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March 26, 2019; 92 (13) Article

A novel biomarker-based prognostic score in acute ischemic stroke

The CoRisk score

Gian Marco De Marchis, Theresa Dankowski, Inke R. König, Joachim Fladt, Felix Fluri, Henrik Gensicke, Christian Foerch, Oliver Findling, Rebekka Kurmann, Urs Fischer, Andreas Luft, Daniela Buhl, Stefan T. Engelter, Philippe A. Lyrer, Mirjam Christ-Crain, Marcel Arnold, Mira Katan
First published March 1, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007177
Gian Marco De Marchis
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Theresa Dankowski
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Inke R. König
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Joachim Fladt
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Felix Fluri
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Henrik Gensicke
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Christian Foerch
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Oliver Findling
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Rebekka Kurmann
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Urs Fischer
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Andreas Luft
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Daniela Buhl
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Stefan T. Engelter
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Philippe A. Lyrer
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Mirjam Christ-Crain
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Marcel Arnold
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Mira Katan
From the Department of Neurology & Stroke Center (G.M.D.M., J.F., H.G., S.T.E., P.A.L.), Department of Internal Medicine (M.C.-C.), and Department of Clinical Research (M.C.-C.), Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, University of Basel, Switzerland; Institute of Medical Biometry and Statistics (T.D., I.R.K.), University of Lübeck, University Hospital Schleswig-Holstein, Campus Lübeck; Department of Neurology (F.F.), University Hospital Würzburg; Department of Neurology (C.F.), Goethe University, Frankfurt a.M., Germany; Department of Neurology (O.F.), Cantonal Hospital Aarau; Department of Neurology (R.K., U.F., M.A.), Inselspital, University Hospital Bern; Department of Neurology (A.L., M.K.), University Hospital Zurich; Department of Laboratory Medicine (D.B.), Kantonsspital, Lucerne; and Neurorehabilitation Unit (S.T.E.), University Center for Medicine of Aging and Rehabilitation, Felix Platter Hospital, University of Basel, Switzerland.
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Citation
A novel biomarker-based prognostic score in acute ischemic stroke
The CoRisk score
Gian Marco De Marchis, Theresa Dankowski, Inke R. König, Joachim Fladt, Felix Fluri, Henrik Gensicke, Christian Foerch, Oliver Findling, Rebekka Kurmann, Urs Fischer, Andreas Luft, Daniela Buhl, Stefan T. Engelter, Philippe A. Lyrer, Mirjam Christ-Crain, Marcel Arnold, Mira Katan
Neurology Mar 2019, 92 (13) e1517-e1525; DOI: 10.1212/WNL.0000000000007177

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Abstract

Objectives To derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS).

Methods The derivation cohort consisted of patients with AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6.

Results Overall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval [CI] 0.787–0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72–78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32–60).

Conclusions The biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin.

ClinicalTrials.gov identifier NCT00390962 (derivation cohort) and NCT00878813 (validation cohort).

Glossary

ASTRAL=
Acute Stroke Registry and Analysis of Lausanne;
AUC=
area under the receiver operating characteristic curve;
CI=
confidence interval;
CoRisk=
Copeptin for Risk Stratification in Acute Stroke Patients;
COSMOS=
Copeptin in Osmoregulation and Stress Assessment;
JURaSSIC=
Clinician Judgment Versus Risk Score to Predict Stroke Outcomes;
mRS=
modified Rankin Scale;
NIHSS=
NIH Stroke Scale;
NRI=
net reclassification index;
PLAN=
preadmission comorbidities, level of consciousness, age, and neurologic deficit;
SOAR=
stroke subtype, Oxfordshire Community Stroke Project, age, and prestroke modified Rankin Scale;
THRIVE=
Totaled Health Risks in Vascular Events;
VISTA=
Virtual International Stroke Trials Archive

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • CME Course: NPub.org/cmelist

  • Received July 20, 2018.
  • Accepted in final form November 14, 2018.
  • © 2019 American Academy of Neurology
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Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

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