Relationship between red cell distribution width and stroke in patients with stable chronic heart failure: a propensity score matching analysis.

AIM: We aimed to investigate the association between baseline red cell distribution width (RDW) level and the risk of stroke in patients with heart failure (HF). METHODS: A total of 153 consecutive patients with HF (New York Heart Association [NYHA] I-III and left ventricular ejection fraction of <40%) were included in this prospective study. All the patients were followed up for 1 year, and during this period the cerebrovascular disease was questioned. RESULTS: In matched population, using propensity score matching comparing patients with HF having stroke with patients without stroke, we found significantly increased basal RDW and serum uric acid. The receiver-operating characteristic curves of RDW for predicting stroke are performed. An RDW ≥ 15.2% measured on admission had 87% sensitivity and 74% specificity in predicting stroke in patients with HF (area under the curve: 0.923, 95% confidence interval: 0.852-0.994, P < .001). CONCLUSION: In conclusion, this study demonstrated that RDW may be important hematological indices for stroke in patients with HF using propensity score analysis.

Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS: A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS: The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36-6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49-1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS: Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.

Recurrent depression, cardiovascular disease, and diabetes among middle-aged and older adult women.

BACKGROUND: The goal of this study was to investigate the concurrent and prospective relationships between a history of single and recurrent major depression disorder (MDD) and the medical conditions of cardiovascular disease (CVD) and diabetes using a community sample of middle- and older-aged women. METHODS: Data from women (n=557 at baseline; mean age=55.7 years) participating in a two-wave longitudinal study (5-year interval) were used to examine associations between single and recurrent MDD, assessed with a structured clinical interview, and three self-report indicators of CVD (heart attack or myocardial infarction, stroke, angina), major CVD risk markers (hypertension, high cholesterol), and diabetes. Analyses were conducted to evaluate hypotheses which proposed that recurrent depression would be significantly associated with the three medical outcomes, but not single episode MDD. RESULTS: After controlling for a range of important covariates (e.g., BMI, smoking, alcohol use), cross-sectional analyses indicated that recurrent MDD, but not single episode MDD, significantly predicted CVD risk and diabetes. Prospective analyses indicated that recurrent MDD, but not single episode MDD, increased the risk for CVD and diabetes. LIMITATIONS: The sample was a predominantly white, middle-class sample so generalizability of findings may be limited for minorities and men. Reliance on self-report data may have biased the findings. CONCLUSIONS: These findings suggest the benefits of measuring single versus recurrent MDD when investigating the risk of depression on chronic diseases. Findings also suggest the importance of identifying individuals suffering from recurrent MDD early in their lifespan with the goal of preventing future depressive episodes.

[Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients]. / Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.

INTRODUCTION. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. PATIENTS AND METHODS. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. RESULTS. None of the 10 patients studied presented any relevant events in the mothers' medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. CONCLUSIONS. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible.

TITLE: Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.Introduccion. El accidente cerebrovascular (ACV) fetal o prenatal se define como un suceso isquemico, trombotico o hemorragico arterial o venoso que acontece entre las 14 semanas de gestacion y el inicio del parto. Pacientes y metodos. Estudio retrospectivo de una serie de 10 pacientes afectos de un ictus, presumiblemente fetal, desapercibido durante el embarazo y diagnosticado en la etapa de lactante; se destacan cuales han sido los sintomas y la edad en que se han identificado. Resultados. De los 10 pacientes estudiados, ninguno presentaba antecedentes maternos relevantes, pero se detectaron cuatro amenazas de parto pretermino que se resolvieron con las medidas habituales y sin hallazgos de alteracion fetal posterior. Entre el segundo y tercer trimestre de vida es cuando se han realizado los estudios que han llevado al diagnostico, y se ha indicado por la familia una menor movilidad de un hemicuerpo respecto al contralateral como motivo de consulta. Dos pacientes presentaban una trombofilia. Con una media de seguimiento de seis años, todos asocian una paralisis cerebral infantil, la tercera parte una epilepsia y el 75% tiene dificultades de aprendizaje o discapacidad intelectual. Conclusion. Cuando los ACV no se detectan prenatalmente, es importante que en la atencion primaria se busquen y detecten los signos de alarma del desarrollo psicomotor del lactante de forma precoz para iniciar su estudio y procurar una rehabilitacion lo mas pronto posible.

[New developments in spastic unilateral cerebral palsy]. / Hémiplégie cérébrale infantile: épidémiologie, aspects étiologiques et développements thérapeutiques récents.

INTRODUCTION: Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. STATE OF THE ART: Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. PERSPECTIVES: In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

Linkage of cell cycle kinetics between embryonic and adult stroke models: an analytical approach.

In the adult brain, neurogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle. The proliferating population and the cell cycle kinetics in the ventricular zone regulate cortical neurogenesis during the development. Using the embryonic model, we investigated kinetics of SVZ cells in adult rats after stroke, incorporating migration of SVZ cells to the ischemic boundary. Concurrent linear regressions were considered through iteration to improve precision of parameter estimation. We found no model-fit difference in stroke with and without the migration (p=0.31), suggesting no migration effect on assessment of the cell kinetics. Stroke increased SVZ cell proliferation (20% in non-stroke and 31% in stroke p<0.01). Cell cycle durations in stroke were reduced for the total cycle length (19h for non-stroke and 15.3h for stroke, p<0.05), in G1 phase (12.6 h for non-stroke and 9.6 h for stroke, p<0.01), but were the same in S, M2, and in G2 phases compared to non-stroke, indicating that stroke reduces the total cell cycle length, specially in G1 phase. We conclude that cell cycle kinetic models for cortical development can be adapted to the kinetics of adult SVZ cells after stroke. The analytical approach may be useful for studying neural progenitor cell proliferation under different treatments.

Fetal stroke and congenital parvovirus B19 infection complicated by activated protein C resistance.

UNLABELLED: Parvovirus B19 infection in gestation has been associated with severe fetal complications such as anaemia, hydrops and fetal demise. Fetal infection in the first trimester poses the greatest risk for these complications, but infection during the third trimester is more common than previously appreciated and can be associated with severe complications, i.e. fetal death, in the absence of hydrops or classical clinical symptoms. Parvovirus B19 infection has been associated with vasculitis and pathological changes in the central nervous system, which may cause stroke. We report a newborn infant with a rare combination of a recent central nervous system infection with parvovirus B19 and a factor V Leiden mutation, who developed fetal stroke. CONCLUSION: Factor V Leiden mutation leads to activated protein C resistance and increases the risk of thromboembolism. Thromboembolism occurs rarely in newborns with activated protein C resistance, but can be precipitated by dehydration, asphyxia and infection. Although parvovirus B19 infection of the central nervous system may be a precipitant in neonatal and/or fetal stroke, it can also cause stroke independent of a thrombophilic mutation. In this case, both causative factors may have coincided.

Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development.

INTRODUCTION: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNA(leu) gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. MATERIALS AND METHODS: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. RESULTS: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months-3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months-6 years. CONCLUSION: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.

Perinatal stroke--risk factors and management.

Stroke is an uncommon but increasingly recognised cause of mortality and long-term neurological morbidity in children. A significant number of these events appear to be caused by thromboembolic disease and, as with other childhood thrombotic problems, the incidence of central nervous system events appears highest during the neonatal period. In contrast to peripheral arterial and venous thrombotic problems, it is likely that a proportion of cerebral thromboembolic events occur either in utero or perinatally and reflect different risk factors from those occurring in older infants and children. The pathophysiology of perinatal stroke is complex and in many cases is likely to be multifactorial. It is now recognised that risk factors may relate to both maternal and placental problems as well as fetal and neonatal disorders. Large prospective studies of perinatal stroke are currently lacking and efforts to define the relative contribution from each of these areas are at an early stage. The complex nature of these disorders requires collaboration between a number of different disciplines including obstetrics, fetal medicine, pathology, neonatology and neurology. Of particular interest to haematologists is the possible impact of prothrombotic abnormalities in the pathophysiology of these events and also the potential for the use of antithrombotic agents in both management and prevention.