移植策略
已经在实验和临床情况下研究了神经和非神经胶质组织的移植。[62]Xu XM, Onifer SM. Transplantation-mediated strategies to promote axonal regeneration following spinal cord injury. Respir Physiol Neurobiol. 2009;169:171-182.http://www.ncbi.nlm.nih.gov/pubmed/19665611?tool=bestpractice.com[63]Baptiste DC, Fehlings MG. Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008;13:63-80.http://www.ncbi.nlm.nih.gov/pubmed/18321149?tool=bestpractice.com[64]Bauchet, L. Lonjon N, Perrin FE, et al. Strategies for spinal cord repair after injury: a review of the literature and information. Ann Phys Rehabil Med. 2009;52:330-351.http://www.ncbi.nlm.nih.gov/pubmed/19886026?tool=bestpractice.com[65]Ding JG. Transfection gene treatment of spinal cord injury with spinal cord-derived neural stem cells. J Clin Rehabil Tissue Engineer Res. 2007;11:1321-1324.[66]Kwon BK, Sekhon LH, Fehlings MG. Emerging repair, regeneration, and translational research advances for spinal cord injury. Spine (Phila Pa 1976). 2010;35(21 Suppl):S263-S270.http://www.ncbi.nlm.nih.gov/pubmed/20881470?tool=bestpractice.com[67]Li W. Neural stem cells for repairing spinal cord injury. J Clin Rehab Tissue Engineering Res. 2011;1:151-154.[68]Hayes Inc. Olfactory ensheathing cell transplantation for spinal cord injury. Lansdale, PA: Hayes Inc.; 2011.[69]Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, et al. A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma. 2011;28:1611-1682.http://online.liebertpub.com/doi/full/10.1089/neu.2009.1177http://www.ncbi.nlm.nih.gov/pubmed/20146557?tool=bestpractice.com[70]Yuan ML, Guo JH, Yang Z, et al. Genetic modified olfactory ensheathing cells for treating spinal cord injury: possibility to be the first choice. J Clin Rehab Tissue Engineering Res. 2010;44:8307-8310. 干细胞、[71]Liu CL, Wu Y. Advances of stem cells transplantation for spinal cord injury. J Clin Rehab Tissue Engineering Res. 2011;15:6051-6055. 祖细胞[72]Nandoe Tewarie RS, Hurtado A, Bartels RH, et al. Stem cell-based therapies for spinal cord injury. J Spinal Cord Med. 2009;32:105-114.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678281/http://www.ncbi.nlm.nih.gov/pubmed/19569457?tool=bestpractice.com 和胚胎神经元[73]Grumbles RM, Sesodia S, Wood PM, et al. Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons. J Neuropathol Exp Neurol. 2009;68:736-746.http://www.ncbi.nlm.nih.gov/pubmed/19535998?tool=bestpractice.com 已经得以研究。[69]Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, et al. A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma. 2011;28:1611-1682.http://online.liebertpub.com/doi/full/10.1089/neu.2009.1177http://www.ncbi.nlm.nih.gov/pubmed/20146557?tool=bestpractice.com 临床上通过蛛网膜下腔或鞘内注射进行。[74]Shen YX, Zhang P, Zhao JG. A potential therapeutic approach for human spinal cord injuries: Subarachnoid puncture for OECs transplantation. Med Hypotheses. 2009;73:863-864.http://www.ncbi.nlm.nih.gov/pubmed/19457620?tool=bestpractice.com 已经有过联合神经营养因子进行移植。 这些因子包括心肌营养素 1、成纤维细胞生长因子2、胰岛素样生长因子1、胶质细胞系源性神经营养因子、白血病抑制因子以及肝细胞生长因子。 因子和细胞的特别组合可以改善运动神经元的存活,增加有髓鞘的轴突数目以及产生肌肉神经再支配。[73]Grumbles RM, Sesodia S, Wood PM, et al. Neurotrophic factors improve motoneuron survival and function of muscle reinnervated by embryonic neurons. J Neuropathol Exp Neurol. 2009;68:736-746.http://www.ncbi.nlm.nih.gov/pubmed/19535998?tool=bestpractice.com 在实验室条件下,通过可塑性改善、轴突出芽以及再生情况评估结果,在临床条件下,通过神经保护作用、肌肉神经再支配、功能恢复以及生活质量改善评估结果。 伦理问题、日常临床应用的高成本以及缺乏长期结果限制了该方法的进展。
软骨素酶 ABC
动物研究显示软骨素酶可诱导可塑性,改善训练技能的相关敏捷性,但是对非训练的运动活动有不良作用。[75]Garcia-Alias G, Barkhuysen S, Buckle M, et al. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci. 2009;12:1145-1151.http://www.ncbi.nlm.nih.gov/pubmed/19668200?tool=bestpractice.com 当前尚未在人类中进行研究。
电刺激
在实验研究中注意到对感受器的同步化学和电刺激有协同效应。 所以针对改善运动功能建立了联合电刺激和药物策略的方案。[76]Musienko P, van den Brand R, Maerzendorfer O, et al. Combinatory electrical and pharmacological neuroprosthetic interfaces to regain motor function after spinal cord injury. IEEE Trans Biomed Eng. 2009;56:2707-2711.http://www.ncbi.nlm.nih.gov/pubmed/19635690?tool=bestpractice.com[77]Nightingale EJ, Raymond J, Middleton JW, et al. Benefits of FES gait in a spinal cord injured population. Spinal Cord. 2007;45:646-657.http://www.ncbi.nlm.nih.gov/pubmed/17646840?tool=bestpractice.com[78]Canadian Agency for Drugs and Technologies in Health. Functional electrical stimulation for children with spinal cord injuries or cerebral palsy: Update of review of clinical effectiveness. August 2015 [internet publication].https://www.cadth.ca/functional-electrical-stimulation-fes-children-spinal-cord-injuries-or-cerebral-palsy-update-review一项结合活动平板训练、重量支撑和硬膜外电刺激的试验初步结果显示,受试者的自主运动有所增加。[79]Angeli CA, Boakye M, Morton RA, et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250.http://www.ncbi.nlm.nih.gov/pubmed/30247091?tool=bestpractice.com 对于脊髓损伤患者,经颅微电流刺激疗法可改善疼痛程度和疼痛干扰,且副作用很少。[80]Tan G, Rintala DH, Jensen MP, et al. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. J Spinal Cord Med. 2011;34:285-296.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127367/http://www.ncbi.nlm.nih.gov/pubmed/21756567?tool=bestpractice.com
普阿氯芬
普阿氯芬是巴氯芬的前体药物。 这是一种肌肉松弛剂和解痉剂。 随机对照试验显示高剂量普阿氯芬口服缓释剂耐受性良好,并且可以减轻脊髓损伤患者的痉挛状态。[81]Nance PW, Huff FJ, Martinez-Arizala A, et al. Efficacy and safety study of arbaclofen placarbil in patients with spasticity due to spinal cord injury. Spinal Cord. 2011;49:974-980.http://www.ncbi.nlm.nih.gov/pubmed/21577221?tool=bestpractice.com
肉毒素
初步研究已论述了肉毒毒素在治疗神经性疼痛方面的使用。 这些研究是队列研究。 一项随机对照临床试验表明,肉毒毒素 A(在美国称为 onabotulinumtoxinA、incabotulinumtoxinA 或 abobotulinumtoxinA)可减少脊髓损伤患者的顽固性慢性神经性疼痛。 证据是初步的;然而,鉴于治疗神经性疼痛的困难,可以使用肉毒毒素。[82]Han ZA, Song DH, Oh HM, et al. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. Ann Neurol. 2016;79:569-578.http://onlinelibrary.wiley.com/doi/10.1002/ana.24605/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26814620?tool=bestpractice.com