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Inflammatory factor in the cerebrospinal fluid and correlation analysis of cerebral vasospasm after acute aneurysmal subarachnoid hemorrhage

Author: NiWei
Tutor: GuYuXiang
School: Fudan University
Course: Neurosurgery
Keywords: aneurysmal subarachnoid hemorrhage cerebral vasospasm cerebro-spinal fluid interleukin-6 endothelin-1 tumor necrosis factor-α
CLC: R743.3
Type: Master's thesis
Year: 2010
Downloads: 71
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Abstract


Background and ObjectiveIntracranial aneurysm is a kind of local ballon-like apophysis of cerebrovascular which is always originated from the Willis’circle in skull base. The incidence in the general population was 3.6% to 6%. Subrachnoid hemorrhage (SAH), caused by aneurysm rupture, is the most dangerous factor for the crowd. Its annual incidence rate was 6-35.3/100000 person, meanwhile the morbitity and mortality is over 65%. Therefore, intracranial aneurysm is a common cerebovascular disease resulting in the disability or fatality. Cerebral vasospasm is one of the major complications after aneurysmal subrachnoid hemorrhage. Except for rehaemorrhagia, vasospasm and/or delayed cerebral ischemia are the major cause of morbidity and mortality. Although vasospasm is confirmed by angiography in 70% of the patients suffering from subrachnoid hemorrhage, only 20% are symptomatically manifested.And nearly half of the patients eventually develop to cerebral infarction who are diagnosed as vasospasm after spasmolysis,15%-20% become dead or disabled. At present, a number of researches foucusing on the the relationship between cytokines and cerebral vasospasm have made spot on some kinds of markers including interleukin-6 (IL-6), endothelin-1 (ET-1), tumor necrosis factor-α(TNF-) which currently attract more attention. This research is contributed to evaluate IL-6, ET-1 and TNF-αin cerebrospinal fluid (CSF) after SAH and the correlation between these inflammatory factors and vasospasm.MethodsWe selected 64 patients who were made definite diagnosis of aneurysmal subarachnoid hemorrhage by digital subtraction angiogram(DSA) in department of neurosurgery, Huanshan Hospital, Shanghai and gave these series microsurgical aneurysm clipping or endovascular treatment in the acute phase after aneurysm rupture(within≦72hrs). Both Intravenous injection of nimodipine and triple-H therapy are routinely given in combination after the treatment aiming at aneurysm. Transcranial Doppler detection is adopted daily at the same time before surgery,1-14 days after treatment for aneurysm, pointing at bilateral M2 segment of middle cerebral artery point via the temporal window, to determine whether the occurrence of vasospasm. Meanwhile, continuous lumbar drainage device was placed on each patient on first after operation. After that we collected 10ml cerebro-spinal fluid(CSF) respectively on 1,2,3,5,7 days after operation, kept 4ml supernatant after centrifugation for reservation in-80℃refrigerator for two months, and then used double antibody sandwich Elisa assay to measured the content of IL-6, ET-1 and TNF-a in CSF, studied the relationship between the quantities of these inflammatory factors with the TCD value. All the laboratory data of various inflammatory factors were divided into two sub-groups based on the parameters of vasospasm or non-vasospasm. All clinical data was compared by T-test. P value of all the statistic processes is set at 0.05.Results1. In our group,29(29/64,45.3%) patients were diagnosed as vasospasm. The average occurrence time of vasospasm is 5.8d±2.6 days after treatment.27 patients had symptoms, occupying 93.1%(27/29) of vasospasm patients diagnosed by TCD.14 patients could be found new hypodense lesion in CT scan.12 patients had psychiatric disorders(agitation/lethargy/coma/).10 patients had motor disability.5 patients suffered from motor disability combining with barylalia.2. Male is in statistically higher risk of vasospasm than female(P<0.05).On the other hand, patients in poor Hunt-Hess Grade take higher risk of vasospasm(P<0.05). Patients who are graded in Fisher Scale 3 revealed statistically significant higher incidence rate of vasospasm than others(P<0.05). Moreover, patients who were afflicted by developing vasospasm should obtained higher GOS evaluation than non-vasospasm group.3. The value of IL-6 in patients suffering from vasospasm later is significantly higher on Day 1,2,3,5,7(P=0.008,0.001,0.001,0.001,0.001) than non-vasospasm group. We chose Day 5 to conduct theχ2 analysis with the cut-off of IL-6 in 400pg/ml, found when 400pg/ml on Day 5 was chosen as the cut-off, which is earlier than the average occurrence time of vasospasm(Day 5.8±2.6 after treatment), the relative risk is 7.56 (95%confidence interval [CI],2.09-11.0).The positive predictive value is 75%,as the sensitivity is 82.76%,the specificity is 77.14%, indicating the predictive effect on vasospasm.4. The value of ET-1 in patients suffering from vasospasm later is significantly higher on Day 1,2,3,5,7(P=0.0013,0.002,0.002,0.006,0.004) than non-vasospasm group. We chose Day 2 to conduct theχ2 analysis with the cut-off of ET-1 in 20pg/ml,30pg/ml or 40pg/ml, found when 20pg/ml on Day 2 was chosen as the cut-off, which is earlier than the average occurrence time of vasospasm(Day 5.8±2.6 after treatment), the relative risk is 3.40(95%confidence interval [CI],2.11-5.48).The positive predictive value is 94.12%,as the sensitivity is 65.52%,the specificity is 97.14%, indicating the predictive effect on vasospasm.5. The value of TNF-αin patients suffering from vasospasm later is significantly higher on Day 5(P=0.0034) than non-vasospasm group. No significant difference on Day 1,2,3,7 (P=0.525,0.285.0.051 and 0.233). We chose Day 5 to conduct theχ2 analysis with the cut-off of TNF-αin 500pg/ml, found when 500pg/ml on Day 5 was chosen as the cut-off, which is earlier than the average occurrence time of vasospasm(Day 5.8±2.6 after treatment), the relative risk is 2.21(95%confidence interval [CI],1.29-3.80).The positive predictive value is 68.00%, as the sensitivity is 58.62%, the specificity is 77.14%, indicating the predictive effect on vasospasm.ConclusionWe found the correlation between the quantity increase of IL-6 ET-1 and TNF-αin CSF and cerebral vasospasm. Meanwhile we settled the cut-off value in 400pg/ml on Day 5 after treatment for IL-6,500pg/ml on Day 5 after treatment for TNF-α, and 40pg/ml on Day 2 after treatment for ET-1 to predict vasospasm. These conclusions provided with a new reference index for predicting cerebral vasospasm after subarachnoid hemorrhage.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke)
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