Natural history of nonbacterial thrombotic endocarditis treated with warfarin.

We report on the natural history of a cohort of patients presenting with transient ischemic attack or stroke and nonbacterial thrombotic endocarditis treated with warfarin.Patients with valvular vegetations on echocardiography, stroke, or transient ischemic attack presenting to a single neurologist were included. All patients were treated with warfarin until the vegetation resolved or for two years, then were switched to aspirin and had at least one clinical and echocardiographic follow-up.Twenty-nine patients were included and followed for a median of 27 months. Average age was 42 years and 72% were female. Two patients had vegetations on two valves. Five patients (17%) had recurrent strokes, three had systemic lupus erythematosus and antiphospholipid antibodies, one had antiphospholipid antibodies alone and one had neither condition. Three of the five patients did not have resolution of the vegetation at the time of the event. The valvular vegetations resolved in 23 of the 31 affected valves (74%) after a median of 11 months (range 4.5-157.5). Eleven patients had at least one follow-up echocardiogram after resolution of the vegetation and none had recurrent vegetations after warfarin was stopped.This study should serve to provide general recommendations regarding treatment of patients with TIA/stroke with nonbacterial thrombotic endocarditis. Valvular vegetations resolve in most patients and the risk of recurrent stroke is low. Warfarin can safely be switched to aspirin in most patients when the vegetation resolves or after two years if it does not resolve. Prolonged warfarin may be warranted in patients with systemic lupus erythematosus, positive antiphospholipid antibodies, and a persistent vegetation.

Predictors for the extent of pial collateral recruitment in acute ischemic stroke.

BACKGROUND: Pial arterioles can provide a variable degree of collateral flow to ischemic vascular territories during acute ischemic stroke. This study sought to identify predictive factors of the degree of pial collateral recruitment in acute ischemic stroke. METHODS: Clinical information and arteriograms from 62 consecutive patients with stroke due to either middle cerebral artery (MCA) M1 segment or internal carotid artery (ICA) terminus occlusion within 6 h following symptom onset were retrospectively reviewed. Pial collaterals were defined based on the extent of reconstitution of the MCA territory. Patients with slow antegrade flow distal to the occlusion site were excluded and no anesthetics were used prior or during angiography. Results were analyzed using multivariate nominal logistic regression. RESULTS: Better pial collateral recruitment was associated with proximal MCA versus ICA terminus occlusion (p = 0.005; odds ratio (OR) = 9.3; 95% confidence interval (CI), 2.16-53.3), lower presenting National Institutes of Health Stroke Scale Score (NIHSSS) (p = 0.023; OR = 6.51; 95% CI, 1.49-41.7), and lower diastolic blood pressure (p = 0.0411; OR = 5.05; 95% CI, 1.20-29.2). Age, gender, symptom duration, diabetes, laterality, systolic blood pressure, glucose level, hematocrit, platelet level, and white blood cell count at presentation were not found to have a statistically significant association with pial collateral recruitment. CONCLUSIONS: Extent of pial collateral recruitment is strongly associated with the occlusion site (MCA M1 segment versus ICA terminus) and less strongly associated with presenting NIHSSS and diastolic blood pressure.

Factors associated with rapid neurological improvement 24 h following intra-arterial thrombolytic treatment for acute ischemic stroke.

BACKGROUND AND PURPOSE: Significant 24 h improvement is the strongest indicator of functional recovery following thrombolytic treatment for acute ischemic stroke. This study sought to analyze factors contributing to rapid neurological improvement (RNI) following intra-arterial thrombolytic treatment (IATT). METHODS: Angiograms and clinical information derived from consecutive patients receiving treatment initiated within 6 h of stroke onset were retrospectively reviewed. RNI was defined as at least 50% 24 h improvement on the National Institutes of Health Stroke Scale score. Logistic regression analysis identified factors associated with RNI. Variables tested included: age, gender, serum glucose, platelet count, pial collateral formation, presenting National Institutes of Health Stroke Scale score, time to treatment, extent of reperfusion, site and location of occlusion, treatment agent and systolic blood pressure. RESULTS: Greater than 50% reperfusion of the involved territory, time to treatment within 270 min and good pial collateral formation (large penumbra zone) significantly predicted RNI. RNI occurred in 31% of the 112 patients studied. RNI occurred in 21/26 (80.8%) patients exhibiting all three favorable variables whereas patients with only one favorable variable had a 6.5% chance of RNI. 94% of patients displaying RNI had a modified Rankin Scale score of 2 or less at 3 months compared with 28.6% without RNI. CONCLUSIONS: RNI following IATT for stroke is more likely when at least two of the following are present: good reperfusion, good pial collateral formation and treatment within 4.5 h of symptom onset, and is strongly predictive of 3 month outcomes. Important to clinical management, IATT may need to be reconsidered in patients with poor pial collateral formation if time to treatment exceeds 4.5 h.

An endovascular canine middle cerebral artery occlusion model for the study of leptomeningeal collateral recruitment.

OBJECTIVES: This work aimed to refine a large animal in minimally invasive reversible middle cerebral artery (MCA) occlusion (MCAO) model to account for leptomeningeal collateral formation. MATERIALS AND METHODS: An angiographically based methodology allowed for transient MCA and carotid terminus occlusion in 12 mongrel dogs and assessment of pial collateral recruitment. Outcome measures included 1- and 24-hour magnetic resonance imaging-based infarct volume calculation, a behavioral scale and histopathologic sections. RESULTS: MCAO succeeded in 8 of 12 dogs (67% efficiency). One-hour postreperfusion infarct volume predicted 24-hour postreperfusion infarct volume (r = 0.997, P < 0.0001). Pial collateral recruitment varied with time and reproducibly assessed predicted infarct volume on 1-hour postreperfusion mean diffusivity maps (P < 0.0001; r = 0.946) and 24-hour fluid-attenuated inversion recovery FLAIR magnetic resonance imaging (P = 0.0033; r = 0.961). The canine stroke scale score correlated with infarct volumes and pial collateral score. CONCLUSION: This canine MCAO model produces defined cerebral infarct lesions whose volumes correlate with leptomeningeal collateral formation and canine behavior.

Qureshi grading scheme predicts subsequent volume of brain infarction following intra-arterial thrombolysis in patients with acute anterior circulation ischemic stroke.

BACKGROUND: The importance of the site of occlusion and the presence or absence of collaterals on initial angiography in patients with acute ischemic stroke has been recognized. Qureshi recently proposed a scheme that categorizes patients with ischemic stroke based on findings observed on initial angiography. METHODS: We determined the relationship between severity of angiographic occlusion using Qureshi grading scheme and volume of brain infarction on follow-up computed tomography in 55 patients with anterior circulation ischemic stroke who underwent intra-arterial thrombolysis. RESULTS: A strong association was observed between Qureshi grades and volume of brain infarction (F ratio 6.2, P= .0005) after adjusting for patients' age, sex, National Institutes of Health Stroke Scale (NIHSS) score, thrombolytic used, and time interval between symptom onset and angiography. The relationship persisted after further adjustment for final angiographic recanalization (F ratio 5.1, P= .001). A significant relationship between initial grades and volume of brain infarction was separately observed in both patients with or without recanalization following treatment. CONCLUSIONS: Qureshi grading scheme can be effectively used to stratify patients with anterior circulation ischemic stroke undergoing intra-arterial thrombolysis using initial angiographic findings.

Effect of propranolol on naming in chronic Broca's aphasia with anomia.

Previous research suggests that the noradrenergic system modulates flexibility of access to the lexical-semantic network, with propranolol benefiting normal subjects in lexical-semantic problem solving tasks. Patients with Broca's aphasia with anomia have impaired ability to access appropriate verbal output for a given visual stimulus in a naming task. Therefore, we tested naming in a pilot study of chronic Broca's aphasia patients with anomia after propranolol and after placebo in a double-blinded crossover manner. Naming was better after propranolol than after placebo, suggesting a potential benefit from propranolol in chronic Broca's aphasia with anomia. Larger follow-up studies are necessary to further investigate this effect.

Clinical predictors of cerebrovascular occlusion for patients presenting with acute stroke.

OBJECTIVE: We sought to determine clinical predictors of vascular occlusion in patients with stroke. METHODS: From November 1994 to December 1999, 88 patients who were thrombolytic candidates and seen within 6 hours of stroke symptom onset had cerebral angiography. The Oxford Community Stroke Project clinical classification system, admission National Institutes of Health Stroke Scale score, and time from symptom onset until angiography were used to predict vascular occlusion. RESULTS: In all, 79% of patients with total anterior circulation infarctions and 73% with partial anterior circulation infarctions had vascular occlusions, whereas only 29% with lacunar infarcts had occlusion. Strokes were more severe in patients with occlusion than in those without occlusion. Time to angiography was also associated with vascular occlusion. CONCLUSIONS: Clinical classification of stroke, stroke scales, and time to angiography are useful screening tools to predict cerebral occlusion in acute stroke patients.

Intra-arterial thrombolysis of a distal internal carotid artery occlusion in an adolescent.

INTRODUCTION: This article describes the first reported case of an adolescent being treated with intra-arterial urokinase for a distal internal carotid artery occlusion. METHODS: A 15-year-old male presenting with an acute ischemic stroke caused by a distal internal carotid artery occlusion was treated with intra-arterial urokinase at 5 hours and 45 minutes after symptom onset. RESULTS: The artery completely recanalized, and the patient improved significantly from an admission National Institutes of Health Stroke Scale (NIHSS) score of 28 to a NIHSS score of 8 at a 2.5-month follow-up, despite an asymptomatic intraparenchymal hemorrhage. CONCLUSION: This article reviews the only two reported cases of intravenous thrombolysis and three cases of intra-arterial thrombolysis in children with ischemic stroke and suggests that thrombolytic therapy should be considered a treatment option in selected pediatric patients with stroke, especially in adolescents who are generally treated as young adults.

Angiographic assessment of pial collaterals as a prognostic indicator following intra-arterial thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: This study examines whether anatomic extent of pial collateral formation documented on angiography during acute thromboembolic stroke predicts clinical outcome and infarct volume following intra-arterial thrombolysis, compared with other predictive factors. METHODS: Angiograms, CT scans, and clinical information were retrospectively reviewed in 65 consecutive patients who underwent thrombolysis for acute ischemic stroke. Clinical data included age, sex, time to treatment, National Institutes of Health Stroke Scale (NIHSS) score on presentation of symptoms, NIHSS score at the time of hospital discharge, and modified Rankin scale score at time of hospital discharge. Site of occlusion, scoring of anatomic extent of pial collaterals before thrombolysis, and recanalization (complete, partial, or no recanalization) were determined on angiography. Infarct volume was measured on CT scans performed 24-48 hours after treatment. RESULTS: Fifty-three patients (82%) qualified for review. Both infarct volume and discharge modified Rankin scale scores were significantly lower for patients with better pial collateral scores than those with worse pial collateral scores, regardless of whether they had complete (P < .0001) or partial (P = .0095) recanalization. Adjusting for other factors, regression analysis models indicate that the infarct volume was significantly larger (P < .0001) and modified discharge Rankin scale score and discharge NIHSS score significantly higher for patients with worse pial collateral scores. Similarly, adjusting for other factors, the infarct volume was significantly lower (P = .0006) for patients with complete recanalization than patients with partial or no recanalization. CONCLUSIONS: Evaluation of pial collateral formation before thrombolytic treatment can predict infarct volume and clinical outcome for patients with acute stroke undergoing thrombolysis independent of other predictive factors. Thrombolytic treatment appears to have a greater clinical impact in those patients with better pial collateral formation.

Clinical and imaging outcomes after stroke with normal angiograms.

BACKGROUND AND PURPOSE: Information about the prognosis of patients with acute ischemic stroke and normal angiography is limited. We report clinical and imaging outcomes of patients seen within 6 hours of symptom onset who were considered candidates for thrombolysis. METHODS: Between November 1994 and December 1999, patients with stroke onset of less than 6 hours who were thrombolytic candidates underwent cerebral angiography. Patients with normal angiograms (defined as no sign of occlusive disease in the head or neck in the symptomatic artery) were included. Admission National Institutes of Health Stroke Scale (NIHSS) scores and discharge modified Rankin scores (mRS) were obtained. CT or MR images were obtained 24 hours or longer after symptom onset. Good outcome was defined as an mRS score < or =2. For analysis, follow-up CT or MR imaging findings were classified as showing cortical infarct, subcortical infarct > or =1.5 cm, subcortical infarct < or =1.5 cm, or no new infarct. The mechanism of the normal angiogram was assumed on the basis of these results. RESULTS: Twenty-one patients with stroke had normal angiograms. About 43% (9/21) of the patients had a favorable hospital discharge clinical outcome, and an additional 33% (7/21) had favorable clinical outcomes at subsequent follow-up. New infarct on follow-up imaging was seen in 71% (15/21). Discharge mRS scores were not correlated with admission NIHSS scores or the mechanism of the normal angiogram. CONCLUSION: Approximately 76% of acute stroke patients with normal angiograms have a favorable clinical outcome, and 71% have associated new infarctions. Given these outcomes, further study is needed before recommendations regarding thrombolytic treatment can be made in this population.

Intraarterial thrombolytic therapy within 3 hours of the onset of stroke.

OBJECTIVE: The National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study Group showed that recombinant tissue plasminogen activator (rt-PA) administered intravenously within 3 hours of the onset of ischemic stroke can improve clinical outcome. Intraarterial (IA) thrombolysis has been shown to offer advantages over intravenous (IV) thrombolysis, but experience with this type of therapy within 3 hours of the onset of symptoms has not been reported previously. This study is the first retrospective analysis of a two-institution experience with IA thrombolysis within 3 hours of stroke onset. METHODS: A total of 36 patients with angiographically demonstrated occlusions were treated with urokinase or rt-PA within 3 hours of stroke onset. Outcome measures included the percentage of patients with no or minimal neurological disability at 30 to 90 days as measured by the modified Rankin Scale, percentage recanalization, incidence of symptomatic intracranial hemorrhage, and mortality rate. The results were compared with those of the NINDS rt-PA study. RESULTS: The median admission National Institutes of Health Stroke Scale score was 14. Fifty percent of treated patients had a modified Rankin Scale score of 0 or 1 indicating no or little disability at 1 to 3 months compared with 39% of treated patients in the NINDS trial. Recanalization was 75%, symptomatic intracranial hemorrhage was 11% (versus 6.4% with IV rt-PA in the NINDS trial), and the mortality rate was 22% (versus 17% with IV rt-PA in the NINDS trial). CONCLUSION: The results suggest that IA thrombolysis administered within 3 hours of stroke onset is a feasible and viable alternative to IV rt-PA on the basis of improved clinical outcomes, high recanalization percentage, and comparable mortality rate and despite increased symptomatic intracranial hemorrhage. Whether IA thrombolysis is superior to IV therapy awaits further study.