Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Our objective was to characterize the etiologic factors and outcome for stroke in children. We retrospectively reviewed the charts of patients between the ages of 40 days and 94 months (36.5 +/- 23.7 months) with stroke seen at Istanbul Medical Faculty, Department of Pediatrics between January 1995 and December 2003. We found 79 cases of stroke: 57 ischemic and 22 hemorrhagic strokes. Seventeen children had vitamin K deficiency dependent hemorrhage. In 14 children stroke occurred as a complication of cardiac disease, 7 had moyamoya disease, 3 had protein C deficiency, 2 had thalassemia, 2 had hyperhomocysteinemia (methylene tetrahydrofolate reductase gene mutation), 2 were heterozygote for factor V Leiden, 3 had Down's syndrome, 1 was diagnosed with antiphospholipid syndrome, 1 had glycogen storage disease, and in 28 children no underlying cause could be found. Multiple risk factors were found in 4 children. The outcome in all 79 stroke patients was as follows: asymptomatic 60%; symptomatic epilepsy or persistent neurologic deficit 37%; death 3%; and recurrent stroke 5%. Thus, an underlying cause for stroke was identified in 65% of the children in the study group; 40% of the children either died or suffered motor and/or cognitive sequelae.
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PMID:Stroke in childhood: experience in Istanbul, Turkey. 1663 11

Puerperal cerebral veno-sinus thrombosis (PCVT) is a common form of stroke in young women in India, which is associated with high morbidity and mortality. The frequency of PCVT in India is 10 to 12 times more compared to western population. As yet, the etiology of this condition is unclear. Our aim was to study the prevalence and the role of the common genetic polymorphisms associated with thrombophilia such as factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T, in aseptic PCVT. We investigated 86 women with PCVT and 86 age-matched women with no post-partum complications. Polymerase chain reaction (PCR)/restriction fragment length polymorphism analysis was used to identify their genotypes. The frequency of the three polymorphisms in cases and controls were: factor V Leiden, 2.3% versus 1.2% (OR 0.49, 95% CI=0.02-7.12, p=1.000) and MTHFR C677T, 16.3% versus 17.4% (OR 0.92, 95% CI=0.39-2.19, p=0.838). The prothrombin G20210A variant was not detected in either patients or controls. The clinical characteristics of the PCVT patients with the polymorphisms did not differ significantly from those without them. In our series of PCVT patients, the risk associated with the established thrombophilic risk factors is insignificant. Exploration of these gene polymorphisms seems to be of limited value in the investigation of PCVT in south Indian women.
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PMID:Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis. 1683 69

Palladium(0) nanoparticle has been used as an efficient catalyst for the allylation of active methylene compounds. Very efficient bisallylation is achieved for a variety of active methylene compounds by allyl acetate and its derivatives in one stroke in THF solvent. The reaction in water provides monoallylated product selectively by allyl acetate only. The recovered Pd(0) nanoparticle is recycled. A probable mechanism is suggested.
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PMID:Solvent-controlled highly selective bis- and monoallylation of active methylene compounds by allyl acetate with palladium(0) nanoparticle. 1790 86

Iridodonesis or tremulous iris is a clinical sign of ectopia lentis which is frequently associated with homocystinuria. We present a forty-two-year-old woman victim of a left middle cerebral artery ischemic stroke. The clinical examination found bilateral iridodonesis and laboratory tests showed an increased level of serum homocysteine and homocystinuria. Homocystinuria was caused by a compound heterozygous I278T and D444N mutation of cystathionine beta-synthase (CBS) gene and also a C667T heterozygous polymorphism of methylene-tetrahydrofolate-reductase gene. This case was atypical because of the incomplete phenotype, development of complications in adulthood and the association of a rare compound heterozygous mutation of the CBS gene.
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PMID:[Stroke and iridodonesis revealing a homocystinuria caused by a compound heterozygous mutation of cystathionine beta-synthase]. 1880 5

Genes involved in the hemostatic mechanism are logical candidate genes for association studies in prothrombotic conditions such as stroke. Since the underlying etiology in pediatric strokes is different than adults, looking for genetic causes would be the logical thing to do in the pediatric stroke population. Fifty-eight Asian-Indian stroke patients below 15 years of age and equal number of age- and sex-matched healthy controls were the subjects for the study. The subjects were screened for 13 polymorphisms and three mutations spread across seven different candidate genes involved in the hemostatic system. Of the 13 polymorphisms and three mutations studied, four polymorphisms, HPA-I, TAFI 147Ala>Thr, methylene tetrahydrofolate reductase (MTHFR) 677 C>T, and MTHFR 1298 A>C, showed significant association with the disease phenotype. MTHFR 677 C>T showed the strongest association and therefore may have a strong predisposing role for pediatric strokes. Gene-gene interaction studies showed a strong interaction between HPA-I and MTHFR 677 C>T polymorphism. The wild type of both these polymorphisms synergistically showed a strong protective effect [p < 0.0001, O.R: 10.06(4.26-23.71)]. Polymorphisms in HPA-I and MTHFR may have important predisposing roles in the development of pediatric stroke.
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PMID:Prothrombotic polymorphisms, mutations, and their association with pediatric non-cardioembolic stroke in Asian-Indian patients. 1883 20

Numerous clinical trials using folic acid for prevention of cardiovascular disease, stroke, cognitive decline, and neural tube defects have been completed or are underway. Yet, all functions of folate are performed by tetrahydrofolate and its one-carbon derivatives. Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Increasing evidence suggests that this process may be slow in humans. Here we show, using a sensitive assay we developed, that the reduction of folic acid by DHFR per gram of human liver (n = 6) obtained from organ donors or directly from surgery is, on average, less than 2% of that in rat liver at physiological pH. Moreover, in contrast to rats, there was almost a 5-fold variation of DHFR activity among the human samples. This limited ability to activate the synthetic vitamer raises issues about clinical trials using high levels of folic acid. The extremely low rate of conversion of folic acid suggests that the benefit of its use in high doses will be limited by saturation of DHFR, especially in individuals possessing lower than average activity. These results are also consistent with the reports of unmetabolized folic acid in plasma and urine.
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PMID:The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. 1970 81

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function.
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PMID:Hyperhomocysteinemia in uremia--a red flag in a disrupted circuit. 1970 80

The objective of this study is to report a new manifestation of acute stroke following antifibrinolytic agent administration in young women carrying heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study included two young women who developed an acute ischaemic stroke following three days of tranexamic acid administration for bleeding gynaecological disorders. Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto-temporal lesion due to subocclusion of the right middle cerebral artery. Case 2, a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed left capsular and periventricular infarcts due to near occlusion of the left internal carotid artery. Thrombophilia screening, coagulation parameters, homocysteine testing, 12-lead electrocardiography, and transthoracic and transoesophageal echocardiography were unremarkable. Genetic assay showed that both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is replaced by thymidine (T) at base position 677. To our knowledge, this is the first report describing the association between genetic factors and the onset of stroke following antifibrinolytic drugs intake. These data suggest a synergic effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on the pathogenetic mechanisms leading to ischaemic stroke in young people.
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PMID:Ischaemic stroke following tranexamic acid in young patients carrying heterozygosity of MTHFR C677T. 2190 3

Antiphospholipid antibodies are a recognised prothrombotic risk factor associated with acute ischaemic infarction. Most autoimmune diseases are rare in infants, and in the neonatal period, autoimmunity is related to transplacental passage of maternal immunoglobulin G autoantibodies. Distinguishing between de novo and acquired autoimmunity has important therapeutic implications and is crucial for determining the prognosis. We present a case of a neonatal thrombotic stroke associated with de novo synthesis of antiphospholipid antibodies, a homozygous 1298C/C methylene-tetrahydrofolate reductase mutation and a double-homozygous plasminogen activator inhibitor 1 polymorphism (PAI-1 844A/A and 675 4G/4G), which may have increased the final thrombotic risk. Her mother was not positive for antiphospholipid antibodies. The authors highlight an unequivocal evidence of a de novo case of paediatric antiphospholipid antibody syndrome and emphasise the need for a thorough investigation in cases of neonatal stroke including molecular thrombophilia study.
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PMID:Neonatal stroke associated with de novo antiphospholipid antibody and homozygous 1298C/C methylenetetrahydrofolate reductase mutation. 2316 20


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