Rapid Point-of-Care-Tests for Stroke Monitoring


Rapid Point-of-Care-Tests for Stroke Monitoring

Dorin Harpaz, Evgeni Eltzov, Raymond C.S. Seet , Robert S. Marks, Alfred I.Y. Tok

Stroke contributes to at least 7 million deaths annually and is the second leading cause of death globally. Ischemic stroke is the most common type of stroke where an interruption of blood flow within brain tissues can lead to cessation of brain activities. Central to existing reperfusion treatment strategies is prompt restoration of blood supply to compromised brain tissues. Existing methods of monitoring the progress of stroke evolution are limited to clinical evaluation and neuroimaging techniques. With advances in biomarker research, there is now a growing interest in the use of stroke biomarkers to guide clinical decision-making, especially for on-site biomarker measurements, to make time-sensitive decisions on stroke prognosis. This chapter presents an overview on point-of-care-tests (POCT) used to guide stroke prognosis, with the aim of shortening time-to-treatment, classifying stroke subtypes and improving patient’s outcome. First, the current stroke monitoring workflow is presented, which highlights gaps for an improved bedside biomarker assessment. Second, a detailed overview on the different POCTs used for stroke monitoring is specified. Last, a novel approach for the creation of a future successful stroke POCT is presented, which combines the use of a quantitative and multiplex POCT for the detection of stroke-specific biomarkers.

Stroke, Prognosis, Point-of-Care-Test, Biomarkers, Time-Dependent Treatment, Multiplex and Quantitative Detection

Published online 9/20/2019, 50 pages

Citation: Dorin Harpaz, Evgeni Eltzov, Raymond C.S. Seet , Robert S. Marks, Alfred I.Y. Tok, Rapid Point-of-Care-Tests for Stroke Monitoring, Materials Research Foundations, Vol. 56, pp 233-282, 2019

DOI: https://doi.org/10.21741/9781644900376-8

Part of the book on Organic Bioelectronics for Life Science and Healthcare

[1] Strong, K., C. Mathers, and R. Bonita, Preventing stroke: saving lives around the world. Lancet Neurol, 2007. 6(2): p. 182-7. https://doi.org/10.1016/S1474-4422(07)70031-5
[2] Goldstein, L.B., et al., Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline. Stroke, 2006. 37(6): p. 1583-633. https://doi.org/10.1161/01.STR.0000223048.70103.F1
[3] Wellesley MA USA, B.J., project analyst, Stroke Diagnostics and Therapeutics: Global Markets, BCC Research. 2015. HLC180A.
[4] Harpaz, D., et al., Point-of-Care-Testing in Acute Stroke Management: An Unmet Need Ripe for Technological Harvest. Biosensors, 2017. 7(3): p. 30. https://doi.org/10.3390/bios7030030
[5] American Heart & Stroke Association, I., 2016.
[6] Govindarajan, P., et al., Comparative evaluation of stroke triage algorithms for emergency medical dispatchers (MeDS): prospective cohort study protocol. BMC Neurol, 2011. 11: p. 14. https://doi.org/10.1186/1471-2377-11-14
[7] Watkins, C.L., et al., Training emergency services’ dispatchers to recognise stroke: an interrupted time-series analysis. BMC Health Serv Res, 2013. 13: p. 318. https://doi.org/10.1186/1472-6963-13-318
[8] Deng, Y.Z., et al., IV tissue plasminogen activator use in acute stroke: experience from a statewide registry. Neurology, 2006. 66(3): p. 306-12. https://doi.org/10.1212/01.wnl.0000196478.77152.fc
[9] Wojner-Alexandrov, A.W., et al., Houston paramedic and emergency stroke treatment and outcomes study (HoPSTO). Stroke, 2005. 36(7): p. 1512-8. https://doi.org/10.1161/01.STR.0000170700.45340.39
[10] Zhai, S., et al., The Cost-Effectiveness of a Stroke Unit in Providing Enhanced Patient Outcomes in an Australian Teaching Hospital. J Stroke Cerebrovasc Dis, 2017. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.05.025
[11] Miller, E.C., C. Blum, and S.K. Rostanski, Developing a Stroke Center. Stroke, 2017. 48(7): p. e155-e156. https://doi.org/10.1161/STROKEAHA.117.017745
[12] E., F.-L., Stroke prevention and care in France: report for the Minister of Health and Sport. 2009.
[13] Weber, J.E., et al., Prehospital thrombolysis in acute stroke: results of the PHANTOM-S pilot study. Neurology, 2013. 80(2): p. 163-8. https://doi.org/10.1212/WNL.0b013e31827b90e5
[14] Handschu, R., et al., Telemedicine in emergency evaluation of acute stroke: interrater agreement in remote video examination with a novel multimedia system. Stroke, 2003. 34(12): p. 2842-6. https://doi.org/10.1161/01.STR.0000102043.70312.E9
[15] Demaerschalk, B.M., et al., Smartphone teleradiology application is successfully incorporated into a telestroke network environment. Stroke, 2012. 43(11): p. 3098-101. https://doi.org/10.1161/STROKEAHA.112.669325
[16] Audebert, H.J., et al., Prehospital stroke care: new prospects for treatment and clinical research. Neurology, 2013. 81(5): p. 501-8. https://doi.org/10.1212/WNL.0b013e31829e0fdd
[17] Katz, B.S., et al., Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study. Stroke, 2017. https://doi.org/10.1161/STROKEAHA.116.015971
[18] Waqar Faiz, K., et al., Prehospital path in acute stroke. Tidsskr Nor Laegeforen, 2017. 137(11): p. 798-802. https://doi.org/10.4045/tidsskr.16.0512
[19] Brott, T., et al., Measurements of acute cerebral infarction: a clinical examination scale. Stroke, 1989. 20(7): p. 864-70. https://doi.org/10.1161/01.STR.20.7.864
[20] Kidwell, C.S., et al., Comparison of MRI and CT for detection of acute intracerebral hemorrhage. Jama, 2004. 292(15): p. 1823-30. https://doi.org/10.1001/jama.292.15.1823
[21] Assis, Z.A., B.K. Menon, and M. Goyal, Imaging department organization in a stroke center and workflow processes in acute stroke. Eur J Radiol, 2017. https://doi.org/10.1016/j.ejrad.2017.06.014
[22] Ferro, J.M., A.R. Massaro, and J.L. Mas, Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol, 2010. 9(11): p. 1085-96. https://doi.org/10.1016/S1474-4422(10)70251-9
[23] Singh, T.P., J.R. Weinstein, and S.P. Murphy, Stroke: Basic and Clinical. Adv Neurobiol, 2017. 15: p. 281-293. https://doi.org/10.1007/978-3-319-57193-5_10
[24] Patel, R.A.G. and C.J. White, Stroke Treatment and Prevention. Prog Cardiovasc Dis, 2017. 59(6): p. 525-526. https://doi.org/10.1016/j.pcad.2017.05.006
[25] Tsivgoulis, G., O. Kargiotis, and A.V. Alexandrov, Intravenous thrombolysis for acute ischemic stroke: a bridge between two centuries. Expert Rev Neurother, 2017. 17(8): p. 819-837. https://doi.org/10.1080/14737175.2017.1347039
[26] Glickman, S.W., et al., Discriminative capacity of biomarkers for acute stroke in the emergency department. J Emerg Med, 2011. 41(3): p. 333-9. https://doi.org/10.1016/j.jemermed.2010.02.025
[27] Group, T.N.I.o.N.D.a.S.r.-P.S.S., Tissue plasminogen activator for acute ischemic stroke. N Engl J Med, 1995. 333(24): p. 1581-7. https://doi.org/10.1056/NEJM199512143332401
[28] Adams, H.P., Jr., et al., Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, 2007. 115(20): p. e478-534.
[29] Radu, R.A., et al., Etiologic classification of ischemic stroke: Where do we stand? Clin Neurol Neurosurg, 2017. 159: p. 93-106. https://doi.org/10.1016/j.clineuro.2017.05.019
[30] Amarenco, P., et al., Classification of stroke subtypes. Cerebrovasc Dis, 2009. 27(5): p. 493-501. https://doi.org/10.1159/000210432
[31] Ingelheim, B., 2015.
[32] Lee, L.J., et al., Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography. Stroke, 2000. 31(5): p. 1081-9. https://doi.org/10.1161/01.STR.31.5.1081
[33] Adams, H.P., Jr., et al., Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke, 1993. 24(1): p. 35-41. https://doi.org/10.1161/01.STR.24.1.35
[34] Landau, W.M. and A. Nassief, Editorial comment–time to burn the TOAST. Stroke, 2005. 36(4): p. 902-4. https://doi.org/10.1161/str.36.4.902
[35] Amarenco, P., Patent foramen ovale and the risk of stroke: smoking gun guilty by association? Heart, 2005. 91(4): p. 441-3. https://doi.org/10.1136/hrt.2004.052241
[36] Gokcal, E., E. Niftaliyev, and T. Asil, Etiological classification of ischemic stroke in young patients: a comparative study of TOAST, CCS, and ASCO. Acta Neurol Belg, 2017. https://doi.org/10.1007/s13760-017-0813-8
[37] Sacco, R.L., et al., Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol, 1989. 25(4): p. 382-90. https://doi.org/10.1002/ana.410250410
[38] Bamford, J., et al., Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet, 1991. 337(8756): p. 1521-6. https://doi.org/10.1016/0140-6736(91)93206-O
[39] Lindley, R.I., et al., Interobserver reliability of a clinical classification of acute cerebral infarction. Stroke, 1993. 24(12): p. 1801-4. https://doi.org/10.1161/01.STR.24.12.1801
[40] Thomas S. Maldonado, M.D., and Thomas S. Riles, M.D., F.A.C.S, Stroke and Transient Ischemic Attack – 1 1 STROKE AND TRANSIENT ISCHEMIC ATTACK. © WebMD, Inc. All rights reserved. , 2007. 6 VASCULAR SYSTEM 1(ACS Surgery: Principles and Practice ).
[41] Go, A.S., et al., Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation, 2013. 127(1): p. e6-e245.
[42] Teo, K. and J. Slark, A systematic review of studies investigating the care of stroke survivors in long-term care facilities. Disabil Rehabil, 2015: p. 1-9.
[43] Chollet, F. and J.F. Albucher, Strategies to augment recovery after stroke. Curr Treat Options Neurol, 2012. 14(6): p. 531-40. https://doi.org/10.1007/s11940-012-0196-3
[44] Lees, K.R., et al., Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet, 2010. 375(9727): p. 1695-703. https://doi.org/10.1016/S0140-6736(10)60491-6
[45] Siegel, J., et al., Update on Neurocritical Care of Stroke. Curr Cardiol Rep, 2017. 19(8): p. 67. https://doi.org/10.1007/s11886-017-0881-7
[46] Khaku, A.D., S., Stroke, in StatPearls. 2017, StatPearls Publishing LLC.: Treasure Island (FL).
[47] Nolte, C.H. and H.J. Audebert, [Management of acute ischemic stroke]. Dtsch Med Wochenschr, 2015. 140(21): p. 1583-6. https://doi.org/10.1055/s-0041-106309
[48] Hacke, W., et al., Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med, 2008. 359(13): p. 1317-29. https://doi.org/10.1056/NEJMoa0804656
[49] Sandercock, P., et al., The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet, 2012. 379(9834): p. 2352-63. https://doi.org/10.1016/S0140-6736(12)60768-5
[50] Leys, D., et al., Facilities available in European hospitals treating stroke patients. Stroke, 2007. 38(11): p. 2985-91. https://doi.org/10.1161/STROKEAHA.107.487967
[51] Evenson, K.R., W.D. Rosamond, and D.L. Morris, Prehospital and in-hospital delays in acute stroke care. Neuroepidemiology, 2001. 20(2): p. 65-76. https://doi.org/10.1159/000054763
[52] Tai, Y.J. and B. Yan, Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke. Intern Med J, 2013. 43(11): p. 1176-82. https://doi.org/10.1111/imj.12204
[53] Bustamante, A., et al., Ischemic stroke outcome: A review of the influence of post-stroke complications within the different scenarios of stroke care. Eur J Intern Med, 2015. https://doi.org/10.1016/j.ejim.2015.11.030
[54] McMullan, J.T., et al., Time-critical neurological emergencies: the unfulfilled role for point-of-care testing. Int J Emerg Med, 2010. 3(2): p. 127-31. https://doi.org/10.1007/s12245-010-0177-9
[55] Rooney, K.D. and U.M. Schilling, Point-of-care testing in the overcrowded emergency department – can it make a difference? Critical Care, 2014. 18(6): p. 692. https://doi.org/10.1186/s13054-014-0692-9
[56] Ng, G.J., et al., Stroke biomarkers in clinical practice: A critical appraisal. Neurochem Int, 2017. https://doi.org/10.1016/j.neuint.2017.01.005
[57] Yokobori, S., et al., Biomarkers for the clinical differential diagnosis in traumatic brain injury–a systematic review. CNS Neurosci Ther, 2013. 19(8): p. 556-65. https://doi.org/10.1111/cns.12127
[58] Cata, J.P., B. Abdelmalak, and E. Farag, Neurological biomarkers in the perioperative period. Br J Anaesth, 2011. 107(6): p. 844-58. https://doi.org/10.1093/bja/aer338
[59] AP., D., Biomarkers: coming of age for environmental health and risk assessment. Environ Sci Technol, 1997. 31: 1837-48. https://doi.org/10.1021/es960920a
[60] Cummins, B.M., F.S. Ligler, and G.M. Walker, Point-of-care diagnostics for niche applications. Biotechnol Adv, 2016. 34(3): p. 161-76. https://doi.org/10.1016/j.biotechadv.2016.01.005
[61] Vasan, A.S., et al., Point-of-care biosensor system. Front Biosci (Schol Ed), 2013. 5: p. 39-71. https://doi.org/10.2741/S357
[62] Price, C.P., Point of care testing. BMJ : British Medical Journal, 2001. 322(7297): p. 1285-1288. https://doi.org/10.1136/bmj.322.7297.1285
[63] St John, A. and C.P. Price, Existing and Emerging Technologies for Point-of-Care Testing. The Clinical Biochemist Reviews, 2014. 35(3): p. 155-167.
[64] Yoo, E.H. and S.Y. Lee, Glucose biosensors: an overview of use in clinical practice. Sensors (Basel), 2010. 10(5): p. 4558-76. https://doi.org/10.3390/s100504558
[65] Shah, D. and D. Maghsoudlou, Enzyme-linked immunosorbent assay (ELISA): the basics. British Journal of Hospital Medicine, 2016. 77(7): p. C98-C101. https://doi.org/10.12968/hmed.2016.77.7.C98
[66] Drain, P.K., et al., Diagnostic point-of-care tests in resource-limited settings. Lancet Infect Dis, 2014. 14(3): p. 239-49. https://doi.org/10.1016/S1473-3099(13)70250-0
[67] Kumar, S., et al., Microfluidic-integrated biosensors: prospects for point-of-care diagnostics. Biotechnol J, 2013. 8(11): p. 1267-79. https://doi.org/10.1002/biot.201200386
[68] Eltzov, E., A. Cohen, and R.S. Marks, Bioluminescent liquid light guide pad biosensor for indoor air toxicity monitoring. Anal Chem, 2015. 87(7): p. 3655-61. https://doi.org/10.1021/ac5038208
[69] Eltzov, E., et al., Lateral Flow Immunoassays – from Paper Strip to Smartphone Technology. Electroanalysis, 2015. 27(9): p. 2116-2130. https://doi.org/10.1002/elan.201500237
[70] Eltzov, E. and R.S. Marks, Colorimetric stack pad immunoassay for bacterial identification. Biosens Bioelectron, 2016. 87: p. 572-578. https://doi.org/10.1016/j.bios.2016.08.044
[71] Eltzov, E. and R.S. Marks, Miniaturized Flow Stacked Immunoassay for Detecting Escherichia coli in a Single Step. Anal Chem, 2016. 88(12): p. 6441-9. https://doi.org/10.1021/acs.analchem.6b01034
[72] Algaar, F., et al., Fiber-optic immunosensor for detection of Crimean-Congo hemorrhagic fever IgG antibodies in patients. Anal Chem, 2015. 87(16): p. 8394-8. https://doi.org/10.1021/acs.analchem.5b01728
[73] Eltzov, E., S. Cosnier, and R.S. Marks, Biosensors based on combined optical and electrochemical transduction for molecular diagnostics. Expert Rev Mol Diagn, 2011. 11(5): p. 533-46. https://doi.org/10.1586/erm.11.38
[74] Eltzov, E. and R.S. Marks, Fiber-optic based cell sensors. Adv Biochem Eng Biotechnol, 2010. 117: p. 131-54. https://doi.org/10.1007/10_2009_6
[75] Thevenot, D.R., et al., Electrochemical biosensors: recommended definitions and classification. Biosensors & Bioelectronics, 2001. 16(1-2): p. 121-131. https://doi.org/10.1016/S0956-5663(01)00115-4
[76] Eltzov, E., S. Cosnier, and R.S. Marks, Biosensors based on combined optical and electrochemical transduction for molecular diagnostics. Expert Review of Molecular Diagnostics, 2011. 11(5): p. 533-546. https://doi.org/10.1586/erm.11.38
[77] Eltzov, E. and R.S. Marks, Whole-cell aquatic biosensors. Analytical and Bioanalytical Chemistry, 2011. 400(4): p. 895-913. https://doi.org/10.1007/s00216-010-4084-y
[78] Collings, A.F. and F. Caruso, Biosensors: recent advances. Reports on Progress in Physics, 1997. 60(11): p. 1397-1445. https://doi.org/10.1088/0034-4885/60/11/005
[79] Eltzov, E., A. Kushmaro, and R.S. Marks, Biosensors and related techniques for endocrine disruptors, in Endocrine disrupting chemicals in food, I. Snow, Editor. 2009, Woodhead Publishing: Cambridge, UK. https://doi.org/10.1201/9781439829158.ch8
[80] Marks, R.S., et al., Handbook of biosensors and biochips. 2007: John Wiley & Sons, Ltd.
[81] Chin, C.D., V. Linder, and S.K. Sia, Commercialization of microfluidic point-of-care diagnostic devices. Lab on a Chip, 2012. 12(12): p. 2118-2134. https://doi.org/10.1039/c2lc21204h
[82] Walter, S., et al., Point-of-care laboratory halves door-to-therapy-decision time in acute stroke. Ann Neurol, 2011. 69. https://doi.org/10.1002/ana.22355
[83] Karlinski, M., M. Gluszkiewicz, and A. Czlonkowska, The accuracy of prehospital diagnosis of acute cerebrovascular accidents: an observational study. Arch Med Sci, 2015. 11(3): p. 530-5. https://doi.org/10.5114/aoms.2015.52355
[84] Brandler, E.S., et al., Prehospital stroke scales in urban environments: a systematic review. Neurology, 2014. 82(24): p. 2241-9. https://doi.org/10.1212/WNL.0000000000000523
[85] Drescher, M.J., et al., Point-of-Care Testing for Coagulation Studies in an Emergency Department Stroke Protocol: A Time-Saving Innovation. Annals of Emergency Medicine, 2007. 50(3): p. S25. https://doi.org/10.1016/j.annemergmed.2007.06.109
[86] Rizos, T., et al., Point-of-Care International Normalized Ratio Testing Accelerates Thrombolysis in Patients With Acute Ischemic Stroke Using Oral Anticoagulants. Stroke, 2009. 40(11): p. 3547-3551. https://doi.org/10.1161/STROKEAHA.109.562769
[87] Fassbender, K., et al., Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges. Lancet Neurol, 2017. 16(3): p. 227-237. https://doi.org/10.1016/S1474-4422(17)30008-X
[88] Walter, S., et al., Diagnosis and treatment of patients with stroke in a mobile stroke unit versus in hospital: a randomised controlled trial. Lancet Neurol, 2012. 11(5): p. 397-404. https://doi.org/10.1016/S1474-4422(12)70057-1
[89] Fassbender, K., et al., “Mobile stroke unit” for hyperacute stroke treatment. Stroke, 2003. 34(6): p. e44. https://doi.org/10.1161/01.STR.0000075573.22885.3B
[90] Parker, S.A., et al., Establishing the first mobile stroke unit in the United States. Stroke, 2015. 46(5): p. 1384-91. https://doi.org/10.1161/STROKEAHA.114.007993
[91] Ebinger, M., et al., PHANTOM-S: the prehospital acute neurological therapy and optimization of medical care in stroke patients – study. Int J Stroke, 2012. 7(4): p. 348-53. https://doi.org/10.1111/j.1747-4949.2011.00756.x
[92] Wendt, M., et al., Improved prehospital triage of patients with stroke in a specialized stroke ambulance: results of the pre-hospital acute neurological therapy and optimization of medical care in stroke study. Stroke, 2015. 46(3): p. 740-5. https://doi.org/10.1161/STROKEAHA.114.008159
[93] Gomes, J.A., et al., Prehospital Reversal of Warfarin-Related Coagulopathy in Intracerebral Hemorrhage in a Mobile Stroke Treatment Unit. Stroke, 2015. 46(5): p. e118-e120. https://doi.org/10.1161/STROKEAHA.115.008483
[94] Samsung/Neurologica, CereTom®. http://www.neurologica.com/ceretom, 2018.
[95] Siemens, SOMATOM Scope https://www.healthcare.siemens.com/computed-tomography/single-source-ct/somatom-scope, 2018.
[96] Kraft, P., et al., Feasibility and diagnostic accuracy of point-of-care handheld echocardiography in acute ischemic stroke patients – a pilot study. BMC Neurology, 2017. 17(1): p. 159. https://doi.org/10.1186/s12883-017-0937-8
[97] Healthcare, G., Vivid q®. http://www3.gehealthcare.com.sg/en-gb/products/categories/ultrasound/vivid/vivid_q, 2018.
[98] Nusa, D., et al., Assessment of point-of-care measurement of international normalised ratio using the CoaguChek XS Plus system in the setting of acute ischaemic stroke. Intern Med J, 2013. 43(11): p. 1205-9. https://doi.org/10.1111/imj.12255
[99] Green, T.L., et al., Reliability of point-of-care testing of INR in acute stroke. Can J Neurol Sci, 2008. 35(3): p. 348-51. https://doi.org/10.1017/S0317167100008945
[100] Roche, CoaguChek® http://www.coaguchek.com/coaguchek_patient/landing, 2017.
[101] Thorne, K., H. McNaughton, and M. Weatherall, An audit of coagulation screening in patients presenting to the emergency department for potential stroke thrombolysis. Intern Med J, 2017. 47(2): p. 189-193. https://doi.org/10.1111/imj.13323
[102] Zenlander, R., et al., Point-of-care versus central laboratory testing of INR in acute stroke. Acta Neurol Scand, 2018. 137(2): p. 252-255. https://doi.org/10.1111/ane.12860
[103] Nick Dale, T.P., Diagnostics by Sarissa Biomedical, SMARTChip. School of Life Sciences, Gibbet Hill Campus, The University of Warwick, Coventry, CV4 7AL, 2016. diagnostics@sarissa-biomedical.com.
[104] Trust, U.H.C.a.W.N., SMARTCap Stroke Study: A Field Deployable Blood Test for Stroke (SMARTCAP). ClinicalTrials.gov Identifier: NCT02308605. https://clinicaltrials.gov/ct2/show/NCT02308605, 2015 December
[105] sponsor: University Hospitals Coventry and Warwickshire NHS Trust, c.U.H.o.N.M.N.T., Validation of a Purine Biosensor in Detecting Acute Cerebral Ischaemia: Carotid Endarterectomy Model in SMARTChip (CEMS). ClinicalTrials.gov Identifier: NCT02545166. https://clinicaltrials.gov/ct2/show/NCT02545166, 2017, July 6.
[106] Trust, U.H.C.a.W.N., The SMARTChip Stroke Study. ClinicalTrials.gov Identifier: NCT02795481. https://clinicaltrials.gov/ct2/show/NCT02795481, 2016 July.
[107] Inc., A.P.o.C., i-STAT®. https://www.pointofcare.abbott/int/en/home, 2017.
[108] Drescher, M.J., et al., Point-of-care testing for coagulation studies in a stroke protocol: a time-saving innovation. Am J Emerg Med, 2011. 29(1): p. 82-5. https://doi.org/10.1016/j.ajem.2009.09.020
[109] Nanduri, S., et al., An analysis of discrepancy between point-of-care and central laboratory international normalized ratio testing in ED patients with cerebrovascular disease. Am J Emerg Med, 2012. 30(9): p. 2025-9. https://doi.org/10.1016/j.ajem.2012.04.003
[110] Inc., A.P.o.C., 2016.
[111] Abbott, i-STAT®. https://www.pointofcare.abbott/int/en/offerings/istat/istat-handheld, 2017.
[112] Briggs, C., et al., Performance evaluation of a new compact hematology analyzer, the Sysmex pocH-100i. Lab Hematol, 2003. 9(4): p. 225-33.
[113] Sysmex, PocH-100iTM http://www.sysmex-ap.com/products/diagnostics/hematology/poch-100i/, 2018.
[114] Diagnostics, I.A., Hemochron®. Accriva Diagnostics, representing ITC and Accumetrics. All rights reserved. Accriva is ISO 13485 certified. , © 2015 http://www.accriva.com/products#.
[115] Diagnostics, I.A., Hemochron® http://www.accriva.com/products/hemochron-signature-elite-whole-blood-microcoagulation-system, 2015.
[116] Ltd, R.D.I., Reflotron® plus analyzer http://www.cobas.com/home/product/point-of-care-testing/reflotron-plus-sprint-system.html, © 2017 .
[117] Roche, Reflotron® plus analyzer. http://www.cobas.com/home/product/point-of-care-testing/reflotron-plus-sprint-system.html, 2017.
[118] Wu, Z., et al., Experiences and the use of BNP POCT platform on suspected ischemic stroke patients in the emergency department setting. Clin Neurol Neurosurg, 2014. 123: p. 199-200. https://doi.org/10.1016/j.clineuro.2014.04.033
[119] He, M., et al., A new algorithm of suspected stroke patient management with brain natriuretic peptide/N-terminal pro-brain natriuretic peptide point of care testing platform in the emergency department. Ann Indian Acad Neurol, 2017. 20(1): p. 81-82. https://doi.org/10.4103/0972-2327.194316
[120] Wu, Z., et al., Validation of the use of B-type natriuretic peptide point-of-care test platform in preliminary recognition of cardioembolic stroke patients in the ED. Am J Emerg Med, 2015. 33(4): p. 521-6. https://doi.org/10.1016/j.ajem.2015.01.013
[121] Nayer, J., P. Aggarwal, and S. Galwankar, Utility of point-of-care testing of natriuretic peptides (brain natriuretic peptide and n-terminal pro-brain natriuretic peptide) in the emergency department. International Journal of Critical Illness and Injury Science, 2014. 4(3): p. 209-215. https://doi.org/10.4103/2229-5151.141406
[122] Gils, C., et al., NT-proBNP on Cobas h 232 in point-of-care testing: Performance in the primary health care versus in the hospital laboratory. Scandinavian Journal of Clinical and Laboratory Investigation, 2015. 75(7): p. 602-609. https://doi.org/10.3109/00365513.2015.1066846
[123] Llombart, V., et al., B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis. Stroke, 2015. 46(5): p. 1187-95. https://doi.org/10.1161/STROKEAHA.114.008311
[124] Kawase, S., et al., Plasma Brain Natriuretic Peptide is a Marker of Prognostic Functional Outcome in Non-Cardioembolic Infarction. J Stroke Cerebrovasc Dis, 2015. 24(10): p. 2285-90. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.06.006
[125] Clerico, A., et al., State of the art of immunoassay methods for B-type natriuretic peptides: An update. Crit Rev Clin Lab Sci, 2015. 52(2): p. 56-69. https://doi.org/10.3109/10408363.2014.987720
[126] Chaudhuri, J.R., et al., Association of plasma brain natriuretic peptide levels in acute ischemic stroke subtypes and outcome. J Stroke Cerebrovasc Dis, 2015. 24(2): p. 485-91. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.09.025
[127] Yang, H.L., et al., Predicting cardioembolic stroke with the B-type natriuretic peptide test: a systematic review and meta-analysis. J Stroke Cerebrovasc Dis, 2014. 23(7): p. 1882-9. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.02.014
[128] Qihong, G., et al., Experiences and the use of BNP POCT platform on suspected stroke patients by a Chinese emergency department. Ann Indian Acad Neurol, 2014. 17(2): p. 243-4. https://doi.org/10.4103/0972-2327.132670
[129] Maruyama, K., et al., Brain natriuretic peptide in acute ischemic stroke. J Stroke Cerebrovasc Dis, 2014. 23(5): p. 967-72. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.08.003
[130] Kara, K., et al., B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification. Eur J Neurol, 2014. 21(6): p. 914-21. https://doi.org/10.1111/ene.12411
[131] Balion, C., et al., B-type natriuretic peptide-guided therapy: a systematic review. Heart Fail Rev, 2014. 19(4): p. 553-64. https://doi.org/10.1007/s10741-014-9451-x
[132] Sakai, K., et al., Brain natriuretic peptide as a predictor of cardioembolism in acute ischemic stroke patients: brain natriuretic peptide stroke prospective study. Eur Neurol, 2013. 69(4): p. 246-51. https://doi.org/10.1159/000342887
[133] Hajsadeghi, S., et al., The diagnostic value of N-terminal pro-brain natriuretic peptide in differentiating cardioembolic ischemic stroke. J Stroke Cerebrovasc Dis, 2013. 22(4): p. 554-60. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.01.012
[134] Cojocaru, I.M., et al., Could pro-BNP, uric acid, bilirubin, albumin and transferrin be used in making the distinction between stroke subtypes? Rom J Intern Med, 2013. 51(3-4): p. 188-95.
[135] Shibazaki, K., et al., Plasma brain natriuretic peptide can be a biological marker to distinguish cardioembolic stroke from other stroke types in acute ischemic stroke. Intern Med, 2009. 48(5): p. 259-64. https://doi.org/10.2169/internalmedicine.48.1475
[136] Garcia-Berrocoso, T., et al., B-type natriuretic peptides and mortality after stroke: a systematic review and meta-analysis. Neurology, 2013. 81(23): p. 1976-85. https://doi.org/10.1212/01.wnl.0000436937.32410.32
[137] Jickling, G.C. and C. Foerch, Predicting stroke mortality: BNP could it be? Neurology, 2013. 81(23): p. 1970-1. https://doi.org/10.1212/01.wnl.0000436949.75473.79
[138] Shibazaki, K., et al., Brain natriuretic peptide on admission as a biological marker of long-term mortality in ischemic stroke survivors. Eur Neurol, 2013. 70(3-4): p. 218-24. https://doi.org/10.1159/000351777
[139] Chen, X., et al., The prognostic value of combined NT-pro-BNP levels and NIHSS scores in patients with acute ischemic stroke. Intern Med, 2012. 51(20): p. 2887-92. https://doi.org/10.2169/internalmedicine.51.8027
[140] Montaner, J., et al., Brain natriuretic peptide is associated with worsening and mortality in acute stroke patients but adds no prognostic value to clinical predictors of outcome. Cerebrovasc Dis, 2012. 34(3): p. 240-5. https://doi.org/10.1159/000341858
[141] Mäkikallio, A.M., et al., Natriuretic Peptides and Mortality After Stroke. Stroke, 2005. 36(5): p. 1016-1020. https://doi.org/10.1161/01.STR.0000162751.54349.ae
[142] Shibazaki, K., et al., Plasma Brain Natriuretic Peptide as an Independent Predictor of In-Hospital Mortality after Acute Ischemic Stroke. Internal Medicine, 2009. 48(18): p. 1601-1606. https://doi.org/10.2169/internalmedicine.48.2166
[143] Jensen, J.K., et al., Usefulness of Natriuretic Peptide Testing for Long-Term Risk Assessment Following Acute Ischemic Stroke. American Journal of Cardiology, 2009. 104(2): p. 287-291. https://doi.org/10.1016/j.amjcard.2009.03.029
[144] Shibazaki, K., et al., Brain natriuretic peptide level on admission predicts recurrent stroke after discharge in stroke survivors with atrial fibrillation. Clin Neurol Neurosurg, 2014. 127: p. 25-9. https://doi.org/10.1016/j.clineuro.2014.09.028
[145] Shibazaki, K., et al., Plasma brain natriuretic Peptide as a predictive marker of early recurrent stroke in cardioembolic stroke patients. J Stroke Cerebrovasc Dis, 2014. 23(10): p. 2635-40. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.06.003
[146] Mortezabeigi, H.R., et al., ABCD2 score and BNP level in patients with TIA and cerebral stroke. Pak J Biol Sci, 2013. 16(21): p. 1393-7. https://doi.org/10.3923/pjbs.2013.1393.1397
[147] Roche, Cobas® h 232 http://www.cobas.com/home/product/point-of-care-testing/cobas-h-232.html, 2017.
[148] Alere, Triage® BNP Test https://www.alere.com/kr/en/product-details/triage-bnp-test.html, 2018.
[149] Cohen, R., et al., Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection. PLoS ONE, 2015. 10(11): p. e0142326. https://doi.org/10.1371/journal.pone.0142326
[150] Dash, P.K., et al., Biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy for traumatic brain injury. Neurotherapeutics, 2010. 7(1): p. 100-14. https://doi.org/10.1016/j.nurt.2009.10.019
[151] Ahmad, O., J. Wardlaw, and W.N. Whiteley, Correlation of levels of neuronal and glial markers with radiological measures of infarct volume in ischaemic stroke: a systematic review. Cerebrovasc Dis, 2012. 33(1): p. 47-54. https://doi.org/10.1159/000332810
[152] Wunderlich, M.T., et al., Neuron-specific enolase and tau protein as neurobiochemical markers of neuronal damage are related to early clinical course and long-term outcome in acute ischemic stroke. Clin Neurol Neurosurg, 2006. 108(6): p. 558-63. https://doi.org/10.1016/j.clineuro.2005.12.006
[153] Wevers, R.A., A.A. Jacobs, and O.R. Hommes, A bioluminescent assay for enolase (EC activity in human serum and cerebrospinal fluid. Clin Chim Acta, 1983. 135(2): p. 159-68. https://doi.org/10.1016/0009-8981(83)90131-6
[154] Viallard, J.L., M.R. Murthy, and B. Dastugue, An ultramicro bioluminescence assay of enolase: application to human cerebrospinal fluid. Neurochem Res, 1985. 10(12): p. 1555-66. https://doi.org/10.1007/BF00988598
[155] Wevers, R.A., A.W. Theunisse, and G. Rijksen, An immunobioluminescence assay for gamma-gamma enolase activity in human serum and cerebrospinal fluid. Clin Chim Acta, 1988. 178(2): p. 141-50. https://doi.org/10.1016/0009-8981(88)90220-3
[156] Harrison, P., et al., Screening for Aspirin Responsiveness After Transient Ischemic Attack and Stroke. Comparison of 2 Point-of-Care Platelet Function Tests With Optical Aggregometry, 2005. 36(5): p. 1001-1005. https://doi.org/10.1161/01.STR.0000162719.11058.bd
[157] Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Bmj, 2002. 324(7329): p. 71-86. https://doi.org/10.1136/bmj.324.7329.71
[158] Altman, R., et al., The antithrombotic profile of aspirin. Aspirin resistance, or simply failure? Thromb J, 2004. 2(1): p. 1.
[159] Gum, P.A., et al., Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol, 2001. 88(3): p. 230-5. https://doi.org/10.1016/S0002-9149(01)01631-9
[160] Helgason, C.M., et al., Aspirin response and failure in cerebral infarction. Stroke, 1993. 24(3): p. 345-50. https://doi.org/10.1161/01.STR.24.3.345
[161] Howard, P.A., Aspirin resistance. Ann Pharmacother, 2002. 36(10): p. 1620-4. https://doi.org/10.1345/aph.1C013
[162] McKee, S.A., D.C. Sane, and E.N. Deliargyris, Aspirin resistance in cardiovascular disease: a review of prevalence, mechanisms, and clinical significance. Thromb Haemost, 2002. 88(5): p. 711-5. https://doi.org/10.1055/s-0037-1613290
[163] Patrono, C., Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost, 2003. 1(8): p. 1710-3. https://doi.org/10.1046/j.1538-7836.2003.00284.x
[164] Hankey, G.J. and J.W. Eikelboom, Aspirin resistance. Bmj, 2004. 328(7438): p. 477-9. https://doi.org/10.1136/bmj.328.7438.477
[165] Eikelboom, J.W. and G.J. Hankey, Failure of aspirin to prevent atherothrombosis: potential mechanisms and implications for clinical practice. Am J Cardiovasc Drugs, 2004. 4(1): p. 57-67. https://doi.org/10.2165/00129784-200404010-00006
[166] Gum, P.A., et al., A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol, 2003. 41(6): p. 961-5. https://doi.org/10.1016/S0735-1097(02)03014-0
[167] Eikelboom, J.W. and G.J. Hankey, Aspirin resistance: a new independent predictor of vascular events? J Am Coll Cardiol, 2003. 41(6): p. 966-8. https://doi.org/10.1016/S0735-1097(02)03013-9
[168] Baigent, C., et al., Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet, 2009. 373(9678): p. 1849-60. https://doi.org/10.1016/S0140-6736(09)60503-1
[169] Rothwell, P.M., et al., Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet, 2016. 388(10042): p. 365-75. https://doi.org/10.1016/S0140-6736(16)30468-8
[170] Harrison, P., Progress in the assessment of platelet function. Br J Haematol, 2000. 111(3): p. 733-44. https://doi.org/10.1046/j.1365-2141.2000.02269.x
[171] Rand, M.L., R. Leung, and M.A. Packham, Platelet function assays. Transfus Apher Sci, 2003. 28(3): p. 307-17. https://doi.org/10.1016/S1473-0502(03)00050-8
[172] Pearson, C., et al., Utility of point of care assessment of platelet reactivity (using the PFA-100(R)) to aid in diagnosis of stroke. Am J Emerg Med, 2017. 35(5): p. 802.e1-802.e5. https://doi.org/10.1016/j.ajem.2016.11.036
[173] Lordkipanidzé, M., et al., A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. European Heart Journal, 2007. 28(14): p. 1702-1708. https://doi.org/10.1093/eurheartj/ehm226
[174] Diagnostics, A.A., VerifyNow®. http://www.accriva.com/products/verifynow-system-platelet-reactivity-test, 2015.
[175] Dade/Siemens, PFA-100® https://usa.healthcare.siemens.com/hemostasis/systems/pfa-100/technical-specifications, 2018.
[176] SBIR*STTR, A.s.S.F.b.S., Development of Stroke Point of Care Immunoassay for Cellular Fibronectin. 2009(Agency Tracking Number: NS057921, Contract: 2R44NS057921-02A1 ).
[177] Bio, V., ReST™, a rapid evaluation stroke triage test. Eight Medical Center Drive | Morgantown, WV 26506 | 304-825-3131 2014. http://valtaribio.com/executive-overview/.
[178] Monbailliu, T., J. Goossens, and S. Hachimi-Idrissi, Blood protein biomarkers as diagnostic tool for ischemic stroke: a systematic review. Biomark Med, 2017. 11(6): p. 503-512. https://doi.org/10.2217/bmm-2016-0232
[179] Herrmann, M. and H. Ehrenreich, Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci, 2003. 21(3-4): p. 177-90.
[180] Herrmann, M., et al., Release of glial tissue-specific proteins after acute stroke: A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke, 2000. 31(11): p. 2670-7. https://doi.org/10.1161/01.STR.31.11.2670
[181] Wunderlich, M.T., et al., Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Stroke, 1999. 30(6): p. 1190-5. https://doi.org/10.1161/01.STR.30.6.1190
[182] Kapural, M., et al., Serum S-100beta as a possible marker of blood-brain barrier disruption. Brain Res, 2002. 940(1-2): p. 102-4. https://doi.org/10.1016/S0006-8993(02)02586-6
[183] Gazzolo, D., et al., Neuromarkers and unconventional biological fluids. J Matern Fetal Neonatal Med, 2010. 23 Suppl 3: p. 66-9. https://doi.org/10.3109/14767058.2010.507960
[184] Mir, I.N. and L.F. Chalak, Serum biomarkers to evaluate the integrity of the neurovascular unit. Early Hum Dev, 2014. 90(10): p. 707-11. https://doi.org/10.1016/j.earlhumdev.2014.06.010
[185] Brouns, R., et al., Neurobiochemical markers of brain damage in cerebrospinal fluid of acute ischemic stroke patients. Clin Chem, 2010. 56(3): p. 451-8. https://doi.org/10.1373/clinchem.2009.134122
[186] Lian, T., et al., Identification of Site-Specific Stroke Biomarker Candidates by Laser Capture Microdissection and Labeled Reference Peptide. Int J Mol Sci, 2015. 16(6): p. 13427-41. https://doi.org/10.3390/ijms160613427
[187] Pelinka, L.E., et al., GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma, 2004. 21(11): p. 1553-61. https://doi.org/10.1089/neu.2004.21.1553
[188] Dvorak, F., et al., Characterisation of the diagnostic window of serum glial fibrillary acidic protein for the differentiation of intracerebral haemorrhage and ischaemic stroke. Cerebrovasc Dis, 2009. 27(1): p. 37-41. https://doi.org/10.1159/000172632
[189] Yang, Z. and K.K. Wang, Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci, 2015. 38(6): p. 364-74. https://doi.org/10.1016/j.tins.2015.04.003
[190] Teunissen, C.E., C. Dijkstra, and C. Polman, Biological markers in CSF and blood for axonal degeneration in multiple sclerosis. Lancet Neurol, 2005. 4(1): p. 32-41. https://doi.org/10.1016/S1474-4422(04)00964-0
[191] Shibata, D., et al., Myelin basic protein autoantibodies, white matter disease and stroke outcome. J Neuroimmunol, 2012. 252(1-2): p. 106-12. https://doi.org/10.1016/j.jneuroim.2012.08.006
[192] Zierath, D., et al., Promiscuity of autoimmune responses to MBP after stroke. J Neuroimmunol, 2015. 285: p. 101-5. https://doi.org/10.1016/j.jneuroim.2015.05.024
[193] Becker, K.J., et al., Antibodies to myelin basic protein are associated with cognitive decline after stroke. J Neuroimmunol, 2016. 295-296: p. 9-11. https://doi.org/10.1016/j.jneuroim.2016.04.001
[194] Basile, A.M., et al., S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study. Eur Neurol, 2001. 45(3): p. 151-9. https://doi.org/10.1159/000052114
[195] Karkela, J., E. Bock, and S. Kaukinen, CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. J Neurol Sci, 1993. 116(1): p. 100-9. https://doi.org/10.1016/0022-510X(93)90095-G
[196] Liu, M.C., et al., Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats. Eur J Neurosci, 2010. 31(4): p. 722-32. https://doi.org/10.1111/j.1460-9568.2010.07097.x
[197] Papa, L., et al., Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit Care Med, 2010. 38(1): p. 138-44. https://doi.org/10.1097/CCM.0b013e3181b788ab
[198] Ren, C., et al., Different expression of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin in ischemic and hemorrhagic stroke: Potential biomarkers in diagnosis. Brain Res, 2013. 1540: p. 84-91. https://doi.org/10.1016/j.brainres.2013.09.051
[199] Tongaonkar, P., et al., Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome. Mol Cell Biol, 2000. 20(13): p. 4691-8. https://doi.org/10.1128/MCB.20.13.4691-4698.2000
[200] Vaagenes, P., et al., Enzyme level changes in the cerebrospinal fluid of patients with acute stroke. Arch Neurol, 1986. 43(4): p. 357-62. https://doi.org/10.1001/archneur.1986.00520040043017
[201] Ingebrigtsen, T. and B. Romner, Biochemical serum markers for brain damage: a short review with emphasis on clinical utility in mild head injury. Restor Neurol Neurosci, 2003. 21(3-4): p. 171-6.
[202] Atisha, D., et al., A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction. Am Heart J, 2004. 148(3): p. 518-23. https://doi.org/10.1016/j.ahj.2004.03.014
[203] Ioannou, A., et al., Biomarkers associated with stroke risk in atrial fibrillation. Curr Med Chem, 2017.
[204] Bustamante, A., et al., Blood Biomarkers for the Early Diagnosis of Stroke: The Stroke-Chip Study. Stroke, 2017. https://doi.org/10.1161/STROKEAHA.117.017076
[205] Castellanos, M., et al., Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke, 2003. 34(1): p. 40-6. https://doi.org/10.1161/01.STR.0000046764.57344.31
[206] Sood, R., et al., Increased apparent diffusion coefficients on MRI linked with matrix metalloproteinases and edema in white matter after bilateral carotid artery occlusion in rats. J Cereb Blood Flow Metab, 2009. 29(2): p. 308-16. https://doi.org/10.1038/jcbfm.2008.121
[207] Laskowitz, D.T., et al., Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke, 2009. 40(1): p. 77-85. https://doi.org/10.1161/STROKEAHA.108.516377
[208] Zhang, X.Q., et al., Exploring the optimal operation time for patients with hypertensive intracerebral hemorrhage: tracking the expression and progress of cell apoptosis of prehematomal brain tissues. Chin Med J (Engl), 2010. 123(10): p. 1246-50.
[209] Taurino, M., et al., Metalloproteinase expression in carotid plaque and its correlation with plasma levels before and after carotid endarterectomy. Vasc Endovascular Surg, 2007. 41(6): p. 516-21. https://doi.org/10.1177/1538574407307405
[210] Tayal, V. and B.S. Kalra, Cytokines and anti-cytokines as therapeutics–an update. Eur J Pharmacol, 2008. 579(1-3): p. 1-12. https://doi.org/10.1016/j.ejphar.2007.10.049
[211] Rostene, W., et al., Neurochemokines: a menage a trois providing new insights on the functions of chemokines in the central nervous system. J Neurochem, 2011. 118(5): p. 680-94. https://doi.org/10.1111/j.1471-4159.2011.07371.x
[212] Tuttolomondo, A., et al., Inflammation in ischemic stroke subtypes. Curr Pharm Des, 2012. 18(28): p. 4289-310. https://doi.org/10.2174/138161212802481200
[213] Licata, G., et al., Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost, 2009. 101(5): p. 929-37. https://doi.org/10.1160/TH08-06-0375
[214] Abbott, N.J., L. Ronnback, and E. Hansson, Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci, 2006. 7(1): p. 41-53. https://doi.org/10.1038/nrn1824
[215] Bailey, S.L., et al., Innate and adaptive immune responses of the central nervous system. Crit Rev Immunol, 2006. 26(2): p. 149-88. https://doi.org/10.1615/CritRevImmunol.v26.i2.40
[216] Vela, J.M., et al., Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells. Mol Cell Neurosci, 2002. 20(3): p. 489-502. https://doi.org/10.1006/mcne.2002.1127
[217] Rodriguez-Yanez, M. and J. Castillo, Role of inflammatory markers in brain ischemia. Curr Opin Neurol, 2008. 21(3): p. 353-7. https://doi.org/10.1097/WCO.0b013e3282ffafbf
[218] Gokhan, S., et al., Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack. Eur Rev Med Pharmacol Sci, 2013. 17(5): p. 653-7.
[219] Huang, G., et al., Significance of white blood cell count and its subtypes in patients with acute coronary syndrome. Eur J Clin Invest, 2009. 39(5): p. 348-58. https://doi.org/10.1111/j.1365-2362.2009.02107.x
[220] Papa, A., et al., Predictive value of elevated neutrophil-lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease. Clin Chim Acta, 2008. 395(1-2): p. 27-31. https://doi.org/10.1016/j.cca.2008.04.019
[221] Cook, E.J., et al., Post-operative neutrophil-lymphocyte ratio predicts complications following colorectal surgery. Int J Surg, 2007. 5(1): p. 27-30. https://doi.org/10.1016/j.ijsu.2006.05.013
[222] Karabinos, I., et al., Neutrophil count on admission predicts major in-hospital events in patients with a non-ST-segment elevation acute coronary syndrome. Clin Cardiol, 2009. 32(10): p. 561-8. https://doi.org/10.1002/clc.20624
[223] Buck, B.H., et al., Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke, 2008. 39(2): p. 355-60. https://doi.org/10.1161/STROKEAHA.107.490128
[224] Elkind, M.S., et al., Relative elevation in baseline leukocyte count predicts first cerebral infarction. Neurology, 2005. 64(12): p. 2121-5. https://doi.org/10.1212/01.WNL.0000165989.12122.49
[225] Petzold, A., Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci, 2005. 233(1-2): p. 183-98. https://doi.org/10.1016/j.jns.2005.03.015
[226] Chen, X.H., et al., Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig. J Neuropathol Exp Neurol, 1999. 58(6): p. 588-96. https://doi.org/10.1097/00005072-199906000-00003
[227] Jafari, S.S., et al., Axonal cytoskeletal changes after non-disruptive axonal injury. J Neurocytol, 1997. 26(4): p. 207-21. https://doi.org/10.1023/A:1018588114648
[228] Ost, M., et al., Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology, 2006. 67(9): p. 1600-4. https://doi.org/10.1212/01.wnl.0000242732.06714.0f
[229] Folkerts, M.M., et al., Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. J Neurotrauma, 1998. 15(5): p. 349-63. https://doi.org/10.1089/neu.1998.15.349
[230] Zemlan, F.P., et al., C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res, 2002. 947(1): p. 131-9. https://doi.org/10.1016/S0006-8993(02)02920-7
[231] Zemlan, F.P., J.J. Mulchahey, and G.A. Gudelsky, Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau). Neuroscience, 2003. 121(2): p. 399-409. https://doi.org/10.1016/S0306-4522(03)00459-7
[232] Olmsted, J.B., Microtubule-associated proteins. Annu Rev Cell Biol, 1986. 2: p. 421-57. https://doi.org/10.1146/annurev.cb.02.110186.002225
[233] Matus, A., Neurofilament protein phosphorylation–where, when and why. Trends Neurosci, 1988. 11(7): p. 291-2. https://doi.org/10.1016/0166-2236(88)90086-0
[234] Garner, C.C., R.P. Tucker, and A. Matus, Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites. Nature, 1988. 336(6200): p. 674-7. https://doi.org/10.1038/336674a0
[235] Kobeissy, F.H., et al., Neuroproteomics and systems biology-based discovery of protein biomarkers for traumatic brain injury and clinical validation. Proteomics Clin Appl, 2008. 2(10-11): p. 1467-83. https://doi.org/10.1002/prca.200800011
[236] Buki, A., et al., The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury. J Neuropathol Exp Neurol, 1999. 58(4): p. 365-75. https://doi.org/10.1097/00005072-199904000-00007
[237] Reeves, T.M., et al., Proteolysis of submembrane cytoskeletal proteins ankyrin-G and alphaII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain Pathol, 2010. 20(6): p. 1055-68. https://doi.org/10.1111/j.1750-3639.2010.00412.x
[238] Wang, K.K., et al., Simultaneous degradation of alphaII- and betaII-spectrin by caspase 3 (CPP32) in apoptotic cells. J Biol Chem, 1998. 273(35): p. 22490-7. https://doi.org/10.1074/jbc.273.35.22490
[239] Cox, C.D., et al., Dicyclomine, an M1 muscarinic antagonist, reduces biomarker levels, but not neuronal degeneration, in fluid percussion brain injury. J Neurotrauma, 2008. 25(11): p. 1355-65. https://doi.org/10.1089/neu.2008.0671
[240] Adam, S.S., N.S. Key, and C.S. Greenberg, D-dimer antigen: current concepts and future prospects. Blood, 2009. 113(13): p. 2878-87. https://doi.org/10.1182/blood-2008-06-165845
[241] Mai, H., et al., Clinical presentation and imaging characteristics of occult lung cancer associated ischemic stroke. J Clin Neurosci, 2015. 22(2): p. 296-302. https://doi.org/10.1016/j.jocn.2014.05.039
[242] Kim, K. and J.H. Lee, Risk factors and biomarkers of ischemic stroke in cancer patients. J Stroke, 2014. 16(2): p. 91-6. https://doi.org/10.5853/jos.2014.16.2.91
[243] Liu, L.B., et al., The role of hs-CRP, D-dimer and fibrinogen in differentiating etiological subtypes of ischemic stroke. PLoS One, 2015. 10(2): p. e0118301. https://doi.org/10.1371/journal.pone.0118301
[244] Zi, W.J. and J. Shuai, Plasma D-dimer levels are associated with stroke subtypes and infarction volume in patients with acute ischemic stroke. PLoS One, 2014. 9(1): p. e86465. https://doi.org/10.1371/journal.pone.0086465
[245] Zecca, B., et al., A bioclinical pattern for the early diagnosis of cardioembolic stroke. Emerg Med Int, 2014. 2014: p. 242171. https://doi.org/10.1155/2014/242171
[246] Yuan, W. and Z.H. Shi, The relationship between plasma D-dimer levels and outcome of Chinese acute ischemic stroke patients in different stroke subtypes. J Neural Transm (Vienna), 2014. 121(4): p. 409-13. https://doi.org/10.1007/s00702-013-1113-y
[247] Wiseman, S., et al., Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis. Cerebrovasc Dis, 2014. 37(1): p. 64-75. https://doi.org/10.1159/000356789
[248] Okazaki, T., et al., The ratio of D-dimer to brain natriuretic peptide may help to differentiate between cerebral infarction with and without acute aortic dissection. J Neurol Sci, 2014. 340(1-2): p. 133-8. https://doi.org/10.1016/j.jns.2014.03.011
[249] Isenegger, J., et al., D-dimers predict stroke subtype when assessed early. Cerebrovasc Dis, 2010. 29(1): p. 82-6. https://doi.org/10.1159/000256652
[250] Ilhan, D., et al., Evaluation of platelet activation, coagulation, and fibrinolytic activation in patients with symptomatic lacunar stroke. Neurologist, 2010. 16(3): p. 188-91. https://doi.org/10.1097/NRL.0b013e318198d8bc
[251] Haapaniemi, E. and T. Tatlisumak, Is D-dimer helpful in evaluating stroke patients? A systematic review. Acta Neurol Scand, 2009. 119(3): p. 141-50. https://doi.org/10.1111/j.1600-0404.2008.01081.x
[252] Montaner, J., et al., Etiologic diagnosis of ischemic stroke subtypes with plasma biomarkers. Stroke, 2008. 39(8): p. 2280-7. https://doi.org/10.1161/STROKEAHA.107.505354
[253] Dougu, N., et al., Differential diagnosis of cerebral infarction using an algorithm combining atrial fibrillation and D-dimer level. Eur J Neurol, 2008. 15(3): p. 295-300. https://doi.org/10.1111/j.1468-1331.2008.02063.x
[254] Squizzato, A., et al., D-dimer is not a long-term prognostic marker following acute cerebral ischemia. Blood Coagul Fibrinolysis, 2006. 17(4): p. 303-6. https://doi.org/10.1097/01.mbc.0000224850.57872.d0
[255] Squizzato, A. and W. Ageno, D-dimer testing in ischemic stroke and cerebral sinus and venous thrombosis. Semin Vasc Med, 2005. 5(4): p. 379-86. https://doi.org/10.1055/s-2005-922484
[256] Koch, H.J., et al., The relationship between plasma D-dimer concentrations and acute ischemic stroke subtypes. J Stroke Cerebrovasc Dis, 2005. 14(2): p. 75-9. https://doi.org/10.1016/j.jstrokecerebrovasdis.2004.12.002
[257] Ageno, W., et al., Plasma measurement of D-dimer levels for the early diagnosis of ischemic stroke subtypes. Arch Intern Med, 2002. 162(22): p. 2589-93. https://doi.org/10.1001/archinte.162.22.2589
[258] Takano, K., T. Yamaguchi, and K. Uchida, Markers of a hypercoagulable state following acute ischemic stroke. Stroke, 1992. 23(2): p. 194-8. https://doi.org/10.1161/01.STR.23.2.194
[259] Elkind, M.S., et al., High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med, 2006. 166(19): p. 2073-80. https://doi.org/10.1001/archinte.166.19.2073
[260] Muir, K.W., et al., C-reactive protein and outcome after ischemic stroke. Stroke, 1999. 30(5): p. 981-5. https://doi.org/10.1161/01.STR.30.5.981
[261] Audebert, H.J., et al., Systemic inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis. Stroke, 2004. 35(9): p. 2128-33. https://doi.org/10.1161/01.STR.0000137607.61697.77
[262] Suwanwela, N.C., A. Chutinet, and K. Phanthumchinda, Inflammatory markers and conventional atherosclerotic risk factors in acute ischemic stroke: comparative study between vascular disease subtypes. J Med Assoc Thai, 2006. 89(12): p. 2021-7.
[263] Masotti, L., et al., Prognostic role of C-reactive protein in very old patients with acute ischaemic stroke. J Intern Med, 2005. 258(2): p. 145-52. https://doi.org/10.1111/j.1365-2796.2005.01514.x
[264] Hirano, K., et al., Study of hemostatic biomarkers in acute ischemic stroke by clinical subtype. J Stroke Cerebrovasc Dis, 2012. 21(5): p. 404-10. https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.08.013
[265] Iskra, T., et al., [Hemostatic markers of endothelial injury in ischaemic stroke caused by large or small vessel disease]. Pol Merkur Lekarski, 2006. 21(125): p. 429-33.
[266] Bang, O.Y., et al., Association of serum lipid indices with large artery atherosclerotic stroke. Neurology, 2008. 70(11): p. 841-7. https://doi.org/10.1212/01.wnl.0000294323.48661.a9
[267] Slowik, A., et al., LDL phenotype B and other lipid abnormalities in patients with large vessel disease and small vessel disease. J Neurol Sci, 2003. 214(1-2): p. 11-6. https://doi.org/10.1016/S0022-510X(03)00166-7
[268] Iskra, T., et al., [LDL phenotype A and B in ischemic stroke]. Przegl Lek, 2002. 59(1): p. 7-10.
[269] Zimmermann-Ivol, C.G., et al., Fatty acid binding protein as a serum marker for the early diagnosis of stroke: a pilot study. Mol Cell Proteomics, 2004. 3(1): p. 66-72. https://doi.org/10.1074/mcp.M300066-MCP200
[270] Watson, M.A. and M.G. Scott, Clinical utility of biochemical analysis of cerebrospinal fluid. Clin Chem, 1995. 41(3): p. 343-60.
[271] Sun, G.J., et al., Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Stroke Subtypes and Severity in Chinese Patients with Acute Ischemic Stroke. World Neurosurg, 2015. 84(5): p. 1299-304. https://doi.org/10.1016/j.wneu.2015.06.006
[272] Zambrelli, E., et al., Apo(a) size in ischemic stroke: relation with subtype and severity on hospital admission. Neurology, 2005. 64(8): p. 1366-70. https://doi.org/10.1212/01.WNL.0000158282.83369.1D
[273] Iskra, T., et al., [Lipoprotein (a) in stroke patients with large and small vessel disease]. Przegl Lek, 2002. 59(11): p. 877-80.
[274] Saidi, S., et al., Association of apolipoprotein E gene polymorphism with ischemic stroke involving large-vessel disease and its relation to serum lipid levels. J Stroke Cerebrovasc Dis, 2007. 16(4): p. 160-6. https://doi.org/10.1016/j.jstrokecerebrovasdis.2007.03.001
[275] Lampl, Y., et al., Cerebrospinal fluid lactate dehydrogenase levels in early stroke and transient ischemic attacks. Stroke, 1990. 21(6): p. 854-7. https://doi.org/10.1161/01.STR.21.6.854
[276] Alvarez-Perez, F.J., M. Castelo-Branco, and J. Alvarez-Sabin, Albumin level and stroke. Potential association between lower albumin level and cardioembolic aetiology. Int J Neurosci, 2011. 121(1): p. 25-32. https://doi.org/10.3109/00207454.2010.523134
[277] Xu, Y.Z., et al., Dynamic reduction of plasma decorin following ischemic stroke: a pilot study. Neurochem Res, 2012. 37(9): p. 1843-8. https://doi.org/10.1007/s11064-012-0787-0
[278] Department, C.C.E.I.E.E., Mobile Stroke Unit. Copyright © All rights reserved, 2015.