Candidate Biomarkers for the Diagnosis of Transient Ischemic Attack: A Systematic Review

Background and Purpose: A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review current evidence for the diagnostic accuracy of blood biomarkers in the early diagnosis of TIA. Methods: This is a systematic review with quality appraisal of individual studies using the QUADAS-2 tool. MEDLINE and EMBASE databases were searched up to May 1, 2017, to select primary diagnostic accuracy studies evaluating potential biomarkers in blood for the diagnosis of TIA or ischemic stroke. Results: Of 4,215 studies retrieved, 78 met our eligibility criteria. Forty-five studies restricted their population to ischemic stroke patients, 32 included both TIA and ischemic stroke patients, and only one study was restricted to TIA patients. In total 62/78 (79.5%) studies had a case-control design comparing TIA or stroke patients with healthy subjects. Overall, 125 single biomarkers and 5 biomarker panels were studied, with a median number of participants per study of 92.0 (interquartile range 44.8–144.5), varying from 8 to 915. Sufficient information to extract 2 × 2 tables was available for 35 (44.9%) articles, and for 60 (48.0 %) biomarkers. Several markers, such as NR2A/B (antibodies), Parkinson 7, nucleoside diphosphate kinase A, ubiquitin fusion degradation protein-1, and heart-type fatty acid binding protein, have shown moderate to high diagnostic accuracy in multiple studies. Conclusions: Although the methodological quality of studies evaluating biomarkers of brain ischemia was poor, several biomarkers have shown the potential to detect transient brain ischemia in an early phase. Diagnostic accuracy studies in suspected cases of TIA are needed to determine their true clinical value.