title: An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.
abstract: Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues.
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Sheldon
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Kwon
authors.affiliation: 1] Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania [2] Children's Hospital of Philadelphia, Philadelphia, Pennsylvania [3] Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Grant T
authors.initials: GT
authors.lastname: Liu
authors.affiliation: 1] Children's Hospital of Philadelphia, Philadelphia, Pennsylvania [2] Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Shana E
authors.initials: SE
authors.lastname: McCormack
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002648:Child; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D057446:Hydrodynamics; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011559:Pseudotumor Cerebri / Q000503:physiopathology*; D019802:Succinic Acid / Q000378:metabolism; D013577:Syndrome
chemical_list: D054392:Adipokines; D012739:Gonadal Steroid Hormones; D007656:Ketoglutaric Acids; D018698:Glutamic Acid; D000450:Aldosterone; D019802:Succinic Acid; D006854:Hydrocortisone