Abstract
Recent studies have indicated that early brain injury may be responsible for the detrimental effects seen in patients after subarachnoid hemorrhage (SAH). In this study, we investigated the relationship between apolipoprotein E gene (APOE) polymorphism and the change of brain function in the early stage of aneurysmal SAH. A total of 79 patients admitted within 5 days after aneurysmal SAH were recruited in the study. Patient characteristics, such as age, gender, Fisher and Hunt–Hess grade were collected when admitted. Electroencephalogram (EEG) was recorded on admission and at 3–5 days after onset to assess the change of brain function of the patients in acute stage of SAH. The result of the second EEG recording was defined as EEG deterioration if the decrease in alpha wave frequency, increase in slow wave or decline in amplitude were observed when compared with the first EEG recording. The APOE polymorphism was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Ten of 17 patients with APOEε4 (58.8%) showed the deteriorated EEGs, which was significantly different from those without APOEε4 (18 of 62 patients, 29.0%, p = 0.023). However, neither the presence of ε2 nor of ε3 was significantly different from those absent of it (p > 0.05). Univariate logistic regression analyses showed that both high Fisher grade (p = 0.028, OR = 2.917, 95% CI = 1.124–7.572) and APOEε4 (p = 0.027, OR = 3.492, 95% CI = 1.150–10.604) were risk factors to EEG aggravation after aneurysmal SAH. The association of APOEε4 for deteriorated EEG was more significant after adjustment for age, gender, Hunt–Hess grade on admission, and Fisher grade (p = 0.007, OR = 5.741, 95% CI = 1.625–20.280). Our findings suggest that APOEε4 allele is a risk factor to brain function aggravation in the early stage of aneurysmal SAH, and it may contribute to early brain injury after SAH.
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Ingall T, Asplund K, Mahonen M, Bonita R. A multinational comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke 2000;31:1054–61.
Huang J, van Gelder JM. The probability of sudden death from rupture of intracranial aneurysms: a meta-analysis. Neurosurgery 2002;51:1101–7.
Aver RE, Zhanf JH. The clinical significance of acute brain injury in subarachnoid hemorrhage and opportunity for intervention. Acta Neurochir Suppl. 2008;105:179–84.
Sudlow C, Martinez Gonzalez NA, Kim J, Clark C. Does apolipoprotein E genotype influence the risk of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage? Systematic review and meta-analyses of 31 studies among 5961 cases and 17,965 controls. Stroke 2006;37:364–70.
Dunn LT, Stewart E, Murray GD, Nicoll JA, Teasdale GM. The influence of apolipoprotein E genotype on outcome after spontaneous subarachnoid hemorrhage: a preliminary study. Neurosurgery 2001;48(5):1006–11.
Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8:635–42.
Jiang Y, Sun X, Xia Y, Tang W, Cao Y, Gu Y. Effect of APOE polymorphisms on early responses to traumatic brain injury. Neurosci Lett. 2006;408:155–8.
Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009;40:994–1025.
Dreier JP, Ebert N, Priller J, Megow D, Lindauer U, Klee R et al. Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage? J Neurosurg. 2000;93:658–66.
Mineharu Y, Inoue K, Inoue S, Yamada S, Nozaki K, Takenaka K et al. Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm. Stroke 2006;37:1189–94.
Martinez-Gonzalez N A, Sudlow C L. Effects of apolipoprotein E genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2006;77:1329–35.
Tang J, Zhao J, Zhao Y, Wang S, Chen B, Zeng W. Apolipoprotein E epsilon4 and the risk of unfavorable outcome after aneurysmal subarachnoid hemorrhage. Surg Neurol. 2003;60:391–7.
Gao J, Wang H, Sheng H, Lynch JR, Warner DS, Durham L et al. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocrit Care. 2006;4:25–31.
Leung CH, Poon WS, Yu LM, Wong GK, Ng HK. Apolipoprotein e genotype and outcome in aneurysmal subarachnoid hemorrhage. Stroke 2002;33:548–52.
Gallek MJ, Conley YP, Sherwood PR, Horowitz MB, Kassam A, Alexander SA. APOE genotype and functional outcome following aneurysmal subarachnoid hemorrhage. Biol Res Nurs. 2009;10:205–12.
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Lin, B., Dan, W., Jiang, L., Yin, Xh., Wu, Ht., Sun, Xc. (2011). Association of APOE Polymorphism with the Change of Brain Function in the Early Stage of Aneurysmal Subarachnoid Hemorrhage. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0353-1_7
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DOI: https://doi.org/10.1007/978-3-7091-0353-1_7
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