Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke : The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study
One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide...
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| Veröffentlicht in: | Stroke (1970) 2009, Vol.40 (1), p.77-85 |
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| creator | LASKOWITZ, Daniel T KASNER, Scott E SAVER, Jeffrey REMMEL, Kerri S JAUCH, Edward C |
| description | One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.
A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P |
| doi_str_mv | 10.1161/STROKEAHA.108.516377 |
| format | Article |
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A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.
These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/STROKEAHA.108.516377</identifier><identifier>PMID: 18948614</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers - analysis ; Biomarkers - blood ; Brain Ischemia - blood ; Brain Ischemia - diagnosis ; Brain Ischemia - physiopathology ; Cerebral Hemorrhage - blood ; Cerebral Hemorrhage - diagnosis ; Cerebral Hemorrhage - physiopathology ; Cohort Studies ; Female ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Male ; Matrix Metalloproteinase 9 - analysis ; Matrix Metalloproteinase 9 - blood ; Medical sciences ; Middle Aged ; Natriuretic Peptide, Brain - analysis ; Natriuretic Peptide, Brain - blood ; Nerve Growth Factors - analysis ; Nerve Growth Factors - blood ; Nervous system (semeiology, syndromes) ; Neurology ; Predictive Value of Tests ; Prospective Studies ; Reproducibility of Results ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins - analysis ; S100 Proteins - blood ; Stroke - blood ; Stroke - diagnosis ; Stroke - physiopathology ; Time Factors ; Vascular diseases and vascular malformations of the nervous system ; Young Adult</subject><ispartof>Stroke (1970), 2009, Vol.40 (1), p.77-85</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c318t-2c058352664a8323ebee2e9dd3077dcf9c242e8f8876cbdd5f38264d5d8cb6953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21039207$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18948614$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LASKOWITZ, Daniel T</creatorcontrib><creatorcontrib>KASNER, Scott E</creatorcontrib><creatorcontrib>SAVER, Jeffrey</creatorcontrib><creatorcontrib>REMMEL, Kerri S</creatorcontrib><creatorcontrib>JAUCH, Edward C</creatorcontrib><creatorcontrib>BRAIN Study Group</creatorcontrib><title>Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke : The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.
A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.
These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.</description><subject>Acute Disease</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers - blood</subject><subject>Brain Ischemia - blood</subject><subject>Brain Ischemia - diagnosis</subject><subject>Brain Ischemia - physiopathology</subject><subject>Cerebral Hemorrhage - blood</subject><subject>Cerebral Hemorrhage - diagnosis</subject><subject>Cerebral Hemorrhage - physiopathology</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Humans</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - analysis</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Natriuretic Peptide, Brain - analysis</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>Nerve Growth Factors - analysis</subject><subject>Nerve Growth Factors - blood</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Reproducibility of Results</subject><subject>S100 Calcium Binding Protein beta Subunit</subject><subject>S100 Proteins - analysis</subject><subject>S100 Proteins - blood</subject><subject>Stroke - blood</subject><subject>Stroke - diagnosis</subject><subject>Stroke - physiopathology</subject><subject>Time Factors</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><subject>Young Adult</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU1vEzEQhi0EoqHwDxDyBQSHTf21Xm9vm9DSqBWV0vS8cuxZ6nY_gmf3kN_An8ZVovY00uh5H2nmJeQzZ3PONT-726xvry-qq2rOmZnnXMuieENmPBcqU1qYt2TGmCwzocryhHxAfGSMCWny9-SEm1IZzdWM_Fu2oQ_OtvQeoZnaHhDp0FBLF2HobHyCmC0sgqc_g_3TDzgGRzeAI22GSCs3jUDvxjg8AT2nmwd4jdG13QVPK8Sk7KAfaejpCt0DdEmx6h-nuKffF-tq9ftHUkx-_5G8a2yL8Ok4T8n95cVmeZXd3P5aLaubzEluxkw4lhuZC62VNVJI2AIIKL2XrCi8a0onlADTGFNot_U-b6QRWvncG7fVZS5PybeDdxeHv1O6pe4COmhb28MwYa11YQQTLIHqALo4IEZo6l0M6bp9zVn9XEL9UkLamPpQQop9OfqnbQf-NXT8egK-HgGL6fVNtL0L-MIJnnoTrJD_AZVDkHY</recordid><startdate>2009</startdate><enddate>2009</enddate><creator>LASKOWITZ, Daniel T</creator><creator>KASNER, Scott E</creator><creator>SAVER, Jeffrey</creator><creator>REMMEL, Kerri S</creator><creator>JAUCH, Edward C</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2009</creationdate><title>Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke : The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study</title><author>LASKOWITZ, Daniel T ; KASNER, Scott E ; SAVER, Jeffrey ; REMMEL, Kerri S ; JAUCH, Edward C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c318t-2c058352664a8323ebee2e9dd3077dcf9c242e8f8876cbdd5f38264d5d8cb6953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acute Disease</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Biomarkers - blood</topic><topic>Brain Ischemia - blood</topic><topic>Brain Ischemia - diagnosis</topic><topic>Brain Ischemia - physiopathology</topic><topic>Cerebral Hemorrhage - blood</topic><topic>Cerebral Hemorrhage - diagnosis</topic><topic>Cerebral Hemorrhage - physiopathology</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</topic><topic>Humans</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - analysis</topic><topic>Matrix Metalloproteinase 9 - blood</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Natriuretic Peptide, Brain - analysis</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>Nerve Growth Factors - analysis</topic><topic>Nerve Growth Factors - blood</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Reproducibility of Results</topic><topic>S100 Calcium Binding Protein beta Subunit</topic><topic>S100 Proteins - analysis</topic><topic>S100 Proteins - blood</topic><topic>Stroke - blood</topic><topic>Stroke - diagnosis</topic><topic>Stroke - physiopathology</topic><topic>Time Factors</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LASKOWITZ, Daniel T</creatorcontrib><creatorcontrib>KASNER, Scott E</creatorcontrib><creatorcontrib>SAVER, Jeffrey</creatorcontrib><creatorcontrib>REMMEL, Kerri S</creatorcontrib><creatorcontrib>JAUCH, Edward C</creatorcontrib><creatorcontrib>BRAIN Study Group</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LASKOWITZ, Daniel T</au><au>KASNER, Scott E</au><au>SAVER, Jeffrey</au><au>REMMEL, Kerri S</au><au>JAUCH, Edward C</au><aucorp>BRAIN Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke : The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2009</date><risdate>2009</risdate><volume>40</volume><issue>1</issue><spage>77</spage><epage>85</epage><pages>77-85</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><abstract>One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.
A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.
These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>18948614</pmid><doi>10.1161/STROKEAHA.108.516377</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Acute Disease Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers - analysis Biomarkers - blood Brain Ischemia - blood Brain Ischemia - diagnosis Brain Ischemia - physiopathology Cerebral Hemorrhage - blood Cerebral Hemorrhage - diagnosis Cerebral Hemorrhage - physiopathology Cohort Studies Female Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Male Matrix Metalloproteinase 9 - analysis Matrix Metalloproteinase 9 - blood Medical sciences Middle Aged Natriuretic Peptide, Brain - analysis Natriuretic Peptide, Brain - blood Nerve Growth Factors - analysis Nerve Growth Factors - blood Nervous system (semeiology, syndromes) Neurology Predictive Value of Tests Prospective Studies Reproducibility of Results S100 Calcium Binding Protein beta Subunit S100 Proteins - analysis S100 Proteins - blood Stroke - blood Stroke - diagnosis Stroke - physiopathology Time Factors Vascular diseases and vascular malformations of the nervous system Young Adult |
| title | Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke : The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study |
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