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基于 MRI 的脑容量测量和视网膜光学相干断层扫描作为急性甲醇中毒预后的生物标志物。

MRI-based brain volumetry and retinal optical coherence tomography as the biomarkers of outcome in acute methanol poisoning.

机构信息

Toxicological Information Centre, General University Hospital, Prague, Czech Republic; Department of Occupational Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

出版信息

Neurotoxicology. 2020 Sep;80:12-19. doi: 10.1016/j.neuro.2020.06.006. Epub 2020 Jun 15.

Abstract

BACKGROUND

Basal ganglia lesions are typical findings on magnetic resonance imaging (MRI) of the brain in survivors of acute methanol poisoning. However, no data are available on the association between the magnitude of damaged brain regions, serum concentrations of markers of acute methanol toxicity, oxidative stress, neuroinflammation, and the rate of retinal nerve ganglion cell loss.

OBJECTIVES

To investigate the association between MRI-based volumetry of the basal ganglia, retinal nerve fibre layer (RNFL) thickness and prognostic laboratory markers of outcomes in acute methanol poisoning.

METHODS

MRI-based volumetry of putamen, nucleus caudatus and globus pallidus was performed and compared with laboratory parameters of severity of poisoning and acute serum markers of oxidative damage of lipids (8-isoprostan, MDA, HHE, HNE), nucleic acids (8-OHdG, 8-OHG, 5-OHMU), proteins (o-Thyr, NO-Thyr, Cl-Thyr) and leukotrienes (LTC4, LTD4, LTE4, LTB4), as well as with the results of RNFL measurements by optic coherence tomography (OCT) in 16 patients with acute methanol poisoning (Group I) and in 28 survivors of poisoning two years after discharge with the same markers measured within the follow-up examination (Group II). The control group consisted of 28 healthy subjects without methanol poisoning.

RESULTS

The survivors of acute methanol poisoning had significantly lower volumes of basal ganglia than the controls. The patients with MRI signs of methanol-induced toxic brain damage had significantly lower volumes of basal ganglia than those without these signs. A positive correlation was found between the volume of putamen and arterial blood pH on admission (r = 0.45; p = 0.02 and r = 0.44; p = 0.02 for left and right putamen, correspondingly). A negative correlation was present between the volumes of putamen and acute serum lactate (r = -0.63; p < 0.001 and r = -0.59; p = 0.01), creatinine (r = -0.53; p = 0.01 and r = -0.47; p = 0.01) and glucose (r = -0.55; p < 0.001 and r = -0.50; p = 0.01) concentrations. The volume of basal ganglia positively correlated with acute concentrations of markers of lipoperoxidation (8-isoprostan: r = 0.61; p < 0.05 and r = 0.59; p < 0.05 for left and right putamen, correspondingly) and inflammation (leukotriene LTB4: r = 0.61; p < 0.05 and r = 0.61; p < 0.05 for left and right putamen, correspondingly). The higher the volume of the basal ganglia, the higher the thickness of the RNFL, with the strongest positive association between global RNFL and the volume of putamen bilaterally (all p < 0.01). In the follow-up markers of oxidative stress and inflammation, only o-Thyr concentration negatively correlated with the volume of putamen bilaterally (r = -0.39; p < 0.05 and r = -0.37; p < 0.05 for left and right putamen, correspondingly).

CONCLUSION

In survivors of acute methanol poisoning with signs of toxic brain damage, the magnitude of affected areas correlated with acute parameters of severity of poisoning, markers of oxidative stress and neuroinflammation. There was a positive association between the basal ganglia volume and the thickness of RNFL, making OCT an important screening test and MRI-based volumetry the confirmative diagnostic method for the detection of CNS sequelae of methanol poisoning.

摘要

背景

基底节病变是急性甲醇中毒幸存者脑部磁共振成像(MRI)的典型发现。然而,目前尚无关于受损脑区的严重程度、急性甲醇毒性标志物的血清浓度、氧化应激、神经炎症与视网膜神经节细胞丢失率之间的关系的数据。

目的

研究急性甲醇中毒患者基于 MRI 的基底节容积、视网膜神经纤维层(RNFL)厚度与预后实验室标志物之间的关系。

方法

对 16 例急性甲醇中毒患者(I 组)和 28 例出院后两年随访时用相同标志物测量的幸存者(II 组)进行基于 MRI 的壳核、尾状核和苍白球容积测量,并与中毒严重程度的实验室参数和急性血清脂质氧化损伤标志物(8-异前列腺素、MDA、HHE、HNE)、核酸(8-OHdG、8-OHG、5-OHMU)、蛋白质(o-Thyr、NO-Thyr、Cl-Thyr)和白三烯(LTC4、LTD4、LTE4、LTB4)进行比较。并通过光学相干断层扫描(OCT)测量 RNFL 结果。对照组由 28 例无甲醇中毒的健康受试者组成。

结果

急性甲醇中毒幸存者的基底节容积明显低于对照组。有 MRI 表现为甲醇诱导的毒性脑损伤的患者的基底节容积明显低于无这些表现的患者。入院时,壳核的体积与动脉血 pH 值呈正相关(左侧壳核 r = 0.45;p = 0.02,右侧壳核 r = 0.44;p = 0.02)。壳核体积与急性血清乳酸(r = -0.63;p < 0.001 和 r = -0.59;p = 0.01)、肌酐(r = -0.53;p = 0.01 和 r = -0.47;p = 0.01)和葡萄糖(r = -0.55;p < 0.001 和 r = -0.50;p = 0.01)浓度呈负相关。基底节的体积与脂过氧化标志物的急性浓度呈正相关(8-异前列腺素:r = 0.61;p < 0.05,左、右侧壳核 r = 0.59;p < 0.05)和炎症(白三烯 LTB4:r = 0.61;p < 0.05,左、右侧壳核 r = 0.61;p < 0.05)。基底节体积越大,RNFL 厚度越高,双侧壳核的全球 RNFL 与壳核体积之间存在最强的正相关(均 p < 0.01)。在随访的氧化应激和炎症标志物中,只有 o-Thyr 浓度与双侧壳核体积呈负相关(r = -0.39;p < 0.05,左、右侧壳核 r = -0.37;p < 0.05)。

结论

在有中毒性脑损伤表现的急性甲醇中毒幸存者中,受累区域的严重程度与中毒的急性严重程度参数、氧化应激和神经炎症标志物相关。基底节体积与 RNFL 厚度呈正相关,使 OCT 成为重要的筛查试验,基于 MRI 的容积测量成为检测甲醇中毒中枢神经系统后遗症的确认性诊断方法。

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