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Is there a relationship between NR-2 antibody peptide level and diagnosis, prognosis and coma scores in acute ischemic stroke?

Year 2022, Volume: 6 Issue: 2, 145 - 150, 20.08.2022
https://doi.org/10.30565/medalanya.1116544

Abstract

Aim: This study aimed to demonstrate the diagnostic and prognostic value of NR-2 peptides as a biomarker in acute ischemic stroke and to evaluate their correlation with the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS).

Materials and Methods: The importance of NR-2 peptide level in diagnosis and prognosis in acute stroke was investigated cross-sectional and prospectively. The study included 101 patients, who presented to a tertiary healthcare facility and were diagnosed with acute stroke, and 57 healthy controls. In the whole study population, serum NR-2 peptide levels were measured using the ELISA method.

Results: The NR-2 peptide level was 6.32 ± 8.30 in the patient group and 3.91 ± 1.64 in the study group. The NR-2 peptide level was significantly higher in the patient group (p = 0.006). No correlation was detected between NR-2 peptide levels and scores in the GCS or NIHSS. The results indicated that NR-2 was a potential biomarker elevated in the early phase of acute stroke, but had no correlation with the prognosis of acute stroke.

Conclusion: Although our data shed light on the use of the NR-2 peptide level as a biomarker in the acute phase in patients with stroke, data are insufficient to predict prognosis. We think that larger, multicenter studies with longer follow-up periods are needed.

References

  • 1. Rothstein L, Jickling GC. Ischemic stroke biomarkers in blood. Biomark Med. 2013;7(1):37-47. doi: 10.2217/bmm.12.104.
  • 2. Ng GJ, Quek AM, Cheung C, Arumugam TV, Seet RCS. Stroke biomarkers in clinical practice: A critical appraisal. Neurochem Int. 2017;107:11-22. doi: 10.1016/j.neuint.2017.01.005.
  • 3. Montanera J, Mendioroza M, Delgadoa P, García-Berrocosoa T, Giralt D, Merino C. et al. Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: The S100B/RAGE pathway. J Proteomics. 2012;75(15):4758-65. doi: 10.1016/j.jprot.2012.01.033.
  • 4. Laborde CM, Mourino-Alvarez L, Akerstorm F, PadialLR. Potential blood biomarkers for stroke. Expert Rev Proteomics. 2012;9(4):437-49. doi:10.1586/epr.12.33.
  • 5. Whiteley W, Tseng MC, Sandercock P. Blood biomarkers in the diagnosis of ischemic stroke: A systematic review. Stroke. 2008;39(10):2902-9. doi: 10.1161/STROKEAHA.107.511261.
  • 6. Bhatia R, Warrier AR, Sreenivas V, Bali P, Sisodia P, Gupta A, et al. Role of Blood Biomarkers in Differentiating Ischemic Stroke and Intracerebral Hemorrhage. Neurol India. 2020;68(4):824-9. doi: 10.4103/0028-3886.293467.
  • 7. Weissman JD, Khunteev GA, Heath R, Dambinova SA. NR-2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci. 2011;300(1-2):97-102. doi: 10.1016/j.jns.2010.09.023.
  • 8. Dambinova SA, Khounteev GA, Skorometz AA. Multiple panel of biomarkers for TIA/stroke evaluation. Stroke. 2002;33(5):1181–2. doi: 10.1161/01.str.0000014922.83673.86.
  • 9. Gascón S, Sobrado M, Roda JM, Rodríguez-Peña A, Díaz-Guerra M. Excitotoxicity and focal cerebral ischemia induce truncation of the NR-2A and NR-2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95. Mol Psychiatry. 2008;13(1):99–114. doi: 10.1038/sj.mp.4002017.
  • 10. Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. 2006;37(6):1432–6. doi: 10.1161/01.STR.0000221295.14547.c8.
  • 11. McCarthy DJ, Tonetti DA, Stone J, Starke RM, Narayanan S, Lang MJ, et al. More expansive horizons: a review of endovascular therapy for patients with low NIHSS scores. J Neurointerv Surg. 2021;13(2):146-151. doi: 10.1136/neurintsurg-2020-016583.
  • 12. Cook NF. The Glasgow Coma Scale: A European and Global Perspective on Enhancing Practice. Crit Care Nurs Clin North Am. 2021;33(1):89-99. doi: 10.1016/j.cnc.2020.10.005.
  • 13. Ng GJ, Quek AM, Cheung C, Arumugam TV, Seet RCS. Stroke biomarkers in clinical practice: A critical appraisal. Neurochem Int. 2017;107:11-22. doi: 10.1016/j.neuint.2017.01.005.
  • 14. Lynch JR, Blessing R, White WD, Grocott HP, Newman MF, Laskowitz DT. Novel diagnostic test for acute stroke. Stroke. 2004;35(1):57-63. doi: 10.1161/01.STR.0000105927.62344.4C.
  • 15. Jane J, Lo R, Graham CA. Blood biomarkers as an alternative to imaging in diagnosing acute ischaemic stroke. Emerg Med J. 2018;35(5):336-8. doi: 10.1136/emermed-2018-207686.2.
  • 16. Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC; BRAIN Study Group. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke. 2009;40(1):77-85. doi: 10.1161/STROKEAHA.108.516377.
  • 17. Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, et al. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem. 2012;58(1):237-45. doi: 10.1373/clinchem.2011.172676.
  • 18. Misra S, Kumar A, Kumar P, Yadav AK, Mohania D, Pandit AK, et al. Blood-based protein biomarkers for stroke differentiation: A systematic review. Proteomics Clin Appl. 2017;11(9-10). doi: 10.1002/prca.201700007.
  • 19. Bhasin A, Srivastava MV, Vivekanandhan S, Moganty R, Talwar T, Sharma S, et al. Vascular endothelial growth factor as predictive biomarker for stroke severity and outcome; An evaluation of a new clinical module in acute ischemic stroke. Neurol India. 2019;67(5):1280-5. doi: 10.4103/0028-3886.271241.
  • 20. Sharp CD, Fowler M, Jackson TH, Houghton J, Warren A, Nanda A, et al. Human neuroepithelial cells express NMDA receptors. BMC Neuro sci. 2003;4:28. doi: 10.1186/1471-2202-4-28.
  • 21. Cao J, Yan P, Zhou Y, Zhou X, Sun Z, Zhu XQ. Clinical Utility of the Serum Level of Lipoprotein-Related Phospholipase A2 in Acute Ischemic Stroke With Cerebral Artery Stenosis. Front Neurol. 2021;12:642483. doi: 10.3389/fneur.2021.642483.
  • 22. Chen C, Gu L, Chen L, Hu W, Feng X, Qiu F, et al. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Potential Predictors of Prognosis in Acute Ischemic Stroke. Front Neurol. 2021;11:525621. doi: 10.3389/fneur.2020.525621.
  • 23. Yu S, Luo Y, Zhang T, Huang C, Fu Y, Zhang Q, et al. Eosinophil-to-monocyte ratio is a potential biomarker in the prediction of functional outcome among patients with acute ischemic stroke. BMC Neurosci. 2021;22(1):8. doi: 10.1186/s12868-021-00610-x.
  • 24. Yang P, Zhu Z, Zang Y, Bu X, Xu T, Zhong C, et al. Increased Serum Complement C3 Levels Are Associated With Adverse Clinical Outcomes After Ischemic Stroke. Stroke. 2021;52(3):868-77. doi: 10.1161/STROKEAHA.120.031715.
  • 25. Xu M, Xu L, Du H, Shan W, Feng J, Zhai G, et al. Decreased Serum Retinoic Acid May Predict Poor Outcome in Ischemic Stroke Patients. Neuropsychiatr Dis Treat. 2020;16:1483-91. doi: 10.2147/NDT.S254591.

NR-2 antikor peptid düzeyinin akut iskemik inmede tanı, prognoz ve koma skorları ile ilişkisi var mıdır?

Year 2022, Volume: 6 Issue: 2, 145 - 150, 20.08.2022
https://doi.org/10.30565/medalanya.1116544

Abstract

Amaç: Bu çalışmanın birincil amacı akut iskemik inme’de biyobelirteç olarak NR-2 peptidinin tanısal ve prognostik değerini göstermek, ayrıca Glasgow koma skoru (GKS) ve Ulusal Sağlık Enstitüleri İnme Ölçeği (NIHSS) arasındaki ile ilişkisinin araştırılmasıdır.

Yöntemler: Akut inme de NR-2 peptid düzeyinin tanı ve prognozdaki önemi prospektif kesitsel olarak araştırılmıştır. Çalışmaya üçüncü basamak sağlık kuruluşuna bir yıl içerisinde başvurup akut inme tanısı kesinleşen 101 hasta ve 57 sağlıklı kontrol grubu alınmıştır. Tüm çalışma grubunda serumda NR-2 peptid düzeyi ELISA yöntemi ile ölçülmüştür. Elde olunan sonuçlar hastaların prognoz kriterini öngörebilecek olan koma skorlamaları ile ilişkisine bakılmıştır.

Bulgular: Elisa yöntemi ile ölçülen NR-2 peptid düzeyi hasta grubunda 6,32±8,30, kontrol grubunda 3,91±1,64 saptandı. NR-2 düzeyi hasta grubunda daha yüksek olup istatistiksel olarak anlamlı fark vardır (p:0,006). NR-2 düzeyi ile GKS ve NIHSS arasında ilişki saptanmamıştır. Bu sonuçlar ile NR-2 düzeyi akut inmede erken dönemde yüksek saptanılan potansiyel bir biyobelirteç olmasına karşın bu protein düzeyinin akut inme prognozu ile ilişkisi saptanmadı.

Sonuç: Sonuçlarımız NR-2 düzeyinin inmeli hastalarda biyomarker olarak akut dönemde kullanılabilmesi için ışık tutmakla birlikte, hastalığın prognozunu öngörmede yeterli verilere sahip değildir. Bu konuda daha fazla hasta popülasyonu ile çok merkezli, hastaların daha uzun süre takip prognozlarının izlenildiği çalışmalara ihtiyaç olduğunu düşünmekteyiz.

References

  • 1. Rothstein L, Jickling GC. Ischemic stroke biomarkers in blood. Biomark Med. 2013;7(1):37-47. doi: 10.2217/bmm.12.104.
  • 2. Ng GJ, Quek AM, Cheung C, Arumugam TV, Seet RCS. Stroke biomarkers in clinical practice: A critical appraisal. Neurochem Int. 2017;107:11-22. doi: 10.1016/j.neuint.2017.01.005.
  • 3. Montanera J, Mendioroza M, Delgadoa P, García-Berrocosoa T, Giralt D, Merino C. et al. Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: The S100B/RAGE pathway. J Proteomics. 2012;75(15):4758-65. doi: 10.1016/j.jprot.2012.01.033.
  • 4. Laborde CM, Mourino-Alvarez L, Akerstorm F, PadialLR. Potential blood biomarkers for stroke. Expert Rev Proteomics. 2012;9(4):437-49. doi:10.1586/epr.12.33.
  • 5. Whiteley W, Tseng MC, Sandercock P. Blood biomarkers in the diagnosis of ischemic stroke: A systematic review. Stroke. 2008;39(10):2902-9. doi: 10.1161/STROKEAHA.107.511261.
  • 6. Bhatia R, Warrier AR, Sreenivas V, Bali P, Sisodia P, Gupta A, et al. Role of Blood Biomarkers in Differentiating Ischemic Stroke and Intracerebral Hemorrhage. Neurol India. 2020;68(4):824-9. doi: 10.4103/0028-3886.293467.
  • 7. Weissman JD, Khunteev GA, Heath R, Dambinova SA. NR-2 antibodies: risk assessment of transient ischemic attack (TIA)/stroke in patients with history of isolated and multiple cerebrovascular events. J Neurol Sci. 2011;300(1-2):97-102. doi: 10.1016/j.jns.2010.09.023.
  • 8. Dambinova SA, Khounteev GA, Skorometz AA. Multiple panel of biomarkers for TIA/stroke evaluation. Stroke. 2002;33(5):1181–2. doi: 10.1161/01.str.0000014922.83673.86.
  • 9. Gascón S, Sobrado M, Roda JM, Rodríguez-Peña A, Díaz-Guerra M. Excitotoxicity and focal cerebral ischemia induce truncation of the NR-2A and NR-2B subunits of the NMDA receptor and cleavage of the scaffolding protein PSD-95. Mol Psychiatry. 2008;13(1):99–114. doi: 10.1038/sj.mp.4002017.
  • 10. Bokesch PM, Izykenova GA, Justice JB, Easley KA, Dambinova SA. NMDA receptor antibodies predict adverse neurological outcome after cardiac surgery in high-risk patients. Stroke. 2006;37(6):1432–6. doi: 10.1161/01.STR.0000221295.14547.c8.
  • 11. McCarthy DJ, Tonetti DA, Stone J, Starke RM, Narayanan S, Lang MJ, et al. More expansive horizons: a review of endovascular therapy for patients with low NIHSS scores. J Neurointerv Surg. 2021;13(2):146-151. doi: 10.1136/neurintsurg-2020-016583.
  • 12. Cook NF. The Glasgow Coma Scale: A European and Global Perspective on Enhancing Practice. Crit Care Nurs Clin North Am. 2021;33(1):89-99. doi: 10.1016/j.cnc.2020.10.005.
  • 13. Ng GJ, Quek AM, Cheung C, Arumugam TV, Seet RCS. Stroke biomarkers in clinical practice: A critical appraisal. Neurochem Int. 2017;107:11-22. doi: 10.1016/j.neuint.2017.01.005.
  • 14. Lynch JR, Blessing R, White WD, Grocott HP, Newman MF, Laskowitz DT. Novel diagnostic test for acute stroke. Stroke. 2004;35(1):57-63. doi: 10.1161/01.STR.0000105927.62344.4C.
  • 15. Jane J, Lo R, Graham CA. Blood biomarkers as an alternative to imaging in diagnosing acute ischaemic stroke. Emerg Med J. 2018;35(5):336-8. doi: 10.1136/emermed-2018-207686.2.
  • 16. Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC; BRAIN Study Group. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke. 2009;40(1):77-85. doi: 10.1161/STROKEAHA.108.516377.
  • 17. Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, et al. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem. 2012;58(1):237-45. doi: 10.1373/clinchem.2011.172676.
  • 18. Misra S, Kumar A, Kumar P, Yadav AK, Mohania D, Pandit AK, et al. Blood-based protein biomarkers for stroke differentiation: A systematic review. Proteomics Clin Appl. 2017;11(9-10). doi: 10.1002/prca.201700007.
  • 19. Bhasin A, Srivastava MV, Vivekanandhan S, Moganty R, Talwar T, Sharma S, et al. Vascular endothelial growth factor as predictive biomarker for stroke severity and outcome; An evaluation of a new clinical module in acute ischemic stroke. Neurol India. 2019;67(5):1280-5. doi: 10.4103/0028-3886.271241.
  • 20. Sharp CD, Fowler M, Jackson TH, Houghton J, Warren A, Nanda A, et al. Human neuroepithelial cells express NMDA receptors. BMC Neuro sci. 2003;4:28. doi: 10.1186/1471-2202-4-28.
  • 21. Cao J, Yan P, Zhou Y, Zhou X, Sun Z, Zhu XQ. Clinical Utility of the Serum Level of Lipoprotein-Related Phospholipase A2 in Acute Ischemic Stroke With Cerebral Artery Stenosis. Front Neurol. 2021;12:642483. doi: 10.3389/fneur.2021.642483.
  • 22. Chen C, Gu L, Chen L, Hu W, Feng X, Qiu F, et al. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Potential Predictors of Prognosis in Acute Ischemic Stroke. Front Neurol. 2021;11:525621. doi: 10.3389/fneur.2020.525621.
  • 23. Yu S, Luo Y, Zhang T, Huang C, Fu Y, Zhang Q, et al. Eosinophil-to-monocyte ratio is a potential biomarker in the prediction of functional outcome among patients with acute ischemic stroke. BMC Neurosci. 2021;22(1):8. doi: 10.1186/s12868-021-00610-x.
  • 24. Yang P, Zhu Z, Zang Y, Bu X, Xu T, Zhong C, et al. Increased Serum Complement C3 Levels Are Associated With Adverse Clinical Outcomes After Ischemic Stroke. Stroke. 2021;52(3):868-77. doi: 10.1161/STROKEAHA.120.031715.
  • 25. Xu M, Xu L, Du H, Shan W, Feng J, Zhai G, et al. Decreased Serum Retinoic Acid May Predict Poor Outcome in Ischemic Stroke Patients. Neuropsychiatr Dis Treat. 2020;16:1483-91. doi: 10.2147/NDT.S254591.
There are 25 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research Article
Authors

Alpay Tuncar 0000-0002-3889-819X

Basar Cander 0000-0002-3308-5843

Kadir Küçükceran 0000-0001-9758-0803

Fatma Hümryra Yerlikaya 0000-0002-4107-5389

Early Pub Date August 20, 2022
Publication Date August 20, 2022
Submission Date May 13, 2022
Acceptance Date July 7, 2022
Published in Issue Year 2022 Volume: 6 Issue: 2

Cite

Vancouver Tuncar A, Cander B, Küçükceran K, Yerlikaya FH. Is there a relationship between NR-2 antibody peptide level and diagnosis, prognosis and coma scores in acute ischemic stroke?. Acta Med. Alanya. 2022;6(2):145-50.

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