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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
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PMID:Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. 1569 61

We report the results of three years of the population-based, prospective Swiss NeuroPaediatric Stroke Registry (SNPSR) of children (up to 16 years) with childhood arterial ischaemic stroke (AIS1), neonatal stroke (AIS2), or symptomatic sinus venous thrombosis (SVT). Data on risk factors (RF), presentation, diagnostic work-up, localisation, and short-term neurological outcome were collected. 80 children (54 males) have been included, 40 AIS1, 23 AIS2, and 17 SVT. The data presented will be concentrated on AIS. The presentation for AIS1 was hemiparesis in 77% and cerebellar symptoms and seizures in 20%, respectively. AIS2 presented in 83% with seizures and in 38% with abnormality of muscle tone. Two or more RF were detected in 54%, one RF in 35%. The most prominent RF for AIS1 were infections (40%), followed by cardiopathies and coagulopathies (25% each). AIS2 were frequently related to birth problems. Neurological outcomes in AIS1 and AIS2 were moderate/severe in 45 % and 32 %, respectively. The outcome correlated significantly with the size of infarction (p = 0.013) and age at stroke (p = 0.027). The overall mortality was 6%. Paediatric stroke is a multiple risk problem, which leads to important long-term sequelae.
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PMID:The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors. 1582 21

We investigated the plasma levels of D-dimer, fibrinogen, beta-thromboglobulin (BTG) and platelet factor-4 (PF-4), indices of the occurrence of platelet activation in vivo, to find out their role in pathophysiology of ischemic stroke and whether or not such a role has any effect on the disability and the prognosis of stroke patients. A total of 76 patients with AIS aged from 26 to 85 (32 men, 44 women) and 30 cases as controls with similar age (18 men, 12 women) were included in the study. The plasma levels of D-dimer, BTG and PF-4 were measured by ELISA method using a special commercial kit. The cases were allocated into two groups as non-embolic (NEI) and cardioembolic stroke (CEI). The D-dimer levels in 76% of 42 patients in NEI group (p<0.05) and 85.2% of 34 patients in CEI group (p<0.05) were outside the confidence interval (CI) defined for the control group. The levels of BTG were elevated in 81% of 42 cases with NEI (p<0.05) and in 76% of 34 cases with CEI, with reference to CI of control group. The levels of PF-4 were significantly increased in 86% of cases with NEI (p<0.05) and in 88% of cases with CEI than controls (p<0.05). It was observed that the cases with high Rankin scores had higher levels of D-dimer (p<0.005), BTG (p<0.01) and PF-4 (p<0.01) than those with lower scores. There was a correlation between hemostatic markers, platelet activation and functional disability. D-dimer levels were an important marker that determined to degree of the activation of hemostatic system, especially in CEI subtype. The platelet aggregation had an important role in pathophysiology of ischemic stroke and this condition is significant in NEI subgroup and subjects with large infarcts and high disability scores.
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PMID:Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction. 1592 75

Childhood ischaemic stroke, incorporating arterial ischaemic stroke and cerebral sinus venous thrombosis, is associated with significant morbidity and mortality in children. The majority of cases in children present with well-recognised risk factors. The appreciation of the role prothrombotic abnormalities have in disease states is developing rapidly. Prothrombotic abnormalities are abnormalities of the coagulation system, fibrinolytic system, endothelial cells or platelets that lead to a reduced threshold for pathological thrombus formation. Our understanding of the role of prothrombotic abnormalities in childhood ischaemic stroke is increasing and has a direct bearing on the development of effective management and prevention strategies. We provide a brief background of prothrombotic abnormalities and review the available literature on prothrombotic markers in childhood ischaemic stroke. Overall, prothrombotic abnormalities have been identified in 20-50% of children presenting with AIS and 33-99% of children with cerebral sinus venous thrombosis. There appear to be a number of associations emerging including an increased frequency of factor V Leiden mutation, elevated lipoprotein (a), protein C deficiency and antiphospholipid antibodies in children presenting with arterial ischaemic stroke. The pathogenic role of prothrombotic abnormalities as predisposing to initial and recurrent childhood ischaemic stroke is becoming increasingly evident. The impact on treatment, however, will only be clarified with carefully designed, multi-institutional prospective studies.
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PMID:Prothrombotic abnormalities in childhood ischaemic stroke. 1603 97

Acute ischemic stroke is one of the leading causes of mortality and chronic disability in the western world. Yet, despite the enormous socioeconomic burden that it imposes, therapies to combat AIS are not widely available. Moreover, revascularization of the ischemic tissue with tissue plasminogen activator, the only FDA-approved therapy for AIS, is hampered by a very narrow therapeutic time window and is only used in a minority of patients. Cerebral ischemia leads to brain damage caused by several pathologic mechanisms that can potentially be blocked by neuroprotective drugs that aim to salvage the ischemic penumbra. However, despite numerous clinical trials, no single drug candidate has proved efficacious in AIS. The current situation calls for novel therapeutic strategies to be used in acute ischemic stroke. This review surveys some of these novel and promising cutting edge therapies.
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PMID:Novel therapies for acute ischemic stroke. 1718 Aug 32

MMP-9 plays an important role in the pathogenesis of AIS and predicts haemorrhagic transformation of the ischaemic focus. The aim of our study was to analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1) levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastatin) affects the MMP-9/TIMP-1 ratio value. Fifty patients with AIS were randomly divided into two groups: Group I (N = 25) treated with 40 mg/day with simvastatin within 24 hours after the onset of stroke and Group II (N = 25) non-treated with statin. To evaluate MMP-9 and TIMP-1 serum levels, the ELISA method was used. The serum MMP-9 level was significantly elevated on the 7th day of stroke in both groups (from 668 to 862 ng/ml and 670 to 855 ng/ml, respectively, in Group I and II). The serum TIMP-1 level was also elevated on the 7th day of stroke in both groups but the results were not significant. The MMP-9/TIMP-1 ratio was elevated on the 7th day of stroke in both groups, but the result was significant only in the Group II (P < 0.01). These findings indicate that simvastatin given during 24 hours after the onset of stroke could have an influence on the MMP-9/TIMP-1 ratio during AIS.
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PMID:Simvastatin could prevent increase of the serum MMP-9/TIMP-1 ratio in acute ischaemic stroke. 1718 95

Traditional risk factors associated with adult arterial ischemic stroke (AIS; ie, hypertension, hyperlipidemia, diabetes, smoking, and atherosclerosis) are relatively rare in children. Childhood AIS is instead associated with a variety of conditions including cerebral arteriopathies, congenital heart disease, infection, head and neck trauma, sickle cell anemia, and prothrombotic abnormalities. Although the pathophysiology and outcomes of adult AIS differ significantly from those in childhood AIS, therapeutic management remains similar, largely because of the paucity of evidence from devoted pediatric observational studies and clinical trials. The purpose of this article is to review the current guidelines and evidence in the treatment of childhood AIS, within the context of that which exists in adult AIS. Medical management of hypoxia, hyperglycemia, fever, blood pressure, and increased intracranial pressure has been insufficiently investigated in childhood stroke, resulting in a lack of guidance in these areas. Although acute antithrombotic management in childhood AIS has received relatively greater attention in published recommendations, it is based almost exclusively on consensus and expert opinion, and differs considerably among existing pediatric guidelines. Rehabilitation therapy in childhood AIS has great potential for meaningful improvements in long-term outcomes, especially given the plasticity of the young brain; however, little guidance for rehabilitative measures is provided by published recommendations. Ongoing and future multicenter cohort study efforts, and ultimately devoted pediatric clinical trials, will be essential to establish comprehensive evidence-based guidelines for the treatment of childhood AIS.
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PMID:Treatment of childhood arterial ischemic stroke. 1849 44

Edaravone is a lipophilic drug with multiple mechanisms of action. Because edaravone is a promising drug candidate for the treatment of stroke, we tested the hypothesis that edaravone would be neuroprotective following cerebral ischemia using a rabbit embolic stroke model with a well-defined behavioral endpoint. Using the rabbit small clot embolic stroke model (RSCEM), a drug or drug combination is considered beneficial if it significantly increases the amount of microclots (mg) measured in brain that produce neurologic dysfunction in 50% of a group of animals (P(50)) compared to the control group. Edaravone (100 mg/kg, s.c.), increased the P(50) value to 1.80+/-0.24 mg (p<0.05) when administered 5 min following embolization and increased P(50) values by 195% and 161% (compared to control) when administered 1 and 3 h following embolization, respectively, but was inactive when applied 6 h following embolization, compared to the cumulative control group (P(50)=0.93+/-0.16 mg). To simulate the design of current clinical trials, edaravone was also given following a standard tPA regimen, which by itself increased the P(50) value to 2.72+/-0.28 mg. When tPA was infused 1 h following embolization and edaravone was given 3 h following embolization, the P(50) was 2.68+/-0.56 mg. This study indicates that edaravone may have substantial therapeutic benefit for the treatment of AIS since it had a therapeutic widow of at least 3 h in rabbits. Edaravone can also be administered with a thrombolytic to improve behavior.
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PMID:The lipophilic multifunctional antioxidant edaravone (radicut) improves behavior following embolic strokes in rabbits: a combination therapy study with tissue plasminogen activator. 1885 64

The role of DCs (dendritic cells) as potent mediators of inflammation has not been sufficiently investigated in stroke. Therefore, in the present study, circulating mDCPs (myeloid DC precursors), pDCPs (plasmacytoid DCPs) and tDCPs (total DCPs) were analysed by flow cytometry in (i) healthy controls (n=29), (ii) patients with ACI-S (asymptomatic cerebral infarction stenosis; n=46), (iii) patients with TIA (transient ischaemic attack; n=39), (iv) patients with AIS (acute ischaemic stroke; n=73), and (v) patients with AHS (acute haemorrhagic stroke; n=31). The NIHSS (National Institutes of Health Stroke Scale) and infarction size on a CT (computer tomography) scan were evaluated after stroke. In a patient subgroup, post-mortem immunohistochemical brain analyses were performed to detect mDCs (CD209), pDCs (CD123), T-cells (CD3) and HLA-DR. In AIS and AHS, the numbers of circulating mDCPs (P<0.005), pDCPs (P<0.005) and tDCPs (P<0.001) were significantly reduced. A significant inverse correlation was found between the NIHSS and circulating DCPs (P<0.02), as well as between hsCRP (high-sensitivity C-reactive protein) and circulating DCPs (P<0.001). Patients with large stroke sizes on a CT scan had significantly lower numbers of mDCPs (P=0.007), pDCPs (P=0.05) and tDCPs (P=0.01) than those with smaller stroke sizes. Follow-up analysis showed a significant recovery of circulating DCPs in the first few days after stroke. In the infarcted brain, a dense infiltration of mDCs co-localized with T-cells, single pDCs and high HLA-DR expression were observed. In conclusion, acute stroke leads to a decrease in circulating DCPs. Potentially, circulating DCPs are recruited from the blood into the infarcted brain and probably trigger cerebral immune reactions there.
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PMID:Transient decrease in circulating dendritic cell precursors after acute stroke: potential recruitment into the brain. 1950 33

Previous studies have indicated a male predominance in pediatric stroke. To elucidate this gender disparity, total testosterone concentration was measured in children with arterial ischemic stroke (AIS; n = 72), children with cerebral sinovenous thrombosis (CSVT; n = 52), and 109 healthy controls. Testosterone levels above the 90th percentile for age and gender were documented in 10 children with AIS (13.9%) and 10 with CSVT (19.2%), totaling 16.7% of patients with cerebral thromboembolism overall, as compared with only 2 of 109 controls (1.8%; p = 0.002). In multivariate analysis with adjustment for total cholesterol level, hematocrit, and pubertal status, elevated testosterone was independently associated with increased disease risk (odds ratio [95% confidence interval]: overall = 3.98 [1.38-11.45]; AIS = 3.88 [1.13-13.35]; CSVT = 5.50 [1.65-18.32]). Further adjusted analyses revealed that, for each 1nmol/l increase in testosterone in boys, the odds of cerebral thromboembolism were increased 1.3-fold.
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PMID:Role of endogenous testosterone concentration in pediatric stroke. 2003


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