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)

Beta 2-glycoprotein I (beta2-GPI) is an antigenic target recognised by antiphospholipid antibodies found in association with the antiphospholipid syndrome (APS). In this study, the prevalence of Immunoglobulin M (IgM) and IgA anti-beta2-GPI antibodies was examined in APS patients and compared with IgG antibodies. In addition the value of measuring antibody isotypes and IgG subclass was investigated in the laboratory diagnosis of APS. A solid phase enzyme linked immunosorbent assay was established to measure IgG, IgM and IgA and IgG subclass antibodies to beta2-GPI in patients with APS and a variety of other thrombotic and non-thrombotic disorders. Raised levels of IgM anti-beta2-GPI antibodies were observed in 65% of patients with APS, 21% with systemic lupus erythematosus (SLE), 23% with rheumatoid factor, 4% with stroke, 5% carotid artery stenosis (CAS), 17% with a biological false positive serology for syphilis, 43% with infectious mononucleosis (IM) and 27% with human immunodeficiency virus (HIV). The median value for IgM antibodies to beta2-GPI for all these groups ranged from 2 to 7 arbitrary units (AU). Elevated levels of IgA antibodies to beta2-GPI were found in patients with APS (47%), SLE (13%), rheumatoid factor (26%), CAS (48%), stroke (25%), VDRL false positive serology for syphilis (33%), IM (47%) and HIV (7%). The median value of IgA antibodies to beta2-GPI in all of these groups ranged from 2 to 4 AU. Conversely the median value for IgG anti-beta2-GPI in APS patients was 112 AU compared to 1-4 AU in the other conditions examined. The presence of IgM and IgA antibodies to beta2-GPI was much less specific and sensitive for APS than IgG, with raised levels of these isotypes seen in a variety of thrombotic and non-thrombotic disorders. Elevated levels of IgG1, IgG2, IgG3 and IgG4 antibodies to beta2-GPI were detected in APS patients. While all four IgG anti-beta2-GPI antibody subclasses were represented in APS patients there appeared to be a significant overall skewing towards to the IgG2 subclass.
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PMID:Anti-Beta 2-glycoprotein I antibody isotype and IgG subclass in antiphospholipid syndrome patients. 1068 Jul 49

The diagnosis of stroke in children and young adults can be difficult, and the causes of ischemic stroke often remains unexplained even after extensive evaluation. We present a 13-year-old girl who had two ischemic strokes within a period of 3 weeks. A carotid duplex study and magnetic resonance angiography confirmed total occlusion of the left internal carotid artery. Serum immunologic examination revealed a high titer of immunoglobulin G anticardiolipin antibody (45.7 GPL U/mL; normal range, 0-16.2 GPL U/mL). The patient received long-term anticoagulation treatment with warfarin 5 to 7.5 mg per day, and international normalized ratios were maintained between 2.4 and 4.0. She recovered completely 5 weeks after the first stroke and has been well during the 6 months of follow-up after the onset. This is the first reported case of childhood ischemic stroke secondary to primary antiphospholipid antibody syndrome in Taiwan. This case emphasizes the importance of evaluating antiphospholipid antibody levels in patients with unexplained ischemic strokes.
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PMID:Ischemic stroke in a teenage girl with primary antiphospholipid antibody syndrome. 1074 50

Antiphospholipid syndrome is an uncommon cause of stroke. A 12 year old girl with this syndrome is reported who presented with thrombotic stroke and high titres of anticardiolipin (aCL) and lupus anticoagulant (LAC). The patient improved subsequently and was put on aspirin. The present report highlights the importance of screening for aCL and LAC in cases of stroke in young patients.
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PMID:Primary antiphospholipid syndrome in stroke in the young. 1077 34

A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti-tissue-type plasminogen activator (t-PA) antibodies and anti-fibrin-bound t-PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t-PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti-t-PA antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and anti-t-PA fibrin-bound antibodies were measured by a solid-phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti-t-PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin-bound t-PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti-t-PA than patients without thrombosis (P = 0.029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti-t-PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti-t-PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t-PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.
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PMID:Antibodies to tissue-type plasminogen activator in plasma from patients with primary antiphospholipid syndrome. 1079 98

We report a case of acute adrenal insufficiency in a context of probable bilateral adrenal haemorrhage, as revealed by CT-scan in a 52-year-old woman with a history of spontaneous abortion and repeated ischaemic stroke without symptoms or signs of collagen vascular disease. The symptoms began after the patient had successfully been treated for pneumonia. She had persistently high titres of IgG anticardiolipin antibodies, antibodies against beta 2-glycoprotein I and a lupus anticoagulant. The diagnosis of primary antiphospholipid syndrome with adrenal insufficiency was postulated.
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PMID:[Bilateral adrenal hemorrhage with adrenal insufficiency in the framework of primary antiphospholipid antibody syndrome]. 1082

The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serum is considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomography (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE).
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PMID:Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome. 1134 Nov 10

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.
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PMID:Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. 1089 70

beta(2)-Glycoprotein I, an anionic phospholipid-binding 50-kDa plasma protein, circulates in the plasma at a concentration of 30-200 microg/ml. Its physiological role remains uncertain, but an important clue to this role is suggested by the finding that antibodies to this protein are frequently found in patients with antiphospholipid antibodies and thrombosis. beta(2)-Glycoprotein I belongs to the complement control protein (CCP) superfamily with five CCP domains. The fifth CCP domain of beta(2)-glycoprotein I has a unique structure and contains a stretch of positively charged amino acids that mediates the binding to phospholipids. This interaction may mediate the clearance of anionic phospholipid-containing surfaces from the circulation. Mutations in this domain affect its binding to phospholipids. We have identified a patient with primary antiphospholipid syndrome who is a compound heterozygous for two mutations in the fifth CCP. One mutation is located in exon 7 (codon 306), and the second mutation is in exon 8 (codon 316). The mutant beta(2)-glycoprotein I was present in normal quantities in his plasma but did not bind to cardiolipin. He had recurrent deep vein thrombosis and pulmonary embolism at age 28 and a thrombotic stroke at age 35, with no other identifiable risk factor for a hypercoagulable state. This report offers some insight into the mechanism of formation of antiphospholipid antibodies and suggests the possible role of the deficiency of beta(2)-glycoprotein I in the pathogenesis of thrombosis.
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PMID:Primary antiphospholipid antibody syndrome with mutations in the phospholipid binding domain of beta(2)-glycoprotein I. 1099 35

Moyamoya disease is an uncommon clinical entity, characterized by bilateral occlusion of the internal carotid artery and the development of collateral arteries. An 18-year-old Saudi male with systemic lupus erythematosus (SLE) presented with mild right hemiparesis, followed by recurrent ischemic stroke. Cerebral angiography showed bilateral internal carotid artery stenosis associated with the development of collateral circulation (moyamoya vessels). There was no evidence of active SLE or other risk factors for cerebral occlusion, such as antiphospholipid antibody syndrome. Medical and surgical interventions did not influence the poor outcome of the recurrent ischemic insults.
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PMID:Systemic lupus erythematosus associated with moyamoya syndrome. 1103 39

When the diagnosis of antiphospholipid antibody syndrome (aPS) is being considered in persons who have experienced an ischemic stroke or a transient ischemic attack, it is important to gauge how well the history and laboratory data fit with this diagnosis as opposed to other causes of infarct. The fewer the number of typical vascular disease risk factors and the more confirmatory the laboratory findings (ie, high anticardiolipin antibody titers or presence of lupus anticoagulant), the stronger the suspicion of aPS. There are no good prospective randomized data on stroke prevention with any form of therapy following a first stroke or transient ischemic attack associated with antiphospholipid antibody (aPL). Short-term anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0 may be considered in these cases, as could antiplatelet agents if no clear cardiac source is found. If anticoagulation is chosen, if there is no recurrence, and if the level of aPL appears to decline, a change to a stroke prevention medication that may carry less risk, such as an antiplatelet agent, may be appropriate. In patients with more typical vascular disease risk factors and less confirmatory laboratory evidence of aPS (ie, low to moderate titer of anticardiolipin antibodies and lack of other clinical or serologic evidence of aPS), a more conservative approach may be considered and antiplatelet therapy initiated. In either situation, close follow-up for recurrent thrombosis and aPL can help determine whether more or less aggressive (risky) therapies should be considered. Results of randomized controlled trials of different treatment options for aPS are awaited.
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PMID:Antiphospholipid Antibody Syndrome. 1109 70


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