Shelagh B. Coutts

Atrial Fibrillation in Patients with Cryptogenic Stroke

BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). METHODS We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P=0.01). CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924.).

Embolic strokes of undetermined source: the case for a new clinical construct

Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.

Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging.

We examined whether the presence of diffusion‐weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤ 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90‐day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90‐day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence. Ann Neurol 2005;57:848–854

Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis, Prognostic Value of the Alberta Stroke Program Early CT Score in ECASS II

Background and Purpose— The significance of early ischemic changes (EICs) on computed tomography (CT) to triage patients for thrombolysis has been controversial. The Alberta Stroke Program Early CT Score (ASPECTS) semiquantitatively assesses EICs within the middle cerebral artery territory using a10-point grading system. We hypothesized that dichotomized ASPECTS predicts response to intravenous thrombolysis and incidence of secondary hemorrhage within 6 hours of stroke onset. Methods— Data from the European-Australian Acute Stroke Study (ECASS) II study were used in which 800 patients were randomized to recombinant tissue plasminogen activator (rt-PA) or placebo within 6 hours of symptom onset. We retrospectively assessed all baseline CT scans, dichotomized ASPECTS at ≤7 and >7, defined favorable outcome as modified Rankin Scale score 0 to 2 after 90 days, and secondary hemorrhage as parenchymal hematoma 1 (PH1) or PH2. We performed a multivariable logistic regression analysis and assessed for an interaction between rt-PA treatment and baseline ASPECTS score. Results— We scored ASPECTS >7 in 557 and ≤7 in 231 patients. There was no treatment-by-ASPECTS interaction with dichotomized ASPECTS (P=0.3). This also applied for the 0- to 3-hour and 3- to 6-hour cohorts. However, a treatment-by-ASPECTS effect modification was seen in predicting PH (0.043 for the interaction term), indicating a much higher likelihood of thrombolytic-related parenchymal hemorrhage in those with ASPECTS ≤7. Conclusion— In ECASS II, the effect of rt-PA on functional outcome is not influenced by baseline ASPECTS. Patients with low ASPECTS have a substantially increased risk of thrombolytic-related PH.

Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score.

Background In ischemic stroke, functional outcomes vary depending on site of intracranial occlusion. We tested the prognostic value of a semiquantitative computed tomography angiography-based clot burden score. Methods Clot burden score allots major anterior circulation arteries 10 points for presence of contrast opacification on computed tomography angiography. Two points each are subtracted for thrombus preventing contrast opacification in the proximal M1, distal M1 or supraclinoid internal carotid artery and one point each for M2 branches, A1 and infraclinoid internal carotid artery. We retrospectively studied patients with disabling neurological deficits (National Institute of Health Stroke Scale score ≥ 5) and computed tomography angiography within 24-hours from symptom onset. We analyzed percentages independent functional outcome (modified Rankin Scale score ≤ 2), final infarct Alberta Stroke Program Early Computed Tomography Score and parenchymal hematoma rates across categorized clot burden score groups and performed multivariable analysis. Results We identified 263 patients (median age 73-years, National Institute of Health Stroke Scale score 10, onset-to-computed tomography angiography time 165 min). Clot burden score < 10 was associated with reduced odds of independent functional outcome (odds ratio 0.09 for clot burden score ≤5; odds ratio 0.22 for clot burden score 6–7; odds ratio 0.48 for clot burden score 8–9; all versus clot burden score 10; P <0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early CT Scores (P <0.001) and higher parenchymal hematoma rates (P = 0.008). Inter-rater reliability for clot burden score was 0.87 (lower 95% confidence interval 0.71) and intra-rater reliability 0.96 (lower 95% confidence interval 0.92). Conclusion The quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The score needs external validation and could be useful for patient stratification in stroke trials.

Systematic Review of Associations Between the Presence of Acute Ischemic Lesions on Diffusion-Weighted Imaging and Clinical Predictors of Early Stroke Risk After Transient Ischemic Attack

Background and Purpose— Early risk of stroke after a transient ischemic attack can be reliably predicted with risk scores based on clinical features of the patient and of the ischemic event, but it is unclear how these features correlate with findings on brain imaging. Methods— We performed a systematic review of the literature and identified all previous studies which reported patient characteristics and the nature of transient ischemic attack symptoms in relation to appearances on diffusion-weighted imaging (DWI). We then performed a meta-analysis of the associations between the components of the risk scores and positive DWI. Authors were contacted for additional unpublished data. Results— Nineteen studies were identified by the systematic review, and additional unpublished data were obtained from 11 of these studies. On meta-analysis, several components of the risk scores were associated with positive DWI, including symptom duration ≥60 minutes (13 studies, odds ratio [OR], 1.50; 95% CI, 1.16 to 1.96; P=0.004), dysphasia (9 studies, OR, 2.25; 95% CI, 1.57 to 3.22; P<0.001), dysarthria (8 studies, OR, 1.73; 95% CI, 1.11 to 2.68; P=0.03) and motor weakness (9 studies, OR, 2.20; 95% CI, 1.56 to 3.10; P<0.001). However patient age, sex, hypertension and diabetes were not associated with the presence of DWI lesions. From an etiologic perspective, atrial fibrillation (9 studies, OR, 2.75; 95% CI, 1.78 to 4.25; P<0.001) and ipsilateral ≥50% carotid stenosis (10 studies, OR, 1.93; 95% CI, 1.34 to 2.76; P=0.001) were associated with positive DWI. Conclusions— Presence of acute ischemic lesions on DWI correlates with several clinical features known to predict stroke risk after transient ischemic attack. Large studies (sample size >1000) will therefore be required to determine the independent prognostic value of DWI and its interactions with these clinical characteristics.

Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal

Background and Purpose Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC. Methods We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality. Results Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy. Conclusions PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.

Addition of Brain Infarction to the ABCD2 Score (ABCD2I) A Collaborative Analysis of Unpublished Data on 4574 Patients

Background and Purpose— The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD2 score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD2I). Methods— Twelve centers provided unpublished data on ABCD2 scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD2I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis. Results— Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD2 score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD2 score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P<0.001). Incorporation of infarction in the ABCD2I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD2 score to 0.78 (0.72 to 0.85) for the ABCD2I score. Conclusions— In secondary care, incorporation of brain infarction into the ABCD system (ABCD2I score) improves prediction of stroke in the acute phase after transient ischemic attack.

Hyperperfusion Syndrome: Toward a Stricter Definition

OBJECTIVEHyperperfusion syndrome is a rare and potentially devastating complication of carotid endarterectomy or carotid artery angioplasty and stenting. With the advent of new imaging techniques, we reviewed our experience with this phenomenon. METHODSThis report is a retrospective review of 129 consecutive cases of carotid endarterectomy performed between June 1, 2000, and May 31, 2002, and 44 consecutive cases of carotid artery angioplasty and stenting performed between January 1, 1997, and May 31, 2002. We specifically searched for examples of patients who developed postprocedural nonthrombotic neurological deficits that typified the hyperperfusion syndrome. RESULTSSeven cases of hyperperfusion syndrome occurred, four after endarterectomy (3.1% of carotid endarterectomy cases) and three after stenting (6.8% of stenting cases). The cases of hyperperfusion were classified as presenting with 1) acute focal edema (two cases with stroke-like presentation, attributable to edema immediately after revascularization), 2) acute hemorrhage (two cases of intracerebral hemorrhage immediately after stenting and one case immediately after endarterectomy), or 3) delayed classic presentation (two cases with seizures, focal motor weakness, and/or late intracerebral hemorrhage at least 24 hours after endarterectomy). CONCLUSIONHyperperfusion syndrome may be more common and more variable in clinical presentation than previously appreciated.

ASPECTS on CTA Source Images Versus Unenhanced CT Added Value in Predicting Final Infarct Extent and Clinical Outcome

Background and Purpose— The Alberta Stroke Program Early CT Score (ASPECTS) is a grading system to assess ischemic changes on CT in acute ischemic stroke. CT angiography–source images (CTA-SI) predict final infarct volume. We examined whether the final infarct ASPECTS and clinical outcome were more related to acute CTA-SI ASPECTS than to the acute noncontrast CT (NCCT) ASPECTS. Methods— ASPECTS was assigned by 2 raters on the acute NCCT, CTA-SI, and follow-up imaging. The mean baseline ASPECTS of acute NCCT and CTA-SI was compared with the follow-up ASPECTS. Rate ratios (RRs) were used to quantify the relationship between the dichotomized baseline ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome. Results— Thirty-nine patients were recruited. Proximal occlusion (internal carotid artery or middle cerebral artery) was seen in 62%, M2 occlusion in 18%, and no occlusion was seen in 20% of patients. The median time between symptom onset and imaging was 1.9 (1.2 to 2.5) hours. There was a significantly larger difference of 1.4 between the mean baseline NCCT and CTA-SI ASPECTS in patients who had more ischemic changes (follow-up ASPECTS=0 to 3) than a difference of 0.6 in patients who had near-to-normal CT scans (follow-up ASPECTS=8 to 10). The rate of favorable outcome for acute NCCT ASPECTS of 8 to 10 was 51.8% versus 25.0% for 0 to 7 (RR, 2.1, 95% CI: 0.7 to 5.9, P=0.12). For acute CTA-SI ASPECTS of 8 to 10, the rate of favorable outcome was 58.8% versus 31.8% for 0 to 7 (RR, 1.8, 95% CI: 0.9 to 3.8, P=0.09). Conclusions— CTA-SI ASPECTS provides added information in the prediction of final infarct size.