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Published in: BMC Neurology 1/2021

Open Access 01-12-2021 | Computed Tomography | Research article

20-hydroxyeiscosatetraenoic acid may be as a predictor of malignant middle cerebral artery infarction in patients with massive middle cerebral artery infarction

Authors: Xingyang Yi, Qiang Zhou, Ting Qing, Bing Ming, Jing Lin, Jie Li, Jie Lin

Published in: BMC Neurology | Issue 1/2021

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Abstract

Background

Early identification of massive middle cerebral artery infarction (MCAI) at risk for malignant MCAI (m-MCAI) may be useful in selecting patients for aggressive therapies. The aim of this study was to determine whether CYP metabolites may help to predict impending m-MCAI.

Methods

This is a prospective, two-center observational study in 256 patients with acute massive MCAI. Plasma levels of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids, and dihydroxyeicosatrienoic acids were measured at admission. Brain computed tomography (CT) was performed at admission and repeated between day 3 and 7, or earlier if there was neurological deterioration. The primary outcome was m-MCAI. The m-MCAI was diagnosed when follow-up brain CT detected a more than two-thirds space-occupying MCAI with midline shift, compression of the basal cisterns, and neurological worsening.

Results

In total of 256 enrolled patients, 77 (30.1%) patients developed m-MCAI. Among the 77 patients with m-MCAI, 60 (77.9%) patients died during 3 months of stroke onset. 20-HETE level on admission was significantly higher in patients with m-MCAI than those without m-MCAI. There was an increase in the risk of m-MCAI with increase of 20-HETE levels. The third and fourth quartiles of 20-HETE levels were independent predictors of m-MCAI (OR: 2.86; 95% CI: 1.16 – 6.68; P = 0.025, and OR: 4.23; 95% CI: 1.35 – 8.26; P = 0.002, respectively).

Conclusions

Incidence of m-MCAI was high in patients with massive MCAI and the prognosis of m-MCAI is very poor. Elevated plasma 20-HETE may be as a predictor for m-MCAI in acute massive MCAI, and it might useful in clinical practice in therapeutic decision making.
Literature
1.
go back to reference Moulin DE, Lo R, Chiang J, Barnett HJM. Prognosis in middle cerebral artery occlusion. Stroke. 1985;16:282–4.CrossRef Moulin DE, Lo R, Chiang J, Barnett HJM. Prognosis in middle cerebral artery occlusion. Stroke. 1985;16:282–4.CrossRef
2.
go back to reference Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol. 2009;8:949–58.CrossRef Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol. 2009;8:949–58.CrossRef
3.
go back to reference Kasner SE, Demchuk AM, Berrouschot J, Schmutzhard E, Harms L, Verro P, et al. Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke. 2001;32:2117–23.CrossRef Kasner SE, Demchuk AM, Berrouschot J, Schmutzhard E, Harms L, Verro P, et al. Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke. 2001;32:2117–23.CrossRef
4.
go back to reference Dohmen C, Bosche B, Graf R, Staub F, Kracht L, Sobesky J, et al. Prediction of malignant course in MCA infarction by PET and microdialysis. Stroke. 2003;34:2152–8.CrossRef Dohmen C, Bosche B, Graf R, Staub F, Kracht L, Sobesky J, et al. Prediction of malignant course in MCA infarction by PET and microdialysis. Stroke. 2003;34:2152–8.CrossRef
5.
go back to reference Berrouschot J, Sterker M, Bettin S, Köster J, Schneider D. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care. Intensive Care Med. 1998;24:620–3.CrossRef Berrouschot J, Sterker M, Bettin S, Köster J, Schneider D. Mortality of space-occupying (‘malignant’) middle cerebral artery infarction under conservative intensive care. Intensive Care Med. 1998;24:620–3.CrossRef
6.
go back to reference Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. “Malignant” middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol. 1996;53:309–15.CrossRef Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. “Malignant” middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol. 1996;53:309–15.CrossRef
7.
go back to reference Steiner T, Ringleb P, Hacke W. Treatment options for large hemispheric stroke. Neurology. 2001;57(Suppl.2):S61–8.CrossRef Steiner T, Ringleb P, Hacke W. Treatment options for large hemispheric stroke. Neurology. 2001;57(Suppl.2):S61–8.CrossRef
8.
go back to reference Minnerup J, Wersching H, Ringelstein EB, Heindel W, Niederstadt T, Schilling M, et al. Prediction of malignant middle cerebral artery infarction using computed tomography-based intracranial volume reserve measurements. Stroke. 2011;42:3403–9.CrossRef Minnerup J, Wersching H, Ringelstein EB, Heindel W, Niederstadt T, Schilling M, et al. Prediction of malignant middle cerebral artery infarction using computed tomography-based intracranial volume reserve measurements. Stroke. 2011;42:3403–9.CrossRef
9.
go back to reference Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110.CrossRef Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110.CrossRef
10.
go back to reference Neugebauer H, Jüttler E. Hemicraniectomy for malignant middle cerebral artery infarction: current status and future directions. Int J Stroke. 2014;9:460–7.CrossRef Neugebauer H, Jüttler E. Hemicraniectomy for malignant middle cerebral artery infarction: current status and future directions. Int J Stroke. 2014;9:460–7.CrossRef
11.
go back to reference Frank JI. Large hemispheric infarction, deterioration, and intracranial pressure. Neurology. 1995;45:1286–90.CrossRef Frank JI. Large hemispheric infarction, deterioration, and intracranial pressure. Neurology. 1995;45:1286–90.CrossRef
12.
go back to reference Qureshi AI, Suarez JI, Yahia AM, Mohammad Y, Uzun G, Suri MF, et al. Timing of neurologic deterioration in massive middle cerebral artery infarction: a multicenter review. Crit Care Med. 2003;31:272–7.CrossRef Qureshi AI, Suarez JI, Yahia AM, Mohammad Y, Uzun G, Suri MF, et al. Timing of neurologic deterioration in massive middle cerebral artery infarction: a multicenter review. Crit Care Med. 2003;31:272–7.CrossRef
13.
go back to reference Zhou Z, Zhang J, Li X, Xia C, Han Y, Chen H. Protein microarray analysis identifies key cytokines associated with malignant middle cerebralartery infarction. Brain Behav. 2017;7:e00746.CrossRef Zhou Z, Zhang J, Li X, Xia C, Han Y, Chen H. Protein microarray analysis identifies key cytokines associated with malignant middle cerebralartery infarction. Brain Behav. 2017;7:e00746.CrossRef
14.
go back to reference Li J, Zhang P, Wu S, Yi X, Wang C, Liu M. Factors associated with favourable outcome in large hemispheric infarctions. BMC Neurol. 2018;18:152.CrossRef Li J, Zhang P, Wu S, Yi X, Wang C, Liu M. Factors associated with favourable outcome in large hemispheric infarctions. BMC Neurol. 2018;18:152.CrossRef
15.
go back to reference Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem. 2001;276:36059–62.CrossRef Zeldin DC. Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem. 2001;276:36059–62.CrossRef
16.
go back to reference Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie. 2009;91:791–5.CrossRef Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie. 2009;91:791–5.CrossRef
17.
go back to reference Dunn KM, Renic M, Flasch AK, Harder DR, Falck J, Roman RJ. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295:H2455–65.CrossRef Dunn KM, Renic M, Flasch AK, Harder DR, Falck J, Roman RJ. Elevated production of 20-HETE in the cerebral vasculature contributes to severity of ischemic stroke and oxidative stress in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2008;295:H2455–65.CrossRef
18.
go back to reference Imig JD, Simpkins AN, Renic M, Harder DR. Cytochrome P450 eicosanoids and cerebral vascular function. Exp Rev Mol Med. 2011;13:e7.CrossRef Imig JD, Simpkins AN, Renic M, Harder DR. Cytochrome P450 eicosanoids and cerebral vascular function. Exp Rev Mol Med. 2011;13:e7.CrossRef
19.
go back to reference Yi X, Han Z, Zhou Q, Lin J, Liu P. 20-hydroxyeicosatetraenoic acid as a predictor of neurological deterioration in acute minor ischemic stroke. Stroke. 2016;47:3045–7.CrossRef Yi X, Han Z, Zhou Q, Lin J, Liu P. 20-hydroxyeicosatetraenoic acid as a predictor of neurological deterioration in acute minor ischemic stroke. Stroke. 2016;47:3045–7.CrossRef
20.
go back to reference Yi X, Lin J, Li J, Zhou Q, Han Z. Epoxyeicosatrienoic Acids are Mediated by EPHX2 Variants and may be a Predictor of Early Neurological Deterioration in Acute Minor Ischemic Stroke. J Atheroscler Thromb. 2017;24:1258–66.CrossRef Yi X, Lin J, Li J, Zhou Q, Han Z. Epoxyeicosatrienoic Acids are Mediated by EPHX2 Variants and may be a Predictor of Early Neurological Deterioration in Acute Minor Ischemic Stroke. J Atheroscler Thromb. 2017;24:1258–66.CrossRef
21.
go back to reference Yi X, Lin J, Wang C, Zhang B, Chi W. Low-molecular-weight heparin is more effective than aspirin in preventing early neurologic deterioration and improving sixmonth outcome. J Stroke Cerebrovasc Dis. 2014;23:1537–44.CrossRef Yi X, Lin J, Wang C, Zhang B, Chi W. Low-molecular-weight heparin is more effective than aspirin in preventing early neurologic deterioration and improving sixmonth outcome. J Stroke Cerebrovasc Dis. 2014;23:1537–44.CrossRef
22.
go back to reference Uhl E, Kreth FW, Elias B, Goldammer A, Hempelmann RG, Liefner M, et al. Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. J Neurol Neurosurg Psychiatry. 2004;75:270–4.PubMedPubMedCentral Uhl E, Kreth FW, Elias B, Goldammer A, Hempelmann RG, Liefner M, et al. Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. J Neurol Neurosurg Psychiatry. 2004;75:270–4.PubMedPubMedCentral
23.
go back to reference Serena J, Blanco M, Castellanos M, Silva Y, Vivancos J, Moro MA, et al. The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke. 2005;36:1921–6.CrossRef Serena J, Blanco M, Castellanos M, Silva Y, Vivancos J, Moro MA, et al. The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke. 2005;36:1921–6.CrossRef
24.
go back to reference Pexman JH, Barber PA, Hill MD, Sevick RJ, Demchuk AM, Hudon ME, et al. Use of the Alberta stroke program early CT score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol. 2001;22:1534–42.PubMedPubMedCentral Pexman JH, Barber PA, Hill MD, Sevick RJ, Demchuk AM, Hudon ME, et al. Use of the Alberta stroke program early CT score (ASPECTS) for assessing CT scans in patients with acute stroke. AJNR Am J Neuroradiol. 2001;22:1534–42.PubMedPubMedCentral
25.
go back to reference Han SW, Kim SH, Lee JY, Chu CK, Yang JH, Shin HY, et al. A new subtype classification of ischemic stroke based on treatment and etiologic mechanism. Eur Neurol. 2007;57:96–102.CrossRef Han SW, Kim SH, Lee JY, Chu CK, Yang JH, Shin HY, et al. A new subtype classification of ischemic stroke based on treatment and etiologic mechanism. Eur Neurol. 2007;57:96–102.CrossRef
26.
go back to reference Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O, et al. Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke. 1998;29:1888–93.CrossRef Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O, et al. Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke. 1998;29:1888–93.CrossRef
27.
go back to reference Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. Geneva: World Health Organization; 1991. Lwanga SK, Lemeshow S. Sample size determination in health studies: a practical manual. Geneva: World Health Organization; 1991.
29.
go back to reference von Kummer R, Meyding-Lamade U, Forsting M, Rosin L, Rieke K, Hacke W, et al. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol. 1994;15:9–15. von Kummer R, Meyding-Lamade U, Forsting M, Rosin L, Rieke K, Hacke W, et al. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol. 1994;15:9–15.
31.
go back to reference Donnelly MK, Crago EA, Conley YP, Balzer JR, Ren D, Ducruet AF, et al. 20-HETE is associated with unfavorable outcomes in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab. 2015;35:1515–22.CrossRef Donnelly MK, Crago EA, Conley YP, Balzer JR, Ren D, Ducruet AF, et al. 20-HETE is associated with unfavorable outcomes in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab. 2015;35:1515–22.CrossRef
32.
go back to reference Lange A, Gebremedhin D, Narayanan J, Harder D. 20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J Biol Chem. 1997;272:27345–52.CrossRef Lange A, Gebremedhin D, Narayanan J, Harder D. 20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J Biol Chem. 1997;272:27345–52.CrossRef
33.
go back to reference Randriamboavonjy V, Busse R, Fleming I. 20-HETE induced contraction of small coronary arteries depends on the activation of rho-kinase. Hypertension. 2003;41:801–6.CrossRef Randriamboavonjy V, Busse R, Fleming I. 20-HETE induced contraction of small coronary arteries depends on the activation of rho-kinase. Hypertension. 2003;41:801–6.CrossRef
34.
go back to reference Sairanen T, Karjalainen-Lindsberg ML, Paetau A, Ijäs P, Lindsberg PJ. Apoptosis dominant in the periinfarct area of human ischaemic stroke--a possible target of antiapoptotic treatments. Brain. 2006;129:189–99.CrossRef Sairanen T, Karjalainen-Lindsberg ML, Paetau A, Ijäs P, Lindsberg PJ. Apoptosis dominant in the periinfarct area of human ischaemic stroke--a possible target of antiapoptotic treatments. Brain. 2006;129:189–99.CrossRef
35.
go back to reference Gomez-Sanchez JC, Delgado-Esteban M, Rodriguez-Hernandez I, Sobrino T, Perez De La Ossa N, Reverte S, et al. The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke. J Exp Med. 2011;208:429–37.CrossRef Gomez-Sanchez JC, Delgado-Esteban M, Rodriguez-Hernandez I, Sobrino T, Perez De La Ossa N, Reverte S, et al. The human Tp53 Arg72Pro polymorphism explains different functional prognosis in stroke. J Exp Med. 2011;208:429–37.CrossRef
36.
go back to reference Cheng J, Ou JS, Singh H, Falck JR, Narsimhaswamy D, Pritchard KA Jr, et al. 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling. Am J Physiol Heart Circ Physiol. 2008;294:H1018–26.CrossRef Cheng J, Ou JS, Singh H, Falck JR, Narsimhaswamy D, Pritchard KA Jr, et al. 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling. Am J Physiol Heart Circ Physiol. 2008;294:H1018–26.CrossRef
37.
go back to reference Guo AM, Arbab AS, Falck JR, Chen P, Edwards PA, Roman RJ, et al. Activation of vascular endothelial growth factor through reactive oxygen species mediates 20-hydroxyeicosatetraenoic acid-induced endothelial cell proliferation. J Pharmacol Exp Ther. 2007;321:18–27.CrossRef Guo AM, Arbab AS, Falck JR, Chen P, Edwards PA, Roman RJ, et al. Activation of vascular endothelial growth factor through reactive oxygen species mediates 20-hydroxyeicosatetraenoic acid-induced endothelial cell proliferation. J Pharmacol Exp Ther. 2007;321:18–27.CrossRef
38.
go back to reference Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A, et al. Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension. Hypertension. 2007;50:123–9.CrossRef Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A, et al. Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension. Hypertension. 2007;50:123–9.CrossRef
39.
go back to reference Takeuchi K, Renic M, Bohman QC, Harder DR, Miyata N, Roman RJ. Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE. Am J Physiol Heart Circ Physiol. 2005;289:H2203–11.CrossRef Takeuchi K, Renic M, Bohman QC, Harder DR, Miyata N, Roman RJ. Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE. Am J Physiol Heart Circ Physiol. 2005;289:H2203–11.CrossRef
40.
go back to reference Tanaka Y, Omura T, Fukasawa M, Horiuchi N, Miyata N, Minagawa T, et al. Continuous inhibition of 20-HETE synthesis by TS-011 improves neurological and functional outcomes after transient focal cerebral ischemia in rats. Neurosci Res. 2007;59:475–80.CrossRef Tanaka Y, Omura T, Fukasawa M, Horiuchi N, Miyata N, Minagawa T, et al. Continuous inhibition of 20-HETE synthesis by TS-011 improves neurological and functional outcomes after transient focal cerebral ischemia in rats. Neurosci Res. 2007;59:475–80.CrossRef
Metadata
Title
20-hydroxyeiscosatetraenoic acid may be as a predictor of malignant middle cerebral artery infarction in patients with massive middle cerebral artery infarction
Authors
Xingyang Yi
Qiang Zhou
Ting Qing
Bing Ming
Jing Lin
Jie Li
Jie Lin
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2021
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-021-02456-6

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