İnme Biyobelirteçleri
Özet
İnme, merkezi sinir sisteminin vasküler hasarına atfedilen ve klinik olarak tanımlanmış akut, fokal nörolojik defisit sendromudur. Klinik bulgular 24 saatten daha fazla sürmektedir. Morbiditenin ve mortalitenin üçüncü nedenidir. Bütün yaşlar inme açısından risk altındadır. İki çeşit inme tipi bulunmaktadır: iskemik İnme ve hemorajik inme. Tanı klinik değerlendirme ve nöroradyolojik bulgularla koyulmaktadır. Radyolojik olarak normal bulunan inme olgularında inmenin prediksiyonu ve ayırıcı tanısında inme biyobelirteçlerine gereksinim duyulmaktadır. İnme biyobelirteçlerinin başlıcaları şunlardır: S100 kalsiyum bağlayıcı protein B, glial fibriller asidik protein, nöron spesifik enolaz, matriks metaloproteinaz 9, fosfolipaz A2 ile ilişkili lipoprotein, asimetrik dimetilarginin, NMDA reseptör peptitleri ve antikorlar, Parkinson hastalığı proteini 7, beyin natriüretik peptid, C-reaktif protein, D-dimer, fibrinojen, serum β-sinüklein, nöroflament hafif zinciri, enflamatuvar belirteçler, laktat dehidrojenaz/albümin oranı, trombomodulin, mikroRNA, nükleosit difosfat kinaz A, α2-spektrin, sitokinler, ubikuitin C terminal hidrolaz-L1, süperoksit dismutaz, hücresel fibronektin, kopeptin, apolipoprotein C3 ve çoklu belirteç panelleri .
İnme sonrasında kan-beyin bariyerini geçen glial veya nöronal proteinlerin yavaş salınımı, erken tanıyı engellemektedir. Beyin dokusu tiplerinin karışıklığı ve farklılığının yanında bunların fizyolojisinin tamamen bilinmemesi inme spesifik biyobelirteçlerinin az sayıda olmasına neden olmaktadır. Bu nedenle halen ideal bir inme biyobelirteci bulunmamaktadır. Biyobelirteçlerin birçoğu bağımsız tanı ve prognostik değerler göstermesine rağmen, tanıda en büyük katkı çoklu panellerden sağlanabilecek gibi görünmektedir. Yeni kitlerin geliştirilmesi ve kitlerin ölçüm yöntemlerinin standardize edilmesi biyobelirteç kullanımının önünü açacaktır. İnme biyobelirteçlerinin keşfi için yapılan araştırma gayretleri tedavi kalitesini ve hasta sonuçlarını büyük ölçüde düzeltecektir.
Stroke is a clinically defined syndrome of acute, focal neurological deficits attributed to vascular damage of the central nervous system. Clinical findings last more than 24 hours. It is the third cause of morbidity and mortality. All ages are at risk for stroke. There are two types of stroke: ischemic stroke and hemorrhagic stroke. Diagnosis is made by clinical evaluation and neuroradiological findings. Stroke biomarkers are needed in the prediction and differential diagnosis of stroke in radiologically normal stroke cases. The main biomarkers of stroke are: S100 calcium-binding protein B, glial fibrillary acidic protein, neuron-specific enolase, matrix metalloproteinase 9, phospholipase A2-associated lipoprotein, asymmetric dimethylarginine, NMDA receptor peptides and antibodies, Parkinson's disease protein 7, brain natriuretic peptide, C-reactive protein, D-dimer, fibrinogen, serum β-synuclein, neurofilament light chain, inflammatory markers, lactate dehydrogenase/albumin ratio, thrombomodulin, microRNA, nucleoside diphosphate kinase A, α2-spectrin, cytokines, ubiquitin C terminal hydrolase-L1 , superoxide dismutase, cellular fibronectin, copeptin, apolipoprotein C3 and multi-marker panels .
The slow release of glial or neuronal proteins that cross the blood-brain barrier after stroke prevents early diagnosis. The confusion and diversity of brain tissue types, as well as the lack of complete knowledge of their physiology, result in a low number of stroke-specific biomarkers. Therefore, there is still no ideal stroke biomarker. Although many biomarkers show independent diagnostic and prognostic values, the greatest contribution to diagnosis seems to be provided by multiple panels. Developing new kits and standardizing the measurement methods of the kits will pave the way for the use of biomarkers. Research efforts to discover stroke biomarkers will greatly improve treatment quality and patient outcomes.
Referanslar
Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(7): 2064-2089. doi: 10.1161/STR.0b013e318296aeca
Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: Estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8(4):345-354. doi: 10.1016/S1474-4422(09)70023-7.
Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clin Neurol Neurosurg. 2009; 111(6):483-495. doi: 10.1016/j.clineuro.2009.04.001.
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. The Lancet. Neurology. 2006;5(1):53-63. doi: 10.1016/S1474-4422(05)70283-0.
Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the Primary Presenin of Stroke. A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-3832. doi: 10.1161/STR.0000000000000046.
Wityk RJ, Beauchamp NJ Jr. Diagnostic evaluation of stroke. Neurol Clin. 2000;18(2):357-378. doi: 10.1016/s0733-8619(05)70197-3.
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–466. doi: 10.1097/COH.0b013e32833ed177.
Whiteley W, Tseng MC, Sandercock P. Blood biomarkers in the diagnosis of ischemic stroke: a systematic review. Stroke. 2008; 39(10):2902-2909. doi: 10.1161/STROKEAHA.107.511261.
Baudier J, Glasser N, Gerard D. Ions binding to S100 proteins. I. Calcium- and zinc-binding properties of bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein: Zn2+ regulates Ca2+ binding on S100b protein. J Biol Chem. 1986; 261:8192-8203.
Elting JW, de Jager AE, Teelken AW, et al. Comparison of serum S-100 protein levels following stroke and traumatic brain injury. J Neurol Sci. 2000;181(1-2):104-110. doi: 10.1016/s0022-510x(00)00442-1.
Koh SX, Lee JK. S100B as a marker for brain damage and blood-brain barrier disruption following exercise. Sports Med. 2014;44(3):369-385. doi: 10.1007/s40279-013-0119-9.
Eng LF. Glial fibrillary acidic protein (GFAP): The major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol. 1985;8(4-6):203-214. doi: 10.1016/s0165-5728(85)80063-1.
Schiff L, Hadker N, Weiser S, et al. A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury. Mol Diagn Ther. 2012;16(2):79-92. doi: 10.2165/11631580-000000000-00000.
Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015; 867:125-143. doi: 10.1007/978-94-017-7215-0_9.
Mochetti MM, Silva EGP, Correa AAF, et al. Neuron-specific enolase at admission as a predictor for stroke volume, severity and outcome in ischemic stroke patients: a prognostic biomarker review. Sci Rep. 2024;14(1):2688. doi: 10.1038/s41598-024-53080-6.
Ramos-Fernandez M, Bellolio MF, Stead LG. Matrix metalloproteinase-9 as a marker for acute ischemic stroke: a systematic review J Stroke Cerebrovasc Dis. 2011; 20(1):47-54. doi: 10.1016/j.jstrokecerebrovasdis.2009.10.008.
Castellanos M, Leira R, Serena J, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke. 2003; 34(1):40–46.
Lonn E. Lipoprotein-associated phospholipase A2: a new therapeutic target. Can J Cardiol. 2010; 26 Suppl A:27A-31A. doi: 10.1016/s0828-282x (10)71058-8.
Elkind MS, Tai W, Coates K, et al. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med. 2006; 166(19):2073-2080. doi: 10.1001/archinte.166.19.2073.
Shufen Chen 1, Na Li, Milani Deb-Chatterji, Qiang Dong, Jan T Kielstein, Karin Weissenborn, Hans Worthmann. Asymmetric dimethyarginine as marker and mediator in ischemic stroke. Int J Mol Sci. 2012; 13(12):15983-16004. doi: 10.3390/ijms131215983.
Furukawa H, Singh SK, Mancusso R, et al. Subunit arrangement and function in NMDA receptors. Nature. 2005;438(7065):185-192. doi: 10.1038/nature04089.
Dambinova SA, Bettermann K, Glynn T, et al. Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PloS One. 2012;7(7): e42362. doi: 10.1371/journal.pone.0042362.
Allard L, Burkhard PR, Lescuyer P, Burgess JA, Walter N, Hochstrasser DF, Sanchez JC. PARK7 and nucleoside diphosphate kinase A as plasma markers for the early diagnosis of stroke. Clin Chem. 2005; 51(11):2043-2051. doi: 10.1373/clinchem.2005.053942.
Glushakova OY, Glushakov AV, Miller ER, Valadka AB, Hayes RL. Biomarkers for acute diagnosis and management of stroke in neurointensive care units. Brain Circ. 2016; 2(1):28-47. doi: 10.4103/2394-8108.178546.
Jickling GC, Sharp FR. Biomarker panels in ischemic stroke. Stroke. 2015;46(3):915-920. doi: 10.1161/STROKEAHA.114.005604.
Flint AC, Banki NM, Ren X, Rao VA, Go AS. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke. 2012; 43:2788-2790. doi: 10.1161/STROKEAHA.112.665844.
Llombart V, Antolin-Fontes A, Bustamante A, et al. B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis. Stroke. 2015;46(5):1187-1195. doi: 10.1161/STROKEAHA.114.008311.
Bos MJ, Schipper CM, Koudstaal PJ, et al. High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study. Circulation. 2006;114(15):1591-1598. doi:10.1161/CIRCULATIONAHA.106.619833.
Isenegger J, Meier N, Lämmle B, et al. D-dimers predict stroke subtype when assessed early. Cerebrovasc Dis. 2010; 29(1):82-86. doi: 10.1159/000256652.
Matosevic B, Knoflach M, Werner P, et al. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology. 2013;80(13):1216-1224. doi: 10.1212/WNL.0b013e3182897015
Barba L, Vollmuth C, Abu-Rumeileh S, et al. Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke. Sci Rep. 2023;13(1):20941. doi: 10.1038/s41598-023-47765-7.
Fakhari MS, Poorsaadat L, Almasi-Hashiani A, et al. Inflammatory markers and functional outcome score in different subgroups of ischaemic stroke: a prospective cohort study. BMJ Neurology Open. 2024;6(1):e000556. doi: 10.1136/bmjno-2023-000556. eCollection 2024.DOI: 10.1136/bmjno-2023-000556.
Chu M, Niu H, Yang N, et al. High serum lactate dehydrogenase to albumin ratio is associated with increased risk of poor prognosis after ischemic stroke. Clin Neurol Neurosurg. 2024; 237:108120. doi: 10.1016/j.clineuro.2024.108120.
Zaharia AL, Tutunaru D, Oprea VD, et al. Thrombomodulin serum levels- a predictable biomarker for the acute onset of ischemic stroke. Curr Issues Mol Biol. 2024;46(1):677-688. doi: 10.3390/cimb46010044.
Wang T, Zhao W, Liu Y, et al. Differentially expressed miR-511-3p in stroke patients predicts the present of post-stroke cognitive impairment. Dement Geriatr Cogn Disord. 2023 Dec 6. doi: 10.1159/000535631.
Mainali S, Nepal G, Webb A, et al. MicroRNA Expression profile in acute ischemic stroke. Res Sq. [Preprint]. 2024 Jan 3: rs.3.rs-3754883. doi: 10.21203/rs.3.rs-3754883/v1.
Referanslar
Sacco RL, Kasner SE, Broderick JP, et al. An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(7): 2064-2089. doi: 10.1161/STR.0b013e318296aeca
Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: Estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009;8(4):345-354. doi: 10.1016/S1474-4422(09)70023-7.
Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clin Neurol Neurosurg. 2009; 111(6):483-495. doi: 10.1016/j.clineuro.2009.04.001.
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. The Lancet. Neurology. 2006;5(1):53-63. doi: 10.1016/S1474-4422(05)70283-0.
Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the Primary Presenin of Stroke. A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-3832. doi: 10.1161/STR.0000000000000046.
Wityk RJ, Beauchamp NJ Jr. Diagnostic evaluation of stroke. Neurol Clin. 2000;18(2):357-378. doi: 10.1016/s0733-8619(05)70197-3.
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–466. doi: 10.1097/COH.0b013e32833ed177.
Whiteley W, Tseng MC, Sandercock P. Blood biomarkers in the diagnosis of ischemic stroke: a systematic review. Stroke. 2008; 39(10):2902-2909. doi: 10.1161/STROKEAHA.107.511261.
Baudier J, Glasser N, Gerard D. Ions binding to S100 proteins. I. Calcium- and zinc-binding properties of bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein: Zn2+ regulates Ca2+ binding on S100b protein. J Biol Chem. 1986; 261:8192-8203.
Elting JW, de Jager AE, Teelken AW, et al. Comparison of serum S-100 protein levels following stroke and traumatic brain injury. J Neurol Sci. 2000;181(1-2):104-110. doi: 10.1016/s0022-510x(00)00442-1.
Koh SX, Lee JK. S100B as a marker for brain damage and blood-brain barrier disruption following exercise. Sports Med. 2014;44(3):369-385. doi: 10.1007/s40279-013-0119-9.
Eng LF. Glial fibrillary acidic protein (GFAP): The major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol. 1985;8(4-6):203-214. doi: 10.1016/s0165-5728(85)80063-1.
Schiff L, Hadker N, Weiser S, et al. A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury. Mol Diagn Ther. 2012;16(2):79-92. doi: 10.2165/11631580-000000000-00000.
Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015; 867:125-143. doi: 10.1007/978-94-017-7215-0_9.
Mochetti MM, Silva EGP, Correa AAF, et al. Neuron-specific enolase at admission as a predictor for stroke volume, severity and outcome in ischemic stroke patients: a prognostic biomarker review. Sci Rep. 2024;14(1):2688. doi: 10.1038/s41598-024-53080-6.
Ramos-Fernandez M, Bellolio MF, Stead LG. Matrix metalloproteinase-9 as a marker for acute ischemic stroke: a systematic review J Stroke Cerebrovasc Dis. 2011; 20(1):47-54. doi: 10.1016/j.jstrokecerebrovasdis.2009.10.008.
Castellanos M, Leira R, Serena J, et al. Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke. 2003; 34(1):40–46.
Lonn E. Lipoprotein-associated phospholipase A2: a new therapeutic target. Can J Cardiol. 2010; 26 Suppl A:27A-31A. doi: 10.1016/s0828-282x (10)71058-8.
Elkind MS, Tai W, Coates K, et al. High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med. 2006; 166(19):2073-2080. doi: 10.1001/archinte.166.19.2073.
Shufen Chen 1, Na Li, Milani Deb-Chatterji, Qiang Dong, Jan T Kielstein, Karin Weissenborn, Hans Worthmann. Asymmetric dimethyarginine as marker and mediator in ischemic stroke. Int J Mol Sci. 2012; 13(12):15983-16004. doi: 10.3390/ijms131215983.
Furukawa H, Singh SK, Mancusso R, et al. Subunit arrangement and function in NMDA receptors. Nature. 2005;438(7065):185-192. doi: 10.1038/nature04089.
Dambinova SA, Bettermann K, Glynn T, et al. Diagnostic potential of the NMDA receptor peptide assay for acute ischemic stroke. PloS One. 2012;7(7): e42362. doi: 10.1371/journal.pone.0042362.
Allard L, Burkhard PR, Lescuyer P, Burgess JA, Walter N, Hochstrasser DF, Sanchez JC. PARK7 and nucleoside diphosphate kinase A as plasma markers for the early diagnosis of stroke. Clin Chem. 2005; 51(11):2043-2051. doi: 10.1373/clinchem.2005.053942.
Glushakova OY, Glushakov AV, Miller ER, Valadka AB, Hayes RL. Biomarkers for acute diagnosis and management of stroke in neurointensive care units. Brain Circ. 2016; 2(1):28-47. doi: 10.4103/2394-8108.178546.
Jickling GC, Sharp FR. Biomarker panels in ischemic stroke. Stroke. 2015;46(3):915-920. doi: 10.1161/STROKEAHA.114.005604.
Flint AC, Banki NM, Ren X, Rao VA, Go AS. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: the Stroke and Monitoring for PAF in Real Time (SMART) Registry. Stroke. 2012; 43:2788-2790. doi: 10.1161/STROKEAHA.112.665844.
Llombart V, Antolin-Fontes A, Bustamante A, et al. B-type natriuretic peptides help in cardioembolic stroke diagnosis: pooled data meta-analysis. Stroke. 2015;46(5):1187-1195. doi: 10.1161/STROKEAHA.114.008311.
Bos MJ, Schipper CM, Koudstaal PJ, et al. High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study. Circulation. 2006;114(15):1591-1598. doi:10.1161/CIRCULATIONAHA.106.619833.
Isenegger J, Meier N, Lämmle B, et al. D-dimers predict stroke subtype when assessed early. Cerebrovasc Dis. 2010; 29(1):82-86. doi: 10.1159/000256652.
Matosevic B, Knoflach M, Werner P, et al. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology. 2013;80(13):1216-1224. doi: 10.1212/WNL.0b013e3182897015
Barba L, Vollmuth C, Abu-Rumeileh S, et al. Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke. Sci Rep. 2023;13(1):20941. doi: 10.1038/s41598-023-47765-7.
Fakhari MS, Poorsaadat L, Almasi-Hashiani A, et al. Inflammatory markers and functional outcome score in different subgroups of ischaemic stroke: a prospective cohort study. BMJ Neurology Open. 2024;6(1):e000556. doi: 10.1136/bmjno-2023-000556. eCollection 2024.DOI: 10.1136/bmjno-2023-000556.
Chu M, Niu H, Yang N, et al. High serum lactate dehydrogenase to albumin ratio is associated with increased risk of poor prognosis after ischemic stroke. Clin Neurol Neurosurg. 2024; 237:108120. doi: 10.1016/j.clineuro.2024.108120.
Zaharia AL, Tutunaru D, Oprea VD, et al. Thrombomodulin serum levels- a predictable biomarker for the acute onset of ischemic stroke. Curr Issues Mol Biol. 2024;46(1):677-688. doi: 10.3390/cimb46010044.
Wang T, Zhao W, Liu Y, et al. Differentially expressed miR-511-3p in stroke patients predicts the present of post-stroke cognitive impairment. Dement Geriatr Cogn Disord. 2023 Dec 6. doi: 10.1159/000535631.
Mainali S, Nepal G, Webb A, et al. MicroRNA Expression profile in acute ischemic stroke. Res Sq. [Preprint]. 2024 Jan 3: rs.3.rs-3754883. doi: 10.21203/rs.3.rs-3754883/v1.
