Infectious and inflammatory disorders might increase the risk of developing idiopathic intracranial hypertension - a national case-control study.

Anna Sundholm,Elisabet Waldenlind,Shahram Bahmanyar,Sarah Burkill,A Ingela M Nilsson Remahl

doi:10.1177/0333102420928079

Abstract

ObjectiveTo investigate whether conditions causing inflammatory activation are associated with increased risk of idiopathic intracranial hypertension.MethodsAll newly diagnosed idiopathic intracranial hypertension patients (cases) in Sweden between 2000–2016 were identified using pre-determined algorithms (n = 902) and matched with five controls from the general population and five individuals with an obesity diagnosis (n = 4510) for age, sex, region, and vital status. National health registers provided information on infections, inflammatory disorders and dispensed medications. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals.ResultsCompared to general population controls, the cases had fourfold increased odds of having an infection (odds ratio = 4.3, 95% confidence interval 3.3–5.6), and threefold increased odds of an inflammatory disorder the year prior to idiopathic intracranial hypertension diagnosis (odds ratio = 3.2, 95% confidence interval 2.4–4.3). Organ specific analyses showed that odds were increased for the study diseases in the respiratory organ, kidney organ and gastrointestinal tract, but not for female genital infections. Similar results were found when comparing idiopathic intracranial hypertension with obese controls though the odds ratios were of lower magnitude. Sub-analyses on exposure to anti-infectious and anti-inflammatory drugs confirmed the increased odds ratios for idiopathic intracranial hypertension patients.ConclusionsThese findings suggest that major inflammatory activation may be a risk factor in idiopathic intracranial hypertension development.

Highlights

Idiopathic intracranial hypertension (IIH) is a disorder that induces symptoms such as headache, visual disturbances and pulsatile tinnitus due to increased intracranial pressure (ICP) of unknown cause [1]
A validation study was previously performed to investigate to what extent a diagnosis code G93.2 in the Swedish National Patient Register (NPR) fulfilled the clinical diagnosis criteria for IIH according to the modified Dandy Criteria [3]
Educational level was more similar among IIH and obese controls, with 17–18% achieving 9 years or less of compulsory school compared to 10% among the general population (GP) controls as their highest educational attainment

Summary

Introduction

Idiopathic intracranial hypertension (IIH) is a disorder that induces symptoms such as headache, visual disturbances and pulsatile tinnitus due to increased intracranial pressure (ICP) of unknown cause [1]. One potential pathway relates to increased activity of the enzyme 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), which has been shown to be dysregulated with increased activity in both obesity and IIH [6]. Long-standing high cortisol levels have been shown to increase secretion of pro-inflammatory mediators [19] and possibly to increase the production of cerebrospinal fluid by affecting sodium transporters in the choroid plexus [6]. Weight loss and lower ICP values has been shown to reduce 11b-HSD1-levels in IIH patients [20]. Several studies have demonstrated increased or decreased levels of these inflammatory mediators indicating that proinflammatory activation could plausibly be involved in the pathogenesis of IIH [8,21,22,23,24]

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Conclusion