TY - JOUR
T1 - New biomarker for acute ischaemic stroke
T2 - Plasma glycogen phosphorylase isoenzyme BB
AU - Park, Kwang Yeol
AU - Ay, Ilknur
AU - Avery, Ross
AU - Caceres, Juan Alfredo
AU - Siket, Matthew S.
AU - Pontes-Neto, Octavio M.
AU - Zheng, Hui
AU - Rost, Natalia S.
AU - Furie, Karen L.
AU - Sorensen, Alma Gregory
AU - Koroshetz, Walter J.
AU - Ay, Hakan
N1 - Funding Information:
Competing interests KYp was supported by the Basic science Research program through the National Foundation of Korea (NRF) funded by the Ministry of education, science and Technology (2010-0023596). Ia was supported by NIh grants 1OT2OD023867 and hhsN268201400044c and received research support from electrocore. OMpN was funded by cNpq grants 402388/2013-5 and 467322/2014-7 and received speaker fees from Boehringer-Ingelheim and Medtronic. NsR received personal compensation for activities with Genzyme, Omniox, Broadview Ventures and cardioNet as a consultant, and Merck for serving on the clinical events committee. NsR received personal compensation in an editorial capacity for current Treatment Options in cardiovascular Disease and as a section contributor for UpToDate. NsR is funded by NINDs R01Ns086905 and R01Ns082285. KLF is a contributing author of UpToDate, Vice editor of Stroke, Deputy editor of JNNP, pfizer DsMB, NINDs research grant p50 Ns051343. aGs was an employee of siemens until January 2016, serves on the board of IMRIs, and has acted as a consultant for Konica Minolta, permira, eQT partners, GLG, Third Bridge and Guidepoint in 2016 and 2017. ha received personal compensation as a contributing author of UpToDate.
Publisher Copyright:
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2018/4
Y1 - 2018/4
N2 - Background Glycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS). Methods We studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging. Results The mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case-control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume. Conclusion GPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia.
AB - Background Glycogen phosphorylase is the key enzyme that breaks down glycogen to yield glucose-1-phosphate in order to restore depleted energy stores during cerebral ischaemia. We sought to determine whether plasma levels of glycogen phosphorylase BB (GPBB) isoform increased in patients with acute ischaemic stroke (AIS). Methods We studied plasma GPBB levels within 12 hours and again at 48±24 hours of symptom onset in 172 patients with imaging-confirmed AIS and 133 stroke-free individuals. We determined the ability of plasma GPBB to discriminate between cases and controls and examined the predictive value of plasma GPBB for 90-day functional outcome, 90-day survival and acute lesion volumes on neuroimaging. Results The mean (SD) GPBB levels were higher in cases (46.3±38.6 ng/mL at first measurement and 38.6±36.5 ng/mL at second measurement) than in controls (4.1±7.6 ng/mL, p<0.01 for both). The area under the receiver operating characteristic (ROC) curve for case-control discrimination based on first GPBB measurement was 0.96 (95% CI 0.93 to 0.98). The sensitivity and specificity based on optimal operating point on the ROC curve (7.0 ng/mL) were both 93%. GPBB levels increased in 90% of patients with punctate infarcts (<1.5 mL) and in all patients admitted within the first 4.5 hours of onset. There was no correlation between GPBB concentration and either clinical outcome or acute infarct volume. Conclusion GPBB demonstrates robust response to acute ischaemia and high sensitivity for small infarcts. If confirmed in more diverse populations that also include stroke mimics, GPBB could find utility as a stand-alone marker for acute brain ischaemia.
KW - biomarker
KW - cerebrovascular disease/stroke
KW - embolism
KW - infarction
KW - plasma
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U2 - 10.1136/jnnp-2017-316084
DO - 10.1136/jnnp-2017-316084
M3 - Article
C2 - 29030420
AN - SCOPUS:85045045710
SN - 0022-3050
VL - 89
SP - 404
EP - 409
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 4
ER -