Metabolic Dysfunction in New-Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2024-06-22 DOI:10.1002/ana.27010

Johanne Juhl Korsbæk, Rigmor Højland Jensen, Dagmar Beier, Elisabeth Arnberg Wibroe, Snorre Malm Hagen, Laleh Dehghani Molander, Matthew Paul Gillum, Katrine Svart, Thomas Folkmann Hansen, Lisette J.A. Kogelman, Connar Stanley James Westgate

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Abstract

Objective

Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity.

Methods

This is a prospective case–control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new-onset, treatment-naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) -matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non-targeted mass spectrometry.

Results

Serum sphingosine 1-phosphate (S1P), adenosine, and glutamate were 0.46-fold (q < 0.0001), 0.25-fold (q = 0.0048), and 0.44-fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl-lysophosphatidylcholine (LysoPC-18) and 2-palmitoyl-lysophosphatidylcholine (LysoPC-16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) -fold lower. LysoPC-18 was higher in patients with moderate–severe versus mild papilledema (p = 0.022). LysoPC-18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = −0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC-16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new-onset IIH.

Interpretation

We identify perturbed metabolism in new-onset IIH. S1P and LysoPC-16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595–607

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新发特发性颅内高压症的代谢功能障碍：新型生物标记物的鉴定

目的特发性颅内高压症（IIH）是一种神经代谢性疾病，发病率越来越高。该病的病理生理学尚不清楚，但改善诊断和管理需要发现新的生物标志物。我们的目标是确定 IIH 的候选生物标志物，其次是检验已确定的代谢物与疾病严重程度之间的关联。方法这是一项前瞻性病例对照研究，收集了新发、未经治疗的 IIH 患者（n = 60）的脑脊液（CSF）、血清和临床数据。该研究连续纳入了丹麦两家三级头痛中心的患者，并招募了年龄、性别和体重指数（BMI）相匹配的健康对照组（35 人）。在眼部症状缓解时检索临床数据（n = 55）。结果血清鞘磷脂 1-磷酸（S1P）、腺苷和谷氨酸在 IIH 中分别低 0.46 倍（q < 0.0001）、0.25 倍（q = 0.0048）和 0.44 倍（q < 0.0001）。CSF 硬脂酰-异磷脂酰胆碱（LysoPC-18）和 2-棕榈酰-异磷脂酰胆碱（LysoPC-16）分别低 0.42 倍（q = 0.0025）和 0.37 倍（q < 0.001）。中重度乳头水肿患者的 LysoPC-18 比轻度乳头水肿患者高（p = 0.022）。LysoPC-18 与视网膜神经纤维层厚度呈正相关（p = 0.0012，r = 0.42），与自动测距仪的平均偏差呈反相关（p = 0.01，r = -0.35）。较高的基线血清 S1P（p = 0.018）和较低的 CSF LysoPC-16（p = 0.003）与眼部缓解时的视神经萎缩相关。通路分析表明，在新发 IIH 中存在脂质代谢失调和氧化还原紊乱。S1P和LysoPC-16与随后的视神经萎缩有关，因此具有潜在的预后价值。这种特异性差异代谢物与预后之间的关联为具有临床意义的新型生物标志物提供了大量证据，应成为进一步有针对性研究的重点。ann neurol 2024

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.