Transient ischemic attacks characterized by RNA profiles in blood.

OBJECTIVE: Transient ischemic attacks (TIA) are common. Though systemic inflammation and thrombosis are associated with TIA, further study may provide insight into TIA pathophysiology and possibly lead to the development of treatments specifically targeted to TIA. We sought to determine whether gene expression profiles in blood could better characterize the proinflammatory and procoagulant states in TIA patients. METHODS: RNA expression in blood of TIA patients (n = 26) was compared to vascular risk factor control subjects without symptomatic cardiovascular disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially expressed genes in TIA were identified by analysis of covariance and evaluated with cross-validation and functional analyses. RESULTS: Patients with TIA had different patterns of gene expression compared to controls. There were 480 probe sets, corresponding to 449 genes, differentially expressed between TIA and controls (false discovery rate correction for multiple comparisons, p ≤ 0.05, absolute fold change ≥1.2). These genes were associated with systemic inflammation, platelet activation, and prothrombin activation. Hierarchical cluster analysis of the identified genes suggested the presence of 2 patterns of RNA expression in patients with TIA. Prediction analysis identified a set of 34 genes that discriminated TIA from controls with 100% sensitivity and 100% specificity. CONCLUSION: Patients with recent TIA have differences of gene expression in blood compared to controls. The 2 gene expression profiles associated with TIA suggests heterogeneous responses between subjects with TIA that may provide insight into cause, risk of stroke, and other TIA pathophysiology.

Predictors of fatal brain edema in massive hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. METHODS: This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. RESULTS: Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, P=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, P<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/microL, 95% CI 1.01 to 1.14, P=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, P<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, P=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. CONCLUSIONS: Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.

Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study.

CONTEXT: Tissue-type plasminogen activator (tPA) is the only therapy for acute ischemic stroke approved by the Food and Drug Administration. OBJECTIVE: To assess the safety profile and to document clinical outcomes and adverse events in patients treated with intravenous tPA for acute stroke in clinical practice. DESIGN AND SETTING: Prospective, multicenter study of consecutive patients enrolled between February 1997 and December 1998 at 57 medical centers in the United States (24 academic and 33 community). INTERVENTION: Intravenous tPA (recombinant alteplase). PATIENTS: Three hundred eighty-nine patients with a mean age of 69 years (range, 28-100 years); 55% were men. MAIN OUTCOME MEASURES: Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan results, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days. RESULTS: Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score was 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Rankin score, 0-2). Thirteen patients (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 who died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrhage within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hours of tPA administration in 9.3%, and tPA administration despite systolic blood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found predictors of favorable outcome to be a less severe baseline National Institutes of Health Stroke Scale score, absence of specific abnormalities (effacement or hypodensity of >33% of the middle cerebral artery territory or a hyperdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseline. CONCLUSIONS: This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older : the tPA stroke survey experience.

BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator (tPA) administered within 3 hours of symptom onset is the first available effective therapy for acute ischemic stroke (AIS). Few data exist, however, on its use in very elderly patients. We examined the characteristics, complications, and short-term outcome of AIS patients aged >/=80 years treated with tPA. METHODS: Patients aged >/=80 years (n=30) were compared with counterparts aged <80 years (n=159) included in the tPA Stroke Survey, a US retrospective survey of 189 consecutive AIS patients treated with intravenous tPA at 13 hospitals. RESULTS: Risk of intracerebral hemorrhage (fatal, symptomatic, and total) was 3%, 3%, and 7% in the elderly age group and 2%, 6%, and 9%, respectively, in their younger counterparts (P=NS for all comparisons). Likelihood of favorable outcome, defined as modified Rankin score 0 to 1, National Institutes of Health Stroke Scale score /=80 years was identified.

Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group.

We assessed initial clinical experience with IV tissue plasminogen activator (t-PA) treatment of acute ischemic stroke in a standardized retrospective survey of hospitals with experienced acute stroke treatment systems. The incidence of symptomatic intracerebral hemorrhage (ICH) was 6% (11 of 189 patients; 95% CI 3 to 11%), similar to that in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Deviations from the NINDS protocol guidelines were identified in 30% of patients (56 of 189). The incidence of symptomatic ICH was 11% among patients with protocol deviations as compared with 4% in patients who were treated according to the NINDS protocol guidelines, suggesting that strict adherence to protocol guidelines is prudent.

Cerebrovascular ischemic events with high positive anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The aim of our study was to characterize the patient profile and prognostic value associated with high positive IgG (>100 GPL) anticardiolipin antibodies (aCL). METHODS: We studied the clinical, laboratory, radiological, and prospective historical features of ischemic cerebrovascular disease in patients with >100 GPL titers. From our neurology department, 27 consecutive patients were prospectively identified and followed up (mean follow-up time, 34 months). RESULTS: The mean age of our cohort was 41 years. Lupuslike illness occurred in 3; 23 had primary antiphospholipid syndrome, including 3 who met criteria for Sneddon's syndrome; 1 patient had progressive systemic sclerosis. Cerebral infarcts occurred in 74% and were recurrent in 37%. Systemic ischemic events, most commonly deep vein thrombosis, occurred in 37%. Tobacco use was documented in 85%, hyperlipidemia in 74%, hypertension in 44%, and diabetes mellitus in 7% of patients. A prominent headache history was present in 67%. Lupus anticoagulant (LA) was present in 72%, approximately one half had positive antinuclear antibodies and thrombocytopenia, and one quarter had a false-positive VDRL. We compared mean GPL levels in patients testing positive for specific laboratory features of antiphospholipid syndrome with those testing negative for these parameters. Only the LA(+) group had a significantly higher mean GPL than the LA(-) group (P=0.006). Brain imaging showed nonlacunar infarcts in 73% and lacunes in 12%. Of 19 cerebral angiograms, 5 (26%) showed large-vessel occlusive disease and 6 (32%) branch obstruction. Echocardiograms were abnormal in 75%: thickened left-sided valves in 33% and vegetations in 12%. Recurrent cerebrovascular ischemic events were observed in 96%, with transient events (mean rate, 25%/y) occurring 5 times more frequently than strokes (mean rate, 5%/y). Using a standardized disability scale blinded to aCL titer, neurological impairment was severe in 7%, moderate in 30%, and mild or nonexistent in 63%, and unrelated to mean GPL value (P=0.567). Titers fluctuated greatly for individual patients, and most did not consistently test as highly positive. An analysis of fluctuation in symptom severity with concurrent GPL values did not show a statistically significant correlation. Compared with historical controls having a wide range of positive titers, the presence of high IgG aCL titers did not confer a worse prognosis for disability and recurrent ischemic events. CONCLUSIONS: Our data suggest that cerebrovascular events associated with high positive GPL are frequently multiple and minor (with no disability-titer correlation), present in relatively young patients, and often associated with tobacco abuse, hyperlipidemia, LA, systemic ischemic events, and occult cardiac disease.

Magnetic resonance angiography in vertebrobasilar ischemia. Preliminary experience.

Forty-five patients were evaluated for vertebrobasilar ischemic disease by magnetic resonance imaging and magnetic resonance angiography (MRA). Ten also underwent intraarterial digital subtraction angiography. All were sorted into three groups based on results of the MRA and their clinical presentation. In the first group, vertebrobasilar ischemic disease could be reasonably excluded. In the second, such disease was nearly certain. In the third group, the vertebrobasilar system could not readily be assessed by the MRA alone and often required further studies. In 8 of 10 patients a strong correlation was found between MRA and intraarterial digital subtraction angiography. MRA provided valuable information for assessing vertebrobasilar disease and, in many instances, eliminated the need for invasive angiography.