Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.

BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

Reversible cerebral vasoconstriction syndrome: a review of recent research.

Reversible cerebral vasoconstriction syndrome (RCVS) is a collective term used for transient noninflammatory, nonatherosclerotic segmental constriction of cerebral arteries. The angiopathies of RCVS have previously been defined by several nomenclatures. Current opinion favors the unification of these pathophysiologically related angiopathies because of their similar angiographic features and clinical course. RCVS typically presents acutely as headache, delirium, seizure, cerebral ischemia, and/or hemorrhage. The angiographic features make RCVS an important mimic of CNS vasculitides. In contrast to CNS vasculitis, RCVS is typically a transient condition with relatively good clinical outcomes. Although a complete understanding of the etiological and pathological features of RCVS has not yet been achieved, alterations in vascular tone lead to the observed arterial changes. In this review, we aim to provide a summary of RCVS and provide insight into current perspectives of the underlying pathophysiological processes, diagnosis, and treatment.

Hospital prenotification of stroke patients by emergency medical services improves stroke time targets.

BACKGROUND: Prenotification to hospitals by emergency medical services of patients with suspected stroke is recommended to reduce delays in time-dependent therapies. We hypothesized that hospital prenotification would reduce recommended stroke time targets. METHODS: We used the Robert Wood Johnson University Hospital (RWJUH) Brain Attack Database, which includes demographic and clinical data on all emergency department (ED) patients alerted as a Brain Attack between January 1, 2009 and June 30, 2010. Outcome variables included the time from door to stroke team arrival, computed tomographic (CT) scan completion, CT scan interpretation, electrocardiogram, laboratory results, treatment decision, and intravenous (IV) tissue plasminogen activator (tPA) administration. The primary independent variable was brain attack activation before arrival to the emergency department (ED; prenotification) versus on or after ED arrival (no prenotification). Analysis of covariance was used with patient predictors as covariates in addition to the one of interest (prenotification vs no prenotification). P ≤ .05 was considered statistically significant. RESULTS: There were 229 patients (114 prenotification and 115 no prenotification) alerted as having a brain attack within the study period. Patients with prehospital notification were older (69.5 years vs 61.5 years; P = .0002), had more severe strokes (National Institutes of Health Stroke Scale score of 11.1 vs 6.9; P < .0001), and received IV tPA twice as often (27% vs 15%; P = .024). Prenotification resulted in a significant reduction in all stroke time targets except door to treatment decision and tPA administration. CONCLUSIONS: Prehospital notification of suspected stroke patients reduces time to stroke team arrival, CT scan completion, and CT scan interpretation. IV thrombolysis occurred twice as often in the prenotification group.

Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials.

BACKGROUND AND PURPOSE: Statin therapy decreases the risk of ischemic stroke. An increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue, we performed a meta-analysis of randomized controlled trials using statins that reported ICH. METHODS: We performed a literature search of Medline, Web of Science, and The Cochrane Library through January 25, 2012, and identified additional randomized controlled trials by reviewing reference lists of retrieved studies and prior meta-analyses. All randomized controlled trials of statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. Thirty-one randomized controlled trials were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. RESULTS: A total of 91,588 subjects were included in the active group and 91,215 in the control group. There was no significant difference in incidence of ICH observed in the active treatment group versus control (OR, 1.08; 95% CI, 0.88-1.32; P=0.47). ICH risk was not related to the degree of low-density lipoprotein reduction or achieved low-density lipoprotein cholesterol. Total stroke (OR, 0.84; 95% CI, 0.78-0.91; P<0.0001) and all-cause mortality (OR, 0.92; CI, 0.87-0.96; P=0.0007) were significantly reduced in the active therapy group. There was no evidence of publication bias. CONCLUSIONS: Active statin therapy was not associated with significant increase in ICH in this meta-analysis of 31 randomized controlled trials of statin therapy. A significant reduction in all stroke and all-cause mortality was observed with statin therapy.

Safety of thrombolytic therapy for acute ischemic stroke after recent transient ischemic attack.

BACKGROUND: The objective of this study was to assess the rate of symptomatic intracerebral hemorrhage (SICH) in patients given thrombolytic therapy for acute ischemic stroke (AIS) after recent transient ischemic attack (TIA). METHODS: This was a multicenter study of patients with confirmed TIA within 7 days before an AIS that was treated with intravenous (IV), intra-arterial (IA), or mechanical thrombolysis. A total of 23 cases were identified. RESULTS: The median time interval between index TIA and AIS was 9 hours. The median National Institutes of Health Stroke Scale score at the time of AIS was 12. The median time interval between stroke onset and thrombolytic treatment was 90 minutes. Thrombolytic therapies included IV thrombolysis (70%), IA thrombolysis (17%), IA and mechanical thrombolysis (9%), and IV followed by IA and mechanical thrombolysis (4%). The rate of postthrombolysis SICH in this group was 8.6% (2/23). CONCLUSIONS: The rate of SICH in our cohort appears similar to overall postthrombolysis hemorrhage rates.

Noninflammatory cerebral vasculopathy associated with recurrent ischemic strokes.

Recurrent ischemic strokes often have uncommon causes in young adults. Vascular abnormalities may be considered as a possible etiology. We report a 36-year-old man who experienced recurrent cryptogenic ischemic strokes despite medical therapy. Conventional cerebral angiography was unrevealing. Subsequent brain biopsy revealed a distinctive histopathological pattern of abnormal perivascular collagen deposition without inflammation. Recurrent cryptogenic strokes may have novel etiologies, and brain biopsy should be considered when standard diagnostic tests fail.

Comprehensive stroke centers overcome the weekend versus weekday gap in stroke treatment and mortality.

BACKGROUND AND PURPOSE: Hospital staffing may be reduced on weekends. Prior studies of weekend disparities in stroke care have focused on in-hospital mortality with variable results. We hypothesized that 90-day mortality was higher in patients with stroke hospitalized on weekends versus weekdays, and this difference has been minimized over time by improvements in organization and delivery of stroke care. METHODS: We used the Myocardial Infarction Data Acquisition System administrative database, which includes data on patients discharged with a primary diagnosis of cerebral infarction from all nonfederal acute care hospitals in New Jersey between 1996 and 2007. Out-of-hospital deaths were assessed by matching MIDAS records with New Jersey death registration files. New Jersey hospitals are designated by the state as comprehensive stroke centers, primary stroke centers, or nonstroke centers. The primary outcome measure was 90-day all-cause mortality after hospital admission. RESULTS: A total of 134 441 patients were admitted with a primary diagnosis of cerebral infarction during the study period. A total of 23.4% were admitted to a comprehensive stroke center, 51.5% to a primary stroke center, and 25.1% to a nonstroke center. Ninety-day mortality was greater in patients with stroke admitted on weekends compared with weekdays (17.2% versus 16.5%; P=0.002). The adjusted risk of death at 90 days was significantly greater for weekend admission (hazard ratio, 1.05; 95% CI, 1.02 to 1.09). No difference in 90-day mortality was observed for patients admitted to comprehensive stroke centers on weekends versus weekdays (hazard ratio, 1.01; 95% CI, 0.95 to 1.08). CONCLUSIONS: Patients with stroke admitted on weekends to New Jersey hospitals had a significantly higher risk of death by 90 days. No such difference in mortality was observed at comprehensive stroke centers.

De novo formation of large arteriovenous shunting and a vascular nidus mimicking an arteriovenous malformation within an anaplastic oligodendroglioma: treatment with embolization and resection.

The authors report the de novo occurrence and treatment of an arteriovenous lesion within an anaplastic oligodendroglioma in a patient with previously unremarkable brain imaging. Intracranial arteriovenous malformations (AVMs) are believed to be congenitally acquired lesions, and their association with brain neoplasms is extremely rare. Diagnostic imaging revealed a mass lesion with large arteriovenous shunts and a vascular nidus mimicking a true AVM. Histological and immunohistochemical testing showed an anaplastic oligodendroglioma mixed with an AVM. The clinical, radiological, and operative data are reviewed, as are the histopathological findings. To the authors' knowledge this is the first case of de novo occurrence of an arteriovenous lesion with large shunts and a vascular nidus within an anaplastic oligodendroglioma.

Frequency of Stroke After Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting (from an Eleven-Year Statewide Analysis).

We compared stroke rates associated with coronary artery bypass grafting (CABG), both on-pump and off-pump, and percutaneous coronary intervention (PCI) with both drug-eluting stent (DES) and bare-metal stent (BMS) and the impact on 30-day and 1-year all-cause mortality. The Myocardial Infarction Data Acquisition System database was used to study patients who had on-pump CABG (n = 47,254), off-pump CABG (n = 19,118), and PCI with BMS (n = 46,641), and DES (n = 115,942) in New Jersey from 2002 to 2012. Multiple logistic and Cox proportional hazard models were used to compare the risk of stroke and mortality. Adjustments were made for demographics, year of hospitalization, and co-morbidities. The rate of postprocedural stroke was lowest with DES (0.5%), followed by BMS (0.6%), off-pump CABG (1.3%), and on-pump CABG (1.8%). After adjustment, on-pump CABG had a higher risk of stroke compared with off-pump (odds ratio 1.36, 95% CI 1.18 to 1.56, p <0.0001). DES had lower risk of stroke compared with off-pump CABG (odds ratio 0.64, 95% CI 0.55 to 0.74, p <0.0001). There was a significant excess risk of 1-year mortality due to the interaction between stroke and procedure type (on-pump vs off-pump CABG and PCI with DES vs BMS; p value for interaction = 0.02). In conclusion, in this retrospective analysis of nonrandomized data from a statewide database, PCI with DES was associated with the lowest rate of postprocedural stroke, and off-pump CABG had a lower rate of postprocedural stroke than on-pump CABG; there was an excess 1-year mortality risk with on-pump versus off-pump CABG and with DES versus BMS in patients with stroke.

Successful emergent angioplasty of neurosarcoid vasculitis presenting with strokes.

BACKGROUND: Sarcoidosis is a systemic disease with neurologic involvement in approximately 5% of cases. Ischemic events related to neurosarcoid vasculitis are rare. We report the successful treatment of symptomatic neurosarcoid vasculitis with angioplasty. CASE DESCRIPTION: A 41-year-old African American with a diagnosis of neurosarcoid presented with aphasia and right-sided weakness. He was treated medically with antiplatelet agents, heparinization, and hypertensive therapy. Despite this treatment, he experienced clinical worsening and radiographic extension of his infarcts. He underwent successful angioplasty of a severe focal stenosis of the left middle cerebral artery. After the procedure, he experienced marked improvement in his symptoms and at follow-up continues to improve. CONCLUSIONS: We report the angiographic demonstration of neurosarcoidosis with large vessel changes and resultant strokes and its successful treatment with balloon angioplasty.

Comprehensive stroke centers may be associated with improved survival in hemorrhagic stroke.

BACKGROUND: Comprehensive stroke centers (CSCs) provide a full spectrum of neurological and neurosurgical services to treat complex stroke patients. CSCs have been shown to improve clinical outcomes and mitigate disparities in ischemic stroke patients. It is believed that CSCs also improve outcomes in hemorrhagic stroke. METHODS AND RESULTS: We used the Myocardial Infarction Data Acquisition System (MIDAS) database, which includes data on patients discharged with a primary diagnosis of intracerebral hemorrhage (ICH; International Classification of Diseases, Ninth Revision [ICD-9] 431) and subarachnoid hemorrhage (SAH; ICD-9 430) from all nonfederal acute care hospitals in New Jersey (NJ) between 1996 and 2012. Out-of-hospital deaths were assessed by matching MIDAS records with NJ death registration files. The primary outcome variable was 90-day all-cause mortality. The primary independent variable was CSC versus primary stroke center (PSC) and nonstroke center (NSC) admission. Multivariate logistic models were used to measure the effects of available covariates. Overall, 36 981 patients were admitted with a primary diagnosis of ICH or SAH during the study period, of which 40% were admitted to a CSC. Patients admitted to CSCs were more likely to have neurosurgical or endovascular interventions than those admitted to a PSC/NSC (18.9% vs. 4.7%; P<0.0001). CSC admission was associated with lower adjusted 90-day mortality (35.0% vs. 40.3%; odds ratio, 0.93; 95% confidence interval, 0.89 to 0.97) for hemorrhagic stroke. This was particularly true for those admitted with SAH. CONCLUSIONS: Hemorrhagic stroke patients admitted to CSCs are more likely to receive neurosurgical and endovascular treatments and be alive at 90 days than patients admitted to other hospitals.

Internal carotid artery dissection heralded by an oculomotor nerve palsy: case report and literature review.

INTRODUCTION: Acute oculomotor nerve (CN III) palsies are commonly attributed to microvascular disease or compressive lesions and aneurysms, but may rarely be associated with ischemic large vessel disease. We report a case of an extracranial internal carotid artery (ICA) dissection heralded by CN III palsy with review of the relevant literature. CASE REPORT: A 24-year-old right-handed man presented with right-sided weakness preceded by vomiting 2 days earlier. The following day, the family noted his left eye to be deviated outward with enlarged pupil and droopy eyelid. On the day of admission, he had a fall owing to right-sided weakness. His neurological examination revealed significant aphasia, left third nerve palsy, right homonymous hemianopsia, and right-sided hemiplegia with hemisensory deficits. A brain magnetic resonance image showed an acute ischemic infarct in the left middle cerebral artery distribution without mass effect. Magnetic resonance angiogram showed a left extracranial internal cerebral artery (ICA) dissection with absence of flow within the distal cervical and intracranial ICA segments. He underwent a decompressive left hemicraniectomy with partial improvement in his deficits. DISCUSSION: Oculomotor nerve palsy as a result of ICA disease is a rare entity but has been reported in cases of stenosis, occlusion, and dissection. It is likely to be caused by hypoperfusion of CN III secondary to low flow or microembolism in the arteries feeding the nerve. The risk of CN III palsy in patients with ICA disease is higher in the presence of a fetal posterior cerebral artery. CONCLUSIONS: Acute oculomotor nerve palsies with pupillary involvement warrant thorough investigation. When routine work-up fails to elucidate an etiology, extracranial carotid pathology should be considered.

Intracranial vertebrobasilar artery dissection associated with postpartum angiopathy.

Background. Cervicocephalic arterial dissection (CCAD) is rare in the postpartum period. To our knowledge this is the first reported case of postpartum angiopathy (PPA) presenting with ischemic stroke due to intracranial arterial dissection. Case. A 41-year-old woman presented with blurred vision, headache, and generalized seizures 5 days after delivering twins. She was treated with magnesium for eclampsia. MRI identified multiple posterior circulation infarcts. Angiography identified a complex dissection extending from both intradural vertebral arteries, through the basilar artery, and into both posterior cerebral arteries. Multiple segments of arterial dilatation and narrowing consistent with PPA were present. Xenon enhanced CT (Xe-CT) showed reduced regional cerebral blood flow that is improved with elevation in blood pressure. Conclusion. Intracranial vertebrobasilar dissection causing stroke is a rare complication of pregnancy. Eclampsia and PPA may play a role in its pathogenesis. Blood pressure management may be tailored using quantitative blood flow studies, such as Xe-CT.