Qiliang Dai, MD* Wen Sun, MD, PhD* Yunyun Xiong, MD, PhD Graeme J. Hankey, MD, FRACP Lulu Xiao, MD Wusheng Zhu, MD, PhD Minmin Ma, MD, PhD Wenhua Liu, MD, PhD Dezhi Liu, MD Qiankun Cai, MD Yunfei Han, MD Lihui Duan, MD Xiangliang Chen, MD Gelin Xu, MD, PhD Xinfeng Liu, MD, PhD Correspondence to Prof. Xinfeng Liu: xfliu2@vip.163.com Supplemental data at Neurology.org From clinical to tissue-based dual TIA Validation and refinement of ABCD3-I score ABSTRACT Objective: To investigate whether dual tissue-defined ischemic attacks, defined as multiple diffusion-weighted imaging lesions of different age and/or arterial territory (dual DWI), are an independent and stronger predictor of 90-day stroke than dual clinical TIAs (dual TIA). Methods: Consecutive patients with clinically defined TIA were enrolled and assessed clinically and by MRI within 3 days. The predictive ability of the ABCD clinical factors, dual TIA, and dual DWI was evaluated by means of multivariate logistic regression. Results: Among 658 patients who were included in the study and completed 90 days of follow-up, a total of 70 patients (10.6%) experienced subsequent stroke by 90 days. Multivariate logistic regression indicated that dual DWI was an independent predictor for subsequent stroke (odds ratio 4.64, 95% confidence interval 2.15–10.01), while dual TIA was not (odds ratio 1.18, 95% confidence interval 0.69–2.01). C statistics was higher when the item of dual TIA in ABCD3-I score was replaced by dual DWI (0.759 vs 0.729, p 5 0.035). The net reclassification value for 90-day stroke risk was also improved (continuous net reclassification improvement 0.301, p 5 0.017). Conclusion: Dual DWI independently predicted future stroke in patients with TIA. A new ABCD3-I score with dual DWI instead of dual clinical TIA may improve risk stratification for early stroke risk after TIA. Neurology ® 2015;84:1–7 GLOSSARY ABCD 5 age, blood pressure, clinical features, duration of symptoms; ADC 5 apparent diffusion coefficient; DWI 5 diffusion- weighted imaging; NRI 5 net reclassification improvement; NSRP 5 Nanjing Stroke Registry Program. Patients with TIA are at high risk of early subsequent stroke, with stroke rates ranging between 6.8% and 11.5% by 90 days. 1 Different risk scores have been developed to identify high-risk subgroup patients and may be helpful to implement urgent and aggressive treatment. The ABCD2 score was used to triage patients in primary care for admission and further treatment. 2 In 2010, Merwick et al. 3 proposed the ABCD3-I score to further classify the stroke risk for secondary care. By adding 3 more components, dual TIA ($2 TIA symptoms within 7 days), combined with carotid stenosis and positive diffusion-weighted imaging (DWI), the ABCD3-I score showed greater predictive ability than the ABCD2 score. Dual TIA, repeated clinical ischemic symptoms by definition, is thought to represent recur- rent thromboembolism from an unstable cardiovascular lesion or instability of the focal ischemic brain lesion. 4 However, the predictive value of dual TIA is uncertain: some studies indicated it is a risk factor for stroke, 3,5,6 while others did not. 7,8 Although an abnormal DWI has been val- idated as increasing the early stroke risk, 3,9,10 it is uncertain whether multiple ischemic lesions on DWI of different age 11 and/or arterial territory, 12 perhaps indicating repeated tissue-based ische- mic attacks, improve prediction of early stroke. *These authors contributed equally to this work. From the Department of Neurology (Q.D., W.S., Y.X., L.X., W.Z., M.M., W.L., D.L., L.D., X.C., G.X., X.L.), Jinling Hospital, Medical School of Nanjing University, Nanjing, China; School of Medicine and Pharmacology (G.J.H.), The University of Western Australia, Perth, Australia; Department of Neurology (Q.C.), the Second Affiliated Hospital of Fujian Medical University, Fujian, China; and Department of Neurology (Y.H.), Jinling Hospital, Southern Medical University, Nanjing, China. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. © 2015 American Academy of Neurology 1 ª 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Published Ahead of Print on March 6, 2015 as 10.1212/WNL.0000000000001444