Other cerebrovascular occlusive disease.

In this chapter we review the optimal imaging modalities for subacute and chronic stroke. We discuss the utility of computed tomography (CT) and multimodal CT imaging. Further, we analyze the importance of specific magnetic resonance imaging sequences, such as diffusion-weighted imaging for acute ischemic stroke, T2/fluid-attenuated inversion recovery for subacute and chronic stroke, and susceptibility imaging for detection of intracranial hemorrhages. Different ischemic stroke mechanisms are reviewed, and how these imaging modalities may aid in the determination of such. Further, we analyze how topographic patterns in ischemic stroke may provide important clues to the diagnosis, in addition to the temporal evolution of the stroke. Lastly, specific cerebrovascular occlusive diseases are reviewed, with emphasis on the optimal imaging modalities and their findings in each condition.

Field Assessment Stroke Triage for Emergency Destination: A Simple and Accurate Prehospital Scale to Detect Large Vessel Occlusion Strokes.

BACKGROUND AND PURPOSE: Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. METHODS: The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale. RESULTS: LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P=0.28; RACE=0.77, P=0.02; and CPSS=0.75, P=0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, and 0.79, and CPSS ≥2 of 0.56, 0.85, 0.65, and 0.78, respectively. CONCLUSIONS: FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients.

Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography.

IMPORTANCE: Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an anterior circulation proximal intracranial arterial occlusion. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset. EXPOSURE: Anterior circulation proximal intracranial arterial occlusion. MAIN OUTCOMES AND MEASURES: Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months. RESULTS: A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI, 0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. CONCLUSIONS AND RELEVANCE: The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.

Good outcome rate of 35% in IV-tPA-treated patients with computed tomography angiography confirmed severe anterior circulation occlusive stroke.

BACKGROUND AND PURPOSE: To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke. METHODS: Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. RESULTS: Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (P<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P=0.031). The number needed to treat was 7 (95% confidence interval, 3-60). CONCLUSIONS: IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.

Improved outcome prediction using CT angiography in addition to standard ischemic stroke assessment: results from the STOPStroke study.

PURPOSE: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). METHODS: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS>2. Strokes were classified as "major" by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was ≤7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores >10. RESULTS: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p<0.0001). Combining NIHSS with BASIS was highly predictive: 77.6% (114/147) classified as NIHSS>10/BASIS+ had poor outcomes, versus 21.5% (77/358) with NIHSS≤10/BASIS- (p<0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95% CI: 7.9 to 20.0) in patients who are NIHSS>10/BASIS+ compared to patients who are NIHSS≤10/BASIS-; the odds ratio is 5.4 (95% CI: 3.5 to 8.5) when compared to patients who are only NIHSS>10 or BASIS+. CONCLUSIONS: BASIS and NIHSS are independent outcome predictors. Their combination is stronger than either instrument alone in predicting outcomes. The findings suggest that CTA is a significant clinical tool in routine acute stroke assessment.

The pattern of leptomeningeal collaterals on CT angiography is a strong predictor of long-term functional outcome in stroke patients with large vessel intracranial occlusion.

BACKGROUND AND PURPOSE: The role of noninvasive methods in the evaluation of collateral circulation has yet to be defined. We hypothesized that a favorable pattern of leptomeningeal collaterals, as identified by CT angiography, correlates with improved outcomes. METHODS: Data from a prospective cohort study at 2 university-based hospitals where CT angiography was systematically performed in the acute phase of ischemic stroke were analyzed. Patients with complete occlusion of the intracranial internal carotid artery and/or the middle cerebral artery (M1 or M2 segments) were selected. The leptomeningeal collateral pattern was graded as a 3-category ordinal variable (less, equal, or greater than the unaffected contralateral hemisphere). Univariate and multivariate analyses were performed to define the independent predictors of good outcome at 6 months (modified Rankin Scale score ≤2). RESULTS: One hundred ninety-six patients were selected. The mean age was 69±17 years and the median National Institute of Health Stroke Scale score was 13 (interquartile range, 6 to 17). In the univariate analysis, age, baseline National Institute of Health Stroke Scale score, prestroke modified Rankin Scale score, Alberta Stroke Programme Early CT score, admission blood glucose, history of hypertension, coronary artery disease, congestive heart failure, atrial fibrillation, site of occlusion, and collateral pattern were predictors of outcome. In the multivariate analysis, age (OR, 0.95; 95% CI, 0.93 to 0.98; P=0.001), baseline National Institute of Health Stroke Scale (OR, 0.75; 0.69 to 0.83; P<0.001), prestroke modified Rankin Scale score (OR, 0.41; 0.22 to 0.76; P=0.01), intravenous recombinant tissue plasminogen activator (OR, 4.92; 1.83 to 13.25; P=0.01), diabetes (OR, 0.31; 0.01 to 0.98; P=0.046), and leptomeningeal collaterals (OR, 1.93; 1.06 to 3.34; P=0.03) were identified as independent predictors of good outcome. CONCLUSIONS: Consistent with angiographic studies, leptomeningeal collaterals on CT angiography are also a reliable marker of good outcome in ischemic stroke.

Gender differences in outcomes after ischemic stroke: role of ischemic lesion volume and intracranial large-artery occlusion.

BACKGROUND: The reasons for gender disparities in stroke outcome remain unclear, and little is known about the value of acute neuroimaging characteristics in elucidating differential stroke outcomes between the sexes. METHODS: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography (CTA) was performed in all patients within 24 h of symptom onset. CTA source images were used to evaluate lesion volume. The primary outcome measure was a modified Rankin scale (mRS) score ≥ 3 at 6 months. RESULTS: We evaluated 676 consecutive patients (322 women). Women were older than men (p < 0.01), more frequently had a prestroke mRS >0 (p < 0.01), and had higher admission National Institutes of Health Stroke scale scores (p = 0.01). More women had intracranial artery occlusions than men (46 vs. 33.1%, p = 0.01), but there was no significant difference between ischemic lesion volumes (p = 0.21). Using multiple regression, female gender remained an independent predictor of poor mRS scores at 6 months (odds ratio 1.57; 95% confidence interval 1.02-2.36) after adjustment for clinical and imaging covariates. CONCLUSION: Compared with men, women are less likely to achieve independence after acute ischemic stroke. The disparity in stroke outcome is not explained by differences in ischemic lesion volume or the presence of intracranial artery occlusions.

Wake-up stroke: clinical and neuroimaging characteristics.

BACKGROUND: Approximately 25% of ischemic stroke patients awaken with neurological deficits. In these patients, in whom the time from symptom onset is uncertain, brain imaging is a potential strategy to characterize the ischemia duration and the presence of salvageable brain tissue. METHODS: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography and CT perfusion (CTP) were performed in patients within 24 h of symptom onset. The patients were classified into 'known onset', 'indefinite onset but not on awakening' and 'wake-up stroke' groups. RESULTS: Of 676 patients evaluated, 420 had known-onset strokes, 131 wake-up strokes and 125 strokes with an indefinite time of symptom onset. Ischemic lesion volumes were higher in patients with indefinite-onset strokes (p = 0.04). The frequencies of CTP mismatch and of large-vessel intracranial occlusions were similar among the groups (p = 0.9 and p = 0.2, respectively). CONCLUSION: The considerable prevalence of CTP mismatch and of intracranial artery occlusions in our patients with wake-up strokes suggests that arterial and perfusion imaging might be particularly important in this population. Revised indications for thrombolysis by using imaging-based protocols might offer these patients the prospect of receiving acute stroke treatment even without a clear time of symptom onset.

Hyperdense basilar artery sign on unenhanced CT predicts thrombus and outcome in acute posterior circulation stroke.

BACKGROUND AND PURPOSE: In acute stroke patients, the presence of a hyperdense middle cerebral artery sign on unenhanced CT is a specific but insensitive indicator of acute thrombosis. Our purpose was to determine whether the hyperdense basilar artery (HDBA) sign has utility in detecting thrombosis and predicting outcome in patients presenting with signs and symptoms of posterior circulation stroke. METHODS: Unenhanced CT scans obtained within 24 hours of symptom onset in 95 patients with suspected posterior circulation stroke were reviewed. Three neuroimagers blinded to clinical outcome and results of the concurrent CT angiography (which served as the reference standard) rated presence of HDBA sign on a 5-point scale for level of certainty (1=definitely absent; 5=definitely present). Receiver operating characteristic curve analysis was performed. Short-term outcome was measured by discharge National Institute of Health Stroke Scale (NIHSS) scores; long-term outcome was measured by 6-month modified Rankin score (dichotomized, poor outcome defined as modified Rankin score >2). The following variables were correlated with short-term and long-term outcome by univariate analysis: HDBA sign, age, sex, time from stroke onset to imaging, admission NIHSS, history of stroke/TIA, atrial fibrillation, coronary artery disease, hypertension, diabetes, hypercholesterolemia, tobacco use, and thrombolysis. Variables showing correlation with P<0.1 were included in multiple regression analysis. RESULTS: Using a level of certainty cutoff score of >/=4 (probable, definite), HDBA sign had 71% sensitivity, 98% specificity, 94% accuracy, 83% positive predictive value, and 95% negative predictive value for basilar artery occlusion. In univariate analysis, factors significantly correlated with discharge NIHSS were: admission NIHSS (P<0.0001; r=0.77), HDBA sign (P=0.01), and diabetes (P=0.02). Factors showing significant correlation or association with poor long-term outcome were age (P=0.02), admission NIHSS (P=0.007), HDBA sign (P=0.02), and history of stroke or TIA (P=0.007). The odds ratio of HDBA sign for predicting poor long-term outcome was 5.3 (95% CI, 1.1-33.3). In multiple regression analysis, the only independent predictors of discharge NIHSS were admission NIHSS (P<0.0001) and HDBA sign (P=0.004). Significant independent predictors of poor long-term outcome were age (P=0.02), admission NIHSS (P=0.008), history of stroke/TIA (P=0.03), and HDBA sign (P=0.05). CONCLUSIONS: In patients presenting with a high pretest probability of posterior circulation stroke based on clinical symptoms, the presence of the HDBA sign on unenhanced CT is a strong predictor of basilar artery thrombosis, and both short- and long-term outcome.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H(2)) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. METHODS: The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. RESULTS: Over half of CVT patients (52.1%) were heterozygous (H(1)H(2)) or homozygous (H(2)H(2)) carriers of the H(2) haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H(2) haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). CONCLUSIONS: These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

Acute brain infarct: detection and delineation with CT angiographic source images versus nonenhanced CT scans.

PURPOSE: To retrospectively compare sensitivity and specificity of admission nonenhanced computed tomographic (CT) scans with those of CT angiographic source images in detection of early ischemic changes in middle cerebral artery (MCA) stroke and to retrospectively compare admission nonenhanced CT scans with CT angiographic source images in delineation of final infarct extent, with follow-up images as reference. MATERIALS AND METHODS: Informed consent and institutional review board approval were received for this HIPAA-compliant study. Nonenhanced scans and angiographic source images obtained within 12 hours of symptom onset in 51 patients suspected of having MCA stroke were reviewed. Two blinded neuroimagers rated presence and extent of hypoattenuation on nonenhanced scans and angiographic source images with Alberta Stroke Programme Early CT Score (ASPECTS). Level of certainty for hypoattenuation detection was assigned a grade with a five-point scale. With receiver operating characteristic (ROC) curve analysis, nonenhanced scans and angiographic source images were compared for stroke detection. For stroke delineation, linear regression coefficients determined correlations of ASPECTS for nonenhanced scans and angiographic source images with ASPECTS for follow-up images. Multiple linear regressions were used to compare these correlations. RESULTS: Follow-up nonenhanced CT scans, diffusion-weighted magnetic resonance (MR) images, or fluid-attenuated inversion-recovery MR images were obtained (mean time to follow-up, 5.4 days); 33 patients had infarction. With level of certainty cutoff score of 4 or greater (probable, definite) for ischemic hypoattenuation, sensitivity for detection of acute stroke was 48% (nonenhanced scans) and 70% (angiographic source images) (P = .04, ROC analysis); specificity was 100% for both. Linear regression revealed R(2) = 0.42 (P < .001) for correlation between delineation of stroke on nonenhanced scans and on follow-up images evaluated with ASPECTS and 0.73 (P < .001) for correlation between delineation on angiographic source images and follow-up images evaluated with ASPECTS (P < .001, nonenhanced scans vs angiographic source images). CONCLUSION: CT angiographic source images, compared with nonenhanced CT scans, are more sensitive in detection of early irreversible ischemia and more accurate for prediction of final infarct volume.

Generalized periodic EEG activity in two cases of neurosyphilis.

Neurosyphilis is a recognized cause of epileptic seizures and cognitive impairment, but is not usually associated with the finding of generalized periodic activity in the EEG. We report two similar cases characterized by progressive cognitive impairment followed by partial complex seizures, in whom the EEG showed generalized periodic activity. Both cerebrospinal fluid and the response to penicillin therapy confirmed the diagnoses of neurosyphilis in the two cases. The finding of EEG generalized periodic activity in patients with cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob disease, although there are other conditions, some of them potentially reversible, which may also present this EEG abnormality. Neurosyphilis has tended not to be included among them, and our present findings support the importance of first ruling out neurosyphilis in those patients with cognitive or behavioral disorders associated with generalized periodic epileptiform discharges.

Generalized periodic EEG activity in two cases of neurosyphilis

Neurossífilis é uma causa conhecida de crises convulsivas e de comprometimento cognitivo, mas não é associada geralmente a atividade periódica generalizada no eletroencefalograma (EEG). Relatamos dois casos similares caracterizados por declínio cognitivo progressivo seguido de crises parciais complexas, em que o EEG mostra a atividade periódica generalizada. O líquido cefalorraquidiano e uma boa resposta à terapia com penicilina confirmaram os diagnósticos de neurossífilis nos dois casos. Achados de atividade periódica generalizada no EEG de pacientes com distúrbios cognitivos ou de comportamento são associados geralmente com a doença de Creutzfeldt-Jakob, embora haja outras circunstâncias, algumas delas potencialmente reversíveis, que podem também apresentar esta anormalidade no EEG. A neurossífilis tende a não ser incluída entre eles, e nossos achados sustentam a importância de afastar o diagnóstico de neurossífilis naqueles pacientes com declínio cognitivo ou comportamental associados com as descargas periódicas generalizadas no EEG.

Stroke in Latin America.

Stroke is one of the leading causes of mortality in Latin America, with variable incidence and prevalence throughout the continent reflecting regional socioeconomic differences. In Latin America, uncontrolled hypertension is one of the major causes of stroke, but other modifiable risk factors also play a role, such as heavy alcohol consumption and smoking. Intracerebral hemorrhage and lacunar stroke are more frequent in Latin America than in North America and Europe. There are multiple causes of stroke that are endemic to Latin America, including neurocysticercosis, Chagas' disease, sickle cell anemia, malaria, hemorrhagic fever, and snake bites.