Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients
Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients
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DOI：
10.1155/2019/9320791
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发表时间：
2019-09-10
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影响因子：
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通讯作者：
Pugliatti, Maura
中科院分区：
文献类型：
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作者：
Castellazzi, Massimiliano;Lamberti, Giuseppe;Pugliatti, Maura
背景多发性硬化（MS）是一种中枢神经系统的慢性炎症和退行性疾病，其典型特征是免疫介导的局灶性脱髓鞘和继发性轴突变性。在MS患者中已经报道了正常外观的白色物质（NAWM）的脑灌注不足，并且可能由升高的内皮素-1（ET-1）水平介导，ET-1是MS局灶性病变中反应性星形胶质细胞释放的最有效的血管收缩肽。视神经炎（ON）是MS最常见的表现之一，也表现为视乳头周围血管灌注不足伴椎间盘肿胀。目标。我们的目的是比较血清和脑脊液（CSF）的ET-1水平作为MS-ON的一个潜在的预后标志物在两组患者不同的严重程度MS-ON的临床表现。材料和方法。一项根据常规眼科标准（包括光学相干断层扫描）比较临床侵袭性MS-ON（A-MS-ON）和非侵袭性MS-ON（NA-MS-ON）患者血清和CSF ET-1水平的横断面研究。使用市售ELISA方法测量CSF和血清ET-1浓度。结果招募了16名因MS引起的视觉障碍而连续转诊至神经病学单位的患者，A-MS-ON组11例（69%），NA-MS-ON组5例（31%），A-MS-ON组中位CSF ET-1水平及CSF/血清ET-1比值均显著高于NA-MS-ON组与NA-MS-ON（0.16对0.16）相比，NA-MS-ON（0.30对0.56 ng/ml）的平均浓度为0.30 ng/ml。结论. MS患者中从ON恢复的严重性和失败可能取决于由高鞘内产生的ET-1诱导的视神经的血管灌注不足，ET-1是MS中ON恢复的潜在预后标志物。CSF ET-1水平的检测可以允许鉴定可能受益于ET-1拮抗剂治疗的ON患者组（例如，波生坦）。
Background. Multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the central nervous system, typically features immune-mediated focal demyelination and secondary axonal degeneration. Cerebral hypoperfusion of the normal-appearing white matter (NAWM) has been reported in MS patients and may be mediated by elevated levels of endothelin-1 (ET-1), a most potent vasoconstrictive peptide released from reactive astrocytes in MS focal lesions. Optic neuritis (ON) is one of the most frequent manifestations of MS and also shows peripapillary vascular hypoperfusion in combination with disc swelling. Aims. We aimed to compare serum and cerebrospinal fluid (CSF) levels of ET-1 as a potential prognostic marker of MS-ON in two groups of patients differing for severity of MS-ON clinical presentation. Materials and Methods. A cross-sectional study to compare serum and CSF levels of ET-1 between patients with clinically aggressive MS-ON (A-MS-ON) and nonaggressive MS-ON (NA-MS-ON) according to conventional ophthalmological criteria, including optical coherence tomography. CSF and serum concentrations of ET-1 were measured using a commercially available ELISA method. Results. Sixteen patients consecutively referred to the Units of Neurology for visual disturbances attributable to MS were recruited, 11 (69%) patients with A-MS-ON and 5 (31%) with NA-MS-ON. Median CSF ET-1 levels and CSF/serum ET-1 quotient were significantly higher in patients with A-MS-ON (0.30 vs. 0.56 ng/ml) as compared to NA-MS-ON (0.16 vs. 0.16). Conclusions. Severity and failure in the recovery from ON in MS patients may depend from vascular hypoperfusion of the optic nerve induced by high intrathecally produced ET-1, a potential prognostic marker of ON recovery in MS. The detection of CSF ET-1 levels may allow identifying groups of ON patients potentially benefitting from treatment with ET-1 antagonists (e.g., bosentan).