Validation of the ABCD3-I score for 90 day prediction of early stroke risk after transient ischemic attack or minor ischemic stroke

Patients with transient ischemic attack or minor ischemic stroke are at high risk of early subsequent stroke. It might be confusing to determine the exposition to stroke recurrence as a consequence of the aggressive treatment and useful prevention. The objectives were to determine the incidence of early subsequent stroke and evaluate the ABCD3-I score for recurrent stroke risk.

JOURNAL OF MEDICAL RESEARCH VALIDATION OF THE ABCD3-I SCORE FOR 90-DAY PREDICTION OF EARLY STROKE RISK AFTER TRANSIENT ISCHEMIC ATTACK OR MINOR ISCHEMIC STROKE Tran Van Tu1, Nguyen Van Lieu2, Nguyen Huy Thang1 Pham Ngoc Thach University of Medicine, Hanoi Medical University Patients with transient ischemic attack or minor ischemic stroke are at high risk of early subsequent stroke It might be confusing to determine the exposition to stroke recurrence as a consequence of the aggressive treatment and useful prevention The objectives were to determine the incidence of early subsequent stroke and evaluate the ABCD3-I score for recurrent stroke risk A prospective cohort study in 203 patients with transient ischemic attack or minor ischemic stroke was at Department of Cerebrovascular disease, People’s Hospital 115 (HCMC) from Jan 1st 2016 to Jun 30th 2018 All patients were assessed by stroke specialists, performed brain imaging, classified according to ABCD2, ABCD3, ABCD3-I Scores and followed up for 90 days There were 15/203 patients (7.39%) experienced subsequent stroke by 90 days The incidence of stroke recurrence after days, days and 30 days were 1.97% (4/203), 3.94% (8/203) and 4.43% (9/203), respectively The high-risk group (ABCD3-I ≥ 8) was more likely to have recurrent stroke than the low-risk group (ABCD3-I < 8), significantly: within days 10,2% vs 1,95% (p = 0.0097), 30 days 10.2% vs 2.6% (p = 0.0244) and 90 days 16.33% vs 4.55% (p = 0.0061).Furthermore, the ABCD3-I Score had a predictive value with area under the curve ROC with 0.67 The risk of recurrent stroke after TIA or MIS will increase by the time and can be predicted by applying the ABCD3-I Score in clinical practice Key words: transient ischemic attack, minor ischemic stroke, subsequent stroke, ABCD3-I Score I INTRODUCTION Patients who have been diagnosed with of treatment and useful prevention There have transient ischemic attack (TIA) or minor ischemic been various risk scores developed to identify stroke (MIS) are at high risk of early subsequent high-risk subgroup patients which are applied stroke, with the rate ranging between 10 widely by clinical specialists In 2005, Rothwell – 20% [1] This risk is usually variable and et al proposed the ABCD Score based on age, depending on clinical symptoms, pathology, blood pressure, clinical features, duration and urgent medical treatment Determination of symptoms [2] After that, Johnston et al of the likelihood of stroke recurrence is combined this score with a diabetic factor to necessary for determining the aggressiveness establish the ABCD2 Score [3] Merwick et al Corresponding author: Tran Van Tu, Pham Ngọc Thach University of Medicine Email: bstu71@gmai.com Received: 27/11/2018 Accepted: 12/03/2019 74 in anew consolidated the score with factors of dual TIA and features on imaging to introduce the ABCD3and ABCD3-I Score [4] The number of stroke patients is increasing [5] Additionally, in Vietnam, the incidence JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH of recurrent stroke is also increasing at an cord or retinal ischemia without acute infarction” alarming rate [6] Nevertheless, there are a by the criteria of WHO [7] MIS is confirmed few studies about this issue on Vietnamese unless there is intracerebral hemorrhage population to determine high risk patients and stroke severity by National Institutes This is the motivation creating this study with of Health Stroke Scale (NIHSS) > [8] The the following objectives: (1) determine the patients whose symptoms of TIA or MIS had incidence of early subsequent stroke, and occurred within 48 hours were selected for this (2) evaluate the ABCD3-I score for recurrent study After being admitted to the emergency stroke risk department, they were assessed independently is indicated in Figure TIA is defined as “a by one stroke specialist as well as undergoing brain imaging in within 10 minutes, and subsequently classified according to ABCD2, ABCD3, ABCD3-I Scores Before discharge, all participants were asked to be followed up in the clinic for out-patient each month during 90 days In cases of recurrent stroke, TIA or death, the patients or their relatives were asked to transient episode of neurologic dysfunction inform the research team by telephone number within 24 hours, caused by focal brain, spinal immediately II METHODS This is a prospective cohort study and random sampling, performed at the Department of Cerebrovascular disease in People’s Hospital 115 (HCMC) from January 1st 2016 to June 30th 2018 The procedure of the study JMR 118 E4 (2) - 2019 75 JOURNAL OF MEDICAL RESEARCH At first, there were 260 patients diagnosed with TIA or MIS (TIA = 50, MIS = 210) After that, 57 patients (TIA = 16, MIS = 41) were excluded because of hypoglycemia (blood glucose below 70 mg%), migraine headache (have pain one side of head and/or have been diagnosed), epilepsy (have convulsions and/or have been diagnosed), brain tumor (have detected on imaging and/or have been diagnosed), had significant comorbidities (i.e heart failure, liver failure or end-stage kidney disease), their symptoms had occurred more than 48 hours before admission to hospital, or had NIHSS > Statistical analysis was done with SPSS (version 24.0) Parametric and non-parametric comparisons of categorical and continuous variables were done with χ² test, t-test, and Mann-Whitney U test, as appropriate A p-value of 0.05 or less was deemed significant Predictive values for ABCD3-I Scores was expressed as the area under the receiver operating characteristic curve (AUC) Ideal discrimination produces an AUC of 1.0, whereas discrimination that is no better than chance producesan AUC of 0.5 The ethics committee of People’s Hospital 115 approved this study Written informed consent was obtained from all participants III RESULTS Between January 1st 2016 to June 30th 2018, 203 patients who had been diagnosed with TIA or MIS admitted to emergency department (TIA = 34, MIS = 169) Table Clinical features Unilateral weaknes, % 92,1 Speech impairment without weakness, % Duration, 6,4   ≥ 60 mins 69,4 10 - 59 mins 17,9 < 10 mins 12,7 Time to hospital 4,8 Days in-hospital (days) TOAST, % 76   Large vessel disease 21,6 Small vessel disease 47 Carioembolic stroke 7,5 Cryptogenic stroke 23,9 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Population characteristics: The mean age of all patients was 60.56 ± 13.5 years The age of female was higher than male significantly (64.71 vs 58.4; p = 0.0017) The sex ratio male:female was 1.57:1 Comorbidities: Hypertension 62.07%, diabetes mellitus 14.26%, hypercholesterolemia 63.6%, atrial fibrillation 5.91% and previous TIA 5.4% Clinical features (Table 1) and Classification base on the ABCD3-I Score (Figure 2) 50 46 45 42 40 40 35 35 30 26 25 20 15 10 1 ABCD3-I 10 11 12 13 Figure Classification base on the ABCD3-I Imaging features: CT scan or CTA was done in 187/203 patients The percentage of patients with acute ischemic lesions exposed on CT were 21.9% (41/187) One-hundred and thirty-seven patients had been indicated for MRI, where 62.78% (86/137) of them had early infarct signs on DWI; 8.76% (12/137) had MRA stenosis ≥ 50% or completely occlusion Patients underwent carotid artery ultrasound screening; 7.88% (16/203) of cases had carotid artery stenosis > 50% Specifically, the percentages of carotid artery stenosis 50 - 69% and stenosis ≥ 70% were 6.4% and 1.48% of patients, respectively The first diagnosis of atrial fibrillation on ECG was made at 5.91% (12/203) of patients No patient had cardiac thrombosis detected by transthoracic cardiac ultrasound Treatment: All patients were recommended to undergo healthy life-style changes and were treated with a statin Antiplatelet medications (aspirin or clopidogrel or dipyridamole + aspirin) were described in 96% of cases, 3.94% of patients were prescribed anticoagulation medications 71.43% patients needed to use antihypertensive drugs 13.79% of patients had been under pharmacologic therapy for diabetes Recurrent stroke and other event (TIA, death): JMR 118 E4 (2) - 2019 77 JOURNAL OF MEDICAL RESEARCH There were 15 patients (7.39%) who experienced subsequent stroke within 90 days The incidence of stroke recurrence after days, days and 30 days was 1.97% (4/203), 3.94% (8/203) and 4.43% (9/203), respectively Risk subgroup classification based on the ABCD3-I Score is seen in Figure The risk percentages between two subgroups were different significantly: within days 10.2% vs 1.95% (p = 0.0097), 30 days 10.2% vs 2.6% (p = 0.0244) and 90 days 16.33% vs 4.55% (p = 0.0061) 18 16.33 16 14 P = 0,0097 12 P = 0,0244 10.2 10 P=0,0061 10.2 Low-risk (ABCD3-I = 0-7) 4.55 4.08 0.65 days 1.95 days 2.6 30 days High-risk (ABCD3-I=8-13) 90 days Figure Risk subgroup classification base on the ABCD3-I Score The risk estimated by Kaplan - Meier of predictive events within 90 days after TIA or MIS in the high-risk group (ABCD3-I ≥ 8) was more superior than in the low-risk group (ABCD3-I < 8) (Log rank test=7.84, df=1, p=0.0051) Furthermore, the ABCD3-I Score had a predictive value with area under the curve ROC of 0.67 (Figure 4) Figure [4a] The risk of recurrent stroke, TIA or deathe estimated by Kaplan Meier, [4b] The predictive value of ABCD3-I score 78 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH IV DISCUSSION The average patient age in our study was 60.56 ± 14.09 It seemed lower than results of the studies of Kiyohara et al in 2014 [9] and Kelly et al in 2016 [10] with 69 and 68 years old The reason of this difference may be due to the higher life expectancy in developed countries and also their more-developed healthcare systems The percentage of male patients was 61.2%, similar to the results of 62.2% in Kiyohara’s [9] and 59% in Kelly’s [10] The number of patients with hypertension, diabetes mellitus and hypercholesterolemia was similar to other studies in Asian populations, such as the study of Qiliang Dai et al (China) in 2015 [11];owever, the rate of atrial fibrillation was lower, 5.91%, versus 13 to 18.3% [9], [10], [11] This could be explained that the average patient age in our study was younger so the rate of atrial fibrillation was lower than other populations Furthermore, there were more patients with previous stroke or TIA in other foreign countries, from 10 - 21% [9], [10], [11] whereas ours was only 5.4% That might be because citizens in high-income nations had the higher average age than our country Most of these patients had unilateral weakness, a few had unique speech impairment (6.4%) More than a half of our patients were admitted to emergency department after 60 minutes (69.4%) while Qiliang Dai et al [11] had published 82.7% of cases were taken to stroke centers The most popular cause of stroke base on TOAST classification was small vessel disease (47%), similar to the investigation by Purroy et al in 2013 [12] On the other hand, it was dissimilar to the study of Qiliang Dai et al [11] where the most prevalent cause was cardio-embolism (39,4%) Thereby, the treatment would be suitable for each case, depend on the pathology JMR 118 E4 (2) - 2019 The incidence of subsequent stroke within 90 days in our study was 7.39%, compared to 3.1% of Purroy’s [12], 10.4% of Kiyohara’s [9] and 10.6% of Qiliang Dai’s [11] Additionally, the risk would be increasing parallel by the score of ABCD3-I [9], [10] The area under the curve ROC of this score was 0.67, equivalent to the finding of Purroy et al 0,69 [12] On the other hand, Qiliang Dai et al [11] had declared that the value of ABCD3-I Score could be enhanced in case dual TIA factor replaced by DWI on MRI (AUC 0,759 vs 0,729 ; p = 0,035) V CONCLUSION The risk of recurrent stroke after TIA or MIS increases with time and can be predicted by applying the ABCD3-I Score in clinical practice Acknowledgements Special thanks should be given my research project supervisors for their professional guidance and valuable support I also would like to thank my colleagues in Neurology Department, People’s Hospital 115 for their assistance with the collection of my data REFERENCES Giles MF, Rothwell PM (2007), “Risk of stroke early after transient ischemic attack: a systematic review and meta-analysis”, Lancet Neurol, ,1063 – 72 Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JN, et al (2007), “Early use of Existing Preventive Strategies for Stroke (EXPRESS) study Effect of urgent treatment of transient isch- aemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison”, Lancet, 370, 1432 – 1442 Johnston, S C., P M Rothwell, M 79 JOURNAL OF MEDICAL RESEARCH N Nguyen-Huynh, et al (2007),“Validation and refinement of scores to predict very early stroke risk after transient ischemic attack”,The Lancet, 369(9558), 283 - 292 Merwick A, Albers GW, Amarenco P, Arsava EM, Ay H, Calvet D, et al (2010), “Addition of brain and carotid imaging to the ABCD2 score to identify patients at early risk of stroke after transient ischemic attack: a multicentre observational study”, Lancet Neurol, 9, 1060 – 1069 Institute for Health Metrics and Evaluation, “Global burden of diseases, injuries, and risk factors study 2010”, 2301 Fifth Ave., Suite 600 Seattle, WA 98121 USA Ngo Ba Minh, Cao Phi Phong (2011), “Identify the patients with high risk of late stroke after transient ischemic attack or minor ischemic stroke by ABCD2 score”, Y Hoc TP Ho Chi Minh, Vol 15 - Supplement of No – 2011: 603 - 608 Ross, M A., S Compton, P Medado et al (2007), “An Emergency Department Diagnostic Protocol for Patients With Transient Ischemic Attack: A Randomized Controlled Trial’, Annals of emergency medicine, 50(2), 109 - 119 National Institute of Health, National Institute of Neurological Disorders and Stroke 80 Stroke Scale, https://www.ninds.nih.gov/sites/ default/files/NIH_Stroke_Scale_Booklet.pdf Takuya Kiyohara, Masahiro Kamouchi, Yasuhiro Kumai et al (2014), “ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack”, Stroke, 45, 418 - 425 10 Peter J Kelly, Gregory W Albers, AnastasiosChatzikonstatinou, Gian Marco De Marchis, et al (2016), “Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischemic attack: a pooled analysis of individualpatient data from cohort studies”,www thelancet.com/neurology, Vol 15 November 2016 11 Dai Q, Sun W, Xiong Y et al (2015), “From clinical to tissue-based dual TIA: Validation and refinement of ABCD3-I score”, American Academy of Neurology, 84(14),1426 - 32 12 Purroy F, P E Jimenez-Caballero, G Mauri-Capdevila, M J Torres et al (2013), “Predictive value of brain and vascular imaging including intracranial vessels in transient ischemic attack patients: external validation of the ABCD3-I score”, European Journal of Neurology, 20, 1088 – 1093 JMR 118 E4 (2) - 2019 ... and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack , Stroke, 45, 418 - 425 10 Peter J Kelly, Gregory W Albers,... Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischemic attack: a pooled analysis of individualpatient data from cohort studies”,www thelancet.com/neurology,... P=0,0061 10.2 Low -risk (ABCD3-I = 0-7) 4.55 4.08 0.65 days 1.95 days 2.6 30 days High -risk (ABCD3-I= 8-13) 90 days Figure Risk subgroup classification base on the ABCD3-I Score The risk estimated