Serum Neurofilament Light Chain Concentration Correlates with Infarct Volume but Not Prognosis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We studied serum neurofilaments diagnostic value in patients with acute ischemic stroke (AIS) or TIA and evaluated any correlation with symptom severity, cerebral infarction volume, aetiology, and clinical outcome. METHODS: One hundred and thirty-six patients (101 with AIS, and 35 with TIA) were included. Acute-phase serum neurofilament light chain (sNfL) was analyzed with a novel ultrasensitive single molecule array (Simoa). Cerebral infarction volume was measured from brain computed tomography in the subacute phase (>2 days). Stroke aetiology was defined by trial of ORG 10172 in acute stroke treatment classification, severity by National Institute of Health stroke scale (NIHSS) and the degree of disability by the Modified Rankin Scale (mRS) after 90 days. RESULTS: sNfL was markedly higher in patients with AIS (89.5 pg/mL [IQR: 44.7-195.3]) than with TIA (25.2 pg/mL [IQR: 14.6-48.0]), P= <.001), also after adjusting for age, NIHSS, and stroke volume (P= .003). In receiver operating characteristic analysis, sNfL concentration greater than or equal to 49 pg/mL proved to be the best cut-off value to differentiate between patients with stroke and those with TIA (sensitivity of 73% and specificity of 80%). sNfL concentration significantly correlated with cerebral infarction volume (r = .413, P= <.001), this association remained significant after adjusting for established predictors (P= .019). Patients with AIS due to cardioembolism or large artery atherosclerosis had the highest sNfL concentrations. NIHSS on admission (r = .343, P = <.001) and mRS scores after 3 months (r = .306, P = .004) correlated with sNfL concentration, however functional outcome 3 months after stroke was not associated with sNfL after adjusting for potential confounders. CONCLUSIONS: Cases with stroke were distinguishable from those with TIA following the determination of sNfL in the blood samples. The presence and amount of axonal damage estimated by sNfL correlated with the final cerebral infarction volume but was not predictive of degree of disability.

Incidentally detected enhancing lesions found in breast MRI: analysis of apparent diffusion coefficient and T2 signal intensity significantly improves specificity.

OBJECTIVES: To evaluate the value of adding T2- and diffusion-weighted imaging (DWI) to the BI-RADS® classification in MRI-detected lesions. METHODS: This retrospective study included 112 consecutive patients who underwent 3.0T structural breast MRI with T2- and DWI on the basis of EUSOMA recommendations. Morphological and kinetic features, T2 signal intensity (T2 SI) and apparent diffusion coefficient (ADC) findings were assessed. RESULTS: Thirty-three (29.5 %) patients (mean age 57.0 ± 12.7 years) had 36 primarily MRI-detected incidental lesions of which 16 (44.4 %) proved to be malignant. No single morphological or kinetic feature was associated with malignancy. Both low T2 SI (P = 0.009) and low ADC values (≤0.87 × 10-3 mm2s-1, P < 0.001) yielded high specificity (80.0 %/80.0 %). The BI-RADS classification supplemented with information from DWI and T2-WI improved the diagnostic performance of the BI-RADS classification as sensitivity remained 100 % and specificity improved from 30 % to 65.0 %. The numbers of false positive lesions declined from 39 % (N = 14) to 19 % (N = 7). CONCLUSION: MRI-detected incidental lesions may be challenging to characterize as they have few specific malignancy indicating features. The specificity of MRI can be improved by incorporating T2 SI and ADC values into the BI-RADS assessment. KEY POINTS: • MRI-detected incidental lesions have few specific malignancy indicating features. • ≥ 1 suspicious morphologic or kinetic feature may warrant biopsy. • T2 signal intensity and DWI assessment are feasible in primarily MRI-detected lesions. • T2 SI and DWI assessment improve the BI-RADS specificity in MRI-detected lesions.

Etiology, diagnostics and treatment of cardiogenic stroke.

Approximately 15 to 40% of cerebral infarctions and transient ischemic attacks (TIA) are of cardiac origin. Knowledge of a significant cardiac disease arouses the suspicion of cardiogenic embolism, but its diagnosis requires identification of the source of embolism. Atrial fibrillation is the most common cause of cardiogenic embolism, and should be actively sought after an ischemic cerebrovascular attact. The detection of atrial fibrillation or an intracardiac thrombus in these patients requires initiation of permanent anticoagulant therapy. Transesophageal echocardiography (TEE) has proven to be more sensitive than transthoracic echocardiography (TTE) in detecting certain possible cardiogenic sources of embolism.

Effect of middle cerebral artery territory ischemic stroke on QT interval.

BACKGROUND: Prolonged QT interval associates with increased risk for sudden cardiac death after acute ischemic stroke. However, pathophysiology of prolonged QT interval after stroke is poorly elucidated. In this study, we investigated whether QT interval dynamics is different in patients with right and left middle cerebral artery (MCA) territory stroke. METHOD: Electrocardiogram (ECG) intervals were compared between baseline (retrieved retrospectively from medical records) and admission (acquired at the acute hospital admission) in 33 patients (65 ± 9.5 years) with right or left MCA territory ischemic stroke. Head computed tomography (CT), cardiac ultrasound, and cardiac CT scans were undertaken. RESULTS: Stroke was located in the right MCA territory in 21 (64%) and in the left MCA territory in 12 (36%) patients. Patients with right and left MCA stroke were similar with respect to time interval between baseline and admission ECG recordings, positive history of heart disease, and left ventricular dimensions. Increase in heart rate-corrected QT interval (QTc) from baseline to admission was demonstrated to occur more often in patients with right (16 of 21; 76%) than in patients with left (3 of 12; 25%; P < .01) MCA stroke. ΔQTc between baseline and admission was significantly longer in patients with right (23 ± 23 milliseconds) than in patients with left (-11 ± 19 milliseconds; P < .0001) MCA stroke. Percent ΔQTc between baseline and admission was longer in patients with right (5.5% ± 5.5%) than in patients with left (-2.6% ± 4.7%; P < .001) MCA stroke. CONCLUSIONS: Right MCA ischemic stroke results in prolongation of QT interval. Findings indicate cerebral asymmetry in brain-heart interaction during acute ischemic stroke.

Effect of different thresholds for CT perfusion volumetric analysis on estimated ischemic core and penumbral volumes.

PURPOSE: This single-center study compared three threshold settings for automated analysis of the ischemic core (IC) and penumbral volumes using computed tomographic perfusion, and their accuracy for predicting final infarct volume (FIV) in patients with anterior circulation acute ischemic stroke (AIS). METHODS: Fifty-two consecutive AIS patients undergoing mechanical thrombectomy (November 2015-March 2018) were included. Perfusion images were retrospectively analyzed using a single CT Neuro perfusion application (syngo.via 4.1, Siemens Healthcare GmbH). Three threshold values (S1-S3) were derived from another commercial package (RAPID; iSchema View) (S1), up-to-date syngo.via default values (S2), and adapted values for syngo.via from a reference study (S3). The results were compared with FIV determined by non-contrast CT. RESULTS: The median IC volume (mL) was 24.6 (interquartile range: 13.7-58.1) with S1 and 30.1 (20.1-53.1) with S2/S3. After removing the contralateral hemisphere from the analysis, the median IC volume decreased by 1.33(0-3.14) with S1 versus 9.13 (6.24-14.82) with S2/S3. The median penumbral volume (mL) was 74.52 (49.64-131.91), 77.86 (46.56-99.23), and 173.23 (125.86-200.64) for S1, S2, and S3, respectively. Limiting analysis to the affected hemisphere, the penumbral volume decreased by 1.6 (0.13-9.02), 19.29 (12.59-26.52), and 58.33 mL (45.53-74.84) for S1, S2, and S3, respectively. The correlation between IC and FIV was highest in patients with successful recanalization (n = 34, r = 0.784 for S1; r = 0.797 for S2/S3). CONCLUSION: Optimizing thresholds significantly improves the accuracy of estimated IC and penumbral volumes. Current recommended values produce diversified results. International guidelines based on larger multicenter studies should be established to support the standardization of volumetric analysis in clinical decision-making.

Serum High-Sensitive C-reactive Protein May Reflect Periodontitis in Patients With Stroke.

BACKGROUND/AIM: Chronic infectious diseases are believed to increase the risk of stroke. We aimed to evaluate the prevalence of periodontal disease and its association with systemic inflammatory processes in patients suffering an acute stroke/transient ischemic attack (TIA). PATIENTS AND METHODS: Altogether 36 acute stroke/TIA patients underwent clinical, laboratory and radiological examinations. The level of systemic inflammation was analyzed both with routine measurements of plasma C-reactive protein (p-CRP) and serum high-sensitivity CRP (s-hsCRP) to analyze their associations with periodontitis. The diagnostic criteria for periodontitis included increased probing depth (>4 mm) measured from four different sites, bleeding on probing, and horizontal (>1 mm), vertical (>1 mm) or apical bone loss observed on orthopantomography. RESULTS: Twenty-six (72.2%) patients were diagnosed with periodontitis. Only five of the patients with periodontitis (19.2%) had elevated p-CRP values whereas the majority, (17/26; 65.4%) had elevated s-hsCRP values (p<0.01). Absolute s-hsCRP values in patients with periodontitis (8.9±12.5 mg/l) were significantly higher than in patients without periodontitis (2.3±3.0 mg/l; p<0.05). Absolute p-CRP concentrations did not differ (2.3±5.8 vs. 2.4±5.1 mg/l; p=not significant). The total number of periodontitis findings was significantly associated with s-hsCRP values (r=1.83) but not with p-CRP values. Conversely, seventeen of the nineteen patients with elevated s-hsCRP (89.5%) indicative of systemic inflammation had periodontitis. CONCLUSION: Periodontitis is a common finding among patients with acute stroke/TIA as over 80% of patients with cryptogenic stroke/TIA had periodontitis. S-hsCRP is a useful tool for detecting subclinical systemic inflammation.

Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events.

BACKGROUND/AIM: We aimed to analyze the diagnostic value of total tau (T-tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. PATIENTS AND METHODS: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8±50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. RESULTS: T-tau was higher in patients with stroke [1.0 pg/ml (IQR=0.3-2.2)] than with TIA [0.5 pg/ml (IQR=0.2-1.0), p=0.02]. The levels of S100B were also increased in stroke [0.082 µg/l (IQR=0.049-0.157)] patients compared to TIA patients [0.045 µg/l (IQR=0.03-0.073), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 µg/l (IQR=9.30-16.14)] compared to those with TIA [10.96 µg/l (IQR=7.98-15.33), p=0.30] were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). CONCLUSION: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.

Mechanical Thrombectomy of Large Artery Occlusion Is Beneficial in Octogenarians.

AIM: Recent trials have established the benefit of endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large artery occlusion (LAO). However, older patients were often excluded from trials. EVT outcomes were retrospectively compared between octogenarians and younger patients treated for LAO in a tertiary hospital. PATIENTS AND METHODS: A total of 199 consecutive patients with anterior circulation AIS that underwent EVT between 2009 and 2015 in the Kuopio University Hospital were included. Patients were dichotomized into younger (<80 years, N=162) and older (≥80 years, N=37) groups. Baseline, imaging, and procedural characteristics, the 3-month modified Rankin Scale (mRS), and 1-year mortality were assessed. To conduct a number-needed-to-treat (NNT) analysis, data on age-dichotomized control groups from a meta-analysis were acquired. RESULTS: Compared to younger patients, older patients exhibited atrial fibrillation (57% vs. 21%, p<0.01) and coronary artery disease (49% vs. 20%, p<0.01) more frequently and Internal Carotid Artery (ICA) occlusion less frequently (22% vs. 55%, p<0.01). Similar proportions of patients received preprocedural intravenous recombinant tissue-type plasminogen activator (r-tPA; 57% vs. 67%), general anesthesia (35% vs. 41%), and reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3; 76% vs. 75%). Older patients had more complications during hospitalization (41% vs. 24%, p=0.034), higher 3-month mRS values (4.0±2.3 vs. 2.8±1.9, p<0.01), fewer favorable mRS values (mRS≤2: 27% vs. 52%, p<0.01), and higher 3-month (46% vs. 10% p<0.01) and 1-year mortality (49% vs. 11%, p<0.01). The NNT to achieve an additional patient with an independent outcome (mRS≤2) was 12 among older and six among younger patients. CONCLUSION: Despite a poor recovery rate, octogenarians benefitted from EVT for AIS, with a NNT comparable to that of younger patients treated with intravenous r-tPA.

Gadoterate meglumine decreases ADC values of breast lesions depending on the b value combination.

To retrospectively evaluated the influence of administration of the gadolinium based intravenous contrast agent (G-CA) on apparent diffusion coefficient (ADC) values in ADC maps generated using multiple b value combinations. A total of 106 women underwent bilateral 3.0 T breast MRI. As an internal validation, diffusion-weighted imaging (b values of 0, 200, 400, 600, 800 s/mm2) was performed before and after the G-CA (gadoterate meglumine (0.2 ml/kg, 3 ml/s)). Whole lesion and fibroglandular tissue (FGT) covering region-of-interests (ROIs) were drawn on the b = 800 s/mm2 images; ROIs were then propagated to multiple retrospectively generated ADC maps. Twenty-seven patients (mean age 55.8 ± 10.8 years) with 32 mass-like enhancing breast lesions including 25 (78.1 %) histopathologically malignant lesions were enrolled. Lesion ADC values were statistically significantly higher in pre-G-CA than post-G-CA ADC maps (ADC0,200,400,600,800: 1.05 ± 0.35 × 10-3 mm2/s vs. 1.02 ± 0.36 × 10-3 mm2/s (P < 0.05); ADC0,200,400: 1.25 ± 0.42 × 10-3 mm2/s vs. 1.20 ± 0.35 × 10-3 mm2/s (P < 0.05)). ADC values between pre- and post-contrast maps were not statistically different when the maps were generated using other b value combinations. Contrast agent administration did not affect the FGT ADC values. G-CA statistically significantly reduced the ADC values of breast lesions on ADC maps generated using the clinically widely utilized b values.

vWF correlates with visceral and pericardial adipose tissue in patients with a recent stroke of suspected cardiogenic etiology.

AIMS: A chronically elevated level of von Willebrand factor (vWF) is a common finding in patients with cardiovascular diseases. Obesity is a well-recognized risk factor for thrombotic cardiovascular complications including ischemic stroke, and it has been linked with increased plasma vWF. We evaluated whether elevated plasma levels of vWF associate with areas of visceral (VAT), pericardial (PAT), and subcutaneous adipose tissue (SAT) compartments in patients with acute/subacute stroke. METHODS AND RESULTS: A total of 69 patients with stroke of suspected cardiogenic etiology were examined. The plasma level of vWF antigen (vWF-ag) was measured both in the acute phase and in the chronic phase three months after stroke. The areas of VAT and/or PAT were assessed with computed tomography. As expected, in stroke patients, the levels of plasma vWF-ag were significantly higher than in the national reference population both in the acute and in the chronic phase. The level of vWF-ag in the chronic phase correlated with the amounts of VAT and PAT, but not with subcutaneous adipose tissue. CONCLUSIONS: These results agree with previous observations of the chronic inflammation/prothrombotic tendency in patients with cerebrovascular disease. Future studies should seek to clarify the role of visceral type adipose tissue in the pathophysiology of ischemic stroke.

Morphological features of the left atrial appendage in consecutive coronary computed tomography angiography patients with and without atrial fibrillation.

The majority of intracardiac thrombi form in the left atrial appendage (LAA). Enlargement of this structure, together with certain morphological features, may indicate a predisposition to the formation of thrombi and subsequent cardioembolic stroke. Thus far, studies on LAA morphology have largely focused on those patients with atrial fibrillation (AF). Taking a different approach, we investigated the variation in LAA morphology in a consecutive patient population with and without AF. We evaluated 808 consecutive patients (529 females; mean age 52.5±9.9 years) who underwent coronary artery computed tomography angiography (CCTA), the majority of whom (749) had no history of AF. We assessed the length, lobe number, and morphological classification of their LAAs. Demographic data and medical histories were collated from medical records and then correlated with LAA morphology. The proportions of each of the four morphological classes of LAA for the overall vs. non-AF population were: WindSock, 62.3/61.5%; Cactus, 18.6/18.8%; ChickenWing, 10.0/10.0%; and CauliFlower, 9.2/9.6%. Age (p<0.001; r = 0.156) and female gender (p<0.001) were both found to be associated with an increased body surface area (BSA)-related LAA length. Male patients were more likely to manifest multi-lobed (p = 0.003) LAAs, and overweight patients with a greater number of multi-lobed LAA morphological classes (p = 0.010). No associations with morphological LAA features could be found for patients with diabetes, hypertension, or dyslipidemia. Nor did the size of the left atrium exhibit any correlation with BSA-related LAA length. In the overall and non-AF populations, aging and female gender were associated with longer BSA-indexed LAAs.

Soluble Urokinase-type Plasminogen Activator Receptor Predicts All-cause 5-Year Mortality in Ischemic Stroke and TIA.

AIM: We evaluated soluble urokinase-type plasminogen activator receptor (suPAR) levels in different stroke subtypes and assessed their prognostic value regarding 5-year outcomes. MATERIALS AND METHODS: The study included 117 stroke patients (81 males; mean=age 61±11 years) with suspected cardioembolic stroke whose plasma suPAR concentration was assessed. Altogether, 20 (17.1%) patients suffered from stroke as a result of cardioembolism, 12 (10.3%) from large-artery atherosclerosis, 9 (7.7%) from small-vessel disease, 11 (9.4%) from both large-artery and cardioembolic etiology, and 65 (55.6%) had cryptogenic stroke. The mean follow-up period was 5 years. RESULTS: suPAR concentration was higher in patients who suffered from stroke/transient ischemic attack due to large-artery atherosclerosis (3.2±0.9 ng/ml) compared to small-vessel disease (2.0±0.5 ng/ml, p<0.001). An elevated plasma suPAR concentration was associated with all-cause mortality during the follow-up period (p=0.003). CONCLUSION: Elevated plasma suPAR concentrations predicted all-cause mortality during the 5-year follow-up after ischemic stroke. suPAR was not able to differentiate patients with cardioembolic stroke from those with other stroke types.

Cardiac CT Differentiates Left Atrial Appendage Thrombi from Circulatory Stasis in Acute Stroke Patients.

BACKGROUND/AIM: The left atrial appendage (LAA) is the most typical origin for a cardioembolic thrombusins' stroke etiology. Although transesophageal echocardiography (TEE) is widely used, this technique encounters difficulties in differentiating solid thrombus from circulatory stasis/spontaneous echo contrast (SEC). We assessed whether cardiac computed tomography (cCT) could more accurately detect LAA thrombi. MATERIALS AND METHODS: A total of 102 patients with suspected acute cardioembolic stroke/ transient ischemic attack (TIA) without chronic atrial fibrillation underwent arterial and venous phase cCT and TEE. TEE and cCT were consensus read to define LAA thrombus, while TEE alone was used to determine SEC. The LAA/aorta Houndsfield unit (HU) ratio was measured in both phases independently and blinded to prior visual readings. The optimal LAA/aorta HU ratio cut-off value for differentiating thrombi and SEC was estimated. RESULTS: TEE indicated 10 SECs and three thrombi. Consensus reading of cCT and TEE indicated that all thrombi detected in TEE were false-positive but revealed three actual thrombi missed in TEE. The LAA/aorta HU ratio correlated significantly with the presence of SEC both in arterial (p=0.019) and venous phases (p=0.024) and with the presence of thrombi in both phases (p<0.001). The best trade-off values for LAA/aorta HU ratio for the detection of thrombi was <0.245 in both phases. SEC was characterized with HU ratios of >0.245 and <0.577 in the arterial phase and>0.245 and <0.824 in the venous phase. Values of sensitivity, specificity, positive and negative predictive value and accuracy for detection of thrombi were 100% for cCT in both phases. CONCLUSION: cCT is more accurate than TEE in the detection of LAA thrombi, especially when combined with the measurement of LAA/aorta HU ratio.

Diagnostic Performance of Left Atrial Diameter Measurement in Computed Tomography to Detect Increased Left Atrial Volume.

BACKGROUND/AIM: The left atrium (LA) is frequently imaged in cardiac computed tomographic (cCT) examinations. The LA volume can be accurately measured with three-dimensional (3D) volumetry but this method is time consuming and thus not routinely used in clinical practice. Accordingly, increased LA size may be overlooked although volume enlargement is associated with adverse cardiovascular events. We evaluated the accuracy of LA diameter measurement in cCT and in transthoracic echocardiography (TTE) in the diagnosis of LA enlargement using 3D cCT as the reference standard. PATIENTS AND METHODS: Altogether, 146 patients with suspected cardiogenic stroke underwent cCT and TTE. LA volume by cCT was determined for all patients. LA diameter was measured in both modalities. Furthermore, 40 healthy controls were analyzed in order to assess the cut-off values for normal LA volume. Diagnostic performance of cCT and conventional TTE diametrical measurements for detecting enlarged LA volume were analyzed and compared using Cohen's kappa (κ). RESULTS: In controls, the mean LA volume was 59.8±15.3 ml and the mean LA diameter was 30.4±5.0 mm by cCT. The mean value plus twice the standard deviation, which was considered the upper limit, for normal LA volume and diameter were 90.4 ml and 40.4 mm, respectively. Age- and gender-matched patients with stroke had statistically significantly (p<0.001) larger LA volumes (85.5±21.1 vs. 59.8±15.3 ml) and diameters (37.6±5.7 vs. 30.4±5.0 mm) than controls. LA diameter measurement by cCT was more reliable in detecting an LA volume enlargement than the corresponding measurement with TTE (κ=0.489 vs. 0.234; p=0.002). CONCLUSION: An enlarged LA diameter measured by cCT was more reliable than TTE at detecting enlarged LA volume.

Left atrial appendage morphology in patients with suspected cardiogenic stroke without known atrial fibrillation.

The left atrial appendage (LAA) is the typical origin for intracardiac thrombus formation. Whether LAA morphology is associated with increased stroke/TIA risk is controversial and, if it does, which morphological type most predisposes to thrombus formation. We assessed LAA morphology in stroke patients with cryptogenic or suspected cardiogenic etiology and in age- and gender-matched healthy controls. LAA morphology and volume were analyzed by cardiac computed tomography in 111 patients (74 males; mean age 60 ± 11 years) with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology other than known atrial fibrillation (AF). A subgroup of 40 patients was compared to an age- and gender-matched control group of 40 healthy individuals (21 males in each; mean age 54 ± 9 years). LAA was classified into four morphology types (Cactus, ChickenWing, WindSock, CauliFlower) modified with a quantitative qualifier. The proportions of LAA morphology types in the main stroke group, matched stroke subgroup, and control group were as follows: Cactus (9.0%, 5.0%, 20.0%), ChickenWing (23.4%, 37.5%, 10.0%), WindSock (47.7%, 35.0%, 67.5%), and CauliFlower (19.8%, 22.5%, 2.5%). The distribution of morphology types differed significantly (P<0.001) between the matched stroke subgroup and control group. The proportion of single-lobed LAA was significantly higher (P<0.001) in the matched stroke subgroup (55%) than the control group (6%). LAA volumes were significantly larger (P<0.001) in both stroke study groups compared to controls patients. To conclude, LAA morphology differed significantly between stroke patients and controls, and single-lobed LAAs were overrepresented and LAA volume was larger in patients with acute ischemic stroke of cryptogenic or suspected cardiogenic etiology.

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest.

INTRODUCTION: Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer. METHODS: This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI. RESULTS: Intra- and interobserver reproducibility were substantial (κ = 0.616-0.784; Intra-Class Correlation 0.589-0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957-0.962, cut-off ADC values for WL-ROIs: 0.87×10-3 mm2s-1; S-ROIs: 0.69×10-3 mm2s-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67. CONCLUSIONS: ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.

Increased visceral adipose tissue as a potential risk factor in patients with embolic stroke of undetermined source (ESUS).

PURPOSE: The etiology of an ischemic stroke remains undetermined in 20-35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke. METHODS: Altogether 58 patients (mean age 57.7 ± 10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered. RESULTS: Mean VAT area was significantly higher in stroke patients (205 ± 103 cm2 for men and 168 ± 99 cm2 for women) compared to all reference populations (P < 0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors. CONCLUSION: Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.

Acute phase IL-10 plasma concentration associates with the high risk sources of cardiogenic stroke.

BACKGROUND: Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism. METHODS: A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit. RESULTS: Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3-16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3-23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29-34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment. CONCLUSION: IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.

Morphological and volumetric analysis of left atrial appendage and left atrium: cardiac computed tomography-based reproducibility assessment.

OBJECTIVES: Left atrial appendage (LAA) dilatation and morphology may influence an individual's risk for intracardiac thrombi and ischemic stroke. LAA size and morphology can be evaluated using cardiac computed tomography (cCT). The present study evaluated the reproducibility of LAA volume and morphology assessments. METHODS: A total of 149 patients (47 females; mean age 60.9±10.6 years) with suspected cardioembolic stroke/transient ischemic attack underwent cCT. Image quality was rated based on four categories. Ten patients were selected from each image quality category (N = 40) for volumetric reproducibility analysis by two individual readers. LAA and left atrium (LA) volume were measured in both two-chamber (2CV) and transversal view (TV) orientation. Intertechnique reproducibility was assessed between 2CV and TV (200 measurement pairs). LAA morphology (A = Cactus, B = ChickenWing, C = WindSock, D = CauliFlower), LAA opening height, number of LAA lobes, trabeculation, and orientation of the LAA tip was analysed in all study subjects by three individual readers (447 interobserver measurement pairs). The reproducibility of volume measurements was assessed by intra-class correlation (ICC) and the reproducibility of LAA morphology assessments by Cohen's kappa. RESULTS: The intra-observer and interobserver reproducibility of LAA and LA volume measurements was excellent (ICCs>0.9). The LAA (ICC = 0.954) and LA (ICC = 0.945) volume measurements were comparable between 2CV and TV. Morphological classification (ĸ = 0.24) and assessments of LAA opening height (ĸ = 0.1), number of LAA lobes (ĸ = 0.16), trabeculation (ĸ = 0.15), and orientation of the LAA tip (ĸ = 0.37) was only slightly to fairly reproducible. CONCLUSIONS: LA and LAA volume measurements on cCT provide excellent reproducibility, whereas visual assessment of LAA morphological features is challenging and results in unsatisfactory agreement between readers.

Determinants of left atrial appendage volume in stroke patients without chronic atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) volume has been shown to be increased in patients with acute cryptogenic stroke. Atrial fibrillation (AF) is a well-recognized risk factor but it is not the only one associated with LAA enlargement. The aim of the study was to clarify the multifactorial etiology of LAA enlargement in cardiogenic stroke/TIA patients without AF. METHODS: Altogether 149 patients with suspected cardioembolic stroke/TIA (47 females; mean age 61 years) underwent cardiac CT. Diagnosed AF on admittance was an exclusion criteria but 24-hour Holter ambulatory ECG revealed paroxysmal AF (PAF) in 20 patients. Body surface area adjusted LAA volume was evaluated. Eighteen different variables were registered including general characteristics, definite and potential causal risk factors for ischemic stroke/TIA, clinical echoparameters and CT based cardiac volumetric and adipose tissue measurements. A stepwise linear regression analysis was performed to achieve a model adjusted for the number of predictors of LAA volume increase. RESULTS: In linear regression analysis, the best model accounted for 30% of the variability in LAA volume, including PAF (19%) and enlarged left atrial volume (6%), enlarged left ventricle end-systolic diameter (3%) and decreased pericardial adipose tissue (2%). No multi-colinearity between variables was observed. In addition to PAF, no other definitive or potential causal risk factors could account for the LAA volume in these patients. CONCLUSIONS: LAA volume increase seems to be poorly associated with currently known stroke/TIA risk factors, except for AF. Targeting more comprehensive ECG monitoring for stroke patients with increased LAA volume should be considered.