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However, the classic model of disease spread across a disrupted BBB does not explain the focal distribution of lesions seen in a variety of neurological diseases and why lesions are frequently adjacent to the cerebrospinal fluid (CSF) spaces. We have critically reviewed the possible role of a blood\u2013CSF\u2013brain route as a disease entry pathway into the brain parenchyma. The initial step of this pathway is the transfer of pathogens or immune components from the blood into the CSF at the choroid plexuses, where the blood\u2013CSF barrier (BCSFB) is located. The flow of CSF results in disease dissemination throughout the CSF spaces. Access to the brain parenchyma from the CSF can then occur across the ependymal layer at the ventricular surface or across the pial\u2013glial barrier of the subarachnoid space and the Virchow\u2013Robin spaces. We have reviewed the anatomy and physiology of the blood\u2013CSF\u2013brain pathway and the brain barriers controlling this process. We then summarised the evidence supporting this brain entry route in a cross\u2010section of neurological diseases including neuromyelitis optica, multiple sclerosis, neurosarcoidosis, neuropsychiatric lupus, cryptococcal infection and both solid and haematological tumours. This summary highlights the conditions that share the blood\u2013CSF\u2013brain pathway as a pathogenetic mechanism. These include the characteristic proximity of lesions to CSF, evidence of disruption of the brain barriers and the identification of significant pathology within the CSF. An improved understanding of pathological transfer through the CSF and across\n                    <jats:italic>all<\/jats:italic>\n                    brain barriers will inform on more effective and targeted treatments of primary and secondary diseases of the central nervous system.\n                  <\/jats:p>","DOI":"10.1111\/nan.12789","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T22:08:52Z","timestamp":1640124532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["The blood\u2013CSF\u2013brain route of neurological disease: The indirect pathway into the brain"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-3760","authenticated-orcid":false,"given":"Oliver","family":"Cousins","sequence":"first","affiliation":[{"name":"Department of Neuroimaging, IoPPN King's College London  London 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