Ischemia In Young Adults Research Articles

Elevated prothrombin is a risk factor for cerebral arterial ischemia in young adults

The prevalence of elevated prothrombin (PT) in the absence of the G20210A mutation has not been studied in patients with cerebral ischemia. We carried out a case-control study of PT G20210A and PT activity in 49 adult patients aged 45 years or less, with TIA or ischemic stroke without cardiac embolism or large vessel disease, and 87 controls from a group of blood donors. Five patients were heterozygous for PT 20210A (OR=2.3, 95% CI: 0.6–8.0). Even after exclusion of individuals with the PT gene variant, the PT activity was significantly higher in patients than in controls (1.11 vs. 0.97, P=0.0003). The relative risk of cerebral ischemia in patients within the fourth quartile of PT activity (1.10 U/ml or higher), was 3.2 fold (95% CI: 1.03–9.96), than in patients whose level of PT activity was in the second or third quartile. We conclude that, although PT 20210A may be a weak risk factor for TIA and ischemic stroke in young patients, increased PT activity, which is more frequent than the mutation, appears to be more strongly related to cerebral ischemia.

Long-term prognosis of cerebral ischemia in young adults. National Research Council Study Group on Stroke in the Young.

Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P<0.0001, Poisson distribution test, and SMR 7.9, P=0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6. 04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.

Análisis de los resultados ecocardiográficos en pacientes jóvenes con isquemia cerebral

When we consider the importance of cardioembolism in the aetiology of cerebral ischaemia in young adults, echocardiography, both transthoracic and transesophageal, becomes of increasing diagnosis importance. We analyze its usefulness and contribution to the reduction in the number of cerebral ischemias of unknown origin. We selected persons aged between 14 and 45 years who had had cerebral ischaemia during the period between January 1991 and April 1998. The protocol for the diagnosis of stroke in young persons was applied to all of them together with transthoracic echocardiography whenever there was the possibility of embologenous cardiopathy followed by transesophageal echocardiography when the transthoracic echocardiography was not diagnostic. In 114 identified cases, 98 transthoracic echocardiographs were done, of which 14 were diagnostic, together with 32 transesophagic echocardiograms, which showed nine cases of embologenous cardiopathy not detected on transthoracic echography. The most frequent diagnoses were: prolapsed mitral valve (14); patent foramen ovale (8); mitral stenosis (5) and interauricular septal aneurysm (4). A total of 31 patients were diagnosed as having a previously unrecognized cardioembolic origin of their illness. The diagnostic usefulness of transthoracic echography was 22.45% (9.18% were false negatives), and 28.12% for transesophagic echocardiography. These reduced the diagnosis of ischaemia of unknown origin by 32.69% and 20% respectively. Besides, in 75% of the patients with a patent foramen ovale and 100% of those with interauricular septal aneurysms, no other possible cause for their condition was found. Transthoracic echocardiography is a technique to be recommended in all cases of cerebral ischaemia of unknown origin in young adults. Its usefulness may be enhanced by transesophagic ultrasonography when diagnosis cannot be definitely made on transthoracic echosonography alone.

Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients.

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.

High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause.

Anticardiolipin antibodies (aCL) are associated with thrombotic phenomena including cerebral ischemia in young adults. Although aCL are directed to a neoepitope formed by phospholipid and beta2-glycoprotein I (beta2-GPI), immunoassays based on cardiolipin as target antigen are widely used. We previously demonstrated that 47% of aCL-negative systemic lupus erythematosus (SLE) patients had antiphospholipid antibodies (aPL) to epitopes other than cardiolipin, and we found an association between aPL to noncardiolipin antigens and thrombosis. We now assess the prevalence and clinical significance of noncardiolipin aPL in young adults with cerebrovascular disease of undetermined etiology. Seventy-seven non-SLE patients, aged <51 years, with cerebral ischemia were studied. Specificity of aPL were characterized by ELISAs using 7 different phospholipids: cardiolipin (CL), phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (PA), phosphatidylcholine, and phosphatidylethanolamine. Thirty-four patients (44.1%), had aPL to 1 or more of the following antigens: 23.4% to CL, 18.2% to PS, 15.6% to PG, 14.3% to PA, and 28.6% to PI. Fifty-nine patients (76.6%) were aCL negative. Of these subjects 23.4% showed aPL to noncardiolipin epitopes. PI was the specificity with highest prevalence in all subgroups, and in 6 patients anti-PI antibodies were the only detectable aPL. The binding of aPL to the different antigens was beta2-GPI dependent. Our data demonstrate a high prevalence of aPL in young adults with cerebral ischemia of undetermined cause. PI was the specificity with highest prevalence, suggesting that anti-PI antibodies may be an immunological marker in young patients with cerebrovascular disease.

Migrane and Risk of Cerebral Ischemia in Young Adults

Migrane and Risk of Cerebral Ischemia in Young Adults

History of migraine and risk of cerebral ischaemia in young adults

SummaryBackground A history of migraine has been proposed as a risk factor for cerebral ischaemia in women under 45.Methods To investigate the association between history of migraine and cerebral ischaemia, we performed a case-control study of 308 patients aged 15-44, with either transient ischaemic attack (TIA) or stroke, and of 591 age-and sex-matched controls prospectively recruited in seven university hospitals. Crude and adjusted odds ratios were calculated using logistic regression analysis.Findings A history of migraine was more frequent in patients than in controls (14·9% vs 9·1%; adjusted odds ratio 1·9, 95% confidence interval 1·1-3·1). In the prospectively designed subgroup analyses, a history of migraine reached the highest odds ratio (3·7, 95% Cl 1·5-9) and was the only significant risk factor in women below age 35 (p=0·003); atherogenic risk factors were more relevant in men and in patients older than 35; previous migraine attacks with aura were more frequent in stroke patients (odds ratio 8·6, 95% Cl 1-75).Interpretation Our findings indicated that the rare association between migraine and cerebral ischaemia is limited to women below age 35, and suggest a need for careful clinical evaluation of comorbidity in the presence of migraine with aura.

Role and Indication of Two-Dimensional Echocardiography in Young Adults with Cerebral Ischemia: A Prospective Study in 125 Patients

We prospectively evaluated 125 patients with cerebral ischemia aged less than 45 years with cerebral angiography, CT and cardiac tests including two-dimensional echocardiography. Cardiac abnormalities were disclosed in 36 patients (33.6%). Potential sources of embolism were detected in 17 patients (15.8%); in 13 of them the cardiac lesion had previously been unrecognized. Mitral valve prolapse was the commonest cardiac lesion (6.5%). In 5 of these patients carotid atherosclerotic lesions were absent, and associated prothrom-botic factors were always present. In the remaining 2 cases dysplasia and/or dissection of carotid arteries were disclosed. Six patients showed an ''idiopathic'' aortic dilation; in 4 of them dysplasia or dissection of carotid arteries was observed. The ''idiopathic'' pattern of aortic root dilation (dilation limited to the first tract of the aortic root, normal echogenicity and aortic profile) was different from the ''atherosclerotic'' pattern (extensive dilation, increased echogenicity, irregular profile of aortic wall). Only few patients had cardiac lesions with high embolic risk, most patients having asymptomatic, previously unrecognized cardiac diseases. Therefore two-dimensional echocardiography is warranted for the etiological screening of cerebral ischemia in young adults. The detection of a cardiac lesion with low or unknown embolic risk should not preclude a search for other coexisting or prothrombotic factors. Finally, mitral valve prolapse and idiopathic aortic root dilation may be an expression of a minor connective tissue disorder accountable for dysplasia or dissection of carotid arteries.

Zerebrale Ischämien bei jungen Erwachsenen

An overview is given over etiology and prognosis of cerebral ischemias until the age of 40. In a time period of 19 years, 168 patients were diagnosed with cerebral ischemia until the age of 40 (91 females, 77 males). The most frequent etiology is premature atherosclerosis in patients with vascular risk factors (up to 50%). Cardiogenic embolism is responsible for 1 to 34% of the cases: cardiac valve diseases and endocarditis being the most frequent sources. In 2 to 19% a vasculitis is diagnosed. While infectious arteritis is especially frequent in countries of the third world, immunovasculitides are common in Europe and the USA. Noninflammatory vasculopathies include spontaneous or traumatic dissection, fibromuscular dysplasia and vascular malformations. A migrainous stroke is especially frequent in female smokers with intake of oral contraceptives. During pregnancy both sinus thrombosis and arterial ischemia occur. Hematologic causes for ischemia are polycythemia, thrombocytosis and genetic diseases (sickle cell anemia, AT3-deficiency). Cerebral ischemia may occur in connection with the ingestion of ergot-derivates. The prognosis of cerebral ischemia in young adults is better than in older stroke-patients.

Hypercoagulable states and lower limb ischemia in young adults

This study prospectively evaluates hypercoagulable states in patients under 51 years of age undergoing lower extremity revascularization for ischemia and assesses early outcome after operation. Twenty patients whose ages range from 23 to 50 years (mean 40.8 years) were identified prospectively who underwent lower extremity revascularization and evaluation of hypercoagulability. Fifteen patients were male (75%), 10 were black (50%), six had hypertension (30%), and four were diabetic (20%). All but two were cigarette smokers (90%). Seven aortoiliac procedures and 13 infrainguinal procedures were performed. Six patients had one or more abnormalities of regulatory proteins (protein S deficiency, four; protein C deficiency, three; presence of lupus-like anticoagulant, three; plasminogen deficiency, two). Eight of 17 patients in whom platelet aggregation profiles were obtained showed increased reactivity (47%). Only 4 of 17 patients (24%) were normal when tested for all parameters. Arterial or graft thrombosis developed in four of the 20 patients within 30 days after operation. Hypercoagulability was found in all four patients whose revascularizations failed. A high incidence of hypercoagulable states was found in patients under 51 years of age with lower limb ischemia requiring revascularization. Hypercoagulability may have contributed to early postoperative thrombosis of the vascular procedure.

Compression of the coeliac trunk and the angiographic evaluation of its hemodynamic significance

Cases of the recently recognised syndrome of external compression of the coeliac trunk, causing visceral ischaemia in young adults, are reported. A method for the assessment of the functional significance of visceral artery narrowing is described, based on its opacification via collaterals following selective arteriography of a neighbouring artery. The possibility of a varied symptomatology resulting from coeliac insufficiency, and the mechanisms responsible for visceral ischaemia are discussed.