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Journal of Pediatric Neurology 2015; 13(01): 026-030
DOI: 10.1055/s-0035-1555149
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Molecular Modeling of Cerebrospinal Fluid Dynamics in Pediatric Pseudotumor Cerebri Syndrome: Altered Sodium Transport in Choroid Plexus by Lithium Treatment

Conrad E. Johanson
1   Department of Neurosurgery, Alpert Medical School at Brown University, Providence, Rhode Island, United States
,
Vincenzo Salpietro
2   Department of Pediatric Neurology, Chelsea and Westminster Hospital, Imperial College, London, United Kingdom
3   Department of Pediatrics, University of Messina, Messina, Italy
› Author Affiliations
Further Information

Publication History

31 January 2015

10 February 2015

Publication Date:
13 July 2015 (online)

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Abstract

Pseudotumor cerebri syndrome (PTCS), characterized mainly by raised intracranial pressure (ICP), occurs in children as well as adults. Management of PTCS in adolescents (but not necessarily prepubertal children) is similar to that in older patients. Augmented formation of cerebrospinal fluid (CSF) has been implicated in the elevated ICP of PTCS. PTCS can be provoked or exacerbated by lithium (Li) carbonate, a therapeutic agent used for bipolar disease. PTCS associated with Li carbonate usage is rare and can usually be ameliorated by discontinuing Li intake. An analysis of basic and clinical experimentation, assessing the effects of Li on cellular physiology, reveals that Li competes with multiple sodium (Na) transporters and channels in choroid plexus epithelium. Li-stimulated Na-potassium adenosine triphosphatase is of particular interest because of the role of Na pumping in driving CSF formation (which is directly proportional to Na transport from blood to ventricles). We present a transport model of PTCS that links stimulated Na transport at the blood-CSF barrier with increased CSF formation rate and ICP. One possible avenue for future treatment of children and adults with PTCS is to pharmacologically manipulate the Na and water movements across the choroid plexus secretory tissues that generate ICP. This review presents a molecular physiology model, involving Na transporters, to address possible therapeutic targets to reduce CSF production and the associated ICP. Elucidating the common pathophysiologic transport mechanisms of PTCS in children and adults should help identify novel drugs, with fewer side effects than acetazolamide, to control more finely the CSF formation by choroid plexus.

Keywords

Sodium–potassium adenosine triphosphatase - lithium carbonate - sodium transporters - cerebrospinal fluid formation - intracranial pressure - amiloride - acetazolamide - spironolactone
 

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