Role of Brain and Vessel Imaging for the Evaluation of Transient Ischemic Attack and Minor Stroke
2018; Lippincott Williams & Wilkins; Volume: 49; Issue: 7 Linguagem: Inglês
10.1161/strokeaha.118.016618
ISSN1524-4628
Autores Tópico(s)Traumatic Brain Injury and Neurovascular Disturbances
ResumoHomeStrokeVol. 49, No. 7Role of Brain and Vessel Imaging for the Evaluation of Transient Ischemic Attack and Minor Stroke Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBRole of Brain and Vessel Imaging for the Evaluation of Transient Ischemic Attack and Minor Stroke A.Y.X. Yu, MD, MSc and S.B. Coutts, MD, MSc A.Y.X. YuA.Y.X. Yu From the Division of Neurology, Department of Medicine, Sunnybrook Research Institute, University of Toronto, Ontario, Canada (A.Y.X.Y.) and S.B. CouttsS.B. Coutts Correspondence to S.B. Coutts, MD, MSc, Foothills Medical Centre, 1403 29th St NW C1242, Calgary, AB T2N 2T9, Canada. E-mail E-mail Address: [email protected] Department of Clinical Neurosciences (S.B.C.) and Department of Radiology (S.B.C.), Community Health Sciences, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada. Originally published30 Jul 2018https://doi.org/10.1161/STROKEAHA.118.016618Stroke. 2018;49:1791–1795Stroke is a leading cause of death and disability, and 50% to 80% of patients with ischemic stroke first present with transient or mild symptoms.1 These minor events are far from benign. After a transient ischemic attack (TIA) or minor stroke, the 1-year risk of stroke recurrence is 5% to 6%,2,3 and the 3-month risk of disability is 15%, even in the absence of overt stroke recurrence.4 A US Get With The Guidelines–Stroke Registry study of 29 200 patients with ischemic stroke with mild or improving symptoms found that at the time of hospital discharge, 29% needed assistance for ambulation, 11% required nursing home care, and 2% died.5 At 5 years, population-based data showed that 32% of patients with TIA experience another major vascular event (stroke or myocardial infarction), are institutionalized, or have died.6 To sum up these statistics, TIA and minor strokes represent the majority of ischemic cerebrovascular events, but these minor events can have major consequences.The risk of stroke progression or recurrence is highest in the first hours to days after symptom onset, and this risk can be reduced by early risk stratification and institution of disease-specific treatment.4,7 Three challenges currently exist in the management of patients with TIA and minor stroke: (1) making a rapid accurate diagnosis, (2) establishing the mechanism of stroke and the risk of early recurrence, and (3) expediting investigations and treatments through coordinated care. Urgent neurovascular imaging addresses these challenges. In this article, we review the indications for neuroimaging after a suspected TIA or minor stroke and discuss the different imaging modalities. We group TIAs and minor strokes under the umbrella term of minor ischemic cerebrovascular events because both entities are on the milder end of the spectrum of severity of ischemic cerebrovascular diseases, share similar pathophysiology, and require the same urgency in diagnosis, investigation, and treatment. Distinguishing one from the other is not clinically relevant, especially if a patient is assessed soon after symptom onset.Brain Parenchymal ImagingNoncontrast Computed TomographyNoncontrast computed tomography (NCCT) is the first-line imaging modality in the investigation of suspected minor ischemic cerebrovascular events. Readily available in most emergency departments, an NCCT can rule out important stroke mimics (space-occupying lesion, subdural hemorrhage) and intracerebral hemorrhage. In a small proportion of patients with minor ischemic cerebrovascular events (5%), the NCCT confirms acute ischemia,8 which is an important finding for prognostication. Acute ischemia on NCCT has been shown to be associated with increased stroke recurrence and disability.8,9 In addition, the presence of white matter disease and remote infarcts also adds prognostic value. A prospective study of >2000 consecutive patients presenting to the emergency department with TIA or nondisabling strokes found that the presence of acute ischemia, age-indeterminate ischemia, and microangiopathy on NCCT was associated with a 23-fold higher risk of recurrent stroke at 90 days compared with patients without these factors.8Magnetic Resonance Diffusion-Weighted ImagingCompared with NCCT, magnetic resonance diffusion-weighted imaging (DWI) has higher sensitivity in demonstrating acute ischemia in patients with ischemic stroke.10 Predictors of a false-negative DWI scan include strokes that are clinically less severe, are located in the posterior circulation, have small lesion size, or have small vessel pathogenesis. Thin-slice imaging improves the sensitivity in detecting acute ischemia, especially in the posterior circulation. Further, hyperacute DWI findings can be unstable—the DWI scan may initially be falsely negative, and positive scans may later normalize.10 In patients with transient neurological deficits, that is, clinically defined TIA, the DWI scan is positive for acute ischemia in 30% to 50% of the cases.11 A redefinition of TIA has been proposed, departing from the traditional time-based criteria (clinical symptom resolution within an arbitrary 24-hour cutoff) to tissue-based criteria (focal neurological symptoms without tissue ischemia seen on magnetic resonance DWI).12 Changing the definition of TIA and stroke is expected to impact the epidemiology and prognosis of both conditions.13 However, the tissue-based definition is not widely operationalized because magnetic resonance imaging (MRI) scans remain a limited resource, and not all patients are eligible for these tests because of various contraindications or claustrophobia.Distinguishing TIA from minor stroke has little clinical relevance in the acute management of the patient. However, the diagnosis of TIA is largely based on clinical acumen and is challenging. It is subject to disagreement, even among neurologists.14 Although the MRI cannot be used to definitely rule out a stroke, it is a particularly useful tool in the diagnosis of cerebral ischemia in cases with atypical features and diagnostic uncertainty. For example, when assessing a young patient with no vascular risk factors, a history of migraines, and an episode of transient neurological deficit, the differential diagnosis is wide, and the MRI becomes an important diagnostic tool to confirm cerebral ischemia. Having a firm diagnosis of stroke or TIA has implications, including advice on use of lifelong antiplatelet agents, especially when the patient otherwise has no indication for antiplatelet agents, the eligibility for health or travel insurance, and anxiety experienced by patients.The classic teaching that nonfocal symptoms (eg, isolated dizziness and confusion) are rarely because of cerebral ischemia may not be true. Nonfocal symptoms are found in up to a third of patients with minor cerebral ischemic events and are not associated with a benign outcome.15 Most researches on MRI in the TIA and minor stroke population focus on the high-risk patients.10 Few MRI studies included the low-risk population with nonfocal symptoms. A recent study with >1000 participants imaged with acute MRI addressed this gap. The authors enrolled a low-risk population without motor/speech neurological symptoms or transient (≤5 minutes) motor/speech symptoms, and they found that 14% of these patients had MRI DWI-positive scans. All patients were assessed by neurologists with an expertise in stroke. Before the MRI, neurologists rated whether the diagnosis was because of cerebral ischemia (TIA/stroke) or not (migraine, somatoform illness, panic attack, etc). The authors found that DWI was positive for ischemia in 20% of patients who were initially diagnosed as noncerebral ischemia.16 These results suggest that MRI findings need to be combined with clinical acumen to determine whether the transient neurological event was a DWI-negative ischemic event or a nonischemic event.In contrast to the younger patient with focal neurological symptoms, when assessing a similar event in an elderly patient with multiple vascular risk factors, whether the MRI DWI is positive or negative has less impact on the acute management because the pretest probability of cerebral ischemia is high. Nevertheless, identifying acute ischemia with MRI has prognostic implications, establishes the vascular localization(s) of the event and the pattern of the ischemia, and guides the identification of stroke pathogenesis.9,11 Many studies have shown that the risk of recurrent stroke after TIA is 2- to 3-fold higher in patients with DWI lesion compared with those without.17,18 A prospective study of 120 patients with TIA or minor ischemic stroke who underwent MRI and vascular imaging with computed tomographic angiography (CTA) within 24 hours of symptom onset found a DWI lesion in 58% of the patients.17 The risk difference of stroke recurrence within the first 90 days was 11% (15% for patients with a DWI lesion and 4% for patients without). In addition to showing that MRI DWI has important prognostic value, this study highlighted that the risk of stroke recurrence in patients who are DWI-negative is not null.Another important finding in this study is that the association between stroke recurrence and DWI lesion was modified by the presence of a symptomatic intracranial occlusion.19 Patients with minor cerebral ischemic event with DWI lesion and no intracranial occlusion had 11% stroke recurrence at 90 days compared with 33% stroke recurrence in those with DWI lesion and an intracranial occlusion. No patient with an intracranial occlusion had DWI-negative imaging. These findings reinforce the concept that stroke and TIA are symptoms of a disease of the cerebral blood vessels and that vascular imaging is essential.Neurovascular ImagingComputed Tomographic AngiographyCTA is the standard-of-care vascular imaging modality in cerebrovascular diseases because it can be done quickly, at the time of the acute NCCT, and allows for the visualization of the intracranial blood vessels and the posterior circulation. Many groups of researchers have reported the association between symptomatic vascular occlusions or high-grade stenosis and stroke progression, recurrence, and disability.4,20,21 For example, the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients) prospectively enrolled 510 patients with TIA or minor stroke who underwent NCCT, CTA, and MRI acutely.19 The study found that 34% of the patients had an NCCT/CTA-positive metric (acute ischemia on NCCT or symptomatic intracranial or extracranial vessel occlusion or stenosis of ≥50%), and 58% had a DWI lesion. As shown in the Figure, in CATCH, the risk difference in stroke recurrence was larger based on NCCT/CTA findings (panel A) than MRI DWI findings (panel B). In multivariable analyses, only the NCCT/CTA metric was predictive of stroke recurrence at 90 days. Most stroke recurrence occurred in the first few hours or overnight after the initial event. Further, the CATCH study also showed that the presence of intracranial occlusion was associated with 90-day disability: 22% of disabled patients had occlusions versus 9% of nondisabled patients (odds ratio, 2.4; 95% confidence interval, 1.5–3.8).4 Visualizing the blood vessels is, therefore, crucial for determining risk of early stroke recurrence and disability.Download figureDownload PowerPointFigure. Time to recurrent stroke after minor cerebral ischemic event stratified by Noncontrast computed tomography (NCCT)/computed tomographic angiography (CTA; A) and magnetic resonance imaging (MRI; B). Kaplan-Meier survival free from recurrent stroke stratified by diffusion-weighted imaging (DWI)-positive MRI. The upper curve represents those who had positive NCCT/CTA or DWI scans, and the bottom curve represents those with negative NCCT/CTA or DWI scans. The shaded area represents 95% confidence limits. Log-rank tests for equality of survivor functions for NCCT/CTA and DWI MRI were statistically significant (P<0.0001 and P=0.03, respectively). Reprinted from Coutts et al19 with permission. TIA indicates transient ischemic attack. Copyright ©2012, the American Heart Association.Vascular imaging is also important in establishing stroke pathogenesis and guiding evidence-based surgical or medical therapy targeted to the stroke pathogenesis. Patients with high-grade carotid disease are at the highest risk of stroke recurrence and poor outcomes—a risk that can be decreased with carotid revascularization.22 A big driver of early stroke prevention is the fact that the effectiveness of carotid endarterectomy for patients with symptomatic high-grade extracranial carotid disease is highly time sensitive. The number needed to treat to prevent 1 ipsilateral stroke in 5 years is only 5 for patients treated within 2 weeks of their event, but it is 125 for those treated after 12 weeks.22 Patients with symptomatic carotid artery stenosis only represent 10% of all patients; however, they account for ≤50% of recurrence.23 Similarly, patients with high-grade symptomatic intracranial stenosis benefit from early initiation of dual antiplatelet therapy, high-dose statin, and lifestyle interventions (eg, smoking cessation) for secondary stroke prevention.24Although the absence of intracranial stenosis or occlusion does not rule out a cerebral ischemic event, vascular imaging has high negative predictive value for early stroke recurrence and progression. This has important health system implications because the minority of patients with abnormalities on CTA will benefit from admission to hospital for observation, whereas the majority of patients without vascular pathology can be discharged for urgent outpatient follow-up in a Stroke Prevention Clinic. If early neurological deterioration occurs while in hospital, these patients may be considered for treatment with thrombolysis or endovascular thrombectomy. Patients with a proven intracranial occlusion may also be considered for prolonged cardiac monitoring to rule out atrial fibrillation because this is the most common source of embolization. Arguments have also been made that the patients with high-risk TIA and minor stroke with intracranial occlusion could benefit from acute thrombolysis at the time of presentation.25 The currently ongoing TEMPO-2 study (TNK-tPA Evaluation for Minor Ischemic Stroke With Proven Occlusion-2; NCT02398656) is a phase III clinical trial that addresses this question by studying Tenecteplase (TNK-tPA, TNKase) in patients with minor stroke and proven intracranial occlusion using a prospective, randomized, open-blinded end-point design.Other Neurovascular Imaging TechniquesBoth carotid Doppler and magnetic resonance (MR) angiogram are alternative imaging modalities to the CTA, especially in patients who have a clear contraindication to iodinated contrast. The carotid Doppler is a noninvasive ultrasound-based scan that can be used to identify high-grade extracranial carotid disease but offers limited information on the intracranial and posterior circulation. It requires a trained operator and, as a result, is rarely available outside of business hours, leading to delays in imaging. MR angiogram, with or without Gadolinium contrast, can be used to visualize the extracranial and intracranial blood vessels but adds significant imaging time in the MRI scanner and is subject to the same limitations in access as the MRI DWI.Multiphase CTA is another imaging technique used in recent endovascular thrombectomy trials26 that provides time-resolved cerebral angiograms of the intracranial vasculature and has been shown to be highly reliable at identifying intracranial occlusions.27 Compared with perfusion imaging, multiphase CTA has the added advantage that it is relatively resistant to motion artifact, does not require an additional contrast bolus, adds little additional radiation exposure for the patient, has rapid and automated postimaging processing, and is easy to interpret even among nonradiologist clinicians.28 Both perfusion and multiphase CTA imaging can improve the reliability of identification of intracranial occlusions, especially the smaller occlusions in the distal vasculature.27Perfusion imaging, either with MR perfusion or CT perfusion can be added onto the assessment of these patients. Perfusion images can also be done rapidly in patients presenting with acute symptoms and have been shown to improve the sensitivity of the diagnosis of cerebral ischemia and identifying vascular occlusion.29,30 Perfusion defects are associated with early stroke recurrence or progression. In particular, patients with a mismatch in the perfusion versus diffusion-weighted imaging, that is, evidence of perfusion defect without established infarct on DWI, are at higher risk of early infarct growth.31 The presence of a penumbra on CT perfusion has also been proposed to be used to guide decisions on intravenous thrombolysis in patients with minor strokes.32Timing of ImagingA decade ago, the rate of stroke recurrence after minor ischemic cerebrovascular events was as high as 10% to 15%.33,34 More recent studies show that the 90-day stroke recurrence rate has reduced to <5%, suggesting that this condition is highly treatable but a medical emergency nonetheless.3 The EXPRESS study (Early Use of Existing Preventive Strategies for Stroke) showed that urgent evaluation by a neurologist and early neuroimaging and initiation of secondary stroke prevention can reduce the risk of stroke recurrence by 80%.7 Because the risk of stroke recurrence is the highest in the first days after the acute event, early diagnosis, identification of the cause of the event, and institution of treatment is urgent and time sensitive.33,34 Neurovascular imaging is an ideal risk stratification tool because it allows for the confirmation of the diagnosis of ischemic stroke, rapid institution of specific secondary stroke prevention strategies that are targeted to the mechanism of stroke, and has value in prognostication.Many jurisdictions advise for urgent interventions. The American Heart Association/American Stroke Association scientific statement on the evaluation of TIA published in 2009 recommends that patients with TIA should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with MRI DWI and that vascular imaging of the extracranial vessels is needed, while imaging of the intracranial vessels is reasonable.35 The NICE guidelines (The National Institute for Health and Care Excellence) from the United Kingdoms, published in 2008, recommend that patients with TIA at high risk for stroke (crescendo symptoms or high ABCD2 score) should undergo urgent brain imaging, preferably with MRI DWI and early carotid imaging.36 The Canadian Stroke Best Practice Guidelines were recently updated in 2017 and state that patients with suspected TIA at very high risk of recurrent stroke, those presenting to medical attention within 48 hours of symptom onset, should undergo brain imaging with NCCT or MRI and vascular imaging with CTA or MR angiogram from aortic arch to vertex as soon as possible within 24 hours and that patients at high risk of recurrent stroke, those with symptom onset between 48 hours and 2 weeks, should be evaluated by a stroke expert as soon as possible, ideally within 24 hours of first contact with the healthcare system.37Care after TIA and minor strokes has been shown to be heterogeneous.38 Delayed neurovascular imaging leads to important missed opportunities for the prevention of disabling strokes. A population-based study of 8540 patients with TIA and minor stroke found that compared with patients admitted to hospital, those discharged from the emergency department were less likely to undergo timely neurovascular imaging and were more likely to be readmitted with a TIA or stroke at 7 days (8% among discharged patients versus 0.9% among admitted patients), despite stroke clinic referral.39In line with the Canadian Stroke Best Practice Guidelines, we recommend that patients with a suspected minor ischemic cerebrovascular event who present within 48 hours of symptom onset and those with persistent or fluctuating symptoms should be assessed urgently to (1) establish a diagnosis, (2) identify the stroke pathogenesis, and (3) initiate disease-specific treatments. If the diagnosis is clearly a nonischemic event, then alternate management plan should be established. If there is a definite or possible minor ischemic stroke or TIA, patients should be started on an antiplatelet agent, be evaluated with an ECG, and undergo same-day imaging of the brain parenchyma and extracranial and intracranial cerebral vessels with NCCT/CTA or MRI/MR angiogram from aortic arch to vertex. If the neurovascular imaging is abnormal, the patient should be evaluated by a stroke specialist on the same day, and if it is normal, the patient can be referred to an outpatient rapid access clinic for further assessment.37,40ConclusionsAlthough different centers and jurisdictions have variable access to neurovascular imaging, we highlight in this review the importance of early imaging of the brain parenchyma, as well as the extracranial and intracranial blood vessels. In particular, the patients with high-risk TIA and minor stroke—those presenting within 48 hours of their symptom onset or those with persistent or fluctuating symptoms—need neurovascular imaging in the emergency department before discharge. Neurovascular imaging is essential for establishing a diagnosis, understanding early prognosis, identifying the pathogenesis of the event, guiding pathogenesis-specific stroke prevention treatments, and identifying patients eligible for ongoing clinical trials, to improve patient outcomes.DisclosuresNone.FootnotesCorrespondence to S.B. Coutts, MD, MSc, Foothills Medical Centre, 1403 29th St NW C1242, Calgary, AB T2N 2T9, Canada. E-mail [email protected]caReferences1. Reeves M, Khoury J, Alwell K, Moomaw C, Flaherty M, Woo Det al. Distribution of National Institutes of Health stroke scale in the Cincinnati/Northern Kentucky stroke study.Stroke. 2013; 44:3211–3213. doi: 10.1161/STROKEAHA.113.002881.LinkGoogle Scholar2. 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Coutts S, Moreau F, Asdaghi N, Boulanger J, Camden M, Campbell B, Demchuk A, Field T, Goyal M, Krause M, Mandzia J, Menon B, Mikulik R, Penn A, Swartz R and Hill M (2019) Rate and Prognosis of Brain Ischemia in Patients With Lower-Risk Transient or Persistent Minor Neurologic Events, JAMA Neurology, 10.1001/jamaneurol.2019.3063, 76:12, (1439), Online publication date: 1-Dec-2019. 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