postural blood flow regulaion, cerebrovascualar reserve capacty, and cerebral glucose metabolism[J]. J Neurosurgery, 2000,93:5-61.
25 孙双华．外伤后颅骨修补时机的临床观察[J]．中国误诊学杂志，2003，3：879．
26 赵雅度，赵元立，赵继宗等．颅脑创伤患者的后期康复．现代神经疾病杂志，2001，1(1)：20-21
1 Sanan A, Haines SJ. Repairing holes in the head:a history of cranioplasty[J]. Neurosurgery, 1997,40(3):588-603.
2 Gladstone HB, McDermott MW, Cooke DD. Implants for cranioplasty. Otolaryngol Clin North Am, 1995 Apr;28(2):381-400.
3 李文字，宁学权，高英等．颅骨骨膜缘下植入钛网锁边缝合．中华神经志，2003，19(5)：396
4 Guil L, Zuo F, Zhang ZY, et al. Individual prefabricated titanium implant for the reconstruction of the skull bone defect. Zhonghua Zheng Xing Wai Ke Za Zhi. 2004 Mar; 20(2):98-100
5 Lara WC, Schweitzer J, Lewis RP, et al. Technical considerations in the use of polymethylmethacrylate in cranioplasty. J Long Term Eff Med Implants. 1998;8(1):43-53.
6 杨涵铭，杨德泰，鲁守龙等．硅橡胶涤纶丝网颅骨成形处修补颅骨缺损48例报告．中华神经外科杂志，1986．2(2)：123．
7 黄纯真，甘雨．颅骨缺损修补材料的研究．中国临床神经外科杂志，2003，8(2)：157．
8 刘宝梅，李建．硅橡胶颅骨修补手术配合的体会．职业与健康，2002，18(12)：162-163．
9 Frodel JL, Lee S. The use of high-density polyethylene implants In facial Deformities. Arch Otolaryngol Head Neck Surg, 1998,124(11):1219.
10 吴承远，刘玉光．临床神经外科学．人民卫生出版社，2001．217-218．
11 杨尊清．自体骨修补颅骨缺损84例报告．医师进修杂志，1995，18(5)：17．
12 魏建功，黎建明，张日华等．自体颅骨帽状腱膜下保存及回植．中华神经外科杂志，2003，19(2)：152．
13 顾国山，徐启武，毛颖等．颅骨缺损修补新方法-自体颅骨辦牵拉复位应用报告．中国神经精神病杂志，1997，23(3)：148．
14 黄河清，谭英华，陈泉康等．推移颅骨辦减压后牵引复位22例报告．中国神经精神杂志，1997，23,(3)：166．
15 张弘，刘芷明，朱侠等．自体颅骨低温冷藏的研究与应用．中华神经外科杂志，1994，10(4)：205．
16 罗文杰，李军等．低温保存自体颅骨及颅骨钻孔行颅骨修补临床疗效．基层医学论坛．2006，20(8)：703-704．
17 谭国伟，方耀春，姜月明等．自体颅骨瓣离体保存后再植的临床应用．中国临床神经外科杂志，2003，8(5)：371．
18 Hiroji M, Tomio O, Hideo T. A new technique for cranioplasty with L-shaped titanium plates and combination ceraxnic implants composed Of hydroxyapatite and tricalcium phosphate(Ceratite)[J]. Neurosurgery, 2000,46(2):414-418.
19 李鲲，杨述华．可注射磷酸钙骨水泥临床应用新进展[J]．国外医学骨科学分册，2003，24(3)：184-186．
20 孙明林，胡蕴玉．磷酸钙骨水泥的研究和应用进展[J]．中华骨科杂志，2002，22(1)：49-52．
21 李静，曹谊林，崔磊．骨组织工程学研究进展及展望[J]．国外医学骨科学分册，2001，22(1)：5-9．
22 雷德林，羊书勇，杨维东，等．藻酸钙／骨髓基质成骨细胞复合物修复兔颅骨缺损实验研究[J]．中华神经外科疾病研究杂志，2003，2(1)：33-35
23 Yamamoto Y, Mendel E, Raffel C. Acrylic cranioplasty with alginate molding:Technical note[J]. Neurosurgery, 1997,41(1):305-307.
24 孙明林，胡蕴玉．骨形态发生蛋白在矫形外科的应用研究[J]．中华创伤杂志，2001，17(11)：695-697．
25 郑少钦，杨应明．颅骨缺损修复研究进展[J]．中国临床神经外科杂志，2001，6(4)：255-256．
26 Helm GA, Alden TD, Sheehan JP, et al. Bone morphogenetic proteins and bone morphogenetic protein gene therapy in neurologicalsurgery:A review[J]. Neurosurgery, 2000,46(5):1213-1222.
27 汪宇，闫景龙，张滨等．复合骨形态发生蛋白载体材料的研究现状[J]．实用骨科杂志，2003，9(2)：139-142．
28 李静，曹谊林，崔磊．骨组织工程学研究进展及展望[J]．国外医学骨科学分 册，2001，22(1)：5-9．
29 Kubo S, Takimoto H, Kato A, et al. Endoscopic cranioplasty with Calcium phosphate cement for pterional bone defect after frontotemporal craniotomy: technical note[J]. Neurosurgery, 2002,51(4):1094-1096.
30 孙崇然，刘恩重．颅骨缺损的组织工程学修复研究进展[J]．国外医学神经病学神经外科学分册，2004，31(2)：183-186．
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