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Predicting recurrent after minor stroke and transient ischemic attack

Expert Rev. Cardiovasc. Ther. 7(10), 1273–1281 (2009)

Philippe Couillard, The risk of a subsequent stroke following an acute transient ischemic attack or minor stroke is Alexandre Y Poppe high, with 90-day risk at approximately 10%. Identification of those patients at the highest risk and Shelagh B Coutts† for recurrent stroke following a transient ischemic attack or minor stroke may allow risk-specific †Author for correspondence management strategies to be implemented, such as hospital admission with expedited work-up Department of Clinical for those at high risk and emergency room discharge for those at low risk. Predictors of recurrent Neurosciences and Radiology, stroke, including the ABCD2 score, imaging and the stroke mechanism, are reviewed in University of Calgary, C1261, this article, with a focus on recent literature. An emphasis is placed on the importance of early Foothills Medical Centre, imaging of the brain parenchyma (diffusion-weighted imaging) and vascular imaging to identify 1403 29th St NW, Calgary, patients at high risk for recurrence. The need for identification of the cause of the initial event, AB, T2N 2T9, Canada allowing therapies to be tailored to the individual patient, is discussed. Tel.: 1 403 944 1594 Fax: 1 403 283 2270 Keywords: imaging • prevention • prognosis • recurrence • stroke • transient ischemic attack shelagh.coutts@ albertahealthservices.ca Stroke is the second leading cause of and is present very quickly after symptom onset. This a major cause of adult disability in the world [1,2]. provides both an opportunity and a challenge: The incidence of stroke varies throughout the an opportunity to identify high-risk patients world from 240 per 100,000 people in Dijon, early, especially when their deficits are transient; France, to approximately 600 per 100,000 peo- a challenge in managing and triaging a large ple in Novosibirsk, Russia [3]. In the USA contingent of patients in a system often already alone, there are approximately 795,000 new overloaded. This review will focus on deter- each year [101]. In some stroke patients, minants of stroke recurrence, prediction rules the symptoms are mild (minor stroke) or even and imaging in minor stroke and TIA. Most transient – a transient ischemic attack (TIA). of the evidence described in this review is level- Tragically, many of these patients with mild two evidence, as it is derived from single‑center stroke experience either progression of their cohort studies. symptoms or a second, more severe stroke that leaves them disabled. One in five ischemic stroke Definition of recurrent stroke patients report a TIA in the hours to days pre- Ischemic stroke and TIA are on a spectrum of ceding the stroke [4–6]. In addition, 15–30% of serious conditions involving brain . disabling strokes are heralded by nondisabling Both represent inadequate cerebral blood flow stroke or TIAs, usually within 1 week [4]. After and cause patients to incur disability and death a TIA or minor stroke, there is an approximately at higher rates. There are various definitions of 10% risk of subsequent stroke within 90 days, stroke recurrence, but the one that we find of with 4–5% of this risk occurring in the first most practical use is a ‘functional deterioration 48 h [7–15]. Patients with strokes considered too in neurological status or a new sudden focal minor for tissue plasminogen activator represent neurological deficit of vascular origin lasting an interesting group. Studies show that up to a more than 24 h’. This could represent either third of patients die or become dependent at recurrent ischemia or hemorrhage; however, in hospital discharge [16,17]. most cases, the recurrent event after an ischemic With the advent of thrombolysis for acute stroke will be ischemic. The neurologic dysfunc- ischemic stroke, systems of care have improved tion is implicitly ischemic in nature and not epi- and patients with mild or transient deficits often leptic or related to a migrainous phenomenon www.expert-reviews.com 10.1586/ERC.09.105 © 2009 Expert Reviews Ltd ISSN 1477-9072 1273 Review Couillard, Poppe & Coutts or other stroke mimics (e.g., infections, drug abuse and side • Duration of symptoms lasting longer than 60 min (2 points) effects, or intercurrent illnesses). In this article, for the most or 10–59 min (1 point) part, we consider TIA and minor stroke together as a spectrum • Diabetes mellitus (1 point) of the same disease, as patients presenting very early in their event cannot be classified by the traditional method (symptoms The ability of the ABCD2 score to predict recurrent stroke risk resolved within 24 h of symptom onset) [14]. Rather than defining has been validated in independent cohorts, with AUC values rang- TIA and minor stroke as distinct syndromes, we prefer to look ing from 0.62 to 0.83. It allows the stratification of patients into upon these as events causing minimal or no deficits. The Effect high risk (score: 6–7; 8.1% 2-day risk of stroke), moderate risk of Urgent Treatment of Transient Ischemic Attack and Minor (score: 4–5; 4.1% 2-day risk of stroke) and low risk (score: 0–3; Stroke on Early Recurrent Stroke (EXPRESS) study found no 1% 2-day risk of stroke) (Figure 1). These scores are particularly difference in recurrent stroke outcomes in TIA or minor stroke useful for screening by nonexperts, but have some limitations: patients [18]. Other studies have also examined at patients in this Validation studies assessing the ABCD and ABCD2 scores have manner rather than making an arbitrary distinction between the generated mixed results; the applicability is potentially limited to two conditions [19,20]. TIA (although this is not clear), and the score is not informative on event mechanism [28,29]. Table 1 describes some of the factors Short-term stroke risk after TIA? that increase the stroke recurrence. Studies of prognosis after TIA from the early 1990s quoted annual stroke recurrence risk as between 3.7 and 7.8% per year [21]. Recently, Impact of mechanism on risk of recurrence more ominous results have been reported [22]. A Californian study Strokes can be subdivided according to their mechanism for differ- of 1707 patients diagnosed with TIA in the emergency depart- ent purposes: clinical trials, epidemiological studies and for thera- ment found a 10.5% incidence of stroke at 90 days, with half of peutic decision-making. The Trial of Org 10172 in Acute Stroke the strokes occurring in the first 2 days [14]. A Canadian study of Treatment (TOAST) classification, although imperfect, is often 2285 TIA patients produced similar findings, with a 90-day rate of used in clinical practice and research protocols [30]. It uses five stroke of 9.5% and a 1-year stroke risk of 14.5% [13]. A re-analysis categories: large-artery atherosclerosis, small-vessel disease, car- of the Oxford Community Stroke project showed an 8.6% risk of dioembolic, other determined and other undetermined. The risk stroke within 7 days after TIA [6]. Moreover, a large proportion of stroke recurrence is partly dependent on the mechanism under- of ischemic events will recur in the first 24 h, with a risk of 5.1% lying the index event [26]. Early identification of a mechanism at 24 h [23]. National stroke care guidelines echo this need for may, therefore, improve our ability to prognosticate recurrence urgent assessment, in an effort to reduce disability associated with and deterioration. Events due to large-artery disease (primarily disease recurrence [24]. extracranial) have the highest risk of early recurrence, approaching eight times that of those due to small-vessel disease, which have Clinical characteristics the lowest risk. Cardioembolic events fall somewhere in between Studies to identify patients who are at high risk for recurrent these two extremes [26,31]. The early risk of stroke after TIA due stroke after TIA have investigated the features of the patient to large-artery disease has been well demonstrated in a study of (e.g., diabetes mellitus [14] and hypertension [14,25]), of the event patients with more than 50% carotid stenosis, among whom 20% (e.g., symptom duration > 10 min or weakness or speech distur- had a stroke in the first 2 weeks prior to endarterectomy [9]. A bance [14,25]), of the mechanism [26], of the vascular territory and post hoc analysis of the versus Aspirin for Symptomatic of imaging to predict the risk of recurrence. Intracranial Disease study found a 6.7% risk of stroke within Patient variables and event characteristics are used to predict 90 days after TIA in patients with symptom-relevant 50–99% the risk of recurrent stroke. Using a combination of many of intracranial artery stenosis [32]. these factors, clinical stratification tools (e.g., California, ABCD The vascular territory involved in a TIA also has prognostic sig- and ABCD2 scores [14,25,27]) have been developed to help identify nificance. This is perhaps best described as the fact that retinal patients at high risk of recurrent events, with the aim of urgent TIAs () have a more favorable prognosis than events hospitalization and investigation.Conversely, the scoring systems in other vascular territories [33,26]. Vertebrobasilar events may be could identify patients at low risk, who could be managed in the associated with a higher risk of early recurrence [20,34,35], especially outpatient setting (or not enrolled in clinical trials). Recently, if stenosis is demonstrated in the posterior circulation [26,34]. the California and ABCD scores were combined to produce the ABCD2 score. The total ABCD2 score, ranging from 0 to 7, relies Cerebral & vascular imaging as a predictor on the summation of points associated with five clinical factors: of recurrence The limitations of previous predictive clinical scores may be due • Aged 60 years or over (1 point) to the omission of hyperacute imaging data. MRI, specifically • Blood pressure higher than 140/90 mmHg (1 point) diffusion-weighted imaging (DWI), has revolutionized early ischemia detection in TIA and stroke. However, its lack of avail- • Clinical features: unilateral weakness (2 points) or speech ability in a timely fashion has limited widespread use. By contrast, impairment without weakness (1 point) computerized tomography can be obtained expectantly in most

1274 Expert Rev. Cardiovasc. Ther. 7(10), (2009) Predicting recurrent stroke after minor stroke & transient ischemic attack Review settings. Both parenchymal and vascular imaging is important in working up a patient with TIA or stroke. Carotid imaging is 25 particularly important, since symptom-relevant carotid stenosis of 2 days greater than 50% is associated with a higher risk of early stroke 20 7 days after TIA [36], and such patients demonstrate robust benefit from 30 days early carotid revascularization. 90 days Evidence of an acute infarct on noncontrast computerized tomo­ 15 graphy (NCCT) alone has been shown to be predictive of recurrent stroke in TIA patients [37]. In this study, the authors simply rated scans as having an acute infarct or not and found an adjusted odds 10 oke risk (%) ratio of 4.06 (95% CI: 1.16–14.1), for predicting recurrent stroke. Str However, the proportion of patients with evidence of acute infarcts was small (4%), therefore limiting its usefulness. A recent publica- 5 tion indicated that adding NCCT data increased the predictive value of the ABCD score [38]. There was a suggestion of improve- ment of the score with the addition of the NCCT information, but 0 0 1 2 3 4 5 6 7 the effect was minimal, with the AUC being similar to that of the ABCD score in this population, with AUC values of 0.76 for ABCD ABCD2 score and 0.79 for ABCD and computed tomography. This is unsurpris- ing, as it seems unlikely that a NCCT alone would be the imaging Figure 1. Short-term risk of stroke by ABCD2 score in six answer to predicting outcome, as we know that MRI has greater groups combined (n = 4799). Reproduced with permission from [27] (2007) © Elsevier. sensitivity to smaller ischemic lesions compared with NCCT [39]. Computerized tomography angiography (CTA) uses the admin- Hyperacute MRI in TIA and minor stroke patients can also istration of intravenous, ionic contrast material to assess the intra­ stratify the risk of subsequent events and disability [53–57]. The cranial and extracranial vasculature with high spatial resolution. presence of an infarct on brain imaging intuitively portends an The addition of CTA adds less than 5 min to a standard CT brain increased risk of recurrence and has been reported to confer a examination and can be safely completed expediently in most two- to 15-fold increase in the short-term risk of stroke. Patients patients with a small dose of contrast [40]. In most institutions, a with a lesion identified with DWI are at higher risk of having a NCCT is completed in the emergency room immediately after the subsequent stroke as well as a disabled outcome (modified Rankin initial clinical assessment of these patients, and adding a CTA to Scale score ≥ 2) than patients without a lesion [55]. The patients the protocol is more feasible than removing the patient from the at highest risk are those with a lesion according to DWI and an scanner and proceeding to MRI. It has also been demonstrated that intracranial occlusion. In one study of TIA and minor stroke, an intracranial arterial occlusion identified by CTA is an independ- patients with no DWI lesion were at a much lower risk of recur- ent predictor of poor outcome in acute stroke patients [41]. CTA rent events (the definition of recurrent events included patients allows for the emergent identification of internal carotid artery with symptom progression) at 90 days (4.3%), compared with stenosis [42], can provide information regarding intracranial vascu- 10.8% with a DWI lesion and no vessel occlusion, and 32.6% lature missed by carotid ultrasound, has a diagnostic accuracy at with a DWI lesion and a large-vessel occlusion (Figure 2) [55]. The least as high as that of magnetic resonance angiography [43,44], and is number of DWI lesions at baseline also predicts the likelihood of comparable to digital subtraction angiography [45]. Prospective data new lesions (symptomatic or asymptomatic) at 30-day follow-up suggest that the presence of intracranial occlusion or extracranial MRI [58,59]. The presence of lesions of varying ages on the baseline large-artery disease as diagnosed on CTA in TIA and minor stroke MRI, which would suggest an active embolic process, is further patients predicts disability at 90 days [46,47]. The negative prognos- associated with an increased risk of recurrent stroke [60]. MRI tic value of intracranial vessel occlusion has also been shown using also has the capability of acting as a more sensitive measure of magnetic resonance angiography [47] and transcranial Doppler [20]. subclinical or ‘silent’ ischemic events than computed tomography. Magnetic resonance imaging is superior to CT for dem- Up to 9.8% of TIA and minor-stroke patients may have new MRI onstrating focal ischemic change, especially in small-volume lesions at 30-day follow-up, half of which are clinically silent [58]. lesions [39,48]. DWI is particularly sensitive and specific for dem- This is relevant because the accumulation of silent infarcts does onstrating ischemic damage and has revolutionized its detection not appear to be benign in the longer term [61–63]. Recent stud- when compared with standard MRI studies. A substantial pro- ies have shown that a proportion of TIA patients have abnormal portion (40–60%) of patients with TIA have injuries that are imaging despite resolution of symptoms. It is not clear observed on DWI [49,50]. Lesion pattern and location on DWI at the current time whether this population has an increased risk can change the suspected anatomic and vascular TIA localization of recurrent stroke [64,65]. in more than a third of patients [34,51]. Early DWI characteristics Minor stroke and TIA patients with no DWI lesion have a correlate well with etiological classification and allow for earlier low risk of recurrent clinical stroke and asymptomatic lesions determination of stroke mechanism [51,52]. on follow-up imaging [56–58]. It is not clear whether the initial www.expert-reviews.com 1275 Review Couillard, Poppe & Coutts

and recurrent TIA risk by detecting micro- Table 1. Clinical and imaging features that increase the risk of a embolic signals, which are most frequently recurrent stroke or symptom progression after transient ischemic seen in patients with unstable atherosclerotic attack or minor stroke. carotid plaque [74,75]. Emboli counts in excess Feature High risk Low risk of 50 microembolic signals/h appear to be associated with very high risk of impending Timing Hours ago Weeks ago stroke [76]. TCD emboli detection has also been shown to be useful in predicting stroke Age (years) >60 <45 in patients with asymptomatic carotid steno- Blood pressure at presentation >140/90 <140/90 sis [77], perhaps suggesting that large-artery (mmHg) disease is the context in which TCD emboli Diabetes Yes No detection has the most utility. Symptoms Speech, weakness , numbness Combining imaging & clinical risk Duration (min) >60 <10 stratification scores Frequency of events One or few Many The addition of two simple MRI factors Degree of clinical improvement Vanishing severe deficit Improving mild deficit (DWI lesion and intracranial-vessel occlu- Intracranial stenosis Severe None sion) to the clinical factors in the ABCD2 score improves the ability to identify TIA and Extracranial stenosis Present Absent minor stroke patients who are at high risk of Intracranial occlusion Present Absent functional disability [19]. ABCD2 plus MRI DWI lesion Multiple greater than single None is a nine-point score, and patients with a score of 7 or greater had a 90-day risk of stroke TCD emboli detection (MES/h) >50 None of 31.2%, and 22.9% of these patients were Lacunar perfusion abnormality Present Absent functionally impaired at 90 days. The value DWI: Diffusion-weighted imaging; MES: Microembolic signals; TCD: Transcranial Doppler. of MRI is best illustrated by the identification of a risk threshold that splits a group of clini- event in patients without DWI lesions is an ischemic event with cally high-risk patients in half. Among patients who were pre- a more benign prognosis or a nonischemic event, for example, dicted to have a 90-day stroke risk of 20% by ABCD2, ABCD2 migraine or , which was misdiagnosed as stroke or TIA. plus MRI stratified 40% of the patients to a lower stroke risk of It is likely that both of these factors contribute to the better 7.1%, and the remaining 60% of patients to a higher stroke risk prognosis in patients without DWI lesions. Regardless of the of 28.6%. The addition of DWI positivity to the ABCD2 score underlying pathogenesis, the predictive value of a negative DWI has been incorporated into an automated calculator of stroke risk scan for a benign outcome is strong. Thus, the potential for after TIA [57]. Combined clinical and imaging assessment could benefit from enrolling these patients into clinical trials is low. increase the efficient use of resources, as patients could be triaged In a recent systematic review, the presence of a DWI lesion more appropriately into low- and high-risk groups. However, after a TIA correlated well with the known clinical predictors these results should be interpreted with caution until they have of stroke after TIA [66]. Not all studies have confirmed this, and been validated in independent populations. further work is needed into this area. Thus, whether a DWI Neuroimaging can also determine the cause of clinical wors- lesion in isolation from other clinical imaging [67] or etiologic ening more accurately. MRI might help distinguish if deterio- factors [68] predicts recurrent stroke is unclear. Recently, it has ration is due to a new infarct geographically separate from the been shown that almost 50% of TIA patients with DWI lesions initial infarct, growth of the initial infarct, or isolated clinical have evidence of an extracranial or intracranial large-artery worsening without a new infarct or infarct growth [78]. In addi- occlusion or stenosis, suggesting that vascular imaging may be tion, MRI can identify clinically silent new infarcts or infarct the critical factor [56]. growth, both of which are known to occur within weeks after Gradient-echo sequences on MRI also provide information an initial TIA or minor stroke [58]. Therefore, similar to serial regarding the presence of cerebral microhemorrhages. These imaging in multiple sclerosis, attention should be paid to the microhemorrhages may be seen in up to 22% of patients with magnetic resonance lesion burden in TIA and stroke patients acute ischemic stroke, although they are less prevalent in patients and to how this burden changes over time. Use of imaging may with TIA [69–72]. Their presence appears to carry prognostic sig- be beneficial in studies of secondary prevention after TIA and nificance, being associated with an increased risk of recurrent minor stroke by allowing only patients at high risk for recur- fatal and disabling strokes in stroke and TIA patients [70]. rence to be selected for enrolment, thereby reducing sample sizes Transcranial Doppler (TCD) with emboli detection is also without sacrificing statistical power. In addition, as in multiple useful in the assessment and risk stratification of TIA and sclerosis, using both clinical and MRI end points (i.e., new silent minor-stroke patients [73]. TCD can help predict early stroke lesion and/or microhemorrhage accumulation) might also allow

1276 Expert Rev. Cardiovasc. Ther. 7(10), (2009) Predicting recurrent stroke after minor stroke & transient ischemic attack Review for smaller sample sizes by increasing the number of relevant No DWI lesion and outcomes. However, it is important to note that accumulation of 1.0 no occlusion: 4.3%

asymptomatic lesions has not been proven to predict long-term e recurrent stroke, and these data are necessary before imaging ok 0.9 can be used as a surrogate for clinical outcome. Yes DWI lesion and

om str no occlusion: 10.8% Why is it important to identify patients at the highest 0.8 risk of recurrent stroke? Yes DWI lesion and With many recent negative trials in the stroke literature, the acute 0.7 tion free fr yes occlusion: 32.6% ischemic stroke drug market has been described as a ‘graveyard’

opor for pharmaceutical companies [79,80]. During the 20th Century, 0.6 Pr at least 178 randomized clinical trials were conducted in stroke, Likelihood ratio test and of these, only three trials reported positive findings[81] . One p-value = 0.02 0.5 reason for this is stroke pathophysiological heterogeneity [82]. 0 30 60 90 The use of imaging to enrol patients is a potential way of target- Time after presenting with acute ing a more homogeneous population [83]. This approach could TIA or minor stroke (days) remove ‘noise’ from the trial, allowing a therapeutic effect to be seen with a relatively smaller sample size [84]. Accurate iden- Figure 2. Stroke-free survival curves for patients with and tification of those patients at the highest risk of worsening or without diffusion-weighted imaging lesion and having a recurrent event would allow the targeting of therapies intracranial vessel occlusion. Curves are adjusted for NIH to these TIA and minor-stroke patients. Patients with low-risk Stroke Scale score and baseline glucose level. The adjusted risks events who have nothing to gain could be excluded. There are of stroke at 90 days are shown as percentages on the right side above the curves. a number of potential clinical and imaging factors that may be DWI: Diffusion-weighted imaging; TIA: Transient ischemic attack. used to stratify risk in minor stroke and TIA. Clinical tools are Reproduced with permission from [96]. important; however, those based on imaging and clinical factors are potentially better. In an ideal world, acute intervention trials A recent publication suggested that if five, simple evidence- in these patients would be based on MRI criteria; however, as based interventions (i.e., dietary modification, exercise, aspirin, this tool is not available in many (if not most) centers, it would a statin and an antihypertensive agent) were used appropri- limit trial enrolment and generalizability. Table 1 shows some of ately, then the risk of recurrent stroke might be reduced by up the important clinical and imaging factors that predict recurrent to 80% [93]. Thus, it would seem that urgent stroke prevention stroke after TIA or minor stroke. services for TIA promise to reduce recurrent stroke by facilitating There are a number of effective treatments available to prevent more rapid and early access to the effective treatments, as dis- stroke after a TIA. Available treatments include aspirin [85] or cussed earlier. Additionally, two observational studies published other antiplatelet medications [86], antihypertensive agents [87], in 2007 (EXPRESS [Figure 3] and Transient Ischaemic Attack statins [88], anticoagulation for [89], and early Clinic with Round-The-Clock Access [SOS-TIA]) [18,94] indi- for symptomatic internal carotid artery cate that hyper­acute evaluation and treatment after TIA may stenosis of 50% or more [90]. Guidelines have been introduced significantly reduce subsequent stroke by 80% compared with to outline some of the treatment options for these patients [24,91]. expected rates. Although there have been many interesting studies of antiplatelet agents in secondary stroke prevention, discussion of these stud- Expert commentary ies is beyond the scope of this review article. Importantly, vir- The common thinking regarding TIA and minor stroke has been tually all of these trials have avoided enrolling patients within that early risk is assumed primarily by recurrent events. However, 24 h of their event. With regards to emergent treatment (within there is evidence that up to 90% of early clinical deterioration can 24 h), the Fast Assessment of Stroke and Transient Ischaemic actually be attributed to symptom progression or infarct growth Attack to Prevent Early Recurrence (FASTER) study was the first rather than a true recurrent stroke [78]. This distinction may be randomized trial to test the benefit of emergent preventive treat- important because specific therapeutic interventions might be ment of minor-stroke and TIA patients [92]. This study was the tailored to attenuate infarct progression, while others would aim first to assess ‘emergent secondary stroke prevention’. This study to minimize the risk of recurrence. Although EXPRESS [18] and was based in Calgary and was a pilot study testing the emergent SOS-TIA [94] have shown that existing evidence-based therapies use of aspirin versus aspirin plus clopidogrel. It demonstrated a for secondary stroke prevention appear to be of benefit in the promising, although not significant, 35% relative risk reduction in acute phase, novel and potentially more effective therapies are recurrent stroke in the combination treatment arm versus aspirin still lacking. More randomized, controlled trials in the ilk of the monotherapy. A larger, second FASTER trial is planned, to test FASTER study [92] are needed to investigate the value of different the benefit of urgent combination treatment in a patient sample antiplatelet regimens, anticoagulation, blood pressure manage­ of several thousand. ment, high-dose statins, thrombolysis, endovascular stenting and www.expert-reviews.com 1277 Review Couillard, Poppe & Coutts

Five-year view

14 Over the next 5 years, early brain and vascular imaging will be performed in all acute stroke patients – especially in TIA or 12 Phase 1 minor-stroke patients. We expect that 5 years from now, most Phase 2 patients will have a MRI brain scan immediately, including 10 detailed vascular imaging, allowing a more tailored approach 8 to acute treatment immediately after the scan. Early identifica- tion of stroke subtype is important, as it will alter the long- 6 term care of the patient, including secondary stroke prevention, 4 as well as assigning prognosis, identification of patients with

Risk of recurrence (%) increased risk of neurological worsening, recurrent stroke and 2 p < 0.0001 medical complications. Recurrent stroke prevention will involve 0 tailoring therapy to an individual patient based upon imaging 0 10 20 30 40 50 60 70 80 90 results. Clinical trials will investigate specific stroke etiologies Time (days) and response to acute treatment. Currently, we feel that the most obvious treatment strategy to be tested is dual antiplatelet Figure 3. Risk of recurrent stroke after first seeking medical therapy (aspirin and clopidogrel) in large-artery disease [95], but attention in all patients with transient ischemic attack or stroke in the whole study population. there will be other such targeted treatment strategies. Stroke Reproduced with permission from [18]. care will move from an era of negative trials, due to lumping of different mechanisms of stroke together, to a more etiological neuro­protection in TIA patients and minor-stroke patients at approach to the disease. Repeat imaging at a few months post- high, early risk of deterioration. Therapies tailored to particu- stroke, showing ongoing accumulation of disease, will also allow lar TIA and stroke mechanisms are also needed, especially for us to manage their vascular risk factors more aggressively. patients with intracranial atherosclerosis and small-vessel infarcts. For now, the therapeutic paradigm should consist of expedited Financial & competing interests disclosure evaluation, relevant bloodwork, parenchymal and vascular neu- The authors have no relevant affiliations or financial involvement with any roimaging, cardiac investigations and a ‘cocktail’ therapeutic organization or entity with a financial interest in or financial conflict with approach, with attention to mechanisms requiring specific treat- the subject matter or materials discussed in the manuscript. This includes ment. Recurrent events, whether they are progression of the origi- employment, consultancies, honoraria, stock ownership or options, expert nal event or a distinct new event, need emergent investigations testimony, grants or patents received or pending, or royalties. and treatment to prevent recurrent stroke [78]. No writing assistance was utilized in the production of this manuscript.

Key issues • Ischemic strokes are common and costly for the individual and society. • Early identification of patients at high risk for recurrent stroke is essential to reduce morbidity, mortality and allocate resources appropriately. • Identification of stroke mechanism is essential to tailoring treatment to the individual patient. • Diagnostic imaging allows triage and classification of patients into high- and low-risk groups. • Stroke is a disease of blood vessels – intracranial and extracranial vascular imaging is as important as brain parenchymal imaging. • Diffusion-weighted imaging can predict which patients are at high risk for recurrent stroke. • Many recurrent strokes occur in the hours to days after the initial event, making assessment and treatment of these patients an emergency. • Early initiation of treatment can prevent recurrent stroke in up to 80% of transient ischemic attacks and minor-stroke patients.

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Vasc. blood-pressure-lowering regimen among Endovasc. Surg. 14(3), 170–176 (1997). 6105 individuals with previous stroke or Affiliations 77 Molloy J, Markus HS. Asymptomatic transient ischaemic attack. Lancet • Philippe Couillard, MD embolization predicts stroke and TIA risk in 358(9287), 1033–1041 (2001). Department of Clinical Neurosciences, patients with carotid artery stenosis. Stroke 88 Amarenco P, Bogousslavsky J, University of Calgary, Calgary, AB, Canada 30(7), 1440–1443 (1999). Callahan A 3rd et al. High-dose atorvastatin • Alexandre Poppe, MD, FRCPC 78 Coutts SB, Hill MD, Campos CR et al. after stroke or transient ischemic attack. Centre des Maladies Vasculaires Cérébrales Recurrent events in transient ischemic attack N. Engl. J. Med. 355(6), 549–559 (2006). du CHUM Hôpital Notre-Dame, 1560 rue and minor stroke: what events are 89 EAFT (European Atrial Fibrillation Trial) Sherbrooke Est Montréal, Québec, happening and to which patients? Stroke Study Group. Secondary prevention in H2L 4M1, Room GR-1166, Canada 39(9), 2461–2466 (2008). non-rheumatic atrial fibrillation after Tel.: +1 514 890 8000 ext. 26260 Fax: +1 514 412 7556 • Important paper identifying that, in minor transient ischaemic attack or minor stroke. stroke and TIA, many of the cases of Lancet 342(8882), 1255–1262 (1993). • Shelagh B Coutts BSc, MBChB, MD, recurrent stroke are due to progression of 90 Rothwell PM, Eliasziw M, Gutnikov SA FRCPC, FRCP, the initial event and not a distinct et al. Analysis of pooled data from the Stroke Neurologist, AHFMR Clinical Investigator and HSFC Distinguished new event. randomised controlled trials of endarterectomy for symptomatic carotid Clinician Scientist, Assistant Professor, 79 Hacke W, Furlan AJ, Al-Rawi Y et al. stenosis. Lancet 361(9352), 107–116 (2003). Department of Clinical Neurosciences and Intravenous desmoteplase in patients with Radiology, University of Calgary, C1261, 91 Lindsay P, Bayley M, McDonald A, acute ischaemic stroke selected by MRI Foothills Medical Centre, 1403 29th St Graham ID, Warner G, Phillips S. Toward perfusion-diffusion weighted imaging or NW, Calgary, AB, T2N 2T9, Canada a more effective approach to stroke: perfusion CT (DIAS-2): a prospective, Tel.: +1 403 944 1594 canadian best practice recommendations for randomised, double-blind, placebo- Fax: +1 403 283 2270 stroke care. CMAJ 178(11), 1418–1425 controlled study. Lancet Neurol. 8(2), [email protected] 141–150 (2009). (2008).

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