Background/Objectives: The blood–brain barrier and blood-CSF barrier limit the uptake of CNS-targeted therapeutics, warranting utilization of intra-cerebrospinal fluid (CSF) drug delivery. Here we review and compare the safety and distribution of different intra-CSF delivery methods reported in clinical literature.Methods: A retrospective literature review of three common CSF access methods was performed. A search consisting of clinical trials published on PubMed from 2000–2024 using the following search terms—intracerebroventricular/intraventricular/ICV, intrathecal/IT, intralumbar/lumbar puncture, cisterna magna/ICM/IT-CM, drug delivery, drug administration, and CSF—yielded 38 intracerebroventricular (ICV), 110 lumbar intrathecal (LIT), and six intra-cisterna magna (ICM) studies.Results: After final exclusion criteria were applied, there were 12 ICV, two LIT, and zero ICM publications remaining for analysis. ICV-specific safety was addressed in 11 ICV publications, with headache, nausea, and vomiting being among the most frequently mentioned procedure-associated adverse events (AEs). LIT-specific safety was provided in only one of the two studies, reporting mostly grade 1/2 AEs but also an instance of grade 4 myelosuppression. For clinical efficacy, progression-free survival (PFS), overall survival (OS), and disease progression rates were largely variable across studies. Pharmacokinetics were analyzed in four ICV studies.Conclusions: The safety profiles of both ICV and LIT injections are acceptable, showing mostly mild to moderate procedure-associated AEs and less common treatment-related AEs than systemically administered therapies. Additionally, ICV achieves therapeutic goals more consistently than the other intra-CSF delivery methods. To date, there are insufficient data to show dose-related response with intra-CSF delivery. Novel tools are being developed to improve upon intra-CSF delivery that will ideally lead to improved patient outcomes in the near future.
背景/目的：血脑屏障和血脑脊液屏障限制了中枢神经系统靶向治疗药物的摄取，因此有必要采用脑脊液内给药方式。本文回顾并比较了临床文献中报道的不同脑脊液内给药方法的安全性与分布特征。 方法：对三种常见的脑脊液给药途径进行了回顾性文献分析。通过检索PubMed数据库中2000年至2024年发表的临床试验，使用以下检索词——脑室内给药/脑室/ICV、鞘内/IT、腰椎穿刺、枕大池/ICM/IT-CM、药物递送、给药方式和脑脊液——共筛选出38项脑室内给药（ICV）研究、110项腰椎鞘内给药（LIT）研究和6项枕大池内给药（ICM）研究。 结果：应用最终排除标准后，剩余12项ICV研究、2项LIT研究和0项ICM研究纳入分析。11项ICV研究报道了ICV特有的安全性问题，其中头痛、恶心和呕吐是最常提及的操作相关不良事件（AEs）。仅有一项LIT研究提供了LIT特有的安全性数据，报告多为1/2级不良事件，但也出现了一例4级骨髓抑制。在临床疗效方面，不同研究中的无进展生存期（PFS）、总生存期（OS）和疾病进展率存在较大差异。四项ICV研究进行了药代动力学分析。 结论：ICV和LIT注射的安全性均可接受，主要表现为轻至中度的操作相关不良事件，且治疗相关不良事件的发生率低于全身给药疗法。此外，与其他脑脊液内给药方式相比，ICV能更稳定地实现治疗目标。目前尚无足够数据表明脑脊液内给药存在剂量相关性反应。新型工具正在研发中以改进脑脊液内给药技术，有望在不久的将来改善患者预后。
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