Abstract

BackgroundThe management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats.MethodsWe measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate.ResultsAt clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% (p = 0.0009) and 21% (p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% (p = 0.018), compared to 5% reduction with acetazolamide (p = >0.999).ConclusionOur in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

Highlights

  • Idiopathic intracranial hypertension (IIH) typically affects obese woman of childbearing age and is characterised by raised intracranial pressure (ICP)

  • Subcutaneous administration of acetazolamide showed a trend towards a reduction in ICP at clinical (19% reduction) and high doses (20% reduction); it was not

  • The aim of the present study was to ascertain which drug – acetazolamide, topiramate, furosemide, amiloride or octreotide – had the greatest effect on lowering ICP in healthy rats, and so provide pre-clinical evidence to support their use in the pharmacological treatment of IIH

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Summary

Introduction

Idiopathic intracranial hypertension (IIH) typically affects obese woman of childbearing age and is characterised by raised intracranial pressure (ICP). Majority of patients receive pharmacological therapy with the aim of reducing cerebrospinal fluid (CSF) secretion and ICP For those with fulminant IIH and rapidly declining vision, CSF diversion surgery may be necessary [4]. Methods: We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). Results: At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% (p 1⁄4 0.0009) and 21% (p 1⁄4 0.015) respectively. Oral administration of topiramate significantly lowered intracranial pressure by 22% (p 1⁄4 0.018), compared to 5% reduction with acetazolamide (p 1⁄4 >0.999). Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest

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