У пациентов с идиопатической внутричерепной гипертензией выявлены уникальные метаболические нарушения, отличающиеся от профилей при ожирении

Patients with idiopathic intracranial hypertension (IIH) show alterations in circulating lipid and amino acid metabolites that differ from those observed in individuals with obesity without IIH, according to study results published in Neurology Open Access. Obesity is a major risk factor for IIH, but the metabolic mechanisms linking obesity to IIH remain poorly understood. Previous research has implicated metabolic dysfunction in IIH, although it remains unclear whether these abnormalities reflect obesity itself or metabolic changes specific to the disease. Researchers conducted a cross-sectional metabolomic analysis using serum samples from the Idiopathic Intracranial Hypertension Treatment Trial (ClinicalTrials.gov Identifier: NCT01003639 ). Samples from patients with newly diagnosed, untreated IIH were compared with those from control participants matched for age, sex, race/ethnicity, and body mass index (BMI). Metabolites were measured using untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry, and false discovery rate adjustment was used to account for multiple comparisons. These findings suggest metabolic heterogeneity among individuals with obesity and identify potential pathways relevant to IIH pathophysiology. The analysis included 321 serum samples, of which 178 were from participants with IIH and 143 were from matched control participants. Mean age was 29.0 years among participants with IIH and 28.8 years among control participants, while mean BMI was 39.9 and 39.6 kg/m², respectively. Overall, 98% of participants were women and 65% were White. Blood samples from the IIH group were obtained before treatment. Among 967 compounds that passed quality-control criteria, 221 differed between the IIH and control groups ( P <.05). Of these, 90 were higher and 131 were lower among participants with IIH. After false discovery rate adjustment, 60 metabolites remained statistically significant. Between-group differences were modest overall, ranging from approximately 0.5- to 1.6-fold. Chemical enrichment analysis identified higher levels of sphingomyelins ( P <.0001), saturated fatty acids ( P <.0001), lactosylceramides ( P <.0001), and unsaturated fatty acids, including linoleic acid ( P =.0001), among participants with IIH. Unsaturated lysophosphatidylcholines ( P =.0079), hexoses ( P =.014), and dipeptides ( P =.038) were also elevated. In contrast, saturated and unsaturated triglycerides were lower in participants with IIH (both P <.0001), along with phosphatidylethanolamines ( P <.0001), saturated ceramides ( P =.03), and branched-chain amino acids (BCAAs), including valine ( P =.0007). Lower BCAA levels are notable because increased levels are commonly reported in insulin-resistant obesity and type 2 diabetes. The authors noted that this pattern may indicate that the metabolic phenotype associated with IIH differs from the classical insulin-resistant obesity profile. Other findings included lower cystine and tyrosine concentrations and higher linoleic acid levels among participants with IIH. Differences in triglycerides and ceramides also contrasted with metabolic patterns commonly associated with insulin-resistant obesity, while findings for sphingomyelins were consistent with some but not all previous studies. Study limitations include the cross-sectional design, lack of longitudinal data, absence of cerebrospinal fluid and urine samples, lack of dietary intake data, inconsistent fasting conditions, and absence of a comparison group of women with normal BMI. “These findings suggest metabolic heterogeneity among individuals with obesity and identify potential pathways relevant to IIH pathophysiology,” the study authors concluded.  Disclosures: This research was supported by the Neuro-Ophthalmology Research Disease Investigator Consortium. Please see the original reference for a full list of disclosures. References: Liu YA, Krajnovic A, Brydges C, et al. Systemic metabolomic changes in idiopathic intracranial hypertension: a substudy of the IIH Treatment Trial. Neurol Open Access. 2026;2(3):e000119. doi:10.1212/WN9.0000000000000119