Hypercoagulable states and stroke: a selective review

Blood disorders have been implicated in approximately 5% to 10% of ischemic stroke, with an increased frequency in younger patients. Most disorders are associated with an increased thrombotic tendency and, therefore, an increased risk of ischemic stroke. Less commonly, a bleeding diathesis may predispose a patient to intracranial hemorrhage. While many conditions predisposing to thrombosis have been associated with stroke, there are relatively few prospective, epidemiological studies addressing hypercoagulable states and arterial stroke compared with the number of studies on the genetic thrombophilias, which are predominantly associated with venous thrombosis. When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a "hypercoagulable workup". Typically, patients to be screened for coagulation defects will have a prior history of one or more unexplained thromboembolic events. The yield for diagnosing a hypercoagulable state is typically greatest for young stroke patients or those with a family history of thrombosis and who have no other explanations for their stroke (cryptogenic stroke). The yield in typically low in unselected ischemic stroke patients and older patients. Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach.     

Cognitive deficits following coronary artery bypass grafting: prevalence, prognosis, and therapeutic strategies

There is increasing recognition that coronary artery bypass grafting (CABG) may be a risk factor for subtle cognitive decline although the presence and pattern of such decline has varied across studies. Cognitive deficits may present as short-term memory loss, executive dysfunction and psychomotor slowing. Although they are usually are not severe enough to meet criteria for mild cognitive impairment or vascular dementia, they lower quality of life and add to hospitalization and out-of-hospital costs. Proposed mechanisms include surgical-related trauma, genetic susceptibility (eg, apolipoprotein E4 allele), microembolization, other vascular or ischemic changes, and temperature during surgery. Depression and anxiety levels predict subjective perception of these deficits more than objective cognitive performance. Both nonpharmacologic (eg, emboli reduction, temperature, or glucose management) and pharmacologic (eg, dexanabinol, glypromate, nootropics) strategies to prevent post-CABG cognitive deficits are under investigation. Given the large numbers of subjects who may already have CABG associated cognitive deficits, clinical trials of agents being tested for Alzheimer's disease (eg, donepezil, rivastigmine, memantine, neramexane, ginkgo) may also be informative. The results of multicenter long-term outcome studies (with matched control groups) as well as ongoing treatment trials will more conclusively address some of these issues. These data emphasize the need for clinicians to monitor cognitive function before and after coronary bypass surgery, and to educate patients.     

Selective phosphodiesterase type-5 inhibitor treatment of serotonergic reuptake inhibitor antidepressant-associated sexual dysfunction: a review of diagnosis,treatment, and relevance

Sexual dysfunction related to antidepressants, particularly serotonin reuptake inhibitors is a major cause of premature treatment discontinuation. This places patients at increased risk for recurrence, relapse, chronicity, and mortality (eg, suicide). The clinical assessment requires a comprehensive evaluation of sexual function, including libido, arousal, orgasm, and resolution prior to affective disorder, disturbances associated with the emergence of depression, and changes or dysfunctions associated with antidepressant treatment. Other factors to be included for evaluating sexual dysfunction include inquiry for concurrent medical conditions, somatic treatments, lifestyle risk factors, and response to antidepressants. Current treatment approaches to antidepressant-associated sexual dysfunction have relied on open-label reports, literature reviews, and clinical wisdom. Without double-blind, placebo-controlled studies to support them, too much non-evidence-based treatment may be offered to patients. Advances into nonadrenergic-noncholinergic novel signal transduction, specifically phosphodiesterase type-5 inhibitors, offer new opportunities for developing evidence-based treatments for this side effect and improving depression disease management outcomes.     

Post-stroke depression as a predictor of caregivers burden of acute ischemic stroke patients in China

Our aim was to explore the independent attribution of Post-stroke depression (PSD) to caregiver burden of acute ischemic stroke patients. A cross-sectional survey was performed with 271 acute ischemic stroke patients in the Huai-He Hospital and First People’s Hospital of Kaifeng City in China. PSD was assessed by Self-rating Depressive Scale, and caregiver burden was assessed by Zarit Caregiver Burden Interview. Clustered logistic regression was applied to identify the impact of PSD on caregiver burden. As results, female patients, normal muscle strength and PSD were associated with caregiver burden. PSD correlated with an independent influence of 17.2% on the risk of caregiver burden, The independent influence of PSD on caregiver burden was smaller than that of social-demographics of caregivers and clinical factors of stroke patients This study suggests that PSD may have a modest influence on caregiver burden.     

尿微量白蛋白与急性缺血性脑卒中的关系研究

探讨尿微量白蛋白（MA）与急性缺血性脑卒中（AIS）的关系。选取2012年1月1日～2014年3月31日于大连大学附属新华医院神经内科住院的缺血性脑卒中患者175例为研究对象。分为试验组：A1S患者103例;对照组：非AIS患者72例。比较两组的一般资料和MA阳性率情况。结果试验组的MA阳性率为41．75％,显著高于对照组MA的阳性率20．83％（P〈0．05）。MA与AIS可能有相关性,MA可能是AIS的危险因素。     

Diagnosis and prevention of atherosclerotic cerebral infarction

Atherosclerotic disease accounts for approximately 25% of ischemic strokes. Atherosclerotic stroke is caused mainly by embolic events from the carotid artery bifurcation or the aortic arch, although intracranial thrombosis can occur, more often in African Americans, Asians, and diabetes patients. Primary prevention of stroke is critical for patients with risk factors for atherosclerosis, including hypertension, diabetes, smoking and hypercholesterolemia. Stroke can be prevented in patients with established atherosclerotic disease by identification and management of patients with carotid artery stenosis by non-invasive testing. Particular attention must be paid to patients with transient symptoms of brain ischemia.     

Neues in der Akuttherapie des ischämischen Schlaganfalls

Stroke is one of the major causes of mortality and the most important cause of disability in the industrialized world. About 85?% of all strokes are caused by acute occlusion of a cerebral vessel and are, therefore, classified as ischemic stroke. Acute stroke care has seen substantial improvements in the last 20 years with the introduction of specialized acute care units (stroke units) and the implementation of intravenous thrombolysis with rtPA, which can be administered up to 4.5 h after symptom onset. According to recent evidence, even patients with age over 80 years, history of diabetes and stroke, wake up stroke, pretreatment with vitamin K antagonists, or one of the new oral anticoagulants could benefit from rtPA under specific conditions. A new therapeutic option for patients with a severe ischemic stroke could be the combined use of intravenous and intraarterial thrombolysis together with mechanical thrombectomy.     

高尿酸血症与急性脑梗死患者病情严重程度和预后的相关性研究

文章探讨高尿酸血症与急性脑梗死患者病情严重程度和预后的相关性.选择急性脑梗死患者198例,男性115例,女性83例,以前瞻性病例对照的研究方法,分析高尿酸血症与急性脑梗死患者入院时、住院10天时的病情严重程度和90天预后的相关性.高尿酸血症与急性脑梗死患者入院时病情严重程度无关（P＆gt;0.05）,与住院10天时病情严重程度呈负相关（P=0.003）,与10天时的美国国立卫生研究院卒中量表（NIHSS）转归分数呈正相关（P=0.002）,与90天预后呈正相关（P=0.001）.笔者认为高尿酸血症与急性脑梗死患者住院10天时的病情严重程度和90天预后具有独立的相关性.     

The Effect of Non-Stroke Cardiovascular Disease States on Risk for Cognitive Decline and Dementia: A Systematic and Meta-Analytic Review

Cardiovascular disease is associated with increased risk for cognitive decline and dementia, but it is unclear whether this risk varies across disease states or occurs in the absence of symptomatic stroke. To examine the evidence of increased risk for cognitive decline and dementia following non-stroke cardiovascular disease we conducted two independent meta-analyses in accordance with PRISMA guidelines. The first review examined cardiovascular diagnoses (atrial fibrillation, congestive heart failure, periphery artery disease and myocardial infarction) while the second review assessed the impact of atherosclerotic burden (as indicated by degree of stenosis, calcification score, plaque morphology or number of plaques). Studies eligible for review longitudinally assessed risk for clinically significant cognitive decline and/or dementia and excluded stroke and cognitive impairment at baseline. Summary statistics were computed via the inverse variance weighted method, utilising Cox Proportional Hazards data (Hazard Ratios, HR). Both atrial fibrillation (n = 5, HR = 1.26, 95% CI [1.12, 1.43]) and severe atherosclerosis (n = 4, HR = 1.59, 95% CI [1.12, 2.26]) emerged as significant risk factors for cognitive decline and/or dementia. A small set of studies reviewed, insufficient for meta-analysis, examining congestive heart failure, peripheral artery disease and myocardial infarction suggested that these conditions may also be associated with an increased risk of cognitive decline/dementia. In the absence of stroke, patients with atrial fibrillation or generalised atherosclerosis are at heightened risk for cognitive deterioration. Nonetheless, this paper highlights the need for methodologically rigorous and prospective investigation of the relationship between CVD and dementia.     

Alzheimer's disease: progress in the development of anti-amyloid disease-modifying therapies

The amyloid hypothesis--the leading mechanistic theory of Alzheimer's disease--states that an imbalance in production or clearance of amyloid beta (Abeta) results in accumulation of Abeta and triggers a cascade of events leading to neurodegeneration and dementia. The number of persons with Alzheimer's disease is expected to triple by mid-century. If steps are not taken to delay the onset or slow the progression of Alzheimer's disease, the economic and personal tolls will be immense. Different classes of potentially disease-modifying treatments that interrupt early pathological events (ie, decreasing production or aggregation of Abeta or increasing its clearance) and potentially prevent downstream events are in phase II or III clinical studies. These include immunotherapies; secretase inhibitors; selective Abeta42-lowering agents; statins; anti-Abeta aggregation agents; peroxisome proliferator-activated receptor-gamma agonists; and others. Safety and serious adverse events have been a concern with immunotherapy and gamma-secretase inhibitors, though both continue in clinical trials. Anti-amyloid disease-modifying drugs that seem promising and have reached phase III clinical trials include those that selectively target Abeta42 production (eg, tarenflurbil), enhance the activity of alpha-secretase (eg, statins), and block Abeta aggregation (eg, transiposate).     

Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.     

Pregnancy and stroke

The risks of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage are not increased in the 9 months of gestation except for a high risk in the 2 days prior and 1 day postpartum. The remaining 6 weeks postpartum also have an increased risk of ischemic stroke and intracerebral hemorrhage, though less than the peripartum period. Although there are some rare causes of stroke specific to pregnancy and the postpartum period, eclampsia, cardiomyopathy, postpartum cerebral venous thrombosis, and, possibly, paradoxical embolism warrant special consideration. The diagnostic and therapeutic approaches to stroke during pregnancy and the postpartum period are similar to the approaches in the nonpregnant woman with some minor modifications based on consideration of the welfare of the fetus. There is a theoretical risk of magnetic resonance imaging exposure during the first and second trimester but the benefit to the mother of obtaining the information may outweigh the risk. Available evidence suggests that low-dose aspirin (<150 mg/day) during the second and third trimesters is safe for both mother and fetus. Postpartum use of low-dose aspirin by breast-feeding mother is also safe for infant. While proper counseling is imperative, a history of pregnancy-related stroke should not be a contraindication for subsequent pregnancy.     

Hyperperfusion syndromes: insight into the pathophysiology and treatment of hypertensive encephalopathy

Hypertensive encephalopathy is one of the manifestations of a hypertensive crisis. It is not the absolute value of the blood pressure that causes the encephalopathy, rather the presence of an abrupt rise in pressure. In terms of clinical and radiographic findings, there are many similarities among a group of entities, including hypertensive encephalopathy, eclampsia, and immunosuppressant neurotoxicity. Hyperperfusion syndromes may represent these clinical disease states that may share the same pathophysiology. Magnetic resonance imaging fluid attenuated inversion recovery sequences have recognized the prominent cortical involvement of the disease that had been previously missed on computed tomography. Studies have found cortical involvement in 94% of their patients, particularly in mild cases. Animal models demonstrate endothelial damage and enhanced pinocytosis in the cortex as reasons why edema may begin in that region of the brain. Patients diagnosed with hypertensive encephalopathy should be diagnosed and treated promptly in order to avoid further neurological complications. The mean arterial pressure should be lowered by 20% to 25% within the first hour of patient presentation, followed by further gradual reduction in blood pressure over the following 24 hours. Hypertensive emergency in acute ischemic stroke should be managed with more caution. According to the 2003 American Stroke Association treatment guidelines, for patients with ischemic stroke not eligible for thrombolytic therapy, target blood pressures are a diastolic blood pressure <120 mmHg and systolic blood pressure <220 mmHg. The systolic pressure must be <185 mmHg and diastolic pressure <110 mmHg at all times if eligible for thrombolytic therapy.     

Sickle cell disease: primary stroke prevention

Stroke is an important and common complication of sickle cell disease (SCD), affecting children as well as adults. Clinically evident stroke, usually brain infarction, is usually associated with stenosis or occlusion of the intracranial arteries of the Circle of Willis, sometimes with formation of moyamoya (a Japanese word for "hazy" or "like a puff of smoke" that describes the appearance of a abnormal microvasculature on angiography believed secondary to internal carotid artery stenosis or occlusion and the resultant extensive collateralization). Several types of intracranial hemorrhage are observed but usually in older children and adults. Cerebrovascular diseases restricted to small vessels may go unrecognized but is associated with cognitive and learning problems. Prevention of recurrent stroke has been accomplished with chronic blood transfusion. A primary prevention strategy for clinical stroke, based on the Stroke Prevention in Sickle Cell Anemia Trial, has been tested in a randomized clinical trial. Over 2,000 young children with SCD were screened with transcranial Doppler ultrasound (TCD) to detect elevated blood flow velocity indicative of vessel disease and high risk of future stroke. Those randomized to standard care (no transfusion) had a 10%/year risk of stroke, which was reduced >90% with chronic transfusion. This approach is the only primary stroke prevention strategy so far tested in SCD in a randomized controlled trial. Silent lesions on magnetic resonance imaging are associated with an approximately 1.5%/year risk of clinical stroke and a trial is now starting in children with these lesions who do not meet Stroke Prevention in Sickle Cell Anemia Trial criteria for transfusion based on TCD. A controlled trial, based on intervention for nocturnal hypoxemia, is also underway. Hydroxyurea, bone marrow transplantation, antiplatelet, and antithrombotic agents may work but have not been tested in primary prevention in a systematic way. If early and repeated, TCD screening of children, as recommended by National Heart Lung and Blood Institute and the American Stroke Association, were implemented broadly the incidence of new strokes could be greatly reduced in these children.     

Cushing’s disease and melancholia

Striking similarities exist in the endocrinology of Cushing's disease and melancholic depression.Laboratory abnormalities, which have been found in both, include raised urinary,plasma and salivary cortisol, non-suppression of cortisol in the dexamethasone suppression test and adrenocorticotrophin (ACTH) hypersecretion. The hypercortisolism can be so severe in melancholic depression that it is difficult to distinguish from Cushing's disease and has been described as a "pseudo-Cushing's" state. Cerebrospinal fluid corticotrophin-releasing hormone (CRH) levels have been found to be lower in patients with Cushing's disease than in depressed subjects. Dynamic endocrine tests may help to distinguish between the two disorders.An exaggerated response to synacthen has been found in both but a reduced ACTH response to CRH occurs in depression, unlike those with Cushing's disease who show ACTH hyper-responsiveness. Other tests, which may help to distinguish between the two disorders,include the dexamethasone-CRH test, the naloxone test, the insulin-induced hypoglycemia test and the desmopressin stimulation test. Similarities in psychiatric symptoms have been recognised for many years. More recently, the physical complications of melancholic depression have been noted. These include osteoporosis, an increased risk of death from cardiovascular disease, hypertension, a redistribution of fat to intra abdominal sites and insulin resistance. Cushing's disease shares these physical complications and we propose that the common underlying factor is excessive plasma glucocorticoids. The increasing recognition of the physical complications and the increased morbidity and mortality in those who suffer from depression underscores the necessity for early detection and treatment of this illness and screening for undetected physical complications.     

Self-efficacy for health-related behaviour change in patients with TIA or minor ischemic stroke

Abstract

Objective: To assess levels of self-efficacy for health-related behaviour change and its correlates in patients with TIA or ischemic stroke.

Methods: In this prospective cohort study, 92 patients with TIA or ischemic stroke completed questionnaires on self-efficacy for health-related behaviour change and fear, social support and depressive symptoms. Relations between fear, social support, depressive symptoms, cognitive impairment, vascular risk factors and history and demographic characteristics and low-self-efficacy were studied with univariable and multivariable logistic regression.

Results: Median total self-efficacy score at baseline was 4 (IQR 4–5). Older age (OR 1.05, 95% CI 1.01–1.09), depressive symptoms (OR 1.09, 95% CI 1.03–1.16), presence of vascular history (OR 2.42, 95% CI 0.97–6.03), higher BMI (OR 1.15, 95% CI 1.01–1.30), fear (OR 1.06, 95% CI 1.01–1.12) and low physical activity (OR 1.49, 95% CI 1.01–2.21) were significantly associated with low self-efficacy.

Conclusion: Patients with recent TIA or ischemic stroke report high self-efficacy scores for health-related behaviour change. Age, vascular history, more depressive symptoms, higher BMI, less physical activity and fear were correlates of low self-efficacy levels.

Practice implications: These correlates should be taken into account in the development of interventions to support patients in health behaviour change after TIA or ischemic stroke.     

Central Nervous System Complications of Sickle Cell Disease in Children: An Overview

Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, “silent cerebral infarcts” are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined.     

Central nervous system complications of sickle cell disease in children: an overview.

Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, "silent cerebral infarcts" are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined.     

Warriors versus worriers: the role of COMT gene variants

Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val158) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met158) substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.     

Prognostic relevance of quantitative topographical EEG in patients with poststroke aphasia

In this prospective study we analyzed the prognostic value of topographical quantitative EEG (qEEG) in poststroke aphasia. Twenty-three right-handed patients (ages 56 +/- 12 years) with different types of aphasia were studied. Quantitative EEG under resting conditions and an aphasia test battery were applied twice, 2 and 8 weeks after a stroke. EEG power fast Fourier transform was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz), and beta (13.5-20 Hz) frequency bands. EEG abnormalities within and outside speech relevant areas are related to restitution of poststroke aphasia. In the ischemic regions they indicate local disturbances; outside they reflect failures in neuronal networks involved in the generation and propagation of the alpha rhythm.