Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark.
Translational Research Centre, Rigshospitalet, Glostrup, Denmark.
Ann Neurol. 2024 Sep;96(3):595-607. doi: 10.1002/ana.27010. Epub 2024 Jun 22.
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.
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.
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.
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.
特发性颅内高压（IIH）是一种神经代谢疾病，发病率不断上升。其病理生理学尚不清楚，但要改善诊断和治疗，就需要发现新的生物标志物。我们的目的是在 IIH 中确定此类候选生物标志物，并进一步检验鉴定出的代谢物与疾病严重程度之间的相关性。
这是一项前瞻性病例对照研究，对新发病、未经治疗的 IIH 患者（n=60）的脑脊液（CSF）、血清和临床数据进行了采集。患者连续来自丹麦的 2 家三级头痛中心，招募了年龄、性别和体重指数（BMI）匹配的健康对照者（n=35）。在眼部缓解时（n=55）获得了临床数据。使用非靶向质谱法分析样本。
血清中鞘氨醇 1-磷酸（S1P）、腺苷和谷氨酸分别低 0.46 倍（q<0.0001）、0.25 倍（q=0.0048）和 0.44 倍（q<0.0001），CSF 中硬脂酰-溶血磷脂胆碱（LysoPC-18）和 2-棕榈酰-溶血磷脂胆碱（LysoPC-16）分别低 0.42（q=0.0025）和 0.37（q<0.001）倍。中度至重度视乳头水肿患者的 LysoPC-18 高于轻度视乳头水肿患者（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），与自动视野计的平均偏差呈负相关（p=0.01，r=-0.35）。基线时血清 S1P 较高（p=0.018）和 CSF LysoPC-16 较低（p=0.003）与眼部缓解时视神经萎缩相关。途径分析表明，新发病 IIH 存在代谢紊乱。S1P 和 LysoPC-16 由于与随后的视神经萎缩相关，具有潜在的预后价值。这些特定的、不同的代谢物与结局之间的关联为具有临床意义的新型生物标志物提供了实质性证据，应成为进一步靶向研究的重点。
