Neuroimmune predictors of outcome after aneurysmal subarachnoid hemorrhage

Abstract

Aim. To determine the possibility of predicting the course and outcomes of aneurysmal subarachnoid hemorrhage (aSAH) by using the detection of autoantibody level to neurospecific proteins.

Methods. The autoantibody level to neurospecific proteins was detected in 65 people: 30 healthy volunteers and 35 with a confirmed diagnosis of aneurysmal subarachnoid hemorrhage. Autoantibodies to myelin basic protein (MBP), peripheral myelin, dopamine receptors, myosin, N-methyl-D-aspartate (NMDA) receptors and S100 protein detected by using an enzyme immunoassay. The severity of illness in dynamics was defined in all patients by using the following scales: Rivermead mobility index, Hunt–Hess, Graeb and others. Statistical analysis was performed using Statistica 10.0, with the consistent use of descriptive statistics methods, the Mann–Whitney, Kruskal–Wallis and Pearson tests, Spearman coefficient.

Results. At the first stage, neurospecific proteins characterized by a large increase in autoantibody titers were identified. Further, based on the data obtained, a statistically significant correlation between autoantibody ­titers to S100 protein (360.43±40.35 µg/ml, p <0.05), MBP (145.91±12.43 µg/ml, p <0.05), NMDA receptors (66.17±6.42 µg/ml, p <0.05) and aSAH outcome was established.

Conclusion. The study revealed an increase in autoantibody level to neurospecific proteins in the blood plasma of patients, depending on the severity of subarachnoid hemorrhage and the development of delayed cerebral ischemia due to cerebral vasospasm; high antibodies titers to S100 protein in subarachnoid hemorrhage are associated with cerebral vasospasm and the development of secondary (delayed) ischemic changes in the brain.

Keywords

neurospecific proteins / subarachnoid hemorrhage (SAH) / aSAH / cerebral angiospasm / myelin basic protein / autoantibodies to N-methyl-D-aspartate receptors (NMDA receptors) / S100 protein

References

[1] Golovina N.P., Lavrov U.V., Kutashov V.A., Sazonov J.E. Cerebral stroke: a modern view on the problem. Prikladnye informatsionnye aspekty meditsiny. 2015; 18 (5): 56–62. (In Russ.)

[2] Головина Н.П., Лавров Ю.В., Куташов В.А., Сазонов И.Э. Церебральный инсульт: современный взгляд на проблему. Прикладные информационные аспекты медицины. 2015; 18 (5): 56–62.

[3] Baturin V.A., Baturina M.V., Mamtseva G.I., Boev O.I. et al. Levels of neurotropic autoantibodies in patients with schizophrenia. Meditsinsky vestnik Severnogo Kavkaza. 2016; 11 (2): 176–178. (In Russ.) DOI: 10.14300/mnnc.2016.11030.

[4] Батурин В.А., Батурина М.В., Мамцева Г.И., Боев О.И. и др. Изучение уровней нейротропных аутоантител у больных шизофренией. Мед. вестн. Северного Кавказа. 2016; 11 (2): 176–178. DOI: 10.14300/mnnc.2016.11030.

[5] D’Souza S. Aneurysmal subarachnoid hemorrhage. Neurosurg. Anesth. 2015; 27 (3): 22–40. DOI: 10.1097/ANA.0000000000000130.

[6] Kerz T., Boor S., Ulrich A. et al. Endovascular therapy for vasospasm after aneurysmatic subarachnoid hemorrhage. Brit. J. Neurosurg. 2016; 30 (5): 49–53. DOI: 10.3109/02688697.2016.1173193.

[7] Becker K. Modulation of the postischemic immune response to improve stroke outcome. Stroke. 2010; 41: 75–78. DOI: 10.1161/STROKEAHA.110.592881.

[8] Sanchez-Pena P., Pereira A.-R., Sourour N.-A. et al. S100B as an additional prognostic marker in subarachnoid aneurysmal hemorrhage. Crit. Care Med. 2008; 36 (8): 2267–2273. DOI: 10.1097/CCM.0b013e3181809750.

[9] Belokon O.S., Ermakov S.V., Karpov S.M. et al. To the choice of surgical treatment of cerebral angiospasm in patients with aneu­rismatic subarachnoid hemorrhage. Meditsinskii vestnik Severnogo Kavkaza. 2020; 15 (1): 119–120. (In Russ.) DOI: 10.14300/mnnc.2020.15028.

[10] Белоконь О.С., Ермаков С.В., Карпов С.М. и др. К вопросу о выборе метода хирургического лечения церебрального ангиоспазма у пациентов с аневризматическим субарахноидальным кровоизлиянием. Мед. вестн. Северного Кавказа. 2020; 15 (1): 119–120. DOI: 10.14300/mnnc.2020.15028.

[11] Hop J.W., Rinkel G.J., Algra A. et al. Case-fatali­ty rates and functional outcome after subarachnoid hemor­rhage: A systematic re-view. Stroke. 1997; 28: 660–664. DOI: 10.1161/01.str.28.3.660.

[12] Yong-Ke Zheng, Xiao-Qiao Dong, Quan Du. Comparison of plasma copeptin and multiple biomarkers for assessing prognosis of patients with aneurysmal subarachnoid hemorrhage. Clin. Chim. Acta. 2017; 465: 64–69. DOI: 10.1016/j.cca.2017.10.009.

[13] Ayvazyan V.A., Boyadzhyan V.S., Manukyan L.A. et al. Komponenty sistemy komplementa C3 i factor B v krovi bol'nykh s ostrym ishemicheskim insul'tom. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. Prilozhenie Insul't. 2005; (15): 57–60. (In Russ.)

[14] Айвазян В.А., Бояджян В.С., Манукян Л.А. и др. Компоненты системы комплемента С3 и фактор В в крови больных с острым ишемическим инсультом. Ж. неврол. и психиатрии им. С.С. Корсакова. Прил. Инсульт. 2005; (15): 57–60.

[15] Amantea D., Nappi G., Bernardi G. et al. Post-ische­mic brain damage: pathophysiology and role of inflammatory mediators. FEBS J. 2009; 276 (1): 13–26. DOI: 10.1111/j.1742-4658.2008.06766.x.

RIGHTS & PERMISSIONS

Ermakov S.V., Karpov S.M., Вaturin V.A., Belokon O.S., Mozheiko R.A.