Libien J, Kupersmith M J, Blaner W, McDermott M P, Gao S, Liu Y, Corbett J, Wall M
Pathology, State University of New York, Downstate School of Medicine, Brooklyn, NY, United States.
Neurology and Ophthalmology, Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
J Neurol Sci. 2017 Jan 15;372:78-84. doi: 10.1016/j.jns.2016.11.014. Epub 2016 Nov 10.
Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF.
Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months.
At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02).
Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.
维生素A及其代谢产物（称为类视黄醇）被认为在特发性颅内高压（IIH）的发病过程中起作用。IIH治疗试验（IIHTT）显示乙酰唑胺（ACZ）在改善视野功能、视乳头水肿分级、生活质量和脑脊液（CSF）压力方面具有疗效。我们推测IIH患者血清和脑脊液中的维生素A代谢产物水平会升高。
从96名随机分配接受ACZ或安慰剂治疗的IIHTT受试者以及25名性别、年龄和体重指数（BMI）相似的对照者中获取血清维生素A及其代谢产物的综合测量值。这些包括视黄醇、视黄醇结合蛋白、全反式维甲酸（ATRA）、α-和β-胡萝卜素以及β-隐黄质。IIHTT受试者在研究开始时和六个月时还进行了脑脊液和血清维生素A及代谢产物的测量。
在研究开始时，在IIHTT受试者（中位数4.33nM）和对照者（中位数5.04nM，p = 0.02）中，仅血清ATRA这一维生素A代谢产物存在显著差异。IIHTT受试者的BMI与血清ATRA、α-和β-胡萝卜素以及β-隐黄质呈轻度显著负相关。相比之下，对照者的BMI仅与血清ATRA相关。在六个月时，ACZ治疗组的血清视黄醇、α-胡萝卜素、β-胡萝卜素和脑脊液视黄醇较基线水平升高，但与安慰剂组相比，ACZ组仅α-胡萝卜素（p = 0.02）和脑脊液ATRA（p = 0.04）的升高显著更大。在两个治疗组中，六个月内没有其他维生素A测量值发生显著变化。体重减轻仅与血清β-胡萝卜素的变化（r = -0.44，p = 0.006）和脑脊液视黄醇的变化（r = -0.61，p = 0.02）相关。
维生素A毒性不太可能是IIH病因中的一个促成因素。我们的研究结果与先前报告的结果不同，部分原因是我们使用了更准确的定量方法并同时测量了血清和脑脊液中的维生素A代谢产物。ACZ可能会改变IIH患者的类视黄醇代谢。
