Identifying MicroRNA Biomarkers in Idiopathic Intracranial Hypertension: A Pilot Study

Idiopathic intracranial hypertension (IIH) is characterized by raised intracranial pressure (ICP). It predominantly affects women with obesity and can cause disabling headaches and permanent visual loss. IIH is misdiagnosed in up to 40% of cases. Diagnosis and monitoring often rely on frequent invasive lumbar puncture. This pilot study aimed to identify serum microRNA (miRNA) markers associated with a diagnosis of IIH and disease activity and to assess their relevance in the CNS through identification in CSF.

Serum and CSF samples from participants in the IIH-Weight Trial (a randomized controlled trial comparing the effectiveness of bariatric surgery with that of a community weight management intervention in lowering ICP, recruited 2014-2017) were analyzed at baseline (active disease) and 12 months (participants in remission with no papilledema). Eligible participants were adult women with active IIH (those without papilledema were excluded). Disease activity was assessed by quantifying the degree of papilledema using Spectralis spectral-domain optical coherence tomography. A panel of 40 candidate miRNAs was assessed. Comparator groups included participants with obesity or migraine. Analyses used Student t tests and one-way ANOVA followed by Tukey multiple comparisons test. Differentially expressed miRNAs were evaluated in relation to clinical disease activity and metabolic profiles, using linear regression analysis.

Five of 40 serum miRNAs showed significantly lower expression in active IIH (n = 9; 100% female, mean 30.25 ± 4.75 years) compared with IIH in remission. Serum hsa-miR-16-5p had the highest diagnostic performance for active IIH (area under the curve 0.951). Serum hsa-miR-16-5p (p < 0.0001; CI -7.286 to -2.503) and hsa-miR-7-5p (p = 0.0032; CI -7.240 to -1.372) were significantly lower in active IIH compared with obesity controls (n = 9; 100% female, mean 38.22 ± 7.99 years). Serum hsa-miR-7a-5p were significantly higher in active IIH compared with migraine (n = 12; 100% female, mean 44.67 ± 8.88 years). Only hsa-miR-16-5p differentiated active IIH from both participants with migraine and obesity. hsa-miR-16-5p also differentiated active IIH from IIH remission in CSF (p = 0.0354; CI -3.062 to -0.1282). Serum and CSF hsa-miR-16-5p correlated significantly with ICP (serum p < 0.0001; CI -0.1660 to -0.0732; CSF p = 0.046; CI 0.0018-0.1841), papilledema (serum p = 0.0236; CI -0.01548 to -0.0001; CSF p = 0.0241; CI 0.002-0.033). hsa-miR-16-5p was associated with metabolites involved in fatty acid metabolism and lipid biosynthesis.

Serum hsa-miR-16-5p emerged as a candidate biomarker associated with active IIH. It differentiated active disease from remission, migraine, and obesity. It correlated with clinical and metabolic markers of disease activity. These findings warrant validation in larger studies to assess its potential as a minimally invasive biomarker for IIH diagnosis and monitoring.

This study provides Class III evidence that serum microRNA markers may potentially distinguish active idiopathic intracranial hypertension from remission and controls in adult women.