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.

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.

Stroke in Pregnancy: A Multidisciplinary Approach.

Pregnancy confers a substantially increased risk of stroke, especially during the third trimester and until 6 weeks postpartum. Hypertensive disorders of pregnancy and gestational hypercoagulability are important contributors to obstetric stroke. Preeclampsia and eclampsia confer risk for future cardiovascular disease. Hemorrhagic stroke is the most common type of obstetric stroke. Ischemic stroke can result from cardiomyopathy, paradoxical embolism, posterior reversible encephalopathy, reversible cerebral vasoconstriction syndrome, and dissections. Cerebral venous sinus thrombosis is a frequent complication of pregnancy.

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.

Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA.

BACKGROUND AND PURPOSE: Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. METHODS: The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. RESULTS: Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score

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.

Management of Maternal Stroke and Mitigating Risk.

PURPOSE OF REVIEW: Pregnancy places women at a higher risk for hemorrhagic and ischemic strokes. This review discusses the pathophysiological mechanisms underlying this increased risk, management considerations for pregnant patients, and ways to decrease the risk of stroke in this patient population. RECENT FINDINGS: Rates of ischemic and hemorrhagic pregnancy-associated stroke have increased over the past 20 years, particularly events associated with hypertensive disorders of pregnancy. There is a growing body of evidence supporting the use of acute reperfusion therapies in ischemic pregnancy-associated stroke including tissue plasminogen activator (tPA) and endovascular thrombectomy. While the unique physiology of pregnancy places women at a higher risk of stroke, acute ischemic stroke management in pregnant patients should closely mirror the management of non-pregnant patients. Secondary stroke prevention agents should be selected with consideration of the pregnancy.

Antithrombotic Management of Ischemic Stroke.

PURPOSE OF REVIEW: Ischemic stroke describes a condition in which inadequate blood flow leads to lack of oxygenation to the brain tissue and ensuing neuronal death. There are multiple causes of ischemic stroke, each of which may indicate different antithrombotic management strategies. The goal of this review is to provide information about antithrombotic therapies for secondary stroke prevention based on etiology of stroke. RECENT FINDINGS: New studies of existing antiplatelet and antithrombotic therapies have demonstrated varied efficacies of treatments based on the underlying risk factor of ischemic stroke. Understanding the optimal therapies for secondary stroke prevention can enhance care of stroke patients and lower the incidence of recurrent cerebrovascular ischemia.

Stroke in Pregnancy: An Update.

Pregnancy confers a substantially increased risk of stroke in women. The period of highest risk of stroke is the peripartum/postpartum phase, coinciding with the highest risk for hypertensive disorders of pregnancy and peak gestational hypercoagulability. Hemorrhagic stroke is the most common type of obstetric stroke. Hypertensive disorders of pregnancy are important contributors to obstetric stroke and predispose women to premature cardiovascular disease. The rate of stroke associated with hypertensive disorders of pregnancy has increased in the United States. Other conditions associated with obstetric stroke include posterior reversible encephalopathy, reversible cerebral vasoconstriction syndrome, and cerebral venous sinus thrombosis.

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial.

Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

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.

SSRI and Motor Recovery in Stroke: Reestablishment of Inhibitory Neural Network Tonus.

Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control; these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation.

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.

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.

Association of Physical Function with Clinical and Subclinical Brain Disease: The Framingham Offspring Study.

BACKGROUND: Handgrip strength and gait speed are simple measures of physical capability and have been associated with current and future health outcomes. However, studies on their associations with brain structure and function in middle-aged adults are lacking. OBJECTIVE: To assess the relationship of fast-paced walking speed and handgrip strength with risk of dementia, Alzheimer's disease (AD), and stroke, as well as the cross-sectional associations with cognitive and brain magnetic resonance imaging (MRI) measures in a middle-aged community sample. METHODS: Framingham Offspring (n = 2,176; mean age 62, 54% female) had physical function, brain MRI, and cognitive evaluations between 1999 and 2005 and were followed-up for incident dementia AD and stroke until 11 years later. We related walking speed and handgrip strength to incident dementia, AD, and stroke using Cox models, and to brain and cognitive measures using multivariable linear and logistic regression. Models were adjusted for age, sex, education, and vascular risk factors. RESULTS: Slow walking and weak handgrip were associated with more than 2.5-fold increase in risk of AD. Weaker handgrip was associated with an increased risk of incident stroke (HR 1.74, 95% CI: 1.12-2.70/SDU, p = 0.01) in persons ≥65 years. Both measures were associated with lower total brain volume and poorer performance on tests of visual memory, language, executive function, and visuoperceptual function. Slower gait was also related to poorer verbal memory, and weaker handgrip to poorer abstraction. CONCLUSION: Tests of walking speed and handgrip strength may serve as clinical markers of brain structure and function and may improve dementia risk prediction.