Brett L. Cucchiara

Use of statins in CNS disorders

It is well established that 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cholesterol levels and prevent coronary heart disease (CHD). Although a causal relation between elevated cholesterol levels and stroke has not been well defined, a number of large secondary prevention studies and meta-analyses have shown that statin therapy reduces stroke in patients with CHD and hypercholesterolemia. In addition to the vascular effects of statins (stabilization of atherosclerotic plaques, decreased carotid intimal-medial thickness), there are increasing data to suggest that these agents have additional properties that are potentially neuroprotective. These include endothelial protection via actions on the nitric oxide synthase system, as well as antioxidant, anti-inflammatory and anti-platelet effects. These actions of statins might have potential uses in other neurological disorders such as Alzheimers disease and certain types of brain tumors.

Who will participate in acute stroke trials

Background: Despite the high incidence of acute stroke, only a minority of patients are enrolled in acute stroke treatment trials. We aimed to identify factors associated with participation in clinical trials of novel therapeutic agents for acute stroke. Methods: Prospective survey of patients with acute stroke <72 hours from onset. A structured interview was administered to the patient or primary decision-maker. If offered participation in an actual acute treatment trial, questions focused on decisions about that trial; otherwise a similar mock trial was proposed. The primary outcome was whether the subject agreed to participate in the proposed trial. Results: A total of 200 subjects (47% patients, 53% proxies) completed the survey: mean age 63 ± 14 years, 47% women, 44% white, 50% black. A real acute trial was offered to 22%; others were offered a mock trial. Overall, 57% (95% confidence interval: 50%–64%) of respondents stated they would participate in the proposed acute treatment trial. There were no differences with respect to age, sex, race, educational level, self-assessed stroke severity or stroke type, vascular risk factors, or comorbidities. Misconceptions about key research concepts were found in 50% but did not impact participation. Participation was associated with the perceived risk of the proposed trial intervention (p < 0.001), prior general attitudes about research (p < 0.001), and influences attributed to family, religion, and other personal beliefs (p < 0.001). Patients were more likely to participate than proxy decision-makers (p = 0.04). Conclusions: Demographic factors, clinical factors, and prior knowledge about research have little impact on the decision to participate in acute stroke clinical trials. Preexisting negative attitudes and external influences about research strongly inhibit participation. Patients are more inclined to participate than their proxy decision-makers.

Anti-Adrenergic Medications and Edema Development after Intracerebral Hemorrhage

BackgroundUse of antihypertensive medications is common after intracerebral hemorrhage (ICH). Medications that block adrenergic activation (e.g., beta-blockers and the alpha(2)-agonist, clonidine) may reduce the inflammatory response and therefore have secondary benefit after ICH.MethodsThe patients with acute ICH enrolled in the placebo arm of the CHANT trial were included. Univariate and multivariate analyses were undertaken for factors associated with blood pressure medication use, edema at 72xa0h, and clinical outcome at 90xa0days.ResultsOf the 303 patients, 87.8% received some antihypertensive treatment during the first 72xa0h of hospitalization. Edema volume on neuroimaging at 72xa0h was independently associated with clinical outcome. Use of anti-adrenergic medications was associated with less edema after controlling for hemorrhage volume and blood pressure.ConclusionsAntihypertensive medications that antagonize the sympathetic nervous system may reduce perihematomal edema after ICH.

Dosing Errors Did Not Have a Major Impact on Outcome in the NINDS t-PA Stroke Study

Intravenous tissue plasminogen activator (IV t-PA) for acute stroke is dosed by weight, which is typically estimated, and requires a multistep infusion, which may lead to administration errors. We evaluated the impact of dosing errors on outcome in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Using logistic regression, we investigated the relationship between actual weight-based dose (administered dose divided by actual weight, capped at 100 kg) and intracerebral hemorrhage (ICH) at 36 hours and likelihood of good recovery (modified Rankin score of 0 or 1) at 3 months. Estimated weight, actual weight, and total t-PA dose administered were available for 311 of 312 patients; 3 received only the bolus and were excluded. In multivariable logistic regression, there was no association between the risk of any ICH using actual dose as a continuous variable (P = .65), or when comparing the highest quintile of actual dose (>0.944 mg/kg) to the lower 4 quintiles (9.8% vs 10.9%; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.22-1.61; P = .31), adjusting for age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and changes on baseline computed tomography. Similarly, there was no association between likelihood of good outcome and actual dose as a continuous variable (Pxa0=xa0.87), or when comparing the lowest quintile (<0.879 mg/kg) of actual dose to the 4 higher quintiles (44.3% vs 42.5%; OR, 1.08; 95% CI, 0.55-2.09; P = .83), adjusting for age, baseline NIHSS score, and time of onset to treatment. Our findings indicate that it is reasonable to estimate weight when administering IV t-PA for acute stroke, because dosing errors did not have a major impact on the risk of ICH or the likelihood of good outcome in the NINDS t-PA Stroke Study.

Safety of Thrombolytic Therapy for Acute Ischemic Stroke after Recent Transient Ischemic Attack

BACKGROUNDnThe 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).nnnMETHODSnThis 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnThe rate of SICH in our cohort appears similar to overall postthrombolysis hemorrhage rates.

Internal carotid artery “spring sign”

A 62-year-old woman had a minor left hemispheric ischemic stroke due to atherosclerotic complete occlusion of the left internal carotid artery (ICA), shown by ultrasound and MR angiography (MRA). She was treated with warfarin for several months, followed by antiplatelet therapy. MRA obtained 1 year later revealed that the ICA had partially recanalized …

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.

Chapter 14 Antithrombotic Therapy for Acute Ischemic Stroke

Publisher Summary This chapter discusses antithrombotic therapy for acute ischemic stroke. The various available antithrombotic therapies target different steps in the coagulation pathway, and this heterogeneity of mechanism of action may have implications for their effectiveness at achieving the goals and their risk of causing untoward side effects, primarily bleeding. Available antithrombotic agents with potential use in acute ischemic stroke include oral antiplatelet agents, glycoprotein IIb/IIIa (GIIb/IIIa) inhibitors, heparins, heparinoids, and direct thrombin inhibitors. Aspirin is an oral antiplatelet agents that irreversibly inhibits cyclooxygenase, thus blocking production of thromboxane A 2 , an important promoter of platelet activation. The antiplatelet effect of aspirin occurs within an hour of oral administration, and being irreversible, persists for the entire platelet life span. GIIb/IIIa inhibitors function as antiplatelet agents by binding directly to the GIIb/IIIa receptor on the platelet membrane, blocking fibrinogen-platelet binding and platelet aggregation. In contrast to aspirin, GIIb/IIIa inhibitors not only decrease platelet aggregation, but also reduce the rate of tissue factor initiated thrombin generation in vitro .