Background: Idiopathic intracranial hypertension (IIH) is an enigmatic syndrome of raised intracranial pressure and papilledema with metabolic underpinnings, although the exact etiology remains obscure. We aimed to evaluate routine blood and cerebrospinal fluid (CSF) markers covering several organ systems in newly diagnosed IIH and compared to controls. Methods: We registered the results of routine blood and CSF analyses in patients consecutively included in a prospective cohort by clinically suspected IIH. We compared females with confirmed IIH (2013 criteria) to “IIH mimics” in whom IIH was refuted (controls). We excluded patients with secondary pseudotumor cerebri syndrome, pregnancy, IIH relapse, age > 50 years, male sex, other significant disease, or use of medications associated with multiorgan biochemical abnormalities with a prevalence of > 1%. Results: We compared 139 females with IIH to 78 controls of similar sex, age, and body mass index (BMI). In IIH, we found relatively higher plasma levels of leukocytes (p=0.02), neutrophils (p=0.04), and alkaline phosphatase (p=0.03), and lower levels of plasma urea (p=0.04) and CSF protein (p=0.02). Leukocytes and neutrophils correlated with lumbar opening pressure and were significantly higher in severe papilledema. Findings were not explained by BMI, smoking, or statistically influential covariates. Conclusion: In a well-defined prospective cohort of newly diagnosed IIH restricted by careful censoring of secondary cases and confounding factors, we found relatively increased systemic inflammation in plasma which correlated with markers of more severe IIH disease activity. IIH is likely a heterogeneous and complex disease in which inflammation seems to be involved. Plain Language Summary: Idiopathic intracranial hypertension (IIH) is a poorly understood neuro-metabolic disorder in which adiposity is somehow related to raised intracranial pressure (ICP) causing optic nerve swelling. To explore possible indices of pathophysiology and comorbidity, we compared results of routine blood and cerebrospinal fluid (CSF) analyses obtained from individuals with newly diagnosed IIH (hence, naïve to ICP-lowering treatment) to results from healthy control patients disproven of IIH. Analyses covered multiple organ systems. We carefully censored individuals with conditions or drugs that could confound biomarker analyses. We included 139 individuals with IIH and 78 controls of similar age, BMI, and sex. In IIH, we observed relatively higher levels of blood leukocytes, neutrophils, and alkaline phosphatase, and lower levels of urea and CSF protein. Elevation of leukocytes was not explained by BMI, or active smoking, was associated with severe optic nerve edema and correlated with lumbar opening pressure, a surrogate measure of ICP. These findings support established hypotheses of a role of inflammation in IIH and confirms previous observations of lower CSF protein, possibly related to altered CSF flow. Lower urea may reflect disrupted amino acid metabolism and warrants further study. Keywords: pseudotumor cerebri syndrome, inflammation, urea, protein, amino acid metabolism, biomarkers
Hansen et al. (Sun,) studied this question.