硬膜囊内减压治疗创伤性脊髓损伤的研究进展

梁兵　董健　唐家广

硬膜囊内减压治疗创伤性脊髓损伤的研究进展

梁兵董健唐家广

脊髓损伤；病理过程；减压术，外科；治疗学

创伤性脊髓损伤 ( traumatic spinal cord injury，TSCI )多见于交通事故、砸伤、摔伤、运动性损伤等，由直接作用于脊柱或脊髓的机械性损害所致，可导致全身多器官、系统长期的功能紊乱，甚至永久性的功能改变，如损伤平面以下的感觉、运动功能障碍，致使患者生活质量明显下降，给个人、家庭和社会带来沉重负担，在全球呈现高发生率与高致残率[1-4]。

TSCI 的发生主要是由于原发机械性损伤和继发性缺血性损伤导致脊髓组织破坏。原发性损伤发生在机械性损伤的即刻，它是不可逆的过程。继发性损伤是一种细胞分子水平的主动调节过程，具有可逆性和可控性。因此，早期正确积极的干预，对于保留残存神经组织的功能至关重要。药物学方法促进神经再生进程、抑制炎症有害方面，是目前脊髓损伤 ( spinal cord injury，SCI ) 治疗研究的前沿；然而，迄今为止，国际上虽然已经有 5 种药物学治疗方案用于临床试验，但它们并没有任何一种成为有效的治疗方法[5]，尚未发现任何药物在脊髓损伤临床转化应用治疗中具有显著疗效[6-9]。因此，外科手术干预，硬膜囊内减压，清除血肿，解除压迫，释放坏死物质，以减轻脊髓组织水肿、恢复脊髓血流灌注以及降低继发性损害，是有希望治疗脊髓损伤的途径之一，也是未来脊髓损伤治疗研究的重要发展方向。笔者对硬膜囊内减压的作用及手术时机的研究进行如下综述。

一、脊髓损伤的病理生理学

TSCI 的病理生理改变主要由两大机制引起：原发性损伤机制 ( 即刻的机械性损伤 ) 和继发性损伤机制 ( 由血管、细胞和生化事件改变引发的一系列级联瀑布反应 )[10-14]。

原发性损伤指即刻的机械物理性损伤，以脊髓内微脉管系统、神经细胞损伤坏死以及轴突断裂为特征，具体表现为血管痉挛、脊髓内微血管破裂致灰白质内出血、实质细胞出血性坏死、白质水肿、轴突的断裂以及凝血因子和血管活性胺的释放等，其可导致血栓形成，加重血管痉挛，进一步引起脊髓组织缺氧、坏死，引起继发性损伤[10]。而原发性损伤的机械物理学机制可分为 4 种类型：( 1 ) 挤压 / 挫伤型；( 2 ) 牵张型；( 3 ) 撕裂或横断型；( 4 )剪切型[15]。

继发性损伤是指在原发损伤基础上，主要是由原发性水肿的扩展，激发一系列细胞和分子机制，触发细胞坏死和凋亡等系列效应，最终造成了不可逆性的损伤，包括局部缺血、谷氨酸受体过度激活、脂质过氧化作用、钙离子超载等，导致残存或未完全损伤的神经细胞继续破坏死亡[11,16]。原发性损伤发生在损伤即刻，是不可逆的；而继发性损伤是一种细胞分子水平的主动调节过程，具有可逆性和可控性[17]。脊髓损伤后的继发性变化是非常复杂的，由多种机制混合而成，它们之间相互作用、相互影响。

二、脊髓损伤的分期

根据脊髓损伤后的病理生理学改变，其发生发展过程被分为五期：

1. 速发期 ( immediate phase )：为原发损伤后 2 h 内[18]。其特点是原发机械性损伤导致脊髓实质内血管破裂，灰质和白质内出血、水肿[11,19]；血肿进一步加重局部缺血和神经元及胶质细胞死亡[15,20]。轴突发生创伤性断裂、水肿。创伤导致脊髓内的小胶质细胞活化，同时细胞膜的破坏导致离子平衡紊乱、大量细胞基质和细胞因子释放，如白介素-1 ( IL-1β )、白介素-6 ( IL-6 ) 和肿瘤坏死因子-α等[21-24]。局部缺血低氧增加神经元和胶质细胞对谷氨酸盐的敏感性，导致兴奋期延长，神经细胞坏死[25-30]。神经元细胞破坏，释放出的促炎性细胞因子进入脊髓损伤区域，预示速发期的终结。

2. 急性早期 ( early acute phase )：为损伤后 2～48 h。其特点为脊髓持续出血和坏死；血管和细胞水肿；自由基产生，尤其是氧自由基和活性氧簇 ( ROS )，导致脂质过氧化[31-33]；谷氨酸兴奋性毒性作用[27-30,34]；血－脑屏障破坏，通透性增加[23,35]；嗜中性粒细胞、单核－巨噬细胞、淋巴细胞等浸润，导致炎症反应更明显；少突胶质细胞死亡，导致早期的脱髓鞘作用[21-24]；轴突水肿加重；并发全身系统事件，如休克、脊髓休克、低血压和组织缺氧等[10-11,36-37]。这个时期自由基的产生和谷氨酸兴奋性毒性作用达到高峰。

3. 亚急性期 ( subacute phase )：紧随在急性期之后，为损伤后 2 天至 2 周。其特点为脊髓损伤区域巨噬细胞浸润加重，吞噬清理坏死组织，另外损伤区域星形胶质细胞增生、活化为反应性星形胶质细胞，形成胶质瘢痕，重建障血－脑屏障和恢复离子平衡[23,38-39]。星形胶质瘢痕不仅阻止巨噬细胞和中性粒细胞的进一步浸润，而且可以减少组织水肿。另一方面，星形胶质瘢痕同时也抑制了神经元轴突的再生。

4. 中期 ( intermediate phase )：为损伤后 2 周至 6 个月。其特点为胶质瘢痕继续形成，脊髓内空洞囊腔形成，脊髓损伤区域趋于稳定[40-41]。在可能存活的地方持续的轴突再生，同时胶质瘢痕也在生长和成熟[41]。

5. 慢性期 ( chronic / late phase )：开始于伤后 6 个月，可能持续到 1～2 年。其特点为持久的瓦勒氏变性( Wallerian degeneration ) 出现，伴随胶质瘢痕最终成熟、轴突脱髓鞘病变、脊髓囊性空洞形成以及残存脊髓组织的结构和功能重塑[40,42-44]。脊髓损伤最终病变特点表现为脊髓软化坏死和囊性空洞形成。

然而，相对于基础病理生理学研究，临床上的急性期( acute phase ) 通常被定义为受伤后的 4～5 周[45]。

三、硬膜囊内减压的必要性与机制

TSCI 的治疗策略包括手术、药物、细胞疗法、组织工程和再生修复等[46]。手术疗法的目的主要是用于脊髓减压，此外还用于维持脊柱正常序列和稳定性。然而，手术去除骨组织和韧带的硬脊膜外减压并不能解除脊髓实质内的血肿和肿胀，而这也是脊髓创伤后导致硬膜囊完整患者中髓内压力增高、脊髓局部缺血和缺氧加重的原因。迄今为止，虽然研究脊髓损伤治疗的药物疗法、细胞疗法，乃至组织工程修复等方法种类繁多，但尚未形成治疗脊髓损伤的诊疗标准或指南。

1911 年，Allen[47]利用犬类的脊髓损伤模型，证明了脊髓背部纵向切口可以改善脊髓的运动功能和结构。此后，大量的实验研究和临床研究结果也证明硬膜内减压在治疗脊髓损伤中的作用，可以改善脊髓损伤后的功能恢复，降低脊髓损伤后的继发性损伤[47-60]。

1988 年，Perkins 和 Deane[51]对 6 例急性脊髓损伤患者采用了硬脊膜切开方式进行硬膜囊内减压，术中见硬膜囊正常搏动消失，硬脊膜表面静脉充盈；硬脊膜纵行切开后，可见脑脊液自硬膜囊内以约 15 mm Hg ( 1 mm Hg＝0.133 kPa ) 的压力“射”出；术后随访 4～5 年，患者神经功能 ASIA 分级获得明显改善。作者认为，急性脊髓损伤后的组织水肿限制了正常的脑脊液循环和动脉灌注，加重硬脊膜内的压力，最终引起类似“骨筋膜室综合征”的“脊髓筋膜室综合征”，这一结果被认为是硬脊膜切开减压阻断继发性损害的有力措施。

1989 年，日本学者 Koyanagi 等[58]对 4 例急性颈脊髓损伤患者采用脊髓切开的方式进行硬膜囊内减压，术后患者上肢运动功能均有所恢复，感觉障碍有一定程度的减退。

Zhu 等[49]对 30 例急性完全性脊髓损伤的患者 ( ASIA A 级 ) 采用硬脊膜切开、蛛网膜下腔松解和脊髓切开的方式进行硬膜囊内减压治疗，术后所有患者均获得一定的步行功能，其中 43% 的患者 ( 13 例 ) 可借助拐杖、手杖或不需要任何支撑行走，40% 的患者 ( 12 例 ) 可在轮式步行练习器的辅助下行走。

外科手术减压在脊髓损伤功能恢复中具有重要作用[61-63]。TSCI 发生时，脊髓受到硬膜外骨折碎片、脊髓剪切力等原发性损伤和硬膜内脊髓水肿、血肿等继发性损伤作用，同时受到骨性椎管和硬脊膜囊限制，导致脊髓内、外同时受压，引起髓内压力增高，使硬膜囊或蛛网膜下腔狭窄粘连、脑脊液阻断、动静脉阻塞，进而促使局部缺血、缺氧和加重继发性损伤，而缺血缺氧反过来又加重水肿蔓延、血肿坏死以及髓内高压，形成恶性循环。因此，硬膜囊内减压可减轻受伤脊髓节段水肿或血肿引起的硬膜内压力，清除病灶部位的出血、坏死的组织，进而增加脊髓的血流灌注，减轻缺血，减少炎性介质持续对脊髓的刺激，阻断或终止脊髓的继发性损伤过程，为脊髓的神经恢复、再生创造一个良好的微环境[49,51,64]。国内鞠躬院士认为，硬脊膜内减压能够终止继发性脊髓损伤，而解除压迫也有利于残余神经的恢复[65-67]。亦有研究认为，脊髓损伤处的软化病灶或出血具有占位性病变的损伤效果，可持续性压迫其周围正常神经组织；清除病灶或出血可减轻周围神经组织的压迫，改变正常组织中神经元及轴突生存的微环境，恢复脊髓血流灌注，有利于残存神经组织的功能恢复[49,68-69]。

四、硬膜囊内减压的手术时机

尽管许多基础研究结果表明，脊髓减压能够明显改善神经功能，降低继发性损伤，但对于手术时机还存在不同的意见。Batchelor 等[70]荟萃分析结果提示，伤后 12 h 内减压可以获得稳定受益，而在伤后 12～24 h 内减压，其受益较少。最近的临床研究亦提示，伤后 24 h 内减压可使 15%～20% 的患者获得稳定受益，而超过 24 h 后的减压效果不甚明显，也有学者认为在脊髓休克期过后再行手术[62,68,71-76]。Fehlings 等[77]学者基于手术减压时间的研究认为，早期减压 ( ＜24 h 或＜72 h ) 可以促进脊髓损伤后的功能恢复，具有统计学意义。La Rosa 等[78]Meta 荟萃分析结果证实，与保守治疗和延期 ( 晚期 ) 手术减压 ( ＞24 h )相比，24 h 内手术减压可使脊髓损伤的患者的 ASIA 分级得到显著改善。Fehlings 和 Perrin[79]检索了 1966～2004 年间 Medline 所收录的关于脊髓损伤的文献进行回顾分析，研究发现“早期减压对脊髓损伤治疗有效”的文献数量要较“治疗结果无效或消极”的文献数量多，进一步说明早期减压有益于脊髓损伤的功能恢复。尽管支持尽早手术的研究占多数，但缺乏充分的证据证明早期手术的益处，手术是否存在时间窗还存在很多的争议；而且急诊来院患者往往处于应激状态，需要调节全身状况，防止术中、术后并发症，因此不一定适合急诊手术，应选择最佳手术时机。

笔者认为脊髓损伤后应积极手术，不放弃任何能够减轻患者伤残程度、降低致残率的微小机会。最好于伤后24 h 内行手术减压治疗，由于各种原因不能早期手术时，可在伤后 2 个月内，最迟也不要晚于伤后 12 个月手术，因为到达脊髓恢复平台期 ( 停滞不前 ) 中位时间为 1.8 个月。而当脊髓恢复到达平台期 ( 停滞不前 )，但影像学显示仍有脊髓受压时，亦应行手术治疗[80-81]。

目前，开展针对手术干预治疗脊髓损伤的临床与实验研究，尤其侧重于手术减压的时机、最佳的减压组合方式( 椎板切除的硬膜囊外骨性减压、硬脊膜切开或脊髓切开的硬膜囊内减压 ) 以及是否联合药物辅助疗法，为将来研究脊髓损伤治疗的策略、模式提供了潜在、有效的方向。硬膜囊内减压可释放硬脊膜等膜结构对脊髓组织的约束，清除血肿和坏死组织，减轻受伤脊髓的压迫，降低硬膜囊内压，促进脊髓的血流灌注，减少脊髓组织缺血、缺氧，减少或抑制继发性损伤的蔓延，防止细胞的进一步坏死，保存残余的脊髓组织，促进神经功能的恢复。未来，利用动物模型及临床试验，研究外科手术减压的时间窗、最佳的减压方式，以及减压对受伤脊髓节段继发的炎症、瘢痕形成的影响及其组织学和神经学结果，具有良好的前景。

[1] Barker RN, Kendall MD, Amsters DI, et al. The relationship between quality of life and disability across the lifespan for people with spinal cord injury. Spinal Cord, 2009, 47(2): 149-155.

[2] Hagen EM, Lie SA, Rekand T, et al. Mortality after traumatic spinal cord injury: 50 years of follow-up. J Neurol Neurosurg Psychiatry, 2010, 81(4):368-373.

[3] Furlan JC, Sakakibara BM, Miller WC, et al. Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci, 2013, 40(4):456-464.

[4] Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma, 2004, 21(10): 1355-1370.

[5] Wilson JR, Forgione N, Fehlings MG. Emerging Therapies for acute traumatic spinal cord injury. CMAJ, 2013, 185(6):485-492.

[6] Hall ED, Braughler JM. Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale. Surg Neurol, 1982, 18(5):320-327.

[7] Nagata S, Golstein P. The Fas death factor. Science, 1995, 267(5203):1449-1456.

[8] Juurlink BH, Paterson PG. Review of oxidative stress in brain and spinal cord injury: suggestions for pharmacological and nutritional management strategies. J Spinal Cord Med, 1998, 21(4):309-334.

[9] Park E, Velumian AA, Fehlings MG. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma, 2004, 21(6):754-774.

[10] Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg, 1991, 75(1):15-26.

[11] Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg, 1997, 86(3):483-492.

[12] Ray SK, Dixon CE, Banik NL. Molecular mechanisms in the pathogenesis of traumatic brain inury. Histol Histopathol, 2002, 17(4):1137-1152.

[13] Rossignol S, Schwab M, Schwartz M, et al. Spinal cord injury: time to move? J Neurosci, 2007, 27(44):11782-11792.

[14] Rowland JW, Hawryluk GW, Kwon B, et al. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus, 2008, 25(5):E2.

[15] Baptiste DC, Fehlings MG. Pharmacological approaches to repair the injured spinal cord. J Neurotrauma, 2006, 23(3-4): 318-334.

[16] Silva NA, Sousa N, Reis RL, et al. From basics to clinical: a comprehensive review on spinal cord injury. Prog Neurobiol, 2014, 114(1):25-57.

[17] Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA, 1997, 277(20):1597-1604.

[18] Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma, 2004, 21(4):429-440.

[19] Kakulas BA. Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord, 2004, 42(10):549-563.

[20] Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine, 2001, 26(24 Suppl):S2-12.

[21] Klusman I, Schwab ME. Effects of pro-inflammatory cytokines in experimental spinal cord injury. Brain Res, 1997, 762(1-2): 173-184.

[22] Pineau I, Lacroix S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol, 2007, 500(2):267-285.

[23] Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol, 2007, 209(2):378-388.

[24] Fleming JC, Norenberg MD, Ramsay DA, et al. The cellularinflammatory response in human spinal cords after injury. Brain, 2006, 129(Pt 12):3249-3269.

[25] Agrawal SK, Fehlings MG. Mechanisms of secondary injury to spinal cord axons in vitro: role of Na+, Na(+)-K(+)-ATPase, the Na(+)-H+ exchanger, and the Na(+)-Ca++ exchanger. J Neurosci, 1996, 16(2):545-552.

[26] Young W, Koreh I. Potassium and calcium changes in injured spinal cords. Brain Res, 1986, 365(1):42-53.

[27] Farooque M, Hillered L, Holtz A, et al. Changes of extracellular levels of amino acids after graded compression trauma to the spinal cord: an experimental study in the rat using microdialysis. J Neurotrauma, 1996, 13(9):537-548.

[28] Liu D, Xu GY, Pan E, et al. Neurotoxicity of glutamate at the concentration released upon spinal cord injury. Neuroscience, 1999, 93(4):1383-1389.

[29] McAdoo DJ, Xu GY, Robak G, et al. Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord. Exp Neurol, 1999, 159(2):538-544.

[30] Xu W, Chi L, Xu R, et al. Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. J Spine Cord, 2005, 43(4):204-213.

[31] Means ED, Anderson DK. Neuronophagia by leukocytes in experimental spinal cord injury. J Neuropathol Exp Neurol, 1983, 42(6):707-719.

[32] Mabon PJ, Weaver LC, Dekaban GA. Inhibition of monocyte/ macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol, 2000, 166(1):52-64.

[33] Taoka Y, Okajima K, Uchiba M, et al. Role of neutrophils in spinal cord injury in the rat. Neuroscience, 1997, 79(4): 1177-1182.

[34] Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med, 1994, 330(9):613-622.

[35] Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res, 1989, 482(1):57-66.

[36] Kwon BK, Tetzlaff W, Grauer JN, et al. Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J, 2004, 4(4):451-464.

[37] Ditunno JF, Little JW, Tessler A, et al. Spinal shock revisited: a four-phase model. Spinal Cord, 2004, 42(7):383-395.

[38] Hagg T, Oudega M. Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma, 2006, 23(3-4):264-280.

[39] Karimi-Abdolrezaee S, Eftekharpour E, Wang J, et al. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci, 2006, 26(13):3377-3389.

[40] Rowland JW, Hawryluk GW, Kwon B, et al. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus, 2008, 25(5):E2.

[41] Hill CE, Beattie MS, Bresnahan JC. Degeneration and sprouting of identified descending supraspinal axons after contusive spinal cord injury in the rat. Exp Neurol, 2001, 171(1):153-169.

[42] Beattie MS, Hermann GE, Rogers RC, et al. Cell death in models of spinal cord injury. Prog Brain Res, 2002, 137:37-47. [43] Coleman MP, Perry VH. Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurosci, 2002, 25(10):532-537.

[44] Ehlers MD. Deconstructing the axon: Wallerian degeneration and the ubiquitin-proteasome system. Trends Neurosci, 2004, 27(1):3-6.

[45] Hagen EM. Acute complications of spinal cord injuries. World J Orthop, 2015, 6(1):17-23.

[46] Silva NA, Sousa N, Reis RL, et al. From basics to clinical: a comprehensive review on spinal cord injury. Prog Neurobiol, 2014, 114(1):25-57.

[47] Allen A. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. JAMA, 1911, 2(11):878-880.

[48] Smith JS, Anderson R, Pham T, et al. Role of early surgical decompression of the intradural space after cervical spinal cord injury in an animal model. J Bone Joint Surg Am, 2010, 92(5): 1206-1214.

[49] Zhu H, Feng YP, Young W, et al. Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases. Chin Med J (Engl), 2008, 121(24):2473-2478.

[50] Kalderon N, Muruganandham M, Koutcher JA, et al. Therapeutic strategy for acute spinal cord contusion injury: cell elimination combined with microsurgical intervention. PLos One, 2007, 2(6):e565.

[51] Perkins PG, Deane RH. Long-term follow-up of six patients with acute spinal injury following dural decompression. Injury, 1988, 19(6):397-401.

[52] Brodkey JS, Richards DE, Blasingame JP, et al. Reversible spinal cord trauma in cats. Additive effects of direct pressure and ischemia. J Neurosurg, 1972, 37(5):591-593.

[53] Rivlin AS, Tator CH. Effect of vasodilators and myelotomy on recovery after acute spinal cord injury in rats. J Neurosurg, 1979, 50(3):349-352.

[54] Freeman LW, Wright TW. Experimental observations of concussion and contusion of the spinal cord. Ann Surg, 1953, 137(4):433-443.

[55] Carlson GD, Minato Y, Okada A, et al. Early time-dependent decompression for spinal cord injury: vascular mechanisms of recovery. J Neurotrauma, 1997, 14(12):951-962.

[56] Dimar JR 2nd, Glassman SD, Raque GH, et al. The influenceof spinal canal narrowing and timing of decompression on neurologic recovery after spinal cord contusion in a rat model. Spine, 1999, 24(16):1623-1633.

[57] Dolan EJ, Tator CH, Endrenyi L. The value of decompression for acute experimental spinal cord compression injury. J Neurosurg, 1980, 53(6):749-755.

[58] Koyanagi I, Iwasaki Y, Isu T, et al. Myelotomy for acute cervical cord injury. Report of four cases. Neurol Med Chir (Tokyo), 1989, 29(4):302-306.

[59] Iwasaki Y, Ito T, Isu T, et al. Effect of combined treatment of mannitol and myelotomy on experimental spinal cord injury (author’s transl). Neurol Med Chir (Tokyo), 1981, 21(9): 917-921.

[60] Iwasaki Y, Ito T, Isu T, et al. Effects of pial incision and steroid administration on experimental spinal cord injury (author’s transl). Neurol Med Chir (Tokyo), 1980, 20(9):965-970.

[61] Fehlings MG, Arvin B. The timing of surgery in patients with central spinal cord injury. J Neurosurg Spine, 2009, 10(1):1-2.

[62] Fehlings MG, Vaccaro A, Wilson JR, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLos ONE, 2012, 7(2):e32037.

[63] Wilson JR, Singh A, Craven C, et al. Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal Cord, 2012, 50(11):840-843.

[64] Soubeyrand M, Laemmel E, Court C, et al. Rat model of spinal cord injury preserving dura mater integrity and allowing measurements of cerebrospinal fluid pressure and spinal cord blood flow. Eur Spine J, 2013, 22(8):1810-1819.

[65] Shi M, You SW, Meng JH, et al. Direct protection of inosine on PC12 cells against zinc-induced injury. Neuroreport, 2002, 13(4):477-479.

[66] 张欲凯, 沈学锋, 贾利云, 等. 脊髓损伤后即刻清除出血对脊髓修复的影响. 神经解剖学杂志, 2009, 25(2):115-120.

[67] 阳刚, 张朝跃. 髓内病灶清除减压术对脊髓损伤的疗效分析.骨科, 2010, 1(1):40-42.

[68] Li Y, Walker CL, Zhang YP, et al. Surgical decompression in acute spinal cord injury: A review of clinical evidence, animal model studies, and potential future directions of investigation. Front Biol (Beijing), 2014, 9(2):127-136.

[69] 张少成, 修先论, 李全华, 等. 截瘫后下肢神经病理改变的初步研究. 第二军医大学学报, 1999, 20(9):684-685.

[70] Batchelor PE, Wills TE, Skeers P, et al. Meta-analysis of preclinical studies of early decompression in acute spinal cord injury: a battle of time and pressure. PLoS One, 2013, 8(8): e72659.

[71] Fehlings MG, Tator CH. An evidence-based review of decompressive surgery in acute spinal cord injury: rationale, indications, and timing based on experimental and clinical studies. J Neurosurg, 1999, 91(1 Suppl):1-11.

[72] Fehlings MG, Sekhon LH, Tator C. The role and timing of decompression in acute spinal cord injury: what do we know? What should we do? Spine, 2001, 26(24 Suppl):S101-110.

[73] Jazayeri SB, Firouzi M, Abdollah Zadegan S, et al. The effect of timing of decompression on neurologic recovery and histopathologic findings after spinal cord compression in a rat model. Acta Med Iran, 2013, 51(7):431-437.

[74] Furlan JC, Noonan V, Cadotte DW, et al. Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma, 2011, 28(8):1371-1399.

[75] van Middendorp JJ, Barbagallo G, Schuetz M, et al. Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study. Spinal Cord, 2012, 50(9):686-694.

[76] Gupta DK, Vaghani G, Siddiqui S, et al. Early versus delayed decompression in acute subaxial cervical spinal cord injury: A prospective outcome study at a Level I trauma center from India. Asian J Neurosurg, 2015, 10(3):158-165.

[77] Fehlings MG, Perrin RG. The timing of surgical intervention in the treatment of spinal cord injury: a systematic review of recent clinical evidence. Spine, 2006, 31(11 Suppl):S28-35.

[78] La Rosa G, Conti A, Cardali S, et al. Does early decompression improve neurological outcome of spinal cord injured patients? Appraisal of the literature using a meta-analytical approach. Spinal Cord, 2004, 42(9):503-512.

[79] Fehlings MG, Perrin RG. The role and timing of early decompression for cervical spinal cord injury: update with a review of recent clinical evidence. Injury, 2005, 36(Suppl 2): B13-26.

[80] Carlson GD, Minato Y, Okada A, et al. Early time-dependent decompression for spinal cord injury: vascular mechanisms of recovery. J Neurotrauma, 1997, 14(12):951-962.

[81] McKinley W, Meade MA, Kirshblum S, et al. Outcomes of early surgical management versus late or no surgical intervention after acute spinal cord injury. Arch Phys Med Rehabil, 2004, 85(11):1818-1825.

( 本文编辑：王萌 )

Research progress on intra-dural decompression for traumatic spinal cord injury

LIANG Bing, DONG Jian, TANG Jia-guang. Department of Orthopaedics, Zhongshan Hospital of Fudan University, Shanghai, 200032, PRC Corresponding author: TANG Jia-guang, Email: tangjiaguang2013@163.com

Traumatic spinal cord injury ( TSCI ) consists of primary spinal cord injury and secondary spinal cord injury, with a high morbidity and disability rate globally. Primary spinal cord injury occurs at the time of theinjury, which is an irreversible process. And it cannot be improved. Following the primary injury, secondary injury is a kind of molecular and cellular level of active adjustment process. It is reversible and controllable. Currently, the treatment options for spinal cord injury ( SCI ) include pharmacological agents, surgical intervention, cellular therapies and rehabilitative care. Nonetheless, SCI is still a harmful condition for which there is yet no cure. None of pharmacologic therapies have become the standard of care. Nevertheless, recent clinical and basic science research has shown surgical decompression is a potentially valuable modality for the treatment of SCI. This review provides an overview of research progress on intra-dural decompression for SCI, covering areas from pathophysiology and phases to the role and timing of surgical decompression.

Spinal cord injuries; Pathologic processes; Decompression, surgical; Therapeutics

10.3969/j.issn.2095-252X.2016.11.012

R683.2

200032 上海，复旦大学附属中山医院骨科 ( 梁兵、董健 )；100048 北京，解放军总医院第一附属医院骨科( 梁兵、唐家广 )

唐家广，Email: tangjiaguang2013@163.com

2016-08-31 )