Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Department of Neurosurgery, Innsbruck Medical University, Innsbruck, Austria.
J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):79-86. doi: 10.1136/jnnp-2013-307326. Epub 2014 Apr 16.
Recent evidence suggests axonal injury after aneurysmal subarachnoid haemorrhage (aSAH). The microtubule-associated protein, tau, has been shown to be elevated in the cerebrospinal fluid after aSAH, however, brain extracellular tau levels and their relation to long-term neurological and cognitive outcomes have not been investigated.
Serial cerebral microdialysis (CMD) samples were collected from 22 consecutive aSAH patients with multimodal neuromonitoring to determine CMD-total-tau by ELISA. CMD-total-tau was analysed considering other brain metabolic parameters, brain tissue oxygen tension (PbtO2), and functional and neuropsychological outcome at 12 months. All outcome models were analysed using generalised estimating equations with an autoregressive working correlation matrix to account for multiple measurements of brain extracellular proteins per subject.
CMD-total-tau levels positively correlated with brain extracellular fluid levels of lactate (r=0.40, p<0.001), glutamate (r=0.45, p<0.001), pyruvate (r=0.26, p<0.001), and the lactate-pyruvate ratio (r=0.26, p<0.001), and were higher in episodes of hypoxic (PbtO2<20 mm Hg) brain extracellular lactate elevation (>4 mmol/L) (p<0.01). More importantly, high CMD-total-tau levels were associated with poor functional outcome (modified Rankin Scale ≥4) 12 months after aSAH even after adjusting for disease severity and age (p=0.001). A similar association was found with 3/5 neuropsychological tests indicative of impairments in cognition, psychomotor speed, visual conceptualisation and frontal executive functions at 1 year after aSAH (p<0.01).
These results suggest that CMD-total tau may be an important biomarker for predicting long-term outcome in patients with severe aSAH. The value of axonal injury needs further confirmation in a larger patient cohort, preferably combined with advanced imaging techniques.
最近的证据表明，蛛网膜下腔出血（aSAH）后存在轴突损伤。微管相关蛋白 tau 已被证明在 aSAH 后脑脊液中升高，然而，脑细胞外 tau 水平及其与长期神经和认知结局的关系尚未得到研究。
对 22 例连续行多模态神经监测的 aSAH 患者进行连续脑微透析（CMD）采样，通过 ELISA 测定 CMD 总 tau。分析 CMD 总 tau 与其他脑代谢参数、脑组织氧张力（PbtO2）以及 12 个月时的功能和神经心理学结局之间的关系。所有结局模型均采用广义估计方程分析，并使用自回归工作相关矩阵，以解释每个患者脑细胞外蛋白的多次测量。
CMD 总 tau 水平与脑细胞外液中乳酸（r=0.40，p<0.001）、谷氨酸（r=0.45，p<0.001）、丙酮酸（r=0.26，p<0.001）和乳酸-丙酮酸比值（r=0.26，p<0.001）呈正相关，且在缺氧（PbtO2<20mmHg）脑细胞外乳酸升高（>4mmol/L）发作时（p<0.01）更高。更重要的是，即使在调整疾病严重程度和年龄后，CMD 总 tau 水平较高与 aSAH 后 12 个月功能结局较差（改良 Rankin 量表≥4）相关（p=0.001）。在 aSAH 后 1 年，与认知、运动速度、视觉概念化和额叶执行功能受损的 3/5 项神经心理学测试相关的类似关联（p<0.01）。
这些结果表明，CMD 总 tau 可能是预测严重 aSAH 患者长期结局的重要生物标志物。轴突损伤的价值需要在更大的患者队列中进一步确认，最好结合先进的成像技术。
