Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis.
Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis.
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DOI：
10.1093/brain/awv203
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Larsson HB
中科院分区：
文献类型：
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作者：
Cramer SP;Modvig S;Simonsen HJ;Frederiksen JL;Larsson HB
请参阅Naismith and Cross （doi:）对本文的科学评论。视神经炎与多发性硬化症的发展高度相关。Cramer等人的研究表明，与单独的t2病变计数相比，MRI测量血脑屏障通透性可以提高2年内转化为多发性硬化症的预测。渗透性测量也与脑脊液细胞运输和血脑屏障破坏的生物标志物相关。请参阅Naismith and Cross （doi:）对本文的科学评论。视神经炎与多发性硬化症的发展高度相关。Cramer等人的研究表明，与单独的t2病变计数相比，MRI测量血脑屏障通透性可以提高2年内转化为多发性硬化症的预测。渗透性测量也与脑脊液细胞运输和血脑屏障破坏的生物标志物相关。视神经炎是一种与多发性硬化症高度相关的急性炎症。目前，磁共振成像显示的T2病变数量是预测多发性硬化症未来发展的最佳指标。以往的研究发现，在多发性硬化症患者的正常白质中，血脑屏障的通透性异常。在这里，我们首次研究了血脑屏障通透性预测视神经炎向多发性硬化症转变的能力，并与脑脊液炎症、细胞运输和血脑屏障破坏的标志物进行了直接比较。为此，我们应用动态对比增强磁共振成像在3t测量39例单症状视神经炎患者的血脑屏障通透性，所有患者在诊断时都将成像作为诊断检查的一部分。纳入18名健康对照进行比较。患者在视神经炎发病4周内行磁共振成像和腰椎穿刺。从视神经炎发病2年后的医院记录中获得多发性硬化症转化的信息。Logistic回归分析显示，与单纯T2病变计数相比，正常白质的基线通透性显著提高了2年内多发性硬化症转化的预测（根据2010年修订的McDonald诊断标准）。通透性与T2病变计数无相关性。外观正常的白质通透性增加0.1 ml/100 g/min，多发性硬化的风险增加8.5倍，而T2病变超过9个，其风险增加52.6倍。正常白质通透性的受试者工作特征曲线分析的截止值为0.13 ml/100 g/min，预测多发性硬化的敏感性为88%，特异性为72%。我们发现通透性与脑脊液白细胞计数以及脑脊液中CXCL10和MMP9水平之间存在显著相关性。这些发现表明，通过磁共振成像测量的血脑屏障通透性可能提供新的病理信息，作为多发性硬化相关神经炎症的标志物，在一定程度上反映了血脑屏障的细胞通透性，而T2病变计数可能更多地反映了亚临床复发前期的长度。请参阅Naismith and Cross （doi:）对本文的科学评论。
See Naismith and Cross (doi:) for a scientific commentary on this article. Optic neuritis is highly associated with development of multiple sclerosis. Cramer et al. show that MRI measures of blood-brain barrier permeability improve prediction of conversion to multiple sclerosis within 2 years, compared to T2-lesion count alone. Permeability measures also correlate with CSF biomarkers of cellular trafficking and blood-brain barrier breakdown. See Naismith and Cross (doi:) for a scientific commentary on this article. Optic neuritis is highly associated with development of multiple sclerosis. Cramer et al. show that MRI measures of blood-brain barrier permeability improve prediction of conversion to multiple sclerosis within 2 years, compared to T2-lesion count alone. Permeability measures also correlate with CSF biomarkers of cellular trafficking and blood-brain barrier breakdown. Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood–brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood–brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison with cerebrospinal fluid markers of inflammation, cellular trafficking and blood–brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood–brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2 years after optic neuritis onset. Logistic regression analysis showed that baseline permeability in normal-appearing white matter significantly improved prediction of multiple sclerosis conversion (according to the 2010 revised McDonald diagnostic criteria) within 2 years compared to T2 lesion count alone. There was no correlation between permeability and T2 lesion count. An increase in permeability in normal-appearing white matter of 0.1 ml/100 g/min increased the risk of multiple sclerosis 8.5 times whereas having more than nine T2 lesions increased the risk 52.6 times. Receiver operating characteristic curve analysis of permeability in normal-appearing white matter gave a cut-off of 0.13 ml/100 g/min, which predicted conversion to multiple sclerosis with a sensitivity of 88% and specificity of 72%. We found a significant correlation between permeability and the leucocyte count in cerebrospinal fluid as well as levels of CXCL10 and MMP9 in the cerebrospinal fluid. These findings suggest that blood–brain barrier permeability, as measured by magnetic resonance imaging, may provide novel pathological information as a marker of neuroinflammation related to multiple sclerosis, to some extent reflecting cellular permeability of the blood–brain barrier, whereas T2 lesion count may more reflect the length of the subclinical pre-relapse phase. See Naismith and Cross (doi:) for a scientific commentary on this article.