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Neurosurgical shunting to reduce CSF volume is the default treatment that intends to reinstate normal CSF homeostasis, yet neurodevelopmental disability often persists in hydrocephalic children despite optimal surgical management. Here, we discuss recent human genetic and animal model studies that are shifting the view of pediatric hydrocephalus from an impaired fluid plumbing model to a new paradigm of dysregulated neural stem cell (NSC) fate. NSCs are neuroprogenitor cells that comprise the germinal neuroepithelium lining the prenatal brain ventricles. We propose that heterogenous defects in the development of these cells converge to disrupt cerebrocortical morphogenesis, leading to abnormal brain\u2013CSF biomechanical interactions that facilitate passive pooling of CSF and secondary ventricular distention. A significant subset of pediatric hydrocephalus may thus in fact be due to a developmental brain malformation leading to secondary enlargement of the ventricles rather than a primary defect of CSF circulation. If hydrocephalus is indeed a neuroradiographic presentation of an inborn brain defect, it suggests the need to focus on optimizing neurodevelopment, rather than CSF diversion, as the primary treatment strategy for these children.<\/jats:p>","DOI":"10.1093\/cercor\/bhac341","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T12:02:47Z","timestamp":1661342567000},"page":"4262-4279","source":"Crossref","is-referenced-by-count":31,"title":["A neural stem cell paradigm of pediatric hydrocephalus"],"prefix":"10.1093","volume":"33","author":[{"given":"Phan Q","family":"Duy","sequence":"first","affiliation":[{"name":"Yale University School of Medicine Department of Neuroscience, , New Haven, CT 06510 , USA"},{"name":"Yale University School of Medicine Medical Scientist Training Program, , New Haven, CT 06510 , USA"},{"name":"Yale University School of Medicine Department of Neurosurgery, , New Haven, CT 06510 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasko","family":"Rakic","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine Department of Neuroscience, , New Haven, CT 06510 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth L","family":"Alper","sequence":"additional","affiliation":[{"name":"Harvard Medical School Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center and Department of Medicine, , Boston, MA 02215 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M","family":"Robert","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine Department of Neurosurgery, , New Haven, CT 06510 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J","family":"Kundishora","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine Department of Neurosurgery, , New Haven, CT 06510 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Butler","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Department of Neurosurgery, , Boston, MA 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Walsh","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Department of Pediatrics, and Howard Hughes Medical Institute, , Boston, MA 02115 , USA"},{"name":"Harvard Medical School Departments of Pediatrics and Neurology, , Boston, MA 02115 , USA"},{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nenad","family":"Sestan","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine Department of Neuroscience, , New Haven, CT 06510 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H","family":"Geschwind","sequence":"additional","affiliation":[{"name":"University of California Los Angeles Department of Human Genetics, David Geffen School of Medicine, , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng Chih","family":"Jin","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine Department of Genetics, , St. Louis, MO 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher T","family":"Kahle","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Department of Neurosurgery, , Boston, MA 02114 , USA"},{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142 , USA"},{"name":"Massachusetts General Hospital Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, , Boston, MA 02114 , 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