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1.  Large-Artery Stenosis Predicts Subsequent Vascular Events in Patients with Transient Ischemic Attack 
Background and purpose
We investigated subsequent vascular events in patients with transient ischemic attack (TIA) and determined the predictors of such events among vascular risk factors including large-artery disease, TIA-symptom duration, and acute ischemic lesions on diffusion-weighted imaging (DWI).
We identified 98 consecutive patients with TIA who visited a tertiary university hospital and underwent DWI and brain magnetic resonance angiography within 48 hours of symptom onset. We reviewed the medical records to assess the clinical characteristics of TIA, demographics, and the subsequent vascular events including acute ischemic stroke, TIA, and myocardial infarction.
Large-artery disease was detected in 55 patients (56%). Ten patients (10%) experienced TIA symptoms for longer than 1 hour, and acute infarctions on DWI were identified in 30 patients (31%). During the mean follow-up period of 19 months, seven patients (7%) had an acute ischemic stroke and 20 patients (20%) had TIA. Retinal artery occlusion in two patients, spinal cord infarction in one patient, and peripheral vascular claudication in one patient were also recorded. Cox proportional-hazards multivariate analysis revealed that large-artery disease was an independent predictor of subsequent cerebral ischemia (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.1-7.1; p=0.02) and subsequent vascular events (HR, 2.9; 95% CI, 1.2-6.7; p=0.01).
In patients with TIA, large-artery disease is an independent predictor of subsequent vascular events. Acute infarction on DWI and a symptom duration of more than 1 hour are not significantly correlated with a higher risk of subsequent vascular events. These findings suggest that the underlying vascular status is more important than symptom duration or acute ischemic lesion on DWI.
PMCID: PMC2686947  PMID: 19513127
Transient ischemic attack; Prognosis; Large-artery stenosis; Diffusion-weighted imaging
2.  Risk factors of short-term stroke recurrence in patients with minor ischemic cerebrovascular events 
ARYA Atherosclerosis  2013;9(2):119-127.
Assessing the risk of recurrent ischemic events in patients with transient ischemic attack (TIA) and minor ischemic stroke (MIS) is of a great importance in clinical practice.
Consecutive patients with TIA or MIS who were visited in Ghaem Hospital, (Mashhad, Iran) were enrolled in a prospective cohort study during 2010 to 2011. Diagnosis of TIA or MIS was accomplished by a stroke neurologist. Only those who presented within 24 hours from the onset of symptoms were recruited. MIS was considered as an ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) < 4. The endpoint of the study was a new ischemic cerebrovascular event or vascular death in 90 days and additionally in 3 days. The decision to admit and type of treatment in each case was left to the discretion of the stroke neurologist. The association between 20 potential factors with recurrent ischemic events in 3 and 90 days was investigated using univariate and multivariate analysis (MVA).
393 TIA patients (238 males and 155 females) and 118 MIS patients (77 males and 41 females) were enrolled in the study. Stroke occurred in 117 (23.2%) patients, TIA in 99 (19.6%), and there was 11 (2.2%) vascular deaths within 3 months in the total 511 patients with minor ischemic events. Crescendo TIAs and multiple TIAs were associated with greater risk of stroke in 3 days in a univariate analysis (OR = 5.12, P < 0.001) and (OR = 3.98, P = 0.003), respectively. Patients with index stroke had 11.5% lower risk of recurrent stroke in 3 days than patients with index TIA in multivariate analysis (OR = 0.115, P = 0.039). Diabetes was independently associated with 3 months stroke recurrence in the patients with minor ischemic events (OR = 2.65, P = 0.039).
Multiple and crescendo TIAs are the main predictors of stroke recurrence, derived from the univariate analysis of the patients with minor ischemic events.
PMCID: PMC3653243  PMID: 23690811
Transient Ischemic Attacks; Infarction; Brain; Recurrence; Risk
3.  Short-Term Prognosis of Transient Ischemic Attack and Predictive Value of the ABCD2 Score in Hong Kong Chinese 
Literature on prognosis of transient ischemic attack (TIA) in Chinese is scarce. The short-term prognosis of TIA and the predictive value of the ABCD2 score in Hong Kong Chinese patients attending the emergency department (ED) were studied to provide reference for TIA patient management in our ED.
A cohort of TIA patients admitted through the ED to 13 acute public hospitals in 2006 was recruited through the centralized electronic database by the Hong Kong Hospital Authority (HA). All inpatients were e-coded by the HA according to the International Classification of Diseases, Ninth Revision (ICD9). Electronic records and hard copies were studied up to 90 days after a TIA. The stroke risk of a separate TIA cohort diagnosed by the ED was compared.
In the 1,000 recruited patients, the stroke risk after a TIA at days 2, 7, 30, and 90 was 0.2, 1.4, 2.9, and 4.4%, respectively. Antiplatelet agents were prescribed in 89%, warfarin in 6.9%, statin in 28.6%, antihypertensives in 39.3%, and antidiabetics in 11.9% of patients after hospitalization. Before the index TIA, the prescribed medications were 27.6, 3.7, 11.3, 27.1, and 9.7%, respectively. The accuracy of the ABCD2 score in predicting stroke risk was 0.607 at 7 days, 0.607 at 30 days, and 0.574 at 90 days. At 30 days, the p for trend across ABCD2 score levels was 0.038 (OR for every score point = 1.36, p = 0.040). Diabetes mellitus, previous stroke and carotid bruit were associated with stroke within 90 days (p = 0.038, 0.045, 0.030, respectively). A total of 45.4% of CTs of the brain showed lacunar infarcts or small vessel disease. There was an increased stroke risk at 90 days in patients with old or new infarcts on CT or MRI. Patients with carotid stenosis ≥70% had an increased stroke risk within 30 (OR = 6.335, p = 0.013) and 90 days (OR = 3.623, p = 0.050). Stroke risks at days 2, 7, 30, and 90 in the 289 TIA patients diagnosed by the ED were 0.35, 2.4, 5.2, and 6.2%, respectively.
The short-term stroke risk in Hong Kong Chinese TIA patients is low. The administered nonurgent treatment cannot solely explain the favorable outcome, the lower risk can be due to the different pathophysiological mechanisms of stroke between Caucasians and Chinese. The predictive value of the ABCD2 score is low in our population.
PMCID: PMC3975175  PMID: 24715897
Chinese ethnicity; Transient ischemic attack; Prognosis; Stroke; Carotid stenosis; Lacunar infarct

4.  The prognosis of hospital-referred transient ischaemic attacks. 
A cohort of 469 hospital-referred patients with transient ischaemic attacks (TIA) of the brain (66%) or eye (34%) due to presumed atheromatous thromboembolism, lipohyalinosis or cardiogenic embolism, without prior stroke, was assembled between 1976-86. Follow up was prospective and complete until the patients death or the end of 1986. During a mean period of follow up of 4.1 years there were 82 deaths (58 vascular, 24 non-vascular), 63 first-ever strokes and 58 patients with coronary events. A coronary event accounted for 51% of deaths whilst stroke was the cause in 12%. The average risk of death over the first five years after TIA was 4.5% per year. The risk of stroke was 6.6% in the first year and 3.4% per year on average over the first five years. Stroke occurred in the same vascular territory as the initial TIA in about two-thirds of cases, and was of lacunar type in one fifth of these strokes. The average risk of a coronary event over the first five years after TIA was 3.1% per year, similar to that of stroke. However, the risk of a coronary event, and also death, was fairly constant each year after a TIA, in contrast to the risk of stroke which was highest in the first year. The average risk of stroke, myocardial infarction or vascular death over the first five years after TIA was 6.5% per year and the average risk of stroke, myocardial infarction or death from any cause was 7.5% per year. The prognosis of this cohort of hospital-referred TIA patients was better than that of TIA patients in the same community who presented to the Oxfordshire Community Stroke Project (OCSP), and reflected the impact of referral bias. The hospital-referred patients were younger, assessed at a later date after their last TIA, and comprised a greater proportion of patients who had had a TIA of the eye (amaurosis fugax), which had a better prognosis than TIA of the brain. Knowledge of the prognosis of different populations of TIA patients not only enhances understanding and interpretation of previous studies but is also required for optimal patient management and the planning of treatment trials.
PMCID: PMC1014519  PMID: 1955898
5.  Predicting value of ABCD2 in early ischemic stroke in patients diagnosed with transient ischemic attack 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 60.
As a significant number of patients diagnosed with transient ischemic attack (TIA) at emergency department are at risk to develop TIA or cerebral vascular accident (CVA), several attempts have been made to figure out a predictive method to detect those at higher risk of such attacks. Therefore, the present study was aimed to evaluate the role of ABCD2 scoring including age, blood pressure, clinical features, duration, and diabetes mellitus (DM), in predicting short term outcome of the patients presenting with TIA.
One hundred consecutive patients who have attended Hazrat Rasoul Akram Hospital (Kermanshah, Iran) during 2009 to 2010 and diagnosed with TIA were enrolled in the study. Their ABCD2 scores were recorded. The incidences of death, CVA, and TIA during the first week after the attack were recorded.
Eleven patients suffered from new TIA/CVA after 1 week. Sensitivity and specificity of ABCD2 score for predicting CVA/TIA at cut-off point of the 4th day were 72.7% and 52.8%, respectively. At the same cut-off point for ABCD2, positive and negative predictive values were 16% and 94 %, respectively.
Our results show that although patients with ABCD2 score greater than 4 were more likely to develop recurrent TIA/CVA in short term, those with lower scores are still susceptible to a considerable risk of TIA/CVA. Though ABCD2 as an easily applicable tool is very helpful in management of TIA patients at emergency department, but it should not be the only measure to rely on in our decision making.
Ischemic stroke, Transient ischemic attack, Cerebral vascular accident, ABCD2 scoring
PMCID: PMC3571586
6.  Magnetic Resonance Imaging versus Computed Tomography in Transient Ischemic Attack and Minor Stroke: The More Υou See the More You Know 
Cerebrovascular Diseases Extra  2013;3(1):130-136.
Magnetic resonance imaging (MRI) is proposed as the preferred imaging modality to investigate patients with transient ischemic attack (TIA). This is mainly based on a higher yield of small acute ischemic lesions; however, direct prospective comparisons are lacking. In this study, we aimed to directly compare the yield of acute ischemic lesions on MRI and computed tomography (CT) in the emergency diagnosis of suspected TIA or minor stroke.
Consecutive patients aged 18 years or older presenting with minor stroke (NIHSS <4) or high-risk TIA and who were examined by a stroke neurologist within 24 h of symptom onset were prospectively enrolled in the CATCH study. Patients who had undergone both a baseline CT and an MRI within 24 h of symptom onset were included in this substudy. Baseline MRI and CT were interpreted independently to identify an acute ischemic lesion. The rates of acute ischemic lesions on CT and MRI were compared, and the volume of acute ischemic lesions was measured on MRI. In addition, the volume of acute ischemic lesions on MRI was compared between patients who had evidence of acute ischemia on CT and in those who did not.
A total of 347 patients were included, 168 with TIAs, 147 with minor strokes and 32 with a final diagnosis of a mimic. Acute ischemic lesions were detected in 39% of TIAs by using MRI versus 8% by using CT (p < 0.0001) and in 86% of minor strokes by using MRI versus 18% by using CT (p < 0.0001). Compared to MRI, CT had a sensitivity of 20% and a specificity of 98% in identifying an acute ischemic lesion. The infarct volume on diffusion-weighted MRI was larger in cases where the CT also showed an acute ischemic lesion (median 5.07 ml, IQR 10) as compared to lesions seen only on MRI (median 0.68 ml, IQR 1.31, p < 0.0001).
MRI is superior to CT in detecting the small ischemic lesions occurring after TIA and minor stroke. Since these lesions are clinically relevant, MRI should be the preferred imaging modality in this setting.
PMCID: PMC3884208  PMID: 24403904
Transient ischemic attack; Mild stroke; Magnetic resonance imaging; Diffusion-weighted magnetic resonance imaging; Computed tomography

7.  Prognostic value of the ABCD2 score beyond short-term follow-up after transient ischemic attack (TIA) - a cohort study 
BMC Neurology  2010;10:50.
Transient ischemic attack (TIA) patients are at a high vascular risk. Recently the ABCD2 score was validated for evaluating short-term stroke risk after TIA. We assessed the value of this score to predict the vascular outcome after TIA during medium- to long-term follow-up.
The ABCD2 score of 176 TIA patients consecutively admitted to the Stroke Unit was retrospectively calculated and stratified into three categories. TIA was defined as an acute transient focal neurological deficit caused by vascular disease and being completely reversible within 24 hours. All patients had to undergo cerebral MRI within 5 days after onset of symptoms as well as extracranial and transcranial Doppler and duplex ultrasonography. At a median follow-up of 27 months, new vascular events were recorded. Multivariate Cox regression adjusted for EDC findings and heart failure was performed for the combined endpoint of cerebral ischemic events, cardiac ischemic events and death of vascular or unknown cause.
Fifty-five patients (32.0%) had an ABCD2 score ≤ 3, 80 patients (46.5%) had an ABCD2 score of 4-5 points and 37 patients (21.5%) had an ABCD2 score of 6-7 points. Follow-up data were available in 173 (98.3%) patients. Twenty-two patients (13.8%) experienced an ischemic stroke or TIA; 5 (3.0%) a myocardial infarction or acute coronary syndrome; 10 (5.7%) died of vascular or unknown cause; and 5 (3.0%) patients underwent arterial revascularization. An ABCD2 score > 3 was significantly associated with the combined endpoint of cerebral or cardiovascular ischemic events, and death of vascular or unknown cause (hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.21 to 13.27). After adjustment for extracranial ultrasonographic findings and heart failure, there was still a strong trend (HR 3.13, 95% CI 0.94 to 10.49). Whereas new cardiovascular ischemic events occurred in 9 (8.3%) patients with an ABCD2 score > 3, this happened in none of the 53 patients with a score ≤ 3.
An ABCD2 score > 3 is associated with an increased general risk for vascular events in the medium- to long-term follow-up after TIA.
PMCID: PMC2906428  PMID: 20565966
8.  Transient ischaemic attacks: which patients are at high (and low) risk of serious vascular events? 
The aims of this study were to determine the important prognostic factors at presentation which identify patients with transient ischaemic attacks (TIA) who are at high risk (and low risk) of serious vascular events and to derive a prediction model (equation) for each of the major vascular outcome events. A cohort of 469 TIA patients referred to a University hospital, without prior stroke, were evaluated prospectively and followed up over a mean period of 4.1 years (range 1-10 years). The major outcome events of interest were 1) stroke 2) coronary event and 3) stroke, myocardial infarction or vascular death (whichever occurred first). Prognostic factors and their hazard ratios were identified by means of the Cox proportional hazards multiple regression analysis. The significant adverse prognostic factors (in order of strength of association) for stroke were an increasing number of TIAs in the three months before presentation, increasing age, peripheral vascular disease, left ventricular hypertrophy and TIAs of the brain (compared with the eye); the prognostic factors for coronary event were increasing age, ischaemic heart disease, male sex, and a combination of carotid and vertebrobasilar TIAs at presentation; and for stroke, myocardial infarction or vascular death they were increasing age, peripheral vascular disease, increasing number of TIAs in the three months before presentation, male sex, a combination of carotid and vertebrobasilar TIAs at presentation, TIAs of the brain (compared with the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the eye), left ventricular hypertrophy and the presence of residual neurological signs after the TIA. Prediction models (equations) of both the relative risk and absolute risk of each of the major outcome events were produced, based on the presence or level of the significant prognostic factors and their hazard. Before it can be concluded that our equations accurately predict prognosis and can be generalised to other populations, their predictive power needs to be validated in other, independent samples of TIA patients (which we are currently doing).
PMCID: PMC489198  PMID: 1527533
9.  Stroke Among Patients With Dizziness, Vertigo, and Imbalance in the Emergency Department: A Population-Based Study 
Background and Purpose
Dizziness, vertigo, and imbalance are common presenting symptoms in the emergency department. Stroke is a leading concern even when these symptoms occur in isolation. The objective of the present study was to determine the “real-world” proportion of stroke among patients presenting to the emergency department with these dizziness symptoms (DS).
From a population-based study, patients >44 years of age presenting with DS to the emergency department, or directly admitted to the hospital, were identified. Demographics, the frequency of new cerebrovascular events, and the frequency of isolated DS (ie DS with no other stroke screening term or accompanying neurologic signs or symptoms) were assessed. Multivariable logistic regression was used to evaluate the association of age, gender, ethnicity, and isolated DS with stroke/transient ischemic attack (TIA). The association of the presenting symptoms with stroke/TIA was also assessed.
Stroke/TIA was diagnosed in 3.2% (53 of 1666) of all patients with DS. Only 0.7% (9 of 1297) of those with isolated DS had a stroke/TIA. Patients with stroke/TIA were slightly older than those without stroke/TIA (69.3±11.7 vs 65.3±12.9, P=0.02). Male gender was associated with stroke/TIA, whereas isolated DS was negatively associated with stroke/TIA. Patients with imbalance (dizziness as referent) were more likely to have stroke/TIA.
The proportion of cerebrovascular events in patients presenting with dizziness, vertigo, or imbalance is very low. Isolated dizziness, vertigo, or imbalance strongly predicts a noncerebrovascular cause. The symptom of imbalance is a predictor of stroke/TIA.
PMCID: PMC1779945  PMID: 16946161
cerebrovascular accident; dizziness; gait disorders; population surveillance; vertigo
10.  Heart dysfunction in patients with acute ischemic stroke or TIA does not predict all-cause mortality at long-term follow-up 
BMC Neurology  2013;13:122.
Despite heart failure being a substantial risk factor for stroke, few studies have evaluated the predictive value of heart dysfunction for all-cause mortality in patients with acute ischemic stroke, in particular in the elderly. The aim of this study was to investigate whether impaired heart function in elderly patients can predict all-cause mortality after acute ischemic stroke or transient ischemic attack (TIA).
A prospective long-term follow-up analysis was performed on a hospital cohort consisting of n = 132 patients with mean age 73 ± 9 years, presenting with acute ischemic stroke or transient ischemic attack, without atrial fibrillation. All patients were examined by echocardiography during the hospital stay. Data about all-cause mortality were collected at the end of the follow-up period. The mean follow-up period was 56 ± 22 months.
In this cohort, 58% of patients with acute ischemic stroke or TIA had heart dysfunction. Survival analysis showed that heart dysfunction did not predict all-cause mortality in this cohort. Furthermore, in multivariate regression analysis age (HR 5.401, Cl 1.97-14.78, p < 0.01), smoking (HR 3.181, Cl 1.36-7.47, p < 0.01), myocardial infarction (HR 2.826, Cl 1.17-6.83, p < 0.05) were independent predictors of all-cause mortality.
In this population with acute ischemic stroke or TIA and without non-valvular atrial fibrillation, impaired heart function does not seem to be a significant predictor of all-cause mortality at long-term follow-up.
PMCID: PMC3852256  PMID: 24053888
Echocardiography; Heart failure; Mortality; Stroke; TIA
11.  Post-Stroke Epilepsy in Young Adults: A Long-Term Follow-Up Study 
PLoS ONE  2013;8(2):e55498.
Little is known about the incidence and risk of seizures after stroke in young adults. Especially in the young seizures might dramatically influence prognosis and quality of life. We therefore investigated the long-term incidence and risk of post-stroke epilepsy in young adults with a transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH).
Methods and Findings
We performed a prospective cohort study among 697 consecutive patients with a first-ever TIA, IS or ICH, aged 18–50 years, admitted to our hospital between 1-1-1980 till 1-11-2010. The occurrence of epilepsy was assessed by standardized questionnaires and verified by a neurologist. Cumulative risks were estimated with Kaplan-Meier analysis. Cox proportional hazard models were used to calculate relative risks. After mean follow-up of 9.1 years (SD 8.2), 79 (11.3%) patients developed post-stroke epilepsy and 39 patients (5.6%) developed epilepsy with recurrent seizures. Patients with an initial late seizure more often developed recurrent seizures than patients with an initial early seizure. Cumulative risk of epilepsy was 31%, 16% and 5% for patients with an ICH, IS and TIA respectively (Logrank test ICH and IS versus TIA p<0.001). Cumulative risk of epilepsy with recurrent seizures was 23%, 8% and 4% respectively (Logrank ICH versus IS p = 0.05, ICH versus TIA p<0.001, IS versus TIA p = 0.01). In addition a high NIHSS was a significant predictor of both epilepsy and epilepsy with recurrent seizures (HR 1.07, 95% CI 1.03–1.11 and 1.08, 95% CI 1.02–1.14).
Post-stroke epilepsy is much more common than previously thought. Especially patients with an ICH and a high NIHSS are at high risk. This calls upon the question whether a subgroup could be identified which benefits from the use of prophylactic antiepileptic medication. Future studies should be executed to investigate risk factors and the effect of post-stroke epilepsy on quality of life.
PMCID: PMC3563638  PMID: 23390537
12.  Stroke: secondary prevention  
Clinical Evidence  2010;2010:0207.
People with a history of stroke or transient ischaemic attack (TIA) are at high risk of all vascular events, such as myocardial infarction (MI), but are at particular risk of subsequent stroke (about 10% in the first year and about 5% each year thereafter).
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive non-surgical interventions in people with previous stroke or transient ischaemic attack? What are the effects of preventive surgical interventions in people with previous stroke or transient ischaemic attack? What are the effects of preventive anticoagulant and antiplatelet treatments in people with atrial fibrillation and previous stroke or transient ischaemic attack? What are the effects of preventive anticoagulant and antiplatelet treatments in people with atrial fibrillation and without previous stroke or transient ischaemic attack? What are the effects of preventive anticoagulant and antiplatelet treatments in people with atrial fibrillation and without previous stroke or transient ischaemic attack and with low to moderate risk of stroke or transient ischaemic attack? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 130 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alternative antiplatelet regimens to aspirin, anticoagulation (oral dosing, or in those with sinus rhythm), aspirin (high or low dose), blood pressure reduction, carotid and vertebral percutaneous transluminal angioplasty (PTA), carotid endarterectomy (in people with: asymptomatic but severe carotid artery stenosis, less than 0% symptomatic carotid artery stenosis, moderate [30%-49%] symptomatic carotid artery stenosis, moderately severe [50%-69%] symptomatic carotid artery stenosis, severe [greater than 70%] symptomatic carotid artery stenosis, or symptomatic near occlusion of the carotid artery), cholesterol reduction, vitamin B supplements (including folate), and different regimens to lower blood pressure.
Key Points
Prevention in this context is the long-term management of people with previous stroke or TIA, and of people at high risk of stroke for other reasons, such as atrial fibrillation. Risk factors for stroke include: previous stroke or TIA; increasing age; hypertension; diabetes; cigarette smoking; and emboli associated with atrial fibrillation, artificial heart valves, or MI.
Antiplatelet treatment effectively reduces the risk of stroke in people with previous stroke or TIA. High-dose aspirin (500-1500 mg/day) seems as equally effective as low-dose aspirin (75-150 mg/day), although it may increase GI adverse effects. Adding dipyridamole to aspirin is beneficial in reducing composite vascular end points and stroke compared with aspirin alone. Risk reduction appears greater with extended-release compared with immediate-release dipyridamole.The net risk of recurrent stroke or major haemorrhagic event is similar with clopidogrel and aspirin plus dipyridamole.
Treatments to reduce blood pressure are effective for reducing the risk of serious vascular events in people with previous stroke or TIA. Blood pressure reduction seems beneficial irrespective of the type of qualifying cerebrovascular event (ischaemic or haemorrhagic), or even whether people are hypertensive.Aggressive blood pressure lowering should not be considered in people with acute stenosis of the carotid or vertebral arteries, because of the risk of precipitating a stroke.
Carotid endarterectomy effectively reduces the risk of stroke in people with greater than 50% carotid stenosis, is not effective in people with 30% to 49% carotid stenosis, and increases the risk of stroke in people with less than 30% stenosis. However, it does not seem beneficial in people with near occlusion.
Cholesterol reduction using statins seems to reduce the risk of stroke irrespective of baseline cholesterol or coronary artery disease (CAD). Non-statin cholesterol reduction does not seem to reduce the risk of stroke.
We found insufficient evidence to judge the efficacy of carotid percutaneous transluminal angioplasty, carotid percutaneous transluminal angioplasty plus stenting, or vertebral percutaneous transluminal angioplasty in people with recent carotid or vertebral TIA or stenosis.
Vitamin B supplements (including folate) do not seem beneficial in reducing mortality or the risk of stroke.
Anticoagulation does not seem beneficial in reducing stroke in people with previous ischaemic stroke and normal sinus rhythm, but does increase the risk of intra- and extracranial haemorrhage. This is especially true for patients with TIAs or minor ischaemic stroke as the qualifying event.
In people with atrial fibrillation, oral anticoagulants reduce the risk of stroke in people with previous stroke or TIA, and in people with no previous stroke or TIA who are at high risk of stroke or TIA, but we don't know whether they are effective in people with no previous stroke or TIA who are at low risk of stroke or TIA. In people with atrial fibrillation, we don't know whether aspirin reduces the risk of stroke in people with previous stroke or TIA, or in people without previous stroke or TIA who are at low risk of stroke or TIA, but they may be unlikely to be effective in people without previous stroke or TIA who are at high risk of stroke or TIA.
PMCID: PMC2907594
13.  Duration of Symptom and ABCD2 Score as Predictors of Risk of Early Recurrent Events after Transient Ischemic Attack: A Hospital-Based Case Series Study 
The aim of this study was to refine clinical risk factor stratification and make an optimal intervention plan to prevent ischemic stroke.
Clinical data, including diffusion-weighted imaging (DWI) findings, were collected in a cohort of hospitalized transient ischemic attack (TIA) patients from January 2010 to December 2011. Recurrent cerebrovascular events after TIA, including recurrent TIA, minor stroke, and major stroke, were identified by face-to-face follow-up. A multivariate, ordinal, logistic regression model was used to determine significant predictors of recurrent events.
Of 106 TIA patients, 24 (22.6%) had recurrent TIA and 20 (18.9%) had a stroke within 7 days. Hypertension, dyslipidemia, a history of ischemic stroke or TIA, and ABCD2 score were significantly associated with the recurrent events after TIA (P<0.001, P=0.02, P<0.001, P=0.02). Hypertension (RR=9.21; 95% CI, 3.07–27.61, P<0.001) and duration of symptom (RR=1.10; 95% CI, 1.02–1.17, P=0.01) as an item of ABCD2 score were highly predictive of the severity of recurrent events, whereas ABCD2 score as a whole (P=0.18) proved to be less strongly predictive.
A history of hypertension and long duration of symptom independently and significantly predict severe recurrent events after TIA within 7 days, but a high ABCD2 score was less strongly predictive of severe recurrent events.
PMCID: PMC4310715  PMID: 25604068
Ischemic Attack, Transient; Recurrence; Risk Assessment
14.  Ischaemic stroke in young adults: predictors of outcome and recurrence 
Background: There is limited information about predictors of outcome and recurrence of ischaemic stroke affecting young adults.
Objective: To assess the predictive value of the presenting characteristics for both outcome and recurrence in young stroke victims.
Methods: Clinical and radiological data for 203 patients aged 16 to 45 years were collected prospectively; they comprised 11% of 1809 consecutive patients with ischaemic stroke. The National Institutes of Health stroke scale (NIHSS), the Bamford criteria, and the trial of ORG 10172 in acute stroke treatment (TOAST) classification were used to define stroke severity, subtype, and aetiology. The clinical outcome of 198 patients (98%) was assessed using the modified Rankin scale (mRS) and categorised as favourable (score 0–1) or unfavourable (score 2–6).
Results: Stroke was caused by atherosclerotic large artery disease in 4%, cardioembolism in 24%, small vessel disease in 9%, another determined aetiology in 30%, and undetermined aetiology in 33%. Clinical outcome at three months was favourable in 68%, unfavourable in 29%, and lethal in 3%. Thirteen non-fatal stroke, two fatal strokes, and six transient ischaemic attacks (TIA) occurred during a mean (SD) follow up of 26 (17) months. High NIHSS score, total anterior circulation stroke, and diabetes mellitus were independent predictors of unfavourable outcome or death (p<0.0001, p = 0.011, and p = 0.023). History of TIA predicted stroke recurrence (p = 0.02).
Conclusions: Severe neurological deficits at presentation, total anterior circulation stroke, and diabetes mellitus predict unfavourable outcome. Previous TIA are associated with increased risk of recurrence.
PMCID: PMC1739502  PMID: 15654030
15.  CT Angiography and Presentation NIH stroke Scale in Predicting TIA in Patients Presenting with Acute Stroke Symptoms 
Patient candidacy for acute stroke intervention, is currently assessed using brain computed tomography angiography (CTA) evidence of significant stenosis/occlusion (SSO) with a high National Institutes of Health Stroke Scale (NIHSS) (>6). This study examined the association between CTA without significant stenosis/occlusion (NSSO) and lower NIHSS (≤ 6) with transient ischemic attack (TIA) and other good clinical outcomes at discharge. Patients presenting <8 hours from stroke symptom onset, had an NIHSS assessment and brain CTA performed at presentation. Good clinical outcomes were defined as: discharge diagnosis of TIA, modified Rankin Score [mRS] ≤ 1, and home as the discharge disposition. Eighty-five patients received both an NIHSS at presentation and a CTA at 4.2 ± 2.2 hours from stroke symptom onset. Patients with NSSO on CTA as well as those with NIHSS≤6 had better outcomes at discharge (p<0.001). NIHSS ≤ 6 were more likely than NSSO (p=0.01) to have a discharge diagnosis of TIA (p<0.001). NSSO on CTA and NIHSS ≤ 6 also correlated with fewer deaths (p<0.001). Multivariable analyses showed NSSO on CTA (Adjusted OR: 5.8 95% CI: 1.2-27.0, p=0.03) independently predicted the discharge diagnosis of TIA. Addition of NIHSS ≤ 6 to NSSO on CTA proved to be a stronger independent predictor of TIA (Adjusted OR 18.7 95% CI: 3.5-98.9, p=0.001).
PMCID: PMC4025925  PMID: 24851234
Ischemic stroke; Neuroimaging; TIA; Discharge; Clinical outcome
16.  Long term evolution of patients treated in a TIA unit 
Transient ischemic attacks (TIA) entail a high risk of stroke recurrence, which depends on the etiology. New organizational models have been created, but there is not much information about the long-term evolution of patients managed according to these premises. Our aim is to refer the follow-up of patients attended according to our model of TIA Unit.
TIA Unit is located in the Emergency Department and staffed by vascular neurologists. Patients admitted during the Neurology night shift stayed in such Unit <48h with complete etiological study. Preventive treatment is instituted in patients discharged to a high resolution Neurology consult, in order to review in <2 weeks and subsequent follow-up.
During a year 161 patients were attended, being admitted to the hospital 8.6%. A total of 1470 hospital days were avoided. Recurrence at 90 days was of 0.6%. Mean follow-up was 18.14 ± 8.02 months (0–34), total recurrence 6.2% (70% cardioembolic strokes). There were no complications derived from treatment. Cardiological events were recorded in 10.6%, neoplastic in 5%, cognitive impairment in 11%. There were 3 deaths unrelated nor to the stroke or its treatment.
This model allows an early diagnosis and treatment of TIA, preventing recurrences of stroke in a long term. It detects atherothrombotic strokes, most of them admitted to the hospital, and it shows a greater difficulty for detecting all cardioembolic strokes. TIA Unit appeared to be safe in using anticoagulation therapy, as the follow-up shows. It shows the same quality of management than hospital admission, with a significant saving in hospital stays.
PMCID: PMC3716896  PMID: 23635082
TIA; Mild stroke; TIA unit; Stroke care models; TIA management
17.  Incorporating Diffusion-Weighted Magnetic Resonance Imaging into an Observation Unit Transient Ischemic Attack Pathway 
The Neurohospitalist  2014;4(2):66-73.
Background and Purpose:
National guidelines advocate for early, aggressive transient ischemic attack (TIA) evaluations and recommend diffusion-weighted magnetic resonance imaging (MRI) for brain imaging. The purpose of this study is to examine clinician compliance, the yield of MRI, and patient-centered clinical outcomes following implementation of an emergency department observation unit (EDOU) clinical pathway incorporating routine MRI into the acute evaluation of patients with TIA.
This is a prospective observational study of patients with TIA admitted from the ED. Patients with low-risk TIA were transferred to an EDOU for diagnostic testing including MRI; high-risk patients were directed to hospital admission. Clinical variables, diagnostic tests, and treatment were recorded for all patients. The primary clinical outcome was the rate of stroke or recurrent TIA, determined through telephone follow-up and medical record review at 7 and 30 days.
A total of 116 patients with TIA were enrolled. In all, 92 (79.3%) patients were transferred to the EDOU, of whom 69 (59.5%) were discharged without hospitalization. Compliance with the EDOU pathway was 83 (91.2%) of 92. Magnetic resonance imaging demonstrated acute infarct in 16 (15.7%) of 102 patients. Stroke (n = 2) or TIA (n = 3) occurred in 5 patients with TIA (4.3%, 95% confidence interval: 1.6%-10.0%) within 30 days; no strokes occurred after discharge.
Implementation of a TIA clinical pathway incorporating MRI effectively encouraged guideline-compliant diagnostic testing; however, patient-important outcomes appear similar to diagnostic protocols without routine MRI. Further study is needed to assess the benefits and costs associated with routinely incorporating MRI into TIA evaluation.
PMCID: PMC3975796  PMID: 24707334
outcomes; techniques; imaging; techniques; ischemic attack; transient; cerebrovascular disorders; stroke and cerebrovascular disease; clinical specialty
18.  Migraine and Functional Outcome from Ischemic Cerebral Events in Women 
Circulation  2010;122(24):2551-2557.
Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.
Methods and Results
Prospective cohort study among 27,852 women enrolled in the Women’s Health Study for whom we had information on migraine and measured cholesterol values and who had no prior stroke or transient ischemic attack (TIA). Migraine was classified into no history of migraine, active migraine with aura, active migraine without aura, and past history of migraine. Possible functional outcomes were no stroke or TIA, TIA, and stroke with modified Rankin Scale (mRS) score 0–1, mRS 2–3, and mRS 4–6. We used multinomial logistic regression to evaluate the relationship of migraine with functional outcomes after ischemic stroke. During a mean of 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred. Compared with women without history of migraine and who did not experience a TIA or stroke, women who reported migraine with aura had adjusted relative risk (95% confidence interval) of 1.56 (1.03–2.36) for TIA, 2.33 (1.37–3.97) for stroke with mRS 0–1, 0.82 (0.30–2.24) for mRS 2–3, and 1.18 (0.28–4.97) for mRS 4–6. The risk of any outcome was not significantly elevated for women who experienced migraine without aura or who had a past history of migraine.
Results of this large prospective cohort suggest that women with migraine with aura are at increased risk of experiencing TIA or ischemic stroke with good functional outcome.
PMCID: PMC3058846  PMID: 21126968
Migraine; stroke; epidemiology; women
19.  The prognostic impact of the stroke unit care versus conventional care in treatment of patients with transient ischemic attack: a prospective population-based German study 
Background and purpose:
The risk of a stroke after a transient ischemic attack (TIA) is high in the short time following a TIA. The German Stroke Society recommends an early hospitalization of patients with TIA preferably in a stroke unit (SU). This study aims to compare the impact of SU care with conventional care (CC) in patients with TIA.
In a prospective study, during a 36-month phase (starting November 2007), patients with TIA who were admitted to the hospital within 48 h of symptom onset were enrolled. Stroke rate during hospitalization and the 90-day rates of stroke and mortality were studied. Logistic regression analyses were used to estimate the odds ratio (OR).
Of 2,200 patients (mean age, 17.6 ± 12 years, 49% female), 1,347 (61%) treated in a SU and 853 (39%) received CC at general departments. Patients treated in SU were significantly younger than those received a CC (69.9 vs. 71.7 years; P = 0.001). TIA patients treated on SU received more ultrasound investigations of the neck arteries (98 vs. 96%; P = 0.003) and of the brain arteries (97 vs. 82%; P < 0.001) than those of CC. The primary outcomes (stroke during hospitalization, stroke after 90 days, and mortality after 90 days) did not show a difference between the SU and CC groups. In patients of male sex, the 90-day stroke rate was significantly lower in the SU group than the CC group (1.8 vs. 4.5%; P = 0.033). Using the adjusted logistic regression analysis, treatment in a SU revealed a reduction of 90-day stroke rate in patients of male sex (OR 0.38; 95% CI 0.15–0.95; P = 0.04).
The impact of evaluation and treatment of patients with TIA in SU and CC appears to differ only among patients of male sex. Further randomized trials are necessary.
PMCID: PMC3584817  PMID: 23459173
TIA; prognosis; stroke; stroke unit; mortality; management; hospitalization
20.  Population-based study of risk and predictors of stroke in the first few hours after a TIA 
Neurology  2009;72(22):1941-1947.
Several recent guidelines recommend assessment of patients with TIA within 24 hours, but it is uncertain how many recurrent strokes occur within 24 hours. It is also unclear whether the ABCD2 risk score reliably identifies recurrences in the first few hours.
In a prospective, population-based incidence study of TIA and stroke with complete follow-up (Oxford Vascular Study), we determined the 6-, 12-, and 24-hour risks of recurrent stroke, defined as new neurologic symptoms of sudden onset after initial recovery.
Of 1,247 first TIA or strokes, 35 had recurrent strokes within 24 hours, all in the same arterial territory. The initial event had recovered prior to the recurrent stroke (i.e., was a TIA) in 25 cases. The 6-, 12-, and 24-hour stroke risks after 488 first TIAs were 1.2% (95% confidence interval [CI]: 0.2–2.2), 2.1% (0.8–3.2), and 5.1% (3.1–7.1), with 42% of all strokes during the 30 days after a first TIA occurring within the first 24 hours. The 12- and 24-hour risks were strongly related to ABCD2 score (p = 0.02 and p = 0.0003). Sixteen (64%) of the 25 cases sought urgent medical attention prior to the recurrent stroke, but none received antiplatelet treatment acutely.
That about half of all recurrent strokes during the 7 days after a TIA occur in the first 24 hours highlights the need for emergency assessment. That the ABCD2 score is reliable in the hyperacute phase shows that appropriately triaged emergency assessment and treatment are feasible.
= accident and emergency department;
= confidence interval;
= Fast Assessment of Stroke and Transient Ischemic Attack to prevent Early Recurrence;
= Oxford Vascular Study.
PMCID: PMC2690971  PMID: 19487652
21.  Management and outcomes of transient ischemic attacks in Ontario 
Canadian data on the characteristics, management and outcomes of patients with transient ischemic attack (TIA) are lacking. We studied prospectively a cohort of consecutive patients presenting with TIA to the emergency department of 4 regional stroke centres in Ontario.
Using data from the Ontario Stroke Registry linked with provincial administrative databases, we determined the short-term outcomes after TIA and assessed patient management in the emergency department and within 30 days after the index TIA. We compared the TIA patients with a cohort of patients who had ischemic stroke.
Three-quarters of the TIA patients were discharged from the emergency department. After discharge, the 30-day stroke risk was 5% (13/265) overall and 8% (13/167) among those with a first-ever TIA; the 30-day risk of stroke or death was 9% (11/127) among the TIA patients with a speech deficit and 12% (9/76) among those with a motor deficit. Half of the cases of stroke occurred within the first 2 days after the TIA. Diagnostic investigations were underused in hospital and on an outpatient basis within 30 days after the index TIA, the rates being as follows: CT scanning, 58% (211/364); carotid Doppler ultrasonography, 44% (162/364); echocardiography, 19% (70/364); cerebral angiography, 5% (19/364); and MRI, 3% (11/364). Antithrombotic therapy was not prescribed for more than one-third of the patients at discharge. Carotid endarterectomy was performed in 2% within 90 days.
Patients in whom TIA is diagnosed in the emergency department have high immediate and short-term risks of stroke. However, their condition is underinvestigated and undertreated compared with stroke: many do not receive the minimum recommended diagnostic tests within 30 days. We need greater efforts to improve the timely delivery of care for TIA patients, along with investigation of treatments administered early after TIA to prevent stroke.
PMCID: PMC374216  PMID: 15051693
22.  How Much Would Performing Diffusion-Weighted Imaging for All Transient Ischemic Attacks Increase MRI Utilization? 
The American Heart Association recently redefined transient ischemic attack (TIA) to exclude patients with infarction on neuroimaging. Given its advantages, MRI/DWI was recommended as the preferred imaging modality. We determined how frequently MRI/DWI was performed for TIA and ascertained the proportion of clinically-defined TIA patients who had ischemic lesions on DWI in our community in 2005.
All clinically-defined TIA cases among residents of a five-county region around Cincinnati who presented to emergency departments were identified during 2005. Demographics and medical history, whether MRI/DWI was done, and DWI findings were recorded. Generalized estimating equations were used to compare groups in order to account for the design of the study and multiple events per patient.
Of 834 TIA events in 799 patients, 323 events (40%) had MRI/DWI performed. Patients who had MRI/DWI were younger (mean 66 vs. 70yrs, p=0.03), had less severe pre-stroke disability (baseline modified Rankin Scale zero, 44% vs. 34%, p=0.02), were less likely to have prior stroke or TIA (42% vs 56%, p=0.002), and were less likely to have atrial fibrillation (10% vs. 16%, p=0.01). Of the 323 events with DWI, 51 (15%) had evidence of acute infarction. Patients with positive DWI were older (75 vs. 64yrs, p=0.0001) and more likely to have atrial fibrillation (21% vs. 7%, p=0.002).
Performing MRI/DWI on all clinically-defined TIA patients in our community would reveal more cases of actual infarction, but would more than double current use. Future studies should assess whether MRI/DWI is warranted for all TIA patients.
PMCID: PMC2952926  PMID: 20798366
TIA; MRI; Imaging
23.  Dabigatran etexilate for secondary stroke prevention: the first year experience from a multicenter short-term registry 
There are growing concerns for the side effects of dabigatran etexilate (dabigatran), including higher incidence of dyspepsia and gastrointestinal bleeding. We conducted a multicenter early implementation study to prospectively evaluate the safety, efficacy and adherence to dabigatran for secondary stroke prevention.
Consecutive atrial fibrillation (AF) patients with ischemic stroke (IS) or transient ischemic attack (TIA) received dabigatran for secondary stroke prevention during their hospital stay according to American Heart Association recommendations at five tertiary care stroke centers. The study population was prospectively followed and outcomes were documented. The primary and secondary safety outcomes were major hemorrhage and all other bleeding events respectively defined according to RE-LY trial methodology.
A total of 78 AF patients (mean age 71 ± 9years; 54% men; 81% IS, 19% TIA; median CHADS2 (Congestive heart failure, Hypertension, diabetes mellitus, age >75 years, prior stroke or TIA); range 2–5) score 4 were treated with dabigatran [(110mg bid (74%); 150mg bid (26%)]. During a mean follow-up period of 7 ± 5 months (range 1–18) we documented no cases of IS, TIA, intracranial hemorrhage, systemic embolism or myocardial infarction in AF patients treated with dabigatran. There were two (2.6%) major bleeding events (lower gastrointestinal bleeding) and two (2.6%) minor bleedings [hematuria (n = 1) and rectal bleeding (n = 1)]. Dabigatran was discontinued in 26% of the study population with high cost being the most common reason for discontinuation (50%).
Our pilot data indicate that dabigatran appears to be safe for secondary stroke prevention during the first year of implementation of this therapy. However, high cost may limit the long-term treatment of AF patients with dabigatran, leading to early discontinuation.
PMCID: PMC3994923  PMID: 24790645
atrial fibrillation; dabigatran etexilate; secondary prevention; stroke; transient ischemic attack
24.  Acute Isolated Dysarthria Is Associated with a High Risk of Stroke 
Cerebrovascular Diseases Extra  2014;4(2):182-185.
Isolated dysarthria is an uncommon presentation of transient ischemic attack (TIA)/minor stroke and has a broad differential diagnosis. There is little information in the literature about how often this presentation is confirmed to be a TIA/stroke, and therefore there is debate about the risk of subsequent vascular events. Given the uncertain prognosis, it is unclear how to best manage patients presenting to the emergency department (ED) with isolated dysarthria. The objective of this study was to prospectively identify and follow a cohort of patients presenting to EDs with isolated dysarthria in order to explore their natural history and risk of recurrent cerebrovascular events. Specifically, we sought to determine early outcomes of individuals with this nonspecific and atypical presentation in order to appropriately expedite their management.
Patients with isolated dysarthria having presented to 8 Canadian EDs between October 2006 and April 2009 were analyzed as part of a prospective multicenter cohort study of patients with acute neurological symptoms as assessed by emergency physicians. The study inclusion criteria were age ≥18 years, a normal level of consciousness, and a symptom onset <1 week prior to presentation without an established nonvascular etiology. The primary outcome was a subsequent stroke within 90 days of the index visit. The secondary outcomes were the rate of TIA, myocardial infarction, and death. Isolated dysarthria was defined as slurring with imprecise articulation but without evidence of language dysfunction. The overall rate of stroke in this cohort was compared with that predicted by the median ABCD2 score for this group.
Between 2006 and 2009, 1,528 patients were enrolled and had a 90-day follow-up. Of these, 43 patients presented with isolated acute-onset dysarthria (2.8%). Recurrent stroke occurred in 6/43 (14.0%) within 90 days of enrollment. The predicted maximal 90-day stroke rate was 9.8% (based on a median ABCD2 score of 5 for the isolated dysarthria cohort). After adjusting for covariates, isolated dysarthria independently predicted stroke within 90 days (aOR: 3.96; 95% CI: 1.3-11.9; p = 0.014).
The isolated dysarthria cohort carried a recurrent stroke risk comparable to that predicted by the median ABCD2 scores. Although isolated dysarthria is a nonspecific and uncommon clinical presentation of TIA, these findings support the need to view it first and foremost as a vascular presentation until proven otherwise and to manage such patients as if they were at high risk of stroke in accordance with established high-risk TIA guidelines.
PMCID: PMC4176400  PMID: 25298772
Stroke; Transient ischemic attack; Risk stratification; Outcome; Dysarthria
25.  Validation and Refinement of the ABCD2 Score: a population-based analysis 
Background and Purpose
Transient ischemic attacks (TIAs) are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow up and need for hospitalization differs widely. Recently, an effort has been made to risk stratify patients presenting with TIAs through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort.
Using the data from the Rochester Stroke and TIA Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, MN with a diagnosis of incident TIA from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The endpoints of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data.
Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9/36 cases, 25%) occurred in patients with low or intermediate risk scores (≤ 4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days.
Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a TIA. Adding hyperglycemia and a history of hypertension to the predictive model could be useful but the value of these additions need to be evaluated further.
PMCID: PMC2753856  PMID: 19520983
TIA; stroke; risk; prediction; score

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