Dynamic changes of inflammatory indicators in patients with malignant cerebral edema after acute cerebral infarction_West China Medical Journal

Authors：

GUO Wen ¹ , WANG Lu ² ,  LIU Ming ¹

1. Center of Cerebrovascular Disease, Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

LIU Ming, Email: wyplmh@hotmail.com

Keywords：

Malignant cerebral edema; inflammatory biomarker; acute ischemic stroke; dynamic change

DOI：

10.7507/1002-0179.202204076

Video：

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Objective To understand the dynamic changes of inflammatory indicators in the peripheral blood of patients with malignant cerebral edema at different time points after acute cerebral infarction, and provide a basis for early prediction and prevention of malignant cerebral edema. Methods Consecutive patients with acute cerebral infarction within 24 h of onset who were admitted to the Department of Neurology, West China Hospital of Sichuan University between January 1st, 2017 to December 31st, 2018 were collected. The basic clinical data of the patients were collected, and the data of inflammatory cells (white blood cell count, absolute neutrophil count, absolute lymphocyte count, and neutrophil to lymphocyte ratio) and acute phase reactants (blood glucose, fibrinogen, albumin, and fibrinogen to albumin ratio) were dynamically collected at admission and 1, 3, and 7 d after admission, respectively. Differences between groups were compared using generalized estimating equations. Results A total of 798 patients with acute cerebral infarction were included, of whom 93 (11.65%) developed malignant cerebral edema. At all time points examined, the white blood cell counts, absolute neutrophil counts, and neutrophil to lymphocyte ratios were higher in the malignant cerebral edema group than those in the non-malignant cerebral edema group (Wald χ²=63.737, P<0.001; Wald χ²=91.848, P<0.001; Wald χ²=75.197, P<0.001); 1 and 3 d after admission, the absolute lymphocyte counts were lower in the malignant cerebral edema group than those in the non-malignant cerebral edema group (Wald χ²=18.580, P<0.001). The blood glucose levels were higher in the malignant cerebral edema group compared with the non-malignant cerebral edema group 1, 3, and 7 d after admission (Wald χ²=16.722, P<0.001); no significant between-group effect was found in the albumin levels (Wald χ²=3.643, P=0.056); the fibrinogen levels were significantly different between groups 3 d after admission (Wald χ²=8.923, P=0.003), and the fibrinogen to albumin ratios differed between the two groups 3 and 7 d after admission (Wald χ²=6.739, P=0.009). Dynamic analysis of multiple time points in the malignant cerebral edema group found that these inflammatory markers mostly reached their extreme values 3 d after admission. Conclusions Compared with the non-malignant cerebral edema group, the inflammatory cell-related indicators (except lymphocytes) and the acute phase inflammatory reactant-related indicators in malignant cerebral edema patients are significantly higher, and the absolute lymphocyte count is significantly lower. Three days after admission to hospital is probably the most significant time point for the change of each inflammatory indicator.

Citation： GUO Wen, WANG Lu, LIU Ming. Dynamic changes of inflammatory indicators in patients with malignant cerebral edema after acute cerebral infarction. West China Medical Journal, 2022, 37(6): 816-822. doi: 10.7507/1002-0179.202204076 Copy

1.	Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet, 2016, 387(10015): 251-272.
2.	Wu SM, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
3.	Wu S, Yuan R, Wang Y, et al. Early prediction of malignant brain edema after ischemic stroke. Stroke, 2018, 49(12): 2918-2927.
4.	Liebeskind DS, Jüttler E, Shapovalov Y, et al. Cerebral edema associated with large hemispheric infarction. Stroke, 2019, 50(9): 2619-2625.
5.	吳思緲, 吳波, 郭富強, 等. 重癥腦梗死優化診治方案及流程建議草案. 華西醫學, 2019, 34(10): 1096-1108.
6.	Serena J, Blanco M, Castellanos M, et al. The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke, 2005, 36(9): 1921-1926.
7.	Rosell A, Cuadrado E, Ortega-Aznar A, et al. MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type Ⅳ collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke, 2008, 39(4): 1121-1126.
8.	Hallenbeck JM, Dutka AJ, Tanishima T, et al. Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke, 1986, 17(2): 246-253.
9.	Peerschke EI, Yin W, Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol, 2010, 47(13,SI): 2170-2175.
10.	Zhang Y, Liu G, Wang Y, et al. Procalcitonin as a biomarker for malignant cerebral edema in massive cerebral infarction. Sci Rep, 2018, 8(1): 993.
11.	Kasner SE, Demchuk AM, Berrouschot J, et al. Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke, 2001, 32(9): 2117-2123.
12.	中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南 2014. 中華神經科雜志, 2015, 48(4): 246-257.
13.	Emsley HC, Tyrrell PJ. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab, 2002, 22(12): 1399-1419.
14.	Whiteley W, Jackson C, Lewis S, et al. Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study. Stroke, 2011, 42(1): 10-16.
15.	Moldes O, Sobrino T, Millán M, et al. High serum levels of endothelin-1 predict severe cerebral edema in patients with acute ischemic stroke treated with t-PA. Stroke, 2008, 39(7): 2006-2010.
16.	Ibrahim F, Menezes S, Buhnerkempe M, et al. systemic white blood cell count as a biomarker for malignant cerebral edema in large vessel ischemic MCA stroke. J Stroke Cerebrovasc Dis, 2022, 31: 106550.
17.	符少萍, 王彤. 急性腦卒中外周血白細胞的臨床觀察. 新醫學, 1998(增刊 2): 62-63.
18.	Ritter LS, Orozco JA, Coull BM, et al. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke, 2000, 31(5): 1153-1161.
19.	Nagaraja D, Christopher R, Tripathi M, et al. Preceding infection as a risk factor of stroke in the young. J Assoc Physicians India, 1999, 47(7): 673-675.
20.	Ka?mierski R, Guzik P, Ambrosius W, et al. Leukocytosis in the first day of acute ischemic stroke as a prognostic factor of disease progression. Wiadomosci lekarskie, 2001, 54: 143-151.
21.	Vogelgesang A, Grunwald U, Langner S, et al. Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke, 2008, 39(1): 237-241.
22.	方媛. 腦卒中急性期血糖變化及其與預后的關系. 成都: 四川大學, 2006.
23.	Christensen H, Boysen G. Blood glucose increases early after stroke onset: a study on serial measurements of blood glucose in acute stroke. Eur J Neurol, 2002, 9(3): 297-301.
24.	Bielewicz J, Kurzepa J, Czekajska-Chehab E, et al. Worse neurological state during acute ischemic stroke is associated with a decrease in serum albumin levels. J Mol Neurosci, 2016, 58(4): 493-496.
25.	Alvarez-Perez FJ, Castelo-Branco M, Alvarez-Sabin J. Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. J Neurol Neurosurg Psychiatry, 2011, 82(9): 986-992.
26.	Acharya P, Jakobleff WA, Forest SJ, et al. Fibrinogen albumin ratio and ischemic stroke during venoarterial extracorporeal membrane oxygenation. ASAIO J, 2020, 66(3): 277-282.

1. Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet, 2016, 387(10015): 251-272.
2. Wu SM, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
3. Wu S, Yuan R, Wang Y, et al. Early prediction of malignant brain edema after ischemic stroke. Stroke, 2018, 49(12): 2918-2927.
4. Liebeskind DS, Jüttler E, Shapovalov Y, et al. Cerebral edema associated with large hemispheric infarction. Stroke, 2019, 50(9): 2619-2625.
5. 吳思緲, 吳波, 郭富強, 等. 重癥腦梗死優化診治方案及流程建議草案. 華西醫學, 2019, 34(10): 1096-1108.
6. Serena J, Blanco M, Castellanos M, et al. The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke, 2005, 36(9): 1921-1926.
7. Rosell A, Cuadrado E, Ortega-Aznar A, et al. MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type Ⅳ collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke, 2008, 39(4): 1121-1126.
8. Hallenbeck JM, Dutka AJ, Tanishima T, et al. Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke, 1986, 17(2): 246-253.
9. Peerschke EI, Yin W, Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol, 2010, 47(13,SI): 2170-2175.
10. Zhang Y, Liu G, Wang Y, et al. Procalcitonin as a biomarker for malignant cerebral edema in massive cerebral infarction. Sci Rep, 2018, 8(1): 993.
11. Kasner SE, Demchuk AM, Berrouschot J, et al. Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke, 2001, 32(9): 2117-2123.
12. 中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性腦卒中診治指南 2014. 中華神經科雜志, 2015, 48(4): 246-257.
13. Emsley HC, Tyrrell PJ. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab, 2002, 22(12): 1399-1419.
14. Whiteley W, Jackson C, Lewis S, et al. Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study. Stroke, 2011, 42(1): 10-16.
15. Moldes O, Sobrino T, Millán M, et al. High serum levels of endothelin-1 predict severe cerebral edema in patients with acute ischemic stroke treated with t-PA. Stroke, 2008, 39(7): 2006-2010.
16. Ibrahim F, Menezes S, Buhnerkempe M, et al. systemic white blood cell count as a biomarker for malignant cerebral edema in large vessel ischemic MCA stroke. J Stroke Cerebrovasc Dis, 2022, 31: 106550.
17. 符少萍, 王彤. 急性腦卒中外周血白細胞的臨床觀察. 新醫學, 1998(增刊 2): 62-63.
18. Ritter LS, Orozco JA, Coull BM, et al. Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke, 2000, 31(5): 1153-1161.
19. Nagaraja D, Christopher R, Tripathi M, et al. Preceding infection as a risk factor of stroke in the young. J Assoc Physicians India, 1999, 47(7): 673-675.
20. Ka?mierski R, Guzik P, Ambrosius W, et al. Leukocytosis in the first day of acute ischemic stroke as a prognostic factor of disease progression. Wiadomosci lekarskie, 2001, 54: 143-151.
21. Vogelgesang A, Grunwald U, Langner S, et al. Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke, 2008, 39(1): 237-241.
22. 方媛. 腦卒中急性期血糖變化及其與預后的關系. 成都: 四川大學, 2006.
23. Christensen H, Boysen G. Blood glucose increases early after stroke onset: a study on serial measurements of blood glucose in acute stroke. Eur J Neurol, 2002, 9(3): 297-301.
24. Bielewicz J, Kurzepa J, Czekajska-Chehab E, et al. Worse neurological state during acute ischemic stroke is associated with a decrease in serum albumin levels. J Mol Neurosci, 2016, 58(4): 493-496.
25. Alvarez-Perez FJ, Castelo-Branco M, Alvarez-Sabin J. Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. J Neurol Neurosurg Psychiatry, 2011, 82(9): 986-992.
26. Acharya P, Jakobleff WA, Forest SJ, et al. Fibrinogen albumin ratio and ischemic stroke during venoarterial extracorporeal membrane oxygenation. ASAIO J, 2020, 66(3): 277-282.

West China Medical Journal

Dynamic changes of inflammatory indicators in patients with malignant cerebral edema after acute cerebral infarction

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