Biomarkers of CSF Predicting Shunt-Dependent Hydrocephalus and Outcome after Aneurysmal SAH
Date Issued
2015
Date
2015
Author(s)
Wang, Kuo-Chuan
Abstract
Background and objective Spontaneous subarachnoid hemorrhage (SAH) is most frequently caused by aneurysmal rupture. The cortical vessels were immersed in cerebrospinal fluid. In the normal cerebrospinal fluid circulation, CSF flow through three holes of the fourth ventricle into subarachnoid space; once a large number of subarachnoid hemorrhage, as shown, cerebral spinal fluid, although anatomically not blocked, but the functionally may be separated, fresh cerebrospinal fluid in the ventricles can’t flush into subarachnoid space. Thus, subarachnoid clots and its metabolites, will become high viscosity. Our hypothesis is that compartmentalization happened if hydrocephalus presented. Thus, blood clots and inflammation metabolites in subarachnoid space certainly are much higher than the ventricle. According to our hypothesis, after subarachnoid hemorrhage, lactic acid will accumulate in the subarachnoid space, especially under conditions resulting in hydrocephalus. Therefore, the aim of the first study was to analyze its biochemical differences between ventricle and lumbar cerebrospinal fluid, in patients with modified Fisher''s Grade III and IV subarachnoid hemorrhage, and further analyze the relationship between lactate and shunt dependent hydrocephalus. After subarachnoid hemorrhage, red blood cells will be broken down and released hemoglobin, followed by further metabolized to heme and iron. Free iron ions are toxic to brain cells, and protein should be combined into ferritin. In this process, which may be induced by an enzyme known as heme oxygenase (HO) 1, is the rate determining step of metabolism of hemoglobin. Many reports about head trauma or SAH previously showed that heme metabolism is related to outcome.. Materials and Methods Our first step is to confirm that after subarachnoid hemorrhage, the difference between ventricle and lumbar cerebrospinal fluid. So, we collected both ventricle and lumbar CSF on the seventh day after SAH. We further analysis of lumbar cerebrospinal fluid lactate and correlate with the hydrocephalus relevance. The Second study enrolled ptients with Fisher’s grade III aneurysmal SAH receiving early obliteration. The levels of heme oxygenase 1 (HO1), oxyhemoglobin, ferritin, and bilirubin in intra-thecal CSF were measured on the seventh day post-hemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. Results The first study showed Intra-thecal CSF had significantly higher levels of total protein, ferritin, hemoglobin, and lactate but lower glucose level than intra-ventricular CSF (all p<0.0001). By multivariate analysis of clinical and CSF parameters, elevated intra-thecal CSF lactate (p=0.036) and the presence of intra-ventricular hemorrhage (p=0.05) were independent factors associated with SDHC. Moreover, intra-thecal lactate >5.5 μM effectively predicted the occurrence of SDHC (odds ratio: 32, 95% confidence interval: 3.8-270.8; p=0.0015). The second study showed age >60 years, admission World Federation of Neurosurgeons Score ≥3, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (odds ratio=0.934, 95% CI: 0.883–0.989; p=0.018). Further analysis using a generalized additive model identified a cut-off value of HO1 > 81.2 uM to predict patients with an unfavorable outcome (82.4% accuracy). Conclusion and Prospect We suggested that there was compartalization between ventricle and subarachnoid space after massive SAH and intra-thecal lactate level is a useful predictive parameter for long-term SDHC in patients with aneurysmal SAH patients. Further, the second study found that the concentration of HO1 significantly associated with prognosis. Since SAH may cause compartalization of the ventricle and subarachnoid space, then how can we accelerate metabolism of the blood clot may possible improve patient prognosis. Therefore, we propose that continuous lumbar drainage may improve the outcome, clinical trials have been carried out. In order to verified the pathophysiology of DIND after SAH, we develop a new, in vivo observation of microcirculation after subarachnoid hemorrhage in rat. We can monitor cerebral blood flow and oxygen partial pressure at the same time. We found significant spasm of microcirculation, accompanied with decreased regional blood flow and oxygen partial pressure. This result is quite consistent with some recent studies, the treatment of spasm of the great vessels do not meet expectations, perhaps microcirculaiotn and microthrombus have a greater impact for the delayed ischemic brain lesions.
Subjects
subarachnoid hemorrhage
lactate
heme oxygenase
Type
thesis
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