Chinese expert consensus on neurorestorative therapy with cerebrospinal fluid administration (2022)

doi:10.12307/2023.442

Abstract

Abstract: BACKGROUND: The nervous system is highly protected by the blood-brain barrier and the blood-cerebrospinal fluid barrier and the development and administration of neurorestorative drugs are still challenging. Therefore, the clinical therapeutic effects of most drugs are limited. Direct administration to the nervous system through the cerebrospinal fluid route is also an important clinical treatment strategy, but there is currently no unified clinical application standard.
OBJECTIVE: To explain the current status of cerebrospinal fluid administration and the indications, specific methods and precautions in clinical practice, thereby popularizing the application and improving the clinical efficacy.
METHODS: The Expert Committee of Neurorestoratology of Beijing Medical Doctor Association and the Professional Branch of Neurorestoratology of Guangdong Medical Doctor Association organized and compiled this expert consensus by organizing relevant expert seminars from various disciplines across the country.
RESULTS AND CONCLUSION: Direct administration to the nervous system through the cerebrospinal fluid route for neurorestorative therapy has a wide range of clinical indications and application prospects. However, attention should be paid to the safety and efficiency of cerebrospinal fluid administration, the combination of compound formulations, the maximum tolerated dose and full informed consent during the application process.

Key words: cerebrospinal fluid route, nerve repair, blood-brain barrier, neurotrophy, nervous system disease

CLC Number:

References

[1] 黄红云,陈琳.神经修复学—21世纪新学科、新理念、新领域[J].中国修复重建外科杂志,2008,22(4):439-445.
[2] 陈琳,黄红云.神经修复学学科体系若干问题探讨[J].中国修复重建外科杂志,2009,23(3):366-370.
[3] HUANG HY, CHEN L, MAO GS, et al. The 2019 yearbook of Neurorestoratology. Neurorestoratology. 2020;8(1):1-11.
[4] 石立科,王玉海,邱丽颖,等.鞘内注射亚胺培南/西司他丁在家兔体内的药代动力学实验研究[J].中华医院感染学杂志,2012, 22(13):2763-2766.
[5] 李志勇,漆松涛,方陆雄,等.不同给药途径万古霉素在脑脊液和血液中药物浓度及疗效比较[J].中国神经精神疾病杂志,2007, 33(10):601-604.
[6] Deisenhammer F, Sellebjerg F, Teunissen CE, et al. 脑脊液检验与临床神经病学[M].关明,赵曜,主译.北京:科学出版社.2021:20.
[7] GAZARIAN M, KELLY M, MCPHEE JR, Et al. Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust. 2006;185(10):544-548.
[8] 中国药理学会治疗药物监测研究专业委员会药品风险管理学组.超说明书用药专家共识[J].药物不良反应杂志,2015,17(2):101-103.
[9] 广东省药学会.超药品说明书用药中患者知情同意权的保护专家共识[J].今日药学,2019,29(6):361-367.
[10] 陈琳,黄红云,左焕琮.神经修复学若干新概念、新名词、新假说[J].中华临床医师杂志(电子版),2011,5(19):5557-5559.
[11] VÁZQUEZ-ROQUE RA, RAMOS B, TECUATL C, et al. Chronic administration of the neurotrophic agent cerebrolysin ameliorates the behavioral and morphological changes induced by neonatal ventral hippocampus lesion in a rat model of schizophrenia. J Neurosci Res. 2012;90(1):288-306.
[12] SHARMA HS, SHARMA A. New strategies for CNS injury and repair using stem cells, nanomedicine, neurotrophic factors and novel neuroprotective agents. Expert Rev Neurother. 2011;11(8):1121-1124.
[13] ROCKENSTEIN E, UBHI K, PHAM E, et al. Beneficial effects of a neurotrophic peptidergic mixture persist for a prolonged period following treatment interruption in a transgenic model of Alzheimer’s disease]. J Neurosci Res. 2011;89(11):1812-1821.
[14] GUÉGAN C, CEBALLOS-PICOT I, CHEVALIER E, et al. Reduction of ischemic damage in NGF-transgenic mice: correlation with enhancement of antioxidant enzyme activities. Neurobiol Dis. 1999; 6(3):180-189.
[15] 苏淑杰,李志洁.鼠神经生长因子对新生大鼠缺氧缺血性脑损伤后神经修复的作用[J].中国实用神经疾病杂志,2011,14(3): 15-17.
[16] 高爱鲜,张云书,等.鞘内注射神经生长因子治疗脑梗死临床观察[J].实用心脑肺血管病杂志,1999,7(2):122.
[17] 窦荣花,于庋麟,韩国杰,等.鞘内注射神经生长因子治疗脑血管后遗症30例临床疗效观察[J].微循环学杂志,1997,7(3):52-53.
[18] CHIARETTI A, PIASTRA M, POLIDORI G, et al. Correlation between neurotrophic factor expression and outcome of children with severe traumatic brain injury. Intensive Care Med. 2003;29(8):1329-1338.
[19] 陈刚.纳洛酮治疗急性中重型颅脑损伤的系统评价[J].航空航天医学杂志,2014,25(11):1576-1577.
[20] 孙永安,马正春,窦玉明,等.胞二磷胆碱鞘内注射治疗重度脑功能障碍11例[J].人民军医,1993(5):55-56.
[21] 陈琳,黄红云,左焕琮.鞘内注射药物神经修复治疗颅脑损伤后遗症[J].中华临床医师杂志(电子版),2013,7(13):6159-6160.
[22] 郭春杰,曲怀谦.鞘内注射胞二磷胆碱治疗去皮层状态5例报告[J].中风与神经疾病杂志,1989,6(4):244.
[23] 李秀杰,王亚林,李荣.高压氧联合鞘内给药治疗重度一氧化碳中毒迟发性脑病的临床观察[J].黑龙江医药,2016,29(1):166-168.
[24] 陈永刚,耿彬,王栓科,等.神经节苷脂对大鼠脊髓损伤后微管相关蛋白-2表达的影响及意义[J].中国矫形外科杂志,2011,19(10): 840-845.
[25] 潘伟,尹宗生,张辉,等.鞘内注射神经生长因子对脊髓损伤大鼠运动功能恢复及神经细胞变化的影响[J].安徽医科大学学报,2011, 46(9): 875-879.
[26] 张磊,梅元武.神经生长因子干预大鼠脊髓损伤模型白质轴突计数和运动功能恢复的变化[J].中国组织工程研究,2007,11(6): 1192-1194.
[27] 莫家驹,李敏,贾院生,等.糖皮质激素并用胞二磷胆碱治疗多发性硬化症3例报告[J].安徽医科大学学报,1991(4):296-312.
[28] 刘生荣,尚宏亮,张鹏辽,等.鞘内联合给药治疗神经系统脱髓鞘疾病的临床观察[J].临床神经病学杂志,2004,17(5): 373-374.
[29] 宗碧云.神经生长因子治疗帕金森病的临床观察[J].中国老年学杂志,1998,18(4):249-250.
[30] HEFTI F, DRAVID A, HARTIKKA J. Chronic intraventricular injections of nerve growth factor elevate hippocampal choline acetyltransferase activity in adult rats with partial septo-hippocampal lesions. Brain Res. 1984;293(2):305-311.
[31] SEILER M, SCHWAB ME. Specific retrograde transport of nerve growth factor (NGF) from neocortex to nucleus basalis in the rat. Brain Res. 1984;300(1):33-39.
[32] ALOE L, ROCCO ML, BIANCHI P, et al. Nerve growth factor: from the early discoveries to the potential clinical use. J Trans Med. 2012;10(1): 239-239.
[33] OLSON L, NORDBERG A, HOLST HV, et al. Nerve growth factor affects11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (Case Report). J Neural Transm Park Dis Dement Sect. 1992;4(1):79-95.
[34] ERIKSDOTTER JÖNHAGEN M, NORDBERG A, AMBERLA K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 1998;9(5):246-257.
[35] OLSON L. NGF and the Treatment of Alzheimer’s Disease. Exp Neurol. 1993;124(1):5-15.
[36] 于德华.鞘内注射胞二磷胆碱治疗老年痴呆100例[J].中国民政医学杂志,1997(1):44.
[37] 赵雪,何芸,王虎清,等.鞘内注射治疗34例脊髓亚急性联合变性的临床观察[J].神经损伤与功能重建,2015,10(6):499-502.
[38] 邹伯常,林剑峰.维生素B_(12)鞘内注射治疗小脑型共济失调一例[J].广西医学,1982(6):327.
[39] 车向新,卢金活,朱长庚,等.鞘内注射神经生长因子对大鼠痛阈、脊神经节脊髓后角CGRP免疫反应的影响[J].九江医学,2002,17(2): 68-70,73.
[40] CIRILLO G, CAVALIERE C, BIANCO MR, et al. Intrathecal NGF administration reduces reactive astrocytosis and changes neurotrophin receptors expression pattern in a rat model of neuropathic pain. Cell Mol Neurobiol. 2010;30(1):51-62.
[41] 陈琳,王庆苗,黄红云,等.颈椎病脊髓出血后顽固性疼痛神经修复学治疗1例[J].中国医疗前沿,2010,5(19):56-57.
[42] 王丽华,姜虹.不同剂量神经生长因子对神经源性疼痛大鼠脊髓Fos蛋白的影响[J].中国组织工程研究与临床康复,2009,13(50): 9866-9869.
[43] 鼠神经生长因子神经外科(中国)临床应用专家共识委员会.鼠神经生长因子神经外科临床应用专家共识[J].中国临床神经外科杂志,2019,24(11):717-720.
[44] MAINO B, SPAMPINATO A G, SEVERINI C, et al. The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti-inflammatory and immunosuppressive transcriptional program. J Cell Physiol. 2018;233(10):7178-7187.
[45] SKAPER SD. Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology. 2017;151(1):1-15.
[46] 张瑞,郭慧琴,王清秀,等.鞘内注射Ad-hNGFβ对神经痛大鼠的镇痛作用及背根神经节Kv1 mRNA表达的影响[J].郧阳医学院学报, 2010,29(4):325-329.
[47] 谭俊铭,史建刚,史国栋,等.急性重度狗马尾束缢和鞘内注射脑源性神经生长因子对背根神经节的影响[J].脊柱外科杂志,2009, 7(4):201-204,208.
[48] CIRILLO G, CAVALIERE C, BIANCO MR, et al. Intrathecal NGF administration reduces reactive astrocytosis and changes neurotrophin receptors expression pattern in a rat model of neuropathic pain. Cell Mol Neurobiol. 2010;30(1):51-62.
[49] CHIARETTI A, ANTONELLI A, GENOVESE O, et al. Intraventricular nerve growth factor infusion improves cerebral blood flow and stimulates doublecortin expression in two infants with hypoxic-ischemic brain injury. Neurol Res. 2008;30(3):223-238.
[50] NAUTA HJ, WEHMAN JC, KOLIATSOS VE, et al. Intraventricular infusion of nerve growth factor as the cause of sympathetic fiber sprouting in sensory ganglia.J Neurosurg. 1999;91(3):447-453.
[51] KOBAYASHI S, OGREN SO, EBENDAL T, et al. Intraventricular injection of NGF, but not BDNF, induces rapid motor activation that is inhibited by nicotinic receptor antagonists. Exp Brain Res. 1997;116(2):315-325.
[52] VENERO JL, HEFTI F, KNUSEL B. Trophic effect of exogenous nerve growth factor on rat striatal cholinergic neurons:comparison between intraparenchymal and intraventricular administration. Mol Pharmacol. 1996;49(2):303-310.
[53] MONTERO CN, HEFTI F. Intraventricular nerve growth factor administration prevents lesion-induced loss of septal cholinergic neurons in aging rats. Neurobiol Aging. 1989;10(6):739-743.
[54] 刘兴波,刘明,翟峰,等.NGF/奥德金鞘内给药治疗脊髓损伤的试验研究[J].中外医疗,2008,27(29):63-64.
[55] 罗选翔,经历,潘彬,等.甲钴胺联合鼠神经生长因子促进脊髓型颈椎病术后神经功能的恢复[J]. 中国组织工程研究,2021,25(5): 719-722.
[56] 韦佩珊,卢燕君.甲钴胺用于腰椎间盘突出症的临床疗效观察[J]. 深圳中西医结合杂志,2021,31(3):154-155.
[57] 李敏,陈超阳,陈哲晖,等.钴胺素代谢及其不同形式的临床应用[J].中华实用儿科临床杂志,2020,35(9):716-720.
[58] 郭姗姗.腺苷钴胺多晶型研究[D].郑州:郑州大学,2019.
[59] 尚学军,胡卫国,姚福鑫,等.腺苷钴胺的药理及临床作用[J].临床合理用药杂志,2013,6(23):80.
[60] 鲁玉霞,杨淑明.维生素B12联合鼠神经生长因子对脑瘫幼鼠智力的改善作用及机制探讨[J].中华生物医学工程杂志,2019,25(3): 360-366.
[61] 李彩梅.维生素B12对小于胎龄儿脑发育的影响及干预研究[D].苏州:苏州大学,2015.
[62] 尚肖肖,王志萍,赵仲堂.维生素B12在神经管缺陷一级预防中的作用研究进展[J].中华流行病学杂志,2010,31(5):579-583.
[63] POURZITAKI C, TSAOUSI G, PAPAZISIS G, et al . Fentanyl and naloxone effects on glutamate and GABA release rates from anterior hypothalamus in freely moving rats. Eur J Pharmacol. 2018;834(5):169-175.
[64] 关雪莲.脑出血患者血浆和脑脊液中阿片肽含量及纳洛酮干预的研究[D].佳木斯:佳木斯大学,2005.
[65] 王满,任国庆,刘艳,等.纳洛酮鞘内给药治疗高血压脑室内出血15例[J].白求恩军医学院学报,2011,9(1): 44-45.
[66] 赵力学,张建龙,王满,等.超早期腰穿并鞘内注入纳洛酮治疗脑出血破入脑室1例报告[J].山东医药,2010,50(14):114.
[67] 段强,樊继军,周翔鱼.静脉注射结合鞘内注射盐酸纳洛酮治疗重型颅脑损伤[J].河北医药,2003,25(12):925-926.
[68] 蒋春英,李亚杰,陶丽.单唾液酸四己糖神经节苷脂对新生儿缺氧缺血性脑病血清基质金属蛋白酶 -9 水平的影响及疗效观察[J].中国儿童保健杂志,2011,19(5):470-472.
[69] 赵玉萍,彭晓康.单唾液酸四己糖神经节苷脂钠注射液治疗中、重度新生儿缺氧缺血性脑病疗效观察[J].中国妇幼保健,2012,27(24): 3810-3811.
[70] LIU L, LIU C, LIU Y, et al. ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy. Int J Clin Exp Pathol. 2015;8(6):6950-6966.
[71] 安红霞,郑兴惠.凋亡相关基因程序化细胞死亡基因５在新生儿缺氧缺血性脑病中的表达[J].中国儿童保健杂志,2015,23(8):788-791.
[72] FRONTCZAK-BANIEWICZ M, GADAMSKI R, BARSKOV I, et al. Beneficial effects of GM1 ganglioside on photochemically- induced microvascular injury in cerebral cortex and hypophysis in rat. Exp Toxicol Pathol. 2000; 52(2):111-118.
[73] 董强.神经节苷脂GM1与神经系统疾病[J].国际脑血管病杂志, 2009,17(12):881-888.
[74] 熊云彪,周飞鹏,杨承勇,等. 神经节苷脂对急性颅脑损伤患者的脑保护作用[J].中华创伤杂志,2012,28(8):685-686.
[75] COOMBS DW, COLBURN RW, MCCARTHY LE, et al. Neurotoxicology of chronic infusion of the ganglioside GM1 in the ewe:phase I.intrathecal administration. Anesth Analg. 1993;77(3):507-515.
[76] 赖福生,李惠俊,焦冬生,等.单唾液酸神经节苷脂鞘内注射治疗恢复期脊髓损伤的临床研究[J].中国实用神经疾病杂志,2015, 18(15):10-12.
[77] MAO J, PRICE DD, HAYES RL, et al. Intrathecal GM1 ganglioside and local nerve anesthesia reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy. Brain Res. 1992;584(1-2): 28-53.
[78] WU G, LU ZH, XIE X, et al. Mutant NG108-15 cells (NG-CR72) deficient in GM1 synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with LIGA-20. J Neurochem. 2001;76(3):690-702.
[79] HIGASHI H, CHEN NH. Ganglioside/protein kinase signals triggering cytoskeletal actin reorganization. Glycoconj J. 2004;20(1):49-58.
[80] 孙砚辉,陆雪芬神经节苷脂GMl及其脑保护机制[J].现代临床医学生物工程学杂志,2000,6(4):319-320．
[81] 蔡廷凯,权青云.脑苷肌肽注射液在急性脑梗死病人治疗中的应用[J].实用医技杂志,2005,12(17):2382-2383．
[82] 廖铭芳,何以鉴.脑苷肌肽治疗急性脑梗死40例疗效观察[J].现代医院,2006,6(2):16-17.
[83] 嵇国平,管亮.脑苷肌肽治疗脑梗死疗效观察[J].现代中西医结合杂志,2006,15(2):181．
[84] 杨向方,王永生.脑苷肌肽注射液治疗脑梗死的疗效观察[J].临床医学,2004,24(3):49．
[85] 熊小明,侯伟,孙良玉,等.高压氧联合复方脑肽节苷脂治疗脊髓损伤的疗效观察[J].临床合理用药杂志,2017,10(2):155-156.
[86] 汤忠平,李伟琳,唐集敏,等.胞磷胆碱在神经科的临床应用[J].中国现代药物应用,2014,8(17):225-228．
[87] 吴家阳,黄民权,杨大金,等.胞二磷胆碱鞘内注射治疗颅脑伤长期昏迷29例[J].人民军医,1997(9):512-513.
[88] 何俊瑛,贾丽景,刘澜,等.鞘内注射胞二磷胆碱治疗多发性硬化临床观察(附3例报道)[J].脑与神经疾病杂志,2003,11(5):314.
[89] 沈新囡.鞘内注射胞二磷胆碱治疗儿科神经系统感染性疾病5例[J].浙江医学,1999,21(2):62-63.
[90] 李军谦,李小玲.胞二磷胆碱鞘内注射治疗肝性脑病49例[J].人民军医,1995(10):45.
[91] 詹月红,许丽珍.鞘内注射胞二磷胆碱治疗遗传性共济失调症[J].苏州医学院学报,1991,11(2):119-120.
[92] 沈寻,靳文毅,盛森,等.地塞米松鞘内注射在脑神经微血管减压术后的应用[J].中国全科医学,2011,14(9): 972-974.
[93] 王秀丽,孟庆云.糖皮质激素对神经损伤后各种介质因子影响的研究进展[J].国外医学麻醉学与复苏分册,2000,21(4):238-240.
[94] 陈琳,黄红云,左焕琮.鞘内注射氧气联合地塞米松对神经修复效果的临床观察[J].中华细胞与干细胞杂志(电子版),2013,3(4): 203-207.
[95] 寇小格,梁东良,石金河,等.激素和鞘内给药治疗急性一氧化碳中毒迟发性脑病的临床研究[J]. 中国工业医学杂志,2007,20(1): 30-31.
[96] 郭泽.中枢神经系统脱髓鞘疾病甲泼尼龙联合鞘内注射激素治疗的效果分析[J].健康前沿,2017,26(2):167,170.
[97] 杨承志,陈佳俊,徐忠信.免疫球蛋白联合鞘内注射激素治疗重症格林-巴利综合征[J].吉林医学(综合版),2004,25(3):19-20.
[98] 孟志斌,周建强,付昆,等.后路脊柱显微内镜下髓核摘除类固醇激素神经根鞘内注射的临床疗效观察[J].脊柱外科杂志,2012, 10(3):139-142.
[99] 陈琳,黄红云,左焕琮,鞘内药物注射神经修复方法临床应用五例[J].中华细胞与干细胞杂志(电子版),2014,4(3):201-205.
[100] OLMOS-JIMÉNEZ R, ESPUNY-MIRÓ A, CÁRCELES RODRÍGUEZ C, et al. Practical aspects of the use of intrathecal chemotherapy. Farm Hosp. 2017;41(n01):105-129.
[101] 章沿锋,杨旖欣,冯智英.鞘内药物输注系统植入术适应证和药物选择的进展[J].中国疼痛医学杂志,2018,24(10):723-728.
[102] 李琳,冯智英.鞘内药物输注治疗中重度癌痛的研究进展[J].中华医学杂志,2021,101(43):3604-3608.
[103] NAGEL SJ, REDDY CG, FRIZON LA, et al. Intrathecal Therapeutics: Device Design, Access Methods, and Complication Mitigation. Neuromodulation. 2018;21(7):625-640.
[104] ZUBAIR A, DE JESUS O. Ommaya Reservoir. In: StatPearls. Treasure Island (FL): StatPearls Publishing,2021.
[105] MAGILL ST, CHOY W, NGUYEN MP, et al. Ommaya Reservoir Insertion: A Technical Note. Cureus. 2020;12(4):e7731.
[106] HAFEEZ U, CHER LM. Biomarkers and smart intracranial devices for the diagnosis, treatment, and monitoring of high-grade gliomas: a review of the literature and future prospects. Neurooncol Adv. 2019;1(1): vdz013.
[107] LIU HG, LIU DF, ZHANG K, et al. Clinical Application of a Neurosurgical Robot in Intracranial Ommaya Reservoir Implantation. Front Neurorobot. 2021;15:638633.
[108] LAU JC, KOSTENIUK SE, MACDONALD DR, et al. Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series. Acta Neurochir (Wien). 2018;160(3):539-544.
[109] COHEN-PFEFFER JL, GURURANGAN S, LESTER T, et al. Intracerebroventricular Delivery as a Safe, Long-Term Route of Drug Administration. Pediatr Neurol. 2017;67:23-35.
[110] WANG A, TENNER MS, SCHMIDT M, et al. Placement of Ommaya Reservoirs Using Electromagnetic Neuronavigation and Neuroendoscopy: A Retrospective Study with Cost-Benefit Analysis. World Neurosurgery. 2018;122:e723-e728.
[111] NAU R, BLEI C, EIFFERT H. Intrathecal Antibacterial and Antifungal Therapies. Clin Microbiol Rev. 2020;33(3):e00190-19.
[112] MONTES DE OCA DELGADO M, CACHO DÍAZ B, SANTOS ZAMBRANO J, et al. The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis. Front Oncol. 2018;8:509.
[113] DEER TR, POPE JE, HAYEK SM, et al. The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines. Neuromodulation. 2017; 20(2):96-132.
[114] 张令霞,马改英,韩旭,等.鞘内注射药物治疗在多发性硬化的探索[J].临床神经病学杂志,2019,32(3):234-237.
[115] FOWLER MJ, COTTER JD, KNIGHT BE, et al. Intrathecal drug delivery in the era of nanomedicine. Adv Drug Deliv Rev. 2020;165-166:77-95.
[116] SCHAFERNAK KT, JACOBSEN JR, HERNANDEZ D, et al. Cytochemical Characterization of Cerebrospinal Fluid Macrophage Inclusions in Pediatric Patients Receiving Intrathecal Nusinersen (SPINRAZA®) for Spinal Muscular Atrophy. Acta Cytol. 2022;66(1):79-84.