脊髓损伤研究进展

脊髓损伤研究进展,中国康复研究中心北京博爱医院脊柱脊髓外科 关 骅,脊髓损伤是可导致患者终生致残的灾难性损伤，完全性损伤至今尚无有效的治愈方法。长期以来，世界各国学者对此进行了大量基础与临床研究，在脊髓继发性损伤的预防、脊髓损伤功能康复、脊髓神经结构与功能的重建等方面取得了一定进展。,脊髓继发性损伤的预防,脊髓二次损伤的预防,伤后制动与固定手术固定与减压,长期以来认为早期减压有利于脊髓损伤的治疗效果，但缺乏临床证据支持。近来，STASCIS的多中心研究结果支持早期（伤后24小时内）减压治疗。Early decompression has long been believed to be beneficial for the treatment of SCI,although clinical evidence to support this belief has been lacking. STASCIS,a multicenter,randomized clinical trial,is addressing this issue.,脊髓损伤-外科治疗,临床与试验研究一直在探索减少脊髓继发性损伤的方法。现有许多关于脊髓损伤药物治疗的高价值的研究。Clinical and experimental studies have been conducted to determine mathods to reduce secondary SCI,and to search for effective treatment.There is a long list of high value research manuscripts in many different aspects of spinal cord medicine.（2011，Spinal Cord Vol 49：321）,继发性损伤的药物治疗,试验药物治疗,alterneuroinflammation (immunomodulator drugs such as minocycline or antibodies against leukocyte adhesion molecules)reduce free radical damage (glucocorticoids, iron chelators, and glutathione promoters) reduce excitotoxic damage to neurons (N-methyl-D-aspartate (NMDA) receptor antagonists)improve blood flow (opioid antagonists or calcium channel blockers) seal damaged membranes (surfactants)counter the effects of local ionic imbalances (sodium and calcium channel blocker)So far, none of these treatments have been useful for treating spinal cord injury.,Aubrey A. Webb, Sybil Ngan, J. David Fowler, Spinal cord injury I: A synopsis of the basic science, Can Vet J 2010;51:485492,Marsh等证明Reparixin在脊髓损伤动物模型急性期治疗中减轻了急性炎症，改善了运动功能。Marsh and Flemming demonstrated in an animal SCI model that acute treatment with Reparixin reduces acute inflammation and is associated with minor improvements in motor function and a significant reduction in the severity of autonomic dysreflexia.,对于甲基强的松龙的临床应用仍存在争论，且出现否定应用的证据。最近，动物试验结果显示，甲强龙联合放射疗法，可减少神经胶质增生，利于神经轴突再生，对脊髓损伤后神经功能恢复产生协同效应。The clinical use of MP continue to be controversial,with emerging evidence arguing against its use.Recently,the result of combined therapy of irradiation and MP in animal model,suggesting it has been effective for the regeneration of the axons of nerve cell by reducing gliosis and provide synergistic effects for nrurologic recovery after SCI.（Spine,2011,Vol 36:434）,临床药物治疗,GM1,脊髓损伤药物治疗动物实验评估分级,脊髓损伤功能康复,康复训练,动物实验与临床研究显示，康复训练可促进脊髓损伤后残留的功能改善。,脊髓损伤-康复治疗,近年来，硬膜外神经电刺激，康复机器人及脊髓损伤后功能重建等新的技术得以广泛应用。Recently,ESCS,Lokomat and functional reconstruction have been applied in rehabilitation program.,动物实验： 步行或踏车训练有助于动物肢体功能的恢复与中枢模式发生器（central pattern generators，CPGs）及脊髓记忆有关。 机制：训练可使脊髓运动神经元中GABA水平的提升，可促使轴突出芽生殖、轴突生长及神经重塑。Barriere G, Leblond H, Provencher J, Rossignol S. Prominent role of the spinal central pattern generator in the recovery of locomotion after partial spinal cord injuries. J Neurosci 2008;28:39763987.Tillakaratne NJ, de Leon RD, Hoang TX, et al. Use-dependent modulation of inhibitory capacity in the feline lumbar spinal cord. J Neurosci 2002;22:31303143.,临床研究： 多中心研究证实康复训练可改善脊髓损伤患者肢体功能。 最近研究显示机器人辅助步行训练（robotic-assisted gait training， RAGT ）可明显改善患者的运动功能，但与传统运动功能训练方法相比尚无是否存在显著差异仍需进一步多中心研究。,饮食疗法,动物实验： 研究显示脊髓损伤后的饮食控制（禁食/饥饿疗法）可促进神经功能的恢复。 病理基础：饮食控制可使神经损伤范围缩小并促进脊髓内神经元的出芽生殖。Plunet WT, Streijger F, Lam CK, et al. Dietary restriction started after spinal cord injury improves functional recovery. Exp Neurol 2008;213:2835.,功能性电刺激,功能性电刺激( functional electrical stimulation ,FES) 是使用电刺激的手段、用精确的刺激顺序和强度激活瘫痪或轻瘫的肌肉来帮助患者提高日常生活活动能力。 上肢表面FES系统 上肢经皮FES系统 上肢植入式FES系统 用于站立和行走的下肢表面刺激系统 用于站立和行走的混合刺激系统 带有植入电极的多通道刺激系统,脊髓神经结构与功能的重建,细胞移植,动物实验： 国内外对脊髓损伤区域及其邻近部位的细胞移植（干细胞、嗅鞘细胞、Schwann细胞）进行了大量研究。 干细胞移植是一种针对脊髓损伤的潜在有效治疗方法，但仍存在诸多风险。,中枢神经系统损伤后的细胞疗法研究近年来多有成功报告。在动物实验研究中脊髓损伤后应用骨髓间充质干细胞移植已显示有良好作用。Cell-based therapy for CNS injury has been reported in recent years,and transplantation of bone marrow stromal cells(BMSCs)has been shown to have beneficial effects after SCI in animal studies.,脊髓损伤,多种移植细胞导入治疗法已应用于脊髓损伤治疗的动物研究，但尚无最佳导入方法。Several methods to deliver therapeutic cells have been used for the treatment of SCI in animal studies.However the most appropriate administration method for clinical application has not been established.（Spine,2011,Vol 36:933）,脊髓损伤,脊髓损伤,Cell Delivery System,最近，动物实验显示导入磁场定向骨髓间充质干细胞可能是临床应用治疗SCI的有用方法。Animal study shows that cell delivery of magnetic targeting BMSC may be useful for clinical application in treatment of SCI. （Spine,2011,Vol 36:933）,脊髓损伤,来自ISCoS的警告：技术与伦理,骨髓间充质干细胞移植疗法在一些血液或免疫系统疾病的临床治疗中已获得成功，但至今在脊髓损伤临床治疗中并未证实有效。然而，在某些医院中仍在应用细胞移植治疗脊髓损伤患者。It is true that certain bone marrow-derived (hematopoietic)stem cells have been successfully used to treat some blood-borne and immunological disorders,but to date ,this has not been the case for embryonic stem cells or other adult stem cells in the treatment of SCI.Nevertheless,cell transplants into the injurd spinal cord are being offered by several clinics around the world.（Spinal Cord，2011，Vol 49：485）,有严重疾病的患者愿意接受任何可能带来恢复的治疗，甚至完全不了解其高昂的花费及潜在的危险。但是，伤害处于绝望中的人并从其渴望治疗的期愿中获取利益是不道德的。As with any serious medical condition,people are susceptible to claims promising recovery,even when the costs are high and potential risks are unknown.It is morally unacceptable to prey on desperate people and profit from their hope for a cure. （Spinal Cord，2011，Vol 49：485）,来自ISCoS的警告：技术与伦理,ISCoS并不否认细胞移植可能改善患者功能和生活质量，但认为治疗有效的证据必须来自严格规范的临床实验研究。ISCoS认为对接受实验性治疗收取费用是不合理的。ISCoS does not rule out the possibility that cellular transplants may improve function and quality of life for recipients,but insist that the proof of benefit from cell transplants must come from a valid clinical-trail program，and believes it is unethical to charge patients for experimental interventions. （Spinal Cord，2011，Vol 49：485）,来自ISCoS的警告：技术与伦理,脑机接口,脑机接口（brain-computer interface，BCI；或direct neural interface/brain-machine interface），是在人或动物脑（或者脑细胞的培养物）与外部设备间创建的直接连接通路。 A brain-computer interface (BCI) is a hardware and software communicationssystem that permits cerebral activity alone to control computers or external devices.,脑机接口的分类,侵入式脑机接口部分侵入式脑机接口非侵入式脑机接口,感觉型运动型,Luis Fernando Nicolas-Alonso , Jaime GomezGil, Brain Computer Interfaces, a Review,Sensors 2012, 12, 1211-1279,外骨骼,循证医学在脊髓损伤康复中的应用,循证医学的定义,循证医学是指慎重、准确和明智地应用现有的最好研究证据，同时结合临床医生的个人专业技能和多年临床经验，考虑患者的权利、价值和愿望，将三者完美地结合，对患者作出医疗决策。,Evidence-based medicine- the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The best medical practice relies upon the integration of individual clinical expertise,which includes proficiency and judgment from clinical practiceand experience, with the best external clinical evidence from systematic review . (Sackett et al., 1996).,循证医学定义,最佳证 据,临床医生 临床经验和技能,循证医学,患者的参与,经验医学与循证医学差异,循证医学对未来医学的影响,促进临床决策科学化，避免资源浪费；促进临床医师素质提高，有利于终身自我继续教育，紧跟科学发展水平；促进临床科学研究的发展；促进临床教学训练水平提高；有利于卫生行政决策科学化；有利于患者监督医疗，保障自身权利。,实施循证医学应具备的基本技能,（1）能提出临床问题;（2）能用计算机检索相关文献;（3）能解释证据，特别是对证据的研究方法进行评 价，批判性地阅读文献;（4）定量推理技能（统计学知识）;（5）能作临床决策分析。,循证医学证据的分级,按质量和可靠程度大体可分为以下五级(可靠性依此降低)：一级：多中心的RCT系统评价或Meta分析；二级：单个的大样本 RCT三级：有对