Investigation into the Molecular Mechanisms Underlying Idiopathic Intracranial Hypertension (P2.099)

Abstract

Objective: To investigate cerebrospinal fluid (CSF) secretion/drainage rates as putative underlying causes of idiopathic intracranial hypertension (IIH). Background: Various causative factors have been postulated as to the increasing incidence of IIH, however, none with any convincing evidence. Identifying biomarkers, already found to be elevated in patients with IIH, including pro-inflammatory cytokines; chemokine (C-C motif) ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as adipocyte derived hormone leptin and the glucocorticoid hydrocortisone has been used to present an insight into the pathogenesis of IIH. Design/Methods: To assess the effects of the elevated mediators on CSF volume/secretion rates, an in vivo ventriculo-cisternal perfusion was performed. In addition, an in vivo variable rate infusion technique assessed mediator effects on CSF drainage. Results: Hydrocortisone (2.65 μl/min) and TNF-α (2.58 μl/min) significantly increased CSF secretion rate, when compared to controls (1.90μl/min). IL-6 (0.91 μl/min) caused a significant decrease in CSF secretion rate. The volumes of the initial CSF within the cranium following intraperitoneal mediator injection, prior to perfusion of the animal with artificial CSF containing the mediator, were significantly higher for CCL2 (323.6 μl) and IL-17 (327.0 μl) when compared with controls (226.7 μl). CCL2 (55.6 mmH2O.min/μl) and IL-17 (52.7 mmH2O.min/μl) significantly increased pressure and resistance to CSF drainage when compared with controls (28.76mmH2O.min/μl). Conclusions: An impairment within the CSF drainage mechanisms could be postulated due to the significant increase in initial CSF volume; decrease in overall CSF secretion and increased resistance to CSF drainage associated with CCL2 and IL-17. The opposing results of CSF secretion/drainage suggest an altered compensatory mechanism associated with hydrocortisone, TNF-α and IL-6. Study supported by: Prof. Basil Sharrack, Dr. Ignacio A. Romero, Dr. A. Jane Loughlin, Dr. Jane E. Preston. Disclosure: Dr. Alimajstorovic has nothing to disclose.