Ho Wing Mann, Görke Alice S, Glodny Bernhard, Oberacher Herbert, Helbok Raimund, Thomé Claudius, Petr Ondra
Department of Neurosurgery, Medical University Innsbruck, Innsbruck, Austria.
Department of Radiology, Medical University Innsbruck, Innsbruck, Austria.
Front Neurol. 2020 Jun 23;11:589. doi: 10.3389/fneur.2020.00589. eCollection 2020.
The aim of this study was to investigate metabolite levels in cerebrospinal fluid (CSF) in their time-dependent course after aneurysmal subarachnoid hemorrhage (aSAH) comparing them to patients harboring unruptured intracranial aneurysms. Eighty CSF samples of 16 patients were analyzed. The study population included patients undergoing endovascular/microsurgical treatment of ruptured intracranial aneurysms ( = 8), which were assessed for 9 days after aSAH. Control samples were collected from the basal cisterns in elective aneurysm surgery ( = 8). The CSF samples were consecutively collected with extraventricular drain (EVD) placement/intraoperatively, 6 h later, and daily thereafter (day 1-9). The endogenous metabolites were analyzed with a targeted quantitative and quality controlled metabolomics approach using the AbsoluteIDQ®p180Kit. Differences inbetween timepoints and compared to the control group were evaluated. Numerous alterations of amino acid (AA) levels were detected within the first hours after bleeding. The highest mean concentrations occurred 1 week after aSAH. AA levels were continuously increasing over time starting 6 h after aSAH. Taurine concentration was highest briefly after aSAH starting to decrease already after 6 h (vs. day 1-9, = 0.02). The levels of sphingomyelins/ phosphatidylcholines/ lysophosphatidylcholines/mono-unsaturated fatty acid chain were highly elevated on day 0 (compared to other timepoints or controls, < 0.01) and decreased over the next several days to concentrations comparable to the control group. Carnitine concentrations were decreased after SAH (vs. day 7, < 0.01), while they recovered within the next day. The Fischer ratio of branched-chain AA to aromatic AA was lowest immediately after SAH and increased in 7 days ( < 0.001). AA levels in CSF increased overtime and often differ from patients without SAH. There was a peak concentration of structural AA within the first 6 h after aneurysm treatment. Time-dependent alterations of CSF metabolites and compounds may elucidate pathophysiological processes after aSAH, providing potential predictors assessed non-invasively by routine lab testing.
本研究的目的是调查动脉瘤性蛛网膜下腔出血（aSAH）后脑脊液（CSF）中代谢物水平随时间的变化过程，并将其与未破裂颅内动脉瘤患者进行比较。分析了16例患者的80份脑脊液样本。研究人群包括接受破裂颅内动脉瘤血管内/显微手术治疗的患者（n = 8），在aSAH后9天进行评估。对照样本取自择期动脉瘤手术中的基底池（n = 8）。脑脊液样本通过脑室外引流（EVD）放置/术中连续采集，6小时后，此后每天（第1 - 9天）采集。使用AbsoluteIDQ®p180试剂盒，采用靶向定量和质量控制的代谢组学方法分析内源性代谢物。评估各时间点之间以及与对照组相比的差异。出血后的最初几小时内检测到多种氨基酸（AA）水平的改变。最高平均浓度出现在aSAH后1周。AA水平从aSAH后6小时开始随时间持续升高。牛磺酸浓度在aSAH后短暂达到最高，6小时后即开始下降（与第第1 - 9天相比，P = 0.02）。鞘磷脂/磷脂酰胆碱/溶血磷脂酰胆碱/单不饱和脂肪酸链的水平在第0天显著升高（与其他时间点或对照组相比，P < 0.01），并在接下来的几天内下降至与对照组相当的浓度。SAH后肉碱浓度降低（与第7天相比，P < 0.01），但在第二天内恢复。SAH后立即支链AA与芳香族AA的费舍尔比值最低，并在7天内升高（P < 0.001）。脑脊液中的AA水平随时间增加，且通常与无SAH的患者不同。动脉瘤治疗后的最初6小时内结构AA浓度达到峰值。脑脊液代谢物和化合物的时间依赖性改变可能阐明aSAH后的病理生理过程，为通过常规实验室检测进行非侵入性评估提供潜在的预测指标。
