Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients.

Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.

Predicting Failure to Recover Swallowing in Patients with Severe Post-stroke Dysphagia: The DIsPHAGIc Score.

In post-stroke dysphagia, early identification of patients at highest risk of failing swallowing recovery (SR) would be useful to decide which of them should undergo percutaneous endoscopic gastrostomy. The studies on this subject were numerous but generally based on small statistical samples. In this retrospective study, 1232 patients with ischemic or hemorrhagic stroke (73.7 ± 13.0 years, 51% men) were assessed: 593 non-dysphagic, 351 partially dysphagic and 288 totally dysphagic. Among the latter, 45.1% could not recover oral intake. A score to assess the risk of failing SR was obtained from the group with total dysphagia, and further 210 patients with total post-stroke dysphagia were utilized for validation. A regular progression of stroke severity markers, complications and mortality was observed from non-dysphagic, to partially dysphagic, up to totally dysphagic patients. Among the latter, seven variables were independently associated with failure of SR, and formed the "DIsPHAGIc score": cerebral lesion Diameter ≥ 6 cm (+ 1), left frontal Ischemia (- 1), Partial anterior circulation syndrome (- 1), Hypoxia (+ 1), Antiplatelet drug (+ 1), GCS verbal reaction < 4 (+ 1), Internal capsule ischemia (- 1). The area under the ROC curve was 0.79 (95% CI 0.74-0.85). For total scores ≥ 2 there was a high risk of failing SR, with specificity 76.9%, sensitivity 72.1% and accuracy 74.7%. The application of the DIsPHAGIc score to the validation sample provided almost identical results. The evolution of post-stroke dysphagia towards irreversibility can be predicted by a simple, reproducible and robust scoring system based on 7 variables commonly available during hospitalization.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease.

OBJECTIVES: Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. MATERIALS AND METHODS: This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. RESULTS: In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. CONCLUSIONS: Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. METHODS: Two samples of ischemic stroke patients with a cerebral lesion diameter ≥ 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 ± 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 ± 11.1 years). HT severity was quantified according to the ECASS study (HT score). RESULTS: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39-0.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18-0.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14-0.82, P = 0.015). CONCLUSIONS: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial.

Usefulness of the ACTEL Score to Predict Atrial Fibrillation in Patients with Cryptogenic Stroke.

INTRODUCTION: To assess the probability of undetected atrial fibrillation (AF) in patients with ischemic stroke, we previously compared patients who were first diagnosed with AF with patients with large or small artery disease and obtained the MrWALLETS 8-item scoring system. In the present study, we utilized cryptogenic strokes (CS) as the control group, as AF is normally sought among CS patients. METHODS: We retrospectively examined 191 ischemic stroke patients (72.5 ± 12.6 years), 68 with first diagnosed AF and 123 with CS, who had undergone 2 brain CT scans, echocardiography, carotid/vertebral ultrasound, continuous electrocardiogram monitoring and anamnestic/laboratory search for cardiovascular risk factors. RESULTS: In logistic regression, 5 variables were independently associated with AF, forming the "ACTEL" score: Age ≥75 years (OR 2.42, 95% CI 1.18-4.96, p = 0.02; +1 point); hyperCholesterolemia (OR 0.38, 95% CI 0.18-0.78, p = 0.009; -1 point); Tricuspid regurgitation ≥ mild-to-moderate (OR 4.99, 95% CI 1.63-15.27, p = 0.005; +1 point); left ventricular End-diastolic volume <65 mL (OR 7.43, 95% CI 2.44-22.6, p = 0.0004; +1 point); Left atrium ≥4 cm (OR 4.57, 95% CI 1.97-10.62, p = 0.0004; +1 point). The algebraic sum of these points may range from -1 to +4. For AF identification, the area under the receiver operating characteristic curve was 0.80 (95% CI 0.73-0.87). With a cutoff of ≥2, positive predictive value was 80.8%, specificity 92.7% and sensitivity 55.9%. CONCLUSIONS: The ACTEL score, a simplified and improved version of the MrWALLETS score, allows the identification of patients with first diagnosed AF, in the context of CSs, with a high positive predictive value.

Predicting hemorrhagic transformation and its timing from maximum cerebral lesion diameter in nonlacunar ischemic strokes.

OBJECTIVES: We performed this retrospective cohort study to establish which factors are mostly indicative of the appearance of hemorrhagic transformation (HT) and of its time course in a sample of nonlacunar ischemic strokes. MATERIALS AND METHODS: In 402 patients with nonlacunar ischemic stroke (75.0 ± 12.7 years, 192 male), clinical, laboratory, and neuroimaging variables obtained during the first 3 days of hospitalization were compared between patients with and without HT at computer tomography scan. RESULTS: HT was documented in 129 patients (32.1%), including 36 with parenchymal hematoma (PH), after a median time of 6 days (range 1-27). Many variables were univariately associated with HT, but only 5 of them were confirmed in Cox regression (Hazard Ratio, 95% Confidence Interval): maximum cerebral lesion diameter (CLD) in cm (1.12, 1.06-1.18; p = .0001), hemoglobin in g/dl (1.16, 1.06-1.27; p = .002), blood glucose in mmol/L (1.10, 1.03-1.18; p = .007), prior anticoagulant therapy (1.82, 1.10-3.03; p = .02), and edema with mass effect (1.72, 1.08-2.75; p = .02). Thus, the most significant predictor was CLD. The overall risk of HT was minimum for CLD < 2 cm (1.5%), intermediate for CLD ≥ 2 and < 5 cm (22%), and maximum for CLD ≥ 5 cm (58%). The residual probability of having HT decreased progressively over time, and a simple formula is proposed to predict, from CLD in cm, when the probability of HT falls below 10%. CONCLUSIONS: The main determinant of HT was CLD, a simple quantitative parameter that could prove useful, in particular, in deciding the timing of anticoagulation in cardioembolic stroke patients.

Predicting cerebral edema in ischemic stroke patients.

OBJECTIVES: To produce a scoring system for predicting the development of edema in ischemic stroke patients without edema on admission. METHODS: This retrospective study included 572 ischemic stroke patients (73.3 ± 13.0 years, 300 male) without signs of cerebral edema on the first CT scan, which was performed on admission. Another scan was normally performed 3 days later, and subsequently whenever needed. Edema was defined as cerebral hypodensity with compression of lateral ventricles. The main clinical, laboratory, and instrumental variables obtained during the first 24 h were related to the appearance of edema on the CT scans performed after the first one. RESULTS: Cerebral edema occurred in 158 patients (27.6%) after a median time of 4 days. The variables independently associated with edema development were (odds ratio, 95% CI) the following: (1) total anterior circulation syndrome (4.20, 2.55-6.93; P < 0.0001), (2) hyperdense appearance of middle cerebral artery (4.12, 2.03-8.36; P = 0.0001), (3) closed eyes (2.53, 1.39-4.60; P = 0.002), (4) vomiting (3.53, 1.45-8.60; P = 0.006), (5) lacunar cerebral syndrome (0.36, 0.17-0.77; P = 0.008); and (6) white matter lesions (0.53, 0.33-0.86; P = 0.01). Counting one positive point for the first four variables and one negative point for the last two variables, a scoring system (E-score) was built. Cerebral edema could be predicted when the score was ≥ 1 (positive predictive value 61.6%, specificity 85.3%, sensitivity 62.0%). The area under the receiver operating characteristic curve was 0.78. CONCLUSIONS: In ischemic stroke patients, six variables obtained during the first 24 h of hospitalization were predictive of subsequent cerebral edema development.

Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

Prognostic significance of carotid and vertebral ultrasound in ischemic stroke patients.

OBJECTIVES: The ultrasound investigation of carotid and vertebral arteries is routinely performed in stroke patients to determine the etiopathogenetic classification and possible need of revascularization. However, the medium and long-term prognostic implications of carotid and vertebral ultrasound in ischemic stroke patients are not yet known. METHODS: This study included 309 ischemic stroke patients (mean age 76.3; 160 men). They all had undergone carotid and vertebral ultrasound (carotid stenoses were measured according to the European Carotid Surgery Trial [ECST] method). After a median interval of 9.4 months, a telephone follow-up was performed to determine their outcome. Dependency or death (modified Rankin scale-mRS >2) and all cause mortality were the study end-points. RESULTS: At follow-up, 158 patients had a mRS >2. In multivariate analysis, of 13 variables univariately predictive of dependency or death, only National Institutes of Health Stroke Scale (NIHSS) score (P < 0.0001), age (P < 0.0001) and ipsi- or contralateral carotid stenosis ≥60% (O.R. 3.5, 95% C.I. 1.5-8.6, P = 0.006) remained associated with a mRS >2. Sixty-nine patients had died. In a Cox proportional hazards regression, of 10 variables univariately predictive of mortality, only NIHSS score (P < 0.0001), age (P = 0.003), total anterior circulation syndrome (P = 0.004), vertebral Doppler abnormalities (O.R. 2.2, 95% C.I. 1.3-3.6, P = 0.006), male sex (P = 0.02), and hypercholesterolemia (P = 0.04, inverse relationship) remained associated with mortality. CONCLUSIONS: In stroke patients, carotid stenoses ≥60%, ipsi- or contralateral to cerebral lesions, were associated with an increased medium and long-term probability of dependency or death, and abnormalities of vertebrobasilar flow were a significant indicator of death risk, independent of stroke severity and age.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

BACKGROUND: The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid-femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. METHODS: We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. RESULTS: In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. CONCLUSIONS: The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

Hypertension and Other Determinants of White Matter Lesions in Stroke Patients.

Hypertension is the main risk factor for both white matter lesions (WMLs) and stroke, but many stroke patients do not have WMLs. To find specific determinants of WMLs, the authors assessed 321 ischemic and hemorrhagic stroke patients who had undergone echocardiography. The patients with WMLs (n=160) were more often hypertensive and had a higher systolic blood pressure than the patients without WMLs. However, in a multivariate analysis, only the following variables remained associated with WMLs: (1) age: odds ratio [OR], 1.08 per year (95% confidence interval [CI], 1.06-1.11); (2) left ventricular relative wall thickness (RWT) ≥0.52: OR, 2.78 (95% CI, 1.59-4.88); (3) lacunar strokes: OR, 4.15 (95% CI, 1.83-9.44); (4) hemorrhagic strokes: OR, 5.36 (95% CI, 1.57-18.39); and (5) female: OR, 1.91 (95% CI, 1.12-3.27). Thus, the main modifiable risk factor for WMLs was RWT, which proved to be an even stronger risk factor than hypertension. This suggests that RWT might be a useful target in the treatment of hypertension to counteract the appearance of WMLs.

Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance.

BACKGROUND: Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood. METHODS: On days 0, 3, 7, and 14 after admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices. RESULTS: During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP. CONCLUSIONS: The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels.

Factors predisposing to small lacunar versus large non-lacunar cerebral infarcts: is left ventricular mass involved?

OBJECTIVES: To find some specific determinants of lacunar strokes (LS), this study compared LS and non-LS patients using the size and location of cerebral lesions as discriminant between the two groups. METHODS: The main cardiovascular risk factors and some echocardiographic parameters were assessed in 225 ischemic stroke patients aged 75·1±11·4 (SD) years, including 101 patients with symptoms and lesions of lacunar type (deep hypodensities with diameter ≤ 1·5 cm) and 124 patients with non-lacunar lesions. RESULTS: LS patients tended to be younger and had a higher prevalence of smokers than non-LS patients. In a subgroup undergoing echocardiogram, those with LS had a higher left ventricular mass index (LVMI) than non-LS patients (141·6±44·9 vs. 115·1±31·8 g/m(2), P = 0·005). The prevalence of hypertension, diabetes, and carotid stenoses > 50% was similar in the two groups. In multivariable analysis the ever-smoker status (OR = 1·9, P = 0·02), atrial fibrillation (inverse association, OR = 0·5, P = 0·03), LVMI ≥ 130 g/m(2) (OR = 6·6, P = 0·001), and age ≤ 72 years (OR = 5·9, P = 0·003) remained independently associated with LS. CONCLUSIONS: The patients with lacunar cerebral lesions had a greater left ventricular mass than those with non-lacunar lesions, while blood pressure values did not differ. Lacunar lesions were also associated with smoking and a younger age.

Predictors of short-term improvement of ischemic stroke.

OBJECTIVES: Several studies have sought factors predictive of early neurological deterioration during acute stroke; however, no study carried out a systematic search for factors capable of predicting early improvement. This investigation is aimed at identifying the variables associated with short-term neurological improvement in patients with ischemic stroke not undergoing thrombolysis. METHODS: Two-hundred and fifty-two patients with ischemic stroke were retrospectively examined (mean age: 76.7 ± 10.6 years, 120 males, median delay of admission 8 hours). Stroke severity was assessed both on admission and at discharge (median stay: 4 days) by the National Institutes of Health Stroke Scale (NIHSS). Improvement was defined as a difference between initial and final assessment (ΔNIHSS) ≥ the median value (2 points). Thus, 127 patients improved (mean change: +3.8 points) and 125 did not (mean change: -1.4 points). RESULTS: During the first 48 hours of hospitalization, 263 clinical, laboratory, instrumental, and therapeutic variables were collected. These were preliminarily compared between two subgroups of patients, improved and non-improved, which were matched for initial NIHSS score, and 17 possible predictors of improvement were found. The subsequent multivariable analysis led to the identification of four factors independently associated with improvement (odds ratio, 95% confidence interval): total anterior circulation syndrome (TACS) (0.20, 0.10-0.39, P<0.0001), aphasia (3.58, 1.89-6.77, P = 0.0001), average systolic blood pressure (0.98 per mmHg, 0.96-0.99, P = 0.002), and age (0.97 per year, 0.94-0.99, P = 0.02). CONCLUSIONS: The ischemic strokes that are not TACS, with aphasia, with normal/low blood pressure, or occurring in younger subjects, may have a significant tendency to short-term improvement.

Recurrent ischemic strokes in a young celiac woman with MTHFR gene mutation.

Celiac disease (CD) is frequently associated with neurological disorders, but very few reports concern the association with ischemic stroke. A 26-year-old woman affected by CD with secondary amenorrhea, carrier of a homozygous 5,10-methylenetetrahydrofolate reductase mutation with hyperhomocysteinemia, was affected by two occipital ischemic strokes within a period of 5 mo. At the time of the second stroke, while she was being treated with folic acid, acetylsalicylic acid and a gluten-free diet, she had left hemianopsia, left hemiparesthesias, and gait imbalance. Brain magnetic resonance imaging showed a subacute right occipital ischemic lesion, which was extended to the dorsal region of the right thalamus and the ipsilateral thalamo-capsular junction. Antitransglutaminase and deamidated gliadin peptide antibodies were no longer present, while antinuclear antibodies, antineuronal antibodies and immune circulating complexes were only slightly elevated. Since the patient was taking folic acid, her homocysteine ​​levels were almost normal and apparently not sufficient alone to explain the clinical event. A conventional cerebral angiography showed no signs of vasculitis. Finally, rare causes of occipital stroke in young patients, such as Fabry's disease and mitochondrial myopathy, encephalomyopathy, lactic acidosis and stroke-like symptoms, were also excluded by appropriate tests. Thus, the most probable cause for the recurrent strokes in this young woman remained CD, although the mechanisms involved are still unknown. The two main hypotheses concern malabsorption (with consequent deficiency of vitamins known to exert neurotrophic and neuroprotective effects) and immune-mediated mechanisms. CD should be kept in mind in the differential diagnosis of ischemic stroke in young patients.

Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications.

Uric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed.

The atorvastatin during ischemic stroke study: a pilot randomized controlled trial.

OBJECTIVES: Statins have antioxidant, anti-inflammatory, anticoagulant, and profibrinolytic properties that might play a useful role in the acute phase of ischemic stroke. This pilot study assessed the possible neuroprotective action of high-dose atorvastatin administration during the first week after an ischemic stroke, to obtain data for planning a wider multicenter study. METHODS: Sixty-two patients with ischemic stroke, aged 75.3 (SD, ±11.9) years (68% women), were randomized into a placebo (n = 31) and an atorvastatin 80 mg/d (n = 31) group. The double-blind treatment lasted 7 days. The primary end point was a decrease of National Institutes of Health Stroke Scale score of 4 points or higher after 7 days. Infarct volume measured on computed tomographic scan after 3 days and a modified Rankin Scale of less than 2 at 3 months were secondary end points. RESULTS: There was no difference in the primary end point between the 2 groups (odds ratio, atorvastatin vs placebo, 0.74; 95% confidence interval, 0.26-2.17). Infarct volume also was similar in the 2 groups. Instead, there were more patients with modified Rankin Scale of less than 2 at 3 months in the atorvastatin than in the placebo group (adjusted odds ratio, 6.7; 95% confidence interval, 1.0-45.0; P = 0.05). This prevalence concerned only the subgroup with mild strokes (National Institutes of Health Stroke Scale, ≤10; 53.8% vs 15.4%, respectively; P = 0.04). Atorvastatin was well tolerated. CONCLUSIONS: This pilot study was unable to show any short-term benefit of atorvastatin during the acute phase of ischemic stroke. However, it suggested a possible favorable functional effect at 3 months in the least severe strokes, which could be the primary end point for a future multicenter trial.

The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases.

Microparticles (MPs) are small vesicles, ranging in size from 0.1 microm to 2 microm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.

The functional role of dendritic cells in atherogenesis (Review).

Accumulating evidence suggests that dendritic cells (DCs) play a crucial role in the generation and progression of atherosclerosis (ATS), a lipid-related immuno-inflammatory disease. DCs have the ability to process and present antigens (mainly oxidized low-density lipoproteins, heat shock proteins and fragments of necrotic or apoptotic cells) to naive T cells, and the activation of T cells is a key step for the progression of atherosclerotic disease. The existence of some distinct DC subtypes has now become evident. The main categories of DC subsets are the 'conventional or myeloid' and the 'plasmacytoid', which differ in toll-like receptor type and site of expression, pathogens and antigens recognized, and effector cytokines and functions. Studies on the potential impact of DCs in the pathogenesis of ATS may lead to novel therapies to regulate the immunoreactions occurring in atherogenesis. In particular, diltiazem, peroxisome proliferator activated receptor agonists and statins have been shown to protect endothelial cell function by inhibiting DCs, a mechanism that may play a significant role in the prevention of ATS.