Showing papers on "Cerebral infarction published in 2007"
TL;DR: The data suggest that RCVS is more frequent than previously thought, is more often secondary particularly to vasoactive substances, and should be considered in patients with recurrent thunderclap headaches, cSAH or cryptogenic strokes with severe headaches.
Abstract: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by the association of severe headaches with or without additional neurological symptoms and a 'string and beads' appearance on cerebral arteries, which resolves spontaneously in 1-3 months. We present the clinical, neuroimaging and outcome data of 67 consecutive patients prospectively diagnosed over 3 years in our institution with an angiographically confirmed RCVS. There were 43 females and 24 males with a mean age of 42 years (19-70). RCVS was spontaneous in 37% of patients and secondary in the 63% others, to postpartum in 5 and to exposure to various vasoactive substances in 37, mainly cannabis, selective serotonin-recapture inhibitors and nasal decongestants. The main pattern of presentation (94% of patients) was multiple thunderclap headaches recurring over a mean period of 1 week. In 51 patients (76%), headaches resumed the clinical presentation. Various complications were observed, with different time courses. Cortical subarachnoid haemorrhage (cSAH) (22%), intracerebral haemorrhage (6%), seizures (3%) and reversible posterior leukoencephalopathy (9%) were early complications, occurring mainly within the first week. Ischaemic events, including TIAs (16%) and cerebral infarction (4%), occurred significantly later than haemorrhagic events, mainly during the second week. Significant sex differences were observed: women were older, had more frequent single-drug exposure and a higher rate of stroke and cSAH. Sixty-one patients were treated by nimodipine: 36% had recurrent headaches, 7% TIAs and one multiple infarcts. The different time courses of thunderclap headaches, vasoconstriction and strokes suggest that the responsible vasospastic disorder starts distally and progresses towards medium sized and large arteries. No relapse was observed during the 16 +/- 12.4 months of follow-up. Our data suggest that RCVS is more frequent than previously thought, is more often secondary particularly to vasoactive substances, and should be considered in patients with recurrent thunderclap headaches, cSAH or cryptogenic strokes with severe headaches.
859 citations
TL;DR: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms and the hypothesis that N XY-059 would reduce alteplase-related intracranial hemorrhages was tested.
Abstract: Background The free-radical–trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke–Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke We sought confirmation of efficacy in a second, larger trial Methods We enrolled 3306 patients with acute ischemic stroke in a randomized, double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days We examined scores on neurologic and activities-of-daily-living scales as secondary end points We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages Results The efficacy analysis was based on 3195 patients Prognostic factors were well balanced between the treatment groups Mortality was equal in the two groups, and adverse-event rates were similar The distribution of
694 citations
TL;DR: Various rodent animal models, pathogenic mechanisms, and promising therapeutic approaches of ischemic stroke are focused on.
Abstract: Ischemic stroke is a devastating disease with a complex pathophysiology. Animal modeling of ischemic stroke serves as an indispensable tool first to investigate mechanisms of ischemic cerebral injury, secondly to develop novel antiischemic regimens. Most of the stroke models are carried on rodents. Each model has its particular strengths and weaknesses. Mimicking all aspects of human stroke in one animal model is not possible since ischemic stroke is itself a very heterogeneous disorder. Experimental ischemic stroke models contribute to our understanding of the events occurring in ischemic and reperfused brain. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. Trials aimed to evaluate effectiveness of recombinant tissue-type plasminogen activator in longer time windows with finer selection of patients based on magnetic resonance imaging tools and trials of novel recanalization methods are ongoing. Despite the failure of most neuroprotective drugs during the last two decades, there are good chances to soon have effective neuroprotectives with the help of improved preclinical testing and clinical trial design. In this article, we focus on various rodent animal models, pathogenic mechanisms, and promising therapeutic approaches of ischemic stroke.
677 citations
TL;DR: Although most prognostic factors for outcome after SAH are present on admission and are not modifiable, a substantial contribution to outcome is made by factors developing after admission and which may be more easily influenced by treatment.
Abstract: Background and Purpose— The purpose of this study was to describe prognostic factors for outcome in a large series of patients undergoing neurosurgical clipping of aneurysms after subarachnoid hemorrhage (SAH). Methods— Data were analyzed from 3567 patients with aneurysmal SAH enrolled in 4 randomized clinical trials between 1991 and 1997. The primary outcome measure was the Glasgow outcome scale 3 months after SAH. Multivariable logistic regression with backwards selection and Cox proportional hazards regression models were derived to define independent predictors of unfavorable outcome. Results— In multivariable analysis, unfavorable outcome was associated with increasing age, worsening neurological grade, ruptured posterior circulation aneurysm, larger aneurysm size, more SAH on admission computed tomography, intracerebral hematoma or intraventricular hemorrhage, elevated systolic blood pressure on admission, and previous diagnosis of hypertension, myocardial infarction, liver disease, or SAH. Variables present during hospitalization associated with poor outcome were temperature >38°C 8 days after SAH, use of anticonvulsants, symptomatic vasospasm, and cerebral infarction. Use of prophylactic or therapeutic hypervolemia or prophylactic-induced hypertension were associated with a lower risk of unfavorable outcome. Time from admission to surgery was significant in some models. Factors that contributed most to variation in outcome, in descending order of importance, were cerebral infarction, neurological grade, age, temperature on day 8, intraventricular hemorrhage, vasospasm, SAH, intracerebral hematoma, and history of hypertension. Conclusions— Although most prognostic factors for outcome after SAH are present on admission and are not modifiable, a substantial contribution to outcome is made by factors developing after admission and which may be more easily influenced by treatment.
508 citations
TL;DR: The appearance of infection in patients with acute stroke obeys in part to immunological mechanisms triggered by acute brain injury, and it is likely that this immunological response represents an adaptive mechanism to brain ischemia.
Abstract: Background and Purpose— Infection after experimental focal ischemia may result from brain-induced immunodepression, but it is unsettled whether a similar syndrome occurs in human stroke. Summary of Review— Many patients develop infections shortly after acute stroke regardless of optimal management. Mortality is higher in these patients and the severity of stroke is the strongest determinant of the infectious risk. However, it is controversial whether infections promote neurological worsening or alternatively represent a marker of severe disease. The brain and the immune system are functionally linked through neural and humoral pathways, and decreased immune competence with higher incidence of infections has been demonstrated in several acute neurological conditions. In experimental brain ischemia, infections are associated with the activation of the autonomous nervous system and neuroendocrine pathways, which increase the strength of anti-inflammatory signals. A strong cytokine-mediated anti-inflammatory ...
350 citations
TL;DR: Screening consecutive patients with ischemic stroke with routine Holter monitoring will identify new atrial fibrillation/flutter in approximately one in 20 patients, although based on limited data, extended duration of monitoring may improve the detection rate.
Abstract: Background and Purpose— Identifying paroxysmal atrial fibrillation/flutter is an essential part of the etiological workup of patients with ischemic stroke. However, there is controversy in the literature regarding the use of noninvasive cardiac rhythm monitoring with previous reviews reporting a low detection rate with routine monitoring. We performed a systematic review to determine the frequency of occult atrial fibrillation/flutter detected by noninvasive methods of continuous cardiac monitoring after acute ischemic stroke or transient ischemic attack. Methods— Studies were identified from comprehensive searches of PubMed, EMBASE, Science Citation Index, and bibliographies of relevant articles. Only English language articles were included. Randomized controlled trials and prospective cohort studies of consecutive patients with acute ischemic stroke that fulfilled predefined criteria were eligible. Two authors conducted searches and abstracted data from eligible studies independently. Results— Sixty stu...
334 citations
TL;DR: Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke, and among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.
Abstract: OBJECTIVE. Few data exist regarding rates and predictors of recurrence after childhood arterial ischemic stroke. We sought to establish such rates within a large, multiethnic population and determine whether clinical vascular imaging predicts recurrence. PATIENTS AND METHODS. In a population-based cohort study, we collected data on all documented cases of arterial ischemic stroke among 2.3 million children ( RESULTS. Among 181 incident childhood stroke cases (84 perinatal; 97 later childhood), there were 16 recurrent strokes (1 after a perinatal stroke) at a median of 2.7 months. The 5-year cumulative recurrence rates were 1.2% after perinatal stroke and 19% after later childhood stroke. Of the 97 children with later childhood strokes, 52 received cerebrovascular imaging, predominantly magnetic resonance angiography (n = 36) and conventional angiography (n = 26). Although there were no recurrences among children with normal vascular imaging, children with a vascular abnormality had a 5-year cumulative recurrence rate of 66%. CONCLUSIONS. Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke. Among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.
333 citations
TL;DR: Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort and the independent role of ASA needs further assessment in appositely designed and powered studies.
326 citations
TL;DR: Statin withdrawal is associated with increased risk of death or dependency at 90 days and should be continued in the acute phase of ischemic stroke, and patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up.
Abstract: Background: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients. Methods: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126). Results: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p p = 0.002) compared with the non–statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)–fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)–fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p p = 0.048). Conclusion: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.
317 citations
TL;DR: PMVA was associated with an increased risk of stroke, particularly among women without other medical conditions associated with stroke, and Behavioral risk factors, specifically smoking and oral contraceptive use, markedly increased the risk of PMVA, as did recent onset ofPMVA.
Abstract: Background and Purpose—Migraine with aura is associated with ischemic stroke, but few studies have investigated the clinical and anatomic features of this association. We assessed the association of probable migraine with and without visual aura with ischemic stroke within subgroups defined by stroke subtype, vascular territory, probable migraine characteristics, and other clinical features. Methods—Using data from a population-based, case-control study, we studied 386 women ages 15 to 49 years with first ischemic stroke and 614 age- and ethnicity-matched controls. Based on their responses to a questionnaire on headache symptoms, subjects were classified as having no migraine, probable migraine without visual aura, or probable migraine with visual aura (PMVA). Results—Women with PMVA had 1.5 greater odds of ischemic stroke (95% CI, 1.1 to 2.0); the risk was highest in those with no history of hypertension, diabetes, or myocardial infarction compared to women with no migraine. Women with PMVA who were current cigarette smokers and current users of oral contraceptives had 7.0-fold higher odds of stroke (95% CI, 1.3 to 22.8) than did women with PMVA who were nonsmokers and non–oral contraceptive users. Women with onset of PMVA within the previous year had 6.9-fold higher adjusted odds of stroke (95% CI, 2.3 to 21.2) compared to women with no history of migraine. Conclusions—PMVA was associated with an increased risk of stroke, particularly among women without other medical conditions associated with stroke. Behavioral risk factors, specifically smoking and oral contraceptive use, markedly increased the risk of PMVA, as did recent onset of PMVA. (Stroke. 2007;38:2438-2445.)
309 citations
TL;DR: Obtaining a ≥50% lowering in LDL-C was associated with a greater reduction in the risk of stroke and major coronary events with no increase in brain hemorrhages.
Abstract: Background and Purpose—The intention-to-treat analysis of data from the placebo-controlled Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found 80 mg atorvastatin per day reduced the risk of stroke and major coronary events in patients with recent stroke or transient ischemic attack. This benefit was present despite only a 78% net difference in adherence to randomized treatment over the course of the trial. In this exploratory analysis, our aim was to evaluate the benefit and risks associated with achieving a 50% low-density lipoprotein cholesterol (LDL-C) reduction from baseline. Methods—This post hoc analysis was based on 55 045 LDL-C measurements among the 4731 patients enrolled in SPARCL (average, 11.6 measurements per patient) during a mean follow-up of 4.9 years. At each postrandomization LDL-C assessment, percent change in LDL-C from baseline for each patient was classified as no change or increase from baseline (32.7% of measurements), 50% LDL-C reduction (39.4%), or 50% reduction (27.9%). Results—Compared with no change or an increase in LDL-C, analysis of time-varying LDL-C change showed that patients with 50% LDL-C reduction had a 31% reduction in stroke risk (hazard ratio, 0.69, 95% CI, 0.55 to 0.87, P0.0016), a 33% reduction in ischemic stroke (P0.0018), no statistically significant increase in hemorrhagic stroke (P0.8864), and a 37% reduction in major coronary events (P0.0323). There was no increase in the incidence of myalgia or rhabdomyolysis. Persistent liver enzyme elevations were more frequent in the group with 50% LDL-C reduction. Conclusions—As compared with having no change or an increase in LDL-C, achieving a 50% lowering was associated with a greater reduction in the risk of stroke and major coronary events with no increase in brain hemorrhages. (Stroke. 2007;38:3198-3204.)
TL;DR: Serious cardiac events are common in the acute period after stroke and patients at highest risk are identifiable and may benefit from more aggressive strategies to improve survival.
Abstract: Background and Purpose— In the first 3 months after acute ischemic stroke, 2% to 6% of patients die from cardiac causes. This may reflect preexisting cardiac disease, cardiac dysfunction related to the acute neurohumoral and autonomic stress response to stroke, or both. Delineation of a high-risk group could facilitate prevention strategies. We aimed to describe the temporal profile of cardiac risk after stroke and develop a predictive model of serious cardiac adverse events (SCAEs) using baseline variables. Methods— We used data from the one trial in the Virtual International Stroke Trials Archive that matched prespecified criteria. Survival analysis was used to describe the temporal profile of cardiac events after stroke. Prognostic determinants were assessed with multivariable logistic regression, and a risk score was derived from the key predictor variables. Results— Of 846 ischemic stroke patients, 35 (4.1%) died from cardiac causes and 161 (19.0%) suffered at least one SCAE. The hazard of cardiac de...
TL;DR: Imaging of PtiO2 pressure reactivity indicates impaired autoregulation in patients who develop delayed infarction after SAH, and this index may distinguish between patients who finally develop delayedinfarction and those who do not.
Abstract: Background and Purpose— Disturbances of cerebrovascular autoregulation are thought to be involved in delayed cerebral ischemia and infarction after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the continuous monitoring of brain tissue oxygen (PtiO2) pressure reactivity enables the detection of impaired autoregulation after SAH and that impaired autoregulation is associated with delayed infarction. Methods— In 67 patients after severe SAH, continuous monitoring of cerebral perfusion pressure (CPP) and PtiO2 was performed for an average of 7.4 days. For assessment of autoregulation, the index of PtiO2 pressure reactivity (ORx) was calculated as a moving correlation coefficient between values of CPP and PtiO2. Higher ORx values indicate disturbed autoregulation, whereas lower ORx values signify intact autoregulation. Results— Twenty patients developed delayed cerebral infarction, and 47 did not. Mean ORx was significantly higher in the infarction group compared with the noninfarction group ...
TL;DR: Cerebral infarction was strongly associated with poor outcome after aneurysmal SAH and the most important potentially treatable factor associated with infarctions was symptomatic vasospasm.
Abstract: OBJECTIVE Cerebral infarction would be expected to be associated with poor outcome after aneurysmal subarachnoid hemorrhage (SAH), although there are few data on which to base this assumption. The goals of this study were to determine the impact of cerebral infarction on outcome and to examine predictors of infarction in these patients. METHODS Univariate and multivariable statistical methods were used to examine the impact of cerebral infarction on the Glasgow Outcome Scale score 3 months after SAH among 3567 patients entered into four prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997. Patient demographics, clinical variables, radiographic characteristics, and treatment variables associated with cerebral infarction were also determined by the same methods. RESULTS Seven hundred and seven (26%) out of 2741 patients with complete data had cerebral infarction on computed tomographic scans 6 weeks after SAH. Multivariable logistic regression showed that cerebral infarction increased the odds of unfavorable outcome by a factor of 5.4 (adjusted odds ratio, 5.4; 95% confidence interval, 4.2-6.8; P < 0.0001), which was a higher odds ratio than all other factors associated with outcome. The proportion of explained variance in outcome was also highest for cerebral infarction and accounted for 39% of the explained variance. Multivariable analysis found that cerebral infarction was significantly associated with increasing patient age, worse neurological grade on admission, history of hypertension or diabetes mellitus, larger aneurysm, use of prophylactically or therapeutically induced hypertension, temperature more than 38 degrees C 8 days after SAH, and symptomatic vasospasm. CONCLUSION Cerebral infarction was strongly associated with poor outcome after aneurysmal SAH. The most important potentially treatable factor associated with infarction was symptomatic vasospasm.
TL;DR: The increase of circulating EPC after acute ischemic stroke is associated with good functional outcome and reduced infarct growth, suggesting that EPC might participate in neurorepair after ischeMIC stroke.
Abstract: Background and Purpose— Increased circulating endothelial progenitor cells (EPC) have been associated with a low cardiovascular risk and may be involved in endothelial cell regeneration. The present study was designed to evaluate the prognostic value of EPC in acute ischemic stroke. Methods— Forty-eight patients with a first-ever nonlacunar ischemic stroke were prospectively included in the study within 12 hours of symptoms onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale, and functional outcome was assessed at 3 months by the modified Rankin Scale (mRS). Infarct volume growth between admission and days 4 to 7 was measured on multiparametric MRI. EPC colonies were defined as early outgrowth colony-forming unit-endothelial cell (CFU-EC). The increment of CFU-EC was quantified during the first week and defined as the absolute difference between the number of CFU-EC at day 7 and admission. The influence of CFU-EC increase on good functional outcome (mRS ≤2) and infarct g...
TL;DR: In this paper, biochemical and molecular pathways in the vasculature that are rapidly affected by hyperglycemia are reviewed and concluded that these changes result in a pro-vasoconstrictive, pro-thrombotic and pro-inflammatory phenotype that renders the vascular system vulnerable to reperfusion injury.
Abstract: Admission hyperglycemia complicates approximately one-third of acute ischemic strokes and is associated with a worse clinical outcome. Both human and animal studies have showed that hyperglycemia is particularly detrimental in ischemia/reperfusion. Decreased reperfusion blood flow has been observed after middle cerebral artery occlusion in acutely hyperglycemic animals, suggesting the vasculature as an important site of hyperglycemic reperfusion injury. This paper reviews biochemical and molecular pathways in the vasculature that are rapidly affected by hyperglycemia and concludes that these changes result in a pro-vasoconstrictive, pro-thrombotic and pro-inflammatory phenotype that renders the vasculature vulnerable to reperfusion injury. Understanding these pathways should lead to the development of rational therapies that reduce hyperglycemic reperfusion injury and thus improve outcome in this large subset of acute ischemic stroke patients.
TL;DR: The initial functional status at admission, rather than the stroke subgroup, better predicts discharge functional outcomes postrehabilitation, and patients with stroke made significant functional gains and should be offered rehabilitation regardless of stroke vascular territory.
Abstract: Background and Purpose— We aim to compare demographics and functional outcomes of patients with stroke in a variety of vascular territories who underwent inpatient rehabilitation. Such comparative data are important in functional prognostication, rehabilitation, and healthcare planning, but literature is scarce and isolated. Methods— Using data collected prospectively over a 9-year period, we studied 2213 individuals who sustained first-ever ischemic strokes and were admitted to an inpatient stroke rehabilitation program. Strokes were divided into anterior cerebral artery, middle cerebral artery (MCA), posterior cerebral artery, brain stem, cerebellar, small-vessel strokes, and strokes occurring in more than one vascular territory. The main functional outcome measure was the Functional Independence Measure (FIM). Repeated-measures analysis of covariance with post hoc analyses was used to compare functional outcomes of the stroke groups. Results— The most common stroke groups were MCA stroke (50.8%) and sm...
TL;DR: Executive function deficits are common in stroke patients and limitations in information processing due to these deficits may require environmental and procedural accommodations to increase rehabilitation benefit.
TL;DR: The findings revealed that asymptomatic moyamoya disease is not a silent disorder and may potentially cause ischemic or hemorrhagic stroke.
Abstract: Background and Purpose— Although the development of a noninvasive MR examination has increased the opportunity to identify asymptomatic patients with moyamoya disease who have experienced no stroke episodes, their clinical features are still unclear. This was the first multicenter, nation-wide survey focused on asymptomatic moyamoya disease in Japan and was designed to clarify their clinical features.
Methods— A clinical database of asymptomatic patients with moyamoya disease was collected from 12 participating hospitals in Japan between 2003 and 2006. In total, 40 patients were enrolled in this historical prospective cohort study. Of these, 6 underwent surgical revascularization, including superficial temporal artery to middle cerebral artery anastomosis and/or pial synangiosis. Their demographic and radiological findings as well as outcome were evaluated.
Results— On initial evaluation, cerebral infarction and disturbed cerebral hemodynamics were detected in ≈20% and 40% of the involved hemispheres, respectively. Angiographical stage was more advanced in more elderly patients. Of 34 nonsurgically treated patients, 7 experienced transient ischemic attack (n=3), ischemic stroke (n=1), or intracranial bleeding (n=3) during follow-up periods (mean, 43.7 months). The annual risk for any stroke was 3.2%. Disease progression was associated with ischemic events or silent infarction in 4 of 5 patients. No cerebrovascular event occurred in the 6 patients who underwent surgical revascularization.
Conclusions— The findings revealed that asymptomatic moyamoya disease is not a silent disorder and may potentially cause ischemic or hemorrhagic stroke. Asymptomatic patients with moyamoya disease should be carefully followed-up to further clarify their outcome and to establish the management guideline for them.
TL;DR: Patients with large baseline DWI lesion volumes who achieve early reperfusion appear to be at greatest risk of tPA-associated symptomatic intracerebral hemorrhage after tPA therapy.
Abstract: Background— Studies evaluating predictors of tPA-associated symptomatic intracerebral hemorrhage (SICH) have typically focused on clinical and CT-based variables. MRI-based variables have generally not been included in predictive models, and little is known about the influence of reperfusion on SICH risk. Methods— Seventy-four patients were prospectively enrolled in an open-label study of intravenous tPA administered between 3 and 6 hours after symptom onset. An MRI was obtained before and 3 to 6 hours after tPA administration. The association between several clinical and MRI-based variables and tPA-associated SICH was determined using multivariate logistic regression analysis. SICH was defined as a ≥2 point change in National Institutes of Health Stroke Scale Score (NIHSSS) associated with any degree of hemorrhage on CT or MRI. Reperfusion was defined as a decrease in PWI lesion volume of at least 30% between baseline and the early follow-up MRI. Results— SICH occurred in 7 of 74 (9.5%) patients. In univ...
TL;DR: A major role for complement-mediated cell death in ischemic brain injury is suggested and the prospect of using IVIG in relatively low doses as an interventional therapy for stroke is suggested.
Abstract: Stroke is among the three leading causes of death worldwide and the most frequent cause of permanent disability. Brain ischemia induces an inflammatory response involving activated complement fragments. Here we show that i.v. Ig (IVIG) treatment, which scavenges complement fragments, protects brain cells against the deleterious effects of experimental ischemia and reperfusion (I/R) and prevents I/R-induced mortality in mice. Animals administered IVIG either 30 min before ischemia or after 3 h of reperfusion exhibited a 50-60% reduction of brain infarct size and a 2- to 3-fold improvement of the functional outcome. Even a single low dose of IVIG given after stroke was effective. IVIG was protective in the nonreperfusion model of murine stroke as well and did not exert any peripheral effects. Human IgG as well as intrinsic murine C3 levels were significantly higher in the infarcted brain region compared with the noninjured side, and their physical association was demonstrated by immuno-coprecipitation. C5-deficient mice were significantly protected from I/R injury compared with their wild-type littermates. Exposure of cultured neurons to oxygen/glucose deprivation resulted in increased levels of C3 associated with activation of caspase 3, a marker of apoptosis; both signals were attenuated with IVIG treatment. Our data suggest a major role for complement-mediated cell death in ischemic brain injury and the prospect of using IVIG in relatively low doses as an interventional therapy for stroke.
TL;DR: Perinatal ischemic stroke is not rare in term and near-term infants and is an important antecedent of long-term neurological disability, including congenital hemiplegia and seizure and cognitive disorders.
Abstract: Perinatal ischemic stroke is not rare in term and near-term infants and is an important antecedent of long-term neurological disability, including congenital hemiplegia (hemiplegic cerebral palsy) and seizure and cognitive disorders. Changes in maternal hemostasis occur in pregnancy and are amplified in the period immediately surrounding birth; stroke and other thromboembolic events are more frequent in both mother and infant in this period. The vasculature and hemostatic mechanisms of placenta as well as brain are likely to be important in the pathobiology of perinatal stroke. Maternal and infant thrombophilias, genetic and acquired, play a role. Rarely is >1 child in a sibship affected, and environmental factors—substantially less studied, to date—are likely to be key determinants of risk.
TL;DR: It is suggested that acute ischemic stroke is associated with an early activation of the sympathetic adrenomedullar pathway that lowers the threshold of infection and increases the risk of death.
TL;DR: Patients discontinuing statins have a significantly increased mortality during the first year after the acute cerebrovascular event and the findings suggest that patient care should be improved during the transition from a hospital setting to outpatient primary care.
Abstract: Background and Purpose— The majority of patients with previous ischemic stroke are expected to benefit significantly from long-term statin therapy. However, discontinuation of medication therapy frequently occurs in clinical practice. The aim of this study was to assess the impact of discontinued statin therapy on clinical outcome in patients discharged after an acute ischemic stroke. Methods— The study population included 631 consecutive stroke survivors (322 men and 309 women; mean±SD age, 70.2±7.6 years) without clinical evidence of coronary heart disease. All patients were discharged on statin therapy and were followed up for 12 months after the acute ischemic stroke. Results— Within 12 months from discharge, 246 patients (38.9%) discontinued statin therapy; the mean time from discharge to statin discontinuation was 48.6±54.9 days (median time, 30 days; interquartile range, 18 to 55 days). During follow-up, 116 patients died (1-year probability of death=0.18; 95% CI, 0.15 to 0.21). Multivariate analys...
TL;DR: The potential underlying mechanisms that lead to increased incidence of stroke among diabetic patients are explored and the impact of diabetes and hyperglycemia on stroke outcomes are discussed.
Abstract: Stroke affects more than 700,000 individuals each year; it is the third largest cause of death and the largest cause of adult disability in the U.S. Diabetes is a major risk factor for the development of stroke, yet this risk is not realized or understood by patients with diabetes. This likely reflects a lack of understanding within the medical community of how diabetes confers this risk. We will explore the potential underlying mechanisms that lead to increased incidence of stroke among diabetic patients. Beyond diabetes itself, the metabolic syndrome and its components will also be discussed. The impact of diabetes and hyperglycemia on stroke outcomes and a discussion of current approaches to reduce stroke in this high-risk population are included. Because type 2 diabetes affects the vast majority of those diagnosed with diabetes, it will be the primary focus of this discussion.
It has been well documented that diabetes confers a significantly increased risk of stroke, as well as increased mortality following stroke (1–7). Stroke is a preventable disease with high personal and societal cost. While great progress has been made in understanding the link between diabetes and coronary heart disease (CHD), the literature on diabetes and stroke has been less enlightening. CHD is a larger problem that accounts for 40–50% of mortality in diabetes. Because of the overwhelming impact of CHD, the impact of stroke has been relatively underappreciated. Thus, physicians, diabetes educators, and nurses are less equipped to educate patients. We therefore review the relationship between diabetes and stroke.
Given that more than one million people are diagnosed with diabetes yearly, a figure that is expected to rise, the impact of diabetes on the incidence of stroke is of increasing importance. Diabetic patients compose roughly 6.3% of the U.S. population but account for 15–27% of all …
TL;DR: Perfusion lesion size differs markedly depending on the parameter calculated, and some parameters (mainly representing MTT measures) were correlation with clinical scores; others were correlated with final infarct size; and arrival time fitted was correlated with both.
Abstract: Background and Purpose— Several methods are available to assess the magnetic resonance perfusion lesion in acute ischemic stroke. We tested 10 of these to compare perfusion lesion sizes and to assess the relation to clinical scores and final infarct extent. Methods— We recruited patients with acute ischemic stroke, performed diffusion- and perfusion-weighted imaging, and recorded stroke severity at baseline, final infarct size on T2-weighted imaging at ≥1 month, and Rankin Scale score at 3 months. We calculated 10 perfusion parameters (6 of mean transit time, MTT; 3 of cerebral blood flow; 1 of cerebral blood volume; 7 relative and 3 quantitative), measured the perfusion-weighted imaging lesion and diffusion/perfusion mismatch volumes, and compared each with clinical and radiologic outcomes. Results— Among 32 patients, the median perfusion lesion volume varied from 0 to 14 882 voxels (P<0.0001); the proportion of patients with mismatch varied from 9% to 72% (P<0.05), depending on the perfusion parameter. ...
TL;DR: Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the “antiedema” therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger.
Abstract: Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbitu- rate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive. (Stroke. 2007;38:3084-3094.)
TL;DR: CB2 activation is associated with a Reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.
Abstract: Cannabinoid CB(2) Receptor (CB(2)) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB(2) agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB(2) agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB(2) agonists significantly decreased cerebral infarction (30%) and improved motor function (P<0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P<0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB(2) agonists administered either at 1 h before or after MCAO (P<0.05). CB(2) activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.
TL;DR: This prospective study confirmed the high sensitivity and negative predictive value, with retained good specificity, of c-Fn and MMP-9 for the prediction of PH in patients treated with t-PA in patients with acute ischemic stroke.
Abstract: Background and Purpose— Plasma levels of cellular fibronectin (c-Fn) ≥3.6 μg/mL and of matrix metalloproteinase-9 (MMP-9) ≥140 ng/mL have been associated with parenchymal hematoma (PH) after treatment with tissue-type plasminogen activator (t-PA) in patients with acute ischemic stroke. In this prospective study, we sought to validate the predictive capacity of the preestablished cutoff values of these biomarkers for PH in a larger series of patients. Methods— We studied 134 patients treated with t-PA within 3 hours from symptom onset according to the SITS-MOST criteria (median time to infusion, 152 minutes; median National Institutes of Health Stroke Scale score, 14) in 4 university hospitals. Hemorrhagic transformation was classified according to the European-Australasian Acute Stroke Study II definitions on computed tomography scans performed 24 to 36 hours after treatment. Relevant hemorrhagic transformation was defined as hemorrhagic infarction type 2 or any PH. Serum c-Fn and MMP-9 levels were determined by an ELISA om blood samples obtained before treatment. Results— Cranial computed tomography showed hemorrhagic transformation in 27 patients (20%), hemorrhagic infarction in 15 (type 2 in 8 patients), and PH in 12 patients (symptomatic in 4). Serum c-Fn and MMP-9 concentrations at baseline were significantly higher in patients with relevant hemorrhagic transformation and PH than in those without (all P Conclusions— This prospective study confirmed the high sensitivity and negative predictive value, with retained good specificity, of c-Fn and MMP-9 for the prediction of PH in patients treated with t-PA. Development of faster analytic methods will prove the applicability of these biomarkers in routine clinical practice.
TL;DR: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients, and 20% of patients demonstrated evidence of an HIV associated vasculopathy in their cohort.
Abstract: Objective: To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy. Methods: Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed. Results: Between 2000 and 2006, 67 of the 1087 (6,1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation. Conclusion: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy.