Locomotor training after human spinal cord injury: a series of case studies

Many individuals with spinal cord injury (SCI) do not regain their ability to walk, even though it is a primary goal of rehabilitation. Mammals with thoracic spinal cord transection can relearn to step with their hind limbs on a treadmill when trained with sensory input associated with stepping. If humans have similar neural mechanisms for locomotion, then providing comparable training may promote locomotor recovery after SCI. We used locomotor training designed to provide sensory information associated with locomotion to improve stepping and walking in adults after SCI. Four adults with SCIs, with a mean postinjury time of 6 months, received locomotor training. Based on the American Spinal Injury Association (ASIA) Impairment Scale and neurological classification standards, subject 1 had a T5 injury classified as ASIA A, subject 2 had a T5 injury classified as ASIA C, subject 3 had a C6 injury classified as ASIA D, and subject 4 had a T9 injury classified as ASIA D. All subjects improved their stepping on a treadmill. One subject achieved overground walking, and 2 subjects improved their overground walking. Locomotor training using the response of the human spinal cord to sensory information related to locomotion may improve the potential recovery of walking after SCI.     

Is the recovery of stepping following spinal cord injury mediated by modifying existing neural pathways or by generating new pathways? A perspective.

The recovery of stepping ability following a spinal cord injury may be achieved by restoring anatomical connectivity within the spinal cord. However, studies of locomotor recovery in animals with complete spinal cord transection suggest that the adult mammalian spinal cord can acquire the ability to generate stepping after all descending input is eliminated and in the absence of neuronal regeneration. Moreover, rehabilitative gait training has been shown to play a crucial role in teaching existing spinal pathways to generate locomotion and appropriately respond to sensory feedback. This brief review presents evidence that neural networks in the mammalian spinal cord can be modulated pharmacologically and/or with task-specific behavioral training to generate weight-bearing stepping after a spinal injury. Further, the role that spinal learning can play in the management of humans with spinal cord injury is discussed in relation to interventions that are designed primarily to enhance neuronal regeneration.     

Physical rehabilitation as an agent for recovery after spinal cord injury

The initial level of injury and severity of volitional motor and clinically detectable sensory impairment has been considered the most reliable for predicting neurologic recovery of function after spinal cord injury (SCI). This consensus implies a limited expectation for physical rehabilitation interventions as important in the facilitation of recovery of function. The development of pharmacologic and surgical interventions has always been pursued with the intent of altering the expected trajectory of recovery after SCI, but only recently physical rehabilitation strategies have been considered to improve recovery beyond the initial prognosis. This article reviews the recent literature reporting emerging activity-based therapies that target recovery of standing and walking based on activity-dependent neuroplasticity. A classification scheme for physical rehabilitation interventions is also discussed to aid clinical decision making.     

A new age for rehabilitation

In this review we will describe newly developed techniques that are being used to recover levels of motor function after a severe spinal cord injury that have not been observed previously. These new approaches include pharmacological neuromodulation and/or epidural stimulation of the spinal cord circuitries in combination with motor training. By combining the increased levels of excitability of the interneuronal spinal circuitries using these interventions and the ability of the spinal circuitries to interpret and respond appropriately to ongoing complex ensembles of sensory input, the peripheral sensory system can become an effective source for the control of motor function. Similar types of neuromodulation have been shown to enable the brain to regain functional connectivity with the spinal cord circuitries below a clinically complete spinal cord lesion. In fact, some level of voluntary control of movement has been observed in subjects with complete paralysis in the presence of epidural stimulation. The biological mechanisms thought to underlie the recovery of motor function after a severe spinal cord injury are based on decades of research on a wide range of animal models. Fortunately the extensive conservation of neural mechanisms of motor control has provided a window for gaining considerable insight into the mechanisms of recovery of motor function in humans.     

间充质干细胞移植治疗脊髓损伤患者的疗效分析

目的:探讨间充质干细胞(MSCs)移植治疗脊髓损伤的临床疗效。方法:对23例脊髓损伤患者在腰椎穿刺方式下分别行骨髓MSCs或脐血MSCs移植术,术前和术后均进行安全性指标评价,干细胞移植前和移植3个月后分别进行美国脊髓损伤学会损伤分级评分。结果:所有患者干细胞治疗前后安全性指标评价差异无显著性意义(P>0.05),未出现严重的不良反应,同时不完全脊髓损伤患者行干细胞移植3个月后在运动功能、轻触觉及针刺觉方面均有明显改善(P<0.05),而完全性脊髓损伤患者则在轻触觉及针刺觉方面有改善(P<0.05),运动功能未见明显进步(P>0.05),同时骨髓MSCs移植的患者3个月后运动功能的改善优于脐血MSCs移植的患者。结论:MSCs移植治疗可以改善脊髓损伤患者的感觉功能,但不完全脊髓损伤患者运动功能的恢复优于完全性脊髓损伤患者,同时骨髓MSCs移植的患者运动功能的改善优于脐血MSCs移植的患者。     

综合康复治疗对脊髓损伤患者运动功能及日常生活能力的影响

目的探讨综合康复治疗对脊髓损伤后运动功能恢复的影响。方法采用中药、针灸、按摩、脉冲电场刺激和PT、OT康复训练等综合治疗方法对58例脊髓损伤患者进行康复治疗,以FIM功能独立测量方法进行治疗前后的功能评定。结果58例脊髓损伤患者的运动功能ADL能力方面在治疗后得到显著改善,与治疗前相比,差异有非常显著性(P<0.005)。结论脊髓损伤患者进行综合康复治疗能明显地改善运动功能,提高日常生活能力。     

脊髓3/4横断伤动物模型的建立及其电生理评价

背景：建立稳定、标准的脊髓损伤动物模型是研究脊髓损伤修复的前提。目的：建立一种实用、标准、可靠的急性大鼠脊髓损伤模型。方法：将60只成年雌性Wistar大鼠随机均分成两组。脊髓损伤组：打开T8胸椎对应脊髓,剪开硬膜,用特殊设计的眼科维纳斯剪横跨脊髓背侧中线剪断脊髓的后3/4,深度1.5mm。1h后行感觉诱发电位和运动诱发电位检查。对照组：只打开椎板,剪开硬膜,暴露脊髓进行假手术。结果与结论：造模成功率为100%。对照组造模后1周功能恢复接近正常;脊髓损伤组造模后第2周开始恢复,到第4周基本停止,最终运动功能评分未超过10分,两组比较差异有显著性意义。脊髓损伤组可以明显看到感觉诱发电位与运动诱发电位的波幅值急剧降低,且潜伏期明显延长,差异有显著性意义（P〈0.01）。说明3/4横断伤急性大鼠脊髓损伤模型制作法操作简便、重复性好,是研究脊髓再生修复的理想模型。     

脊髓3/4横断伤动物模型的建立及其电生理评价

背景:建立稳定、标准的脊髓损伤动物模型是研究脊髓损伤修复的前提.目的:建立一种实用、标准、可靠的急性大鼠脊髓损伤模型.方法:将60只成年雌性Wistar大鼠随机均分成两组.脊髓损伤组:打开T8胸椎对应脊髓,剪开硬膜,用特殊设计的眼科维纳斯剪横跨脊髓背侧中线剪断脊髓的后3/4,深度1.5 mm.1 h后行感觉诱发电位和运动诱发电位检查.对照组:只打开椎板,剪开硬膜,暴露脊髓进行假手术.结果与结论:造模成功率为100%.对照组造模后1周功能恢复接近正常;脊髓损伤组造模后第2周开始恢复,到第4周基本停止,最终运动功能评分未超过10分,两组比较差异有显著性意义.脊髓损伤组可以明显看到感觉诱发电位与运动诱发电位的波幅值急剧降低,且潜伏期明显延长,差异有显著性意义(P < 0.01).说明3/4横断伤急性大鼠脊髓损伤模型制作法操作简便、重复性好,是研究脊髓再生修复的理想模型.     

超短波对急性脊髓损伤大鼠神经功能及BDNF-TrkB表达的影响

目的:观察无热量超短波对急性脊髓损伤大鼠神经功能恢复和BDNF-TrkB表达的影响,并探讨其可能作用机制。方法:成年雌性SD大鼠72只,随机分为Sham组(24只)、SCI组(24只)和USW组(24只)。应用改良Allen法制备大鼠脊髓损伤模型。Sham组仅行椎板切除术暴露硬脊膜,不予打击,直接缝合,术后不给予任何治疗。USW组在脊髓损伤造模后24h给予受损部位无热量超短波治疗(最大输出功率40W,实际输出功率11.58W),10min/次,1次/d,至取材前。SCI组造模后不给予任何治疗。在造模后1d、7d、14d和21d用BBB评分、体感诱发电位(SEPs)和运动诱发电位(MEPs)评定脊髓损伤后后肢功能恢复情况并获取损伤段脊髓标本,术后4周取材,用免疫组织化学方法检测SCI组和USW组脊髓在损伤后不同时段BDNF及TrkB的表达,并行阳性细胞计数。结果:BBB评分结果提示,USW组大鼠7d、14d、21d时的运动功能恢复较SCI组明显提高(P0.01);SEPs和MEPs结果显示,USW组大鼠7d、14d、21d时的神经功能较SCI组明显改善(P0.05);免疫组织化学方法提示,与SCI组相比,USW组在一定时间段能上调损伤脊髓区BDNF-TrkB的表达(P0.05)。结论:无热量超短波能在一定程度上促进损伤脊髓的神经功能恢复,其机制可能与超短波上调损伤区脊髓BDNF-TrkB的表达有关。     

Incomplete spinal cord injury: neuronal mechanisms of motor recovery and hyperreflexia.

OBJECTIVE: To understand neuronal mechanisms of motor recovery and hyperreflexia after incomplete spinal cord injury (SCI), and their role in rehabilitation. DESIGN: Reviewed and compared clinical, neurophysiologic, and neuropathologic data from human SCI patients with behavioral, neurophysiologic, and neuroanatomic data from animals to postulate underlying neuronal mechanisms. OUTCOME: A postulation that two neuronal mechanisms-receptor up-regulation and synapse growth-act sequentially, to explain the gradual appearance of motor recovery after incomplete SCI. These same mechanisms may also act in spinal reflex pathways to mediate hyperreflexia caudal to SCI. RESULTS: After incomplete SCI, walking ability and hyperreflexia often develop. Initially, cord neurons are hyperpolarized and less excitable because of loss of normal descending facilitation; this is spinal shock. Then, gradually, voluntary movement recovers and hyperreflexia develops. Early (hours to days), these changes develop simultaneously, suggesting a common postsynaptic mechanism-likely, an increase in postsynaptic receptor excitability, possibly receptor up-regulation. Late (weeks to months), recovery and reflex changes occur at a slow rate, are no longer simultaneous, and are long-lasting, which suggests a presynaptic mechanism, such as local synapse growth in spared descending pathways and in reflex pathways. This presumed synapse growth is seemingly enhanced by active use of the growing pathway. Also, developing hyperreflexia appears to limit motor recovery. CONCLUSIONS: These observations suggest that rehabilitation for incomplete SCI should (1) increase activity in spared descending motor pathways, (2) initially use reflex facilitation or central nervous system stimulants to assist spared descending inputs in depolarizing cord neurons, and (3) later minimize reflex input, when spared descending inputs can depolarize cord neurons without reflex facilitation. Better understanding of neuronal mechanisms that underlie motor recovery after incomplete SCI promises better outcomes from rehabilitation.     

Current and future therapeutic strategies for functional repair of spinal cord injury

Spinal cord injury (SCI) is one of the major disabilities dealt with in clinical rehabilitation settings and is multifactorial in that the patients suffer from motor and sensory impairments as well as many other complications throughout their lifetimes. Many clinical trials have been documented during the last two decades to restore damaged spinal cords. However, only a few pharmacological therapies used in clinical settings which still have only limited effects on the regeneration and functional recovery. This review presents recent clinical trials and recent advances in the development of strategies to restore locomotion after SCI. Several approaches toward functional recovery in SCI succeeded in acute and subacute phases in animal models.However, effective strategies against chronic phase of SCI have not been established yet. The strategy aiming to inhibit single molecule sometimes shows controversial results. In SCI, a lot of players participate in motor and sensory dysfunctions. Therefore, sufficient functional recovery may be achieved by regulating multiple targets. Regrowth of tracts connecting the brain and spinal cord, and axonal sprouting of propriospinal interneurons are fundamentally important for neuronal network working. In addition, remyelination, protection of neuronal death, inhibition of inflammation, and upregulation of beneficial influence of astrocytes are also quite crucial to supporting the axonal refining. Combination of several strategies might be useful as practical therapy. Several compounds such as a Sema3A inhibitor, estrogen, withanoside IV and their relating compounds or other neurotrophic factor-mimicking agents may be candidates for useful SCI therapeutic drugs since those have multi-effects on damaged spinal cord.     

Neuroanatomical substrates of functional recovery after experimental spinal cord injury: implications of basic science research for human spinal cord injury

Human spinal cord injury (SCI) is a devastating condition that results in persistent motor deficits. Considerable basic and clinical research is directed at attenuating these deficits. Many basic scientists use animal models of SCI to (1) characterize lesion development, (2) determine the role of spared axons in recovery, and (3) develop therapeutic interventions based on these findings. In this article, current research is reviewed that indicates: (1) most individuals with SCI will have some sparing of white matter at the lesion epicenter even when the lesion appears clinically complete, (2) even minimal tissue sparing has a profound impact on segmental systems and recovery of function, and (3) facilitatory intervention such as weight bearing and locomotor training after SCI may be more effective than compensatory strategies at inducing neuroplasticity and motor recovery. Body weight supported treadmill step training is discussed as an example of new facilitatory interventions based on basic science research using animal models.     

Local delivery of FTY720 and NSCs on electrospun PLGA scaffolds improves functional recovery after spinal cord injury

Spinal cord injury (SCI) is a common issue in the clinic that causes severe motor and sensory dysfunction below the lesion level. FTY720, also known as fingolimod, has recently been reported to exert a positive effect on the recovery from a spinal cord injury. Through local delivery to the lesion site, FTY720 effectively integrates with biomaterials, and the systemic adverse effects are alleviated. However, the effects of the proper mass ratio of FTY720 in biomaterials on neural stem cell (NSC) proliferation and differentiation, as well as functional recovery after SCI, have not been thoroughly investigated. In our study, we fabricated electrospun poly (lactide-co-glycolide) (PLGA)/FTY720 scaffolds at different mass ratios (0.1%, 1%, and 10%) and characterized these scaffolds. The effects of electrospun PLGA/FTY720 scaffolds on NSC proliferation and differentiation were measured. Then, a rat model of spinal transection was established to investigate the effects of PLGA/FTY720 scaffolds loaded with NSCs. Notably, 1% PLGA/FTY720 scaffolds exerted the best effects on the proliferation and differentiation of NSCs and 10% PLGA/FTY720 was cytotoxic to NSCs. Based on the Basso, Beattie, and Bresnahan (BBB) score, HE staining and immunofluorescence staining, the PLGA/FTY720 scaffold loaded with NSCs effectively promoted the recovery of spinal cord function. Thus, FTY720 properly integrated with electrospun PLGA scaffolds, and electrospun PLGA/FTY720 scaffolds loaded with NSCs may have potential applications for SCI as a nerve implant.

Spinal cord injury (SCI) is a common issue in the clinic that causes severe motor and sensory dysfunction below the lesion level.     

下肢外骨骼机器人在重建不完全性脊髓损伤患者步行功能中的应用和研究进展

重建运动功能对不完全性脊髓损伤患者非常重要,主要取决于自身的恢复和有效的康复.康复工程学正努力研发用于辅助步行功能训练的下肢外骨骼机器人.过去10年中,用于重建步行功能训练的下肢外骨骼机器人已有了很大发展,本文综述用于恢复患者步行功能和治疗师评估运动康复疗效的一些新技术和应用.     

Transplantation treatment of spinal cord injury patients.

The minimally manipulated cells from fetal nervous and hemopoietic tissues (gestational age 16-22 weeks) were subarachnoidally implanted into 15 patients (18-52 years old) with severe consequences of traumatic spinal cord injury (SCI) at cervical or thoracic spine level. The times after SCI were from 1 month to 6 years. Each patient underwent from one to four cell transplantations (CT) with various time intervals. In 11 of 15 cases, CT was combined with an operative partial disruption of a connective tissue cyst and with implantation into a spinal cord lesion of a spinal cord fragment together with olfactory ensheathing cells. Before CT the patients showed complete motor and sensory function disorder consistent with a grade A of SCI according to Frankel classification. With CT treatment, six patients improved their neurological status from A to C grade of SCI, exhibiting incomplete restoration of both motor and sensory function. The status of other five CT-treated patients became consistent with SCI grade B and was characterized by appearance of contracting activity in some muscles and incomplete restoration of sensitivity. The remaining four patients did not exhibit any clinical improvements. No serious complications of CT were noted. The results suggest a clinical relevance of the CT-based approach to treating severe consequences of SCI.     

脊髓损伤恢复期运动治疗的临床分析

目的 分析脊髓损伤患者恢复期运动治疗的效果及相关因素。方法 对1998年7月－2001年9月在我院康复医学科运动治疗部门训练的18例脊髓损伤患者进行分析。结果 ASIA运动评分和MBI在训练后有显著提高（P＜0．01），ASIA感觉评分训练前后无差异；痉挛严重程度与损伤时年龄及病程有很好的正相关（P＜0．05）；病程与治疗前MBI有很好的正相关（P＜0．05），MBI与ASIA运动评分有很好的正相关（P＜0．05）；家属护理人数与患者损伤时年龄，病程和治疗前MBI有很好的负相关（P＜0．05）；ASIA运动平均效率为0．13，MBI平均效率为0．56。结论 随着损伤时间的延长，痉挛会逐步加重；运动治疗有助于提高脊髓损伤患者的运动功能；患者生活自理能力的提高，可减少家属护理人数，减轻家庭负担。     

脊髓损伤后大鼠行为学改变及早期腓肠肌的变化

目的探索脊髓损伤后大鼠行为学改变及早期腓肠肌变化。方法108 只Wistar 大鼠,其中38 只为假手术组(n=38),其余制作脊髓切除模型,分为损伤组(n=38)和康复训练组(n=32)。应用BBB 法评价大鼠脊髓损伤后不同时间点的行为学变化;通过免疫组织化学法观察腓肠肌的变化。结果康复训练组BBB 评分从术后3 周开始高于损伤组,但两组得分始终未超过10 分。Dystrophin 免疫荧光染色显示,脊髓损伤后损伤组和康复训练组腓肠肌肌纤维横截面积均减小,但康复训练组萎缩程度较轻。结论脊髓损伤后大鼠后肢运动功能可出现一定的自发性恢复,康复训练有利于脊髓损伤大鼠运动功能的恢复,并能减缓后肢肌肉萎缩。     

3. Rehabilitation outcomes

This self-directed learning module highlights rehabilitation outcomes in spinal cord injury (SCI). It is part of the chapter on SCI medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article focuses on the multiple concerns for functional recovery after SCI, chiefly, the potential for ambulation, upper-extremity recovery, options for functional neuromuscular stimulation (FNS), sexual activity, and optimal outcome after a metastatic lesion. Motor incomplete patients have a better prognosis for ambulation than persons with sensory incomplete injury. Positive predictors for ambulation, including pinprick and lower-extremity motor scores greater than 20, are discussed. Meaningful recovery can occur in the upper extremities for at least 1 year. FNS options have been developed to promote functional control of the upper extremities for persons with tetraplegia, phrenic pacing, and bladder continence. A critical component of an individual's expression of self is his/her sexuality; sexual function after SCI is described in detail, including options for treatment of erectile dysfunction and various birth control methods for women. Expectations for an appropriate rehabilitation stay for a person with metastatic SCI differ for an individual with traumatic SCI. Differences may include changing routine pathways and timelines to focus on patient-centered quality of life for transition to home.Overall Article Objective:To identify potential outcomes in ambulation, upper-extremity function, FNS, and sexual function after SCI and after metastatic cancer.     

神经营养素-3修复脊髓损伤的研究进展

脊髓损伤的修复是神经科学研究领域的一大难题,原因之一是损伤脊髓的再生能力极其有限。近年来大量实验证明神经营养素－3（NT－3）对脊髓损伤的再生修复具有至关重要的作用,其中又以其基因移植效果为佳。本文就NT－3对脊髓损伤的修复研究进展作一综述。     

外伤性脊髓损伤患者提高ADL能力所需住院康复治疗的时间

目的:探讨外伤性脊髓损伤(SCI)患者获取提高ADL能力较为合理的住院康复治疗时间。方法:观察28例外伤性SCI患者的康复过程,在康复治疗开始前及治疗后1、2、3、6和9个月时分别作出ADL评估,比较ADL得分情况及不同时间ADL能力提高的程度。结果:28例患者在经过3个月的住院康复治疗后,26例ADL评分获得显著提高,其中21例ADL能力获得提升,在随后6个月的治疗中,26例患者与治疗3个月时比较ADL评分无明显增高,ADL能力也未进一步提升。结论:外伤性SCI患者提高ADL能力合理的住院康复治疗时间应为3个月。