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This route bypasses the blood\u2013brain barrier, thus enabling the delivery of therapeutics that are restricted from the brain, while reducing the risk of systemic adverse reactions. Nevertheless, projections from studies in patients with other diseases suggest that efficacy of some ICV\u2010delivered therapeutics may be limited when the epileptogenic tissue or network circuits are localized more than a few millimeters away from the ventricles. In this article, we present the characteristics of the cerebrospinal fluid as a drug administration site, the brain barriers, and their relevance to treating focal and generalized epilepsies. We refer to ICV delivery of advanced therapies for treating neurodevelopmental disorders with epilepsy. We describe properties of therapeutic compounds, from small molecules to RNA\u2010based therapeutics, proteins, and viral vectors, which can make them either fitting or poor candidates for ICV administration in epilepsy. We additionally provide an overview of preclinical studies and clinical trials involving the ICV route of delivery. Finally, we compare ICV delivery with other routes of administration that bypass the cerebral circulation. This review aims to provide information that will hopefully help investigators select candidate patients and therapeutics for ICV therapies, and to highlight advantages and challenges inherent to this approach.<\/jats:p>","DOI":"10.1111\/epi.17625","type":"journal-article","created":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T10:24:08Z","timestamp":1682159048000},"page":"1750-1765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Intracerebroventricular administration for delivery of antiseizure therapeutics: Challenges and opportunities"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-5530","authenticated-orcid":false,"given":"Firas","family":"Fahoum","sequence":"first","affiliation":[{"name":"Epilepsy and EEG Unit, Neurology Division, Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv 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