Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

A-G-4G haplotype of PAI-1 gene polymorphisms -844 G/A, HindIII G/C, and -675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (-844 G/A, -675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. METHODS: We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. RESULTS: A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. CONCLUSIONS: Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of -844 G/A, -675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke.

Paraoxonase gene polymorphisms and sporadic ALS.

BACKGROUND: The human paraoxonase (PON) gene family consists of three members, PON1, PON2, and PON3, located adjacent to each other on chromosome 7. PON catalytic activity may be influenced by frequent amino acid variants. Chronic exposure to certain chemicals or to environmental factors causing enhanced lipid peroxidation metabolized by paraoxonases may be a risk factor for sporadic ALS (sALS). OBJECTIVE: The aim of this study was to examine the association between PON1 Q192R, PON1 L55M, and PON2 C311S functional polymorphisms and the risk of sALS in a Polish population. METHODS: The authors included 185 patients with a definite or probable diagnosis of sALS (El Escorial Criteria) and 437 healthy controls of similar age and gender. The paraoxonase polymorphisms were studied by PCR and restriction enzyme digestion. RESULTS: Using logistic regression analyses, the C allele of the C311S polymorphism was associated with sALS in dominant and additive models, whereas the R allele of the Q192R polymorphism was associated with sALS in recessive, additive, and dominant models. The authors compared the distribution of haplotypes between cases and controls. The R-C haplotype was overrepresented among cases (odds ratio 3.44, 95% CI: 1.55 to 7.62, p = 0.002). CONCLUSIONS: Frequent amino acid variants in the paraoxonase 1 and paraoxonase 2 genes are associated with sporadic ALS in a Polish population.

Serum albumin level and nosocomial pneumonia in stroke patients.

Hypoalbuminemia is associated with increased risk of infections. The aim of this study was to determine if serum albumin level is an independent predictor of nosocomial pneumonia in stroke patients. Data of 705 consecutive ischemic stroke patients admitted within 24 h after stroke onset were analyzed retrospectively. Serum albumin level was measured within 36 h after stroke onset. Nosocomial pneumonia was found in 10.5% of stroke patients. Patients with pneumonia had significantly lower serum albumin level than those without pneumonia (31.9 +/- 7.5 g/l vs. 35.5 +/- 6.9 g/l) and serum albumin level was associated with risk of pneumonia on multivariate analysis (OR: 0.95, 95% CI: 0.91-0.98). Our results show that serum albumin level is an independent predictor of nosocomial pneumonia in stroke patients.

DD genotype of ACE gene is a risk factor for intracerebral hemorrhage.

Genetic factors may play a role in susceptibility to stroke. The angiotensin converting enzyme (ACE) gene is a candidate gene for two phenotypically different types of stroke affecting small perforating arteries: spontaneous intracerebral hemorrhage (SIH) and ischemic stroke due to small vessel disease (SVD). The authors report evidence that ACE gene DD homozygosity of the I/D polymorphism in intron 16 is an independent risk factor for SIH, and not for SVD stroke, in a Polish population.

Microalbuminuria and hyperthermia independently predict long-term mortality in acute ischemic stroke patients.

OBJECTIVES: To investigate the association between microalbuminuria (MA) and hyperthermia in acute ischemic stroke and to evaluate their significance as the predictors of long-term mortality after stroke. MATERIAL AND METHODS: We assessed neurologic deficit, urinary albumin excretion and body temperature in 60 patients admitted within 24 h after the onset of their first ischemic stroke. Outcome was assessed by 90-day and 1-year mortality. RESULTS: MA was found in 46.7% of patients. Hyperthermia was found in 18.3% patients on Day 1 and in 25% patients on Day 2. The correlation between albuminuria on Day 2 and the body temperature on Days 1 and 2 was found (r = 0.45, and r = 0.30, respectively; both P < 0.05). The mortality was significantly higher in the group of patients with both MA and hyperthermia on Day 2 (73% vs 10% after 90 days; P < 0.0001 and 73% vs 18% after 1 year, P < 0.005). In the logistic regression analysis, albuminuria (P = 0.017), hyperthermia on Day 1 (P = 0.028) and neurologic deficit on admission (P = 0.044) independently predicted 1-year mortality after ischemic stroke. CONCLUSION: Daily urinary albumin excretion correlates with the body temperature in acute stroke patients, but the predictive power of both these variables is independent of that association.

Transient hyperglycemia in ischemic stroke patients.

The aim of the study was to investigate glucose derangement and its short- and long-term prognostic significance in nondiabetic ischemic stroke patients. The study involved 262 consecutive patients, mean age: 70.1+/-12.4 years, with a supratentorial ischemic stroke. The following data were collected: patients characteristics, risk factors, comorbidities, and stroke severity assessed by the Scandinavian Stroke Scale (SSS). Serum glucose levels were measured on admission, on the next, 2nd, 3rd, 5th, 7th and 14th day after stroke onset. The outcome measures on day 30 were mortality and capacity to perform daily activities: the Barthel Index and Rankin Scale. The 1-year survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression was used to assess predictors of 1-year mortality in nondiabetics. Diabetes mellitus was found in 24.8% of patients and transient hyperglycemia in 36.3% of patients. Patients with transient hyperglycemia scored lower on SSS in the subsequent days of assessment than patients with either diabetes mellitus or normoglycemia. They had larger ischemic lesions on computer tomography (CT) than diabetics and had higher 30-day mortality than normoglycemics (p<0.05). One-year mortality was similar in transient hyperglycemics and diabetics, and both were significantly higher than in normoglycemics (p<0.05). A proportional hazards model analysis showed that transient hyperglycemia is not an independent predictor of death within a year after stroke.

The prognostic significance of microalbuminuria in non-diabetic acute stroke patients.

BACKGROUND: Microalbuminuria (MA) is thought to be a marker of widespread vascular damage. It is associated with increased mortality in diabetes mellitus, hypertension and acute myocardial infarction. The aim of the present study was to evaluate the prognostic significance of MA in non-diabetic acute stroke patients. MATERIAL AND METHODS: We studied 52 patients (mean age 69.3 +/- 12.5 years) diagnosed with ischemic stroke confirmed by computed tomography, who were admitted to the Stroke Unit within 24 hours after the onset of symptoms. The control group consisted of 37 age- and gender-matched subjects (mean age 65.2 +/- 5.7 years), examined 3 to 18 months after ischemic stroke. We excluded patients with diabetes mellitus, positive urinalysis, proteinuria, hepatic or renal insufficiency, neoplastic disease or clinical signs of infection. The severity of the neurological deficit was assessed by the Scandinavian Stroke Scale (SSS). The albumin excretion rate was measured in daily urine collection on the second day of hospitalization, using the immunonephelometric method. The patients were followed up for three months. RESULTS: MA was found in 24 of 52 (46.1%) acute stroke patients and in 5 of 37 (13.5%) controls (p<0.05). Patients with MA scored lower on the SSS than patients without MA, both on admission and later. We found a correlation between the daily excretion of albumin and the severity of neurological deficit on admission, as expressed by the SSS score (r = -0.48, p<0.05). The 90-day mortality rate was higher in patients with MA as compared to patients without MA (45.8% vs 7.1%). Patients with MA scored lower on the Barthel Index on Day 90 (median: 65 vs 100, p<0.01). CONCLUSIONS: We found that MA can be detected in about 46% of non-diabetic patients with acute ischemic stroke. Measuring the albumin excretion rate may be a reliable predictor of increased mortality 3 months after stroke.

[Mechanisms determining the occurrence of microalbuminuria in patients with acute ischemic stroke]. / Mechanizmy powstawania mikroalbuminurii w ostrym okresie udaru niedokrwiennego mózgu.

Microalbuminuria is more prevalent in patients with risk factors for cardiovascular diseases and reflects the widespread vascular damage predisposing to atherosclerosis. It is also found in acute clinical conditions, e.g. myocardial infarction, pancreatitis and stroke, and predicts poor outcome. The mechanism leading to increased albuminuria in these conditions is unknown, therefore we designed the study to investigate the relationship between increased urinary albumin excretion in acute stroke and biochemical markers of stress and inflammatory reaction as well as markers of endothelial damage. Sixty patients with first-time ischemic stroke, admitted within 24 hours to the stroke unit took part in the study. We excluded patients with diabetes, infection, nephropathy and abnormal urinalysis. Neurological deficit was assessed on admission and after 24 hours by Scandinavian Stroke Scale. Daily urinary albumin excretion on Day 2 was measured using the immunonephelometric method. The serum cortisol concentration was measured on Day 1 at 6.00 AM, 10.00 AM, 6.00 PM and 10.00 PM. Daily urinary excretion of epinephrine and norepinephrine was measured on Day 1 and on Day 3. We assessed also hematocrit, ESR, serum glucose and fibrinogen, leukocytosis, thrombocytosis and von Willebrand factor activity. Microalbuminuria was found in 46.7% of patients. There was no difference between patients with micro-albuminuria and those without it regarding sex, age and the prevalence of risk factors for stroke. Patients with micro-albuminuria had greater urinary excretion of epinephrine on Day 1. We did not find any differences regarding von Willebrand factor activity, serum cortisol concentration or other assessed variables. In logistic regression analysis the urinary excretion of epinephrine on Day 1 was the only independent variable predicting the occurrence of microalbuminuria in patients with acute ischemic stroke.

[Prognostic significance of early CT changes in ischemic stroke patients]. / Prognostyczne znaczenie wczesnych zmian w tomografii komputerowej glowy u chorych z udarem niedokrwiennym mózgu.

The aim of the study was to establish the prognostic value of early CT findings in predicting the 30-day mortality after stroke, to assess the prevalence of these findings in acute stroke patients, and to examine the correlation between these findings and the clinical status. 134 patients (mean age 67.5 +/- 12.1) with supratentorial ischaemic stroke and CT performed within 12 hours from onset of the symptoms were included into the study. The neurological deficit and consciousness disturbances were assessed by means of Scandinavian Stroke Scale. The 30-day mortality was registered. CT findings were found in 84 (63.7%) patients, including hypodense lesions in 74 (55.5%), mass effect in 55 (41.0%) and hyperdense middle cerebral artery sign in 5 (3.7%) cases. Patients with mass effect had greater neurological deficit on admission (p < 0.0001), more frequently developed disorders consciousness (p = 0.001) and had greater 30-day mortality (p < 0.0001). Patients with hypodense lesions of at least two types presented with greater neurological deficit observed on the second day of hospitalization (p < 0.05) and had also greater 30-day mortality (p = 0.01). On multivariate analysis mass effect seen in early CT, as well as older age and greater neurological deficit appeared to be independent predictors of 30-day mortality.

Early predictors of 30-day mortality in supratentorial ischemic stroke patients--first episode.

INTRODUCTION: Prognostic factors following stroke remain to be established. The aim of this study was to determine early prognostic factors related with a 30-day mortality in first episode ischemic stroke patients. MATERIALS AND METHODS: The study group comprised 329 consecutive patients, aged between 33 and 99 years (mean age +/- SD 69 +/- 12.6) admitted within 24 hours following their first supratentorial ischemic stroke, confirmed either by computer tomography (CT) and/or autopsy. The following data were assessed within 24 hours of hospitalization: gender, age, history of diabetes mellitus, history of ischemic heart disease, obesity, the neurological deficit at entry and after one day, level of consciousness at entry and after one day, electrocardiographic dysrhythmia at entry, blood pressure at entry and body temperature on the first day following stroke. We also assessed particular serum biochemical and hematological markers including: hematocrit, fibrinogen concentration, platelet count, white blood cell (WBC) count, gamma globulin level, glucose level, cholesterol level, the erythrocyte sedimentation rate (ESR), and creatinine kinase (CK) level. The end-point for assessment was early death (within 30 days). Statistical analysis consisted of univariate analysis and multiple regression. RESULTS: Univariate analysis demonstrated that an older age, increased neurological deficit at entry and on the next day, decreased consciousness at entry and on the next day, electrocardiographic dysrhythmia, increased body temperature and glucose level, decreased cholesterol level and increased CK level were significantly associated with death after 30 days (p < or = 0.05). During multivariate analysis, only a severe neurological deficit (Scandinavian Stroke Scale < or = 15 points) both at entry and on the next day (OR = 8.3; 95% CI: 2.83-24.35), decreased consciousness within the first 24 hours of hospitalization (OR = 19.2; 95% CI: 2.84-127.77) and electrocardiographic dysrhythmia (OR = 5.2; 95% CI: 2.37-13.77) were associated with death after 30 days. CONCLUSION: A severe neurological deficit lasting 24 hours, decreased consciousness within 24 hours of hospitalization and electrocardiographic dysrhythmia are the most important indicators of 30-day mortality in patients with first-time ischemic stroke.

[Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Kraków. V. Disorders of higher cerebral functions in elderly people (65-78 years old)]. / Zaburzenia funkcji poznawczych a czynniki ryzyka chorób ukladu krazenia. Projekt CASCADE Kraków. Czesc V: Zaburzenia wyzszych czynnosci nerwowych u osób w wieku podeszlym (65-78 lat).

Higher cortical dysfunctions, like dysphasia, dysgnosia and dyspraxia, relatively frequent in the elderly, are related to progressive neurodegenerative or vascular disorders with dementia. The aim of the study was to assess the prevalence and the intensity of higher cerebral dysfunctions in the population over 65 years and to investigate the association between these disorders and the presence of other neurological abnormalities, i.e. extrapyramidal signs, primitive reflexes as well as cognitive impairment assessed by Mini-Mental State Examination (MMSE). There were 92 women and 90 men, aged from 65-78 years included in the study. All patients were interviewed for the presence of vascular risk factors. The battery of 21 detailed test of higher cerebral functions testing speech, calculation, reading, writing, praxia and gnosia were performed in each person. Extra-pyramidal signs and primitive reflexes were also examined. Among the disorders of higher cortical functions, slight dyspraxia was the most frequent (33.7%). Finger dysgnosia, dyscalculia and dysgraphia were found less frequently. 25.4% of studied group abnormally performed at least two tests assessing higher cortical functions and when compared with normal persons, they presented significantly more frequent the extrapyramidal signs (63.9% vs. 46.9%, respectively) and had significantly frequent impaired cognitive functions (p < 0.05). Patients with higher cortical dysfunction, when compared with other persons, had more frequent primitive reflexes (p < 0.05). The results of the study showed that slight disorders of higher cortical functions were found in about 25% of studied population; they were more frequent in people with cognitive impairment, primitive reflexes and extrapyramidal signs.

[Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Kraków. VI. Magnetic resonance imaging of the aging brain in elderly persons (65-78 years old)]. / Zaburzenia funkcji poznawczych a czynniki ryzyka chorób ukladu krazenia. Projekt CASCADE Kraków. Czesc VI: Ocena obrazu rezonansu magnetycznego u osób w wieku podeszlym (65-78 lat).

Magnetic resonance imaging (MRI) is the most sensitive non-invasive method for the detection of brain lesions. The aim of the study was to examine the prevalence of brain abnormalities (white matter lesions, atrophy, and infarction) on MRI in an elderly population. Sample of 174 men and women, aged from 65 to 78 years, was examined. MRI scans were made using a mobile MRI 1.0 Tesla machine (Siemens). Imaging was performed with standard spin-echo sequences (slice thickness 5-6 mm thick and 20% gap): proton density, T1 and T2 images. All MRI scans were read using standardized methodology of assessment of deep white matter lesions, periventricular lesions, cortical atrophy and infarction. Medium subcortical white matter lesions (4-10 mm) were present in 55% participants. Large subcortical white matter lesions (> or = 10 mm) were observed in 27% people, 24% had periventricular white matter lesions (score > or = 3), 83% had cortical atrophy (score > or = 4) and 18% had at least 1 infarct. Frequency of cortical atrophy increased gradually by age group (p < 0.01). The cortical atrophy, deep and periventricular white matter lesions were more frequent only in the oldest group (75-78 years).